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PubMed2026

Bipolar Androgen Therapy as a Potential Mechanistic Bridge to Enhance PARP Inhibitor Efficacy in Prostate Cancer.

Prostate cancer remains a leading cause of cancer-related mortality, largely driven by progression to metastatic castration-resistant prostate cancer (mCRPC). Although poly(ADP-ribose) polymerase inhibitors (PARPis) have improved outcomes in patients with homologous recombination repair (HRR) alterations, particularly in BRCA2-mutated disease, their clinical benefit is limited by restricted patient selection, modest efficacy in non-BRCA HRR alterations, and the frequent emergence of resistance. These limitations highlight an unmet need for strategies that can both expand the therapeutic population and overcome PARPi resistance. Bipolar androgen therapy (BAT), which alternates between supraphysiological and near-castrate androgen exposure, has emerged as a paradoxical yet clinically active approach in mCRPC. Unlike conventional androgen deprivation strategies, preclinical evidence suggests that BAT induces acute androgen receptor-mediated DNA damage while simultaneously suppressing HRR gene expression. This dual effect may generate a transcription-coupled homologous recombination-deficient state that is independent of canonical baseline genomic HRR alterations, thereby potentially sensitizing tumors to PARP inhibition. Current clinical trials of BAT combined with PARP inhibitors suggest activity in both HRR-deficient and HRR-proficient disease. Collectively, these findings suggest a preliminary, hypothesis-generating conceptual framework in which BAT may expand the therapeutic scope of PARPis beyond genomically defined HRR-mutated tumors and may help counteract mechanisms of PARPi resistance in mCRPC.

PARP inhibitor↗

PubMed2005

PROQUR: a tool for quality control, epidemiological surveillance, patient follow-up and clinical research activities related to prostate cancer.

Prostate cancer is a leading cancer in Western Europe and epidemiological surveillance is essential to better understand the disease and its treatment. A database for quality control starting with the diagnostic procedure transrectal ultrasound guided core biopsy of the prostate was designed with the aim of monitoring side-events to the procedure, direct printing of reports and forms related to the diagnostic procedure, the National Cancer Registry and the National Prostate Cancer Quality Registry. The programme is flexible, and new folders related to specific research activities can be attached. The programme is easy to handle and aimed at facilitating the daily work of the urologist, epidemiological surveillance and disease progression. We suggest the programme should become a common tool and platform for a standardised approach in diagnostic, therapeutic, administrative reporting to the National Cancer Registry and National Prostate Cancer Quality Registry, and research on prostate diseases in the urologic community in Sweden and eventually abroad.

Adult↗

PubMed2001

Prostate cancer.

Prostate cancer is the most common internal cancer in American males. There are many variables that effect prognosis, with the Gleason scoring system being one of the most important factors. There is controversy regarding the ideal treatment in various subsets of prostate cancer patients. Posttreatment prostate specific antigen values have prognostic significance.

Disease-Free Survival↗

PubMed2001

Prostate cancer, benign prostatic hyperplasia and physical activity in Shanghai, China.

BACKGROUND: Studies suggest that increased levels of physical activity might decrease the risk of prostate cancer. We ascertained lifetime measures of activity in a population-based case-control study of prostate cancer in Shanghai, China to investigate physical activity in a population where the incidence of prostate cancer is low but rising. METHODS: In all, 238 men with prostate cancer, diagnosed 1993-1995, were identified through a rapid reporting system. A second group of 206 men with benign prostatic hyperplasia (BPH) was matched to prostate cancer cases, and 471 age-matched and population-based controls were identified from urban Shanghai. Through personal interviews, we ascertained all daily, occupational, and recreational activities at ages 20-29, ages 40-49, and in 1988 to generate hours spent sleeping, sitting, in moderate activity, and in vigorous activity. Time spent per week in different activities was converted to metabolic equivalents (MET-h) and energy expended. RESULTS: Time spent in, MET-h of, and energy expended in physical activities were not consistently related to either prostate cancer or BPH when compared to controls. Few men reported regular vigorous activity. Occupational activity, based on an energy expenditure index using job titles, was suggestively associated with a decreased risk of BPH, but not associated with prostate cancer. Associations did not vary according to age or stage of prostate cancer at diagnosis. CONCLUSIONS: Our results, based on regular physical activity, occupational activity, hours in activities, MET-h, and energy expended, did not support a protective role of physical activity in prostate cancer or BPH for men in a low-risk population.

Adult↗

PubMed2007

Dual action on promoter demethylation and chromatin by an isothiocyanate restored GSTP1 silenced in prostate cancer.

Prostate carcinoma is characterized by the silencing of pi-class glutathione S-transferase gene (GSTP1), which encodes a detoxifying enzyme. The silencing of GSTP1, due to aberrant methylation at the CpG island in the promoter/5'-UTR, occurs in the vast majority of prostate tumors and precancerous lesions. It is a pathologic marker and probably an underlying cause of oxidative damage and inflammation at tumor initiation. Inhibition of the aberrant promoter methylation could therefore be an effective mean to prevent carcinogenesis. Several isothiocyanates, including phenethyl isothiocyanate (PEITC), found naturally in cruciferous vegetables, induced growth arrest and apoptosis in prostate cancer cells in culture and xenografts. The effects of PEITC to reactivate GSTP1 were investigated. Exposure of prostate cancer LNCaP cells to PEITC inhibited the activity and level of histone deacetylases (HDACs), and induced selective histone acetylation and methylation for chromatin unfolding. Concurrently PEITC demethylated the promoter and restored the unmethylated GSTP1 in both androgen-dependent and -independent LNCaP cancer cells to the level found in normal prostatic cells, as quantified by methylation-specific PCR and pyrosequencing. The dual action of PEITC on both the DNA and chromatin was more effective than 5'-Aza-2'-deoxycytidine, sodium butyrate, or trichostatin A (TSA), and may de-repress the methyl-binding domain (MBD) on gene transcription. The PEITC-mediated cross-talk between the DNA and chromatin in demethylating and reactivating GSTP1 genes, which is critically inactivated in prostate carcinogenesis, underlines a primary mechanism of cancer chemoprevention. Consequently, new approaches could be developed, with isothiocyanates to prevent and inhibit malignancies.

Acetylation↗

PubMed2005

Recent trends in surgical treatment of localized prostate cancer.

Prostate cancer and its various forms of treatment remain a source of significant controversy and morbidity despite recent advances. In response, there is an increasing trend toward the development of treatments aimed at cancer prevention and at maximizing the preservation of function without sacrificing cancer control. This article reviews the current prostate cancer literature and reports on improvements in existing surgical treatments and developing technologies aimed toward achieving these goals. Specific therapies addressed include improvements in surgical techniques, laparoscopy, robotics, cryosurgical and thermal ablation, and high-intensity focused ultrasound.

Humans↗

PubMed1987

[Prostatic specific antigen in the serum in prostatic cancer].

Prostatic specific antigen (PA) level was determined with a Wako test kit (Japan) for prostatic cancer and others. The incidence of abnormal values of PA in untreated prostatic cancer, was 50, 50, 80, and 100% for stage A1, C (pN0, NX), D1 and D2 cancers, respectively. Grade was not related to the level of PA. Prostatic hypertrophy, prostatitis and urinary stone showed a false positive rate of 52, 18 and 0%, respectively. The level of PA was not correlated to those of prostatic acid phosphatase (RIA). In 31% of the cases, the elevated PA decreased 4 weeks after start of endocrine treatment. Elevated PA in low grade cancer was not normalized as much as that in high and moderate grade cancers. The positive rate of PA in the serum of reactivated patients was significantly higher than that of the patients with cancer under good control by endocrine treatment.

Acid Phosphatase↗

PubMed1994

Prostate specific antigen and gleason grade: an immunohistochemical study of prostate cancer.

Prostate cancer is histologically heterogeneous as reflected in the 5 patterns of the Gleason grading system. Gleason grade correlates with volume, extent and prognosis. Serum prostate specific antigen (PSA) levels also correlate with tumor volume but the degree to which grade correlates with PSA has not been precisely defined. To quantify this relationship further, we prepared maps of each grade of cancer in 86 radical prostatectomy specimens from patients with clinical stage T2 cancer. The median per cent of the volume of cancer per prostate composed of grade 1 was 0%, while it was 1% for grade 2, 84% for grade 3, 5% for grade 4 and 0% for grade 5. We stained 95 cancer foci (grades 1 to 5) in 40 of these specimens for PSA. The presence and intensity (0 to 3+) of staining in more than 33,000 acini (or cells) correlated inversely with grade (p < 0.0001). Nearly all acini in grade 1 and most in grade 2 stained positive (2 to 3+) for PSA; 87% were positive but with less intensity in grade 3. While many grade 4 (79%) and grade 5 (49%) cells were positive, the intensity of staining was weak. Serum PSA levels correlated with total tumor volume (r = 0.67) but serum PSA levels per cm.3 of cancer decreased with increasing grade (r = -0.24 and p < 0.02). These studies confirm the strong inverse correlation between Gleason grade and the PSA content of prostate cancer. Since more than 85% of grade 3 acini stained for PSA and grade 3 made up the largest portion (84%) of cancer, the predominant contributor to serum PSA levels from prostate cancer was Gleason grade 3. The other grades contribute relatively little to the serum PSA levels either because of the small volume (grades 1 and 2) or the diminished PSA content (grades 4 and 5).

Adult↗

PubMed2003

Management of high-risk populations with locally advanced prostate cancer.

Prostate cancer that extends beyond the confines of the prostatic gland on clinical and/or radiographic assessment, without evidence of lymph node or distant metastases, is regarded as locally advanced. The locally advanced prostate cancer patient population consists of a heterogeneous group of men, some of whom have tumors that may be amenable to primary curative intent with local definitive therapy associated with acceptable long-term cancer control rates. In order to optimally manage this group of patients, it is important to be able to recognize who is at a high risk of tumor recurrence after primary local therapy. In this brief review, we discuss the factors that contribute to the prediction of high risk in populations with locally advanced disease and the treatment options available.

Cause of Death↗

PubMed1994

Prostate cancer screening. Appropriate choices? Investigators of the American Cancer Society National Prostate Cancer Detection Project.

Early detection of prostate cancer has produced distinct stage migration of prostate cancer to earlier, more curable disease through optimized combined use of digital rectal exam (DRE), transrectal ultrasound, and prostate specific antigen (PSA). Currently available and emerging data can be assessed according to the World Health Organization's established criteria. As a significant public health problem, prostate cancer meets almost all the criteria for screening. While concerns about incomplete natural history, progression rates, and the need for better prognostic factors are valid, important social and public health issues also need to be considered. If future expenditures for terminal cancer care are minimized via reductions in therapy choices or coverage, no economic benefit for prostate cancer screening should exist. Narrow-focused attempts at cost reduction could inappropriately discourage high risk groups from participating in early detection programs, thereby eliminating the greatest potential benefit. Conversely, the greatest immediate cost-control issue for prostate cancer care in the United States could be the marked increased detection in men older than 75 years of age. Current cost savings are possible with improved public health education about the appropriateness of early detection in the oldest age groups or those with significant preexisting medical conditions. Prostate cancer control perhaps requires a tailored approach of screening in high risk groups and more appropriate "case finding" in the lower risk, general population. The initial combination of PSA and DRE can result in early detection, which is both ethical and economic, for individual patients consulting with informed physicians.

Aged↗

PubMed2005

Different approaches of gene therapy used in prostate cancer.

Prostate cancer is the second leading malignancy next to lung cancer among American males. Estimated number of new cases of prostate cancer by the year 2004 will be 230,110 and number of deaths due to this disease will be 29,900 (American Cancer Society, Surveillance Research, 2004). Major progress have been made in gene therapy due to significant advancement of biology including specialized fields like Molecular Biology, Cell Biology, Immunology and Molecular Virology which includes development of viral and non-viral vectors and delivery system, of which targeted delivery of suicide genes using tissue specific promoter-enhancer, combined therapy, gene replacement therapy are most notable. In this report, we will review about various aspects of gene therapy including most recent discoveries in this field.

Animals↗

PubMed1995

Use of transrectal ultrasound and biopsy in the detection of prostate cancer.

Prostate cancer is the most common cancer diagnosed in U.S. men. In today's current urologic practice, there is considerable controversy regarding the appropriate treatment of prostate cancer. Transrectal ultrasound (TRUS) is the preferred modality for prostate imaging with established roles in the assessment of prostate size and guidance of accurate biopsies. This review will emphasize the history of TRUS and biopsy, patient preparation, technique of biopsy, interpretation of biopsies, and indications for repeat biopsies. The information gained by TRUS and biopsy is useful in counseling patients about potential treatment options.

Biopsy↗

PubMedDate not supplied

Epidemiology, diagnosis and treatment of prostate cancer.

Prostate cancer is the most commonly diagnosed cancer in the United States. This article outlines the anatomy of the prostate gland, the epidemiology and natural history of prostate cancer, current diagnostic and screening techniques, treatment options and prognostic implications.

Aged↗

PubMed1997

Risk of multiple primary cancers in prostate cancer patients in the Detroit metropolitan area: a retrospective cohort study.

BACKGROUND: Patterns of excess risk for second primary cancers (SPC) in prostate cancer patients have been observed for urinary bladder, other sites in the urinary tract, and hematolymphopoietic tissues in several, but not all, previously reported cohort studies. METHODS: The risk of SPC was evaluated in 9,794 Detroit metropolitan-area men originally diagnosed with carcinoma of the prostate during 1973-1982. The cohort was assembled using Detroit Surveillance, Epidemiology, and End Results (SEER) Registry data and followed until December 31, 1993. RESULTS: The observed number of SPC of all sites was similar to the expected number in the cohort. A significant excess of invasive SPC of the urinary bladder [Standardized incidence ratio (SIR) = 1.57; 95% CI, 1.34-1.83] was observed in this cohort, but after excluding the first 2 months after prostate cancer diagnosis, the excess (SIR = 1.06) was no longer statistically significant. The cumulative proportion of patients with prostate cancer who developed bladder cancer during a follow-up interval of 20 years was 5.5% (95% CI, 4.1-6.9%). The patients who received first-course radiation treatment were observed to be at increased risk for bladder SPC (all stages; SIR = 1.49; 95% CI, 1.07-2.02) when compared to the Detroit-area male population. CONCLUSIONS: These results underscore the importance of continuing medical surveillance for urinary bladder second primary cancers in patients with prostate cancer, but are reassuring in that the magnitude of relative and absolute risks does not suggest deterring adverse effects of radiation treatment or intrinsic risks for neoplasms in other organs or tissues.

Adult↗

PubMed2003

Transrectal ultrasound imaging and prostate cancer.

Prostate cancer is one of the most important causes of death from cancer in men. Ultrasound imaging is frequently used in the diagnosis of prostate cancer. This paper presents an overview of currently available ultrasound imaging techniques. The underlying principles and methods are discussed briefly and examples of the clinical application are presented. Techniques such as gray-scale imaging, Doppler imaging and contrast enhanced imaging techniques using power Doppler, color Doppler, harmonic imaging and intermittent imaging are discussed.

Adenocarcinoma↗

PubMed2006

Natural and synthetic retinoids in prostate cancer.

Prostate cancer (PCa) is the most common cancer for men in Europe, North America, and some parts of Africa. Initially, growth of prostate cancer is usually androgen-dependent, but often it becomes androgen-independent after androgen-deprivation therapy. Managing hormone-refractory prostate carcinoma remains a difficult challenge for clinicians. Retinoids, vitamin A and its synthetic analogs are one of the most studied class of chemopreventive drugs for PCa. Retinoids play a key role in several vital functions as vision and development, and also exert anti-proliferative actions. Anti-proliferative effects of retinoids rely on the regulation of many biological processes, including differentiation, cell proliferation, and apoptosis. Retinoid actions are mediated by two classes of nuclear proteins called retinoic acid (RARalpha,beta and gamma and retinoic alpha,beta and gamma receptors, which are ligand-regulated transcription factors. Effects of both all-trans-retinoic acid (RA), the natural active derivative of vitamin A, and its synthetic derivatives, on prostate gland or prostate cell lines implicate retinoids in the regulation of prostate growth and suppression of PCa development. Deficient retinoid availability and action at the cellular level because of either decreased content or altered metabolism in PCa cells can play a key role in abnormal cellular differentiation pathways, and the loss of anti-proliferative effects. Here we review the in vitro and in vivo effects of retinoids in PCa.

Animals↗

PubMedDate not supplied

Current status of anti-angiogenesis therapy for prostate cancer.

Prostate cancer is the second leading cause of cancer mortality in American men and the single most diagnosed cancer in men. Despite advances in early detection and conventional treatment strategies, prostate cancer progresses and becomes resistant to treatment. Because tumor growth and establishment of metastases are dependent on angiogenesis, interest in the development of anti-angiogenesis therapies has grown. Preclinical studies and early clinical evaluation show promise in the adjunctive use of anti-angiogenesis to overcome the limitations of current therapeutic approaches. In this review, we outline the basic science principles of angiogenesis and their application in the development of anticancer therapies.

Angiogenesis Inhibitors↗

PubMed1987

Prostate cancer.

Prostate cancer is the most frequent malignancy in elderly men. Common presentations include asymptomatic prostate nodules, unexplained bone pain or bladder outlet obstruction. Histologic grading clearly influences the prognosis. Either potency-saving subcapsular prostatectomy or radiation therapy is effective in treating localized disease. New prospects for hormonal therapy of metastatic prostate cancer include antiandrogens and gonadotropin-releasing analogs.

Age Factors↗