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March 21, 2006

Chili's Heat Kills Prostate Cancer Cells


Chili's Heat Kills Prostate Cancer Cells
Forbes - Mar 16, 2006... can occur between conventional and alternative therapies. ... a jaded eye, toward time-honored herbal treatments. ... For more on prostate cancer, head to the National ...

Prostate Cancer Screening - Modulation of mitogen-activated protein kinase cascades by differentiation-1 protein: acquired drug resistance of hormone independent prostate cancer cells.


Modulation of mitogen-activated protein kinase cascades by differentiation-1 protein: acquired drug resistance of hormone independent prostate cancer cells.
Related Articles Modulation of mitogen-activated protein kinase cascades by differentiation-1 protein: acquired drug resistance of hormone independent prostate cancer cells. J Urol. 2005 Nov;174(5):2022-6 Authors: Lin JC, Chang SY, Hsieh DS, Lee CF, Yu DS PURPOSE: The inhibitor of differentiation-1 protein (Id-1) is over expressed in multidrug resistance prostate cancer cells. We determined the effect of Id-1 expression and its underlying pathways on the development of multidrug resistance in prostate cancer. MATERIALS AND METHODS: AT3 cells were transfected with the Id-1 gene or a blank vector. Id-1 mRNA expression was determined by reverse transcriptase-polymerase chain reaction and Id-1 protein content was detected by immunoblot and flow cytometry. Cellular cytotoxicity was determined by MTT (microculture 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay (Sigma Chemical Co., St. Louis, Missouri). The activation and expression of mitogen-activated protein kinase (MAPK) were measured by transactivation assay and Western blotting, respectively. RESULTS: Id-1 overproduction drove AT3 cells to become resistant to chemotherapeutic agents but did not induce mdr-1 gene expression. The p38MAPK and c-jun N-terminal kinase (JNK) pathways were suppressed, which correlated with increased Id-1 expression. No significant change in extracellular signal-regulated kinase (ERK) activation was observed in Id-1 transfectants compared with that of AT3 or vector control. Treatment of Id-1 expressing cells with p38MAPK and JNK inhibitors resulted in decreased doxorubicin induced apoptosis. In contrast, Id-1 expressing cells treated with ERK inhibitor made cells more sensitive to drug induced apoptosis. CONCLUSIONS: Up-regulation of Id-1 was found in prostate cancer multidrug resistant cells. Sustained ERK activation, and JNK and p38MAPK inhibition by Id-1 in cells may confer drug resistance. These changes in MAPKs could be a mechanism for the acquisition of multidrug resistance in prostate cancer. PMID: 16217386 [PubMed - indexed for MEDLINE]

Maintaining bone health in patients with prostate cancer.


Maintaining bone health in patients with prostate cancer.
Related Articles Maintaining bone health in patients with prostate cancer. Med J Aust. 2006 Feb 20;184(4):176-9 Authors: Holmes-Walker DJ, Woo H, Gurney H, Do VT, Chipps DR Loss of bone mineral density with androgen deprivation therapy (ADT) for prostate cancer is well recognised, with significant loss of bone mineral density (BMD) occurring within 12 months of starting therapy. With ADT, annual loss of BMD is about 2%-8% per year at the lumbar spine and 1.8%-6.5% at the hip; the loss appears to continue indefinitely while treatment continues, and there is no recovery after therapy is ceased. 19.4% of men surviving at least 5 years after diagnosis of prostate cancer have a fracture if treated with ADT compared with 12.6% of men not receiving ADT; this is equivalent to one additional fracture for every 28 men treated with ADT. Vitamin D deficiency exacerbates the development of osteoporosis, so vitamin D status should be evaluated before commencing ADT in men with prostate cancer. Treatment with bisphosphonates (zoledronate, pamidronate and alendronate) in men treated with ADT have been shown to prevent bone loss in prospective studies and to increase BMD in one randomised controlled trial; bisphosphonates have not been shown to prevent fractures in men with prostate cancer. Further prospective trials are required to assess the efficacy and cost-effectiveness of bisphosphonates in men with prostate cancer who require treatment with ADT. All doctors need to take an active role in monitoring bone health in patients with prostate cancer requiring ADT. PMID: 16489902 [PubMed - indexed for MEDLINE]

Gene delivery and gene therapy of prostate cancer.


Gene delivery and gene therapy of prostate cancer.
Related Articles Gene delivery and gene therapy of prostate cancer. Expert Opin Drug Deliv. 2006 Jan;3(1):37-51 Authors: Kaliberov SA, Buchsbaum DJ Surgery, radiation or hormonal therapy are not adequate to control prostate cancer. Clearly, other novel treatment approaches, such as gene therapy, for advanced/recurrent disease are desperately needed to achieve long-term local control and particularly to develop effective systemic therapy for metastatic prostate cancer. In the last decade, significant progress in gene therapy for the treatment of localised prostate cancer has been demonstrated. A broad range of different gene therapy approaches, including cytolytic, immunological and corrective gene therapy, have been successfully applied for prostate cancer treatment in animal models, with translation into early clinical trials. In addition, a wide variety of viral and nonbiological gene delivery systems are available for basic and clinical research. Gene therapy approaches that have been developed for the treatment of prostate cancer are summarised. PMID: 16370939 [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 - indexed for MEDLINE]

Maintaining bone health in patients with prostate cancer.


Maintaining bone health in patients with prostate cancer.
Related Articles Maintaining bone health in patients with prostate cancer. Med J Aust. 2006 Feb 20;184(4):176-9 Authors: Holmes-Walker DJ, Woo H, Gurney H, Do VT, Chipps DR Loss of bone mineral density with androgen deprivation therapy (ADT) for prostate cancer is well recognised, with significant loss of bone mineral density (BMD) occurring within 12 months of starting therapy. With ADT, annual loss of BMD is about 2%-8% per year at the lumbar spine and 1.8%-6.5% at the hip; the loss appears to continue indefinitely while treatment continues, and there is no recovery after therapy is ceased. 19.4% of men surviving at least 5 years after diagnosis of prostate cancer have a fracture if treated with ADT compared with 12.6% of men not receiving ADT; this is equivalent to one additional fracture for every 28 men treated with ADT. Vitamin D deficiency exacerbates the development of osteoporosis, so vitamin D status should be evaluated before commencing ADT in men with prostate cancer. Treatment with bisphosphonates (zoledronate, pamidronate and alendronate) in men treated with ADT have been shown to prevent bone loss in prospective studies and to increase BMD in one randomised controlled trial; bisphosphonates have not been shown to prevent fractures in men with prostate cancer. Further prospective trials are required to assess the efficacy and cost-effectiveness of bisphosphonates in men with prostate cancer who require treatment with ADT. All doctors need to take an active role in monitoring bone health in patients with prostate cancer requiring ADT. PMID: 16489902 [PubMed - indexed for MEDLINE]

Patterns of practice in the management of prostate cancer: results from multidisciplinary surveys of clinicians in Australia and New Zealand in 1995 and 2000.


Patterns of practice in the management of prostate cancer: results from multidisciplinary surveys of clinicians in Australia and New Zealand in 1995 and 2000.
Related Articles Patterns of practice in the management of prostate cancer: results from multidisciplinary surveys of clinicians in Australia and New Zealand in 1995 and 2000. BJU Int. 2006 Mar 17; Authors: Chong CC, Austen L, Kneebone A, Lalak A, Jalaludin B OBJECTIVE To investigate and compare patterns of practice in prostate cancer management in Australia and New Zealand from 1995 to 2000, as there are insufficient randomized trials to guide clinicians in the management of prostate cancer. SUBJECTS AND METHODS This study represents the two largest published surveys of Australian and New Zealand clinicians dealing with prostate cancer. We sent structured questionnaires on the management of prostate cancer patients to 804 urologists, radiation oncologists and medical oncologists in Australia and New Zealand in December 2000. We compared responses to a similar survey of 579 specialist clinicians in 1995. RESULTS The response rates were 56% in 1995 and 62% in 2000. In the management of clinically localized disease, the proportion recommending surgery or radiotherapy remained relatively constant between 1995 and 2000, although there was an increase in the use of brachytherapy and adjuvant hormonal therapy, and a reduced tendency to treat pelvic nodes. In the treatment of locally advanced disease, there was an increased use of hormonal treatment and local radiotherapy, with a reduction in the use of total androgen blockade and orchidectomy. In managing positive margins after prostatectomy, there was a clear lack of consensus, with a wide variety of treatment options proposed. CONCLUSIONS Practice has changed in several areas in 2000 compared to 1995, but not all changes were influenced by the publication of randomized trials or evidence-based guidelines. PMID: 16542341 [PubMed - as supplied by publisher]

A recombinant PSMA-specific single-chain immunotoxin has potent and selective toxicity against prostate cancer cells.


A recombinant PSMA-specific single-chain immunotoxin has potent and selective toxicity against prostate cancer cells.
Related Articles A recombinant PSMA-specific single-chain immunotoxin has potent and selective toxicity against prostate cancer cells. Cancer Immunol Immunother. 2006 Mar 18; Authors: Wolf P, Gierschner D, B hler P, Wetterauer U, Els sser-Beile U Prostate cancer is the most commonly diagnosed form of cancer and the second leading cancer-related death among men in the Western civilization. Since no effective therapy exists for this tumor after progression beyond resectable boundaries, there is an urgent need for new treatment strategies. Prostate specific membrane antigen (PSMA) represents an excellent target on prostate cancer cells, and therefore specific immunotherapy may be a novel therapeutic option for the management of this tumor. We constructed a fully recombinant immunotoxin (A5-PE40) from a single-chain antibody fragment (scFv) against cell-adherent PSMA and a truncated form of Pseudomonas exotoxin A (PE40) lacking its natural binding domain Ia. The scFv A5 was obtained from a mAb elicited with native PSMA by phage display technology and direct selection on cells carrying the antigen. The bacterially expressed and purified immunotoxin A5-PE40 specifically binds to PSMA-positive prostate cancer cells and induces a 50% reduction of viability (IC50) at a concentration of 20 pM, while PSMA-negative cells remain unaffected. Due to its high and specific toxicity this recombinant immunotoxin is a promising candidate for therapeutic applications in patients with prostate cancer. PMID: 16547705 [PubMed - as supplied by publisher]

Macrophage/cancer cell interactions mediate hormone resistance by a nuclear receptor derepression pathway.


Macrophage/cancer cell interactions mediate hormone resistance by a nuclear receptor derepression pathway.
Related Articles Macrophage/cancer cell interactions mediate hormone resistance by a nuclear receptor derepression pathway. Cell. 2006 Feb 10;124(3):615-29 Authors: Zhu P, Baek SH, Bourk EM, Ohgi KA, Garcia-Bassets I, Sanjo H, Akira S, Kotol PF, Glass CK, Rosenfeld MG, Rose DW Defining the precise molecular strategies that coordinate patterns of transcriptional responses to specific signals is central for understanding normal development and homeostasis as well as the pathogenesis of hormone-dependent cancers. Here we report specific prostate cancer cell/macrophage interactions that mediate a switch in function of selective androgen receptor antagonists/modulators (SARMs) from repression to activation in vivo. This is based on an evolutionarily conserved receptor N-terminal L/HX7LL motif, selectively present in sex steroid receptors, that causes recruitment of TAB2 as a component of an N-CoR corepressor complex. TAB2 acts as a sensor for inflammatory signals by serving as a molecular beacon for recruitment of MEKK1, which in turn mediates dismissal of the N-CoR/HDAC complex and permits derepression of androgen and estrogen receptor target genes. Surprisingly, this conserved sensor strategy may have arisen to mediate reversal of sex steroid-dependent repression of a limited cohort of target genes in response to inflammatory signals, linking inflammatory and nuclear receptor ligand responses to essential reproductive functions. PMID: 16469706 [PubMed - indexed for MEDLINE]

Factors contributing to the racial differences in prostate cancer mortality.


Factors contributing to the racial differences in prostate cancer mortality.
Related Articles Factors contributing to the racial differences in prostate cancer mortality. BJU Int. 2005 Dec;96(9):1247-52 Authors: Tewari A, Horninger W, Pelzer AE, Demers R, Crawford ED, Gamito EJ, Divine G, Johnson CC, Bartsch G, Menon M OBJECTIVE: To analyse, in a retrospective cohort study, differences in rates of surgical treatment for prostate cancer between African-Americans and White Americans, and to evaluate the extent to which these differences are associated with disparities in survival rates between these groups. PATIENTS AND METHODS: Clinical, pathological, and demographic data from 4279 men diagnosed with clinically localized prostate cancer between 1980 and 1997 were used. The variables assessed included age, disease stage, tumour grade, comorbidities, treatment method, and socio-economic status (SES). Kaplan-Meier survival curves were generated and compared using log-rank tests. The Cox proportional hazards method was used for analyses involving adjustments for potential confounding factors. RESULTS: The surgical treatment rate was 17% for African-American and 28% for White patients (P < 0.001). In those patients treated conservatively or by radiation therapy, both crude and cancer-specific survival rates were lower for African-Americans than for Whites (P < 0.001). However, for patients undergoing surgery, differences in survival between African-Americans and Whites were not statistically significant. According to our models, SES explained 50% and surgical treatment rates approximately 34% of the differences in survival between African-Americans and Whites. CONCLUSIONS: This analysis suggests that the lower prostate cancer survival rates for the African-Americans in the present population can be largely explained by differences in SES and lower surgical treatment rates. Efforts to increase awareness of treatment options among African-American patients may be a way of improving survival in this group. PMID: 16287439 [PubMed - indexed for MEDLINE]

A dosimetric comparison of 169Yb versus 192Ir for HDR prostate brachytherapy.


A dosimetric comparison of 169Yb versus 192Ir for HDR prostate brachytherapy.
Related Articles A dosimetric comparison of 169Yb versus 192Ir for HDR prostate brachytherapy. Med Phys. 2005 Dec;32(12):3832-42 Authors: Lymperopoulou G, Papagiannis P, Sakelliou L, Milickovic N, Giannouli S, Baltas D For the purpose of evaluating the use of 169Yb for prostate High Dose Rate brachytherapy (HDR), a hypothetical 169Yb source is assumed with the exact same design of the new microSelectron source replacing the 192Ir active core by pure 169Yb metal. Monte Carlo simulation is employed for the full dosimetric characterization of both sources and results are compared following the AAPM TG-43 dosimetric formalism. Monte Carlo calculated dosimetry results are incorporated in a commercially available treatment planning system (SWIFT), which features an inverse treatment planning option based on a multiobjective dose optimization engine. The quality of prostate HDR brachytherapy using the real 192Ir and hypothetical 169Yb source is compared in a comprehensive analysis of different prostate implants in terms of the multiobjective dose optimization solutions as well as treatment quality indices such as Dose Volume Histograms (DVH) and the Conformal Index (COIN). Given that scattering overcompensates for absorption in intermediate photon energies and distances in the range of interest to prostate HDR brachytherapy, 169Yb proves at least equivalent to 192Ir irrespective of prostate volume. This has to be evaluated in view of the shielding requirements for the 169Yb energies that are minimal relative to that for 192Ir. PMID: 16475783 [PubMed - indexed for MEDLINE]

March 16, 2006

New research bruises reputations of many nutrition supplements


New research bruises reputations of many nutrition supplements
Detroit News - "I personally think with the price of health care skyrocketing out of control, you will see a lot more people going the herbal route." Deborah Swegard, Pinckney "I started taking pharmaceutical grade supplements almost two years ago and have noticed

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]

Chemoprevention of rat prostate carcinogenesis by diallyl disulfide, an organosulfur compound of garlic.


Chemoprevention of rat prostate carcinogenesis by diallyl disulfide, an organosulfur compound of garlic.
Related Articles Chemoprevention of rat prostate carcinogenesis by diallyl disulfide, an organosulfur compound of garlic. Biol Pharm Bull. 2006 Feb;29(2):375-9 Authors: Arunkumar A, Vijayababu MR, Venkataraman P, Senthilkumar K, Arunakaran J Diallyl disulfide (DADS), an important component of garlic (Allium sativam) has been demonstrated to exert a potential chemopreventive activity against human cancers. DADS inhibits proliferation of both androgen dependent and independent prostate cancer cells in vitro. However there is no report available on the role of DADS on prostate cancer initiation in in vivo model. So the present chemoprevention study was conducted to evaluate the activity of diallyl disulfide as an anticancer agent in prostate carcinogenesis of male Sprague-Dawley rats. Testosterone and N-Methyl N-Nitroso Urea (MNU) were used to induce prostate carcinogenesis that involves a multi step process like, hyperplasia, dysplasia and prostatic intraepithelial neoplasia (PIN). The rats were induced prostate carcinogenesis by injection of testosterone and single dose of MNU and again the testosterone was continued throughout the experimental period. Forty percentage of animals carried PIN in dorsolateral prostate, while dysplasia and hyperplasia (55 to 65%) were common in ventral as well as dorsolateral prostates of the hormone and carcinogen treated rats. Rats treated with hormone and carcinogen along with DADS developed PIN at incidence of 10% in the ventral and dorsolateral prostates about 20 to 10%. Dysplasia and hyperplasia were less common in these rats. The results of this study provide evidence that DADS may have chemopreventive activity in rat prostate carcinogenesis. PMID: 16462049 [PubMed - indexed for MEDLINE]

The order of genetic events associated with colorectal cancer progression inferred from meta-analysis of copy number changes.


The order of genetic events associated with colorectal cancer progression inferred from meta-analysis of copy number changes.
Related Articles The order of genetic events associated with colorectal cancer progression inferred from meta-analysis of copy number changes. Genes Chromosomes Cancer. 2006 Jan;45(1):31-41 Authors: Diep CB, Kleivi K, Ribeiro FR, Teixeira MR, Lindgjaerde OC, Lothe RA To identify chromosomal aberrations that differentiate among the Dukes' stages of colorectal cancer (CRC) as well as those that are responsible for the progression into liver metastases, we performed a meta-analysis of data obtained from 31 comparative genomic hybridization (CGH) studies comprising a total of 859 CRCs. Individual copy number profiles for 373 primary tumors and 102 liver metastases were recorded and several statistical analyses, such as frequency, multivariate logistic regression, and trend tests, were performed. In addition, time of occurrence analysis was applied for the first time to copy number changes identified by CGH, and each genomic imbalance was thereby classified as an early or late event in colorectal tumorigenesis. By combining data from the different statistical tests, we present a novel genetic pathway for CRC progression that distinguishes the Dukes' stages and identifies early and late events in both primary carcinomas and liver metastases. Results from the combined analyses suggest that losses at 17p and 18 and gains of 8q, 13q, and 20 occur early in the establishment of primary CRCs, whereas loss of 4p is associated with the transition from Dukes' A to B-D. Deletion of 8p and gains of 7p and 17q are correlated with the transition from primary tumor to liver metastasis, whereas losses of 14q and gains of 1q, 11, 12p, and 19 are late events. We supplement these findings with a list of potential target genes for the specific alterations from a publicly available microarray expression dataset of CRC. PMID: 16145679 [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 - indexed for MEDLINE]

Urinary incontinence and voiding dysfunction after radical retropubic prostatectomy (prospective urodynamic study).


Urinary incontinence and voiding dysfunction after radical retropubic prostatectomy (prospective urodynamic study).
Related Articles Urinary incontinence and voiding dysfunction after radical retropubic prostatectomy (prospective urodynamic study). Neurourol Urodyn. 2006;25(1):2-7 Authors: Majoros A, Bach D, Keszthelyi A, Hamvas A, Romics I AIMS: During this prospective study we analyzed the effects of radical retropubic prostatectomy (RRP) on bladder and sphincter function by comparing preoperative and postoperative urodynamic data. The aim of the study was to determine the reason for urinary incontinence after RRP and explain why one group of patients will be immediately continent after catheter removal, while others need some time to reach complete continence. METHODS: Urodynamic examination was performed in 63 patients 3-7 days before and 2 months after surgery. RESULTS: Forty-three (68.2%) and 53 (84.1%) patients regained continence at 2 and 9 months following RRP, respectively. Ten patients (15.9%) were immediately continent after catheter removal. Urodynamic stress incontinence was detected in 18 (28.6%), and detrusor overactivity incontinence in 2 (3.2%) patients 2 months after surgery. The amplitude of preoperative maximal voluntary sphincteric contractions was significantly higher in the postoperative continent group (125 vs. 96.5 cmH(2)O, P < 0.0001). The patients who were immediately continent following catheter removal had no lower urinary tract symptoms (LUTS) and urodynamic abnormality preoperatively, and they had significantly higher preoperative and postoperative maximum urethral closure pressure (at rest and during voluntary sphincter contraction) than those who became continent later on. CONCLUSIONS: These data suggest that the main cause of incontinence after RRP is sphincteric weakness. In the continent group, those who became immediately continent had significantly higher maximum urethral closure pressure values at rest and at voluntary sphincteric contraction even before the surgery. PMID: 16224797 [PubMed - indexed for MEDLINE]

Genitourinary small cell carcinoma: a retrospective review of treatment and survival patterns at The Ottawa Hospital Regional Cancer Center.


Genitourinary small cell carcinoma: a retrospective review of treatment and survival patterns at The Ottawa Hospital Regional Cancer Center.
Genitourinary small cell carcinoma: a retrospective review of treatment and survival patterns at The Ottawa Hospital Regional Cancer Center. BJU Int. 2006 Apr;97(4):711-5 Authors: Asmis TR, Reaume MN, Dahrouge S, Malone S OBJECTIVE To review patients with genitourinary (GU) small cell carcinoma (SCC) treated at a regional cancer centre, as due to its rarity and aggressive nature, GU SCC remains a therapeutic challenge. PATIENTS AND METHODS The charts of patients managed at a regional cancer centre between 1991 and 2002 for any GU diagnosis were manually reviewed to identify GU SCC. Demographic, staging, treatment and outcome data were extracted. The Veterans Administration small cell lung cancer staging classification of 'limited' or 'extensive' disease was adapted for SCC of the prostate and bladder (with 'limited' defined as disease localized to the true and false pelvis, and 'extensive' as disease beyond the pelvis). RESULTS In all, 555, 858 and 5066 new cases of primary renal, bladder and prostate cancer, respectively, were identified. Of these patients, 22 had GU SCC (12 bladder and 10 prostate; there were no cases of SCC of the kidney). Eight of 12 patients with bladder SCC had limited disease; five of 12 are alive (all with limited disease at diagnosis), and the median survival was 19.8 months. Surviving patients received similar therapy, with transurethral resection of the bladder tumour, platinum-based chemotherapy, etoposide (4-6 cycles), and radical radiotherapy (56-60 Gy). Two of 10 patients with SCC of the prostate had limited-stage disease, but all 10 died, the median survival being 9.5 months. Survival by stage for both types combined was 59 months for limited disease and 8 months for extensive disease. CONCLUSIONS These results indicate that GU SCC is an aggressive cancer; limited-stage SCC of the bladder or prostate, when treated with platinum/etoposide chemotherapy and radical radiotherapy, has a more favourable outcome than that of extensive GU SCC. PMID: 16536759 [PubMed - in process]

[Prostate cancer gene therapy]


[Prostate cancer gene therapy]
Related Articles [Prostate cancer gene therapy] Nippon Rinsho. 2005 Dec;63 Suppl 12:544-7 Authors: Nasu Y, Abarzua F, Kumon H PMID: 16416850 [PubMed - indexed for MEDLINE]

Management strategies for locally advanced prostate cancer.


Management strategies for locally advanced prostate cancer.
Management strategies for locally advanced prostate cancer. Drugs Aging. 2006;23(2):119-29 Authors: Jani AB Locally advanced prostate cancer represents a subpopulation of prostate cancer diagnosed in patients who are either untouched by screening efforts or whose disease has an unusually rapidly progressive natural history. The diagnostic work-up for the locally advanced patient is distinct from that of early stage disease in several respects in that it is related principally to ruling out metastases. The typical metastatic work-up consists of a serum alkaline phosphatase, bone scan, CT of the abdomen/pelvis, and chest x-ray. Once metastatic disease has been ruled out, individual components of the management of locally advanced prostate cancer patients may include surgery (palliative or curative), external beam radiation therapy (with photons or particles) or brachytherapy (with low-dose rate/permanent or high-dose rate/temporary radiation sources), and hormone therapy. Unlike in early stage disease, observation/watchful waiting is typically not a treatment option in locally advanced prostate cancer.Of the curative local control modalities, the one most commonly used, and the one which has emerged as the clinical standard, is photon external beam radiotherapy (EBRT). Numerous randomised studies have shown that androgen ablation has an established role in conjunction with radiotherapy for locally advanced disease - the current standard of care is thus photon EBRT plus neoadjuvant and adjuvant androgen ablation. Long-term androgen ablation appears to be better than short-term ablation, even when hormone complications are considered. EBRT is typically delivered to the prostate, seminal vesicles and pelvic lymph nodes, although in some circumstances local fields to the prostate and seminal vesicles may be adequate. New treatment planning and delivery techniques, such as intensity-modulated radiotherapy and organ motion tracking, are being developed to reduce the morbidity of radiotherapy while permitting a higher delivered dose.Further work is necessary to determine the precise sequencing and duration of hormone therapy in conjunction with radiotherapy and the optimum radiotherapy treatment volume. Additional work is also needed to determine the precise groups benefiting from other local control modalities such as surgery and brachytherapy. Finally, novel investigational strategies such as chemotherapy and gene therapy are being applied in an attempt to improve outcomes of locally advanced prostate cancer patients. PMID: 16536635 [PubMed - in process]

Promise for prostatitis?


Promise for prostatitis?
Related Articles Promise for prostatitis? BJU Int. 2005 Nov;96(7):1137-8 Authors: Wyllie MG PMID: 16225543 [PubMed - indexed for MEDLINE]

Genitourinary small cell carcinoma: a retrospective review of treatment and survival patterns at The Ottawa Hospital Regional Cancer Center.


Genitourinary small cell carcinoma: a retrospective review of treatment and survival patterns at The Ottawa Hospital Regional Cancer Center.
Genitourinary small cell carcinoma: a retrospective review of treatment and survival patterns at The Ottawa Hospital Regional Cancer Center. BJU Int. 2006 Apr;97(4):711-5 Authors: Asmis TR, Reaume MN, Dahrouge S, Malone S OBJECTIVE To review patients with genitourinary (GU) small cell carcinoma (SCC) treated at a regional cancer centre, as due to its rarity and aggressive nature, GU SCC remains a therapeutic challenge. PATIENTS AND METHODS The charts of patients managed at a regional cancer centre between 1991 and 2002 for any GU diagnosis were manually reviewed to identify GU SCC. Demographic, staging, treatment and outcome data were extracted. The Veterans Administration small cell lung cancer staging classification of 'limited' or 'extensive' disease was adapted for SCC of the prostate and bladder (with 'limited' defined as disease localized to the true and false pelvis, and 'extensive' as disease beyond the pelvis). RESULTS In all, 555, 858 and 5066 new cases of primary renal, bladder and prostate cancer, respectively, were identified. Of these patients, 22 had GU SCC (12 bladder and 10 prostate; there were no cases of SCC of the kidney). Eight of 12 patients with bladder SCC had limited disease; five of 12 are alive (all with limited disease at diagnosis), and the median survival was 19.8 months. Surviving patients received similar therapy, with transurethral resection of the bladder tumour, platinum-based chemotherapy, etoposide (4-6 cycles), and radical radiotherapy (56-60 Gy). Two of 10 patients with SCC of the prostate had limited-stage disease, but all 10 died, the median survival being 9.5 months. Survival by stage for both types combined was 59 months for limited disease and 8 months for extensive disease. CONCLUSIONS These results indicate that GU SCC is an aggressive cancer; limited-stage SCC of the bladder or prostate, when treated with platinum/etoposide chemotherapy and radical radiotherapy, has a more favourable outcome than that of extensive GU SCC. PMID: 16536759 [PubMed - in process]

March 15, 2006

New research bruises reputations of many nutrition supplements


New research bruises reputations of many nutrition supplements
Detroit News - "I personally think with the price of health care skyrocketing out of control, you will see a lot more people going the herbal route." Deborah Swegard, Pinckney "I started taking pharmaceutical grade supplements almost two years ago and have noticed

Prostate Cancer Screening - Sexual, psychological and dyadic qualities of the prostate cancer 'couple'.


Sexual, psychological and dyadic qualities of the prostate cancer 'couple'.
Related Articles Sexual, psychological and dyadic qualities of the prostate cancer 'couple'. J Urol. 2005 Nov;174(5):1939 Authors: Seftel A PMID: 16217353 [PubMed - indexed for MEDLINE]

Chemoprevention of rat prostate carcinogenesis by diallyl disulfide, an organosulfur compound of garlic.


Chemoprevention of rat prostate carcinogenesis by diallyl disulfide, an organosulfur compound of garlic.
Related Articles Chemoprevention of rat prostate carcinogenesis by diallyl disulfide, an organosulfur compound of garlic. Biol Pharm Bull. 2006 Feb;29(2):375-9 Authors: Arunkumar A, Vijayababu MR, Venkataraman P, Senthilkumar K, Arunakaran J Diallyl disulfide (DADS), an important component of garlic (Allium sativam) has been demonstrated to exert a potential chemopreventive activity against human cancers. DADS inhibits proliferation of both androgen dependent and independent prostate cancer cells in vitro. However there is no report available on the role of DADS on prostate cancer initiation in in vivo model. So the present chemoprevention study was conducted to evaluate the activity of diallyl disulfide as an anticancer agent in prostate carcinogenesis of male Sprague-Dawley rats. Testosterone and N-Methyl N-Nitroso Urea (MNU) were used to induce prostate carcinogenesis that involves a multi step process like, hyperplasia, dysplasia and prostatic intraepithelial neoplasia (PIN). The rats were induced prostate carcinogenesis by injection of testosterone and single dose of MNU and again the testosterone was continued throughout the experimental period. Forty percentage of animals carried PIN in dorsolateral prostate, while dysplasia and hyperplasia (55 to 65%) were common in ventral as well as dorsolateral prostates of the hormone and carcinogen treated rats. Rats treated with hormone and carcinogen along with DADS developed PIN at incidence of 10% in the ventral and dorsolateral prostates about 20 to 10%. Dysplasia and hyperplasia were less common in these rats. The results of this study provide evidence that DADS may have chemopreventive activity in rat prostate carcinogenesis. PMID: 16462049 [PubMed - indexed for MEDLINE]

Large differences in testosterone excretion in Korean and Swedish men are strongly associated with a UDP-glucuronosyl transferase 2B17 polymorphism.


Large differences in testosterone excretion in Korean and Swedish men are strongly associated with a UDP-glucuronosyl transferase 2B17 polymorphism.
Related Articles Large differences in testosterone excretion in Korean and Swedish men are strongly associated with a UDP-glucuronosyl transferase 2B17 polymorphism. J Clin Endocrinol Metab. 2006 Feb;91(2):687-93 Authors: Jakobsson J, Ekstr m L, Inotsume N, Garle M, Lorentzon M, Ohlsson C, Roh HK, Carlstr m K, Rane A CONTEXT: The reproductive endocrinology in Asians and Caucasians is of great interest in view of large differences in prostate cancer rate and sensitivity to pharmacological male contraception. In addition, interpretation of certain antidoping tests is confounded by interethnic variation in androgen disposition. Uridine diphosphoglucuronosyl transferases have a key role in the homeostasis and metabolism of androgens. Recently a deletion polymorphism was detected in the UGT2B17 gene. OBJECTIVE: The objective of the study was to evaluate the contribution of the UGT2B17 deletion polymorphism to the interindividual and interethnic variation of androgen metabolism and excretion. METHODS AND RESULTS: Urine from 122 Swedish and 74 Korean healthy men was analyzed for several androgen glucuronides including testosterone. The distribution of the natural logarithms of urinary testosterone concentrations showed a distinct bimodal pattern in both groups, suggesting a monogenic inheritance. When the UGT2B17 genotypes were compared with urinary testosterone levels, all of the individuals of the UGT2B17 homozygous deletion/deletion genotype had no or negligible amounts of urinary testosterone. The deletion/deletion genotype was seven times more common in the Korean (66.7%) than the Swedish population (9.3%). In addition, the Swedes had significantly higher levels of serum testosterone, compared with the Koreans. CONCLUSIONS: Our results show that the UGT2B17 polymorphism is strongly associated with the bimodal distribution of the testosterone excretion and also with the large differences in testosterone excretion between Koreans and Swedes. PMID: 16332934 [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 - indexed for MEDLINE]

[Volume and health outcomes: an overview of systematic reviews]


[Volume and health outcomes: an overview of systematic reviews]
Related Articles [Volume and health outcomes: an overview of systematic reviews] Epidemiol Prev. 2005 May-Aug;29(3-4 Suppl):3-63 Authors: Davoli M, Amato L, Minozzi S, Bargagli AM, Vecchi S, Perucci CA BACKGROUND: Improving quality and effectiveness of health care is one of the priorities of health policies. Hospital or physician volume of activity may be a measurable variable with a relevant impact on effectiveness of health care. There are several studies and systematic reviews evaluating the association between volume and outcome of health care. The aim of this review is to identify: areas, clinical conditions or interventions (prevention, diagnostic, therapeutic, surgical or clinical) for which an association between volume and outcome has been investigated; those for which an association between volume and outcome has been proved METHODS: Overview of systematic reviews and Health Technology Assessment reports; search of MEDLINE, EMBASE, The Cochrane Library, Web sites of Health Technology Assessment, other HTA Agencies, National guideline Clearinghouse, National Health Care quality tools (1995-february 2005). For each studied area results are described separately for each review due to the heterogeneity of outcomes, volume thresholds and results reported. No metanalysis has been conducted. Completeness of reporting of the systematic reviews has been evaluated using the QUOROM statement. For each review we evaluated the number of studies included and the proportion of studies with statistically significant results (p < 0,05). As far as in-hospital mortality is concerned, the different areas have been classified in the following groups: Strong evidence ofpositive association: areas with > or =10 studies included in the reviews, and high prevalence (> or =50%) of positive studies (p <0. 05) in the majority of reviews. Weak evidence of association: areas with 5 to 9 studies included in the reviews and high prevalence (> or =50%) of positive studies (p <0.05) in the majority of reviews. Weak evidence of lack of association: areas with 5 to 9 studies included in the reviews and high prevalence (>50%) of not statistically significant studies (p >0.05) in the majority of reviews. No suficient evidence of association: areas with less than 5 studies included in the reviews. No evidence of association: areas with > or =10 studies included in the reviews, and high prevalence (>50%) of not statistically significant studies (p >0.05) in the majority of reviews. The same literature search was then applied to identify primary studies published in each considered area following the most recent systematic review published. RESULTS AND DISCUSSION: We identified 21 systematic reviews and included 11 of them analysing 46 different areas. The majority of studies evaluate the effect of specific surgical procedures; the main outcomes considered are hospital mortality and 5 year survival for cancers. Considering in-hospital mortalilty as outcome, in 11 areas there is strong evidence ofassociation between volume of activity and outcome: abdominalaortic aneurysm (unruptured), percutaneous transluminal coronary angioplasty knee arthroplasty coronary artery bypass, surgery for oesophageal and pancreatic cancer, surgery for prostate cancer, colecistectomy, carotid endarterectomy, myocardial infarction, neonatal intensive care. It is never possible however to identify a unique volume threshold. For some of these areas, particularly coronary angioplasty and coronary artery bypass, there are many new studies published following the last systematic review; some specific aspects are being investigated such as the role of temporal changes in the association, the effect of different risk adjustment procedures and the separate role of physician or hospital volume. In some cases, for example knee arthroplasty in-hospital mortality could be an inadequate outcome on which judging the strength of association, in fact, the few studies evaluating other outcomes such as complications provide inconsistent results. For a range of areas the evidence of association is weak: AIDS, appendicectomy, cardiac catheterization, surgery for breast, lung, stomach cancer, hernia repair, hip fracture, hysterectomy and injuries. As far as AIDS is concerned, the few number of studies found is probably due to the lack of studies published after the introduction of effective therapies. All the included studies show an evidence of association between volume and in-hospital mortality. In no case we found weak evidence of lack of association while we identified three conditions for which the number of studies included in the reviews together with the prevalence of non significant studies do suggest lack of association; these are abdominal aortic aneurysm (ruptured), hip arthroplasty and surgery for colorectal cancer. In the case of hip arthroplasty as well, inhospital mortality could be an inadequate outcome, but only one old study found a positive association with risk of complications. Eventually there is a group of areas (n=22) for which there is not enough evidence to draw conclusions about the association between volume and outcome due to a small number of studies. In some cases, such as transplants, this could be due to the low rate of events; in this case all the few published studies show positive results. There are some limitations which should be taken into account in the interpretation of these results: despite the overall good completeness of reporting of the included reviews, the majority of studies included in the reviews themselves are cross-sectional studies representing a very weak study design to evaluate causality of the investigated association. Moreover the methodology of risk adjustment applied is heterogenous among studies and it is difficult to know the extent to which this can affect the observed results. It is eventually necessary to consider the possible occurrence of publication bias which could lead to an overestimation of the positive effect of volume on health care outcomes attributable to the lack of publication of negative studies. CONCLUSIONS: In some areas the evidence seems strong enough to guide health care organizational choices, although it is not possible to identify well defined volume thresholds. In other areas, particularly for non surgical conditions, where there is not enough evidence, it seems necessary to conduct proper epidemiological studies. Also the evaluation of effectiveness of using volume as an instrument of health policy requires further research. Taking into account the rapid and continuing process of technology development, the definition of standard and prerequisite volumes of care should be specific of each temporal period and health care system. It is therefore a dynamic process requiring a continuous review of the available evidence. In the area of evidence based public health, the limited available evidence should not impair the choice of actions based on limited evidence, but rather it should lead to the application of thefew available evidence on one side and to the planning of proper research in the areas of lack of evidence. PMID: 16529350 [PubMed - in process]

Hyperglycemia and insulin resistance in men with prostate carcinoma who receive androgen-deprivation therapy.


Hyperglycemia and insulin resistance in men with prostate carcinoma who receive androgen-deprivation therapy.
Related Articles Hyperglycemia and insulin resistance in men with prostate carcinoma who receive androgen-deprivation therapy. Cancer. 2006 Feb 1;106(3):581-8 Authors: Basaria S, Muller DC, Carducci MA, Egan J, Dobs AS BACKGROUND: Prostate carcinoma (PCa) is one of the most common malignancies in men. Androgen-deprivation therapy (ADT) is used frequently in the treatment of recurrent and metastatic PCa, rendering these men hypogonadal. Because male hypogonadism is associated with an unfavorable metabolic profile, and men with PCa have high cardiovascular mortality, the authors evaluated the effects of long-term ADT on fasting glucose levels, insulin levels, and insulin resistance. METHODS: To evaluate the long-term effects of ADT on fasting glucose and insulin resistance in men with PCa who received ADT and to determine whether these metabolic alterations are a result of hypogonadism, the authors conducted a cross-sectional study at a university-based research institution in the United States. In total, 53 men were evaluated, including 18 men with PCa who received ADT for at least 12 months prior to the onset of the study (the ADT group), 17 age-matched men with nonmetastatic PCa who had undergone prostatectomy and/or received radiotherapy and who were not receiving ADT (the non-ADT group), and 18 age-matched controls (the control group). None of the men had a known history of diabetes mellitus. RESULTS: The mean age was similar in all 3 groups (P=0.33). Serum total testosterone levels (P<0.0001) and free testosterone levels (P<0.0001) were significantly lower in the ADT group compared with the other groups. Men in the ADT group had a higher BMI compared with the other groups (overall P=0.005). After adjustment for age and BMI, men in the ADT group had significantly higher fasting levels of the following parameters: 1) Glucose levels were 131.0+/-7.43 mg/dL in the ADT group compared with 103.0+/-7.42 mg/dL in the non-ADT group (P=0.01) and 99.0+/-7.58 mg/dL in the control group (P<0.01). 2) Insulin levels were 45.0+/-7.25 uU/mL in the ADT group compared with 24.0+/-7.24 uU/mL in the non-ADT group (P=0.05) and 19.0+/-7.39 uU/mL in the control group (P=0.02). 3) Leptin levels were 25.0+/-2.57 ng/mL in the ADT group compared with 12.0+/-2.56 ng/mL in the non-ADT group (P<0.01) and 6.0+/-2.62 ng/mL in the control group (P<0.01). 4) The homeostatic model assessment for insulin resistance (HOMAIR)=17.0+/-2.78 in the ADT group compared with HOMAIR=6.0+/-2.77 in the non-ADT group (P<0.01) and HOMAIR=5.0+/-2.83 in the control group (P=0.01). There was a significant negative correlation between total and free testosterone levels with fasting glucose, insulin, leptin, and HOMAIR. CONCLUSIONS: The current data suggested that men with PCa who are receiving long-term ADT are at risk for developing insulin resistance and hyperglycemia, thus leading to their increased risk of cardiovascular disease. This adverse metabolic profile developed independent of age and BMI and appeared to be a direct result of androgen deprivation. PMID: 16388523 [PubMed - indexed for MEDLINE]

Antibody-based therapeutics: focus on prostate cancer.


Antibody-based therapeutics: focus on prostate cancer.
Related Articles Antibody-based therapeutics: focus on prostate cancer. Cancer Metastasis Rev. 2005 Dec;24(4):521-37 Authors: Ross JS, Gray KE, Webb IJ, Gray GS, Rolfe M, Schenkein DP, Nanus DM, Millowsky MI, Bander NH The recent clinical and commercial success of anti-cancer antibodies such as rituximab, trastuzumab, cetuximab and bevacizumab has continued to foster great interest in antibody-based therapeutics for the treatment of both hematopoietic malignancies and solid tumors. Given the likely lower toxicity for antibodies which, in contrast with traditional cytotoxic small molecule drugs, target tumor cells and have a lower impact on non-malignant by-stander organs, the potential increases in efficacy associated with conjugation to radioisotopes and other cellular toxins and the ability to characterize the target with clinical laboratory diagnostics to improve the drugs clinical performance, it is anticipated that current and future antibody therapeutics will find substantial roles alone and in combination therapy strategies for the treatment of patients with cancer. A significant number of cell surface proteins, glycoproteins, receptors, enzymes and peptides have been discovered that have become targets for the treatment of advanced hormone-refractory prostate cancer. A variety of naked antibodies and antibody conjugates have currently progressed through preclinical development and are in early or more advanced stages of clinical development. Clinicians, scientists and prostate cancer patients are all keenly interested to learn whether these agents when administered alone or in combination with other hormonal-based and cytotoxic therapies will show lasting benefit for sufferers of this common disease. PMID: 16408160 [PubMed - indexed for MEDLINE]

Thermally induced injury and heat-shock protein expression in cells and tissues.


Thermally induced injury and heat-shock protein expression in cells and tissues.
Thermally induced injury and heat-shock protein expression in cells and tissues. Ann N Y Acad Sci. 2006 Mar;1066:222-42 Authors: Rylander MN, Feng Y, Bass J, Diller KR Heat-shock proteins (HSPs) are critical components of a cell's defense mechanism against injury associated with adverse stresses. Initiating insults, such as elevated or depressed temperature, diminished oxygen, and pressure, increase HSP expression and can protect cells against subsequent, otherwise lethal, insults. Although HSPs are very beneficial to the normal cell, cancer cells can also use HSPs in response to stresses associated with various therapies (hyperthermia, chemotherapy, radiation), mitigating injury incurred by these treatments. Hyperthermia is a common treatment option for prostate cancer. HSPs can be induced in regions of the tumor where temperatures are insufficient to cause lethal thermal necrosis. Elevated HSP expression can enhance tumor cell viability and impart increased resistance to subsequent chemotherapy and radiation treatments, thereby promoting tumor recurrence. An understanding of the structure, function, and thermally stimulated HSP kinetics and cell injury for prostate cancer cells is essential to designing effective hyperthermia protocols. Measured thermally induced cellular HSP expression and injury data can be employed to develop a treatment planning model for optimization of the tissue response to therapy based on accurate prediction of the HSP expression and cell damage distribution. PMID: 16533928 [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]

Quercetin-induced growth inhibition and cell death in prostatic carcinoma cells (PC-3) are associated with increase in p21 and hypophosphorylated retinoblastoma proteins expression.


Quercetin-induced growth inhibition and cell death in prostatic carcinoma cells (PC-3) are associated with increase in p21 and hypophosphorylated retinoblastoma proteins expression.
Related Articles Quercetin-induced growth inhibition and cell death in prostatic carcinoma cells (PC-3) are associated with increase in p21 and hypophosphorylated retinoblastoma proteins expression. J Cancer Res Clin Oncol. 2005 Nov;131(11):765-71 Authors: Vijayababu MR, Kanagaraj P, Arunkumar A, Ilangovan R, Aruldhas MM, Arunakaran J Prostate cancer is the major health problem and the leading cause of male cancer death. Quercetin is a novel antitumor and antioxidant, whose molecular mechanism involved in cell cycle arrest in androgen independent prostate cancer cells remains unclear. In this study, we investigated the effects of quercetin on proliferation and cell cycle arrest by modulation of Cdc2/Cdk-1 protein in prostate cancer cells (PC-3). PC- 3 cells are human androgen independent cancer cells and were cultured with quercetin at concentrations of 50 and 100 microM for 24 h. Cell proliferation, apoptosis and cell cycle distribution were analyzed. Expression of Cdc2/Cdk-1, cyclin B1, cyclin A, p21/Cip1, pRb, pRb2/p130, Bcl-2, Bcl-X(L), Bax and caspase-3 proteins were studied with western blot analysis. Addition of quercetin led to substantial decrease in the expression of Cdc2/Cdk-1, cyclin B1 and phosphorylated pRb and increase in p21. Flowcytometric analysis showed that quercetin blocks G2-M transition, with significant induction of apoptosis. Apoptosis markers like Bcl-2 and Bcl-X(L) were significantly decreased and Bax and caspase-3 were increased. From this study, it was concluded that quercetin inhibits prostate cancer cell proliferation by altering the expression of cell cycle regulators and apoptotic proteins. PMID: 16049707 [PubMed - indexed for MEDLINE]

March 12, 2006

Delayed Prostate Cancer Surgery Poses No Increased Risk for Some ...


Delayed Prostate Cancer Surgery Poses No Increased Risk for Some ...
eMaxHealth.com, NC - Mar 9, 2006... stage, low-grade prostate cancer, an alternative to immediate ... contribute to a decrease in prostate cancer mortality in ... it may lead to invasive treatments of a ...

Prostate Cancer Screening - Obesity and capsular incision at the time of open retropubic radical prostatectomy.


Obesity and capsular incision at the time of open retropubic radical prostatectomy.
Related Articles Obesity and capsular incision at the time of open retropubic radical prostatectomy. J Urol. 2005 Nov;174(5):1798-801; discussion 1801 Authors: Freedland SJ, Grubb KA, Yiu SK, Nielsen ME, Mangold LA, Isaacs WB, Epstein JI, Partin AW PURPOSE: The goal of radical prostatectomy (RP) is complete removal of the intact prostate. Obese men can represent a technical challenge. However, to our knowledge objective data linking obesity with technically inferior surgery are lacking. Therefore, we examined the association between body mass index (BMI) and capsular incision at RP as a surrogate of a poor technical operation in men treated for prostate cancer by several high volume surgeons at a center of excellence. MATERIALS AND METHODS: The study population consisted of 7,027 men treated with anatomical retropubic RP between 1996 and 2004 by 7 high volume surgeons. We evaluated the association between BMI and capsular incision using logistic regression, adjusting for clinical and pathological variables, and for the surgeon. RESULTS: Overall capsular incision was noted in 4.6% of all RP specimens. After adjustment for preoperative prostate specific antigen, patient race, height, year of surgery, clinical stage, pathological Gleason sum, prostate weight, extraprostatic extension and seminal vesicle invasion increased BMI was associated with increased odds of capsular incision (p trend = 0.005). After further adjustment for surgeon mild obesity was associated with 30% increased odds of capsular incision (OR 1.30, 95% CI 0.92 to 1.83), while moderate and severe obesity was associated with 57% increased odds of capsular incision (OR 1.57, 95% CI 0.82 to 3.00) relative to normal weight men (p trend = 0.06). CONCLUSIONS: In a study of more than 7,000 men treated by 7 experienced surgeons BMI was positively related to capsular incision. This suggests that open retropubic RP is technically more difficult in obese men, which results in a greater likelihood of a less than technically ideal operation. Although this may be predicted to have a negative impact on disease-free survival outcomes in obese men, it is unlikely to alone explain the worse outcomes in obese men noted in previous RP series. PMID: 16217290 [PubMed - indexed for MEDLINE]

Lycopene as a chemopreventive agent in the treatment of high-grade prostate intraepithelial neoplasia.


Lycopene as a chemopreventive agent in the treatment of high-grade prostate intraepithelial neoplasia.
Related Articles Lycopene as a chemopreventive agent in the treatment of high-grade prostate intraepithelial neoplasia. Urol Oncol. 2005 Nov-Dec;23(6):383-5 Authors: Mohanty NK, Saxena S, Singh UP, Goyal NK, Arora RP OBJECTIVE: Because of its long latency, slow growing nature, and high prevalence, prostate cancer is the best model for chemoprevention. High-grade prostate intraepithelial neoplasia (HGPIN) is a precursor of prostate cancer. Chemoprevention with lycopene has shown definite results in prostate cancer. We undertook a study to use lycopene as a chemopreventive agent in the treatment of HGPIN for preventing prostate cancer from developing in this vulnerable group of patients. MATERIALS AND METHODS: A total of 40 patients with HGPIN were randomized into 2 groups: one received 4 mg lycopene twice a day for one year, and the other was periodically followed up. Total follow-up was one year. RESULTS: Our results show that lycopene can delay or prevent HGPIN from developing into occult prostate cancer, and there exists an inverse relationship between lycopene and prostate-specific antigen. Being a vegetable carotenoid, lycopene is a safe drug to be used for a longer period without any adverse reaction. CONCLUSION: Lycopene is an effective chemopreventive agent in the treatment of HGPIN, with no toxicity and good patient tolerance. PMID: 16301113 [PubMed - indexed for MEDLINE]

Association between polymorphisms in the DNA repair genes XRCC1 and APE1, and the risk of prostate cancer in white and black Americans.


Association between polymorphisms in the DNA repair genes XRCC1 and APE1, and the risk of prostate cancer in white and black Americans.
Related Articles Association between polymorphisms in the DNA repair genes XRCC1 and APE1, and the risk of prostate cancer in white and black Americans. J Urol. 2006 Jan;175(1):108-12; discussion 112 Authors: Chen L, Ambrosone CB, Lee J, Sellers TA, Pow-Sang J, Park JY PURPOSE: XRCC1 and APE1 are enzymes involved in the repair of DNA strand breaks and base damage that arise from various endogenous and exogenous oxidants. We determined whether polymorphisms in XRCC1 and APE1 increase the risk of prostate cancer. MATERIALS AND METHODS: We performed a case-control study in 228 white American men, 124 black American men, and 335 age, sex and race matched controls. Polymorphisms at codon 399 in XRCC1, and at codons 51 and 148 in APE1 were determined using an restriction fragment length polymorphism method. Frequencies were compared between cases and controls. RESULTS: A significantly increased risk of prostate cancer was observed in white men with the XRCC1(399Gln) allele (OR 1.6, 95% CI 1.1 to 2.4). When APE1 and XRCC1 polymorphisms were evaluated together, we found an increased risk of the XRCC1(399Arg/Gln+Gln/Gln)/APE1(51Gln/Gln) (OR 4.0, 95% CI 1.3 to 12.5) and XRCC1(399Arg/Gln+Gln/Gln)/APE1(148Asp/Asp) (OR 2.9, 95% CI 1.4 to 6.1) genotypes in white men. Significant associations were found between combined genotypes and prostate cancer risk with a dose-effect relationship in white men (trend test p = 0.035 and 0.039, respectively). No significant associations were observed between polymorphisms in these genes and prostate cancer risk in black men. CONCLUSIONS: Our results suggest that inherited variability in DNA repair capacity, as reflected by polymorphisms in XRCC1 and APE1, is a risk factor for prostate cancer. PMID: 16406883 [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 - indexed for MEDLINE]

prostate cancer surgery; +83 new citations


prostate cancer surgery; +83 new citations
83 new PubMed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: prostate cancer surgery These PubMed results were generated on 2006/03/12PubMed, 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.

prostate cancer Radiation therapy; +44 new citations


prostate cancer Radiation therapy; +44 new citations
44 new PubMed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: prostate cancer Radiation therapy These PubMed results were generated on 2006/03/12PubMed, 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.

Immunotherapy for prostate cancer.


Immunotherapy for prostate cancer.
Related Articles Immunotherapy for prostate cancer. Curr Pharm Des. 2006;12(7):807-17 Authors: Karnes RJ, Whelan CM, Kwon ED The absence of curative therapies for advanced or recurrent forms of prostate cancer has prompted a vigorous search for novel treatment strategies. Immunotherapy encompasses one particularly promising systemic approach to treat prostate cancer. Immune-based strategies to treat prostate cancer have recently been facilitated by the identification of a number of prostate tissue/tumor antigens that can be targeted, either by antibody or T cells, to promote prostate tumor cell injury or death. These same prostate antigens can also be used for the construction of vaccines to induce prostate-specific T cell-mediated immunity. Greater insight into specific mechanisms that govern antigen-specific T cell activation has brought with it a number of innovative methods to induce and enhance T cell-mediated responses against prostate tumors. For instance, autologous dendritic cells loaded with prostate antigens have proved useful to induce prostate-specific T cell activation. Similarly, in vivo manipulations of the T cell costimulatory pathway receptors can greatly facilitate tumor-specific T cell activation and potentiate T cell-mediated responses against a number of malignancies, including prostate cancer. Therefore, in this review we summarize recent advances pertaining to immunotherapeutic approaches to treat prostate cancer. PMID: 16515497 [PubMed - in process]

prostate cancer chemotherapy; +64 new citations


prostate cancer chemotherapy; +64 new citations
64 new PubMed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: prostate cancer chemotherapy These PubMed results were generated on 2006/03/12PubMed, 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.

Factors contributing to the racial differences in prostate cancer mortality.


Factors contributing to the racial differences in prostate cancer mortality.
Related Articles Factors contributing to the racial differences in prostate cancer mortality. BJU Int. 2005 Dec;96(9):1247-52 Authors: Tewari A, Horninger W, Pelzer AE, Demers R, Crawford ED, Gamito EJ, Divine G, Johnson CC, Bartsch G, Menon M OBJECTIVE: To analyse, in a retrospective cohort study, differences in rates of surgical treatment for prostate cancer between African-Americans and White Americans, and to evaluate the extent to which these differences are associated with disparities in survival rates between these groups. PATIENTS AND METHODS: Clinical, pathological, and demographic data from 4279 men diagnosed with clinically localized prostate cancer between 1980 and 1997 were used. The variables assessed included age, disease stage, tumour grade, comorbidities, treatment method, and socio-economic status (SES). Kaplan-Meier survival curves were generated and compared using log-rank tests. The Cox proportional hazards method was used for analyses involving adjustments for potential confounding factors. RESULTS: The surgical treatment rate was 17% for African-American and 28% for White patients (P < 0.001). In those patients treated conservatively or by radiation therapy, both crude and cancer-specific survival rates were lower for African-Americans than for Whites (P < 0.001). However, for patients undergoing surgery, differences in survival between African-Americans and Whites were not statistically significant. According to our models, SES explained 50% and surgical treatment rates approximately 34% of the differences in survival between African-Americans and Whites. CONCLUSIONS: This analysis suggests that the lower prostate cancer survival rates for the African-Americans in the present population can be largely explained by differences in SES and lower surgical treatment rates. Efforts to increase awareness of treatment options among African-American patients may be a way of improving survival in this group. PMID: 16287439 [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])); +262 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])); +262 new citations
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