Prostate Cancer Research

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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]

Posted by blogposter at 10:36 PM | Permalink

Cancer of the prostate.

Crit Rev Oncol Hematol. 2005 Nov 22;56(3):379-396

Authors: Bracarda S, de Cobelli O, Greco C, Prayer-Galetti T, Valdagni R, Gatta G, de Braud F, Bartsch G

Prostate carcinoma, with about 190,000 new cases occurring each year (15% of all cancers in men), is the most frequent cancer among men in northern and western Europe. Causes of the disease are essentially unknown, although hormonal factors are involved, and diet may exert an indirect influence; some genes, potentially involved in hereditary prostate cancer (HPC) have been identified. A suspect of prostate cancer may derive from elevated serum prostate-specific antigen (PSA) values and/or a suspicious digital rectal examination (DRE) finding. For a definitive diagnosis, however, a positive prostate biopsy is requested. Treatment strategy is defined according to initial PSA stage, and grade of the disease and age and general conditions of the patient. In localized disease, watchful waiting is indicated as primary option in patients with well or moderately differentiated tumours and a life expectancy <10 years, while radical prostatectomy and radiotherapy (with or without hormone-therapy) could be appropriate choices in the remaining cases. Hormone-therapy is the treatment of choice, combined with radiotherapy, for locally advanced or bulky disease and is effective, but not curative, in 80-85% of the cases of advanced disease. Patients who develop a hormone-refractory prostate cancer disease (HRPC) have to be evaluated for chemotherapy because of the recent demonstration of improved overall survival (2-2.5 months) and quality of life with docetaxel in more than 1600 cases.

PMID: 16310371 [PubMed - as supplied by publisher]

Posted by blogposter at 10:32 PM | Permalink

Posted by blogposter at 10:11 PM | Permalink

Link between exercise and lower risk for prostate cancer found.

J Am Vet Med Assoc. 2005 Sep 15;227(6):858-9

Authors:

PMID: 16190576 [PubMed - indexed for MEDLINE]

Posted by blogposter at 10:11 PM | Permalink

[Therapy of hormone-refractory prostate cancer.]

Urologe A. 2005 Nov 26;

Authors: Heidenreich A

PSA-progression following primary ADT defines an androgen-refractory but still hormone sensitive PCA which might respond to secondary hormonal manipulations. Secondary hormonal manipulations will result in a PSA decline >50% in about 60-80% of the patients with a mean duration of 7-17 months depending on the type of treatment. PSA-progression following secondary endocrine treatment defines hormone-refractory prostate cancer (HRPCA) which might be treated by systemic chemotherapy. Based on the results of 2 prospective, randomized clinical phase-III trials comparing docetaxel and mitoxantrone, docetaxel results in a statistically significant survival benefit of 2.5 months, a significantly higher PSA- and pain response and represents the treatment of choice in the management of HRPCA. Bisphosphonates such as zoledronate represent another cornerstone in the management of PSA-progressive PCA demonstrating a significant benefit with regard to the prevention of skeletal related events. Furthermore, bisphosphonates might be indicated in the treatment of symptomatic bone pain. The current article critically reflects the various therapeutic options in the management of PSA progression following primary androgen deprivation for advanced prostate cancer.

PMID: 16311709 [PubMed - as supplied by publisher]

Posted by blogposter at 10:10 PM | Permalink

Related Articles

Effects of 2,4-D and DCP on the DHT-induced androgenic action in human prostate cancer cells.

Toxicol Sci. 2005 Nov;88(1):52-9

Authors: Kim HJ, Park YI, Dong MS

2,4-Dichlorophenoxyacetic acid (2,4-D) and its metabolite 2,4-dichlorophenol (DCP) are used extensively in agriculture as herbicides, and are suspected of potential endocrine disruptor activity. In a previous study, we showed that these compounds exhibited synergistic androgenic effects by co-treatment with testosterone in the Hershberger assay. To elucidate the mechanisms of the synergistic effects of these compounds on the androgenicity of testosterone, the androgenic action of 2,4-D and DCP was characterized using a mammalian detection system in prostate cancer cell lines. In in vitro assay systems, while 2,4-D or DCP alone did not show androgenic activity, 2,4-D or DCP with 5alpha-dihydroxytestosterone (DHT) exhibited synergistic androgenic activities. Co-treatment of 10 nM 2,4-D or DCP with 10 nM DHT was shown to stimulate the cell proliferation by 1.6-fold, compared to 10 nM DHT alone. In addition, in transient transfection assays, androgen-induced transactivation was also increased to a maximum of 32-fold or 1.28-fold by co-treatment of 2,4-D or DCP with DHT, respectively. However, 2,4-D and DCP exerted no effects on either mRNA or protein levels of AR. In a competitive AR binding assay, 2,4-D and DCP inhibited androgen binding to AR, up to 50% at concentrations of approximately 0.5 microM for both compounds. The nuclear translocation of green fluorescent protein-AR fusion protein in the presence of DHT was promoted as the result of the addition of 2,4-D and DCP. Collectively, these results that 2,4-D and DCP enhanced DHT-induced AR transcriptional activity might be attributable, at least in part, to the promotion of AR nuclear translocation.

PMID: 16107550 [PubMed - indexed for MEDLINE]

Posted by blogposter at 10:10 PM | Permalink

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]

Posted by blogposter at 10:10 PM | Permalink

Epidural spinal cord compression.

Crit Rev Oncol Hematol. 2005 Nov 22;56(3):397-406

Authors: Spinazz S, Caraceni A, Schrijvers D

Spinal cord compression from epidural metastases (epidural spinal cord compression, ESCC) is the most common neurological complication of cancer after brain metastases. Extradural compression represents 97% of spinal cord metastatic lesions. ESCC usually occurs in patients with disseminated disease. The most common tumours associated with ESCC are lung and breast cancers, followed by lymphoma, myeloma, prostate cancer and sarcoma. ESCC represents a medical emergency because delayed treatment can be responsible for irreversible deficits, such as paralysis and loss of sphincter control. Patients with ESCC require a multidisciplinary diagnostic and therapeutic approach. Clinical suspect is radiologically detected for confirmation. The median expected survival time from diagnosis usually ranges from 3 to 6 months. The nature of the primary tumour and the degree of the neurological deficit are the most important factors affecting survival. The lack of prospective randomized trials makes the optimal treatment of ESCC controversial and the decision is to be tailored to the individual. Treatment options include: bed rest, administration of corticosteroids, surgery followed by radiation therapy, radiotherapy alone and, to a limited extent, chemotherapy and hormonal therapy.

PMID: 16310372 [PubMed - as supplied by publisher]

Posted by blogposter at 10:10 PM | Permalink

Epidural spinal cord compression.

Crit Rev Oncol Hematol. 2005 Nov 22;56(3):397-406

Authors: Spinazzé S, Caraceni A, Schrijvers D

Spinal cord compression from epidural metastases (epidural spinal cord compression, ESCC) is the most common neurological complication of cancer after brain metastases. Extradural compression represents 97% of spinal cord metastatic lesions. ESCC usually occurs in patients with disseminated disease. The most common tumours associated with ESCC are lung and breast cancers, followed by lymphoma, myeloma, prostate cancer and sarcoma. ESCC represents a medical emergency because delayed treatment can be responsible for irreversible deficits, such as paralysis and loss of sphincter control. Patients with ESCC require a multidisciplinary diagnostic and therapeutic approach. Clinical suspect is radiologically detected for confirmation. The median expected survival time from diagnosis usually ranges from 3 to 6 months. The nature of the primary tumour and the degree of the neurological deficit are the most important factors affecting survival. The lack of prospective randomized trials makes the optimal treatment of ESCC controversial and the decision is to be tailored to the individual. Treatment options include: bed rest, administration of corticosteroids, surgery followed by radiation therapy, radiotherapy alone and, to a limited extent, chemotherapy and hormonal therapy.

PMID: 16310372 [PubMed - as supplied by publisher]

Posted by blogposter at 10:10 PM | Permalink

[Expression of prostate stem cell antigen (PSCA) and selection of its specific binding peptide]

Sheng Wu Gong Cheng Xue Bao. 2004 Sep;20(5):694-8

Authors: Hou LH, Du Y, Zhang XP, An XP, Chen W

Prostate stem cell antigen (PSCA), a homologue of the Ly-6/Thy-1 family of cell surface antigen, is expressed by a majority of human prostate cancers and is a promising target for prostate cancer immunotherapy. To obtain the specific peptide binding with PSCA for targeted immunotherapy, PSCA gene was obtained by RT-PCR from human prostate cancer cell line DU145 and the transcated PSCA (tPSCA) gene was cloned into vector pQE30 for soluble expression in E. coli. The identity of recombinant tPSCA was confirmed through ELISA and western blot by use of anti-PSCA monoclonal antibody. Then the 12-peptide phage display library was screened with the purified tPSCA protein for its specific binding peptide through 3 rounds panning. For identifying the peptide's specificity, the peptide was coupled with EGFP (enhanced green fluorecent protein) by recombinant DNA technology and the recombinant coupled protein was termed 11-EGFP. The binding specificity with tPSCA of 11-EGFP was further confirmed by ELISA and competitive inhibition experiment. Flow cytometry demonstrated its binding specificity with cell line DU145. In conclusion, a 12-amino-acid peptide which could bind with PSCA specifically was found and it may be a potential tool for targeted immunotherapy of prostate carcinoma.

PMID: 15973992 [PubMed - in process]

Posted by blogposter at 10:10 PM | Permalink

[Therapy of hormone-refractory prostate cancer.]

Urologe A. 2005 Nov 26;

Authors: Heidenreich A

PSA-progression following primary ADT defines an androgen-refractory but still hormone sensitive PCA which might respond to secondary hormonal manipulations. Secondary hormonal manipulations will result in a PSA decline >50% in about 60-80% of the patients with a mean duration of 7-17 months depending on the type of treatment. PSA-progression following secondary endocrine treatment defines hormone-refractory prostate cancer (HRPCA) which might be treated by systemic chemotherapy. Based on the results of 2 prospective, randomized clinical phase-III trials comparing docetaxel and mitoxantrone, docetaxel results in a statistically significant survival benefit of 2.5 months, a significantly higher PSA- and pain response and represents the treatment of choice in the management of HRPCA. Bisphosphonates such as zoledronate represent another cornerstone in the management of PSA-progressive PCA demonstrating a significant benefit with regard to the prevention of skeletal related events. Furthermore, bisphosphonates might be indicated in the treatment of symptomatic bone pain. The current article critically reflects the various therapeutic options in the management of PSA progression following primary androgen deprivation for advanced prostate cancer.

PMID: 16311709 [PubMed - as supplied by publisher]

Posted by blogposter at 10:09 PM | Permalink

[Therapy of hormone-refractory prostate cancer.]

Urologe A. 2005 Nov 26;

Authors: Heidenreich A

PSA-progression following primary ADT defines an androgen-refractory but still hormone sensitive PCA which might respond to secondary hormonal manipulations. Secondary hormonal manipulations will result in a PSA decline >50% in about 60-80% of the patients with a mean duration of 7-17 months depending on the type of treatment. PSA-progression following secondary endocrine treatment defines hormone-refractory prostate cancer (HRPCA) which might be treated by systemic chemotherapy. Based on the results of 2 prospective, randomized clinical phase-III trials comparing docetaxel and mitoxantrone, docetaxel results in a statistically significant survival benefit of 2.5 months, a significantly higher PSA- and pain response and represents the treatment of choice in the management of HRPCA. Bisphosphonates such as zoledronate represent another cornerstone in the management of PSA-progressive PCA demonstrating a significant benefit with regard to the prevention of skeletal related events. Furthermore, bisphosphonates might be indicated in the treatment of symptomatic bone pain. The current article critically reflects the various therapeutic options in the management of PSA progression following primary androgen deprivation for advanced prostate cancer.

PMID: 16311709 [PubMed - as supplied by publisher]

Posted by blogposter at 10:09 PM | Permalink

Posted by blogposter at 03:17 PM | Permalink

Related Articles

Effects of 2,4-D and DCP on the DHT-induced androgenic action in human prostate cancer cells.

Toxicol Sci. 2005 Nov;88(1):52-9

Authors: Kim HJ, Park YI, Dong MS

2,4-Dichlorophenoxyacetic acid (2,4-D) and its metabolite 2,4-dichlorophenol (DCP) are used extensively in agriculture as herbicides, and are suspected of potential endocrine disruptor activity. In a previous study, we showed that these compounds exhibited synergistic androgenic effects by co-treatment with testosterone in the Hershberger assay. To elucidate the mechanisms of the synergistic effects of these compounds on the androgenicity of testosterone, the androgenic action of 2,4-D and DCP was characterized using a mammalian detection system in prostate cancer cell lines. In in vitro assay systems, while 2,4-D or DCP alone did not show androgenic activity, 2,4-D or DCP with 5alpha-dihydroxytestosterone (DHT) exhibited synergistic androgenic activities. Co-treatment of 10 nM 2,4-D or DCP with 10 nM DHT was shown to stimulate the cell proliferation by 1.6-fold, compared to 10 nM DHT alone. In addition, in transient transfection assays, androgen-induced transactivation was also increased to a maximum of 32-fold or 1.28-fold by co-treatment of 2,4-D or DCP with DHT, respectively. However, 2,4-D and DCP exerted no effects on either mRNA or protein levels of AR. In a competitive AR binding assay, 2,4-D and DCP inhibited androgen binding to AR, up to 50% at concentrations of approximately 0.5 microM for both compounds. The nuclear translocation of green fluorescent protein-AR fusion protein in the presence of DHT was promoted as the result of the addition of 2,4-D and DCP. Collectively, these results that 2,4-D and DCP enhanced DHT-induced AR transcriptional activity might be attributable, at least in part, to the promotion of AR nuclear translocation.

PMID: 16107550 [PubMed - indexed for MEDLINE]

Posted by blogposter at 03:17 PM | Permalink

[Therapy of hormone-refractory prostate cancer.]

Urologe A. 2005 Nov 26;

Authors: Heidenreich A

PSA-progression following primary ADT defines an androgen-refractory but still hormone sensitive PCA which might respond to secondary hormonal manipulations. Secondary hormonal manipulations will result in a PSA decline >50% in about 60-80% of the patients with a mean duration of 7-17 months depending on the type of treatment. PSA-progression following secondary endocrine treatment defines hormone-refractory prostate cancer (HRPCA) which might be treated by systemic chemotherapy. Based on the results of 2 prospective, randomized clinical phase-III trials comparing docetaxel and mitoxantrone, docetaxel results in a statistically significant survival benefit of 2.5 months, a significantly higher PSA- and pain response and represents the treatment of choice in the management of HRPCA. Bisphosphonates such as zoledronate represent another cornerstone in the management of PSA-progressive PCA demonstrating a significant benefit with regard to the prevention of skeletal related events. Furthermore, bisphosphonates might be indicated in the treatment of symptomatic bone pain. The current article critically reflects the various therapeutic options in the management of PSA progression following primary androgen deprivation for advanced prostate cancer.

PMID: 16311709 [PubMed - as supplied by publisher]

Posted by blogposter at 03:17 PM | Permalink

Related Articles

Health motivation and emotional vigilance in genetic testing for prostate cancer risk.

Clin Genet. 2004 Dec;66(6):512-6

Authors: Li Y, Doukas DJ

Actual uptake of genetic testing for cancer susceptibility is generally lower than 50%, despite a high initial interest above 80%. As population-based genetic testing for cancer susceptibility becomes more widespread, there will be an increasing need to understand the relationship of patient-affective factors to test intention and actual uptake behavior. Using hypothetical genetic testing for prostate cancer susceptibility as an example, we used surveys of 400 men in the general population of Philadelphia to develop a Structural Equation Modeling diagram to reveal the influence of affective factors implicated in the intention to undergo genetic testing for prostate cancer risk. Results showed that most men want genetic testing for prostate cancer, believe strongly in its benefits, and are not deterred by negative affect. Our data suggest that high positive expectations, plus a high desire to comply with physician and family suggestions, result in an increased test intention. Informed consent assessment, therefore, requires an appreciation not only of patient risk, but awareness of patient motivation and affect as well.

PMID: 15521978 [PubMed - indexed for MEDLINE]

Posted by blogposter at 03:17 PM | Permalink

Related Articles

Human CTLs to wild-type and enhanced epitopes of a novel prostate and breast tumor-associated protein, TARP, lyse human breast cancer cells.

Cancer Res. 2004 Apr 1;64(7):2610-8

Authors: Oh S, Terabe M, Pendleton CD, Bhattacharyya A, Bera TK, Epel M, Reiter Y, Phillips J, Linehan WM, Kasten-Sportes C, Pastan I, Berzofsky JA

Vaccine therapy for prostate and breast cancer may have potential for treating these major causes of death in males and females, respectively. Critical to the development of tumor-specific vaccines is finding and characterizing novel antigens to be recognized by CD8(+) T cells. To define new CD8(+) T-cell tumor antigens, we determined two wild-type HLA-A2 epitopes from a recently found tumor-associated protein, TARP (T-cell receptor gamma alternate reading frame protein), expressed in prostate and breast cancer cells. We were also able to engineer epitope-enhanced peptides by sequence modifications. Both wild-type and enhanced epitopes induced peptide-specific CD8(+) T-cell responses in A2K(b) transgenic mice. In vitro restimulation of human CD8(+) T cells from a prostate cancer patient resulted in CD8(+) T cells reactive to the peptide epitopes that could lyse HLA-A2(+) human breast cancer cells (MCF-7) expressing TARP. Epitope-specific human CD8(+) T cells were also enumerated in patients' peripheral blood by tetramer staining. Our data suggest that HLA-A2-binding TARP epitopes and enhanced epitopes discovered in this study could be incorporated into a potential vaccine for both breast and prostate cancer.

PMID: 15059918 [PubMed - indexed for MEDLINE]

Posted by blogposter at 03:17 PM | Permalink

Epidural spinal cord compression.

Crit Rev Oncol Hematol. 2005 Nov 22;56(3):397-406

Authors: Spinazz S, Caraceni A, Schrijvers D

Spinal cord compression from epidural metastases (epidural spinal cord compression, ESCC) is the most common neurological complication of cancer after brain metastases. Extradural compression represents 97% of spinal cord metastatic lesions. ESCC usually occurs in patients with disseminated disease. The most common tumours associated with ESCC are lung and breast cancers, followed by lymphoma, myeloma, prostate cancer and sarcoma. ESCC represents a medical emergency because delayed treatment can be responsible for irreversible deficits, such as paralysis and loss of sphincter control. Patients with ESCC require a multidisciplinary diagnostic and therapeutic approach. Clinical suspect is radiologically detected for confirmation. The median expected survival time from diagnosis usually ranges from 3 to 6 months. The nature of the primary tumour and the degree of the neurological deficit are the most important factors affecting survival. The lack of prospective randomized trials makes the optimal treatment of ESCC controversial and the decision is to be tailored to the individual. Treatment options include: bed rest, administration of corticosteroids, surgery followed by radiation therapy, radiotherapy alone and, to a limited extent, chemotherapy and hormonal therapy.

PMID: 16310372 [PubMed - as supplied by publisher]

Posted by blogposter at 03:16 PM | Permalink

Cancer of the prostate.

Crit Rev Oncol Hematol. 2005 Nov 22;56(3):379-396

Authors: Bracarda S, de Cobelli O, Greco C, Prayer-Galetti T, Valdagni R, Gatta G, de Braud F, Bartsch G

Prostate carcinoma, with about 190,000 new cases occurring each year (15% of all cancers in men), is the most frequent cancer among men in northern and western Europe. Causes of the disease are essentially unknown, although hormonal factors are involved, and diet may exert an indirect influence; some genes, potentially involved in hereditary prostate cancer (HPC) have been identified. A suspect of prostate cancer may derive from elevated serum prostate-specific antigen (PSA) values and/or a suspicious digital rectal examination (DRE) finding. For a definitive diagnosis, however, a positive prostate biopsy is requested. Treatment strategy is defined according to initial PSA stage, and grade of the disease and age and general conditions of the patient. In localized disease, watchful waiting is indicated as primary option in patients with well or moderately differentiated tumours and a life expectancy <10 years, while radical prostatectomy and radiotherapy (with or without hormone-therapy) could be appropriate choices in the remaining cases. Hormone-therapy is the treatment of choice, combined with radiotherapy, for locally advanced or bulky disease and is effective, but not curative, in 80-85% of the cases of advanced disease. Patients who develop a hormone-refractory prostate cancer disease (HRPC) have to be evaluated for chemotherapy because of the recent demonstration of improved overall survival (2-2.5 months) and quality of life with docetaxel in more than 1600 cases.

PMID: 16310371 [PubMed - as supplied by publisher]

Posted by blogposter at 03:16 PM | Permalink

Posted by blogposter at 01:11 PM | Permalink

Related Articles

Satraplatin in the treatment of hormone-refractory prostate cancer.

BJU Int. 2005 Nov;96(7):990-4

Authors: Sternberg CN

PMID: 16225514 [PubMed - indexed for MEDLINE]

Posted by blogposter at 01:11 PM | Permalink

Operating characteristics of prostate-specific antigen in men with an initial PSA level of 3.0 ng/ml or lower Thompson IM, Ankerst DP, Chi C, Lucia MS, Goodman PJ, Crowley JJ, Parnes HL, Coltman CA Jr., Department of Urology, University of Texas Health Science Center at San Antonio, TX.

Urol Oncol. 2005 Nov-Dec;23(6):459

Authors: Carroll PR

CONTEXT: Three fourths of US men older than 50 years have been screened with prostate-specific antigen (PSA) for prostate cancer. OBJECTIVE: To estimate the receiver operating characteristic (ROC) curve for PSA. DESIGN, SETTING, AND PARTICIPANTS: Calculation of PSA ROC curves in the placebo group of the Prostate Cancer Prevention Trial, a randomized, prospective study conducted from 1993 to 2003 at 221 US centers. Participants were 18 882 healthy men aged 55 years or older without prostate cancer and with PSA levels less than or equal to 3.0 ng/mL and normal digital rectal examination results, followed up for 7 years with annual PSA measurement and digital rectal examination. If PSA level exceeded 4.0 ng/mL or rectal examination result was abnormal, a prostate biopsy was recommended. After 7 years of study participation, an end-of-study prostate biopsy was recommended in all cancer-free men. MAIN OUTCOME MEASURES: Operating characteristics of PSA for prostate cancer detection, including sensitivity, specificity, and ROC curve. RESULTS: Of 8575 men in the placebo group with at least 1 PSA measurement and digital rectal examination in the same year, 5587 (65.2%) had had at least 1 biopsy; of these, 1225 (21.9%) were diagnosed with prostate cancer. Of 1213 cancers with Gleason grade recorded, 250 (20.6%) were Gleason grade 7 or greater and 57 (4.7%) were Gleason grade 8 or greater. The areas under the ROC curve (AUC) for PSA to discriminate any prostate cancer vs no cancer, Gleason grade 7 or greater cancer vs no or lower-grade cancer, and Gleason grade 8 or greater cancer vs no or lower-grade cancer were 0.678 (95% confidence interval [CI] 0.666-0.689), 0.782 (95% CI 0.748-0.816), and 0.827 (95% CI 0.761-0.893), respectively (all P values <.001 for AUC vs 50%). For detecting any prostate cancer, PSA cutoff values of 1.1, 2.1, 3.1, and 4.1 ng/mL yielded sensitivities of 83.4%, 52.6%, 32.2%, and 20.5%, and specificities of 38.9%, 72.5%, 86.7%, and 93.8%, respectively. Age-stratified analyses showed slightly better performance of PSA in men younger than 70 years vs those 70 years or older with AUC values of 0.699 (SD, 0.013) vs 0.663 (SD, 0.013) (P = .03). CONCLUSION: There is no cutpoint of PSA with simultaneous high sensitivity and high specificity for monitoring healthy men for prostate cancer, but rather a continuum of prostate cancer risk at all values of PSA.

PMID: 16301130 [PubMed - in process]

Posted by blogposter at 01:11 PM | Permalink

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]

Posted by blogposter at 01:10 PM | Permalink

Related Articles

Delayed disease progression after allogeneic cell vaccination in hormone-resistant prostate cancer and correlation with immunologic variables.

Clin Cancer Res. 2005 Jun 15;11(12):4469-78

Authors: Michael A, Ball G, Quatan N, Wushishi F, Russell N, Whelan J, Chakraborty P, Leader D, Whelan M, Pandha H

PURPOSE: There are a significant number of patients with asymptomatic hormone-resistant prostate cancer who have increasing prostate-specific antigen (PSA) levels but little or no evaluable disease. The immunogenicity and minimal toxicity associated with cell-based vaccine therapy makes this approach attractive for these patients. EXPERIMENTAL DESIGN: We have evaluated a vaccine comprising monthly intradermal injection of three irradiated allogeneic prostate cell lines (8 x 10(6) cells each) over 1 year. The first two doses were supplemented with bacille Calmette-Gu rin as vaccine adjuvant. Twenty-eight hormone-resistant prostate cancer patients were enrolled. Patients were assessed clinically and PSA levels were measured monthly. Radiologic scans (X-ray, computed tomography, and bone scan) were taken at baseline and at intervals throughout the treatment period. Comprehensive monthly immunologic monitoring was undertaken including proliferation studies, activation markers, cytokine protein expression, and gene copy number. This longitudinal data was analyzed through predictive modeling using artificial neural network feed-forward/back-propagation algorithms with multilayer perceptron architecture.RESULTS: Eleven of the 26 patients showed statistically significant, prolonged decreases in their PSA velocity (PSAV). None experienced any significant toxicity. Median time to disease progression was 58 weeks, compared with recent studies of other agents and historical control values of around 28 weeks. PSAV-responding patients showed a titratable T(H)1 cytokine release profile in response to restimulation with a vaccine lysate, while nonresponders showed a mixed T(H)1 and T(H)2 response. Furthermore, immunologic profile correlated with PSAV response by artificial neural network analysis. We found predictive power not only in expression of cytokines after maximal stimulation with phorbol 12-myristate 13-acetate, but also the method of analysis (qPCR measurement of IFN-gamma > qPCR measurement tumor necrosis factor-alpha > protein expression of IFN-gamma > protein expression of interleukin 2). CONCLUSIONS: Whole cell allogeneic vaccination in hormone-resistant prostate cancer is nontoxic and improves the natural history of the disease. Longitudinal changes in immunologic function in vaccinated patients may be better interpreted through predictive modeling using tools such as the artificial neural network rather than periodic "snapshot" readouts.

PMID: 15958632 [PubMed - indexed for MEDLINE]

Posted by blogposter at 01:10 PM | Permalink

CXCL12 overexpression and secretion by aging fibroblasts enhance human prostate epithelial proliferation in vitro.

Aging Cell. 2005 Dec;4(6):291-8

Authors: Begley L, Monteleon C, Shah RB, Macdonald JW, Macoska JA

Summary The direct relationship between the aging process and the incidence and prevalence of both benign prostatic hyperplasia (BPH) and prostate cancer (PCa) implies that certain risk factors associated with the development of both diseases increase with the aging process. In particular, both diseases share an overly proliferative phenotype, suggesting that mechanisms that normally act to suppress cellular proliferation are disrupted or rendered dysfunctional as a consequence of the aging process. We propose that one such mechanism involves changes in the prostate microenvironment, which 'evolves' during the aging process and disrupts paracrine interactions between epithelial and associated stromal fibroblasts. We show that stromal fibroblasts isolated from the prostates of men 63-81 years of age at the time of surgery express and secrete higher levels of the CXCL12 chemokine compared with those isolated from younger men, and stimulate CXCR4-mediated signaling pathways that induce cellular proliferation. These studies represent an important first step towards a mechanistic elucidation of the role of aging in the etiology of benign and malignant prostatic diseases.

PMID: 16300481 [PubMed - in process]

Posted by blogposter at 01:10 PM | Permalink

Monotherapeutic brachytherapy for clinically organ-confined prostate cancer.

W V Med J. 2005 Jul-Aug;101(4):168-71

Authors: Merrick GS, Butler WM, Wallner KE, Galbreath RW, Adamovich E

Since the mid-1980s, permanent prostate brachytherapy has been utilized increasingly as a potentially curative treatment for patients of all ages with clinically localized prostate cancer To determine the 8-year biochemical progression-free survival rate for patients who had undergone monotherapeutic brachytherapy for clinically organ-confined prostate cancer, we conducted a study of 202 patients at Schiffler Cancer Center at Wheeling Hospital in Wheeling, W.Va. These patients had undergone brachytherapy without supplemental external beam radiation therapy or androgen deprivation therapy for clinical T1b-T2c NxM0 (2002 AJCC) prostate cancer from April 1995 through May 2001. No patient underwent seminal vesicle biopsy or pathologic lymph node staging. The median follow-up was 5.2 years. All patients underwent brachytherapy more than 3 years prior to analysis. Biochemical success was defined as a PSA < 0.4 ng/mL after a nadir. Clinical, treatment and dosimetric parameters evaluated for biochemical progression-free survival included patient age, clinical T-stage, Gleason score, pretreatment PSA, risk group, percent positive biopsies, isotope, prostate volume, brachytherapy planning volume, V100/150/200, D90, tobacco status, hypertension and diabetes. For the entire group, 8-year biochemical progression-free survival was 97.4% for Pd-103 and 93.3% for I-125. The median post-treatment PSA for the entire group was < 0.1 ng/mL. In multivariate analysis, only pretreatment PSA predicted biochemical outcome with a trend for better outcome with younger patient age and lesser percent positive biopsies. The results of our study indicate that permanent interstitial brachytherapy as a monotherapeutic approach for patients with clinically organ-confined disease results in a high probability of 8-year biochemical progression-free survival with a median PSA < 0.1 ng/mL. Generous periprostatic treatment margins with documented high quality day 0 postoperative dosimetry are mandatory for such outcomes.

PMID: 16296198 [PubMed - in process]

Posted by blogposter at 01:10 PM | Permalink

Advanced prostate cancer: the future.

Can J Urol. 2005 Jun;12 Suppl 2:42-7

Authors: Armstrong AJ, Carducci MA

The demonstration of a survival benefit with docetaxel for the treatment of metastatic hormone refractory prostate cancer (HRPC) is an important step forward in advancing treatment options for advanced prostate cancer. While docetaxel-based therapy has demonstrated improvement in symptomatic and quality-of-life endpoints, certainly there is a pressing need for improvement in outcomes. A number of novel agents are in basic and clinical development for advanced prostate cancer, some of which are specific to mechanisms that may be important in the development and spread of prostate cancer. Novel approaches including novel cytotoxics, immunotherapy, PSMA targeted monoclonal antibodies are among the broad categories that will be discussed in this brief review.

PMID: 16018833 [PubMed - indexed for MEDLINE]

Posted by blogposter at 01:10 PM | Permalink

[Prostate cancer chemotherapy, myth or reality?]

Actas Urol Esp. 2005 Sep;29(8):723-4

Authors: Rioja Sanz LA

PMID: 16304901 [PubMed - in process]

Posted by blogposter at 01:09 PM | Permalink

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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]

Posted by blogposter at 01:09 PM | Permalink

20-year outcomes following conservative management of clinically localized prostate cancer Albertsen PC, Hanley JA, Fine J, Division of Urology, University of Connecticut Health Center, Farmington, CT.

Urol Oncol. 2005 Nov-Dec;23(6):459-60

Authors: Carroll PR

CONTEXT: The appropriate therapy for men with clinically localized prostate cancer is uncertain. A recent study suggested an increasing prostate cancer mortality rate for men who are alive more than 15 years following diagnosis. OBJECTIVE: To estimate 20-year survival based on a competing risk analysis of men who were diagnosed with clinically localized prostate cancer and treated with observation or androgen withdrawal therapy alone, stratified by age at diagnosis and histological findings. DESIGN, SETTING, AND PATIENTS: A retrospective population-based cohort study using Connecticut Tumor Registry data supplemented by hospital record and histology review of 767 men aged 55 to 74 years with clinically localized prostate cancer diagnosed between January 1, 1971, and December 31, 1984. Patients were treated with either observation or immediate or delayed androgen withdrawal therapy, with a median observation of 24 years. MAIN OUTCOME MEASURES: Probability of mortality from prostate cancer or other competing medical conditions, given a patient's age at diagnosis and tumor grade. RESULTS: The prostate cancer mortality rate was 33 per 1000 person-years during the first 15 years of follow-up (95% confidence interval [CI] 28-38) and 18 per 1000 person-years after 15 years of follow-up (95% CI 10-29). The mortality rates for these 2 follow-up periods were not statistically different, after adjusting for differences in tumor histology (rate ratio 1.1; 95% CI 0.6-1.9). Men with low-grade prostate cancers have a minimal risk of dying from prostate cancer during 20 years of follow-up (Gleason score of 2-4, 6 deaths per 1000 person-years; 95% CI 2-11). Men with high-grade prostate cancers have a high probability of dying from prostate cancer within 10 years of diagnosis (Gleason score of 8-10, 121 deaths per 1000 person-years; 95% CI 90-156). Men with Gleason score of 5 or 6 tumors have an intermediate risk of prostate cancer death. CONCLUSION: The annual mortality rate from prostate cancer appears to remain stable after 15 years from diagnosis, which does not support aggressive treatment for localized low-grade prostate cancer.

PMID: 16301129 [PubMed - in process]

Posted by blogposter at 01:09 PM | Permalink

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Pretreatment predictors of posttreatment PSA doubling times for patients undergoing three-dimensional conformal radiotherapy for clinically localized prostate cancer.

Urology. 2005 Nov;66(5):1020-3

Authors: Beard C, Chen MH, Cote K, Loffredo M, Renshaw A, Hurwitz M, D'Amico AV

OBJECTIVES: To determine whether pretreatment risk groups also predict for posttreatment prostate-specific antigen (PSA) doubling times (PSADTs). Pretreatment risk groups predict for posttreatment biochemical failure (BF) after conformal radiotherapy in patients with prostate cancer and posttreatment PSADTs can predict for prostate cancer-related deaths. METHODS: The study cohort consisted of 416 patients with clinically localized prostate cancer treated with conformal radiotherapy between 1989 and 2001. The patients were divided into low, intermediate, and high-risk groups. BF was defined using the American Society for Therapeutic Radiology and Oncology consensus definition. Patients with BF were grouped according to their PSADT (3 months or less, longer than 3 months to less than 6 months, 6 months to less than 12 months, and 12 months or longer). A Mantle-Haenszel chi-square metric tested for an association between the pretreatment risk group and the PSADT. Logistic regression multivariate analysis was performed to evaluate whether the pretreatment risk group predicted the PSADT. RESULTS: Of the 416 patients, 96 (23%), 194 (47%), and 126 (30%) were categorized as low, intermediate, and high risk, respectively. A total of 92 patients (22%) experienced BF. Of these 92 patients, the PSADT was 3 months or less in 6 (7%), longer than 3 months to less than 6 months in 13 (14%), 6 months to less than 12 months in 35 (36%), and 12 months or longer in 38 (41%). The pretreatment risk group correlated significantly with the PSADT (P = 0.026). Logistic regression analysis revealed that intermediate and high-risk disease was significantly associated with shorter PSADTs (P = 0.039). CONCLUSIONS: A significant association between the pretreatment risk group and posttreatment PSADT was demonstrated. Use of this selection criterion at diagnosis for more aggressive treatment appears warranted.

PMID: 16286116 [PubMed - in process]

Posted by blogposter at 08:22 PM | Permalink

[In Process Citation]

Ann Urol (Paris). 2005 Oct;39 Suppl 3:S56-8

Authors: Bouchard P

Antagonists act by competitive inhibition of pituitary GnRH receptors for which they have a high affinity with a dose-dependent activity. The inhibition concerns LH but also FSH by inhibiting their secretion for 24 hours. At this time, only three molecules are available. Cetrorelix is mainly used for in vitro fertilization protocols, but research is currently being carried out in benign prostatic hypertrophy. Ganirelix is only used in medically assisted procreation. Abarelix is used in the United States as a monthly "depot" injection for the treatment of prostate cancer resistant to other therapies. Other molecules including orally active antagonists are in the course of clinical evaluation or in preclinical phases. The development of this therapeutic class is hampered by conflicting industrial interests and also by problems of tolerability in particular because of the side effects due to induced histamine release. The current indications in France are therefore limited to Assisted Reproductive Technology, and, recently, prostate cancer pending comparative studies versus agonists. The indications under development are endometriosis, myoma and precocious puberty, fields in which agonists have already been found to be effective. Male contraception seems to have a future however this therapeutic regimen remains very expensive. Finally, in benign prostatic hypertrophy, the antagonists administrated intermittently may be used to rapidly improve urinary flow.

PMID: 16302712 [PubMed - in process]

Posted by blogposter at 08:22 PM | Permalink

Related Articles

Role of SRC-1 in the promotion of prostate cancer cell growth and tumor progression.

Cancer Res. 2005 Sep 1;65(17):7959-67

Authors: Agoulnik IU, Vaid A, Bingman WE, Erdeme H, Frolov A, Smith CL, Ayala G, Ittmann MM, Weigel NL

Prostate cancer is initially androgen dependent and there is evidence that androgen receptor continues to play a role in androgen-independent prostate cancer. Androgen receptor activity depends both on the level of androgens and on the level of coactivators that interact with androgen receptor. Our goal was to evaluate the role of the androgen receptor coactivator SRC-1 in prostate cancer progression. Using tissue arrays to measure SRC-1 protein levels, we found that increased SRC-1 expression in clinically localized, androgen-dependent cancer is associated with clinical and pathologic variables of increased tumor aggressiveness. Interestingly, there was variable expression of SRC-1 in normal prostate tissue which correlated with the staining intensity of the corresponding cancer tissue. To test the contribution of SRC-1, we examined its role in androgen-dependent LNCaP and androgen-independent C4-2 prostate cancer cell lines. Using small interfering RNA to reduce expression of androgen receptor, we found that androgen receptor was required both for cell growth and for basal expression of prostate-specific antigen in the androgen-independent C4-2 cell line. Thus, although the cells can grow in an androgen-depleted medium, they remained androgen receptor dependent. Reduction of SRC-1 expression significantly reduced growth and altered androgen receptor target gene regulation in both LNCaP and C4-2 cell lines whereas it had no effect on the growth of the androgen receptor-negative PC-3 and DU145 prostate cancer cell lines. Although the requirement for androgens and androgen receptor in the development of prostate cancer is well established, our study implicates enhanced androgen receptor activity through elevated expression of SRC-1 in the development of more aggressive disease in men with prostate cancer.

PMID: 16140968 [PubMed - indexed for MEDLINE]

Posted by blogposter at 12:09 PM | Permalink

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Effect of methylprednisolone on return of sexual function after nerve-sparing radical retropubic prostatectomy.

Urology. 2004 Nov;64(5):987-90

Authors: Parsons JK, Marschke P, Maples P, Walsh PC

OBJECTIVES: To determine whether postoperative methylprednisolone improves the recovery of sexual function after nerve-sparing radical retropubic prostatectomy. METHODS: We randomized men undergoing bilateral nerve-sparing radical retropubic prostatectomy by a single surgeon to receive 6 days of placebo or methylprednisolone beginning on postoperative day 1. At 3, 6, and 12 months postoperatively, we assessed potency with the abbreviated International Index of Erectile Function questionnaire and urinary continence with participant-reported pad use. We used the chi-square test, Fisher's exact test, and the two-sample t test with equal variances for comparisons between study groups. RESULTS: No operative complications occurred and 70 (100%) of 70 participants experienced normal wound healing. The odds of being potent for participants who received methylprednisolone (n = 34) compared with those who received placebo (n = 36) did not significantly differ at 3 (odds ratio 0.29, 95% confidence interval 0.08 to 1.05), 6 (odds ratio 0.63, 95% confidence interval 0.17 to 2.4), or 12 (odds ratio 1.18, 95% confidence interval 0.29 to 4.8) months. The mean International Index of Erectile Function scores did not significantly differ at 3 (P = 0.08), 6 (P = 0.50), or 12 (P = 0.71) months. At 12 months, 74% of the methylprednisolone and 71% of the placebo participants were potent (P = 0.8). The proportions of participants who were continent did not differ significantly at 3 (P = 0.89), 6 (P = 0.25), or 12 (P = 0.49) months. At 12 months, 96% of the methylprednisolone and 100% of the placebo participants were continent. CONCLUSIONS: At doses sufficient to produce a systemic anti-inflammatory effect, postoperative methylprednisolone was not associated with improved potency at up to 12 months after bilateral nerve-sparing radical retropubic prostatectomy in men 40 to 60 years old.

PMID: 15533491 [PubMed - indexed for MEDLINE]

Posted by blogposter at 12:07 PM | Permalink

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The need to reduce patient discomfort during transrectal ultrasonography-guided prostate biopsy: what do we know?

BJU Int. 2005 Nov;96(7):977-83

Authors: De Sio M, D'Armiento M, Di Lorenzo G, Damiano R, Perdonà S, De Placido S, Autorino R

PMID: 16225512 [PubMed - indexed for MEDLINE]

Posted by blogposter at 01:43 PM | Permalink

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[Prostate neoplasms--tumor grading and magnetic resonance spectroscopy]

Rofo. 2005 Oct;177(10):1342

Authors:

PMID: 16170697 [PubMed - indexed for MEDLINE]

Posted by blogposter at 01:42 PM | Permalink

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[The study landscape for prostate cancer.]

Urologe A. 2005 Nov 15;

Authors: Miller K

Current prostate cancer studies in Germany encompass the indications "adjuvant therapy", "rising PSA following radical prostatectomy", "metastasized, hormone sensitive prostate cancer", and "hormone refractory prostate cancer". In the adjuvant field, the potential of zoledronic acid for the prevention of bone metastases is being investigated in a large phase III trial. The activity of imatinib in low volume prostate cancer is being tested in patients with rising PSA following radical prostatectomy (phase II). The randomized phase III trial intermittent versus continuous hormone therapy in D1 and D2 patients has finished accrual and follow-up will be extended until the end of 2006. In hormone refractory prostate cancer(HRPC), the results of a recent phase II study (Association of Urological Oncology; AOU AP 33/02) were promising. This led to a currently activate phase III trial comparing intermittent with continuous chemotherapy in HRPC. The interdisciplinary study group of the AUO (Urology) and the ARO (Radio-oncology) has developed several new protocols which are currently under review by the German Cancer Aid (Deutsche Krebshilfe).

PMID: 16292461 [PubMed - as supplied by publisher]

Posted by blogposter at 01:41 PM | Permalink

Related Articles

Prostate cancer cells promote osteoblastic bone metastases through Wnts.

Cancer Res. 2005 Sep 1;65(17):7554-60

Authors: Hall CL, Bafico A, Dai J, Aaronson SA, Keller ET

Prostate cancer produces painful osteoblastic bone metastases. Although prostate cancer cells produce numerous osteogenic factors, to date, none have been shown to mediate osteoblastic bone metastases in an in vivo model of prostate cancer. Wnts are a large family of proteins that promote bone growth. Wnt activity is antagonized by endogenous proteins including dickkopf-1 (DKK-1). We explored if prostate cancer cells mediate osteoblastic activity through Wnts using DKK-1 as a tool to modify Wnt activity. A variety of Wnt mRNAs were found to be expressed in prostate cancer cell lines and Wnt mRNA expression was increased in primary prostate cancer compared with nonneoplastic prostate tissue. In addition to expressing Wnts, PC-3 prostate cancer cells expressed the Wnt inhibitor DKK-1. To determine if DKK-1 masked Wnt-mediated osteoblastic activity in osteolytic PC-3 cells, the cells were stably transfected with DKK-1 short hairpin RNA. Decreasing DKK-1 enabled PC-3 cells to induce osteoblastic activity, including alkaline phosphatase production and mineralization, in murine bone marrow stromal cells indicating that DKK-1 blocked Wnt-mediated osteoblastic activity in PC-3 cells. Another prostate cancer cell line, C4-2B, induces mixed osteoblastic/osteolytic lesions. To determine if Wnts contribute to C4-2B's ability to induce mixed osteoblastic/osteolytic lesions, C4-2B cells were stably transfected with either empty vector or DKK-1 expression vector to block Wnt activity. The cells were then injected in the tibiae of mice and allowed to grow for 12 weeks. Blocking Wnt activity converted the C4-2B cells to a highly osteolytic tumor. Taken together, these data show that Wnts contribute to the mechanism through which prostate cancer induces osteoblastic activity.

PMID: 16140917 [PubMed - indexed for MEDLINE]

Posted by blogposter at 01:41 PM | Permalink

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Pilot trial of unlabeled and indium-111-labeled anti-prostate-specific membrane antigen antibody J591 for castrate metastatic prostate cancer.

Clin Cancer Res. 2005 Oct 15;11(20):7454-61

Authors: Morris MJ, Divgi CR, Pandit-Taskar N, Batraki M, Warren N, Nacca A, Smith-Jones P, Schwartz L, Kelly WK, Slovin S, Solit D, Halpern J, Delacruz A, Curley T, Finn R, O'donoghue JA, Livingston P, Larson S, Scher HI

BACKGROUND: Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein primarily expressed on benign and malignant prostatic epithelial cells. J591 is an IgG1 monoclonal antibody that targets the external domain of the PSMA. The relationship among dose, safety, pharmacokinetics, and antibody-dependent cellular cytotoxicity (ADCC) activation for unlabeled J591 has not been explored. PATIENTS AND METHODS: Patients with progressive metastatic prostate cancer despite androgen deprivation were eligible. Each patient received 10, 25, 50, and 100 mg of J591. Two milligrams of antibody, conjugated with the chelate 1,4,7,10-tetraazacyclododecane-N, N',N'',N'''-tetraacetic acid, were labeled with 5 mCi indium-111 (111In) as a tracer. One group of patients received unlabeled J591 before the labeled antibody; the other received both together. Toxicities, pharmacokinetic properties, biodistribution, ADCC induction, immunogenicity, and clinical antitumor effects were assessed. RESULTS: Fourteen patients were treated (seven in each group). Treatment was well tolerated. Biodistribution of 111In-labeled J591 was comparable in both groups. The mean T1/2 was .96, 1.9, 2.75, and 3.47 days for the 10, 25, 50, and 100 mg doses, respectively. Selective targeting of 111In-labeled J591 to tumor was seen. Hepatic saturation occurred by the 25-mg dose. ADCC activity was proportional to dose. One patient showed a >50% prostate-specific antigen decline. CONCLUSIONS: J591 is well tolerated in repetitive dose-escalating administrations. The rate of serum clearance decreases with increasing antibody mass. ADCC activation is proportional to antibody mass. The optimal dose is 25 mg for radioimmunotherapy and 100 mg for immunotherapy. Phase II studies using J591 as a radioconjugate are under way.

PMID: 16243819 [PubMed - in process]

Posted by blogposter at 01:41 PM | Permalink

CXCL12 overexpression and secretion by aging fibroblasts enhance human prostate epithelial proliferation in vitro.

Aging Cell. 2005 Dec;4(6):291-8

Authors: Begley L, Monteleon C, Shah RB, Macdonald JW, Macoska JA

Summary The direct relationship between the aging process and the incidence and prevalence of both benign prostatic hyperplasia (BPH) and prostate cancer (PCa) implies that certain risk factors associated with the development of both diseases increase with the aging process. In particular, both diseases share an overly proliferative phenotype, suggesting that mechanisms that normally act to suppress cellular proliferation are disrupted or rendered dysfunctional as a consequence of the aging process. We propose that one such mechanism involves changes in the prostate microenvironment, which 'evolves' during the aging process and disrupts paracrine interactions between epithelial and associated stromal fibroblasts. We show that stromal fibroblasts isolated from the prostates of men 63-81 years of age at the time of surgery express and secrete higher levels of the CXCL12 chemokine compared with those isolated from younger men, and stimulate CXCR4-mediated signaling pathways that induce cellular proliferation. These studies represent an important first step towards a mechanistic elucidation of the role of aging in the etiology of benign and malignant prostatic diseases.

PMID: 16300481 [PubMed - in process]

Posted by blogposter at 11:19 PM | Permalink

[In Process Citation]

Ann Urol (Paris). 2005 Oct;39 Suppl 3:S66-72

Authors: Zerbib M

Prostate cancer is currently the main indication of LH-RH analogs. This class, which in recent years has replaced diethylstilbestrol and surgical castration, now plays a major role at all stages of the disease. Numerous studies with contradictory results have compared total hormonal blockage, an alog combined with an anti-androgen, with analog alone in locally advanced prostate cancer. A recent metaanalysis showed a slight though globally non-significant advantage in favour of total blockage, but with a significant advantage in the case of a nonsteroidal anti-androgen. In stage T3 cancers, adjuvant hormone therapy over three years in combination with radiotherapy versus external radiotherapy alone was more effective in terms of local or metastatic progression and survival. Institution during radiotherapy and a prolonged duration of treatment gives a greater benefit though this was only significant for the subgroup of patients with a Gleason score > or = 8. For localized stages but at high risk (PSA > 15 ng / ml and\or Gleason score > 7), adjuvant hormone therapy after prostatectomy improved recurrence-free survival in comparison with prostatectomy followed-up by simple monitoring. On the other hand, the administration of analogs two or three months before radical prostatectomy did not seem to provide any additional benefit. Medical castration prolonged by LH-RH analogs engenders multiple side effects which become all the more worrying as patient survival is prolonged by this hormone therapy. In phase I-II studies, intermittent treatment is equivalent to continuous treatment for "hormone sensitive" patients (PSA nadir at six months < 0.5 ng). Phase III studies are in progress to confirm this equivalence. This intermittent hormone therapy may be a useful solution for elderly patients (> 78 years old) with a biologically highly active cancer and remains to be evaluated in relatively young subjects after radical prostatectomy or radiotherapy. Combination of analogs with chemotherapy has been used very recently for patients who have reached hormonal escape and may be a useful immediate option for patients with cancers with a high risk of progression.

PMID: 16302714 [PubMed - in process]

Posted by blogposter at 10:07 PM | Permalink

Related Articles

Role of SRC-1 in the promotion of prostate cancer cell growth and tumor progression.

Cancer Res. 2005 Sep 1;65(17):7959-67

Authors: Agoulnik IU, Vaid A, Bingman WE, Erdeme H, Frolov A, Smith CL, Ayala G, Ittmann MM, Weigel NL

Prostate cancer is initially androgen dependent and there is evidence that androgen receptor continues to play a role in androgen-independent prostate cancer. Androgen receptor activity depends both on the level of androgens and on the level of coactivators that interact with androgen receptor. Our goal was to evaluate the role of the androgen receptor coactivator SRC-1 in prostate cancer progression. Using tissue arrays to measure SRC-1 protein levels, we found that increased SRC-1 expression in clinically localized, androgen-dependent cancer is associated with clinical and pathologic variables of increased tumor aggressiveness. Interestingly, there was variable expression of SRC-1 in normal prostate tissue which correlated with the staining intensity of the corresponding cancer tissue. To test the contribution of SRC-1, we examined its role in androgen-dependent LNCaP and androgen-independent C4-2 prostate cancer cell lines. Using small interfering RNA to reduce expression of androgen receptor, we found that androgen receptor was required both for cell growth and for basal expression of prostate-specific antigen in the androgen-independent C4-2 cell line. Thus, although the cells can grow in an androgen-depleted medium, they remained androgen receptor dependent. Reduction of SRC-1 expression significantly reduced growth and altered androgen receptor target gene regulation in both LNCaP and C4-2 cell lines whereas it had no effect on the growth of the androgen receptor-negative PC-3 and DU145 prostate cancer cell lines. Although the requirement for androgens and androgen receptor in the development of prostate cancer is well established, our study implicates enhanced androgen receptor activity through elevated expression of SRC-1 in the development of more aggressive disease in men with prostate cancer.

PMID: 16140968 [PubMed - indexed for MEDLINE]

Posted by blogposter at 05:26 PM | Permalink

Related Articles

Differential expression of steroid receptors in prostate tissues before and after radiation therapy for prostatic adenocarcinoma.

Int J Cancer. 2005 Nov 10;117(3):381-6

Authors: Torlakovic E, Lilleby W, Berner A, Torlakovic G, Chibbar R, Furre T, Foss SD

The expression, distribution and the role of steroid receptors in benign and malignant untreated prostate tissues is well recognized, however, the status of steroid receptors in prostate after radiotherapy (RT) for adenocarcinoma has not yet been studied fully. Immunohistochemical evaluation of androgen receptor (AR), estrogen receptor-alpha (ER-alpha), estrogen receptor-beta (ER-beta), and progesterone receptor (PR) was carried out in prostate needle biopsies obtained before and after radiotherapy from 60 patients with adenocarcinoma. The ER-beta transcripts were also studied by RT-PCR in LNCaP prostate carcinoma cell line before and 24 hr after gamma-irradiation at 0.5 Gy and 8.0 Gy. Significantly higher level of ER-beta expression was found in post-radiation samples of prostate adenocarcinoma and benign epithelium. After RT, all steroid receptors were upregulated in prostatic stroma. Tumor AR expression did not change significantly. Although a positive association between AR and ER-beta expression was observed in pre-treatment prostate adenocarcinoma, it was lost after RT suggesting that these 2 steroid receptors respond differently to RT. High levels of pretreatment tumor ER-beta were associated with local recurrence after RT and decreased biochemical recurrence-free survival (p = 0.028). LNCaP cell line that expressed no ER-beta mRNA before gamma-irradiation, clearly expressed ER-beta mRNA 24 hr after 0.5 Gy and 8.0 Gy. Upregulation of all steroid receptors in the prostate stroma and upregulation of ER-beta in the tumor epithelium after RT, may represent a protective tissue response to radiation-induced tissue injury. Although stromal AR was doubled after RT, the tumor and benign epithelium expression of AR seemed resistant to change by RT.

PMID: 15900599 [PubMed - indexed for MEDLINE]

Posted by blogposter at 05:23 PM | Permalink

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Posted by blogposter at 05:20 PM | Permalink

[In Process Citation]

Ann Urol (Paris). 2005 Oct;39 Suppl 3:S66-72

Authors: Zerbib M

Prostate cancer is currently the main indication of LH-RH analogs. This class, which in recent years has replaced diethylstilbestrol and surgical castration, now plays a major role at all stages of the disease. Numerous studies with contradictory results have compared total hormonal blockage, an alog combined with an anti-androgen, with analog alone in locally advanced prostate cancer. A recent metaanalysis showed a slight though globally non-significant advantage in favour of total blockage, but with a significant advantage in the case of a nonsteroidal anti-androgen. In stage T3 cancers, adjuvant hormone therapy over three years in combination with radiotherapy versus external radiotherapy alone was more effective in terms of local or metastatic progression and survival. Institution during radiotherapy and a prolonged duration of treatment gives a greater benefit though this was only significant for the subgroup of patients with a Gleason score > or = 8. For localized stages but at high risk (PSA > 15 ng / ml and\or Gleason score > 7), adjuvant hormone therapy after prostatectomy improved recurrence-free survival in comparison with prostatectomy followed-up by simple monitoring. On the other hand, the administration of analogs two or three months before radical prostatectomy did not seem to provide any additional benefit. Medical castration prolonged by LH-RH analogs engenders multiple side effects which become all the more worrying as patient survival is prolonged by this hormone therapy. In phase I-II studies, intermittent treatment is equivalent to continuous treatment for "hormone sensitive" patients (PSA nadir at six months < 0.5 ng). Phase III studies are in progress to confirm this equivalence. This intermittent hormone therapy may be a useful solution for elderly patients (> 78 years old) with a biologically highly active cancer and remains to be evaluated in relatively young subjects after radical prostatectomy or radiotherapy. Combination of analogs with chemotherapy has been used very recently for patients who have reached hormonal escape and may be a useful immediate option for patients with cancers with a high risk of progression.

PMID: 16302714 [PubMed - in process]

Posted by blogposter at 05:14 PM | Permalink

Related Articles

Low-grade toxicity after conformal radiation therapy for prostate cancer-impact of bladder volume.

Int J Radiat Oncol Biol Phys. 2005 Nov 10;

Authors: Pinkawa M, Fischedick K, Asadpour B, Gagel B, Piroth MD, Eble MJ

PURPOSE: To assess the impact of dose-volume histogram parameters on low-grade toxicity after radiotherapy for prostate cancer. METHODS AND MATERIALS: Eighty patients have been surveyed prospectively before (time A), at the last day (B), 2 months after (C), and 16 months (median) after (D) radiotherapy (70.2 Gy) using a validated questionnaire (Expanded Prostate Cancer Index Composite). Dose-volume histograms were correlated with urinary and bowel function/bother scores. RESULTS: The initial bladder volume and the percentage of the bladder volume receiving 10%-90% of the prescription dose significantly correlated with urinary function/bother scores (significant cutoff levels found for all dose levels). Pain with urination proved to be mainly an acute problem, subsiding faster for patients with larger bladder volumes and smaller volumes inside particular isodose lines. At time D, persisting problems with smaller initial bladder volumes were a weak stream and an increased frequency of urination. Though bladder volume and planning target volume both independently have an influence on dose-volume histogram parameters for the bladder, bladder volume plays the decisive role for urinary toxicity. CONCLUSIONS: The patient's ability to fill the bladder has a major impact on the dose-volume histogram and both acute and late urinary toxicity.

PMID: 16289911 [PubMed - as supplied by publisher]

Posted by blogposter at 06:40 PM | Permalink

Corticosteroid-Induced Chemotherapy Resistance in Urological Cancers.

Cancer Biol Ther. 2006 Jan 25;5(1)

Authors: Zhang C, Mattern J, Haferkamp A, Pfitzenmaier J, Hohenfellner M, Rittgen W, Edler L, Debatin KM, Groene E, Herr I

Purpose: Glucocorticoids such as dexamethasone are widely used for medication of urological diseases, e.g., as cotreatment of advanced prostate cancer, to improve appetite, weight loss, fatigue, relieve bone pain, diminish ureteric obstruction, to reduce the production of adrenal androgens, as an antiemetic in patients undergoing chemo- and/or radiotherapy together with serving as "standard" therapy arm in randomized studies. While the potent pro-apoptotic properties and the supportive effects of glucocorticoids to tumor therapy in lymphoid cells are well studied, the impact to growth of prostate and other urological carcinomas is unknown. Methods: We isolated cells from surgical resections of 21 prostate tumors and measured apoptosis and viability in these primary cells and 17 established cell lines from human prostate, bladder, renal cell and testicular carcinomas. Results: We found that dexamethasone induces resistance regarding exposure to several cytotoxic agents such as taxol, gemcitabine, cisplatin, 5-FU and gamma-irradiation in 86% of the freshly isolated prostate tumors and in 100% of the established urological cell lines. No difference in dexamethasone-mediated protection was found in normal, benign and malignant prostate tumors. Conclusions: These data show for the first time that dexamethasone induced therapy resistance in urological carcinomas is not the exception but a more common phenomenon and implicate that glucocorticoids may have two faces in cancer therapy, a beneficial and a dangerous one.

PMID: 16294015 [PubMed - as supplied by publisher]

Posted by blogposter at 08:49 PM | Permalink

Novel therapeutic approaches to advanced prostate cancer.

Clin Adv Hematol Oncol. 2005 Apr;3(4):271-82

Authors: Armstrong AJ, Carducci MA

Considerable progress in the treatment of advanced prostate cancer was made in 2004 with the approval by the US Food and Drug Administration of docetaxel for the treatment of metastatic hormone-refractory prostate cancer. The survival benefit with docetaxel and prednisone, however, has been modest, on the order of 2-3 months compared with mitoxantrone and prednisone. While docetaxel-based therapy has demonstrated improvement in symptomatic and quality-of-life endpoints, certainly there is a pressing need for improvement in outcomes. A number of novel agents are in basic and clinical development for advanced prostate cancer, some of which are specific to mechanisms that may be important in the development and spread of prostate cancer. Novel approaches including immunotherapy, antiangiogenic compounds, and cell growth and survival pathway inhibitors, as well as targeted cytotoxic compounds, are among the broad categories that will be discussed in this review. Clinical advances in meaningful endpoints such as survival and quality of life are eagerly awaited in large-scale trials of active and rationally designed agents.

PMID: 16167000 [PubMed - in process]

Posted by blogposter at 07:53 PM | Permalink

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]

Posted by blogposter at 07:49 PM | Permalink

81 new PubMed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

prostate cancer

These PubMed results were generated on 2005/11/20

PubMed, 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.

Posted by blogposter at 07:32 PM | Permalink

70 new PubMed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

prostate cancer treatment

These PubMed results were generated on 2005/11/20

PubMed, 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.

Posted by blogposter at 07:28 PM | Permalink

[The study landscape for prostate cancer.]

Urologe A. 2005 Nov 15;

Authors: Miller K

Current prostate cancer studies in Germany encompass the indications "adjuvant therapy", "rising PSA following radical prostatectomy", "metastasized, hormone sensitive prostate cancer", and "hormone refractory prostate cancer". In the adjuvant field, the potential of zoledronic acid for the prevention of bone metastases is being investigated in a large phase III trial. The activity of imatinib in low volume prostate cancer is being tested in patients with rising PSA following radical prostatectomy (phase II). The randomized phase III trial intermittent versus continuous hormone therapy in D1 and D2 patients has finished accrual and follow-up will be extended until the end of 2006. In hormone refractory prostate cancer(HRPC), the results of a recent phase II study (Association of Urological Oncology; AOU AP 33/02) were promising. This led to a currently activate phase III trial comparing intermittent with continuous chemotherapy in HRPC. The interdisciplinary study group of the AUO (Urology) and the ARO (Radio-oncology) has developed several new protocols which are currently under review by the German Cancer Aid (Deutsche Krebshilfe).

PMID: 16292461 [PubMed - as supplied by publisher]

Posted by blogposter at 12:01 PM | Permalink

70 new PubMed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

prostate cancer treatment

These PubMed results were generated on 2005/11/20

PubMed, 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.

Posted by blogposter at 12:01 PM | Permalink

Corticosteroid-Induced Chemotherapy Resistance in Urological Cancers.

Cancer Biol Ther. 2006 Jan 25;5(1)

Authors: Zhang C, Mattern J, Haferkamp A, Pfitzenmaier J, Hohenfellner M, Rittgen W, Edler L, Debatin KM, Groene E, Herr I

Purpose: Glucocorticoids such as dexamethasone are widely used for medication of urological diseases, e.g., as cotreatment of advanced prostate cancer, to improve appetite, weight loss, fatigue, relieve bone pain, diminish ureteric obstruction, to reduce the production of adrenal androgens, as an antiemetic in patients undergoing chemo- and/or radiotherapy together with serving as "standard" therapy arm in randomized studies. While the potent pro-apoptotic properties and the supportive effects of glucocorticoids to tumor therapy in lymphoid cells are well studied, the impact to growth of prostate and other urological carcinomas is unknown. Methods: We isolated cells from surgical resections of 21 prostate tumors and measured apoptosis and viability in these primary cells and 17 established cell lines from human prostate, bladder, renal cell and testicular carcinomas. Results: We found that dexamethasone induces resistance regarding exposure to several cytotoxic agents such as taxol, gemcitabine, cisplatin, 5-FU and gamma-irradiation in 86% of the freshly isolated prostate tumors and in 100% of the established urological cell lines. No difference in dexamethasone-mediated protection was found in normal, benign and malignant prostate tumors. Conclusions: These data show for the first time that dexamethasone induced therapy resistance in urological carcinomas is not the exception but a more common phenomenon and implicate that glucocorticoids may have two faces in cancer therapy, a beneficial and a dangerous one.

PMID: 16294015 [PubMed - as supplied by publisher]

Posted by blogposter at 08:34 PM | Permalink

Advanced prostate cancer: the future.

Can J Urol. 2005 Jun;12 Suppl 2:42-7

Authors: Armstrong AJ, Carducci MA

The demonstration of a survival benefit with docetaxel for the treatment of metastatic hormone refractory prostate cancer (HRPC) is an important step forward in advancing treatment options for advanced prostate cancer. While docetaxel-based therapy has demonstrated improvement in symptomatic and quality-of-life endpoints, certainly there is a pressing need for improvement in outcomes. A number of novel agents are in basic and clinical development for advanced prostate cancer, some of which are specific to mechanisms that may be important in the development and spread of prostate cancer. Novel approaches including novel cytotoxics, immunotherapy, PSMA targeted monoclonal antibodies are among the broad categories that will be discussed in this brief review.

PMID: 16018833 [PubMed - indexed for MEDLINE]

Posted by blogposter at 08:34 PM | Permalink

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Calcitonin increases invasiveness of prostate cancer cells: role for cyclic AMP-dependent protein kinase A in calcitonin action.

Int J Cancer. 2005 Nov 20;117(4):551-60

Authors: Sabbisetti VS, Chirugupati S, Thomas S, Vaidya KS, Reardon D, Chiriva-Internati M, Iczkowski KA, Shah GV

Calcitonin (CT) is synthesized and secreted in prostate epithelium, and its secretion from malignant prostates is several-fold higher than from benign prostates. CT receptor (CTR) is expressed in malignant prostate epithelium, and its activation stimulates growth of prostate cancer (PC) cells via activation of adenylyl cyclase and calcium/phospholipid pathways. To identify the role of "CT System" in prostate cancer, we tested the expression of CT and CTR mRNAs in invading tumor cells of prostate cancer specimens. The effect of CT on in vitro invasion of PC cell lines and on activation of gelatinases was also examined. The cells of primary tumors and those invading stroma co-expressed CT/CTR mRNAs. Exogenously added CT increased in vitro invasion of PC cell lines and caused a rapid, several-fold but transient increase in protein kinase A activity. In contrast, anti-CT serum caused a dose-dependent inhibition of in vitro invasion of PC-3M cells. CT also increased the concentration and activities of MMP-2 and MMP-9. Rp.cAMP, a competitive inhibitor of cAMP-dependent protein kinase A, myristoylated protein kinase A inhibitory peptide (PKI) as well as the expression of dominant negative form of PKA all attenuated basal in vitro invasion of PC-3M cells, and CT could not increase in vitro invasiveness in their presence. These results suggest that overexpression of "CT System" in invasive PC tumors significantly contributes to increased invasiveness of prostate cancer cells. The action of CT may be mediated by protein kinase A signaling, which subsequently leads to increased cell invasion and secretion of gelatinases.

PMID: 15929083 [PubMed - indexed for MEDLINE]

Posted by blogposter at 12:33 PM | Permalink

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Differential expression of steroid receptors in prostate tissues before and after radiation therapy for prostatic adenocarcinoma.

Int J Cancer. 2005 Nov 10;117(3):381-6

Authors: Torlakovic E, Lilleby W, Berner A, Torlakovic G, Chibbar R, Furre T, Fosså SD

The expression, distribution and the role of steroid receptors in benign and malignant untreated prostate tissues is well recognized, however, the status of steroid receptors in prostate after radiotherapy (RT) for adenocarcinoma has not yet been studied fully. Immunohistochemical evaluation of androgen receptor (AR), estrogen receptor-alpha (ER-alpha), estrogen receptor-beta (ER-beta), and progesterone receptor (PR) was carried out in prostate needle biopsies obtained before and after radiotherapy from 60 patients with adenocarcinoma. The ER-beta transcripts were also studied by RT-PCR in LNCaP prostate carcinoma cell line before and 24 hr after gamma-irradiation at 0.5 Gy and 8.0 Gy. Significantly higher level of ER-beta expression was found in post-radiation samples of prostate adenocarcinoma and benign epithelium. After RT, all steroid receptors were upregulated in prostatic stroma. Tumor AR expression did not change significantly. Although a positive association between AR and ER-beta expression was observed in pre-treatment prostate adenocarcinoma, it was lost after RT suggesting that these 2 steroid receptors respond differently to RT. High levels of pretreatment tumor ER-beta were associated with local recurrence after RT and decreased biochemical recurrence-free survival (p = 0.028). LNCaP cell line that expressed no ER-beta mRNA before gamma-irradiation, clearly expressed ER-beta mRNA 24 hr after 0.5 Gy and 8.0 Gy. Upregulation of all steroid receptors in the prostate stroma and upregulation of ER-beta in the tumor epithelium after RT, may represent a protective tissue response to radiation-induced tissue injury. Although stromal AR was doubled after RT, the tumor and benign epithelium expression of AR seemed resistant to change by RT.

PMID: 15900599 [PubMed - indexed for MEDLINE]

Posted by blogposter at 09:06 PM | Permalink

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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]

Posted by blogposter at 09:05 PM | Permalink

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Acute genitourinary toxicity after high-dose-rate (HDR) brachytherapy combined with hypofractionated external-beam radiation therapy for localized prostate cancer: correlation between the urethral dose in HDR brachytherapy and the severity of acute genitourinary toxicity.

Int J Radiat Oncol Biol Phys. 2005 Oct 1;63(2):463-71

Authors: Akimoto T, Ito K, Saitoh J, Noda SE, Harashima K, Sakurai H, Nakayama Y, Yamamoto T, Suzuki K, Nakano T, Niibe H

PURPOSE: Several investigations have revealed that the alpha/beta ratio for prostate cancer is atypically low, and that hypofractionation or high-dose-rate (HDR) brachytherapy regimens using appropriate radiation doses may be expected to yield tumor control and late sequelae rates that are better or at least as favorable as those achieved with conventional radiation therapy. In this setting, we attempted treating localized prostate cancer patients with HDR brachytherapy combined with hypofractionated external beam radiation therapy (EBRT). The purpose of this study was to evaluate the feasibility of using this approach, with special emphasis on the relationship between the severity of acute genitourinary (GU) toxicity and the urethral dose calculated from the dose-volume histogram (DVH) of HDR brachytherapy. METHODS AND MATERIALS: Between September 2000 and December 2003, 70 patients with localized prostate cancer were treated by iridium-192 HDR brachytherapy combined with hypofractionated EBRT at the Gunma University Hospital. Hypofractionated EBRT was administered in fraction doses of 3 Gy, three times per week; a total dose of 51 Gy was delivered to the prostate gland and the seminal vesicles using the four-field technique. No elective pelvic irradiation was performed. After the completion of EBRT, all the patients additionally received transrectal ultrasonography (TRUS)-guided HDR brachytherapy. The fraction size and the number of fractions in HDR brachytherapy were prospectively changed, whereas the total radiation dose for EBRT was fixed at 51 Gy. The fractionation in HDR brachytherapy was as follows: 5 Gy x 5, 7 Gy x 3, 9 Gy x 2, administered twice per day, although the biologic effective dose (BED) for HDR brachytherapy combined with EBRT, assuming that the alpha/beta ratio is 3, was almost equal to 138 in each fractionation group. The planning target volume was defined as the prostate gland with 5-mm margin all around, and the planning was conducted based on computed tomography images. The number of patients in each fractionation group was as follows: 13 in the 5-Gy group; 19 in the 7-Gy group, and 38 in the 9-Gy group. The tumor stage was T1 in 10 patients, T2 in 36 patients, and T3 in 24 patients. The Gleason score was 2-6 in 11 patients, 7 in 34 patients, and 8-10 in 25 patients. Androgen ablation was performed in all the patients. The median follow-up duration was 14 months (range 3-42 months). The toxicities were graded based on the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer toxicity criteria. RESULTS: The main symptoms of acute GU toxicity were dysuria and increase in urinary frequency or nocturia. The grade distribution of acute GU toxicity in the patients was as follows: Grade 0-1, 39 patients (56%), and Grade 2-4, 31 patients (44%). One patient who developed acute urinary obstruction was classified as having Grade 4 toxicity. Comparison of the distribution of the grade of acute GU toxicity among the different fractionation groups revealed no statistically significant differences among the groups. The urethral dose in HDR brachytherapy was evaluated using the following DVH parameters: V30 (percentage of the urethral volume receiving 30% of the prescribed radiation dose), V80, V90, V100, V110, V120, V130, and V150. The V30-110 values in the patients with Grade 2-4 acute GU toxicity were significantly higher than those in patients with Grade 0-1 toxicity. On the other hand, there were no significant differences in the V120-150 values between patients with Grade 0-1 and Grade 2-4 toxicity. Regarding the influence of the number of needles implanted for the radiation therapy, patients with 11 needles or less showed a significantly higher incidence of Grade 2-4 acute GU toxicity compared with those with 12 needles or more (p < 0.05). CONCLUSIONS: It was concluded that HDR brachytherapy combined with hypofractionated EBRT is feasible for localized prostate cancer when considered from the viewpoint of acute toxicity. Increase in the fraction dose or reduction in the number of fractions in HDR brachytherapy did not affect the severity of acute GU toxicity, and the volume of urethra receiving an equal or lower radiation dose than the prescribed dose was more closely associated with the grade severity of acute GU toxicity than that receiving a higher than the prescribed dose.

PMID: 16168838 [PubMed - indexed for MEDLINE]

Posted by blogposter at 05:53 PM | Permalink

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Human CTLs to wild-type and enhanced epitopes of a novel prostate and breast tumor-associated protein, TARP, lyse human breast cancer cells.

Cancer Res. 2004 Apr 1;64(7):2610-8

Authors: Oh S, Terabe M, Pendleton CD, Bhattacharyya A, Bera TK, Epel M, Reiter Y, Phillips J, Linehan WM, Kasten-Sportes C, Pastan I, Berzofsky JA

Vaccine therapy for prostate and breast cancer may have potential for treating these major causes of death in males and females, respectively. Critical to the development of tumor-specific vaccines is finding and characterizing novel antigens to be recognized by CD8(+) T cells. To define new CD8(+) T-cell tumor antigens, we determined two wild-type HLA-A2 epitopes from a recently found tumor-associated protein, TARP (T-cell receptor gamma alternate reading frame protein), expressed in prostate and breast cancer cells. We were also able to engineer epitope-enhanced peptides by sequence modifications. Both wild-type and enhanced epitopes induced peptide-specific CD8(+) T-cell responses in A2K(b) transgenic mice. In vitro restimulation of human CD8(+) T cells from a prostate cancer patient resulted in CD8(+) T cells reactive to the peptide epitopes that could lyse HLA-A2(+) human breast cancer cells (MCF-7) expressing TARP. Epitope-specific human CD8(+) T cells were also enumerated in patients' peripheral blood by tetramer staining. Our data suggest that HLA-A2-binding TARP epitopes and enhanced epitopes discovered in this study could be incorporated into a potential vaccine for both breast and prostate cancer.

PMID: 15059918 [PubMed - indexed for MEDLINE]

Posted by blogposter at 10:03 PM | Permalink

Does androgen deprivation improve treatment outcomes in patients with low-risk and intermediate-risk prostate cancer?

Nat Clin Pract Oncol. 2005 May;2(5):236-7

Authors: Miyamoto H, Messing EM, Chang C

PMID: 16264955 [PubMed - in process]

Posted by blogposter at 05:26 PM | Permalink

Posted by blogposter at 05:25 PM | Permalink

Prostate cancer among African-American males: understanding the current issues.

J Natl Black Nurses Assoc. 2005 Jul;16(1):55-62

Authors: Jones RA, Wenzel J

Prostate cancer affects African-American males within the United States in a disproportionate number compared to White males. African-American males are 1.7 times more likely to develop and 2-3 times more likely to die from prostate cancer than White males. Numerous reasons for this disparity exist, including low socioeconomic status, distrust, conflicting cultural beliefs, and past health-care experiences. Controversies surrounding this topic and perhaps contributing to the disparity include cancer-screening recommendations, cancer-related myths, and potential prevention modalities. Nursing research must focus on cancer-related issues among African-Americans to increase the awareness and knowledge of health-care professionals and the public to help decrease morbidity and mortality within African-Americans and other minority populations, and particularly among more vulnerable sections of at-risk minority populations. This article focuses on current issues related to African-American men and prostate health.

PMID: 16255315 [PubMed - in process]

Posted by blogposter at 05:15 PM | Permalink

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Breast-feeding and cancer: the Boyd Orr cohort and a systematic review with meta-analysis.

J Natl Cancer Inst. 2005 Oct 5;97(19):1446-57

Authors: Martin RM, Middleton N, Gunnell D, Owen CG, Smith GD

BACKGROUND: Having been breast-fed has been suggested to influence cancer risk in adulthood. We investigated associations between breast-feeding during infancy and adult cancer incidence and mortality in a cohort study and meta-analyses of published studies. METHODS: The Boyd Orr cohort consisted of 4999 subjects who were originally surveyed in 1937-39, when they were 0-19 years of age. Cancer outcomes from 1948 through 2003 were available for 4379 (88%) subjects, and 3844 had complete data on all covariates. Associations of breast-feeding with cancer were investigated using proportional hazards models. We also identified 14 studies on infant feeding and cancer published from 1966 through July 2005, of which 10 could be combined with the Boyd Orr cohort results in a meta-analysis of breast cancer using random-effect models. RESULTS: In the Boyd Orr cohort, ever having been breast-fed, compared with never having been breast-fed, was not associated with the incidence of all cancers (hazard ratio [HR] = 1.07, 95% confidence interval [CI] = 0.89 to 1.28) or of any individual cancer type examined (prostate HR = 1.43, 95% CI = 0.58 to 3.52; breast HR = 1.62, 95% CI = 0.89 to 2.94; colorectal HR = 0.86, 95% CI = 0.45 to 1.63; gastric HR = 1.22, 95% CI = 0.47 to 3.15). In the meta-analysis, there was also no association between breast-feeding and breast cancer (regardless of menopausal status) (relative risk [RR] = 0.94, 95% CI = 0.85 to 1.04). However, breast-fed women had a reduced risk of premenopausal breast cancer (RR = 0.88, 95% CI = 0.79 to 0.98) but not of postmenopausal breast cancer (RR = 1.00, 95% CI = 0.86 to 1.16). CONCLUSION: Ever having been breast-fed was not associated with overall breast cancer risk, although the meta-analysis revealed a reduced risk of premenopausal breast cancer in women who had been breast-fed.

PMID: 16204694 [PubMed - indexed for MEDLINE]

Posted by blogposter at 04:57 PM | Permalink

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Leptin gene polymorphisms and their phenotypic associations.

Vitam Horm. 2005;71:373-404

Authors: van der Lende T, Te Pas MF, Veerkamp RF, Liefers SC

In an era of rapidly increasing prevalence of human obesity and associated health problems, leptin gene polymorphisms have drawn much attention in biomedical research. Leptin gene polymorphisms have furthermore drawn much attention from animal scientists for their possible roles in economically important production and reproduction traits. Of the polymorphisms reported for exonic, intronic, and promoter regions of the leptin gene, 16 have been included in association studies in humans, 19 in cattle, and 6 (all exonic or intronic) in pigs. In humans, associations have been found with overweight or (early-onset) obesity, non-insulin-dependent diabetes mellitus, prostate cancer, and non-Hodgkin's lymphoma. In cattle, associations have been found with feed intake, milk yield traits, carcass traits, and reproduction-related traits, and in pigs with feed intake, average daily gain, carcass traits (backfat/leanness), and reproduction performance traits. Many of the polymorphisms were only included in a limited number of association studies, or the phenotypes studied varied largely for a given polymorphism between studies. Therefore, many of the associations found for these polymorphisms need to be confirmed in future studies before firm conclusions can be drawn.

PMID: 16112275 [PubMed - indexed for MEDLINE]

Posted by blogposter at 04:50 PM | Permalink

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Delayed disease progression after allogeneic cell vaccination in hormone-resistant prostate cancer and correlation with immunologic variables.

Clin Cancer Res. 2005 Jun 15;11(12):4469-78

Authors: Michael A, Ball G, Quatan N, Wushishi F, Russell N, Whelan J, Chakraborty P, Leader D, Whelan M, Pandha H

PURPOSE: There are a significant number of patients with asymptomatic hormone-resistant prostate cancer who have increasing prostate-specific antigen (PSA) levels but little or no evaluable disease. The immunogenicity and minimal toxicity associated with cell-based vaccine therapy makes this approach attractive for these patients. EXPERIMENTAL DESIGN: We have evaluated a vaccine comprising monthly intradermal injection of three irradiated allogeneic prostate cell lines (8 x 10(6) cells each) over 1 year. The first two doses were supplemented with bacille Calmette-Gu rin as vaccine adjuvant. Twenty-eight hormone-resistant prostate cancer patients were enrolled. Patients were assessed clinically and PSA levels were measured monthly. Radiologic scans (X-ray, computed tomography, and bone scan) were taken at baseline and at intervals throughout the treatment period. Comprehensive monthly immunologic monitoring was undertaken including proliferation studies, activation markers, cytokine protein expression, and gene copy number. This longitudinal data was analyzed through predictive modeling using artificial neural network feed-forward/back-propagation algorithms with multilayer perceptron architecture.RESULTS: Eleven of the 26 patients showed statistically significant, prolonged decreases in their PSA velocity (PSAV). None experienced any significant toxicity. Median time to disease progression was 58 weeks, compared with recent studies of other agents and historical control values of around 28 weeks. PSAV-responding patients showed a titratable T(H)1 cytokine release profile in response to restimulation with a vaccine lysate, while nonresponders showed a mixed T(H)1 and T(H)2 response. Furthermore, immunologic profile correlated with PSAV response by artificial neural network analysis. We found predictive power not only in expression of cytokines after maximal stimulation with phorbol 12-myristate 13-acetate, but also the method of analysis (qPCR measurement of IFN-gamma > qPCR measurement tumor necrosis factor-alpha > protein expression of IFN-gamma > protein expression of interleukin 2). CONCLUSIONS: Whole cell allogeneic vaccination in hormone-resistant prostate cancer is nontoxic and improves the natural history of the disease. Longitudinal changes in immunologic function in vaccinated patients may be better interpreted through predictive modeling using tools such as the artificial neural network rather than periodic "snapshot" readouts.

PMID: 15958632 [PubMed - indexed for MEDLINE]

Posted by blogposter at 04:34 PM | Permalink

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[Budd-Chiari syndrome in a patient with paroxysmal nocturnal haemoglobinuria]

Dtsch Med Wochenschr. 2005 Oct 7;130(40):2257-60

Authors: Balta Z, Nattermann J, Flacke S, Sauerbruch T

HISTORY AND CLINICAL FINDINGS: A 61-year-old man with dyspnea and diffuse abdominal pain due to increasing ascites caused by liver cirrhosis of unknown etiology was admitted for consideration of transjugular intrahepatic portosystemic stent-shunting (TIPSS). The patient's medical history included paroxysmal nocturnal hemoglobinuria (PNH), presenting as slight hemolysis diagnosed 24 years previously. One year before the patient underwent radical retropubic prostatectomy for a localized prostate cancer. Shortly after this intervention he developed ascites. INVESTIGATIONS: Color Doppler ultrasonography revealed an abnormal flow in the major hepatic veins. Transjugular liver biopsy indicated hepatic a circulatory disorder. Hepatic venography revealed the so-called "spider web" pattern characteristic for the Budd-Chiari syndrome. The hypercoagulable state due to paroxysmal nocturnal hemoglobinuria was accentuated by manipulation on the prostate during prostatectomy and presumably resulted in a thrombotic obstruction of the hepatic veins. TREATMENT AND CLINICAL COURSE: After exclusion of contraindications a transjugular intrahepatic portosystemic stent shunt (TIPSS) was performed, which led to a decrease of portal pressure. Signs of portal hypertension such as esophageal varices and ascites resolved completely. The patient has been free of complaints for one year. CONCLUSION: We assume that a hypercoagulopathy due to asymptomatic paroxysmal nocturnal hemoglobinuria resulted in Budd-Chiari syndrome when boosted by postoperative release of procoagulation factors in the thrombokinase-rich prostate. TIPSS is a therapeutic option in these patients.

PMID: 16208599 [PubMed - indexed for MEDLINE]

Posted by blogposter at 04:30 PM | Permalink

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Dose-volume impact in high-dose-rate Iridium-192 brachytherapy as a boost to external beam radiotherapy for localized prostate cancer- a phase II study.

Radiother Oncol. 2005 Nov 3;

Authors: Pinkawa M, Fischedick K, Treusacher P, Asadpour B, Gagel B, Piroth MD, Borchers H, Jakse G, Eble MJ

BACKGROUND AND PURPOSE: Evaluation of dose-volume-time-related factors in 64 patients treated with high-dose-rate brachytherapy (HDR-BT) as a boost to external beam radiotherapy (EBRT) for localized prostate cancer. PATIENTS AND METHODS: Clinical parameters were correlated with morbidity scores of the EPIC (Expanded Prostate Cancer Index) questionnaire. Median time after radiotherapy (HDR-BT up to 18Gy in two fractions and EBRT up to a median dose of 50.4Gy) was 1.5 and 3 years (first and second questionnaire). RESULTS: A significant impact of a urethra D1 exceeding 15Gy in at least one HDR fraction concerning urinary morbidity and a rectum D1 exceeding 6Gy to the rectal mucosa in the first and second HDR fraction concerning the rectal bleeding rate was found. A higher number of needles was associated with lower urinary and bowel scores after 1.5 years. A prostate length >4.8cm and a longer duration of EBRT (independently of the dose) predisposed for lower urinary and bowel scores. In contrast to a urethra D1>15Gy as an independent factor, a rectum D1>6Gy per HDR fraction correlated with a higher number of needles and an increased prostate length. CONCLUSIONS: To minimize morbidity in HDR-BT for prostate cancer, a maximum dose to the urethra of 15Gy and a maximum dose to the rectal mucosa of 6Gy is advisable. Treatment- and patient-related factors have a major impact on toxicity.

PMID: 16271785 [PubMed - as supplied by publisher]

Posted by blogposter at 04:16 PM | Permalink

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Tissue-specificity of prostate specific antigens: Comparative analysis of transcript levels in prostate and non-prostatic tissues.

Cancer Lett. 2005 Jul 18;

Authors: Cunha AC, Weigle B, Kiessling A, Bachmann M, Rieber EP

Activation of immune defense mechanisms against tumor antigens appears to be a promising therapeutic option for advanced prostate cancer (PCa). Specific immunotherapy critically depends on target antigens that are selectively expressed in the tumorous and optional in the normal prostate tissue in sufficient amounts. Although several prostate antigens have been described and some have already been used in clinical trials, a detailed comparative evaluation of their tissue-specificity and expression levels is still lacking. We determined the transcript levels of eight prostate targets (PSA, PAP, PSCA, PSGR, Prostein, PSMA, AIbZIP, trp-p8) in 16 different tissues by quantitative PCR and calculated a tissue-specificity index (TSI) for each molecule. Besides a preferential expression in prostate for all targets, striking differences in the expression levels and TSI were revealed which may be important for the selection of appropriate antigens for immunotherapy of PCa.

PMID: 16046056 [PubMed - as supplied by publisher]

Posted by blogposter at 04:09 PM | Permalink

Related Articles

Antisense oligodeoxynucleotide therapy targeting clusterin gene for prostate cancer: Vancouver experience from discovery to clinic.

Int J Urol. 2005 Sep;12(9):785-94

Authors: Miyake H, Hara I, Gleave ME

BACKGROUND: The objective of this study was to review our experience in the development of antisense (AS) oligodeoxynucleotide (ODN) therapy for prostate cancer targeting antiapoptotic gene, clusterin. METHODS: We initially summarized our data demonstrating that clusterin could be an optimal therapeutic target for prostate cancer, then presented the process of developing AS ODN therapy using several preclinical animal models. Finally, the preliminary data of the recently completed phase I clinical trial using AS clusterin ODN as well as the future prospects of this therapy are discussed. RESULTS: Expression of clusterin was highly up-regulated after androgen withdrawal and during progression to androgen-independence, but low or absent in untreated tissues in both prostate cancer animal model systems and human clinical specimens. Introduction of the clusterin gene into human prostate cancer cells confers resistance to several therapeutic stimuli, including androgen ablation, chemotherapy and radiation. AS ODN targeting the translation initiation site of the clusterin gene markedly inhibited clusterin expression in prostate cancer cells in a dose-dependent and sequence-specific manner. Systemic treatment with AS clusterin ODN enhanced the effects of several conventional therapies through the effective induction of apoptosis in prostate cancer xenograft models. Based on these findings, a phase I clinical trial was completed using AS clusterin ODN incorporating 2'-O-(2-methoxy)ethyl-gapmer backbone (OGX-011), showing up to 90% suppression of clusterin in prostate cancer. CONCLUSIONS: The data described above identified clusterin as an antiapoptotic gene up-regulated in an adaptive cell survival manner following various cell death triggers that helps confer a phenotype resistant to therapeutic stimuli. Inhibition of clusterin expression using AS ODN technology enhances apoptosis induced by several conventional treatments, resulting in the delay of AI progression and improved survival. Clinical trials using AS ODN confirm potent suppression of clusterin expression and phase II studies will begin in early 2005.

PMID: 16201973 [PubMed - in process]

Posted by blogposter at 04:00 PM | Permalink

Use of Complementary Therapies Among Breast and Prostate Cancer Patients During Treatment: A Multisite Study.

Integr Cancer Ther. 2005 Dec;4(4):294-300

Authors: Hann DM, Baker F, Roberts CS, Witt C, McDonald J, Livingston M, Ruiterman J, Ampela R, Crammer C, Kaw O

PURPOSE: The purpose of this study was to compare the use of complementary therapies (CT) among breast and prostate cancer patients during active cancer treatment. The authors compared use and beliefs about the role of CT in cancer recovery. METHODS: A self-report survey was completed by 126 breast cancer patients and 82 prostate cancer patients as part of a multisite research project. The self-report questionnaire inquired about the use of various CTs, sources of information about CT, reasons for using CT, beliefs about the benefits and risks of CT, demographic characteristics, and cancer treatment history. RESULTS: Most of the respondents were older than 50 years, Caucasian, married, had attended or completed college, and were less than 1 year postdiagnosis. Prostate cancer patients were significantly older than the breast cancer patients (P < .001). Several differences emerged between the groups. Compared to the prostate cancer patients, significantly more of the breast cancer patients reported using CT because they wanted to reduce the risk of recurrence (P < .01), play a more active role in recovery (P < .01), help manage stress (P < .01), take a more holistic approach (P < .01), or boost the immune system (P < .01). More of the prostate cancer patients reported using CT to have more control of their recovery (P < .05). The 2 groups also differed significantly (P < .01) on several beliefs about the potential benefits and risks of using CT. CONCLUSIONS: Most of the patients in this study had used some form of CT since the time of their diagnosis. Differences among breast and prostate cancer patients with regard to their use of CT during cancer treatment should be considered by oncology professionals who are discussing this topic with their patients.

PMID: 16282506 [PubMed - as supplied by publisher]

Posted by blogposter at 03:55 PM | Permalink

A MULTICENTER CLINICAL TRIAL ON THE USE OF (-5, -7) PRO PROSTATE SPECIFIC ANTIGEN.

J Urol. 2005 Dec;174(6):2150-2153

Authors: Lein M, Semjonow A, Graefen M, Kwiatkowski M, Abramjuk C, Stephan C, Haese A, Chun F, Schnorr D, Loening SA, Jung K

PURPOSE:: The determination of pro prostate specific antigen (proPSA) forms has been suggested to be promising in prostate cancer diagnosis. In this multicenter trial we evaluated the diagnostic usefulness of (-5, -7) proPSA. MATERIALS AND METHODS:: A total of 2,055 white men, including 1,046 with and 1,009 without prostate cancer, with total PSA (tPSA) between 0.28 and 81 ng/ml were retrospectively analyzed. Of these men 2,026 and 1,727 had tPSA less than 20 and less than 10 ng/ml, respectively. All subjects were untreated for prostatic disease and underwent multisector needle biopsy of the prostate. An Elecsys(R) 2010 analyzer was used to determine tPSA, free PSA (fPSA) and (-5, -7) proPSA in the 2,055 serum samples. ROC analyses were performed to discriminate men with biopsy positive and negative results in the entire and in select tPSA ranges. RESULTS:: In the select tPSA range 2 to 4 ng/ml the area under the ROC curve for proPSA (0.53) and proPSA/fPSA (0.59) was not significantly larger than that for tPSA (0.60) or the fPSA/tPSA (f/tPSA) ratio (0.64). In the tPSA range 4 to 10 ng/ml the area under the curve for the ratio proPSA/fPSA (0.67) was larger than for tPSA (0.53) but not larger than for f/tPSA (0.69). The f/tPSA ratio demonstrated the best discriminatory power in this tPSA range of 4 to 10 ng/ml. CONCLUSIONS:: In this multicenter study no improvement in diagnostic accuracy was shown when comparing (-5, -7) proPSA and the corresponding ratios with tPSA or f/tPSA. Further studies using other proPSA forms or tumor associated proteins should be done.

PMID: 16280753 [PubMed - as supplied by publisher]

Posted by blogposter at 03:36 PM | Permalink