Prostate Cancer Research

GU radiation oncologists consensus on bone loss from androgen deprivation.

Can J Urol. 2006 Feb;13(1):2962-6

Authors: Duncan GG, Corbett T, Lukka H, Warde P, Pickles T

The majority of GU radiation oncologists in Canada attended a consensus meeting in November 2004. The topic of osteoporosis in men receiving androgen deprivation therapy (ADT) for prostate cancer was identified as a key theme. A chaired session with keynote speakers and review of the evidence took place followed by open debate. Participants were provided with background information. Osteoporosis was defined as a T-score < or = -2.5, but the importance of risk factors and clinical findings is noted. Dual DEXA is the current standard for assessment of bone density and relates well to fracture risk. The lifetime risk of fracture is 13% for men over the age of 50 years even without the influence of ADT. Lifestyle, dietary and supplementation advice are provided both to prevent and to manage osteoporosis. The role for prophylactic bisphosphonate therapy in men on ADT without osteoporosis has not been established. Follow-up DEXA scans are required to monitor density, risk and response to interventions. Fracture incidence and BMD should be considered in the trial design of studies involving prolonged ADT. Osteoporosis is a treatable condition and the oncologist should employ ADT with this knowledge. A follow-up e-mail survey was carried out regarding the consensus statement. Responses were received from 49 of the 69 attendees (71%), and overall there was an 89% agreement with the consensus statement. This is now adopted as national practice guidelines for radiation oncologists employed prolonged ADT in prostate cancer patients.

PMID: 16515750 [PubMed - indexed for MEDLINE]

Posted by blogposter at 04:53 PM | Permalink

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Prostate Cancer Prevention

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Posted by blogposter at 12:44 PM | Permalink

Some sociodemographic and diagnostic characteristics of military patients treated in the Department of Medical Oncology, G lhane Military Medical Academy.

Mil Med. 2006 May;171(5):420-4

Authors: Acikel CH, Kir T, Komurcu S, Kilic S, Ozett A, Rzayev M, Arpaci F, Ozturk B, Ogur R, Ataergin S, Kuzhan O, Hasde M

Today, chronic diseases have increased importance. Cancer, for which 10 million new cases are diagnosed around the world each year, is in the lead of such diseases. This study included military personnel with cancer who applied to the Department of Medical Oncology, G lhane Military Medical Academy, in the period between 1998 and 2003, and it aims to describe some sociodemographic and diagnostic characteristics of the patients. The total number of cases was 938, which included both active duty and retired military personnel with diagnoses of cancer who were given medical care between 1998 and 2003 in the Department of Medical Oncology. For the study group, the five most common diagnoses were lung cancer, colorectal cancer, testicular cancer, non-Hodgkin's lymphoma, and Hodgkin's disease. Although the first three diagnoses among officers were lung cancer, testicular cancer, and Hodgkin's disease, those among retired officers were colorectal cancer, lung cancer, and prostate cancer. Among noncommissioned officers, the first three diagnoses were colorectal cancer, testicular cancer, and Hodgkin's disease for active duty patients and lung cancer, colorectal cancer, and gastric cancer for retired patients. In the group of privates, testicular cancer, Hodgkin's disease, and non-Hodgkin's lymphoma were the first three diagnoses. When we consider the characteristics of cancers, such as high costs of treatment, loss of manpower, and high mortality rates, prevention of cancers and early diagnosis are very important. Because the frequent types of cancers differed for groups according to age and occupation, those characteristics should be considered when cancer screening programs are being developed for the Armed Forces.

PMID: 16761893 [PubMed - in process]

Posted by blogposter at 08:57 PM | Permalink

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The role of genistein and synthetic derivatives of isoflavone in cancer prevention and therapy.

Mini Rev Med Chem. 2006 Apr;6(4):401-7

Authors: Sarkar FH, Adsule S, Padhye S, Kulkarni S, Li Y

Genistein, one of the predominant soy isoflavones, has been shown to compete with 17beta-estradiol for estrogen receptor binding because of its structural similarity, resulting in agonistic or antagonistic activity. It causes inhibition of cell growth in breast and prostate cancers in vivo and in vitro. From gene expression profiles, genistein has been found to regulate the genes that are critical for the control of cell proliferation, cell cycle, apoptosis, oncogenesis, transcription regulation, and cell signal transduction pathways. It has been reported that genistein induces apoptosis and inhibits activation of NF-kappaB and Akt signaling pathways, both of which are known to maintain a balance between cell survival and apoptosis. Recently, we found that genistein sensitized cancer cells to apoptosis induced by chemotherapeutic agents including docetaxel, gemcitabine and cisplatin through inactivation of NF-kappaB in multiple cancer cell lines. To enhance the anti-cancer activity of genistein, we have synthesized structurally-modified derivatives of isoflavone based on the structural requirements for optimal anti-cancer effect. We found that these synthetic derivatives of isoflavone exerted higher anti-cancer activity with lower IC50. These derivatives of isoflavone also induced more apoptosis compared to genistein. These results suggest that genistein and synthetic structurally-modified derivatives of isoflavone may be promising agents for cancer chemoprevention and therapy either alone or in combination with existing chemotherapeutic agents.

PMID: 16613577 [PubMed - indexed for MEDLINE]

Posted by blogposter at 03:45 PM | Permalink

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France to pilot testing for prostate cancer.

BMJ. 2006 May 6;332(7549):1052

Authors: Spurgeon B

PMID: 16675805 [PubMed - indexed for MEDLINE]

Posted by blogposter at 10:54 AM | 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. 2006 Jan;78(1):41-6

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 18 Gy in two fractions and EBRT up to a median dose of 50.4 Gy) was 1.5 and 3 years (first and second questionnaire). RESULTS: A significant impact of a urethra D1 exceeding 15 Gy in at least one HDR fraction concerning urinary morbidity and a rectum D1 exceeding 6 Gy 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 >4.8 cm and a longer duration of EBRT (independently of the dose) predisposed for lower urinary and bowel scores. In contrast to a urethra D1 > 15 Gy as an independent factor, a rectum D1 > 6 Gy 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 15 Gy and a maximum dose to the rectal mucosa of 6 Gy is advisable. Treatment- and patient-related factors have a major impact on toxicity.

PMID: 16271785 [PubMed - indexed for MEDLINE]

Posted by blogposter at 04:18 PM | Permalink

Role of dietary modification and vitamins in prostate cancer.

J Med Liban. 2005 Apr-Jun;53(2):103-6

Authors: Sommerkamp HW, Khauli RB

Prostate cancer incidence and nutrition are closely connected and show large food-related differences. Lowest cancer incidence in Asian countries is observed under low-calorie, soy-based food. Mediterranean nutrition has cancer protective components (fruit, vegetables, oil, seafood). The highest cancer incidence in the United States goes along with high-calorie food, red meat and fat ingestion. Changes in lifestyle and nutrition can influence the cancer risk. Dietary supplements and vitamins are in wide use and part of a complementary and alternative medicine.

PMID: 16604996 [PubMed - indexed for MEDLINE]

Posted by blogposter at 05:06 PM | Permalink

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Sulforaphane inhibits histone deacetylase activity in BPH-1, LnCaP and PC-3 prostate epithelial cells.

Carcinogenesis. 2006 Apr;27(4):811-9

Authors: Myzak MC, Hardin K, Wang R, Dashwood RH, Ho E

Sulforaphane (SFN), an isothiocyanate first isolated from broccoli, exhibits chemopreventive properties in prostate cancer cells through mechanisms that are poorly understood. We recently reported on a novel mechanism of chemoprotection by SFN in human colon cancer cells, namely the inhibition of histone deacetylase (HDAC). Here, we show that addition of 15 microM SFN also inhibited HDAC activity by 40, 30 and 40% in BPH-1, LnCaP and PC-3 prostate epithelial cells, respectively. The inhibition of HDAC was accompanied by a 50-100% increase in acetylated histones in all three prostate cell lines, and in BPH-1 cells treated with SFN there was enhanced interaction of acetylated histone H4 with the promoter region of the P21 gene and the bax gene. A corresponding 1.5- to 2-fold increase was seen for p21Cip1/Waf1 and Bax protein expression, consistent with previous studies using HDAC inhibitors, such as trichostatin A. The downstream events included cell cycle arrest and activation of apoptosis, as evidenced by changes in cell cycle kinetics and induction of multi-caspase activity. These findings provide new insight into the mechanisms of SFN action in benign prostate hyperplasia, androgen-dependent prostate cancer and androgen-independent prostate cancer cells, and they suggest a novel approach to chemoprotection and chemotherapy of prostate cancer through the inhibition of HDAC.

PMID: 16280330 [PubMed - indexed for MEDLINE]

Posted by blogposter at 11:42 AM | Permalink

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Anti-emetic therapy: updating urological cancer-care providers.

BJU Int. 2006 Apr;97(4):673-5

Authors: Pietrzak P, Arya M, Patel HR

PMID: 16536750 [PubMed - indexed for MEDLINE]

Posted by blogposter at 04:32 PM | Permalink

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Cell adhesion and prostate tumor-suppressor activity of TSLL2/IGSF4C, an immunoglobulin superfamily molecule homologous to TSLC1/IGSF4.

Oncogene. 2006 Mar 9;25(10):1446-53

Authors: Williams YN, Masuda M, Sakurai-Yageta M, Maruyama T, Shibuya M, Murakami Y

The TSLL2/IGSF4C encodes an immunoglobulin (Ig) superfamily molecule showing significant homology with a lung tumor suppressor, TSLC1. The TSLL2 protein of 55 kDa is mainly expressed in the kidney, bladder, and prostate in addition to the brain. Here, we report the biological significance of TSLL2 in the urinary tissues. An immunohistochemical study reveals that TSLL2 is expressed at the cell-cell attachment sites in the renal tubules, the transitional epithelia of the bladder, and the glandular epithelia of the prostate. Confocal microscopy analysis demonstrates that TSLL2 is localized in the lateral membranes in polarized Mardin-Darby canine kidney (MDCK) cells. TSLL2 forms homo-dimers and its overexpression induces aggregation of suspended MDCK cells in a Ca2+/Mg2+-independent manner, suggesting that it is involved in cell adhesion through homophilic trans-interaction. The TSLL2 gene is mapped on the chromosomal region 19q13.2, whose loss of heterozygosity has been frequently reported in prostate cancer. TSLL2 protein is lost in nine of nine primary prostate cancers and in a prostate cancer cell, PPC-1. Introduction of TSLL2 into PPC-1 strongly suppresses subcutaneous tumor formation in nude mice. These results suggest that TSLL2 is a new member of the Ig superfamily cell adhesion molecules and is a tumor-suppressor candidate in prostate cancer.

PMID: 16261159 [PubMed - indexed for MEDLINE]

Posted by blogposter at 05:57 PM | Permalink

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Prostate cancer update: 2005.

Curr Opin Oncol. 2006 May;18(3):284-8

Authors: Ryan CJ, Small EJ

PURPOSE OF REVIEW: The purpose of this review is to highlight the most important developments in the diagnosis, prevention, and management of prostate cancer that have been published in the medical literature in the past year. RECENT FINDINGS: Recent research has shown that prostate specific antigen (PSA) velocity can be utilized as a prognostic tool in patients with localized prostate cancer and at the time of serologic relapse. Several novel biomarkers are, however, demonstrating encouraging results in refining or replacing PSA as a screening and prognostic tool. A number of studies have shown that dose and dose intensity of radiation have important ramifications. SUMMARY: Recent data reported in the past year have significant implications in screening and diagnosis of prostate cancer as well as the management of localized prostate cancer with radiation.

PMID: 16552242 [PubMed - in process]

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Prostate cancer epidemiology.

Front Biosci. 2006 May 1;11:1388-413

Authors: Hsing AW, Chokkalingam AP

Prostate cancer is the most common non-skin cancer among men in most western populations, and it is the second leading cause of cancer death among U.S. men. Despite its high morbidity, the etiology of prostate cancer remains largely unknown. Advancing age, race, and a family history of prostate cancer are the only established risk factors. Many putative risk factors, including androgens, diet, physical activity, sexual factors, inflammation, and obesity, have been implicated, but their roles in prostate cancer etiology remain unclear. It is estimated that as much as 42% of the risk of prostate cancer may be accounted for by genetic influences, including individual and combined effects of rare, highly penetrant genes, more common weakly penetrant genes, and genes acting in concert with each other. Numerous genetic variants in the androgen biosynthesis/metabolism, carcinogen metabolism, DNA repair, and chronic inflammation pathways, have been explored, but the results are largely inconclusive. The pathogenesis of prostate cancer likely involves interplay between environmental and genetic factors. To unravel these complex relationships, large well-designed interdisciplinary epidemiologic studies are needed. With newly available molecular tools, a new generation of large-scale multidisciplinary population-based studies is beginning to investigate gene-gene and gene-environment interactions. Results of these studies may lead to better detection, treatment, and, ultimately, prevention of prostate cancer.

PMID: 16368524 [PubMed - in process]

Posted by blogposter at 09:32 PM | Permalink

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Prospective studies of dairy product and calcium intakes and prostate cancer risk: a meta-analysis.

J Natl Cancer Inst. 2005 Dec 7;97(23):1768-77

Authors: Gao X, LaValley MP, Tucker KL

BACKGROUND: The Dietary Guidelines for Americans 2005 recommends that Americans increase their intake of dairy products. However, some studies have reported that increasing dairy product intake is associated with an increased risk of prostate cancer. We conducted a meta-analysis to examine associations between intakes of calcium and dairy products and the risk of prostate cancer. METHODS: We searched Medline for prospective studies published in English-language journals from 1966 through May 2005. We identified 12 publications that used total, advanced, or fatal prostate cancer as end points and reported associations as relative risks (RRs) with 95% confidence intervals (CIs) by category of dairy product or calcium intake. Data were extracted using standardized data forms. Random-effects models were used to pool study results and to assess dose-response relationships between dairy product or calcium intakes and the risk of prostate cancer. We conducted sensitivity analyses by changing criteria for inclusion of studies or by using fixed-effects models. All statistical tests were two-sided. RESULTS: Men with the highest intake of dairy products (RR =1.11 [95% CI = 1.00 to 1.22], P = .047) and calcium (RR = 1.39 [95% CI = 1.09 to 1.77], P = .018) were more likely to develop prostate cancer than men with the lowest intake. Dose-response analyses suggested that dairy product and calcium intakes were each positively associated with the risk of prostate cancer (Ptrend = .029 and .014, respectively). Sensitivity analyses generally supported these associations, although the statistical significance was attenuated. The pooled relative risks of advanced prostate cancer were 1.33 (95% CI = 1.00 to 1.78; P = .055) for the highest versus lowest intake categories of dairy products and 1.46 (95% CI = 0.65 to 3.25; P > .2) for the highest versus lowest intake categories of calcium. CONCLUSIONS: High intake of dairy products and calcium may be associated with an increased risk of prostate cancer, although the increase appears to be small.

PMID: 16333032 [PubMed - indexed for MEDLINE]

Posted by blogposter at 05:29 PM | Permalink

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Sexual function-preserving cystectomy.

Urology. 2005 Aug;66(2):235-41

Authors: Tal R, Baniel J

PMID: 16040092 [PubMed - indexed for MEDLINE]

Posted by blogposter at 06:18 PM | Permalink

Related Articles

Karyometry in the early detection and chemoprevention of intraepithelial lesions.

Eur J Cancer. 2005 Sep;41(13):1875-88

Authors: Ranger-Moore J, Alberts DS, Montironi R, Garcia F, Davis J, Frank D, Brewer M, Mariuzzi GM, Bartels HG, Bartels PH

The ideal chemopreventive agent targets pre-neoplastic changes and intraepithelial neoplasia, preventing progression over time without notable side effects. Assessment of success of chemopreventive intervention in the short and medium term remains a challenge, and in this review the suggestion is investigated that karyometric measurements constitute suitable markers of chemopreventive efficacy. Karyometry provides the sensitivity required to detect small differences amidst relatively high biological variability. It can help establish progression curves of intraepithelial neoplasia (IEN) to invasive cancer, and thus detect chemopreventive effects. Such effects can be observed in two ways, at the group level (intervention vs. placebo), and at the case (or patient) level. The latter is more difficult to establish, necessitating the development of specialised statistical methods. Analysis of between-case and within-case heterogeneity can reveal useful information about cancer progression and prevention. We suggest that karyometry can objectively quantify IEN progression, providing a framework for statistically securing chemopreventive effects. It can act as an integrating biomarker by detecting chemopreventive activity even when the mechanism for a given progression pathway is unknown, or when multiple pathways exist. The sensitivity of karyometric detection can help optimise the design of clinical trials of novel chemopreventive agents by decreasing trial duration and/or sample size.

PMID: 16087328 [PubMed - indexed for MEDLINE]

Posted by blogposter at 04:16 PM | Permalink

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Selenium in cancer prevention: a review of the evidence and mechanism of action.

Proc Nutr Soc. 2005 Nov;64(4):527-42

Authors: Rayman MP

Se is an unusual trace element in having its own codon in mRNA that specifies its insertion into selenoproteins as selenocysteine (SeCys), by means of a mechanism requiring a large SeCys-insertion complex. This exacting insertion machinery for selenoprotein production has implications for the Se requirements for cancer prevention. If Se may protect against cancer, an adequate intake of Se is desirable. However, the level of intake in Europe and some parts of the world is not adequate for full expression of protective selenoproteins. The evidence for Se as a cancer preventive agent includes that from geographic, animal, prospective and intervention studies. Newly-published prospective studies on oesophageal, gastric-cardia and lung cancer have reinforced previous evidence, which is particularly strong for prostate cancer. Interventions with Se have shown benefit in reducing the risk of cancer incidence and mortality in all cancers combined, and specifically in liver, prostate, colo-rectal and lung cancers. The effect seems to be strongest in those individuals with the lowest Se status. As the level of Se that appears to be required for optimal effect is higher than that previously understood to be required to maximise the activity of selenoenzymes, the question has been raised as to whether selenoproteins are involved in the anti-cancer process. However, recent evidence showing an association between Se, reduction of DNA damage and oxidative stress together with data showing an effect of selenoprotein genotype on cancer risk implies that selenoproteins are indeed implicated. The likelihood of simultaneous and consecutive effects at different cancer stages still allows an important role for anti-cancer Se metabolites such as methyl selenol formed from gamma-glutamyl-selenomethyl-SeCys and selenomethyl-SeCys, components identified in certain plants and Se-enriched yeast that have anti-cancer effects. There is some evidence that Se may affect not only cancer risk but also progression and metastasis. Current primary and secondary prevention trials of Se are underway in the USA, including the Selenium and Vitamin E Cancer Prevention Trial (SELECT) relating to prostate cancer, although a large European trial is still desirable given the likelihood of a stronger effect in populations of lower Se status.

PMID: 16313696 [PubMed - in process]

Posted by blogposter at 09:17 PM | Permalink

Minority recruitment to the Selenium and Vitamin E Cancer Prevention Trial (SELECT).

Clin Trials. 2005;2(5):436-42

Authors: Cook ED, Moody-Thomas S, Anderson KB, Campbell R, Hamilton SJ, Harrington JM, Lippman SM, Minasian LM, Paskett ED, Craine S, Arnold KB, Probstfield JL

BACKGROUND: Previous large chemoprevention studies have not recruited significant numbers of minorities. The Selenium and Vitamin E Cancer Prevention Trial (SELECT) is a large phase III study evaluating the impact of selenium and vitamin E on the clinical incidence of prostate cancer. Over 400 SELECT study sites in the USA, Canada, and Puerto Rico recruited men to this trial. The SELECT recruitment goal was 24% minorities, with 20% black, 3% Hispanic, and 1% Asian participants. The goal for black participants was set at 20% because of their proportion in the United States population and their prevalence of prostate cancer. METHODS: The minority recruitment strategies in SELECT were to: 1) consider minority recruitment during site selection; 2) expand the eligibility criteria by lowering the age criterion for black men and including men with controlled co-morbid illnesses; 3) develop a national infrastructure; 4) give additional funds to sites with the potential to increase black enrollment; and 5) provide resources to maximize free media opportunities to promote SELECT. RESULTS: SELECT recruitment began in August 2001 and was intended to last five years, but concluded two years ahead of schedule in June 2004. Of the 35 534 participants enrolled, 21% were minorities, with 15% black, 5% Hispanic, and 1% Asian. CONCLUSIONS: Careful planning, recruitment of large numbers of clinical centers and adequate resources accomplished by the combined efforts of the National Cancer Institute (NCI), Southwest Oncology Group (SWOG), SELECT Recruitment and Adherence Committee (RAC), SELECT Minority and Medically Underserved Subcommittee (MMUS), and the local SELECT sites resulted in attainment of the estimated sample size ahead of schedule and recruitment of the largest percentage of black participants ever randomized to a cancer prevention trial.

PMID: 16315648 [PubMed - in process]

Posted by blogposter at 09:20 PM | Permalink

Minority recruitment to the Selenium and Vitamin E Cancer Prevention Trial (SELECT).

Clin Trials. 2005;2(5):436-42

Authors: Cook ED, Moody-Thomas S, Anderson KB, Campbell R, Hamilton SJ, Harrington JM, Lippman SM, Minasian LM, Paskett ED, Craine S, Arnold KB, Probstfield JL

BACKGROUND: Previous large chemoprevention studies have not recruited significant numbers of minorities. The Selenium and Vitamin E Cancer Prevention Trial (SELECT) is a large phase III study evaluating the impact of selenium and vitamin E on the clinical incidence of prostate cancer. Over 400 SELECT study sites in the USA, Canada, and Puerto Rico recruited men to this trial. The SELECT recruitment goal was 24% minorities, with 20% black, 3% Hispanic, and 1% Asian participants. The goal for black participants was set at 20% because of their proportion in the United States population and their prevalence of prostate cancer. METHODS: The minority recruitment strategies in SELECT were to: 1) consider minority recruitment during site selection; 2) expand the eligibility criteria by lowering the age criterion for black men and including men with controlled co-morbid illnesses; 3) develop a national infrastructure; 4) give additional funds to sites with the potential to increase black enrollment; and 5) provide resources to maximize free media opportunities to promote SELECT. RESULTS: SELECT recruitment began in August 2001 and was intended to last five years, but concluded two years ahead of schedule in June 2004. Of the 35 534 participants enrolled, 21% were minorities, with 15% black, 5% Hispanic, and 1% Asian. CONCLUSIONS: Careful planning, recruitment of large numbers of clinical centers and adequate resources accomplished by the combined efforts of the National Cancer Institute (NCI), Southwest Oncology Group (SWOG), SELECT Recruitment and Adherence Committee (RAC), SELECT Minority and Medically Underserved Subcommittee (MMUS), and the local SELECT sites resulted in attainment of the estimated sample size ahead of schedule and recruitment of the largest percentage of black participants ever randomized to a cancer prevention trial.

PMID: 16315648 [PubMed - in process]

Posted by blogposter at 12:16 PM | Permalink

Related Articles

Selenium in cancer prevention: a review of the evidence and mechanism of action.

Proc Nutr Soc. 2005 Nov;64(4):527-42

Authors: Rayman MP

Se is an unusual trace element in having its own codon in mRNA that specifies its insertion into selenoproteins as selenocysteine (SeCys), by means of a mechanism requiring a large SeCys-insertion complex. This exacting insertion machinery for selenoprotein production has implications for the Se requirements for cancer prevention. If Se may protect against cancer, an adequate intake of Se is desirable. However, the level of intake in Europe and some parts of the world is not adequate for full expression of protective selenoproteins. The evidence for Se as a cancer preventive agent includes that from geographic, animal, prospective and intervention studies. Newly-published prospective studies on oesophageal, gastric-cardia and lung cancer have reinforced previous evidence, which is particularly strong for prostate cancer. Interventions with Se have shown benefit in reducing the risk of cancer incidence and mortality in all cancers combined, and specifically in liver, prostate, colo-rectal and lung cancers. The effect seems to be strongest in those individuals with the lowest Se status. As the level of Se that appears to be required for optimal effect is higher than that previously understood to be required to maximise the activity of selenoenzymes, the question has been raised as to whether selenoproteins are involved in the anti-cancer process. However, recent evidence showing an association between Se, reduction of DNA damage and oxidative stress together with data showing an effect of selenoprotein genotype on cancer risk implies that selenoproteins are indeed implicated. The likelihood of simultaneous and consecutive effects at different cancer stages still allows an important role for anti-cancer Se metabolites such as methyl selenol formed from gamma-glutamyl-selenomethyl-SeCys and selenomethyl-SeCys, components identified in certain plants and Se-enriched yeast that have anti-cancer effects. There is some evidence that Se may affect not only cancer risk but also progression and metastasis. Current primary and secondary prevention trials of Se are underway in the USA, including the Selenium and Vitamin E Cancer Prevention Trial (SELECT) relating to prostate cancer, although a large European trial is still desirable given the likelihood of a stronger effect in populations of lower Se status.

PMID: 16313696 [PubMed - in process]

Posted by blogposter at 03:23 PM | Permalink

Minority recruitment to the Selenium and Vitamin E Cancer Prevention Trial (SELECT).

Clin Trials. 2005;2(5):436-42

Authors: Cook ED, Moody-Thomas S, Anderson KB, Campbell R, Hamilton SJ, Harrington JM, Lippman SM, Minasian LM, Paskett ED, Craine S, Arnold KB, Probstfield JL

BACKGROUND: Previous large chemoprevention studies have not recruited significant numbers of minorities. The Selenium and Vitamin E Cancer Prevention Trial (SELECT) is a large phase III study evaluating the impact of selenium and vitamin E on the clinical incidence of prostate cancer. Over 400 SELECT study sites in the USA, Canada, and Puerto Rico recruited men to this trial. The SELECT recruitment goal was 24% minorities, with 20% black, 3% Hispanic, and 1% Asian participants. The goal for black participants was set at 20% because of their proportion in the United States population and their prevalence of prostate cancer. METHODS: The minority recruitment strategies in SELECT were to: 1) consider minority recruitment during site selection; 2) expand the eligibility criteria by lowering the age criterion for black men and including men with controlled co-morbid illnesses; 3) develop a national infrastructure; 4) give additional funds to sites with the potential to increase black enrollment; and 5) provide resources to maximize free media opportunities to promote SELECT. RESULTS: SELECT recruitment began in August 2001 and was intended to last five years, but concluded two years ahead of schedule in June 2004. Of the 35 534 participants enrolled, 21% were minorities, with 15% black, 5% Hispanic, and 1% Asian. CONCLUSIONS: Careful planning, recruitment of large numbers of clinical centers and adequate resources accomplished by the combined efforts of the National Cancer Institute (NCI), Southwest Oncology Group (SWOG), SELECT Recruitment and Adherence Committee (RAC), SELECT Minority and Medically Underserved Subcommittee (MMUS), and the local SELECT sites resulted in attainment of the estimated sample size ahead of schedule and recruitment of the largest percentage of black participants ever randomized to a cancer prevention trial.

PMID: 16315648 [PubMed - in process]

Posted by blogposter at 08:26 PM | Permalink

Related Articles

Selenium in cancer prevention: a review of the evidence and mechanism of action.

Proc Nutr Soc. 2005 Nov;64(4):527-42

Authors: Rayman MP

Se is an unusual trace element in having its own codon in mRNA that specifies its insertion into selenoproteins as selenocysteine (SeCys), by means of a mechanism requiring a large SeCys-insertion complex. This exacting insertion machinery for selenoprotein production has implications for the Se requirements for cancer prevention. If Se may protect against cancer, an adequate intake of Se is desirable. However, the level of intake in Europe and some parts of the world is not adequate for full expression of protective selenoproteins. The evidence for Se as a cancer preventive agent includes that from geographic, animal, prospective and intervention studies. Newly-published prospective studies on oesophageal, gastric-cardia and lung cancer have reinforced previous evidence, which is particularly strong for prostate cancer. Interventions with Se have shown benefit in reducing the risk of cancer incidence and mortality in all cancers combined, and specifically in liver, prostate, colo-rectal and lung cancers. The effect seems to be strongest in those individuals with the lowest Se status. As the level of Se that appears to be required for optimal effect is higher than that previously understood to be required to maximise the activity of selenoenzymes, the question has been raised as to whether selenoproteins are involved in the anti-cancer process. However, recent evidence showing an association between Se, reduction of DNA damage and oxidative stress together with data showing an effect of selenoprotein genotype on cancer risk implies that selenoproteins are indeed implicated. The likelihood of simultaneous and consecutive effects at different cancer stages still allows an important role for anti-cancer Se metabolites such as methyl selenol formed from gamma-glutamyl-selenomethyl-SeCys and selenomethyl-SeCys, components identified in certain plants and Se-enriched yeast that have anti-cancer effects. There is some evidence that Se may affect not only cancer risk but also progression and metastasis. Current primary and secondary prevention trials of Se are underway in the USA, including the Selenium and Vitamin E Cancer Prevention Trial (SELECT) relating to prostate cancer, although a large European trial is still desirable given the likelihood of a stronger effect in populations of lower Se status.

PMID: 16313696 [PubMed - in process]

Posted by blogposter at 10:25 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

[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

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

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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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[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

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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