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January 30, 2006

Prostate Cancer Screening - Hand-assisted laparoscopic cystoprostatectomy and urinary diversion.


Hand-assisted laparoscopic cystoprostatectomy and urinary diversion.
Related Articles Hand-assisted laparoscopic cystoprostatectomy and urinary diversion. J Urol. 2005 Nov;174(5):1859-60 Authors: Smith JA PMID: 16217321 [PubMed - indexed for MEDLINE]

Selecting patients with pretreatment postvoid residual urine volume less than 100 mL may favorably influence brachytherapy-related urinary morbidity.


Selecting patients with pretreatment postvoid residual urine volume less than 100 mL may favorably influence brachytherapy-related urinary morbidity.
Related Articles Selecting patients with pretreatment postvoid residual urine volume less than 100 mL may favorably influence brachytherapy-related urinary morbidity. Urology. 2005 Dec;66(6):1266-70 Authors: Beekman M, Merrick GS, Butler WM, Wallner KE, Allen ZA, Galbreath RW OBJECTIVES: To evaluate the relationship between pretreatment postvoid residual urine (PVR) less than 100 mL and brachytherapy-related urinary morbidity. METHODS: A total of 204 patients with a pretreatment PVR measurement underwent permanent prostate brachytherapy with urethral-sparing techniques (100% to 140% minimal peripheral dose) for clinical Stage T1b-T2c (2002 American Joint Committee on Cancer staging system) prostate cancer. The median follow-up was 11.7 months. Evaluation of urinary morbidity consisted of the time to International Prostate Symptom Score (IPSS) resolution, length of catheter dependency, and the need for postimplant surgical intervention. IPSS resolution was defined as a return to within 1 point of the score at baseline. In all patients, an alpha-blocker was initiated before implantation and continued at least until the IPSS returned to baseline. Statistically significant predictors of urinary morbidity were determined using Cox regression analysis of multiple clinical, treatment, and dosimetric parameters. RESULTS: For the entire cohort, the mean time to IPSS resolution was 2.5 months. The urinary catheter was removed on the day of implantation in 171 patients (83.8%), with no patient remaining catheter dependent for more than 3 days. To date, no patient has required postimplant surgical intervention. On multivariate analysis, pretreatment PVR predicted for clinically irrelevant differences in IPSS resolution and did not influence catheter dependency. CONCLUSIONS: The selection of patients with a pretreatment PVR of less than 100 mL was associated with rapid IPSS resolution, the absence of prolonged (more than 3 days) catheter dependency, and the elimination of postbrachytherapy surgical intervention for bladder outlet obstruction. PMID: 16360455 [PubMed - indexed for MEDLINE]

Hypoxia down-regulates DNA double strand break repair gene expression in prostate cancer cells.


Hypoxia down-regulates DNA double strand break repair gene expression in prostate cancer cells.
Related Articles Hypoxia down-regulates DNA double strand break repair gene expression in prostate cancer cells. Radiother Oncol. 2005 Aug;76(2):168-76 Authors: Meng AX, Jalali F, Cuddihy A, Chan N, Bindra RS, Glazer PM, Bristow RG BACKGROUND AND PURPOSE: Intratumoral hypoxia has been correlated with poor clinical outcome in prostate cancer. Prostate cancer cells can be genetically unstable and have altered DNA repair. We, therefore, hypothesized that the expression of DNA double-strand break (DNA-dsb) repair genes in normal and malignant prostate cultures can be altered under hypoxic conditions. METHODS AND MATERIALS: The expression of homologous recombination (HR) and non-homologous recombination (NHEJ) genes following gas hypoxia (0.2%) or exposure to HIF1alpha-inducing agent, CoCl2 (100 microM), was determined for normal diploid fibroblasts (GM05757) and the pre-malignant and malignant prostate cell lines, BPH-1, 22RV-1, DU145 and PC3. RNA and protein levels were determined using RT-PCR and Western blotting. Additionally, p53 genotype and function, the level of hypoxia-induced apoptosis, and cell cycle distribution, were determined to correlate to changes in DNA-dsb gene expression. RESULTS: Induction of hypoxia was confirmed using HIF1alpha and VEGF expression in gas- and CoCl2-treated cultures. Hypoxia (48-72 h of 0.2% O2) decreased RNA expression of a number of HR-related genes (e.g. Rad51, Rad52, Rad54, BRCA1, BRCA2) in both normal and malignant cultures. Similar decreases in RNA pertaining to the NHEJ-related genes (e.g. Ku70, DNA-PKcs, DNA Ligase IV, Xrcc4) were observed. In selected cases, hypoxia-mediated decreases in RNA expression led to decreased DNA-dsb protein expression. CoCl2-treated cultures did not show decreased DNA-dsb protein expression. The ability of hypoxia to down-regulate Rad51 and other HR-associated genes under hypoxia was not correlated to c-Abl or c-Myc gene expression, p53 genotype or function, propensity for hypoxia-mediated apoptosis, or specific changes in cell cycle distribution. CONCLUSIONS: Hypoxia can down-regulate expression of DNA-dsb repair genes in both normal and cancer cells. If associated with a functional decrease in DNA-dsb repair, this observation could provide a potential basis for the observed genetic instability within tumor cells exposed to hypoxia. PMID: 16026872 [PubMed - indexed for MEDLINE]

Cloning and sequencing of the cynomolgus monkey prostate specific antigen cDNA.


Cloning and sequencing of the cynomolgus monkey prostate specific antigen cDNA.
Related Articles Cloning and sequencing of the cynomolgus monkey prostate specific antigen cDNA. J Med Primatol. 2006 Feb;35(1):12-7 Authors: Marshall DJ, Rudnick KA, Lu J, Snyder LA Background Prostate-specific antigen (PSA) is an invaluable tumor marker for the detection of early prostate cancer, and can be a target for active immunotherapy of prostate cancer. We wanted to assess the usefulness of the cynomolgus monkey (Macaca fascicularis) as a relevant animal model to evaluate PSA-specific therapies. Methods RNA was isolated from the prostate of cynomolgus monkeys, and PSA gene products were amplified by reverse transcriptase-polymerase chain reaction using primers from conserved regions of human and rhesus monkey (Macaca mulatta) PSA genes. These amplified products were then sequenced. Results The cynomolgus PSA amino acid sequence is 89.7% identical to the human PSA gene, and 99.2% identical to the rhesus PSA amino acid sequence. Like the human and rhesus PSA genes, an open-reading frame of 261 amino acids was identified for the cynomolgus gene. Expression of the cynomolgus PSA gene appears to be restricted to the prostate, as it is in humans. Conclusions The high identity between human and cynomolgus PSA sequences suggests that the cynomolgus monkey should be studied further for its potential as a large animal model to evaluate PSA-specific therapies. PMID: 16430490 [PubMed - in process]

Recent trends in surgical treatment of localized prostate cancer.


Recent trends in surgical treatment of localized prostate cancer.
Related Articles Recent trends in surgical treatment of localized prostate cancer. Clin Prostate Cancer. 2005 Sep;4(2):130-3 Authors: Link BA, Culkin DJ Prostate cancer and its various forms of treatment remain a source of significant controversy and morbidity despite recent advances. In response, there is an increasing trend toward the development of treatments aimed at cancer prevention and at maximizing the preservation of function without sacrificing cancer control. This article reviews the current prostate cancer literature and reports on improvements in existing surgical treatments and developing technologies aimed toward achieving these goals. Specific therapies addressed include improvements in surgical techniques, laparoscopy, robotics, cryosurgical and thermal ablation, and high-intensity focused ultrasound. PMID: 16197615 [PubMed - indexed for MEDLINE]

Oblique needle segmentation and tracking for 3D TRUS guided prostate brachytherapy.


Oblique needle segmentation and tracking for 3D TRUS guided prostate brachytherapy.
Related Articles Oblique needle segmentation and tracking for 3D TRUS guided prostate brachytherapy. Med Phys. 2005 Sep;32(9):2928-41 Authors: Wei Z, Gardi L, Downey DB, Fenster A An algorithm was developed in order to segment and track brachytherapy needles inserted along oblique trajectories. Three-dimensional (3D) transrectal ultrasound (TRUS) images of the rigid rod simulating the needle inserted into the tissue-mimicking agar and chicken breast phantoms were obtained to test the accuracy of the algorithm under ideal conditions. Because the robot possesses high positioning and angulation accuracies, we used the robot as a "gold standard," and compared the results of algorithm segmentation to the values measured by the robot. Our testing results showed that the accuracy of the needle segmentation algorithm depends on the needle insertion distance into the 3D TRUS image and the angulations with respect to the TRUS transducer, e.g., at a 10 degrees insertion anglulation in agar phantoms, the error of the algorithm in determining the needle tip position was less than 1 mm when the insertion distance was greater than 15 mm. Near real-time needle tracking was achieved by scanning a small volume containing the needle. Our tests also showed that, the segmentation time was less than 60 ms, and the scanning time was less than 1.2 s, when the insertion distance into the 3D TRUS image was less than 55 mm. In our needle tracking tests in chicken breast phantoms, the errors in determining the needle orientation were less than 2 degrees in robot yaw and 0.7 degrees in robot pitch orientations, for up to 20 degrees needle insertion angles with the TRUS transducer in the horizontal plane when the needle insertion distance was greater than 15 mm. PMID: 16266107 [PubMed - indexed for MEDLINE]

Cloning and sequencing of the cynomolgus monkey prostate specific antigen cDNA.


Cloning and sequencing of the cynomolgus monkey prostate specific antigen cDNA.
Related Articles Cloning and sequencing of the cynomolgus monkey prostate specific antigen cDNA. J Med Primatol. 2006 Feb;35(1):12-7 Authors: Marshall DJ, Rudnick KA, Lu J, Snyder LA Background Prostate-specific antigen (PSA) is an invaluable tumor marker for the detection of early prostate cancer, and can be a target for active immunotherapy of prostate cancer. We wanted to assess the usefulness of the cynomolgus monkey (Macaca fascicularis) as a relevant animal model to evaluate PSA-specific therapies. Methods RNA was isolated from the prostate of cynomolgus monkeys, and PSA gene products were amplified by reverse transcriptase-polymerase chain reaction using primers from conserved regions of human and rhesus monkey (Macaca mulatta) PSA genes. These amplified products were then sequenced. Results The cynomolgus PSA amino acid sequence is 89.7% identical to the human PSA gene, and 99.2% identical to the rhesus PSA amino acid sequence. Like the human and rhesus PSA genes, an open-reading frame of 261 amino acids was identified for the cynomolgus gene. Expression of the cynomolgus PSA gene appears to be restricted to the prostate, as it is in humans. Conclusions The high identity between human and cynomolgus PSA sequences suggests that the cynomolgus monkey should be studied further for its potential as a large animal model to evaluate PSA-specific therapies. PMID: 16430490 [PubMed - in process]

A novel dietary triterpene Lupeol induces fas-mediated apoptotic death of androgen-sensitive prostate cancer cells and inhibits tumor growth in a xenograft model.


A novel dietary triterpene Lupeol induces fas-mediated apoptotic death of androgen-sensitive prostate cancer cells and inhibits tumor growth in a xenograft model.
Related Articles A novel dietary triterpene Lupeol induces fas-mediated apoptotic death of androgen-sensitive prostate cancer cells and inhibits tumor growth in a xenograft model. Cancer Res. 2005 Dec 1;65(23):11203-13 Authors: Saleem M, Kweon MH, Yun JM, Adhami VM, Khan N, Syed DN, Mukhtar H In prostate cancer, a fine balance between cell proliferation and apoptotic death is lost, resulting in increased cellular mass and tumor progression. One approach to redress this imbalance and control this malignancy is its preventive intervention through the use of dietary natural agents. Here, we investigated the growth-inhibitory effect and associated mechanisms of Lupeol, a triterpene present in fruits and vegetables, in androgen-sensitive human prostate cancer cells. Lupeol treatment resulted in significant inhibition of cell viability in a dose-dependent manner and caused apoptotic death of prostate cancer cells. Lupeol was found to induce the cleavage of poly(ADP-ribose) polymerase protein and degradation of acinus protein with a significant increase in the expression of FADD protein. Among all death receptor targets examined, Lupeol specifically caused a significant increase in the expression of Fas receptor. The small interfering RNA-mediated silencing of the Fas gene and inhibition of caspase-6, caspase-8, and caspase-9 by their specific inhibitors confirmed that Lupeol specifically activates the Fas receptor-mediated apoptotic pathway in androgen-sensitive prostate cancer cells. The treatment of cells with a combination of anti-Fas monoclonal antibody and Lupeol resulted in higher cell death compared with the additive effect of the two compounds alone, suggesting a synergistic effect. Lupeol treatment resulted in a significant inhibition in growth of tumors with concomitant reduction in prostate-specific antigen secretion in athymic nude mice implanted with CWR22Rnu1 cells. Because early clinical prostate cancer growth is an androgen-dependent response, the results of the present study suggest that Lupeol may have a potential to be an effective agent against prostate cancer. PMID: 16322271 [PubMed - indexed for MEDLINE]

Acute renal failure secondary to imatinib mesylate treatment in prostate cancer.


Acute renal failure secondary to imatinib mesylate treatment in prostate cancer.
Related Articles Acute renal failure secondary to imatinib mesylate treatment in prostate cancer. Ann Pharmacother. 2005 Dec;39(12):2136-8 Authors: Foringer JR, Verani RR, Tjia VM, Finkel KW, Samuels JA, Guntupalli JS OBJECTIVE: To report a case of acute renal failure associated with the administration of imatinib mesylate. CASE SUMMARY: A 64-year-old man diagnosed with prostate cancer was enrolled in a Phase I trial of imatinib mesylate plus taxotere on a protocol that required a run-in period of imatinib mesylate alone. During therapy with imatinib mesylate, the patient developed acute renal failure, requiring hemodialysis. A renal biopsy revealed tubular vacuolization. Renal failure resolved with cessation of imatinib mesylate. DISCUSSION: Imatinib mesylate is a protein tyrosine kinase inhibitor that inhibits the BCR-ABL tyrosine kinase, the receptor tyrosine kinases for platelet-derived growth factor, and stem cell factor c-kit. Prostate cancer has been identified as a target for therapy with imatinib mesylate. This patient had no other confounding factors for the cause of the renal failure. An objective causality assessment determined that imatinib mesylate was the probable cause of the acute renal failure. The presence of a primary glomerular disease was excluded by biopsy. CONCLUSIONS: Imatinib mesylate-induced acute renal failure has now been linked to toxic effects on renal tubular cells in 3 cases. Renal function should be closely monitored during imatinib mesylate therapy. PMID: 16288076 [PubMed - in process]

(((prostate cancer treatment) AND "2005/11/13 17.56"[MHDA]:"2115/11/20 14.01"[MHDA])) NOT (( (((prostate cancer[TIAB] AND treatment[TIAB]))) AND "0001"[EDAT]:"2005/11/13 17.56"[EDAT])); +90 new citations


(((prostate cancer treatment) AND "2005/11/13 17.56"[MHDA]:"2115/11/20 14.01"[MHDA])) NOT (( (((prostate cancer[TIAB] AND treatment[TIAB]))) AND "0001"[EDAT]:"2005/11/13 17.56"[EDAT])); +90 new citations
90 new PubMed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: (((prostate cancer treatment) AND "2005/11/13 17.56"[MHDA]:"2115/11/20 14.01"[MHDA])) NOT (( (((prostate cancer[TIAB] AND treatment[TIAB]))) AND "0001"[EDAT]:"2005/11/13 17.56"[EDAT])) These PubMed results were generated on 2006/01/28PubMed, a service of the National Library of Medicine, includes over 15 million citations for biomedical articles back to the 1950's. These citations are from MEDLINE and additional life science journals. PubMed includes links to many sites providing full text articles and other related resources.

January 29, 2006

Alternative therapy common in prostate cancer 


Alternative therapy common in prostate cancer 
Reuters via Yahoo! News - Jan 24 7:25 AM
About one third of prostate cancer patients in the United States use some type of complementary or alternative medicine, a large national study shows.Save to My Web

Prostate Cancer Screening - Germline mutations of the MSR1 gene in prostate cancer families from Germany.


Germline mutations of the MSR1 gene in prostate cancer families from Germany.
Related Articles Germline mutations of the MSR1 gene in prostate cancer families from Germany. Hum Mutat. 2006 Jan;27(1):98-102 Authors: Maier C, Vesovic Z, Bachmann N, Herkommer K, Braun AK, Surowy HM, Assum G, Paiss T, Vogel W The MSR1 gene at 8p22 has been suggested as a candidate gene for hereditary prostate cancer because germline variants have been found to be associated with the disease. Aside from a single nonsense mutation (R293X) that was found repeatedly at low frequencies in several samples, little evidence has been gained by follow-up studies to confirm the gene's relevance for prostate cancer. Prompted by reasonable support for a linkage to 8p22, we sought to determine the mutation spectrum of MSR1 in our family sample. Screening of 139 probands (representing 139 prostate cancer families) revealed 15 novel and a total of 20 sequence variants within the 10 coding exons and their intronic proximities. Aside from the known mutation c.877C>T (R293X) present in two of our families, we identified a second nonsense allele (c.251C>G; S84X) and a splice-site mutation (c.818-1G>A) that results in mRNA instability (each in a single pedigree). The novel missense alleles were c.703C>T (H235Y), c.856C>T (P286S), c.905C>T (P302L), c.1193C>G (A398G), and c.1289A>G (K430R). Of the eight variants that affect the encoded protein (splice site, nonsense, and missense), only R293X as well as the polymorphism c.823C>G (P275A) were additionally present at remarkable frequencies in further samples of sporadic prostate cancer and controls. Of note, carriers of R293X were equally frequent in 367 sporadic prostate cancer cases (1.9%) and in 197 controls (2.0%). To our knowledge, our study is the first to demonstrate further loss of function variants of MSR1 apart from R293X. Nevertheless, the low frequencies of deleterious alleles, in addition to an apparently moderate penetrance, does not support MSR1 as a major susceptibility gene in this family sample. PMID: 16287155 [PubMed - in process]

BRCA1 and BRCA2 as molecular targets for phytochemicals indole-3-carbinol and genistein in breast and prostate cancer cells.


BRCA1 and BRCA2 as molecular targets for phytochemicals indole-3-carbinol and genistein in breast and prostate cancer cells.
Related Articles BRCA1 and BRCA2 as molecular targets for phytochemicals indole-3-carbinol and genistein in breast and prostate cancer cells. Br J Cancer. 2006 Jan 24; Authors: Fan S, Meng Q, Auborn K, Carter T, Rosen EM Indole-3-carbinol (I3C) and genistein are naturally occurring chemicals derived from cruciferous vegetables and soy, respectively, with potential cancer prevention activity for hormone-responsive tumours (e.g., breast and prostate cancers). Previously, we showed that I3C induces BRCA1 expression and that both I3C and BRCA1 inhibit oestrogen (E2)-stimulated oestrogen receptor (ER-alpha) activity in human breast cancer cells. We now report that both I3C and genistein induce the expression of both breast cancer susceptibility genes (BRCA1 and BRCA2) in breast (MCF-7 and T47D) and prostate (DU-145 and LNCaP) cancer cell types, in a time- and dose-dependent fashion. Induction of the BRCA genes occurred at low doses of I3C (20 muM) and genistein (0.5-1.0 muM), suggesting potential relevance to cancer prevention. A combination of I3C and genistein gave greater than expected induction of BRCA expression. Studies using small interfering RNAs (siRNAs) and BRCA expression vectors suggest that the phytochemical induction of BRCA2 is due, in part, to BRCA1. Functional studies suggest that I3C-mediated cytoxicity is, in part, dependent upon BRCA1 and BRCA2. Inhibition of E2-stimulated ER-alpha activity by I3C and genistein was dependent upon BRCA1; and inhibition of ligand-inducible androgen receptor (AR) activity by I3C and genistein was partially reversed by BRCA1-siRNA. Finally, we provide evidence suggesting that the phytochemical induction of BRCA1 expression is due, in part, to endoplasmic reticulum stress response signalling. These findings suggest that the BRCA genes are molecular targets for some of the activities of I3C and genistein.British Journal of Cancer advance online publication, 24 January 2006; doi:10.1038/sj.bjc.6602935 www.bjcancer.com. PMID: 16434996 [PubMed - as supplied by publisher]

Biochemical nature and mapping of PSMA epitopes recognized by human antibodies induced after immunization with gene-based vaccines.


Biochemical nature and mapping of PSMA epitopes recognized by human antibodies induced after immunization with gene-based vaccines.
Related Articles Biochemical nature and mapping of PSMA epitopes recognized by human antibodies induced after immunization with gene-based vaccines. Anticancer Res. 2005 Nov-Dec;25(6C):4727-32 Authors: Todorova K, Zoubak S, Mincheff M, Kyurkchiev S BACKGROUND: A possible new target for immunotherapy is the prostate-specific membrane antigen (PSMA). The aim of the present study was to define potential PSMA epitopes for antibody binding using sera from patients immunized with gene-based anti-PSMA vaccines. MATERIALS AND METHODS: Sera from prostate cancer patients, immunized repeatedly with plasmid and adenoviral vectors, each encoding for the extracellular portion of human PSMA, were tested for anti-PSMA antibodies by Western blot. PSMA-producing LNCaP cells were used as a control. Recombinant PSMA protein cleaved with different proteinases was used for epitope mapping. Different enzymes were used to cleave the PSMA molecule. RESULTS: Specific anti-PSMA antibodies were detected in the studied patients' sera, mainly against the PSMA protein core. An alignment of the predicted enzyme-cleavage fragments was compared with Western blot results and several antibody epitopes were determined. CONCLUSION: These data demonstrate that multiple gene-based vaccinations induce an anti-PSMA humoral immune response. The antibodies are predominantly specific for the PSMA protein core. PMID: 16334167 [PubMed - indexed for MEDLINE]

Cloning and sequencing of the cynomolgus monkey prostate specific antigen cDNA.


Cloning and sequencing of the cynomolgus monkey prostate specific antigen cDNA.
Related Articles Cloning and sequencing of the cynomolgus monkey prostate specific antigen cDNA. J Med Primatol. 2006 Feb;35(1):12-7 Authors: Marshall DJ, Rudnick KA, Lu J, Snyder LA Background Prostate-specific antigen (PSA) is an invaluable tumor marker for the detection of early prostate cancer, and can be a target for active immunotherapy of prostate cancer. We wanted to assess the usefulness of the cynomolgus monkey (Macaca fascicularis) as a relevant animal model to evaluate PSA-specific therapies. Methods RNA was isolated from the prostate of cynomolgus monkeys, and PSA gene products were amplified by reverse transcriptase-polymerase chain reaction using primers from conserved regions of human and rhesus monkey (Macaca mulatta) PSA genes. These amplified products were then sequenced. Results The cynomolgus PSA amino acid sequence is 89.7% identical to the human PSA gene, and 99.2% identical to the rhesus PSA amino acid sequence. Like the human and rhesus PSA genes, an open-reading frame of 261 amino acids was identified for the cynomolgus gene. Expression of the cynomolgus PSA gene appears to be restricted to the prostate, as it is in humans. Conclusions The high identity between human and cynomolgus PSA sequences suggests that the cynomolgus monkey should be studied further for its potential as a large animal model to evaluate PSA-specific therapies. PMID: 16430490 [PubMed - in process]

High dose brachytherapy (real time) in patients with intermediate- or high-risk prostate cancer: technical description and preliminary experience.


High dose brachytherapy (real time) in patients with intermediate- or high-risk prostate cancer: technical description and preliminary experience.
Related Articles High dose brachytherapy (real time) in patients with intermediate- or high-risk prostate cancer: technical description and preliminary experience. Clin Transl Oncol. 2005 Oct;7(9):389-97 Authors: Prada G mez PJ, de la Rua Calder n A, Romo Fonseca I, Evia Su rez M, Abascal Garc a JM, Juan Rijo G, Fern ndez Garc a J, Gonz lez Sancho JM, Abascal Garc a R, Rodr guez-Fern ndez R INTRODUCTION. It has been well documented that the outcome of prostate cancer treatment depends on the dose administered. Hence, techniques have been developed that allow high-dose administration without increasing the complications, e.g. external radiotherapy combined with high-dose radiation (HDR) brachytherapy. In this article we analyse the technique and protocol of real-time HDR brachytherapy together with the preliminary results that support its use. Materials and methods. Between June 1998 and December 2004, 100 patients with adenoma of the prostate were treated with 46 Gy of external irradiation to the pelvis and 2 HDR brachytherapy fractions (each of 1150 cGy) at the end of weeks 1 and 3 of a 5-week radiotherapy course. The 1997 American Joint Commission on Cancer (AJCC) system was used to establish disease stage. Patients with intermediate-risk (PSA 10-20 ng/ml or Gleason = 7 or T2c) and high-risk (two intermediate risk factors or PSA > 20 ng/ml or Gleason > 7 or > T2c) without metastases were eligible for the brachytherapy. Biochemical failure was defined according to the American Society for Therapeutic Radiology and Oncology (ASTRO) consensus panel statement. SPSS statistical package was used to quantify survival (Kaplan-Meier method). Toxicity was scored according to RTOG guidelines. RESULTS. The mean age of patients was 67 years (range 49-78). Clinical stage was T2a in 22% of the patients, 26% T2b and 52% T3. Initial PSA was = 10 ng/ml in 22% of the patients and > 10 ng/ml in 78%. Median follow-up was 28 months (range: 12-79). The 5-year overall survival and actuarial biochemical control were 99% and 87% respectively. No chronic severe complications were noted. CONCLUSIONS. The good results of local control, disease-free survival and few complications that the external radiotherapy combined with HDR brachytherapy have shown suggest that the method should be considered as first-choice in the treatment of prostate tumours of high- and intermediate-risk. PMID: 16238973 [PubMed - indexed for MEDLINE]

Optimization of intensity-modulated radiation therapy with biological objectives.


Optimization of intensity-modulated radiation therapy with biological objectives.
Related Articles Optimization of intensity-modulated radiation therapy with biological objectives. Phys Med Biol. 2005 Nov 21;50(22):5357-79 Authors: Olafsson A, Jeraj R, Wright SJ IMRT treatment planning via biological objectives gives rise to constrained nonlinear optimization problems. We consider formulations with nonlinear objectives based on the equivalent uniform dose (EUD), with bound constraints on the beamlet weights, and describe fast, flexible variants of the two-metric gradient-projection approach for solving them efficiently and in a mathematically sound manner. We conclude that an approach that calculates the Newton component of the step iteratively, by means of the conjugate-gradient algorithm and an implicit representation of the Hessian matrix, is most effective. We also present an efficient heuristic for obtaining an approximate solution with a smoother distribution of beamlet weights. The effectiveness of the methods is verified by testing on a medium-scale clinical case. PMID: 16264258 [PubMed - indexed for MEDLINE]

Cloning and sequencing of the cynomolgus monkey prostate specific antigen cDNA.


Cloning and sequencing of the cynomolgus monkey prostate specific antigen cDNA.
Related Articles Cloning and sequencing of the cynomolgus monkey prostate specific antigen cDNA. J Med Primatol. 2006 Feb;35(1):12-7 Authors: Marshall DJ, Rudnick KA, Lu J, Snyder LA Background Prostate-specific antigen (PSA) is an invaluable tumor marker for the detection of early prostate cancer, and can be a target for active immunotherapy of prostate cancer. We wanted to assess the usefulness of the cynomolgus monkey (Macaca fascicularis) as a relevant animal model to evaluate PSA-specific therapies. Methods RNA was isolated from the prostate of cynomolgus monkeys, and PSA gene products were amplified by reverse transcriptase-polymerase chain reaction using primers from conserved regions of human and rhesus monkey (Macaca mulatta) PSA genes. These amplified products were then sequenced. Results The cynomolgus PSA amino acid sequence is 89.7% identical to the human PSA gene, and 99.2% identical to the rhesus PSA amino acid sequence. Like the human and rhesus PSA genes, an open-reading frame of 261 amino acids was identified for the cynomolgus gene. Expression of the cynomolgus PSA gene appears to be restricted to the prostate, as it is in humans. Conclusions The high identity between human and cynomolgus PSA sequences suggests that the cynomolgus monkey should be studied further for its potential as a large animal model to evaluate PSA-specific therapies. PMID: 16430490 [PubMed - in process]

A novel dietary triterpene Lupeol induces fas-mediated apoptotic death of androgen-sensitive prostate cancer cells and inhibits tumor growth in a xenograft model.


A novel dietary triterpene Lupeol induces fas-mediated apoptotic death of androgen-sensitive prostate cancer cells and inhibits tumor growth in a xenograft model.
Related Articles A novel dietary triterpene Lupeol induces fas-mediated apoptotic death of androgen-sensitive prostate cancer cells and inhibits tumor growth in a xenograft model. Cancer Res. 2005 Dec 1;65(23):11203-13 Authors: Saleem M, Kweon MH, Yun JM, Adhami VM, Khan N, Syed DN, Mukhtar H In prostate cancer, a fine balance between cell proliferation and apoptotic death is lost, resulting in increased cellular mass and tumor progression. One approach to redress this imbalance and control this malignancy is its preventive intervention through the use of dietary natural agents. Here, we investigated the growth-inhibitory effect and associated mechanisms of Lupeol, a triterpene present in fruits and vegetables, in androgen-sensitive human prostate cancer cells. Lupeol treatment resulted in significant inhibition of cell viability in a dose-dependent manner and caused apoptotic death of prostate cancer cells. Lupeol was found to induce the cleavage of poly(ADP-ribose) polymerase protein and degradation of acinus protein with a significant increase in the expression of FADD protein. Among all death receptor targets examined, Lupeol specifically caused a significant increase in the expression of Fas receptor. The small interfering RNA-mediated silencing of the Fas gene and inhibition of caspase-6, caspase-8, and caspase-9 by their specific inhibitors confirmed that Lupeol specifically activates the Fas receptor-mediated apoptotic pathway in androgen-sensitive prostate cancer cells. The treatment of cells with a combination of anti-Fas monoclonal antibody and Lupeol resulted in higher cell death compared with the additive effect of the two compounds alone, suggesting a synergistic effect. Lupeol treatment resulted in a significant inhibition in growth of tumors with concomitant reduction in prostate-specific antigen secretion in athymic nude mice implanted with CWR22Rnu1 cells. Because early clinical prostate cancer growth is an androgen-dependent response, the results of the present study suggest that Lupeol may have a potential to be an effective agent against prostate cancer. PMID: 16322271 [PubMed - indexed for MEDLINE]

Phase II trial of tesmilifene plus mitoxantrone and prednisone for hormone refractory prostate cancer: high subjective and objective response in patients with symptomatic metastases.


Phase II trial of tesmilifene plus mitoxantrone and prednisone for hormone refractory prostate cancer: high subjective and objective response in patients with symptomatic metastases.
Related Articles Phase II trial of tesmilifene plus mitoxantrone and prednisone for hormone refractory prostate cancer: high subjective and objective response in patients with symptomatic metastases. J Urol. 2005 Nov;174(5):1808-13; discussion 1813 Authors: Raghavan D, Brandes LJ, Klapp K, Snyder T, Styles E, Tsao-Wei D, Lieskovsky G, Quinn DI, Ramsey EW PURPOSE: Symptomatic, hormone refractory prostate cancer (HRCAP) is a major cause of morbidity with a median survival of less than 12 months and a 2-year survival of only up to 10% in most series. Mitoxantrone has been approved by the Food and Drug Administration for HRCAP. Preliminary data suggest that DPPE (N,N-diethyl-2-[4-(phenylmethyl) phenoxy]-ethanamine) or tesmilifene modulates cytotoxics to enhance the anticancer effect. In this phase II trial we assessed whether there is sufficient evidence of enhanced efficacy of DPPE and mitoxantrone to lead to a phase III clinical trial. MATERIALS AND METHODS: A total of 29 patients with a median age of 73 years, of whom 10% were older than 80 years, with progressive HRCAP received 5.3 mg/kg DPPE intravenously every 3 weeks, 12 mg/m mitoxantrone intravenously every weeks and 5 mg prednisone orally twice daily. All patients had pain at presentation, while 97% had bone metastases, 10% had liver metastases and 17% had lung metastases. Median prostate specific antigen (PSA) was 210 ng/ml (IQR 77 to 430). RESULTS: Of the patients 75% had some pain improvement, 66% had decreased analgesia, 59% had a PSA decrease of 50% or greater and 45% had a PSA decrease of 75% or greater. Actual (not actuarial) 2-year survival was 21%. CONCLUSIONS: Despite major limitations of historical comparison the PSA decrease and decreased symptoms with DPPE-mitoxantrone-prednisone compare favorably to those of mitoxantrone-prednisone and docetaxel-estramustine in the literature. The 2-year survival rate of 21% mandates further assessment. This will be tested in a phase III Southwest Oncology Group trial. PMID: 16217292 [PubMed - indexed for MEDLINE]

(((prostate cancer treatment) AND "2005/11/13 17.56"[MHDA]:"2115/11/20 14.01"[MHDA])) NOT (( (((prostate cancer[TIAB] AND treatment[TIAB]))) AND "0001"[EDAT]:"2005/11/13 17.56"[EDAT])); +90 new citations


(((prostate cancer treatment) AND "2005/11/13 17.56"[MHDA]:"2115/11/20 14.01"[MHDA])) NOT (( (((prostate cancer[TIAB] AND treatment[TIAB]))) AND "0001"[EDAT]:"2005/11/13 17.56"[EDAT])); +90 new citations
90 new PubMed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: (((prostate cancer treatment) AND "2005/11/13 17.56"[MHDA]:"2115/11/20 14.01"[MHDA])) NOT (( (((prostate cancer[TIAB] AND treatment[TIAB]))) AND "0001"[EDAT]:"2005/11/13 17.56"[EDAT])) These PubMed results were generated on 2006/01/28PubMed, a service of the National Library of Medicine, includes over 15 million citations for biomedical articles back to the 1950's. These citations are from MEDLINE and additional life science journals. PubMed includes links to many sites providing full text articles and other related resources.

January 28, 2006

Prostate Cancer Screening - Clinical staging of prostate cancer: a computer-simulated study of transperineal prostate biopsy.


Clinical staging of prostate cancer: a computer-simulated study of transperineal prostate biopsy.
Related Articles Clinical staging of prostate cancer: a computer-simulated study of transperineal prostate biopsy. BJU Int. 2005 Nov;96(7):999-1004 Authors: Crawford ED, Wilson SS, Torkko KC, Hirano D, Stewart JS, Brammell C, Wilson RS, Kawata N, Sullivan H, Lucia MS, Werahera PN OBJECTIVE: To identify the precise location of prostate cancer within the gland and thus possibly permit more aggressive therapy of the lesion, while potentially sparing the noncancerous gland from ablative therapy. MATERIALS AND METHODS: Three-dimensional "solid" computer models were reconstructed for 86 autopsy specimens and 20 stage T1c radical prostatectomy specimens. Transperineal biopsies were simulated for grid sizes of 5-mm (method A) and 10-mm (method B) with an 18 G, 23-mm long biopsy needle. One or two biopsies per grid point were obtained for a total of 12-108 biopsies, depending on the size of the prostate. Clinically threatening cancers were defined as having volumes of > or = 0.5 mL or Gleason sum > or = 7. RESULTS: Method A detected significantly more carcinomas than method B in both the autopsy and prostatectomy specimens (autopsy, 72 vs 51; prostatectomy, 50 vs 32, both P < 0.001). Method A also detected more clinically threatening cancers found at autopsy (38/40 vs 31/40, P = 0.008). Among autopsy patients with negative sextant biopsies whose disease was localized to one side, method A detected 72% and method B detected 29-43% (P < 0.001). CONCLUSIONS: The results of this computer simulation show that 5- and 10-mm grid biopsies detect three-quarters and a third, respectively, at autopsy, of patients with the disease localized to one side of the prostate, which may be useful when planning highly selective ablative treatments in the future. PMID: 16225516 [PubMed - indexed for MEDLINE]

Alpha-linolenic acid: a gift from the land?


Alpha-linolenic acid: a gift from the land?
Related Articles Alpha-linolenic acid: a gift from the land? Circulation. 2005 Jun 7;111(22):2872-4 Authors: Harris WS PMID: 15939831 [PubMed - indexed for MEDLINE]

Profiling of signaling molecules in four different human prostate carcinoma cell lines before and after induction of apoptosis.


Profiling of signaling molecules in four different human prostate carcinoma cell lines before and after induction of apoptosis.
Related Articles Profiling of signaling molecules in four different human prostate carcinoma cell lines before and after induction of apoptosis. Int J Oncol. 2006 Jan;28(1):217-29 Authors: Skjøth IH, Issinger OG We have treated four prostate tumor cell lines, DU-145, PC-3, LNCaP and 22RV1 with various concentrations of cisplatin in order to check for influence on viability and for onset of apoptosis induction. At a cisplatin concentration of 20 microM, 22RV1 and DU-145 cells showed approximately 22% and 18% and PC-3 and LNCaP cells showed approximately 4 and 10% dead cells, respectively. When checking for apoptosis induction, the differences among the cell lines became even more evident. DU-145 and 22RV1 cells showed apoptosis induction at 5- and 2-microM cisplatin, whereas in the case of LNCaP and PC-3 cells comparable apoptosis induction was observed at 100-microM cisplatin; hence, the difference between the two groups of cell lines with respect to apoptosis induction is 20- and 50-fold, respectively. We used 37 antibodies to screen the expression levels of key signaling molecules and their phosphorylation status where appropriate. DU-145 and PC-3 cells are androgen-receptor negative and harbor non-functional p53, whereas LNCaP and 22RV1 cells are androgen-receptor positive and harbor wild-type p53. The results of the profiling of DU-145 and PC-3 support the notion that an intact PTEN/AKT pathway (as found in DU-145 and 22RV1 cells) and the presence of active p38 are responsible for the high sensitivity to apoptosis induction and that neither the androgen receptor nor the p53 status is of primary importance for the differences observed with respect to apoptosis induction. PMID: 16327999 [PubMed - indexed for MEDLINE]

Cloning and sequencing of the cynomolgus monkey prostate specific antigen cDNA.


Cloning and sequencing of the cynomolgus monkey prostate specific antigen cDNA.
Related Articles Cloning and sequencing of the cynomolgus monkey prostate specific antigen cDNA. J Med Primatol. 2006 Feb;35(1):12-7 Authors: Marshall DJ, Rudnick KA, Lu J, Snyder LA Background Prostate-specific antigen (PSA) is an invaluable tumor marker for the detection of early prostate cancer, and can be a target for active immunotherapy of prostate cancer. We wanted to assess the usefulness of the cynomolgus monkey (Macaca fascicularis) as a relevant animal model to evaluate PSA-specific therapies. Methods RNA was isolated from the prostate of cynomolgus monkeys, and PSA gene products were amplified by reverse transcriptase-polymerase chain reaction using primers from conserved regions of human and rhesus monkey (Macaca mulatta) PSA genes. These amplified products were then sequenced. Results The cynomolgus PSA amino acid sequence is 89.7% identical to the human PSA gene, and 99.2% identical to the rhesus PSA amino acid sequence. Like the human and rhesus PSA genes, an open-reading frame of 261 amino acids was identified for the cynomolgus gene. Expression of the cynomolgus PSA gene appears to be restricted to the prostate, as it is in humans. Conclusions The high identity between human and cynomolgus PSA sequences suggests that the cynomolgus monkey should be studied further for its potential as a large animal model to evaluate PSA-specific therapies. PMID: 16430490 [PubMed - in process]

Managed care market share and primary treatment for cancer.


Managed care market share and primary treatment for cancer.
Related Articles Managed care market share and primary treatment for cancer. Health Serv Res. 2006 Feb;41(1):9-22 Authors: Keating NL, Landrum MB, Meara E, Ganz PA, Guadagnoli E Objective. Increases in the market share of managed care are associated with decreases in expenditures in the fee-for-service sector. To understand utilization patterns responsible for such savings, we assessed whether increases in managed care market share were related to increases in receipt of equally effective but less costly primary cancer therapies. Data Sources. Cancer registry data linked to Medicare administrative data for a population-based sample of fee-for-service Medicare beneficiaries 66 years and older who were diagnosed with breast or prostate cancer during 1993-1999. Study Design. We used fixed-effects regression models to assess whether county-level increases in the market share of managed care were associated with differences in receipt of cancer therapies that are similar in effectiveness but vary in cost. Principal Findings. Increases in the market share of managed care were not associated with differences in the receipt of mastectomy versus breast-conserving surgery with radiation for women with early stage breast cancer (p=.47) or with the receipt of conservative therapy (versus surgery or radiation therapy) for men with local or regional prostate cancer (p=.30). Conclusions. Increases in the market share of managed care do not appear to influence the receipt of equally effective primary treatments for cancer in the fee-for-service sector. PMID: 16430598 [PubMed - in process]

Thermotherapy using magnetic nanoparticles combined with external radiation in an orthotopic rat model of prostate cancer.


Thermotherapy using magnetic nanoparticles combined with external radiation in an orthotopic rat model of prostate cancer.
Related Articles Thermotherapy using magnetic nanoparticles combined with external radiation in an orthotopic rat model of prostate cancer. Prostate. 2006 Jan 1;66(1):97-104 Authors: Johannsen M, Thiesen B, Gneveckow U, Taymoorian K, Waldöfner N, Scholz R, Deger S, Jung K, Loening SA, Jordan A BACKGROUND: We evaluated the effects of thermotherapy using magnetic nanoparticles, also referred to as magnetic fluid hyperthermia (MFH), combined with external radiation, in the Dunning model of prostate cancer. METHODS: Orthotopic tumors were induced in 96 male Copenhagen rats. Animals were randomly allocated to eight groups, including controls and groups for dose-finding studies of external radiation. Treatment groups received two serial thermotherapy treatments following a single intratumoral injection of magnetic fluid or thermotherapy followed by external radiation (10 Gy). On day 20, after tumor induction, tumor weights in the treatment and control groups were compared and iron measurements in selected organs were carried out. RESULTS: Mean maximal and minimal intratumoral temperatures obtained were 58.7 degrees C (centrally) and 42.7 degrees C (peripherally) during the first thermotherapy and 55.4 degrees C and 42.3 degrees C, respectively, during the second of two treatment sessions. Combined thermotherapy and radiation with 20 Gy was significantly more effective than radiation with 20 Gy alone and reduced tumor growth by 87.5-89.2% versus controls. Mean iron content in the prostates on day 20 was 87.5% of the injected dose of ferrites, whereas only 2.5% was found in the liver. CONCLUSIONS: An additive effect was demonstrated for the combined treatment at a radiation dose of 20 Gy, which was equally effective in inhibiting tumor growth as radiation alone with 60 Gy. Serial heat treatments were possible without repeated injection of magnetic fluid. The optimal treatment schedules of this combination regarding temperatures, radiation dose, and fractionation need to be defined in further experimental studies. PMID: 16114060 [PubMed - indexed for MEDLINE]

Cloning and sequencing of the cynomolgus monkey prostate specific antigen cDNA.


Cloning and sequencing of the cynomolgus monkey prostate specific antigen cDNA.
Related Articles Cloning and sequencing of the cynomolgus monkey prostate specific antigen cDNA. J Med Primatol. 2006 Feb;35(1):12-7 Authors: Marshall DJ, Rudnick KA, Lu J, Snyder LA Background Prostate-specific antigen (PSA) is an invaluable tumor marker for the detection of early prostate cancer, and can be a target for active immunotherapy of prostate cancer. We wanted to assess the usefulness of the cynomolgus monkey (Macaca fascicularis) as a relevant animal model to evaluate PSA-specific therapies. Methods RNA was isolated from the prostate of cynomolgus monkeys, and PSA gene products were amplified by reverse transcriptase-polymerase chain reaction using primers from conserved regions of human and rhesus monkey (Macaca mulatta) PSA genes. These amplified products were then sequenced. Results The cynomolgus PSA amino acid sequence is 89.7% identical to the human PSA gene, and 99.2% identical to the rhesus PSA amino acid sequence. Like the human and rhesus PSA genes, an open-reading frame of 261 amino acids was identified for the cynomolgus gene. Expression of the cynomolgus PSA gene appears to be restricted to the prostate, as it is in humans. Conclusions The high identity between human and cynomolgus PSA sequences suggests that the cynomolgus monkey should be studied further for its potential as a large animal model to evaluate PSA-specific therapies. PMID: 16430490 [PubMed - in process]

A novel dietary triterpene Lupeol induces fas-mediated apoptotic death of androgen-sensitive prostate cancer cells and inhibits tumor growth in a xenograft model.


A novel dietary triterpene Lupeol induces fas-mediated apoptotic death of androgen-sensitive prostate cancer cells and inhibits tumor growth in a xenograft model.
Related Articles A novel dietary triterpene Lupeol induces fas-mediated apoptotic death of androgen-sensitive prostate cancer cells and inhibits tumor growth in a xenograft model. Cancer Res. 2005 Dec 1;65(23):11203-13 Authors: Saleem M, Kweon MH, Yun JM, Adhami VM, Khan N, Syed DN, Mukhtar H In prostate cancer, a fine balance between cell proliferation and apoptotic death is lost, resulting in increased cellular mass and tumor progression. One approach to redress this imbalance and control this malignancy is its preventive intervention through the use of dietary natural agents. Here, we investigated the growth-inhibitory effect and associated mechanisms of Lupeol, a triterpene present in fruits and vegetables, in androgen-sensitive human prostate cancer cells. Lupeol treatment resulted in significant inhibition of cell viability in a dose-dependent manner and caused apoptotic death of prostate cancer cells. Lupeol was found to induce the cleavage of poly(ADP-ribose) polymerase protein and degradation of acinus protein with a significant increase in the expression of FADD protein. Among all death receptor targets examined, Lupeol specifically caused a significant increase in the expression of Fas receptor. The small interfering RNA-mediated silencing of the Fas gene and inhibition of caspase-6, caspase-8, and caspase-9 by their specific inhibitors confirmed that Lupeol specifically activates the Fas receptor-mediated apoptotic pathway in androgen-sensitive prostate cancer cells. The treatment of cells with a combination of anti-Fas monoclonal antibody and Lupeol resulted in higher cell death compared with the additive effect of the two compounds alone, suggesting a synergistic effect. Lupeol treatment resulted in a significant inhibition in growth of tumors with concomitant reduction in prostate-specific antigen secretion in athymic nude mice implanted with CWR22Rnu1 cells. Because early clinical prostate cancer growth is an androgen-dependent response, the results of the present study suggest that Lupeol may have a potential to be an effective agent against prostate cancer. PMID: 16322271 [PubMed - indexed for MEDLINE]

The effect of percentage free prostate-specific antigen (PSA) level on the prostate cancer detection rate in a screening population with low PSA levels.


The effect of percentage free prostate-specific antigen (PSA) level on the prostate cancer detection rate in a screening population with low PSA levels.
Related Articles The effect of percentage free prostate-specific antigen (PSA) level on the prostate cancer detection rate in a screening population with low PSA levels. BJU Int. 2005 Nov;96(7):995-8 Authors: Pelzer AE, Volgger H, Bektic J, Berger AP, Rehder P, Bartsch G, Horninger W OBJECTIVE: To evaluate the prostate cancer detection rate at low total prostate-specific antigen (tPSA) ranges of 2.6-4 and 4.1-10 ng/mL, according to different percentage free (f/t) PSA levels in a screening population. SUBJECTS AND METHODS: In all, 1809 consecutive screening volunteers with a tPSA level of 2.6-10.0 ng/mL were assessed. Ten systematic ultrasonography-guided prostate biopsies and, since 2000, an additional five Doppler-enhanced targeted biopsies were taken on the basis of age-specific tPSA reference ranges. We analysed the detection rate of prostate cancer according to f/tPSA ranges of 0-9%, 10-14%, 15-18% and >18%. RESULTS: The detection rates for the subgroups with tPSA levels of 2.6-4.0 and 4.1-10.0 ng/mL were 20.2% and 27.0%, respectively. The cancer detection rate in the first group (2.6-4.0 ng/mL) at 0-10% fPSA was 22.9%, and that in the second group (4.1-10.0 ng/mL) at 0-10% was 36.9%. There were significant differences between these groups. If the f/tPSA was 10-15%, the cancer detection rate for the two groups were 22.6% and 32.5%, respectively (P < 0.05). There was no statistically significant difference in the cancer detecting rates at an f/tPSA of 15-18% or >18%. CONCLUSION: There is a statistically significantly higher cancer detection rate when the f/tPSA is <15% than in groups of men with a f/tPSA of >15% in screening population assessed primarily using tPSA level. PMID: 16225515 [PubMed - indexed for MEDLINE]

(((prostate cancer treatment) AND "2005/11/13 17.56"[MHDA]:"2115/11/20 14.01"[MHDA])) NOT (( (((prostate cancer[TIAB] AND treatment[TIAB]))) AND "0001"[EDAT]:"2005/11/13 17.56"[EDAT])); +90 new citations


(((prostate cancer treatment) AND "2005/11/13 17.56"[MHDA]:"2115/11/20 14.01"[MHDA])) NOT (( (((prostate cancer[TIAB] AND treatment[TIAB]))) AND "0001"[EDAT]:"2005/11/13 17.56"[EDAT])); +90 new citations
90 new PubMed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: (((prostate cancer treatment) AND "2005/11/13 17.56"[MHDA]:"2115/11/20 14.01"[MHDA])) NOT (( (((prostate cancer[TIAB] AND treatment[TIAB]))) AND "0001"[EDAT]:"2005/11/13 17.56"[EDAT])) These PubMed results were generated on 2006/01/28PubMed, a service of the National Library of Medicine, includes over 15 million citations for biomedical articles back to the 1950's. These citations are from MEDLINE and additional life science journals. PubMed includes links to many sites providing full text articles and other related resources.

January 24, 2006

Prostate Cancer Screening - Cancer chemotherapy by deoxynucleotide depletion and E2F-1 elevation.


Cancer chemotherapy by deoxynucleotide depletion and E2F-1 elevation.
Related Articles Cancer chemotherapy by deoxynucleotide depletion and E2F-1 elevation. Cancer Res. 2005 Sep 1;65(17):7809-14 Authors: Wang A, Li CJ, Reddy PV, Pardee AB We propose that the lethality of commonly used anticancer drugs, e.g., methotrexate and cis-platinum are due, at least in part, to an increase of the E2F-1-mediated apoptotic cascade. The drugs directly or indirectly decrease deoxynucleoside triphosphates. The E2F family acts to provide control of S phase by transcribing genes required for deoxynucleoside triphosphate and DNA synthesis. Thus, a mechanism for control of E2F-1 is essential, a signal safeguarding against aberrant or uncontrolled cell proliferation. We have proposed a feedback control by NTPs that down-regulates E2F-1. Here, we provide evidence in support of this hypothesis. PMID: 16140949 [PubMed - indexed for MEDLINE]

Polo-like kinase (Plk) 1 as a target for prostate cancer management.


Polo-like kinase (Plk) 1 as a target for prostate cancer management.
Related Articles Polo-like kinase (Plk) 1 as a target for prostate cancer management. IUBMB Life. 2005 Oct;57(10):677-82 Authors: Reagan-Shaw S, Ahmad N Prostate cancer (PCa) is the most commonly occurring cancer in American men, next to skin cancer. Existing treatment options and surgical intervention are unable to effectively manage this cancer. Therefore, continuing efforts are ongoing to establish novel mechanism-based targets and strategies for its management. The serine/threonine kinases Polo-like kinase (Plk) 1 plays a key role in mitotic entry of proliferating cells and regulates many aspects of mitosis which are necessary for successful cytokinesis. Plk1 is over-expressed in many tumor types with aberrant elevation frequently constituting a prognostic indicator of poor disease outcome. This review discusses the studies which indicate that Plk1 could be an excellent target for the treatment as well as chemoprevention of prostate cancer. PMID: 16223707 [PubMed - indexed for MEDLINE]

Dual-specificity phosphatase 1 and serum/glucocorticoid-regulated kinase are downregulated in prostate cancer.


Dual-specificity phosphatase 1 and serum/glucocorticoid-regulated kinase are downregulated in prostate cancer.
Related Articles Dual-specificity phosphatase 1 and serum/glucocorticoid-regulated kinase are downregulated in prostate cancer. Int J Cancer. 2005 Dec 10;117(5):738-45 Authors: Rauhala HE, Porkka KP, Tolonen TT, Martikainen PM, Tammela TL, Visakorpi T Inactivation of tumor suppressor genes through deletion, mutation and epigenetic silencing has been shown to occur in cancer. In our study, we combined DNA demethylation and histone deacetylation inhibition treatments with suppression subtraction hybridization (SSH) and cDNA microarrays to identify potentially epigenetically downregulated genes in PC-3 prostate cancer cell line. We found 11 genes whose expression was upregulated after relieving epigenetic regulation. Expression of 3 genes [dual-specificity phosphatase 1 (DUSP1), serum/glucocorticoid regulated kinase (SGK) and spermidine/spermine N1-acetyltransferase (SAT)] was subsequently studied in clinical sample material using real-time quantitative RT-PCR and immunohistochemistry. The DUSP1 and SGK mRNA expression was lower in hormone-refractory prostate carcinomas compared to benign prostate hyperplasia (BPH) or untreated prostate carcinomas. BPH, normal prostate and high-grade prostate intraepithelial neoplasia (PIN) expressed high levels of DUSP1 and SGK proteins. Ninety-two percent and 48% of the prostate carcinomas showed almost complete lack of DUSP1 and SGK proteins, respectively, indicating common downregulation of these genes. The genomic bisulphite sequencing did not reveal dense hypermethylation in the promoter regions of either DUSP1 or SGK. In conclusion, the data suggest that downregulation of DUSP1 and SGK is an early event and could be important in the tumorigenesis of prostate cancer. PMID: 15981206 [PubMed - indexed for MEDLINE]

Telomerase vaccination has no detectable effect on SCID-repopulating and colony-forming activities in the bone marrow of cancer patients.


Telomerase vaccination has no detectable effect on SCID-repopulating and colony-forming activities in the bone marrow of cancer patients.
Related Articles Telomerase vaccination has no detectable effect on SCID-repopulating and colony-forming activities in the bone marrow of cancer patients. Exp Hematol. 2005 Nov;33(11):1275-80 Authors: Danet-Desnoyers GA, Luongo JL, Bonnet DA, Domchek SM, Vonderheide RH OBJECTIVES: The telomerase reverse transcriptase hTERT is a widely expressed tumor-associated antigen recognized by cytotoxic T lymphocytes (CTL). We have previously shown that vaccination of cancer patients against hTERT induces functional anti-tumor CTL in vivo, but it is not known whether hTERT vaccination harms normal cells expressing the enzyme, especially hematopoietic stem cells and progenitors. PATIENTS AND METHODS: We employed colony-forming cell (CFC) assays, long-term in vitro cultures, and nonobese diabetic/severe combined immunodeficient (NOD/SCID) repopulation studies to evaluate the effects of hTERT vaccination on hematopoietic progenitors and stem cells in cancer patients following treatment. RESULTS: Using bone marrow samples obtained from cancer patients before and after vaccination, we found that there was no significant decline in the frequency of granulocyte, macrophage or erythroid CFCs using CFC assays or long-term in vitro cultures. In NOD/SCID mice, human hematopoietic reconstitution was easily detected, without quantitative or qualitative differences between pre- and postvaccine samples. CONCLUSION: These findings suggest that induction of tumor-lytic hTERT-specific T cells in vivo by vaccination does not result in a detectable decline in hematopoietic potential despite the expression of hTERT and major histocompatibility complex class I in bone marrow progenitors and stem cells. Thus, even for self-antigens such as telomerase, tumor immunity does not necessarily involve autoimmunity in normal tissues that share the target. PMID: 16263411 [PubMed - indexed for MEDLINE]

Evaluation of lipophilins as determinants of tumor cell response to estramustine.


Evaluation of lipophilins as determinants of tumor cell response to estramustine.
Related Articles Evaluation of lipophilins as determinants of tumor cell response to estramustine. J Pharmacol Exp Ther. 2005 Dec;315(3):1158-62 Authors: Tucker JM, Lipatova Z, Beljanski V, Townsend DM, Tew KD Estramustine administered orally as estramustine phosphate (EMP) remains a major tool in hormone refractory prostate cancer chemotherapy. The presence of estramustine binding protein, prostatin, in prostate tissue may be a determinant of response to treatment. Lipophilins are secretory proteins with homology to prostatin. Reverse transcription-polymerase chain reaction was performed to estimate expression patterns of lipophilins A to C in human biopsies and cell lines resistant to estramustine. Although lipophilin A was not expressed in prostate tissue, both lipophilins B and C were expressed in normal and tumor prostate without significant differences. For lipophilin C, a somatic mutation (T to C transition at positions 409 and 412) was found in human tumor samples and absent in normal prostate tissue. No consistent response to EMP was observed in enhanced green fluorescent protein (EGFP)-tagged lipophilin C-transfected PC3 cells compared with parental controls. Among these EGFP-lipophilin C clones, no direct correlation between response to EMP treatment (IC50 values) and EGFP expression was observed (p = 0.73). Lipophilin C mRNA levels did not vary significantly between wild-type and estramustine-resistant cells in prostate (DU145 and PC3) and ovarian (SKOV3) cancer cell lines. Overall, these results suggest that lipophilins are not specific determinants of estramustine efficacy. PMID: 16120813 [PubMed - indexed for MEDLINE]

Severity categories of the International Prostate Symptom Score before, and urinary morbidity after, permanent prostate brachytherapy.


Severity categories of the International Prostate Symptom Score before, and urinary morbidity after, permanent prostate brachytherapy.
Related Articles Severity categories of the International Prostate Symptom Score before, and urinary morbidity after, permanent prostate brachytherapy. BJU Int. 2006 Jan;97(1):62-8 Authors: Gutman S, Merrick GS, Butler WM, Wallner KE, Allen Z, Galbreath RW, Adamovich E OBJECTIVE: To determine if the International Prostate Symptom Score (IPSS) before seed implantation, stratified into mild (0-7), moderate (8-19) and severe (>20) categories, predicts brachytherapy-related morbidity in terms of IPSS resolution, catheter dependency and the need for surgical intervention after brachytherapy. PATIENTS AND METHODS: From January 1998 to September 2003, 1034 consecutive patients had permanent interstitial brachytherapy for clinical stage T1b-T3a NXM0 (2002 system) prostate cancer. Of the 1034 patients, 739 (71.5%) presented with an IPSS of 0-7, 287 (27.7%) of 8-19, and eight (0.8%) of > or = 20. The IPSS 8-19 cohort was further stratified into 8-14 (237 men) and 15-19 (50 men) subgroups. The median follow-up was 38.2 months. In all patients, an alpha-blocker was initiated before brachytherapy and continued at least until the IPSS normalized, the latter defined as a return to within 1 point of that before implantation. A median of 21 IPSS questionnaires were obtained per patient. Several clinical, treatment and dosimetric variables were evaluated as predictors of urinary morbidity. RESULTS: For the entire cohort, the IPSS peaked at a mean of 0.5 months after implantation and resolved at a mean of 1.7 months. At 5 years after brachytherapy, 90.1% of patients at risk (88.8%, 95.5%, and four of eight patients with a pre-implant IPSS of 0-7, 8-19 and > or = 20, respectively) were within the IPSS 0-7 category. Compared to the pre-implant IPSS, 13 patients (8%) were assigned to a higher IPSS severity category. Neither prolonged urinary catheter dependency (>5 days; 16 patients, 1.5%) or transurethral resection of the prostate (TURP, 17 patients, 1.6%) depended on the pre-implant IPSS subgroup. In Cox regression analysis, IPSS resolution was best predicted by pre-implant IPSS, prolonged catheter dependency by patient age, and TURP by any catheter dependency, the maximum IPSS increase and the maximum urethral dose. CONCLUSIONS: The IPSS before implantation predicted the resolution of IPSS after brachytherapy, but did not correlate with substantial urinary morbidity, including catheter dependency or the need for TURP. At 5 years after brachytherapy, 90.1% of patients at risk were assigned to the IPSS 0-7 category. PMID: 16336330 [PubMed - indexed for MEDLINE]

Telomerase vaccination has no detectable effect on SCID-repopulating and colony-forming activities in the bone marrow of cancer patients.


Telomerase vaccination has no detectable effect on SCID-repopulating and colony-forming activities in the bone marrow of cancer patients.
Related Articles Telomerase vaccination has no detectable effect on SCID-repopulating and colony-forming activities in the bone marrow of cancer patients. Exp Hematol. 2005 Nov;33(11):1275-80 Authors: Danet-Desnoyers GA, Luongo JL, Bonnet DA, Domchek SM, Vonderheide RH OBJECTIVES: The telomerase reverse transcriptase hTERT is a widely expressed tumor-associated antigen recognized by cytotoxic T lymphocytes (CTL). We have previously shown that vaccination of cancer patients against hTERT induces functional anti-tumor CTL in vivo, but it is not known whether hTERT vaccination harms normal cells expressing the enzyme, especially hematopoietic stem cells and progenitors. PATIENTS AND METHODS: We employed colony-forming cell (CFC) assays, long-term in vitro cultures, and nonobese diabetic/severe combined immunodeficient (NOD/SCID) repopulation studies to evaluate the effects of hTERT vaccination on hematopoietic progenitors and stem cells in cancer patients following treatment. RESULTS: Using bone marrow samples obtained from cancer patients before and after vaccination, we found that there was no significant decline in the frequency of granulocyte, macrophage or erythroid CFCs using CFC assays or long-term in vitro cultures. In NOD/SCID mice, human hematopoietic reconstitution was easily detected, without quantitative or qualitative differences between pre- and postvaccine samples. CONCLUSION: These findings suggest that induction of tumor-lytic hTERT-specific T cells in vivo by vaccination does not result in a detectable decline in hematopoietic potential despite the expression of hTERT and major histocompatibility complex class I in bone marrow progenitors and stem cells. Thus, even for self-antigens such as telomerase, tumor immunity does not necessarily involve autoimmunity in normal tissues that share the target. PMID: 16263411 [PubMed - indexed for MEDLINE]

Radiation Therapy Oncology Group 0521: A Phase III Randomized Trial of Androgen Suppression and Radiation Therapy Versus Androgen Suppression and Radiation Therapy Followed by Chemotherapy with Docetaxel/Prednisone for Localized, High-Risk Prostate Cance


Radiation Therapy Oncology Group 0521: A Phase III Randomized Trial of Androgen Suppression and Radiation Therapy Versus Androgen Suppression and Radiation Therapy Followed by Chemotherapy with Docetaxel/Prednisone for Localized, High-Risk Prostate Cancer.
Related Articles Radiation Therapy Oncology Group 0521: A Phase III Randomized Trial of Androgen Suppression and Radiation Therapy Versus Androgen Suppression and Radiation Therapy Followed by Chemotherapy with Docetaxel/Prednisone for Localized, High-Risk Prostate Cancer. Clin Genitourin Cancer. 2005 Dec;4(3):212-4 Authors: Patel AR, Sandler HM, Pienta KJ PMID: 16425991 [PubMed - in process]

Non-genomic effects of the androgen receptor and Vitamin D agonist are involved in suppressing invasive phenotype of prostate cancer cells.


Non-genomic effects of the androgen receptor and Vitamin D agonist are involved in suppressing invasive phenotype of prostate cancer cells.
Related Articles Non-genomic effects of the androgen receptor and Vitamin D agonist are involved in suppressing invasive phenotype of prostate cancer cells. Steroids. 2005 Nov 8; Authors: Bonaccorsi L, Marchiani S, Ferruzzi P, Muratori M, Crescioli C, Forti G, Maggi M, Baldi E Suppression of invasive phenotype is essential in developing new therapeutic tools to treat prostate cancer (PC). Evidence indicates that androgen-dependent (AD) prostate cancer cells are characterized by a lower malignant phenotype. We have demonstrated that transfection with an androgen receptor (AR) expression vector of the androgen-independent (AI) prostate cancer cell line PC3 decreases invasion of these cells through modulation of alpha6beta4 integrin expression, indicating a genotropic effect of androgens in inhibiting invasion ability of AD PC cells. Later on, we have shown that also a non-genotropic mechanism is involved in such an effect. By using immunoconfocal fluorescent microscopy, we demonstrated that AR in PC3-AR cells co-localizes with the EGFR receptors (EGFR) in PC3-AR cells. Co-immunoprecipitation studies both in PC3-AR cells and in the AD cell line LNCaP that physiologically express both receptors, confirm the occurrence of an interaction between of the two proteins. In PC3-AR cells, we demonstrated a disruption of EGFR signalling properties (reduced EGF-induced EGFR autotransphosphorylation, reduced EGF-stimulated PI3K activity as well as EGFR-PI3K interaction) contributing to the lower invasive phenotype of these cells. In another study, we investigated the effects of a new Vitamin D analogue, BXL628, on invasion in response to KGF in the androgen-independent PC cell line DU145. We found that the compound was able to reduce proliferation and invasion of the cells in response to the growth factor. In addition, we found that KGF-induced autotransphosphorylation of KGF receptor (KGFR) and PI3K activation were suppressed after short-term (5min) pre-treatment with the analogue before addition of KGF. Collectively, these studies demonstrate that a non-genotropic effect due to a direct interaction of the androgen receptor with EGFR and to a rapid effect of a Vitamin D agonist on KGFR may disrupt signalling of GF leading to decreased tumorigenicity and a less malignant phenotype of PC cells in vitro. PMID: 16289173 [PubMed - as supplied by publisher]

Side-effects of treatments for locally advanced prostate cancer.


Side-effects of treatments for locally advanced prostate cancer.
Related Articles Side-effects of treatments for locally advanced prostate cancer. BJU Int. 2006 Jan;97(1):22-8 Authors: O'Connor KM, Fitzpatrick JM PMID: 16336322 [PubMed - indexed for MEDLINE]

January 23, 2006

The mineral selenium proves itself as powerful anti-cancer medicine


The mineral selenium proves itself as powerful anti-cancer medicine
NewsTarget - One of the most effective naturally occurring weapons against cancer is, like most healthy things, something many of us are not getting enough of. The mineral selenium has been shown in multiple studies to be an effective tool in warding off various

Prostate Cancer Screening - Observed effect of age and body mass index on total and complexed PSA: analysis from a National Screening Program.


Observed effect of age and body mass index on total and complexed PSA: analysis from a National Screening Program.
Related Articles Observed effect of age and body mass index on total and complexed PSA: analysis from a National Screening Program. J Urol. 2005 Nov;174(5):1825-6 Authors: Walsh PC PMID: 16217298 [PubMed - indexed for MEDLINE]

Changes in bone mineral density in patients with prostate cancer treated with androgen deprivation therapy.


Changes in bone mineral density in patients with prostate cancer treated with androgen deprivation therapy.
Related Articles Changes in bone mineral density in patients with prostate cancer treated with androgen deprivation therapy. Coll Antropol. 2005 Dec;29(2):589-91 Authors: Bernat MM, Pasini J, Marekovi Z Osteoporosis is a complication of permanent androgen deprivation in men with prostate carcinoma, following either bilateral orchiectomy or treatment with GnRH agonists. The present approach to the problem of osteoporosis includes prevention, adequate follow-up and appropriate treatment as an imperative of contemporary urological and endocrinological management of these patients. Bone densitometry was performed in 18 patients who were on GnRH agonists treatment during 1-3 years. The patients under therapy were followed clinically, PSA (prostate-specific antigen) values were determined and bone scintigraphy was performed. The bone mineral density values in 13 patients indicated osteopenia, whereas in one patient the finding was compatible with osteoporosis. Four patients had normal bone mineral density findings. Bone densitometry should be performed before initiation of treatment with GnRH agonists in order to quantify the therapy-related bone loss. Prevention of development of osteoporosis and its complications depends on the assessment of pharmacological treatment in this group of patients, including e.g. bisphosphonates and possible intermittent androgen deprivation. PMID: 16417166 [PubMed - in process]

Polo-like kinase (Plk) 1 as a target for prostate cancer management.


Polo-like kinase (Plk) 1 as a target for prostate cancer management.
Related Articles Polo-like kinase (Plk) 1 as a target for prostate cancer management. IUBMB Life. 2005 Oct;57(10):677-82 Authors: Reagan-Shaw S, Ahmad N Prostate cancer (PCa) is the most commonly occurring cancer in American men, next to skin cancer. Existing treatment options and surgical intervention are unable to effectively manage this cancer. Therefore, continuing efforts are ongoing to establish novel mechanism-based targets and strategies for its management. The serine/threonine kinases Polo-like kinase (Plk) 1 plays a key role in mitotic entry of proliferating cells and regulates many aspects of mitosis which are necessary for successful cytokinesis. Plk1 is over-expressed in many tumor types with aberrant elevation frequently constituting a prognostic indicator of poor disease outcome. This review discusses the studies which indicate that Plk1 could be an excellent target for the treatment as well as chemoprevention of prostate cancer. PMID: 16223707 [PubMed - indexed for MEDLINE]

Telomerase vaccination has no detectable effect on SCID-repopulating and colony-forming activities in the bone marrow of cancer patients.


Telomerase vaccination has no detectable effect on SCID-repopulating and colony-forming activities in the bone marrow of cancer patients.
Related Articles Telomerase vaccination has no detectable effect on SCID-repopulating and colony-forming activities in the bone marrow of cancer patients. Exp Hematol. 2005 Nov;33(11):1275-80 Authors: Danet-Desnoyers GA, Luongo JL, Bonnet DA, Domchek SM, Vonderheide RH OBJECTIVES: The telomerase reverse transcriptase hTERT is a widely expressed tumor-associated antigen recognized by cytotoxic T lymphocytes (CTL). We have previously shown that vaccination of cancer patients against hTERT induces functional anti-tumor CTL in vivo, but it is not known whether hTERT vaccination harms normal cells expressing the enzyme, especially hematopoietic stem cells and progenitors. PATIENTS AND METHODS: We employed colony-forming cell (CFC) assays, long-term in vitro cultures, and nonobese diabetic/severe combined immunodeficient (NOD/SCID) repopulation studies to evaluate the effects of hTERT vaccination on hematopoietic progenitors and stem cells in cancer patients following treatment. RESULTS: Using bone marrow samples obtained from cancer patients before and after vaccination, we found that there was no significant decline in the frequency of granulocyte, macrophage or erythroid CFCs using CFC assays or long-term in vitro cultures. In NOD/SCID mice, human hematopoietic reconstitution was easily detected, without quantitative or qualitative differences between pre- and postvaccine samples. CONCLUSION: These findings suggest that induction of tumor-lytic hTERT-specific T cells in vivo by vaccination does not result in a detectable decline in hematopoietic potential despite the expression of hTERT and major histocompatibility complex class I in bone marrow progenitors and stem cells. Thus, even for self-antigens such as telomerase, tumor immunity does not necessarily involve autoimmunity in normal tissues that share the target. PMID: 16263411 [PubMed - indexed for MEDLINE]

Long-term outcomes of 60 Gy conventional radiotherapy combined with androgen deprivation for localized or locally advanced prostate cancer.


Long-term outcomes of 60 Gy conventional radiotherapy combined with androgen deprivation for localized or locally advanced prostate cancer.
Related Articles Long-term outcomes of 60 Gy conventional radiotherapy combined with androgen deprivation for localized or locally advanced prostate cancer. Jpn J Clin Oncol. 2005 Nov;35(11):655-9 Authors: Hashine K, Numata K, Azuma K, Sumiyoshi Y, Kataoka M BACKGROUND: Until 1998 in Japan, very few institutions were treating prostate cancer solely with radiotherapy (RT) >70 Gy and most were using < or =65 Gy in combination with hormone therapy. The present study reports the long-term results of RT combined with hormone therapy for localized and locally advanced prostate cancer. METHODS: We investigated 57 patients who were treated by external beam RT plus hormone therapy (median age 79 years, median prostate-specific antigen concentration 15.0 ng/ml) between 1992 and 1998. Patients received 40 Gy of radiation to the pelvis and an additional 20 Gy as a prostatic boost. Hormone therapy was begun on the first day of irradiation and continued thereafter. RESULTS: The median follow-up was 93.3 months and the 5 and 10 year actual overall survival rates were 67.8 and 32.6%, respectively, with 5 and 10 year cause-specific survival rates of 97.9 and 95.0%, respectively. The expected survival rate was 66.2% at 5 years, and overall survival was above expected survival. Only one patient developed severe proctitis (Grade 3). The 5 year occurrence of Grade 1/2 genitourinary toxicity was 23.2%. CONCLUSIONS: Combined RT and hormone therapy has a good long-term outcome without severe adverse events. The overall survival rate compares well with the expected survival rate. PMID: 16275680 [PubMed - indexed for MEDLINE]

L14: erectile dysfunction after radiotherapy for prostate cancer.


L14: erectile dysfunction after radiotherapy for prostate cancer.
Related Articles L14: erectile dysfunction after radiotherapy for prostate cancer. J Sex Med. 2004 Nov;1 Suppl 1:16-7 Authors: Incrocci L PMID: 16422934 [PubMed - in process]

Telomerase vaccination has no detectable effect on SCID-repopulating and colony-forming activities in the bone marrow of cancer patients.


Telomerase vaccination has no detectable effect on SCID-repopulating and colony-forming activities in the bone marrow of cancer patients.
Related Articles Telomerase vaccination has no detectable effect on SCID-repopulating and colony-forming activities in the bone marrow of cancer patients. Exp Hematol. 2005 Nov;33(11):1275-80 Authors: Danet-Desnoyers GA, Luongo JL, Bonnet DA, Domchek SM, Vonderheide RH OBJECTIVES: The telomerase reverse transcriptase hTERT is a widely expressed tumor-associated antigen recognized by cytotoxic T lymphocytes (CTL). We have previously shown that vaccination of cancer patients against hTERT induces functional anti-tumor CTL in vivo, but it is not known whether hTERT vaccination harms normal cells expressing the enzyme, especially hematopoietic stem cells and progenitors. PATIENTS AND METHODS: We employed colony-forming cell (CFC) assays, long-term in vitro cultures, and nonobese diabetic/severe combined immunodeficient (NOD/SCID) repopulation studies to evaluate the effects of hTERT vaccination on hematopoietic progenitors and stem cells in cancer patients following treatment. RESULTS: Using bone marrow samples obtained from cancer patients before and after vaccination, we found that there was no significant decline in the frequency of granulocyte, macrophage or erythroid CFCs using CFC assays or long-term in vitro cultures. In NOD/SCID mice, human hematopoietic reconstitution was easily detected, without quantitative or qualitative differences between pre- and postvaccine samples. CONCLUSION: These findings suggest that induction of tumor-lytic hTERT-specific T cells in vivo by vaccination does not result in a detectable decline in hematopoietic potential despite the expression of hTERT and major histocompatibility complex class I in bone marrow progenitors and stem cells. Thus, even for self-antigens such as telomerase, tumor immunity does not necessarily involve autoimmunity in normal tissues that share the target. PMID: 16263411 [PubMed - indexed for MEDLINE]

Comparison of biological effects of non-nucleoside DNA methylation inhibitors versus 5-aza-2'-deoxycytidine.


Comparison of biological effects of non-nucleoside DNA methylation inhibitors versus 5-aza-2'-deoxycytidine.
Related Articles Comparison of biological effects of non-nucleoside DNA methylation inhibitors versus 5-aza-2'-deoxycytidine. Mol Cancer Ther. 2005 Oct;4(10):1515-20 Authors: Chuang JC, Yoo CB, Kwan JM, Li TW, Liang G, Yang AS, Jones PA DNA cytosine methylation plays a considerable role in normal development, gene regulation, and carcinogenesis. Hypermethylation of the promoters of some tumor suppressor genes and the associated silencing of these genes often occur in certain cancer types. The reversal of this process by DNA methylation inhibitors is a promising new strategy for cancer therapy. In addition to the four well-characterized nucleoside analogue methylation inhibitors, 5-azacytidine, 5-aza-2'-deoxycytidine (5-Aza-CdR), 5-fluoro-2'-deoxycytidine, and zebularine, there is a growing list of non-nucleoside inhibitors. However, a systemic study comparing these potential demethylating agents has not been done. In this study, we examined three non-nucleoside demethylating agents, (-)-epigallocatechin-3-gallate, hydralazine, and procainamide, and compared their effects and potencies with 5-Aza-CdR, the most potent DNA methylation inhibitor. We found that 5-Aza-CdR is far more effective in DNA methylation inhibition as well as in reactivating genes, compared with non-nucleoside inhibitors. PMID: 16227400 [PubMed - indexed for MEDLINE]

Inactivation of Id-1 in prostate cancer cells: A potential therapeutic target in inducing chemosensitization to taxol through activation of JNK pathway.


Inactivation of Id-1 in prostate cancer cells: A potential therapeutic target in inducing chemosensitization to taxol through activation of JNK pathway.
Related Articles Inactivation of Id-1 in prostate cancer cells: A potential therapeutic target in inducing chemosensitization to taxol through activation of JNK pathway. Int J Cancer. 2005 Nov 14; Authors: Zhang X, Ling MT, Wang X, Wong YC Resistance to anticancer drugs is the major problem in the treatment of many advanced cancers, including androgen-independent prostate cancer. Recently, increased expression of Id-1, a basic helix-loop-helix protein, is reported in several types of advanced cancer. It is suggested that high expression of Id-1 may provide an advantage for cancer cell survival and inactivation of Id-1 may be able to increase cancer cells' susceptibility to apoptosis. To test this hypothesis, in this study, by using RNA interfering technology, we inactivated the Id-1 gene in 2 androgen-independent prostate cancer cell lines, DU145 and PC3, and investigated whether downregulation of Id-1 could lead to increased sensitivity to a commonly used anticancer drug, taxol. By using colony forming assay and MTT assay, we found that inactivation of Id-1 resulted in both decreased colony forming ability and cell viability in prostate cancer cells, after taxol treatment. In addition, the si-Id-1-induced sensitization to taxol was associated with activation of apoptosis pathway, which is demonstrated by increased apoptotic index, DNA laddering, sub-G1 phase of the cell cycle, as well as cleaved-PARP and Caspase 3. Furthermore, c-Jun N-terminal kinase (JNK), one of the common pathways responsible for taxol-induced apoptosis, was also activated in the si-Id-1 transfected cells. Inhibition of JNK activity by a specific inhibitor, SP600125, blocked the si-Id-1-induced sensitivity to taxol. These results indicate that increased Id-1 expression in prostate cancer cells may play a protective role against apoptosis, and downregulation of Id-1 may be a potential target to increase sensitivity of taxol-induced apoptosis in prostate cancer cells. (c) 2005 Wiley-Liss, Inc. PMID: 16287090 [PubMed - as supplied by publisher]

Pre-Treatment Nomogram for Disease-Specific Survival of Patients with Chemotherapy-Naive Androgen Independent Prostate Cancer.


Pre-Treatment Nomogram for Disease-Specific Survival of Patients with Chemotherapy-Naive Androgen Independent Prostate Cancer.
Related Articles Pre-Treatment Nomogram for Disease-Specific Survival of Patients with Chemotherapy-Naive Androgen Independent Prostate Cancer. Eur Urol. 2006 Jan 6; Authors: Svatek R, Karakiewicz PI, Shulman M, Karam J, Perrotte P, Benaim E OBJECTIVE: Our objective was to develop a nomogram that predicts the probability of cancer-specific survival in men with untreated androgen-independent prostate cancer (AIPC). METHODS: AIPC was diagnosed in 129 consecutive patients between 1989 and 2002. No patient received cytotoxic chemotherapy. Univariate and multivariate Cox regression models were used to test the association between prostate-specific antigen (PSA) level at initiation of androgen deprivation, PSA doubling time (PSADT), PSA nadir on androgen deprivation therapy (ADT), time from ADT to AIPC, and AIPC-specific mortality. Multivariate regression coefficients were then used to develop a nomogram predicting AIPC-specific survival at 12-60 mo after AIPC diagnosis. Two-hundred bootstrap resamples were used to internally validate the nomogram. RESULTS: AIPC-specific mortality was recorded in 74 of 129 patients (57.4%). Other-cause mortality was recorded in 7 men (5.4%). Median overall survival was 52.0 mo (mean, 36.0 mo) and median AIPC-specific survival was 54.0 mo (mean, 35.0 mo). In univariate regression models, all variables were significant predictors of AIPC-specific survival (p</=0.02). In multivariate models, PSADT and time from androgen deprivation to AIPC remained statistically significant (p</=0.004). Bootstrap-corrected predictive accuracy of the nomogram was 80.9% versus 74.9% for our previous model. CONCLUSIONS: A nomogram predicting AIPC-specific survival is between 13% and 14% more accurate than previous nomograms and 6% more accurate than tree regression-based predictions obtained from the same data. Moreover, a nomogram approach combines several advantages, such as user-friendly interface and precise estimation of individual recurrence probability at several time points after AIPC diagnosis, which all patients deserve to know and all treating physicians need to know. PMID: 16423446 [PubMed - as supplied by publisher]

January 21, 2006

Dr. Manny: Expert Advice on Prostate Cancer


Dr. Manny: Expert Advice on Prostate Cancer
FOX News - Jan 17, 2006... tests for prostate cancer, but none of these have been shown to be more effective in screening that PSA and DRE. Are there any alternative treatments or ...

Prostate Cancer Screening - Intra-operative prostate examination: predictive value and effect on margin status.


Intra-operative prostate examination: predictive value and effect on margin status.
Related Articles Intra-operative prostate examination: predictive value and effect on margin status. BJU Int. 2005 Nov;96(7):1005-8 Authors: Rapp DE, Orvieto MA, Lucioni A, Gong EM, Shalhav AL, Brendler CB OBJECTIVE: To evaluate the ability of intra-operative prostate examination (IOPE) to predict extraprostatic extension (EPE) and its effect on margin status in the region of the neurovascular bundle (NVB) when combined with wide excision. PATIENTS AND METHODS: We retrospectively reviewed 403 patients with clinical stage T1c prostate adenocarcinoma undergoing radical retropubic prostatectomy (RRP). All patients had IOPE during RRP, and those with palpable abnormalities in the region of the NVB underwent wide excision. Pathological outcomes were analysed. RESULTS: Of 403 patients, 49 (12%) had a palpable abnormality in the region of the NVB. After wide excision, 18 (37%) of these 49 patients were found to have EPE at the site of the palpable abnormality; with wide excision of the NVB, only one of these 18 patients (6%) had a corresponding positive surgical margin (PSM). In 354 patients with a normal IOPE and who underwent bilateral NVB preservation, 30 were found to have EPE in the region of the NVB. The PSM rate in this subset was 23% (seven of 30). The positive predictive value of IOPE for detecting EPE was 37%. CONCLUSION: IOPE detects abnormalities in 12% of patients with preoperative stage T1c prostate cancer. Although the predictive value of this test is limited, IOPE may decrease PSMs in a subset of patients with EPE in the region of the NVB. The present study reaffirms the value of IOPE for assessing the risk of extraprostatic disease, and for guiding surgical management. PMID: 16225517 [PubMed - indexed for MEDLINE]

Combined Inhibitory Effects of Curcumin and Phenethyl Isothiocyanate on the Growth of Human PC-3 Prostate Xenografts in Immunodeficient Mice.


Combined Inhibitory Effects of Curcumin and Phenethyl Isothiocyanate on the Growth of Human PC-3 Prostate Xenografts in Immunodeficient Mice.
Combined Inhibitory Effects of Curcumin and Phenethyl Isothiocyanate on the Growth of Human PC-3 Prostate Xenografts in Immunodeficient Mice. Cancer Res. 2006 Jan 15;66(2):613-621 Authors: Khor TO, Keum YS, Lin W, Kim JH, Hu R, Shen G, Xu C, Gopalakrishnan A, Reddy B, Zheng X, Conney AH, Kong AN Earlier studies using prostate cancer cells in culture showed that phenethyl isothiocyanate (PEITC) and curcumin have significant chemopreventive and possibly chemotherapeutic effects. However, their in vivo effects are still lacking. Hence, this study was undertaken to determine the possible in vivo efficacy of prostate cancer-prevention as well as cancer-therapeutic treatment by PEITC and curcumin alone or in combination. We evaluated the effects on tumor growth in vivo, using NCr immunodeficient (nu/nu) mice bearing s.c. xenografts of PC-3 human prostate cancer cells. Molecular biomarkers representing proliferation and apoptosis were determined. Continued i.p. injection of curcumin or PEITC (6 and 5 mumol; thrice a week for 28 days), beginning a day before tumor implantation significantly retarded the growth of PC-3 xenografts. Combination of i.p. administration of PEITC (2.5 mumol) and curcumin (3 mumol) showed stronger growth-inhibitory effects. Next, we evaluated the cancer-therapeutic potential of curcumin and PEITC in mice with well-established tumors, and the results showed that PEITC or curcumin alone had little effect, whereas combination of curcumin and PEITC significantly reduced the growth of PC-3 xenografts. Immunohistochemistry staining and Western blot analysis revealed that the inhibition of Akt and nuclear factor-kappaB signaling pathways could contribute to the inhibition of cell proliferation and induction of apoptosis. Taken together, our results show that PEITC and curcumin alone or in combination possess significant cancer-preventive activities in the PC-3 prostate tumor xenografts. Furthermore, we found that combination of PEITC and curcumin could be effective in the cancer-therapeutic treatment of prostate cancers. (Cancer Res 2006; 66(2): 613-21). PMID: 16423986 [PubMed - as supplied by publisher]

Contact stimulation of prostate cancer cell migration: the role of gap junctional coupling and migration stimulated by heterotypic cell-to-cell contacts in determination of the metastatic phenotype of Dunning rat prostate cancer cells.


Contact stimulation of prostate cancer cell migration: the role of gap junctional coupling and migration stimulated by heterotypic cell-to-cell contacts in determination of the metastatic phenotype of Dunning rat prostate cancer cells.
Related Articles Contact stimulation of prostate cancer cell migration: the role of gap junctional coupling and migration stimulated by heterotypic cell-to-cell contacts in determination of the metastatic phenotype of Dunning rat prostate cancer cells. Biol Cell. 2005 Dec;97(12):893-903 Authors: Miekus K, Czernik M, Sroka J, Czyz J, Madeja Z BACKGROUND INFORMATION: Motile activity of tumour cells is regarded as a critical factor determining their metastatic potential. We have shown previously that contrary to the majority of normal cells, homotypic contacts between some tumour cells, among them low metastatic (AT-2) and highly metastatic (MAT-LyLu) rat prostate cancer cells, increase the speed of their movements. The aim of the present study was to determine the effect of heterotypic cell-to-cell contacts on the migration of rat prostate cancer cells differing in metastatic potential, and to correlate it with the intensity of homo- and heterologous gap junctional coupling. RESULTS: MAT-LyLu and AT-2 cells moving on the surface of fibroblasts displayed significantly greater cell displacement than those moving on plastic substrata. This effect correlated with the polarization (contact guidance) and increased speed of cell movements. However, in contrast with the migration on plastic substrata, where MAT-LyLu cells displayed considerably higher motility than AT-2 cells, no differences between both cell lines were observed on the surface of fibroblasts. On the other hand, in contrast with AT-2, Mat-LyLu cells displayed extensive homologous coupling mediated by connexin43 and were able to couple with normal fibroblasts. CONCLUSION: Heterotypic contacts between migrating prostatic cancer cells and normal fibroblasts can strongly stimulate their migration during invasion; however, this effect does not correlate with the gap junctional coupling between cancer cells and normal fibroblasts. PMID: 15907197 [PubMed - indexed for MEDLINE]

Telomerase vaccination has no detectable effect on SCID-repopulating and colony-forming activities in the bone marrow of cancer patients.


Telomerase vaccination has no detectable effect on SCID-repopulating and colony-forming activities in the bone marrow of cancer patients.
Related Articles Telomerase vaccination has no detectable effect on SCID-repopulating and colony-forming activities in the bone marrow of cancer patients. Exp Hematol. 2005 Nov;33(11):1275-80 Authors: Danet-Desnoyers GA, Luongo JL, Bonnet DA, Domchek SM, Vonderheide RH OBJECTIVES: The telomerase reverse transcriptase hTERT is a widely expressed tumor-associated antigen recognized by cytotoxic T lymphocytes (CTL). We have previously shown that vaccination of cancer patients against hTERT induces functional anti-tumor CTL in vivo, but it is not known whether hTERT vaccination harms normal cells expressing the enzyme, especially hematopoietic stem cells and progenitors. PATIENTS AND METHODS: We employed colony-forming cell (CFC) assays, long-term in vitro cultures, and nonobese diabetic/severe combined immunodeficient (NOD/SCID) repopulation studies to evaluate the effects of hTERT vaccination on hematopoietic progenitors and stem cells in cancer patients following treatment. RESULTS: Using bone marrow samples obtained from cancer patients before and after vaccination, we found that there was no significant decline in the frequency of granulocyte, macrophage or erythroid CFCs using CFC assays or long-term in vitro cultures. In NOD/SCID mice, human hematopoietic reconstitution was easily detected, without quantitative or qualitative differences between pre- and postvaccine samples. CONCLUSION: These findings suggest that induction of tumor-lytic hTERT-specific T cells in vivo by vaccination does not result in a detectable decline in hematopoietic potential despite the expression of hTERT and major histocompatibility complex class I in bone marrow progenitors and stem cells. Thus, even for self-antigens such as telomerase, tumor immunity does not necessarily involve autoimmunity in normal tissues that share the target. PMID: 16263411 [PubMed - indexed for MEDLINE]

Efficacy of sildenafil citrate in men with erectile dysfunction following radical prostatectomy: a systematic review of clinical data.


Efficacy of sildenafil citrate in men with erectile dysfunction following radical prostatectomy: a systematic review of clinical data.
Efficacy of sildenafil citrate in men with erectile dysfunction following radical prostatectomy: a systematic review of clinical data. J Sex Med. 2005 Sep;2(5):658-67 Authors: Montorsi F, McCullough A Introduction. Radical prostatectomy is a frequently used treatment option for prostate cancer; however, prostatectomy is often associated with significant morbidity, including erectile dysfunction (ED). Aim. To analyze the efficacy of sildenafil citrate in treating ED after radical prostatectomy. Materials and Methods. MEDLINE and CANCERLIT (1998 to January 2004) were searched for English language articles using the key words prostatectomy, sildenafil, and phosphodiesterase inhibitors. Eleven studies fulfilled the inclusion criteria: primary, discrete data sets of postprostatectomy patients with ED treated with sildenafil monotherapy. Results. Sample sizes ranged from 13 to 198 (mean age, 61 +/- 3 years). Treatment durations were 4 weeks (or more than four doses) to 1 year, and sildenafil dosing was in the recommended range (25-100 mg). Seven studies reported a response rate (range, 14%-53%) for an end point consistent with the primary analysis outcome (erection sufficient for vaginal intercourse); the combined estimate of probability of response was 35% (95% confidence interval [CI], 24%-48%). There was strong evidence for a lower response rate after non-nerve-sparing (range, 0%-15%) versus nerve-sparing surgery (range, 35%-75%; combined odds ratio [OR] = 12.1; 95% CI, 5.5-26.6) but not after unilateral (range, 10%-80%) versus bilateral nerve-sparing surgery (range, 46%-72%; combined OR = 2.21; 95% CI, 0.75-6.54). Conclusions. The results of these studies demonstrate that with sildenafil, more than one third of patients with postprostatectomy ED achieved erection sufficient for intercourse. The odds of responding improved 12-fold with preservation of at least one neurovascular bundle. Early treatment failure does not necessarily imply lack of efficacy in the future, and patients should be encouraged to continue trying sildenafil, titrating up to 100 mg as needed. Montorsi F, and McCullough A. Efficacy of sildenafil citrate in men with erectile dysfunction following radical prostatectomy: a systematic review of clinical data. J Sex Med 2005;2:658-667. PMID: 16422824 [PubMed - in process]

Expanding the therapeutic index of radiation therapy by combining in situ gene therapy in the treatment of prostate cancer.


Expanding the therapeutic index of radiation therapy by combining in situ gene therapy in the treatment of prostate cancer.
Related Articles Expanding the therapeutic index of radiation therapy by combining in situ gene therapy in the treatment of prostate cancer. Technol Cancer Res Treat. 2006 Feb;5(1):23-36 Authors: Tetzlaff MT, Teh BS, Timme TL, Fujita T, Satoh T, Tabata KI, Mai WY, Vlachaki MT, Amato RJ, Kadmon D, Miles BJ, Ayala G, Wheeler TM, Aguilar-Cordova E, Thompson TC, Butler EB The advances in radiotherapy (3D-CRT, IMRT) have enabled high doses of radiation to be delivered with the least possible associated toxicity. However, the persistence of cancer (local recurrence after radiotherapy) despite these increased doses as well as distant failure suggesting the existence of micro-metastases, especially in the case of higher risk disease, have underscored the need for continued improvement in treatment strategies to manage local and micro-metastatic disease as definitively as possible. This has prompted the idea that an increase in the therapeutic index of radiotherapy might be achieved by combining it with in situ gene therapy. The goal of these combinatorial therapies is to maximize the selective pressure against cancer cell growth while minimizing treatment-associated toxicity. Major efforts utilizing different gene therapy strategies have been employed in conjunction with radiotherapy. We reviewed our and other published clinical trials utilizing this combined radio-genetherapy approach including their associated pre-clinical in vitro and in vivo models. The use of in situ gene therapy as an adjuvant to radiation therapy dramatically reduced cell viability in vitro and tumor growth in vivo. No significant worsening of the toxicities normally observed in single-modality approaches were identified in Phase I/II clinical studies. Enhancement of both local and systemic T-cell activation was noted with this combined approach suggesting anti-tumor immunity. Early clinical outcome including biochemical and biopsy data was very promising. These results demonstrate the increased therapeutic efficacy achieved by combining in situ gene therapy with radiotherapy in the management of local prostate cancer. The combined approach maximizes tumor control, both local-regional and systemic through radio-genetherapy induced cytotoxicity and anti-tumor immunity. PMID: 16417399 [PubMed - in process]

Telomerase vaccination has no detectable effect on SCID-repopulating and colony-forming activities in the bone marrow of cancer patients.


Telomerase vaccination has no detectable effect on SCID-repopulating and colony-forming activities in the bone marrow of cancer patients.
Related Articles Telomerase vaccination has no detectable effect on SCID-repopulating and colony-forming activities in the bone marrow of cancer patients. Exp Hematol. 2005 Nov;33(11):1275-80 Authors: Danet-Desnoyers GA, Luongo JL, Bonnet DA, Domchek SM, Vonderheide RH OBJECTIVES: The telomerase reverse transcriptase hTERT is a widely expressed tumor-associated antigen recognized by cytotoxic T lymphocytes (CTL). We have previously shown that vaccination of cancer patients against hTERT induces functional anti-tumor CTL in vivo, but it is not known whether hTERT vaccination harms normal cells expressing the enzyme, especially hematopoietic stem cells and progenitors. PATIENTS AND METHODS: We employed colony-forming cell (CFC) assays, long-term in vitro cultures, and nonobese diabetic/severe combined immunodeficient (NOD/SCID) repopulation studies to evaluate the effects of hTERT vaccination on hematopoietic progenitors and stem cells in cancer patients following treatment. RESULTS: Using bone marrow samples obtained from cancer patients before and after vaccination, we found that there was no significant decline in the frequency of granulocyte, macrophage or erythroid CFCs using CFC assays or long-term in vitro cultures. In NOD/SCID mice, human hematopoietic reconstitution was easily detected, without quantitative or qualitative differences between pre- and postvaccine samples. CONCLUSION: These findings suggest that induction of tumor-lytic hTERT-specific T cells in vivo by vaccination does not result in a detectable decline in hematopoietic potential despite the expression of hTERT and major histocompatibility complex class I in bone marrow progenitors and stem cells. Thus, even for self-antigens such as telomerase, tumor immunity does not necessarily involve autoimmunity in normal tissues that share the target. PMID: 16263411 [PubMed - indexed for MEDLINE]

RTOG study shows improved survival for prostate cancer patients given adjuvant goserelin.


RTOG study shows improved survival for prostate cancer patients given adjuvant goserelin.
Related Articles RTOG study shows improved survival for prostate cancer patients given adjuvant goserelin. Oncology (Williston Park). 2005 Aug;19(9):1142 Authors: PMID: 16402596 [PubMed - indexed for MEDLINE]

Multidisciplinary treatment of synchronous primary rectal and prostate cancers.


Multidisciplinary treatment of synchronous primary rectal and prostate cancers.
Related Articles Multidisciplinary treatment of synchronous primary rectal and prostate cancers. Nat Clin Pract Oncol. 2005 May;2(5):271-4; quiz 1 p following 274 Authors: Colonias A, Farinash L, Miller L, Jones S, Medich DS, Greenberg L, Miller R, Parda DS BACKGROUND: A 58-year-old Caucasian man with a history of irritable bowel syndrome and occasional rectal bleeding presented with a 4-week history of progressive, bright red blood per rectum. A digital rectal examination revealed a 3 cm distal, midrectal mass. Laboratory tests showed an elevated serum prostate-specific antigen of 32 ng/ml but other physical and medical examinations were unremarkable. INVESTIGATIONS: Digital rectal examination, colonoscopy, rectal mass biopsy, endorectal ultrasound, transrectal ultrasound-guided prostate biopsy, CT scan and MRI. DIAGNOSIS: Clinical stage III (T3N1M0), moderately differentiated adenocarcinoma of the rectum and clinical stage II (T1cN0M0) adenocarcinoma of the prostate. MANAGEMENT: Intensity-modulated radiation therapy, chemoradiation, chemotherapy, hormone therapy and surgery. PMID: 16264963 [PubMed - indexed for MEDLINE]

Histopathological outcome in 167 patients operated on with radical retropubic prostatectomy.


Histopathological outcome in 167 patients operated on with radical retropubic prostatectomy.
Related Articles Histopathological outcome in 167 patients operated on with radical retropubic prostatectomy. Scand J Urol Nephrol. 2005;39(4):283-8 Authors: Solberg A, Viset T, Haugen OA, Mjønes J, Klepp O, Angelsen A OBJECTIVE: To evaluate the histopathological outcome in patients with prostate cancer operated on with radical retropubic prostatectomy. MATERIAL AND METHODS: A total of 167 patients with clinically organ-localized prostate cancer treated with open radical retropubic prostatectomy between 1996 and 2001 were divided into three equally sized consecutive cohorts (cohorts I-III). The prostatectomy specimens were re-examined by two pathologists with respect to pathological tumour stage, tumour grade and surgical tumour margins. RESULTS: The mean preoperative prostate-specific antigen (PSA) value was statistically significantly higher in cohort I compared to cohorts II and III: 13.2, 9.0 and 8.5 ng/ml, respectively (p<0.05). The incidence of locally advanced (pT3a-3b) tumours was 44% in cohort I and 20% in both cohorts II and III (p<0.05). The incidence of positive tumour margins was 58% in cohort I, compared to 30% in cohort II and 13% in cohort III (p<0.05). The incidence of positive intracapsular tumour margins was 55% in cohort I, compared to 25% in cohort II and 8.9% in cohort III (p<0.05). The incidence of positive tumour margins in the pT2 tumours in cohorts I-III was 57%, 26% and 8.9%, respectively (p<0.05). Cohort III had significantly more low-grade tumours (Gleason score 4-6; 58.9%) compared to cohorts I (31.5%) and II (34%). There was a higher incidence of Gleason score >or=7 in the pT3 tumours compared to the pT2 tumours (80% vs 46%) and in margin-positive compared to -negative tumours (69.6% vs 48.6%) (p<0.05). CONCLUSIONS: The decline in pT3 tumours and positive tumour margins between cohorts I-III is probably due to a gradually more strict selection of patients for radical retropubic prostatectomy. The successive reduction in positive intracapsular tumour margins is most likely due to an improved surgical technique. PMID: 16159748 [PubMed - indexed for MEDLINE]

January 18, 2006

Health Calendar


Health Calendar
Quad City Times, IA - Jan 12, 2006... Mona Alqulali will discuss common conditions that affect younger women and available treatments. ... Acupuncture: Your Alternative to Pain Relief. ... Prostate Cancer. ...

Prostate Cancer Screening - The influence of extent of surgical margin positivity on prostate specific antigen recurrence.


The influence of extent of surgical margin positivity on prostate specific antigen recurrence.
Related Articles The influence of extent of surgical margin positivity on prostate specific antigen recurrence. J Clin Pathol. 2005 Oct;58(10):1028-32 Authors: Emerson RE, Koch MO, Jones TD, Daggy JK, Juliar BE, Cheng L BACKGROUND: Positive surgical margins are an adverse prognostic factor in patients undergoing prostatectomy for prostate cancer. The extent of margin positivity varies and its influence on clinical outcome is uncertain. AIMS: To evaluate the linear extent of margin positivity and the number and location of positive sites as prognostic indicators in a series of prostatectomy specimens evaluated with the whole mount technique. METHODS: Eighty six consecutive margin positive prostatectomy specimens were evaluated, and all pathology data were collected prospectively. The linear extent of margin positivity was measured with an ocular micrometer and the total extent of all positive sites was summed. The total number of sites with positive margins and anatomical sites of the positive margins were analysed. RESULTS: The linear extent of margin positivity ranged from 0.01 to 68 mm (mean, 6.8; median, 3.0) and was associated with prostate specific antigen (PSA) recurrence in univariate logistic regression (p = 0.031). In addition, the extent of margin positivity weakly correlated with preoperative PSA (p = 0.017) and tumour volume (p = 0.013), but not with age, prostate weight, Gleason score, pathological stage, or perineural invasion. The total number of positive sites was significantly higher in patients with PSA recurrence (p = 0.037). The location of the positive margin site was not associated with PSA recurrence. The extent of margin positivity correlated with PSA recurrence in univariate analysis, although it had only marginal predictive value when adjusted for Gleason score (p = 0.076). CONCLUSIONS: The extent of margin positivity correlates with PSA recurrence in univariate analysis, although it has no predictive value independent of Gleason score. PMID: 16189146 [PubMed - indexed for MEDLINE]

Rationale for zoledronic acid therapy in men with hormone-sensitive prostate cancer with or without bone metastasis.


Rationale for zoledronic acid therapy in men with hormone-sensitive prostate cancer with or without bone metastasis.
Rationale for zoledronic acid therapy in men with hormone-sensitive prostate cancer with or without bone metastasis. Urol Oncol. 2006 January - February;24(1):4-12 Authors: Saad F, McKiernan J, Eastham J Men with prostate cancer are at risk for bone loss and skeletal complications throughout the course of their disease. Bone loss is prevalent in many men with prostate cancer at initial diagnosis, and initiating androgen deprivation therapy results in accelerated bone resorption, leading to bone loss and an increased risk of fracture. These men are also at high risk for disease progression and bone metastases that can result in significant skeletal morbidity, including pathologic fracture, spinal cord compression, and debilitating bone pain requiring additional therapy. Excessive osteoclast activity plays a central role in the pathophysiology of bone disease at each stage of prostate cancer disease progression. Zoledronic acid, a highly potent inhibitor of osteoclast-mediated bone resorption, has increased bone mineral density in men receiving androgen deprivation therapy and is the only bisphosphonate that has shown statistically significant reductions in skeletal morbidity in patients with bone metastases from prostate cancer. Furthermore, preclinical evidence suggests that zoledronic acid has antitumor activity in prostate cancer models. Recently, a treatment algorithm was developed by the 3rd International Consultation on Prostate Cancer recommending the use of zoledronic acid for the prevention of skeletal complications in patients with bone metastases from prostate cancer, regardless of their hormone status, and for the prevention of treatment-induced bone loss in patients without evidence of bone metastases. According to this algorithm, zoledronic acid should be considered for the prevention of skeletal morbidity in patients with prostate cancer throughout their treatment continuum. PMID: 16414486 [PubMed - as supplied by publisher]

Identification of a positive Cis-element upstream of human NKX3.1 gene.


Identification of a positive Cis-element upstream of human NKX3.1 gene.
Related Articles Identification of a positive Cis-element upstream of human NKX3.1 gene. Acta Biochim Biophys Sin (Shanghai). 2005 Nov;37(11):773-8 Authors: Jiang AL, Zhang PJ, Hu XY, Chen WW, Kong F, Liu ZF, Yuan HQ, Zhang JY NKX3.1 is a prostate-specific homeobox gene related to prostate development and prostate cancer. In this work, we aimed to identify precisely the functional cis-element in the 197 bp region (from -1032 to -836 bp) of the NKX3.1 promoter (from -1032 to +8 bp), which was previously identified to present positive regulatory activity on NKX3.1 expression, by deletion mutagenesis analysis and electrophoretic mobility shift assay (EMSA). A 16 bp positive cis-element located between -920 and -905 bp upstream of the NKX3.1 gene was identified by deletion mutation analysis and proved to be a functional positive cis-element by EMSA. It will be important to further study the functions and regulatory mechanisms of this positive cis-element in NKX3.1 gene expression. PMID: 16270157 [PubMed - indexed for MEDLINE]

Telomerase vaccination has no detectable effect on SCID-repopulating and colony-forming activities in the bone marrow of cancer patients.


Telomerase vaccination has no detectable effect on SCID-repopulating and colony-forming activities in the bone marrow of cancer patients.
Related Articles Telomerase vaccination has no detectable effect on SCID-repopulating and colony-forming activities in the bone marrow of cancer patients. Exp Hematol. 2005 Nov;33(11):1275-80 Authors: Danet-Desnoyers GA, Luongo JL, Bonnet DA, Domchek SM, Vonderheide RH OBJECTIVES: The telomerase reverse transcriptase hTERT is a widely expressed tumor-associated antigen recognized by cytotoxic T lymphocytes (CTL). We have previously shown that vaccination of cancer patients against hTERT induces functional anti-tumor CTL in vivo, but it is not known whether hTERT vaccination harms normal cells expressing the enzyme, especially hematopoietic stem cells and progenitors. PATIENTS AND METHODS: We employed colony-forming cell (CFC) assays, long-term in vitro cultures, and nonobese diabetic/severe combined immunodeficient (NOD/SCID) repopulation studies to evaluate the effects of hTERT vaccination on hematopoietic progenitors and stem cells in cancer patients following treatment. RESULTS: Using bone marrow samples obtained from cancer patients before and after vaccination, we found that there was no significant decline in the frequency of granulocyte, macrophage or erythroid CFCs using CFC assays or long-term in vitro cultures. In NOD/SCID mice, human hematopoietic reconstitution was easily detected, without quantitative or qualitative differences between pre- and postvaccine samples. CONCLUSION: These findings suggest that induction of tumor-lytic hTERT-specific T cells in vivo by vaccination does not result in a detectable decline in hematopoietic potential despite the expression of hTERT and major histocompatibility complex class I in bone marrow progenitors and stem cells. Thus, even for self-antigens such as telomerase, tumor immunity does not necessarily involve autoimmunity in normal tissues that share the target. PMID: 16263411 [PubMed - indexed for MEDLINE]

Recent neuroanatomical studies on the neurovascular bundle of the prostate and cavernosal nerves: clinical reflections on radical prostatectomy.


Recent neuroanatomical studies on the neurovascular bundle of the prostate and cavernosal nerves: clinical reflections on radical prostatectomy.
Related Articles Recent neuroanatomical studies on the neurovascular bundle of the prostate and cavernosal nerves: clinical reflections on radical prostatectomy. Asian J Androl. 2005 Dec;7(4):339-49 Authors: Yucel S, Erdogru T, Baykara M The neurovascular bundle of the prostate and cavernosal nerves have been used to describe the same structure ever since the publication of the first studies on the neuroanatomy of the lower urogenital tract of men, studies that were prompted by postoperative complications arising from radical prostatectomy. In urological surgery every effort is made to preserve or restore the neurovascular bundle of the prostate to avoid erectile dysfunction (ED). However, the postoperative potency rates are yet to be satisfactory despite all advancements in radical prostatectomy technique. As the technology associated with urological surgery develops and topographical studies on neuroanatomy are cultivated, new observations seriously challenge the classical teachings on the topography of the neurovascular bundle of the prostate and the cavernosal nerves. The present review revisits the classical and most recent data on the topographical anatomy of the neurovascular bundle of the prostate and cavernosal nerves and their implications on radical prostatectomy techniques. PMID: 16281080 [PubMed - indexed for MEDLINE]

The Actual Value of the Surgical Margin Status as a Predictor of Disease Progression in Men with Early Prostate Cancer.


The Actual Value of the Surgical Margin Status as a Predictor of Disease Progression in Men with Early Prostate Cancer.
The Actual Value of the Surgical Margin Status as a Predictor of Disease Progression in Men with Early Prostate Cancer. Eur Urol. 2006 Jan 6; Authors: Vis AN, Schröder FH, van der Kwast TH OBJECTIVES: The surgical margin status after radical prostatectomy for prostate cancer has long been considered a powerful prognostic factor, as well as an important risk factor for local recurrent disease after radical prostatectomy. In this study, a critical analysis of the predictive value of the surgical margin status was performed. METHODS: A well-described cohort of 281 participants of a population-based randomized screening trial who underwent radical prostatectomy between 1994 and 2000 was analyzed. Besides pathologic tumor stage, Gleason score, percentage of high-grade cancer, and tumor volume, the prognostic value of the surgical margin status for disease outcome (prostate-specific antigen [PSA] relapse, local recurrence) was statistically evaluated. Specifically, site ('apical' or 'circumferential') and extent of surgical margin negativity ('negative', or 'close') or positivity ('focal' or 'extensive') was assessed. RESULTS: At a median follow-up of 7 yr (range, 5-120 mo), 39 (13.9%) and 7 (2.5%) men had biochemical failure (PSA >/=0.1ng/ml), and local relapse, respectively. The surgical margin status was positive in 66 (23.5%), with 26 (9.3%) at the prostatic apex. The margin status was an independent statistically significant risk factor for biochemical relapse, though not for local relapse. Of those with positive margins, 22 (33.3%) had PSA relapse and 4 (6.1%) had local recurrence, whereas these figures were 17 (7.9%) and 3 (1.4%) for those with a negative surgical margin, respectively. The extent of margin positivity was not predictive of PSA relapse nor was the site of the surgical margin. CONCLUSIONS: In surgically treated prostate cancer, the surgical margin status has, although being a statistically significant prognostic factor, only limited predictive value for PSA relapse and local recurrent disease. The majority of men with (extensive) positive surgical margins will not experience PSA relapse nor local disease progression, even in absence of adjuvant radiotherapy. So, cases with a positive margin of resection may still be cured, although the procedure in itself was not 'radical'. PMID: 16413660 [PubMed - as supplied by publisher]

Telomerase vaccination has no detectable effect on SCID-repopulating and colony-forming activities in the bone marrow of cancer patients.


Telomerase vaccination has no detectable effect on SCID-repopulating and colony-forming activities in the bone marrow of cancer patients.
Related Articles Telomerase vaccination has no detectable effect on SCID-repopulating and colony-forming activities in the bone marrow of cancer patients. Exp Hematol. 2005 Nov;33(11):1275-80 Authors: Danet-Desnoyers GA, Luongo JL, Bonnet DA, Domchek SM, Vonderheide RH OBJECTIVES: The telomerase reverse transcriptase hTERT is a widely expressed tumor-associated antigen recognized by cytotoxic T lymphocytes (CTL). We have previously shown that vaccination of cancer patients against hTERT induces functional anti-tumor CTL in vivo, but it is not known whether hTERT vaccination harms normal cells expressing the enzyme, especially hematopoietic stem cells and progenitors. PATIENTS AND METHODS: We employed colony-forming cell (CFC) assays, long-term in vitro cultures, and nonobese diabetic/severe combined immunodeficient (NOD/SCID) repopulation studies to evaluate the effects of hTERT vaccination on hematopoietic progenitors and stem cells in cancer patients following treatment. RESULTS: Using bone marrow samples obtained from cancer patients before and after vaccination, we found that there was no significant decline in the frequency of granulocyte, macrophage or erythroid CFCs using CFC assays or long-term in vitro cultures. In NOD/SCID mice, human hematopoietic reconstitution was easily detected, without quantitative or qualitative differences between pre- and postvaccine samples. CONCLUSION: These findings suggest that induction of tumor-lytic hTERT-specific T cells in vivo by vaccination does not result in a detectable decline in hematopoietic potential despite the expression of hTERT and major histocompatibility complex class I in bone marrow progenitors and stem cells. Thus, even for self-antigens such as telomerase, tumor immunity does not necessarily involve autoimmunity in normal tissues that share the target. PMID: 16263411 [PubMed - indexed for MEDLINE]

Is dehydroepiandrosterone a hormone?


Is dehydroepiandrosterone a hormone?
Related Articles Is dehydroepiandrosterone a hormone? J Endocrinol. 2005 Nov;187(2):169-96 Authors: Labrie F, Luu-The V, B langer A, Lin SX, Simard J, Pelletier G, Labrie C Dehydroepiandrosterone (DHEA) is not a hormone but it is a very important prohormone secreted in large amounts by the adrenals in humans and other primates, but not in lower species. It is secreted in larger quantities than cortisol and is present in the blood at concentrations only second to cholesterol. All the enzymes required to transform DHEA into androgens and/or estrogens are expressed in a cell-specific manner in a large series of peripheral target tissues, thus permitting all androgen-sensitive and estrogen-sensitive tissues to make locally and control the intracellular levels of sex steroids according to local needs. This new field of endocrinology has been called intracrinology. In women, after menopause, all estrogens and almost all androgens are made locally in peripheral tissues from DHEA which indirectly exerts effects, among others, on bone formation, adiposity, muscle, insulin and glucose metabolism, skin, libido and well-being. In men, where the secretion of androgens by the testicles continues for life, the contribution of DHEA to androgens has been best evaluated in the prostate where about 50% of androgens are made locally from DHEA. Such knowledge has led to the development of combined androgen blockade (CAB), a treatment which adds a pure anti-androgen to medical (GnRH agonist) or surgical castration in order to block the access of the androgens made locally to the androgen receptor. In fact, CAB has been the first treatment demonstrated to prolong life in advanced prostate cancer while recent data indicate that it can permit long-term control and probably cure in at least 90% of cases of localized prostate cancer. The new field of intracrinology or local formation of sex steroids from DHEA in target tissues has permitted major advances in the treatment of the two most frequent cancers, namely breast and prostate cancer, while its potential use as a physiological HRT could well provide a physiological balance of androgens and estrogens, thus offering exciting possibilities for women's health at menopause. PMID: 16293766 [PubMed - indexed for MEDLINE]

Does docetaxel plus prednisone prolong the survival of men with metastatic hormone-refractory prostate cancer?


Does docetaxel plus prednisone prolong the survival of men with metastatic hormone-refractory prostate cancer?
Related Articles Does docetaxel plus prednisone prolong the survival of men with metastatic hormone-refractory prostate cancer? Nat Clin Pract Oncol. 2005 Feb;2(2):68-9 Authors: Protheroe A PMID: 16264873 [PubMed - indexed for MEDLINE]

Down-regulation of cyclooxygenase-2 and telomerase activity by beta-lapachone in human prostate carcinoma cells.


Down-regulation of cyclooxygenase-2 and telomerase activity by beta-lapachone in human prostate carcinoma cells.
Related Articles Down-regulation of cyclooxygenase-2 and telomerase activity by beta-lapachone in human prostate carcinoma cells. Pharmacol Res. 2005 Jun;51(6):553-60 Authors: Lee JH, Cheong J, Park YM, Choi YH Beta-lapachone, the product of a tree Tabebuia avellanedae from South America, is known to exhibit various pharmacologic properties, the mechanisms of which are poorly understood. In the present study, we investigated further possible mechanisms by which beta-lapachone exerts its anti-proliferative action in cultured human prostate carcinoma DU145 cells. Exposure of DU145 cells to beta-lapachone resulted in growth inhibition and induction of apoptosis in a dose-dependent manner as measured by MTT assay, fluorescent microscopy, and flow-cytometry analysis. The increase in apoptosis was associated with a dose-dependent up-regulation in pro-apoptotic Bax expression, down-regulation of anti-apoptotic Bcl-2, and proteolytic activation of caspase-3 protease. We found beta-lapachone decreased the levels of cyclooxygenase (COX)-2 mRNA and protein expression without significant changes in the levels of COX-1, which was correlated with a decrease in prostaglandin E2 (PGE2) synthesis. Furthermore, beta-lapachone treatment markedly inhibited the activity of telomerase in a dose-dependent fashion. Additionally, the expression of human telomerase reverse transcriptase (hTERT), a main determinant of the telomerase enzymatic activity, was progressively down-regulated by beta-lapachone treatment. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of beta-lapachone. PMID: 15829436 [PubMed - indexed for MEDLINE]

January 13, 2006

Medical News Story


Medical News Story
News-Medical.Net - Doctors in Canada are studying the effectiveness of permanent radiation seed implants following lumpectomy as an alternative to whole or partial breast irradiation for early-stage breast cancer patients, according to a study published in the January

Prostate Cancer Screening - Use of tissue recombination to predict phenotypes of transgenic mouse models of prostate carcinoma.


Use of tissue recombination to predict phenotypes of transgenic mouse models of prostate carcinoma.
Related Articles Use of tissue recombination to predict phenotypes of transgenic mouse models of prostate carcinoma. Lab Invest. 2005 Sep;85(9):1086-103 Authors: Ishii K, Shappell SB, Matusik RJ, Hayward SW Transgenic mouse models of cancer represent a powerful approach for exploring disease processes and testing potential therapeutic interventions. Currently, it is difficult to predict if a specific genetic manipulation will result in a desirable phenotype. The present study tests the idea that tissue recombinants recapitulate the pathologic features of the neoplastic prostate seen in transgenic mice, and would thus be suitable predictive models for new mouse design. The large probasin-large T-antigen (LPB-Tag) transgenic lines 12T-7f and 12T-10 were used as a basis for this study. Tissue recombinants of bladder epithelium (BlE) and urogenital sinus mesenchyme (UGM) were implanted under the renal capsule of athymic mice. Recombinants composed of BlE from 12T-10 LPB-Tag and wild-type (wt) UGM faithfully recapitulated the histopathologic and temporal features of intact transgenic mice of this line. Tissue recombinants using BlE from 12T-7f mice and wt UGM developed epithelial proliferation with atypia that lacked the associated hypercellular stroma seen in the intact 12T-7f line. Recombinants using 12T-7f UGM demonstrated that the hypercellular stroma results from stromal cell expression of the SV40 large T antigen. Corresponding to the recombinant phenotypes, stromal Tag immunostaining was observed in prostate tissues from intact 12T-7f but not 12T-10 mice. Similar stromal expression of Tag was also noted in the hypercellular TRAMP prostatic stroma. Further analysis revealed a previously unreported pattern of SV40T expression in the LADY and TRAMP models including ductus deferens and seminal vesicle stroma as well as region and cell type-specific patterns in the epididymis. The present study demonstrates the utility of using tissue recombination to explore organ-specific phenotypes. Recombination strategies should enable quick and cost-effective screening for likely phenotypes in transgenic animals. This comparison of tissue recombination to existing models shows that this approach can elicit new information on well-characterized models. PMID: 15980886 [PubMed - indexed for MEDLINE]

Report from London.


Report from London.
Related Articles Report from London. Prostate Cancer Prostatic Dis. 2005;8(4):299 Authors: Kirby RS PMID: 16319940 [PubMed - indexed for MEDLINE]

The interaction of four genes in the inflammation pathway significantly predicts prostate cancer risk.


The interaction of four genes in the inflammation pathway significantly predicts prostate cancer risk.
Related Articles The interaction of four genes in the inflammation pathway significantly predicts prostate cancer risk. Cancer Epidemiol Biomarkers Prev. 2005 Nov;14(11 Pt 1):2563-8 Authors: Xu J, Lowey J, Wiklund F, Sun J, Lindmark F, Hsu FC, Dimitrov L, Chang B, Turner AR, Liu W, Adami HO, Suh E, Moore JH, Zheng SL, Isaacs WB, Trent JM, Gr nberg H It is widely hypothesized that the interactions of multiple genes influence individual risk to prostate cancer. However, current efforts at identifying prostate cancer risk genes primarily rely on single-gene approaches. In an attempt to fill this gap, we carried out a study to explore the joint effect of multiple genes in the inflammation pathway on prostate cancer risk. We studied 20 genes in the Toll-like receptor signaling pathway as well as several cytokines. For each of these genes, we selected and genotyped haplotype-tagging single nucleotide polymorphisms (SNP) among 1,383 cases and 780 controls from the CAPS (CAncer Prostate in Sweden) study population. A total of 57 SNPs were included in the final analysis. A data mining method, multifactor dimensionality reduction, was used to explore the interaction effects of SNPs on prostate cancer risk. Interaction effects were assessed for all possible n SNP combinations, where n = 2, 3, or 4. For each n SNP combination, the model providing lowest prediction error among 100 cross-validations was chosen. The statistical significance levels of the best models in each n SNP combination were determined using permutation tests. A four-SNP interaction (one SNP each from IL-10, IL-1RN, TIRAP, and TLR5) had the lowest prediction error (43.28%, P = 0.019). Our ability to analyze a large number of SNPs in a large sample size is one of the first efforts in exploring the effect of high-order gene-gene interactions on prostate cancer risk, and this is an important contribution to this new and quickly evolving field. PMID: 16284379 [PubMed - indexed for MEDLINE]

Telomerase vaccination has no detectable effect on SCID-repopulating and colony-forming activities in the bone marrow of cancer patients.


Telomerase vaccination has no detectable effect on SCID-repopulating and colony-forming activities in the bone marrow of cancer patients.
Related Articles Telomerase vaccination has no detectable effect on SCID-repopulating and colony-forming activities in the bone marrow of cancer patients. Exp Hematol. 2005 Nov;33(11):1275-80 Authors: Danet-Desnoyers GA, Luongo JL, Bonnet DA, Domchek SM, Vonderheide RH OBJECTIVES: The telomerase reverse transcriptase hTERT is a widely expressed tumor-associated antigen recognized by cytotoxic T lymphocytes (CTL). We have previously shown that vaccination of cancer patients against hTERT induces functional anti-tumor CTL in vivo, but it is not known whether hTERT vaccination harms normal cells expressing the enzyme, especially hematopoietic stem cells and progenitors. PATIENTS AND METHODS: We employed colony-forming cell (CFC) assays, long-term in vitro cultures, and nonobese diabetic/severe combined immunodeficient (NOD/SCID) repopulation studies to evaluate the effects of hTERT vaccination on hematopoietic progenitors and stem cells in cancer patients following treatment. RESULTS: Using bone marrow samples obtained from cancer patients before and after vaccination, we found that there was no significant decline in the frequency of granulocyte, macrophage or erythroid CFCs using CFC assays or long-term in vitro cultures. In NOD/SCID mice, human hematopoietic reconstitution was easily detected, without quantitative or qualitative differences between pre- and postvaccine samples. CONCLUSION: These findings suggest that induction of tumor-lytic hTERT-specific T cells in vivo by vaccination does not result in a detectable decline in hematopoietic potential despite the expression of hTERT and major histocompatibility complex class I in bone marrow progenitors and stem cells. Thus, even for self-antigens such as telomerase, tumor immunity does not necessarily involve autoimmunity in normal tissues that share the target. PMID: 16263411 [PubMed - indexed for MEDLINE]

A rare prostatic tumor in a 48-year-old man.


A rare prostatic tumor in a 48-year-old man.
Related Articles A rare prostatic tumor in a 48-year-old man. Arch Pathol Lab Med. 2005 Nov;129(11):e202-3 Authors: Angeles RM, Engel G, Weisenberg E PMID: 16253039 [PubMed - indexed for MEDLINE]

[Delay to radiotherapy: a study of three tumour sites]


[Delay to radiotherapy: a study of three tumour sites]
Related Articles [Delay to radiotherapy: a study of three tumour sites] Cancer Radiother. 2005 Dec;9(8):590-601 Authors: Schlienger M In the following review of the literature, the reasons and consequences of a tendency to the increase of the delay between the diagnosis and the first irradiation session will be studied. The duration of the delay varies according to the protocol of treatment, which itself depends on the tumour. Moreover, all types of radiotherapy are concerned by the increase in delay. A retrospective study enables to determine for a given series of similar tumours and treatments the mean duration of delay and find the excessive duration. The increase of delay phenomenon exists in different countries. We know that before irradiation the tumour grows according to its biological characteristics and the TNM initial determination will no longer be true. On the other hand, effective treatments such as chemotherapy and hormone therapy are increasingly used alone, before or in combination with radiotherapy. Consequently, the classical timing of radiation therapy could be modified often delayed. It is difficult to consider that successive treatments are a real increase of delay and compare its results with previous data from radiotherapy alone. We will study its impact in three types of tumours, including tumours of head and neck, of the breast and prostate, which are the most widely reported. The consequences of prolonged delay are not easily evaluated: one of the more important parameters is the possible modification of the stage of tumour. This phenomenon is not restricted to the studied types of tumours. We will try to find possible ways of reducing abnormal delays before irradiation. PMID: 16168693 [PubMed - indexed for MEDLINE]

Telomerase vaccination has no detectable effect on SCID-repopulating and colony-forming activities in the bone marrow of cancer patients.


Telomerase vaccination has no detectable effect on SCID-repopulating and colony-forming activities in the bone marrow of cancer patients.
Related Articles Telomerase vaccination has no detectable effect on SCID-repopulating and colony-forming activities in the bone marrow of cancer patients. Exp Hematol. 2005 Nov;33(11):1275-80 Authors: Danet-Desnoyers GA, Luongo JL, Bonnet DA, Domchek SM, Vonderheide RH OBJECTIVES: The telomerase reverse transcriptase hTERT is a widely expressed tumor-associated antigen recognized by cytotoxic T lymphocytes (CTL). We have previously shown that vaccination of cancer patients against hTERT induces functional anti-tumor CTL in vivo, but it is not known whether hTERT vaccination harms normal cells expressing the enzyme, especially hematopoietic stem cells and progenitors. PATIENTS AND METHODS: We employed colony-forming cell (CFC) assays, long-term in vitro cultures, and nonobese diabetic/severe combined immunodeficient (NOD/SCID) repopulation studies to evaluate the effects of hTERT vaccination on hematopoietic progenitors and stem cells in cancer patients following treatment. RESULTS: Using bone marrow samples obtained from cancer patients before and after vaccination, we found that there was no significant decline in the frequency of granulocyte, macrophage or erythroid CFCs using CFC assays or long-term in vitro cultures. In NOD/SCID mice, human hematopoietic reconstitution was easily detected, without quantitative or qualitative differences between pre- and postvaccine samples. CONCLUSION: These findings suggest that induction of tumor-lytic hTERT-specific T cells in vivo by vaccination does not result in a detectable decline in hematopoietic potential despite the expression of hTERT and major histocompatibility complex class I in bone marrow progenitors and stem cells. Thus, even for self-antigens such as telomerase, tumor immunity does not necessarily involve autoimmunity in normal tissues that share the target. PMID: 16263411 [PubMed - indexed for MEDLINE]

Bone loss after initiation of androgen deprivation therapy in patients with prostate cancer.


Bone loss after initiation of androgen deprivation therapy in patients with prostate cancer.
Related Articles Bone loss after initiation of androgen deprivation therapy in patients with prostate cancer. J Clin Endocrinol Metab. 2005 Dec;90(12):6410-7 Authors: Greenspan SL, Coates P, Sereika SM, Nelson JB, Trump DL, Resnick NM CONTEXT: Although androgen deprivation therapy (ADT) for prostate cancer is associated with bone loss, little is known about when this bone loss occurs. OBJECTIVE: We postulated that men on ADT would experience the greatest bone loss acutely after initiation of ADT. DESIGN AND SETTING: We conducted a 12-month prospective study at an academic medical center. PATIENTS OR OTHER PARTICIPANTS: We studied 152 men with prostate cancer (30 with acute ADT, < 6 months; 50 with chronic ADT, > or = 6 months; and 72 with no ADT) and 43 healthy age-matched controls. MAIN OUTCOME MEASURES: We assessed bone mineral density (BMD) of the hip, wrist, total body, and spine; body composition; and markers of bone turnover. RESULTS: After 12 months, men receiving acute ADT had a significant reduction in BMD of 2.5 +/- 0.6% at the total hip, 2.4 +/- 1.0% at the trochanter, 2.6 +/- 0.5% at the total radius, 3.3 +/- 0.5% at the total body, and 4.0 +/- 1.5% at the posteroanterior spine (all P < 0.05). Men with chronic ADT had a 2.0 +/- 0.6% reduction in BMD at the total radius (P < 0.05). Healthy controls and men with prostate cancer not receiving ADT had no significant reduction in BMD. Both use and duration of ADT were associated with change in bone mass at the hip (P < 0.05). Men receiving acute ADT had a 10.4 +/- 1.7% increase in total body fat and a 3.5 +/- 0.5% reduction in total body lean mass at 12 months, whereas body composition did not change in men with prostate cancer on chronic ADT or in healthy controls (P < 0.05). Markers of bone formation and resorption were elevated in men receiving acute ADT after 6 and 12 months compared with the other men with prostate cancer and controls (P < 0.05). Men in the highest tertile of bone turnover markers at 6 months had the greatest loss of bone density at 12 months. CONCLUSIONS: Men with prostate cancer who are initiating ADT have a 5- to 10-fold increased loss of bone density at multiple skeletal sites compared with either healthy controls or men with prostate cancer who are not on ADT, placing them at increased risk of fracture. Bone loss is maximal in the first year after initiation of ADT, suggesting initiation of early preventive therapy. PMID: 16189261 [PubMed - indexed for MEDLINE]

Acute renal failure secondary to imatinib mesylate treatment in prostate cancer.


Acute renal failure secondary to imatinib mesylate treatment in prostate cancer.
Related Articles Acute renal failure secondary to imatinib mesylate treatment in prostate cancer. Ann Pharmacother. 2005 Dec;39(12):2136-8 Authors: Foringer JR, Verani RR, Tjia VM, Finkel KW, Samuels JA, Guntupalli JS OBJECTIVE: To report a case of acute renal failure associated with the administration of imatinib mesylate. CASE SUMMARY: A 64-year-old man diagnosed with prostate cancer was enrolled in a Phase I trial of imatinib mesylate plus taxotere on a protocol that required a run-in period of imatinib mesylate alone. During therapy with imatinib mesylate, the patient developed acute renal failure, requiring hemodialysis. A renal biopsy revealed tubular vacuolization. Renal failure resolved with cessation of imatinib mesylate. DISCUSSION: Imatinib mesylate is a protein tyrosine kinase inhibitor that inhibits the BCR-ABL tyrosine kinase, the receptor tyrosine kinases for platelet-derived growth factor, and stem cell factor c-kit. Prostate cancer has been identified as a target for therapy with imatinib mesylate. This patient had no other confounding factors for the cause of the renal failure. An objective causality assessment determined that imatinib mesylate was the probable cause of the acute renal failure. The presence of a primary glomerular disease was excluded by biopsy. CONCLUSIONS: Imatinib mesylate-induced acute renal failure has now been linked to toxic effects on renal tubular cells in 3 cases. Renal function should be closely monitored during imatinib mesylate therapy. PMID: 16288076 [PubMed - in process]

Time and PSA threshold model prognosticates long-term overall and disease-specific survival in prostate cancer patients as early as 3 months after external beam radiation therapy.


Time and PSA threshold model prognosticates long-term overall and disease-specific survival in prostate cancer patients as early as 3 months after external beam radiation therapy.
Related Articles Time and PSA threshold model prognosticates long-term overall and disease-specific survival in prostate cancer patients as early as 3 months after external beam radiation therapy. Prostate Cancer Prostatic Dis. 2005;8(4):353-8 Authors: Cavanaugh SX, Fuller CD, Kupelian PA, Reddy C, Bradshaw P, Pollock BH, Fuss M The specific aim of this analysis was to evaluate the capability of a time and prostate-specific antigen (PSA) threshold model to prognosticate overall survival (OS) and disease-specific survival (DSS) based on early PSA kinetics after radiotherapy for prostate cancer by retrospective review of outcomes in 918 patients. Crossing below analyzed PSA thresholds at specific defined time points reduced disease-specific death hazard ratios to relative to the cohort above threshold. The time and PSA threshold model demonstrates the ability to prognosticate OS and DSS as early as 3 months post-radiotherapy for prostate cancer. PMID: 16158079 [PubMed - indexed for MEDLINE]

January 12, 2006

Real Stories: We Should All Be Dead 


Real Stories: We Should All Be Dead 
RedNova - Dec 27 5:56 AM
By HELEN CARROLL I had to stay alive for my daughter Jackie Hackett, 43, a receptionist, lives in Wokingham, Berkshire, with her husband, Desmond, and daughter, Samantha, 16. I WAS only 38 when I discovered that I had breast cancer.Save to My Web

Prostate Cancer Screening - Detection rates and biologic significance of prostate cancer with PSA less than 4.0 ng/mL: observation and clinical implications from Tyrol screening project.


Detection rates and biologic significance of prostate cancer with PSA less than 4.0 ng/mL: observation and clinical implications from Tyrol screening project.
Related Articles Detection rates and biologic significance of prostate cancer with PSA less than 4.0 ng/mL: observation and clinical implications from Tyrol screening project. Urology. 2005 Nov;66(5):1029-33 Authors: Pelzer AE, Tewari A, Bektic J, Berger AP, Frauscher F, Bartsch G, Horninger W OBJECTIVES: To investigate the prostate cancer (PCa) detection rates and Gleason scores in patients with serum prostate-specific antigen (PSA) levels of 2.0 to 3.9 ng/mL and 4.0 to 10 ng/mL (free PSA 18% or less), in a population-based screening project. With the use of prostate-specific antigen (PSA) screening, more PCa is being diagnosed at PSA values of less than 4 ng/mL. METHODS: A total of 3446 consecutive screening volunteers with a PSA level of 2.0 to 10.0 ng/mL (free PSA 18% or less) were assessed. Ten systematic prostate biopsies and an additional five Doppler-enhanced targeted biopsies were performed on the basis of age-specific PSA reference ranges. The cumulative frequency of detection and the Gleason scores were analyzed. RESULTS: The PCa detection rate for patients with a PSA value of 2.0 to 3.9 ng/mL (n = 1522, group 1) and 4.0 to 10.0 ng/mL (n = 1924, group 2) was 21% (n = 320) and 30% (n = 572), respectively. Of the PCa cases detected, 37% were in men with a PSA level of 2 to 4 ng/mL. Statistically significant differences were found in age and prostate volume between groups 1 and 2, with patients in the lower PSA group younger and having a smaller mean prostate volume (P = 0.0001). Of 313 patients with PCa and a PSA value of 2 to 3.9 ng/mL, 24% had a Gleason score of 7 or greater compared with 33% of 560 patients with a PSA value of 4.0 to 10.0 ng/mL (P = 0.004). CONCLUSIONS: Our data suggest that in a screening population, more than one third of PCa cases in men with a PSA level of 2 to 10 ng/mL will occur in those with a PSA value of 2 to 3.9 ng/mL. Also, PCa cases with a low PSA level occur in younger patients and at lower stages with a smaller prostate volume. PMID: 16286118 [PubMed - indexed for MEDLINE]

Prevention of cancer in the older person.


Prevention of cancer in the older person.
Related Articles Prevention of cancer in the older person. Cancer J. 2005 Nov-Dec;11(6):442-8 Authors: Balducci L Cancer is the most common cause of death up to the age of 85 years and is also a major cause of disability. Screening asymptomatic patients for cancer is the most promising strategy to reduce cancer-related morbidity and mortality in the older population. Though the information related to older people is scanty, it is reasonable to recommend that the screening of older individuals be based on life expectancy, tolerance of screening, and tolerance of antineoplastic therapy. Some form of screening for breast cancer appears indicated for individuals with life expectancy of 5 and more years. If screening for prostate cancer is indicated at all, it should be limited to men with a life expectancy of at least 10 years. The value of screening asymptomatic individuals for lung and ovarian cancer is explored in ongoing clinical trials. PMID: 16393478 [PubMed - in process]

[Advances on inhibin genes.]


[Advances on inhibin genes.]
Related Articles [Advances on inhibin genes.] Yi Chuan. 2004 Sep;26(5):749-55 Authors: Xue Y, Chu MX, Zhou ZX Inhibins are gonadal glycoprotein hormones belonging to the transforming growth factor-beta superfamily that act to suppress pituitary follicle-stimulating hormone synthesis and secretion. In this paper, we briefly introduced the cloning, structure, localization, polymorphism, expression, molecular regulation of inhibin-alpha(INHA), -betaA (INHBA) and -beta B (INHBB) subunit genes and their relationships with reproductive performance and cancer. The inhibin genes (INHA, INHBA and INHBB) had significant effect on litter size in sheep. The ovine INHA, INHBA and INHBB genes had been mapped to chromosomes 2q41-->q43, 4q26 and 2q31-->q33, respectively. The female mice carrying INHBB mutations suffered from distinct developmental and reproductive defects. The INHA gene was significantly associated with premature ovarian failure in women. PMID: 15640097 [PubMed - indexed for MEDLINE]

Antiandrogen and vaccine therapy for hormone-refractory prostate cancer.


Antiandrogen and vaccine therapy for hormone-refractory prostate cancer.
Related Articles Antiandrogen and vaccine therapy for hormone-refractory prostate cancer. Nat Clin Pract Oncol. 2005 Nov;2(11):541-2 Authors: King A PMID: 16270083 [PubMed - in process]

Use of a temporary plastic stent to facilitate the placement of multiple self-expanding metal stents in malignant biliary hilar strictures.


Use of a temporary plastic stent to facilitate the placement of multiple self-expanding metal stents in malignant biliary hilar strictures.
Related Articles Use of a temporary plastic stent to facilitate the placement of multiple self-expanding metal stents in malignant biliary hilar strictures. Gastrointest Endosc. 2005 Oct;62(4):605-9 Authors: Hookey LC, Le Moine O, Deviere J BACKGROUND: Although endoscopic palliation of malignant biliary hilar obstruction is preferable to surgery or percutaneous drainage, it remains technically challenging. This is especially true when multiple self-expanding metal stents (SEMS) are placed, because difficulty is commonly encountered in passing the second SEMS at the level of the previously deployed initial stent. We have devised a method of deploying multiple metal stents by using a temporary plastic stent, which makes deployment of the second stent much easier. METHODS: After guidewire placement, a plastic stent is deployed in a subhilar position. The initial SEMS is deployed, with the plastic stent maintaining a passage for the second SEMS. After the second SEMS is deployed, the plastic stent is retrieved. OBSERVATIONS: This technique has been used successfully in 7/8 patients, all of whom presented with symptomatic jaundice secondary to malignant hilar obstruction of various etiologies (cholangiocarcinoma, n=4; metastatic disease, n=3; and hepatocellular carcinoma, n=1). Drainage was successful in all cases, with significant improvement in symptoms and cholestasis. CONCLUSIONS: This simple technique lessens the technical difficulty of placing bilateral hilar SEMS. PMID: 16185978 [PubMed - indexed for MEDLINE]

Defining biochemical failure after radiotherapy with and without androgen deprivation for prostate cancer.


Defining biochemical failure after radiotherapy with and without androgen deprivation for prostate cancer.
Related Articles Defining biochemical failure after radiotherapy with and without androgen deprivation for prostate cancer. Int J Radiat Oncol Biol Phys. 2005 Dec 1;63(5):1455-62 Authors: Buyyounouski MK, Hanlon AL, Eisenberg DF, Horwitz EM, Feigenberg SJ, Uzzo RG, Pollack A PURPOSE: To compare several characteristics of alternative definitions of biochemical failure (BF) in men with extended follow-up after radiotherapy (RT) with or with androgen deprivation therapy (ADT) for prostate cancer. METHODS AND MATERIALS: From December 1, 1991, to April 30, 1998, 688 men with Stage T1c-T3NX-N0M0 prostate cancer received RT alone (n = 586) or RT plus ADT (n = 102) with a minimal follow-up of 4 years and five or more "ADT-free" posttreatment prostate-specific antigen levels. BF was defined by three methods: (1) the ASTRO definition (three consecutive rises in prostate-specific antigen level); (2) a modified American Society for Therapeutic Radiology Oncology (ASTRO) definition requiring two additional consecutive rises when a decline immediately subsequent to three consecutive rises occurred; and (3) the "Houston" or nadir plus 2-ng/mL definition (a rise of at least 2 ng/mL greater than the nadir). The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy were determined for each using clinical progression as the endpoint. Furthermore, the misclassification rates for a steadily rising prostate-specific antigen level, ability to satisfy the proportional hazards (RT with or without ADT), effects of short follow-up, and intervals to the diagnosis of BF were compared. RESULTS: The misclassification rate for BF using the nadir plus 2-ng/mL definition was 2% for RT alone and 0% for RT plus ADT compared with 0% and 0% for the modified ASTRO definition, and 5% and 23% for the ASTRO definition, respectively. The hazard rates for RT alone and RT plus ADT were proportional only for the nadir plus 2 ng/mL definition and seemingly unaffected by the length of follow-up. For RT with or without ADT, the nadir plus 2 ng/mL definition was the most specific (RT, 80% vs. RT plus ADT, 75%) with the greatest positive predictive value (RT, 36% vs. RT plus ADT, 25%) and overall accuracy (RT, 81% vs. RT plus ADT, 77%). A greater proportion of BF was diagnosed in the first 2 years of follow-up with the nadir plus 2 ng/mL definition compared with the ASTRO definition (13% vs. 5%, p = 0.0138, chi-square test). CONCLUSION: The nadir plus 2 ng/mL definition was the best predictor of sustained, true, biochemical, and clinical failure, and was not affected by the use of ADT or follow-up length. PMID: 16169682 [PubMed - indexed for MEDLINE]

Prostate-specific antigen-reactive cytotoxic T lymphocyte precursors in colon cancer patients.


Prostate-specific antigen-reactive cytotoxic T lymphocyte precursors in colon cancer patients.
Related Articles Prostate-specific antigen-reactive cytotoxic T lymphocyte precursors in colon cancer patients. Oncol Rep. 2006 Feb;15(2):317-21 Authors: Wang Y, Harada M, Yano H, Ogasawara S, Tanaka M, Yamada A, Itoh K Prostate-specific antigen (PSA) is a representative of the prostate-related antigens, and has been considered to be a tumor marker of prostate cancer. However, some studies suggest that PSA could be produced by several types of tumors. In the present study, we attempted to determine whether or not PSA could be a target molecule in specific immunotherapy for patients with colon cancer. Five colon cancer cell lines were examined for their PSA expression at the mRNA and protein levels by RT-PCR and immunocytostaining, respectively. As a result, four cell lines were found to be positive for PSA at both the mRNA and protein levels. We also attempted to determine whether PSA-reactive cytotoxic T lymphocytes (CTLs) could be induced from the peripheral blood mononuclear cells (PBMCs) of HLA-A24(+) colon cancer patients by in vitro stimulation with PSA-derived peptides. As a consequence, PSA peptide-specific CTLs could be generated from the PBMCs of male and female colon cancer patients. Their cytotoxicity against HLA-A24(+) PSA-expressing colon cancer cells was dependent on HLA class I-restricted and CD8(+) T cells. These findings indicate that PSA-reactive CTL precursors are present in the periphery of colon cancer patients, and that PSA could be a target molecule in specific immunotherapy to colon cancer. PMID: 16391848 [PubMed - in process]

Defining biochemical failure after radiotherapy with and without androgen deprivation for prostate cancer.


Defining biochemical failure after radiotherapy with and without androgen deprivation for prostate cancer.
Related Articles Defining biochemical failure after radiotherapy with and without androgen deprivation for prostate cancer. Int J Radiat Oncol Biol Phys. 2005 Dec 1;63(5):1455-62 Authors: Buyyounouski MK, Hanlon AL, Eisenberg DF, Horwitz EM, Feigenberg SJ, Uzzo RG, Pollack A PURPOSE: To compare several characteristics of alternative definitions of biochemical failure (BF) in men with extended follow-up after radiotherapy (RT) with or with androgen deprivation therapy (ADT) for prostate cancer. METHODS AND MATERIALS: From December 1, 1991, to April 30, 1998, 688 men with Stage T1c-T3NX-N0M0 prostate cancer received RT alone (n = 586) or RT plus ADT (n = 102) with a minimal follow-up of 4 years and five or more "ADT-free" posttreatment prostate-specific antigen levels. BF was defined by three methods: (1) the ASTRO definition (three consecutive rises in prostate-specific antigen level); (2) a modified American Society for Therapeutic Radiology Oncology (ASTRO) definition requiring two additional consecutive rises when a decline immediately subsequent to three consecutive rises occurred; and (3) the "Houston" or nadir plus 2-ng/mL definition (a rise of at least 2 ng/mL greater than the nadir). The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy were determined for each using clinical progression as the endpoint. Furthermore, the misclassification rates for a steadily rising prostate-specific antigen level, ability to satisfy the proportional hazards (RT with or without ADT), effects of short follow-up, and intervals to the diagnosis of BF were compared. RESULTS: The misclassification rate for BF using the nadir plus 2-ng/mL definition was 2% for RT alone and 0% for RT plus ADT compared with 0% and 0% for the modified ASTRO definition, and 5% and 23% for the ASTRO definition, respectively. The hazard rates for RT alone and RT plus ADT were proportional only for the nadir plus 2 ng/mL definition and seemingly unaffected by the length of follow-up. For RT with or without ADT, the nadir plus 2 ng/mL definition was the most specific (RT, 80% vs. RT plus ADT, 75%) with the greatest positive predictive value (RT, 36% vs. RT plus ADT, 25%) and overall accuracy (RT, 81% vs. RT plus ADT, 77%). A greater proportion of BF was diagnosed in the first 2 years of follow-up with the nadir plus 2 ng/mL definition compared with the ASTRO definition (13% vs. 5%, p = 0.0138, chi-square test). CONCLUSION: The nadir plus 2 ng/mL definition was the best predictor of sustained, true, biochemical, and clinical failure, and was not affected by the use of ADT or follow-up length. PMID: 16169682 [PubMed - indexed for MEDLINE]

Clinical staging of prostate cancer: a computer-simulated study of transperineal prostate biopsy.


Clinical staging of prostate cancer: a computer-simulated study of transperineal prostate biopsy.
Related Articles Clinical staging of prostate cancer: a computer-simulated study of transperineal prostate biopsy. BJU Int. 2005 Nov;96(7):999-1004 Authors: Crawford ED, Wilson SS, Torkko KC, Hirano D, Stewart JS, Brammell C, Wilson RS, Kawata N, Sullivan H, Lucia MS, Werahera PN OBJECTIVE: To identify the precise location of prostate cancer within the gland and thus possibly permit more aggressive therapy of the lesion, while potentially sparing the noncancerous gland from ablative therapy. MATERIALS AND METHODS: Three-dimensional "solid" computer models were reconstructed for 86 autopsy specimens and 20 stage T1c radical prostatectomy specimens. Transperineal biopsies were simulated for grid sizes of 5-mm (method A) and 10-mm (method B) with an 18 G, 23-mm long biopsy needle. One or two biopsies per grid point were obtained for a total of 12-108 biopsies, depending on the size of the prostate. Clinically threatening cancers were defined as having volumes of > or = 0.5 mL or Gleason sum > or = 7. RESULTS: Method A detected significantly more carcinomas than method B in both the autopsy and prostatectomy specimens (autopsy, 72 vs 51; prostatectomy, 50 vs 32, both P < 0.001). Method A also detected more clinically threatening cancers found at autopsy (38/40 vs 31/40, P = 0.008). Among autopsy patients with negative sextant biopsies whose disease was localized to one side, method A detected 72% and method B detected 29-43% (P < 0.001). CONCLUSIONS: The results of this computer simulation show that 5- and 10-mm grid biopsies detect three-quarters and a third, respectively, at autopsy, of patients with the disease localized to one side of the prostate, which may be useful when planning highly selective ablative treatments in the future. PMID: 16225516 [PubMed - indexed for MEDLINE]

January 11, 2006

Prostate Cancer Screening - Use of tissue recombination to predict phenotypes of transgenic mouse models of prostate carcinoma.


Use of tissue recombination to predict phenotypes of transgenic mouse models of prostate carcinoma.
Related Articles Use of tissue recombination to predict phenotypes of transgenic mouse models of prostate carcinoma. Lab Invest. 2005 Sep;85(9):1086-103 Authors: Ishii K, Shappell SB, Matusik RJ, Hayward SW Transgenic mouse models of cancer represent a powerful approach for exploring disease processes and testing potential therapeutic interventions. Currently, it is difficult to predict if a specific genetic manipulation will result in a desirable phenotype. The present study tests the idea that tissue recombinants recapitulate the pathologic features of the neoplastic prostate seen in transgenic mice, and would thus be suitable predictive models for new mouse design. The large probasin-large T-antigen (LPB-Tag) transgenic lines 12T-7f and 12T-10 were used as a basis for this study. Tissue recombinants of bladder epithelium (BlE) and urogenital sinus mesenchyme (UGM) were implanted under the renal capsule of athymic mice. Recombinants composed of BlE from 12T-10 LPB-Tag and wild-type (wt) UGM faithfully recapitulated the histopathologic and temporal features of intact transgenic mice of this line. Tissue recombinants using BlE from 12T-7f mice and wt UGM developed epithelial proliferation with atypia that lacked the associated hypercellular stroma seen in the intact 12T-7f line. Recombinants using 12T-7f UGM demonstrated that the hypercellular stroma results from stromal cell expression of the SV40 large T antigen. Corresponding to the recombinant phenotypes, stromal Tag immunostaining was observed in prostate tissues from intact 12T-7f but not 12T-10 mice. Similar stromal expression of Tag was also noted in the hypercellular TRAMP prostatic stroma. Further analysis revealed a previously unreported pattern of SV40T expression in the LADY and TRAMP models including ductus deferens and seminal vesicle stroma as well as region and cell type-specific patterns in the epididymis. The present study demonstrates the utility of using tissue recombination to explore organ-specific phenotypes. Recombination strategies should enable quick and cost-effective screening for likely phenotypes in transgenic animals. This comparison of tissue recombination to existing models shows that this approach can elicit new information on well-characterized models. PMID: 15980886 [PubMed - indexed for MEDLINE]

[Screening of cancer of the most frequent localizations]


[Screening of cancer of the most frequent localizations]
Related Articles [Screening of cancer of the most frequent localizations] Klin Med (Mosk). 2005;83(10):4-9 Authors: Belialova NS, Belialov FI PMID: 16320836 [PubMed - indexed for MEDLINE]

Androgen receptor signaling intensity is a key factor in determining the sensitivity of prostate cancer cells to selenium inhibition of growth and cancer-specific biomarkers.


Androgen receptor signaling intensity is a key factor in determining the sensitivity of prostate cancer cells to selenium inhibition of growth and cancer-specific biomarkers.
Related Articles Androgen receptor signaling intensity is a key factor in determining the sensitivity of prostate cancer cells to selenium inhibition of growth and cancer-specific biomarkers. Mol Cancer Ther. 2005 Jul;4(7):1047-55 Authors: Dong Y, Zhang H, Gao AC, Marshall JR, Ip C Our previous report showed that methylseleninic acid (MSA) significantly decreases the expression of androgen receptor and prostate-specific antigen (PSA) in LNCaP cells. The present study extended the above observations by showing the universality of this phenomenon and that the inhibitory effect of MSA on prostate cancer cell growth and cancer-specific biomarkers is mediated through androgen receptor down-regulation. First, MSA decreases the expression of androgen receptor and PSA in five human prostate cancer cell lines (LNCaP, LAPC-4, CWR22Rv1, LNCaP-C81, and LNCaP-LN3), irrespective of their androgen receptor genotype (wild type versus mutant) or sensitivity to androgen-stimulated growth. Second, by using the ARE-luciferase reporter gene assay, we found that MSA suppression of androgen receptor transactivation is accounted for primarily by the reduction of androgen receptor protein level. Third, MSA inhibition of five androgen receptor-regulated genes implicated in prostate carcinogenesis (PSA, KLK2, ABCC4, DHCR24, and GUCY1A3) is significantly attenuated by androgen receptor overexpression. Fourth, transfection of androgen receptor in LNCaP cells weakened noticeably the inhibitory effect of MSA on cell growth and proliferation. Androgen receptor signaling has been documented extensively to play an important role in the development of both androgen-dependent and -independent prostate cancer. Our finding that MSA reduces androgen receptor availability by blocking androgen receptor transcription provides justification for a mechanism-driven intervention strategy in using selenium to control prostate cancer progression. PMID: 16020662 [PubMed - indexed for MEDLINE]

Therapeutic vaccines for prostate cancer: a review of clinical data.


Therapeutic vaccines for prostate cancer: a review of clinical data.
Related Articles Therapeutic vaccines for prostate cancer: a review of clinical data. Curr Opin Investig Drugs. 2005 Jun;6(6):592-6 Authors: Arlen PM, Gulley JL Prostate cancer is the most common, non-cutaneous cancer and the second leading cause of cancer death among men in the US. A greater understanding of basic immunological principles has led to the development of a variety of new techniques, which in turn has led to advances in the field of prostate cancer vaccines. This review will discuss the rationale for the development of vaccines involving whole tumor cells and dendritic cells, as well as pox viral vectors, and will summarize selected clinical studies that have incorporated these strategies. PMID: 15988910 [PubMed - indexed for MEDLINE]

IGF-II Serum Levels Increase Discrimination Between Benign Prostatic Hyperplasia and Prostate Cancer and Improve the Predictive Value of PSA in Clinical Staging.


IGF-II Serum Levels Increase Discrimination Between Benign Prostatic Hyperplasia and Prostate Cancer and Improve the Predictive Value of PSA in Clinical Staging.
Related Articles IGF-II Serum Levels Increase Discrimination Between Benign Prostatic Hyperplasia and Prostate Cancer and Improve the Predictive Value of PSA in Clinical Staging. Eur Urol. 2005 Dec 7; Authors: Trojan L, Bode C, Weiss C, Mayer D, Grobholz R, Alken P, Michel MS PURPOSE: IGF-I serum levels have been demonstrated as being associated with prostate cancer (PCa) and can serve as a predictive factor for the risk of PCa development. However, the role of IGF-II in PCa and its importance as a predictive marker is still unclear. Our aim was to determine PSA and IGF-II serum levels in patients with PCa and benign prostatic hyperplasia (BPH) and to analyse the value of IGF-II as an additional predictive factor in the diagnostics of PCa. METHODS: 112 patients who underwent surgery for BPH or PCa (no hormonal treatment, no further malignancies) were included in this study ((I) 38 PCa, PSA</=15ng/ml; (II) 34 PCa, PSA>15ng/ml; (III) 40 BPH). Preoperative serum levels of total PSA and total IGF-II were determined by ELFA and ELISA, respectively. RESULTS: PSA levels were (I) 5.7+/-1.9ng/ml; (II) 25.0+/-11.5ng/ml and (III) 4.0+/-2.8ng/ml. (II) was statistically associated with a high grading (2b/3; p=0.0182), a high Gleason sum score (7-10; p=0.0049) and a non-organ confined tumor (T3/4; p=0.0009) compared to (I), all Chi(2) test. IGF-II levels were significantly higher in PCa (I+II) compared to BPH (833.8+/-238.9ng/ml vs. 633.3+/-141.4ng/ml, p<0.0001, t-test). Both PSA and IGF-II were associated with tumor staging (p=0.0097, p=0.0308; t-test). No significant correlation was observed between PSA and IGF-II levels. Logistic regression analysis revealed that the combination of PSA and IGF-II improves the prediction of tumor staging in PCa (p=0.0175 and p=0.0459, Wald test). Additionally, the combination of PSA and IGF-II can significantly increase discrimination between BPH and PCa; each p<0.0001, Wald test. CONCLUSIONS: This study provides evidence that IGF-II serum levels may serve as an additional parameter for (a) improved determination of tumor staging and (b) better discrimination between BPH and PCa. PMID: 16386354 [PubMed - as supplied by publisher]

A phase III randomized, placebo-controlled, double-blind study of misoprostol rectal suppositories to prevent acute radiation proctitis in patients with prostate cancer.


A phase III randomized, placebo-controlled, double-blind study of misoprostol rectal suppositories to prevent acute radiation proctitis in patients with prostate cancer.
Related Articles A phase III randomized, placebo-controlled, double-blind study of misoprostol rectal suppositories to prevent acute radiation proctitis in patients with prostate cancer. Int J Radiat Oncol Biol Phys. 2005 Dec 1;63(5):1488-93 Authors: Hille A, Schmidberger H, Hermann RM, Christiansen H, Saile B, Pradier O, Hess CF PURPOSE: Acute radiation proctitis is the most relevant complication of pelvic radiation and is still mainly treated supportively. Considering the negative impact of acute proctitis symptoms on patients' daily activities and the potential relationship between the severity of acute radiation injury and late damage, misoprostol was tested in the prevention of acute radiation-induced proctitis. METHODS AND MATERIALS: A total of 100 patients who underwent radiotherapy for prostate cancer were entered into this phase III randomized, placebo-controlled, double-blind study with misoprostol or placebo suppositories. Radiation-induced toxicity was evaluated weekly during radiotherapy using the Common Toxicity Criteria. RESULTS: Between the placebo and the misoprostol groups, no significant differences in proctitis symptoms occurred: 76% of patients in each group had Grade 1 toxicity, and 26% in the placebo group and 36% in the misoprostol group had Grade 2 toxicity. No differences were found in onset or symptom duration. Comparing the peak incidence of patients' toxicity symptoms, significantly more patients experienced rectal bleeding in the misoprostol group (p = 0.03). CONCLUSION: Misoprostol given as a once-daily suppository did not decrease the incidence and severity of radiation-induced acute proctitis and may increase the incidence of acute bleeding. PMID: 16137837 [PubMed - indexed for MEDLINE]

A novel cancer testis antigen that is frequently expressed in pancreatic, lung, and endometrial cancers.


A novel cancer testis antigen that is frequently expressed in pancreatic, lung, and endometrial cancers.
Related Articles A novel cancer testis antigen that is frequently expressed in pancreatic, lung, and endometrial cancers. Clin Cancer Res. 2006 Jan 1;12(1):191-7 Authors: Okada T, Akada M, Fujita T, Iwata T, Goto Y, Kido K, Okada T, Matsuzaki Y, Kobayashi K, Matsuno S, Sunamura M, Kawakami Y PURPOSE: To isolate cancer testis antigens that are expressed in pancreatic cancers and may be useful in clinical applications.EXPERIMENTAL DESIGN: To efficiently isolate cancer testis antigens, a testis cDNA library was immunoscreened (SEREX) with serum from a patient with pancreatic ductal adenocarcinoma. The expression of isolated antigens in various cancer cell lines and tissues was evaluated by reverse transcription-PCR and Northern blot analyses. The immunogenicity of the antigen in cancer patients was evaluated by detection of the IgG antibody in sera from patients with various cancers.RESULTS: Of the three clones isolated through screening of a total of 2 x 10(6) cDNA library clones, one clone (KU-CT-1) was found to be expressed in various cancers but only in testis among normal tissues, indicating that it was a novel cancer testis antigen. The KU-CT-1 gene is located on chromosome 10p12 and produces two splice variants, which encode proteins of 397 and 872 amino acids, respectively. KU-CT-1 was expressed in pancreatic cancer tissues (3 of 9, 33%), lung cancer tissues (9 of 24, 38%), and endometrial cancer tissues (7 of 11, 64%). Specific serum IgG antibodies were detected in 3 of 20 pancreatic cancer patients, 2 of 12 endometrial cancer patients, 1 of 18 colon cancer patients, and 1 of 10 prostate cancer patients but not detected in 30 healthy individuals.CONCLUSIONS: KU-CT-1 is a new cancer testis antigen that is expressed in pancreatic, lung, and endometrial cancers and may be useful for diagnosis and immunotherapy for patients with various cancers. PMID: 16397042 [PubMed - in process]

Defining biochemical failure after radiotherapy with and without androgen deprivation for prostate cancer.


Defining biochemical failure after radiotherapy with and without androgen deprivation for prostate cancer.
Related Articles Defining biochemical failure after radiotherapy with and without androgen deprivation for prostate cancer. Int J Radiat Oncol Biol Phys. 2005 Dec 1;63(5):1455-62 Authors: Buyyounouski MK, Hanlon AL, Eisenberg DF, Horwitz EM, Feigenberg SJ, Uzzo RG, Pollack A PURPOSE: To compare several characteristics of alternative definitions of biochemical failure (BF) in men with extended follow-up after radiotherapy (RT) with or with androgen deprivation therapy (ADT) for prostate cancer. METHODS AND MATERIALS: From December 1, 1991, to April 30, 1998, 688 men with Stage T1c-T3NX-N0M0 prostate cancer received RT alone (n = 586) or RT plus ADT (n = 102) with a minimal follow-up of 4 years and five or more "ADT-free" posttreatment prostate-specific antigen levels. BF was defined by three methods: (1) the ASTRO definition (three consecutive rises in prostate-specific antigen level); (2) a modified American Society for Therapeutic Radiology Oncology (ASTRO) definition requiring two additional consecutive rises when a decline immediately subsequent to three consecutive rises occurred; and (3) the "Houston" or nadir plus 2-ng/mL definition (a rise of at least 2 ng/mL greater than the nadir). The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy were determined for each using clinical progression as the endpoint. Furthermore, the misclassification rates for a steadily rising prostate-specific antigen level, ability to satisfy the proportional hazards (RT with or without ADT), effects of short follow-up, and intervals to the diagnosis of BF were compared. RESULTS: The misclassification rate for BF using the nadir plus 2-ng/mL definition was 2% for RT alone and 0% for RT plus ADT compared with 0% and 0% for the modified ASTRO definition, and 5% and 23% for the ASTRO definition, respectively. The hazard rates for RT alone and RT plus ADT were proportional only for the nadir plus 2 ng/mL definition and seemingly unaffected by the length of follow-up. For RT with or without ADT, the nadir plus 2 ng/mL definition was the most specific (RT, 80% vs. RT plus ADT, 75%) with the greatest positive predictive value (RT, 36% vs. RT plus ADT, 25%) and overall accuracy (RT, 81% vs. RT plus ADT, 77%). A greater proportion of BF was diagnosed in the first 2 years of follow-up with the nadir plus 2 ng/mL definition compared with the ASTRO definition (13% vs. 5%, p = 0.0138, chi-square test). CONCLUSION: The nadir plus 2 ng/mL definition was the best predictor of sustained, true, biochemical, and clinical failure, and was not affected by the use of ADT or follow-up length. PMID: 16169682 [PubMed - indexed for MEDLINE]

Re: luteinizing hormone-releasing hormone agonist effects on skeletal muscle: how hormonal therapy in prostate cancer affects muscular strength.


Re: luteinizing hormone-releasing hormone agonist effects on skeletal muscle: how hormonal therapy in prostate cancer affects muscular strength.
Related Articles Re: luteinizing hormone-releasing hormone agonist effects on skeletal muscle: how hormonal therapy in prostate cancer affects muscular strength. J Urol. 2005 Nov;174(5):2068-9 Authors: Marcora S, Oliver S, Callow N, Lemmey A, Stuart N PMID: 16217402 [PubMed - indexed for MEDLINE]

Differences in clinical characteristics and disease-free survival for Latino, African American, and non-Latino white men with localized prostate cancer.


Differences in clinical characteristics and disease-free survival for Latino, African American, and non-Latino white men with localized prostate cancer.
Related Articles Differences in clinical characteristics and disease-free survival for Latino, African American, and non-Latino white men with localized prostate cancer. Cancer. 2006 Jan 6; Authors: Latini DM, Elkin EP, Cooperberg MR, Sadetsky N, Duchane J, Carroll PR BACKGROUND: Few studies of ethnicity and prostate cancer have included Latino men in analyses of baseline clinical characteristics, treatment selection, and disease-free survival (DFS). The present study examines the impact of Latino ethnicity on these parameters in a large, multiinstitutional database of men with prostate cancer. METHODS: We compared baseline disease characteristics and clinical outcomes for Latino (N = 138), non-Latino White (NLW, N = 5619), and African-American (AA, N = 608) men with localized prostate cancer by using chi-square and ANOVA for baseline variables and survival analysis to examine differences in time to recurrence. RESULTS: Latino men resembled AA men more than NLW on sociodemographic characteristics. AA men had higher Gleason scores and prostate-specific antigen (PSA) at diagnosis than Latino or NLW men (both P < 0.01). 10% of both Latino and AA men presented with advanced disease (T3b/T4/N+/M+) versus 4% of NLW (P < 0.01). Latino men did not receive different treatments than NLW or AA men after controlling for clinical and demographic factors; however, AA men were more likely to receive external beam radiation (OR = 1.51, 95% confidence interval [CI] = 0.99-2.31) and hormone treatment (OR = 1.56, 95% CI = 1.05-2.32) then NLW men. For prostatectomy patients, 3-year actuarial DFS rates were 83% for NLW men and 86% for Latino men versus 69% for AA men (P < 0.01). After controlling for clinical and sociodemographic variables, AA men were somewhat more likely than NLW to experience disease recurrence after radical prostatectomy (RP) (HR = 1.38, 95% CI = 0.98-1.94, P = 0.06). CONCLUSIONS: Latinos are more similar to African Americans on sociodemographic characteristics but more similar to NLW on clinical presentation, treatments received, and DFS. Cancer 2006. (c) 2006 American Cancer Society. PMID: 16400651 [PubMed - as supplied by publisher]

January 07, 2006

Prostate Cancer Screening - Revisiting my personal decision about prostate-specific antigen testing in 2005.


Revisiting my personal decision about prostate-specific antigen testing in 2005.
Related Articles Revisiting my personal decision about prostate-specific antigen testing in 2005. BJU Int. 2005 Nov;96(7):954-6 Authors: Barry MJ PMID: 16225507 [PubMed - indexed for MEDLINE]

Humoral immune response in prostate cancer patients after immunization with gene-based vaccines that encode for a protein that is proteasomally degraded.


Humoral immune response in prostate cancer patients after immunization with gene-based vaccines that encode for a protein that is proteasomally degraded.
Related Articles Humoral immune response in prostate cancer patients after immunization with gene-based vaccines that encode for a protein that is proteasomally degraded. Cancer Immun. 2005 Jan 11;5:1 Authors: Todorova K, Ignatova I, Tchakarov S, Altankova I, Zoubak S, Kyurkchiev S, Mincheff M Prostate-specific membrane antigen (PSMA), whose expression is upregulated in poorly differentiated, metastatic, and hormone refractory prostate cancer, could be targeted by gene-based vaccines. The aim of this study was to characterize the humoral immune response against PSMA in prostate carcinoma patients who have been vaccinated against PSMA with gene-based vaccines. Sera from prostate cancer patients who had been immunized repeatedly with plasmid DNA and a recombinant adenoviral vector, both carrying an expression cassette for human PSMA, and sera from healthy donors were tested for anti-PSMA antibodies by Western blot analysis and immunofluorescence. PSMA-producing LNCaP cells, recombinant PSMA protein, and a specific antibody against PSMA were used as positive controls. Specific anti-PSMA antibodies were detected by both Western blot and immunofluorescence in the sera of patients who had been vaccinated against PSMA with plasmid and recombinant adenoviral vectors. The specificity of the anti-PSMA antibodies was confirmed by preincubation and blocking experiments. Positive reactions were detected in 86% of the vaccinated prostate cancer patients. Anti-PSMA antibodies were not detected either in the patients' sera prior to vaccination or in the sera from healthy men and women. These data demonstrate that PSMA, a specific marker for prostate cancer, is a target for humoral immune response induced by gene-based PSMA vaccination. Detection of anti-PSMA antibodies by immunoblot analysis and by indirect immunofluorescence could be used to monitor the vaccination effect. PMID: 15641767 [PubMed - indexed for MEDLINE]

(99m)Tc-EC-guanine: synthesis, biodistribution, and tumor imaging in animals.


(99m)Tc-EC-guanine: synthesis, biodistribution, and tumor imaging in animals.
Related Articles (99m)Tc-EC-guanine: synthesis, biodistribution, and tumor imaging in animals. Pharm Res. 2005 Sep;22(9):1471-9 Authors: Yang DJ, Ozaki K, Oh CS, Azhdarinia A, Yang T, Ito M, Greenwell A, Bryant J, Kohanim S, Wong VK, Kim EE PURPOSE: DNA markers are useful in assessing cell proliferation. The purpose of this study was to synthesize (99m)Tc-ethylenedicysteine-guanine (EC-Guan) for evaluation of cell proliferation. METHODS: Tumor cells were incubated with (99m)Tc-EC-Guan for cell cycle analysis. Prostate tumor cells that were overexpressing the HSV thymidine kinase gene, or various tumor cells were incubated with (99m)Tc-EC-Guan at 0.5-2 h. Thymidine incorporation assays were performed in lung cancer cells incubated with EC-Guan at 0.1-1 mg/well. Tissue distribution, autoradiography, and planar scintigraphy of (99m)Tc-EC-Guan and (99m)Tc-EC (control) were determined in tumor-bearing rodents at 0.5-4 h. RESULTS: Cell culture assays indicated that EC-Guan was incorporated in DNA, and there was no significant uptake difference between HSVTK overexpressed and normal groups. Biodistribution and scintigraphic imaging studies of (99m)Tc-EC-Guan showed increased tumor/tissue count density ratios as a function of time. CONCLUSIONS: Our results indicate that (99m)Tc-EC-Guan may be useful as a tumor proliferation imaging agent. PMID: 16132359 [PubMed - indexed for MEDLINE]

Therapeutic vaccines for prostate cancer: a review of clinical data.


Therapeutic vaccines for prostate cancer: a review of clinical data.
Related Articles Therapeutic vaccines for prostate cancer: a review of clinical data. Curr Opin Investig Drugs. 2005 Jun;6(6):592-6 Authors: Arlen PM, Gulley JL Prostate cancer is the most common, non-cutaneous cancer and the second leading cause of cancer death among men in the US. A greater understanding of basic immunological principles has led to the development of a variety of new techniques, which in turn has led to advances in the field of prostate cancer vaccines. This review will discuss the rationale for the development of vaccines involving whole tumor cells and dendritic cells, as well as pox viral vectors, and will summarize selected clinical studies that have incorporated these strategies. PMID: 15988910 [PubMed - indexed for MEDLINE]

Photodynamic therapy using meso tetra hydroxy phenyl chlorin (mTHPC) in early prostate cancer.


Photodynamic therapy using meso tetra hydroxy phenyl chlorin (mTHPC) in early prostate cancer.
Photodynamic therapy using meso tetra hydroxy phenyl chlorin (mTHPC) in early prostate cancer. Lasers Surg Med. 2006 Jan 3; Authors: Moore CM, Nathan TR, Lees WR, Mosse CA, Freeman A, Emberton M, Bown SG BACKGROUND AND OBJECTIVES: Prostate cancer is increasing in incidence, but current treatments including surgery and radiotherapy have significant side effects. This pilot study was designed to assess the potential of photodynamic therapy (PDT) using meso tetra hydroxy phenyl chlorin (mTHPC) for organ confined prostate cancer. STUDY DESIGN/PATIENTS AND METHODS: Six men with organ confined prostate cancer were photosensitised with mTHPC (0.15 mg/kg). Between 2 and 5 days later, red light (652 nm) was delivered to areas of biopsy proven cancer via fibres inserted through transperineal needles (50-100 J per site). RESULTS: After 8 of 10 PDT sessions, the prostate specific antigen (PSA) fell by up to 67%. Early MRI scans showed oedema and patchy necrosis, which resolved over 2 months. Biopsies of treated areas revealed necrosis and fibrosis at 1-2 months. CONCLUSIONS: PDT for primary prostate cancer appears safe and can reduce PSA levels. As this was a phase I study, no attempt was made to treat the whole prostate; this or targeted tumour ablation could be attempted in a phase II study with an increased number of fibres. This technique merits further investigation in early prostate cancer. Lasers Surg. Med. (c) 2005 Wiley-Liss, Inc. PMID: 16392142 [PubMed - as supplied by publisher]

[Advances in brachytherapy]


[Advances in brachytherapy]
Related Articles [Advances in brachytherapy] Arch Esp Urol. 2005 May;58(4):279-84 Authors: Green TC PMID: 15989090 [PubMed - indexed for MEDLINE]

Combined antiangiogenic and immune therapy of prostate cancer.


Combined antiangiogenic and immune therapy of prostate cancer.
Related Articles Combined antiangiogenic and immune therapy of prostate cancer. Angiogenesis. 2005;8(1):13-23 Authors: Huang X, Raskovalova T, Lokshin A, Krasinskas A, Devlin J, Watkins S, Wolf SF, Gorelik E Experimental studies of antiangiogenic or immune therapy of cancer have generated a great deal of optimism. However, the results of clinical testing of these therapies are below expectations. We hypothesized that the antitumor efficacy can be increased when immune destruction of tumor cell is combined with destruction of tumor vasculature by antiangiogenic drugs. In the present study the therapeutic efficacy of combined antiangiogenic and immune therapy has been tested against the highly aggressive, MHC class I negative murine RM1 prostate tumor. SU6668 was used as the antiangiogenic drug and recombinant murine B7.2-IgG fusion protein was used to stimulate T cell-mediated immune destruction of tumor cells. SU6668 is an inhibitor of the tyrosine kinase activity of three angiogenic receptors VEGFR2 (Flk-1/KDR), PDGFRbeta and FGFR1 that play a crucial role in tumor-induced vascularization. Our studies show that B7.2-IgG treatment of mice with established RM1 prostate tumors resulted in a significant inhibition of tumor growth. Both CD4+ and CD8+ T cells were responsible for this effect. SU6668 therapy substantially inhibited tumor vascularization and tumor growth. When tumor-bearing mice were treated with SU6668 in combination with B7.2-IgG, the antitumor effects were substantially higher than in mice treated separately with SU6668 or B7.2-IgG. Prolonged treatment of mice with SU6668 did not inhibit the immunoreactivity of T lymphocytes. On the contrary, T cells from mice treated with a combination of SU6668 and B7.2-IgG showed higher proliferative responses and cytokine production following anti-CD3 stimulation than T cells of mice treated separately with these modalities. These results indicate that antiangiogenic and immune therapies using SU6668 and B7.2-IgG are compatible and manifest complementary antitumor effects. Combined antiangiogenic and immune therapy might represent a new strategy for cancer treatment. PMID: 16132614 [PubMed - indexed for MEDLINE]

Selective blockade of androgenic steroid synthesis by novel lyase inhibitors as a therapeutic strategy for treating metastatic prostate cancer.


Selective blockade of androgenic steroid synthesis by novel lyase inhibitors as a therapeutic strategy for treating metastatic prostate cancer.
Related Articles Selective blockade of androgenic steroid synthesis by novel lyase inhibitors as a therapeutic strategy for treating metastatic prostate cancer. BJU Int. 2005 Dec;96(9):1241-6 Authors: Attard G, Belldegrun AS, de Bono JS PMID: 16287438 [PubMed - indexed for MEDLINE]

Re: luteinizing hormone-releasing hormone agonist effects on skeletal muscle: how hormonal therapy in prostate cancer affects muscular strength.


Re: luteinizing hormone-releasing hormone agonist effects on skeletal muscle: how hormonal therapy in prostate cancer affects muscular strength.
Related Articles Re: luteinizing hormone-releasing hormone agonist effects on skeletal muscle: how hormonal therapy in prostate cancer affects muscular strength. J Urol. 2005 Nov;174(5):2068-9 Authors: Marcora S, Oliver S, Callow N, Lemmey A, Stuart N PMID: 16217402 [PubMed - indexed for MEDLINE]

(((prostate cancer treatment) AND "2005/11/13 17.56"[MHDA]:"2115/11/20 14.01"[MHDA])) NOT (( (((prostate cancer[TIAB] AND treatment[TIAB]))) AND "0001"[EDAT]:"2005/11/13 17.56"[EDAT])); +120 new citations


(((prostate cancer treatment) AND "2005/11/13 17.56"[MHDA]:"2115/11/20 14.01"[MHDA])) NOT (( (((prostate cancer[TIAB] AND treatment[TIAB]))) AND "0001"[EDAT]:"2005/11/13 17.56"[EDAT])); +120 new citations
120 new PubMed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: (((prostate cancer treatment) AND "2005/11/13 17.56"[MHDA]:"2115/11/20 14.01"[MHDA])) NOT (( (((prostate cancer[TIAB] AND treatment[TIAB]))) AND "0001"[EDAT]:"2005/11/13 17.56"[EDAT])) These PubMed results were generated on 2006/01/07PubMed, a service of the National Library of Medicine, includes over 15 million citations for biomedical articles back to the 1950's. These citations are from MEDLINE and additional life science journals. PubMed includes links to many sites providing full text articles and other related resources.

Real Stories: We Should All Be Dead 


Real Stories: We Should All Be Dead 
RedNova - Dec 27 5:56 AM
By HELEN CARROLL I had to stay alive for my daughter Jackie Hackett, 43, a receptionist, lives in Wokingham, Berkshire, with her husband, Desmond, and daughter, Samantha, 16. I WAS only 38 when I discovered that I had breast cancer.Save to My Web

Prostate Cancer Screening - The influence of extent of surgical margin positivity on prostate specific antigen recurrence.


The influence of extent of surgical margin positivity on prostate specific antigen recurrence.
Related Articles The influence of extent of surgical margin positivity on prostate specific antigen recurrence. J Clin Pathol. 2005 Oct;58(10):1028-32 Authors: Emerson RE, Koch MO, Jones TD, Daggy JK, Juliar BE, Cheng L BACKGROUND: Positive surgical margins are an adverse prognostic factor in patients undergoing prostatectomy for prostate cancer. The extent of margin positivity varies and its influence on clinical outcome is uncertain. AIMS: To evaluate the linear extent of margin positivity and the number and location of positive sites as prognostic indicators in a series of prostatectomy specimens evaluated with the whole mount technique. METHODS: Eighty six consecutive margin positive prostatectomy specimens were evaluated, and all pathology data were collected prospectively. The linear extent of margin positivity was measured with an ocular micrometer and the total extent of all positive sites was summed. The total number of sites with positive margins and anatomical sites of the positive margins were analysed. RESULTS: The linear extent of margin positivity ranged from 0.01 to 68 mm (mean, 6.8; median, 3.0) and was associated with prostate specific antigen (PSA) recurrence in univariate logistic regression (p = 0.031). In addition, the extent of margin positivity weakly correlated with preoperative PSA (p = 0.017) and tumour volume (p = 0.013), but not with age, prostate weight, Gleason score, pathological stage, or perineural invasion. The total number of positive sites was significantly higher in patients with PSA recurrence (p = 0.037). The location of the positive margin site was not associated with PSA recurrence. The extent of margin positivity correlated with PSA recurrence in univariate analysis, although it had only marginal predictive value when adjusted for Gleason score (p = 0.076). CONCLUSIONS: The extent of margin positivity correlates with PSA recurrence in univariate analysis, although it has no predictive value independent of Gleason score. PMID: 16189146 [PubMed - indexed for MEDLINE]

Prevention of cancer in the older person.


Prevention of cancer in the older person.
Prevention of cancer in the older person. Cancer J. 2005 Nov-Dec;11(6):442-8 Authors: Balducci L Cancer is the most common cause of death up to the age of 85 years and is also a major cause of disability. Screening asymptomatic patients for cancer is the most promising strategy to reduce cancer-related morbidity and mortality in the older population. Though the information related to older people is scanty, it is reasonable to recommend that the screening of older individuals be based on life expectancy, tolerance of screening, and tolerance of antineoplastic therapy. Some form of screening for breast cancer appears indicated for individuals with life expectancy of 5 and more years. If screening for prostate cancer is indicated at all, it should be limited to men with a life expectancy of at least 10 years. The value of screening asymptomatic individuals for lung and ovarian cancer is explored in ongoing clinical trials. PMID: 16393478 [PubMed - in process]

Humoral immune response in prostate cancer patients after immunization with gene-based vaccines that encode for a protein that is proteasomally degraded.


Humoral immune response in prostate cancer patients after immunization with gene-based vaccines that encode for a protein that is proteasomally degraded.
Related Articles Humoral immune response in prostate cancer patients after immunization with gene-based vaccines that encode for a protein that is proteasomally degraded. Cancer Immun. 2005 Jan 11;5:1 Authors: Todorova K, Ignatova I, Tchakarov S, Altankova I, Zoubak S, Kyurkchiev S, Mincheff M Prostate-specific membrane antigen (PSMA), whose expression is upregulated in poorly differentiated, metastatic, and hormone refractory prostate cancer, could be targeted by gene-based vaccines. The aim of this study was to characterize the humoral immune response against PSMA in prostate carcinoma patients who have been vaccinated against PSMA with gene-based vaccines. Sera from prostate cancer patients who had been immunized repeatedly with plasmid DNA and a recombinant adenoviral vector, both carrying an expression cassette for human PSMA, and sera from healthy donors were tested for anti-PSMA antibodies by Western blot analysis and immunofluorescence. PSMA-producing LNCaP cells, recombinant PSMA protein, and a specific antibody against PSMA were used as positive controls. Specific anti-PSMA antibodies were detected by both Western blot and immunofluorescence in the sera of patients who had been vaccinated against PSMA with plasmid and recombinant adenoviral vectors. The specificity of the anti-PSMA antibodies was confirmed by preincubation and blocking experiments. Positive reactions were detected in 86% of the vaccinated prostate cancer patients. Anti-PSMA antibodies were not detected either in the patients' sera prior to vaccination or in the sera from healthy men and women. These data demonstrate that PSMA, a specific marker for prostate cancer, is a target for humoral immune response induced by gene-based PSMA vaccination. Detection of anti-PSMA antibodies by immunoblot analysis and by indirect immunofluorescence could be used to monitor the vaccination effect. PMID: 15641767 [PubMed - indexed for MEDLINE]

[Construction and immunological study of recombinant hBD-2/PSMA chimeric protein eukaryotic expressive plasmid]


[Construction and immunological study of recombinant hBD-2/PSMA chimeric protein eukaryotic expressive plasmid]
Related Articles [Construction and immunological study of recombinant hBD-2/PSMA chimeric protein eukaryotic expressive plasmid] Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2005 Apr;22(2):283-7 Authors: Li M, Sun Y, Feng Y, Wu Q, Huang N, Wang B The recombinant PSMA DNA vaccine for active immunotherapy of prostate cancer was investigated. Two DNA vaccine recombinant plasmids, pcDNA3.1/PSMA and pcDNA3.1/hBD-2-PSMA, were constructed by inserting the hBD-2 gene and PSMA gene into an eukarytoic expression vector pcDNA3.1. Expression of the two recombinants was detected in transfected COS-7 cells and inoculated mouse muscular cells by RT-PCR and immunohistochemical method. When immunized with pcDNA3.1/PSMA and pcDNA3.1/hBD-2-PSMA, the immunized BALB/c mice acquired specific antibody and T cell response to PSMA. The quantity of the spleen lymphocytes and their CTL activity against PSMA gene transfected-BALB/3T3 cells significantly increased in the immunized mice, and the CTL activity of lymphocytes from pcDNA3.1/hBD-2-PSMA immunized mice was significantly higher than that of pcDNA3.1/PSMA immunized mice. This result suggests that pcDNA3.1/hBD-2-PSMA would probably be developed as a DNA vaccine for the immunotherapy of prostate cancer. PMID: 15884536 [PubMed - in process]

An orthotopic metastatic prostate cancer model in SCID mice via grafting of a transplantable human prostate tumor line.


An orthotopic metastatic prostate cancer model in SCID mice via grafting of a transplantable human prostate tumor line.
Related Articles An orthotopic metastatic prostate cancer model in SCID mice via grafting of a transplantable human prostate tumor line. Lab Invest. 2005 Nov;85(11):1392-404 Authors: Wang Y, Xue H, Cutz JC, Bayani J, Mawji NR, Chen WG, Goetz LJ, Hayward SW, Sadar MD, Gilks CB, Gout PW, Squire JA, Cunha GR, Wang YZ Metastasis is the major cause of prostate cancer deaths and there is a need for clinically relevant in vivo models allowing elucidation of molecular and cellular mechanisms underlying metastatic behavior. Here we describe the development of a new in vivo model system for metastatic prostate cancer. Pieces of prostate cancer tissue from a patient were grafted in testosterone-supplemented male NOD-SCID mice at the subrenal capsule graft site permitting high tumor take rates. After five serial transplantations, the tumor tissues were grafted into mouse prostates. Resulting tumors and suspected metastatic lesions were subjected to histopathological and immunohistochemical analysis. Samples of metastatic tissue were regrafted in mouse anterior prostates and their growth and spread examined, leading to isolation from lymph nodes of a metastatic subline, PCa1-met. Orthotopic grafting of PCa1-met tissue in 47 hosts led in all cases to metastases to multiple organs (lymph nodes, lung, liver, kidney, spleen and, notably, bone). Histopathological analysis showed strong similarity between orthotopic grafts and their metastases. The latter were of human origin as indicated by immunostaining using antibodies against human mitochondria, androgen receptor, prostate-specific antigen and Ki-67. Spectral karyotyping showed few chromosomal alterations in the PCa1-met subline. This study indicates that transplantable subrenal capsule xenografts of human prostate cancer tissue in NOD-SCID mice can, as distinct from primary cancer tissue, be successfully grown in the orthotopic site. Orthotopic xenografts of the transplantable tumor lines and metastatic sublines can be used for studying various aspects of metastatic prostate cancer, including metastasis to bone. PMID: 16155594 [PubMed - indexed for MEDLINE]

[Advances in brachytherapy]


[Advances in brachytherapy]
Related Articles [Advances in brachytherapy] Arch Esp Urol. 2005 May;58(4):279-84 Authors: Green TC PMID: 15989090 [PubMed - indexed for MEDLINE]

Combined antiangiogenic and immune therapy of prostate cancer.


Combined antiangiogenic and immune therapy of prostate cancer.
Related Articles Combined antiangiogenic and immune therapy of prostate cancer. Angiogenesis. 2005;8(1):13-23 Authors: Huang X, Raskovalova T, Lokshin A, Krasinskas A, Devlin J, Watkins S, Wolf SF, Gorelik E Experimental studies of antiangiogenic or immune therapy of cancer have generated a great deal of optimism. However, the results of clinical testing of these therapies are below expectations. We hypothesized that the antitumor efficacy can be increased when immune destruction of tumor cell is combined with destruction of tumor vasculature by antiangiogenic drugs. In the present study the therapeutic efficacy of combined antiangiogenic and immune therapy has been tested against the highly aggressive, MHC class I negative murine RM1 prostate tumor. SU6668 was used as the antiangiogenic drug and recombinant murine B7.2-IgG fusion protein was used to stimulate T cell-mediated immune destruction of tumor cells. SU6668 is an inhibitor of the tyrosine kinase activity of three angiogenic receptors VEGFR2 (Flk-1/KDR), PDGFRbeta and FGFR1 that play a crucial role in tumor-induced vascularization. Our studies show that B7.2-IgG treatment of mice with established RM1 prostate tumors resulted in a significant inhibition of tumor growth. Both CD4+ and CD8+ T cells were responsible for this effect. SU6668 therapy substantially inhibited tumor vascularization and tumor growth. When tumor-bearing mice were treated with SU6668 in combination with B7.2-IgG, the antitumor effects were substantially higher than in mice treated separately with SU6668 or B7.2-IgG. Prolonged treatment of mice with SU6668 did not inhibit the immunoreactivity of T lymphocytes. On the contrary, T cells from mice treated with a combination of SU6668 and B7.2-IgG showed higher proliferative responses and cytokine production following anti-CD3 stimulation than T cells of mice treated separately with these modalities. These results indicate that antiangiogenic and immune therapies using SU6668 and B7.2-IgG are compatible and manifest complementary antitumor effects. Combined antiangiogenic and immune therapy might represent a new strategy for cancer treatment. PMID: 16132614 [PubMed - indexed for MEDLINE]

[Indications of the association of radiotherapy and hormonal treatment in prostate cancer]


[Indications of the association of radiotherapy and hormonal treatment in prostate cancer]
Related Articles [Indications of the association of radiotherapy and hormonal treatment in prostate cancer] Cancer Radiother. 2005 Nov;9(6-7):394-8 Authors: Bolla M, Maingon P, Fourneret P, Artignan X, Descotes JL RTOG and EORTC randomised phase III trials investigated combination of radiation therapy and hormonal treatment in locally advanced prostate cancer T2c-T4 N0-1 M0 (UICC 2002). Complete androgen blockade initiated 2 months prior to starting radiotherapy and stopped at the completion of radiotherapy vs radiation therapy alone, increased overall survival in patients with Gleason score 2-6. Adjuvant androgen suppression started at the end of the radiotherapy and continued indefinitely improved significantly overall survival of patients Gleason score 8 to 10. Complete androgen blockade in two months before and two months during radiation followed by 24 additional months of LHRH analogue alone improved overall survival of patients Gleason score 8-10 with respect to CAB alone. EORTC trial 22861 has shown that androgen suppression with LHRH analogue given during and for 3 years after external irradiation improved overall survival whatever the Gleason score. The role of hormonal treatment is currently assessed in localized prostate cancer (T1-2 N0) with poor prognostic factors: Gleason score 8-10, PSA>20 ng/ml. PMID: 16226044 [PubMed - indexed for MEDLINE]

Salvage radiotherapy for biochemical recurrence after radical prostatectomy.


Salvage radiotherapy for biochemical recurrence after radical prostatectomy.
Related Articles Salvage radiotherapy for biochemical recurrence after radical prostatectomy. BJU Int. 2005 Nov;96(7):1009-13 Authors: Terai A, Matsui Y, Yoshimura K, Arai Y, Dodo Y OBJECTIVE: To evaluate the clinical outcome of salvage radiotherapy (RT) for biochemical recurrence after radical prostatectomy (RP) at our institution. PATIENTS AND METHODS: Between March 1999 and January 2004, 37 patients had salvage RT for prostate-specific antigen (PSA) failure after RP, including eight who had had neoadjuvant hormone therapy. After surgery, PSA was measured with ultrasensitive immunoassays. In all patients RT was delivered to the prostatic bed at a total dose of 60 Gy with a four-field box technique. RESULTS: The median (range) PSA level before salvage RT was 0.146 (0.06-3.216) ng/mL and RT was started at a PSA level of <0.5 ng/mL in 34 of the 37 patients (92%). With a median follow-up of 31.9 (0-69.8), months, 11 patients (30%) had disease progression after RT and the 3- and 5-year progression-free probability was 74% and 54%, respectively. Univariate analysis showed that clinical and pathological tumour stages and PSA level before RT (>0.15 vs < or = 0.15 ng/mL) were significant predictors of disease progression. There were no late adverse events related to RT. CONCLUSION: Salvage RT for biochemical failure after RP at a low PSA level, using ultrasensitive immunoassays for monitoring, is a reasonably effective treatment. A relatively low radiation dose (60 Gy) seems to be effective. PMID: 16225518 [PubMed - indexed for MEDLINE]

(((prostate cancer treatment) AND "2005/11/13 17.56"[MHDA]:"2115/11/20 14.01"[MHDA])) NOT (( (((prostate cancer[TIAB] AND treatment[TIAB]))) AND "0001"[EDAT]:"2005/11/13 17.56"[EDAT])); +120 new citations


(((prostate cancer treatment) AND "2005/11/13 17.56"[MHDA]:"2115/11/20 14.01"[MHDA])) NOT (( (((prostate cancer[TIAB] AND treatment[TIAB]))) AND "0001"[EDAT]:"2005/11/13 17.56"[EDAT])); +120 new citations
120 new PubMed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: (((prostate cancer treatment) AND "2005/11/13 17.56"[MHDA]:"2115/11/20 14.01"[MHDA])) NOT (( (((prostate cancer[TIAB] AND treatment[TIAB]))) AND "0001"[EDAT]:"2005/11/13 17.56"[EDAT])) These PubMed results were generated on 2006/01/07PubMed, a service of the National Library of Medicine, includes over 15 million citations for biomedical articles back to the 1950's. These citations are from MEDLINE and additional life science journals. PubMed includes links to many sites providing full text articles and other related resources.

January 02, 2006

MedSpa and Deli Offer Tips for Holiday Fitness -- and Indulgence 


MedSpa and Deli Offer Tips for Holiday Fitness -- and Indulgence 
[Press Release] PR Web - Dec 06 12:23 AM
Nara Luxury MedSpa and Boianis Italian Market provide simple ways to enjoy holiday festivities yet look and feel good all the way through New Years and beyond. [PRWEB Dec 6, 2005]Save to My Web

Prostate Cancer Screening - Use of tissue recombination to predict phenotypes of transgenic mouse models of prostate carcinoma.


Use of tissue recombination to predict phenotypes of transgenic mouse models of prostate carcinoma.
Related Articles Use of tissue recombination to predict phenotypes of transgenic mouse models of prostate carcinoma. Lab Invest. 2005 Sep;85(9):1086-103 Authors: Ishii K, Shappell SB, Matusik RJ, Hayward SW Transgenic mouse models of cancer represent a powerful approach for exploring disease processes and testing potential therapeutic interventions. Currently, it is difficult to predict if a specific genetic manipulation will result in a desirable phenotype. The present study tests the idea that tissue recombinants recapitulate the pathologic features of the neoplastic prostate seen in transgenic mice, and would thus be suitable predictive models for new mouse design. The large probasin-large T-antigen (LPB-Tag) transgenic lines 12T-7f and 12T-10 were used as a basis for this study. Tissue recombinants of bladder epithelium (BlE) and urogenital sinus mesenchyme (UGM) were implanted under the renal capsule of athymic mice. Recombinants composed of BlE from 12T-10 LPB-Tag and wild-type (wt) UGM faithfully recapitulated the histopathologic and temporal features of intact transgenic mice of this line. Tissue recombinants using BlE from 12T-7f mice and wt UGM developed epithelial proliferation with atypia that lacked the associated hypercellular stroma seen in the intact 12T-7f line. Recombinants using 12T-7f UGM demonstrated that the hypercellular stroma results from stromal cell expression of the SV40 large T antigen. Corresponding to the recombinant phenotypes, stromal Tag immunostaining was observed in prostate tissues from intact 12T-7f but not 12T-10 mice. Similar stromal expression of Tag was also noted in the hypercellular TRAMP prostatic stroma. Further analysis revealed a previously unreported pattern of SV40T expression in the LADY and TRAMP models including ductus deferens and seminal vesicle stroma as well as region and cell type-specific patterns in the epididymis. The present study demonstrates the utility of using tissue recombination to explore organ-specific phenotypes. Recombination strategies should enable quick and cost-effective screening for likely phenotypes in transgenic animals. This comparison of tissue recombination to existing models shows that this approach can elicit new information on well-characterized models. PMID: 15980886 [PubMed - indexed for MEDLINE]

The protective effects of green tea in prostate cancer.


The protective effects of green tea in prostate cancer.
Related Articles The protective effects of green tea in prostate cancer. BJU Int. 2005 Dec;96(9):1212-4 Authors: Patel SP, Hotston M, Kommu S, Persad RA PMID: 16287430 [PubMed - indexed for MEDLINE]

[Identification of tumor antigens: strategies and perspectives]


[Identification of tumor antigens: strategies and perspectives]
Related Articles [Identification of tumor antigens: strategies and perspectives] Schweiz Rundsch Med Prax. 2004 Sep 22;93(39):1584-8 Authors: J ger D, Zippelius A, Knuth A The identification of tumor antigens is crucial for the development of antigen-specific immunotherapies in cancer. Ideal target antigens for immunotherapies have a tumor specific expresssion pattern. Antigen expresssion in solid tumors is typically heterogenous. Therefore an effective immunotherapy should target several antigens simultaneously (polyvalent vaccine). Here we discuss strategies how tumor antigens can be identified and further analyzed as potential target antigens for active immunotherapy (cancer vaccine). PMID: 15500242 [PubMed - indexed for MEDLINE]

[Subcapsular orchiectomy in the treatment of prostate cancer: results]


[Subcapsular orchiectomy in the treatment of prostate cancer: results]
Related Articles [Subcapsular orchiectomy in the treatment of prostate cancer: results] Arch Esp Urol. 2005 May;58(4):305-8 Authors: Pascual Mateo C, Luján Galán M, Santos Arrontes D, Berenguer Sánchez A OBJECTIVES: To analyze the role of orchiectomy in the management of metastasic prostate cancer in our environment. METHODS: We studied 76 patients with the diagnosis of prostate cancer who underwent subcapsular orchiectomy. RESULTS: Mean age was 72 years, median Gleason score was 7, and only 17% had organ confined tumors. Mean follow-up was 2.3 yr. and hospital stay median three days. Ten of the 76 patients in the study died from cancer, being overall five-year survival 75%. Regarding cost analysis, surgical castration was cheaper in the long-term but has the disadvantage of its greater psychological impact. CONCLUSIONS: Orchiectomy is a valid hormonal blockade option when estimated patient survival is longer than one year. PMID: 15989093 [PubMed - indexed for MEDLINE]