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Sample records for advanced hormone-dependent prostate

  1. Cholesterol biosynthesis inhibitor RO 48-8071 suppresses growth of hormone-dependent and castration-resistant prostate cancer cells

    PubMed Central

    Liang, Yayun; Mafuvadze, Benford; Aebi, Johannes D; Hyder, Salman M

    2016-01-01

    Standard treatment for primary prostate cancer includes systemic exposure to chemotherapeutic drugs that target androgen receptor or antihormone therapy (chemical castration); however, drug-resistant cancer cells generally emerge during treatment, limiting the continued use of systemic chemotherapy. Patients are then treated with more toxic standard therapies. Therefore, there is an urgent need for novel and more effective treatments for prostate cancer. The cholesterol biosynthetic pathway is an attractive therapeutic target for treating endocrine-dependent cancers because cholesterol is an essential structural and functional component of cell membranes as well as the metabolic precursor of endogenous steroid hormones. In this study, we have examined the effects of RO 48-8071 (4′-[6-(allylmethylamino)hexyloxy]-4-bromo-2′-fluorobenzophenone fumarate; Roche Pharmaceuticals internal reference: RO0488071) (RO), which is an inhibitor of 2, 3-oxidosqualene cyclase (a key enzyme in the cholesterol biosynthetic pathway), on prostate cancer cells. Exposure of both hormone-dependent and castration-resistant human prostate cancer cells to RO reduced prostate cancer cell viability and induced apoptosis in vitro. RO treatment reduced androgen receptor protein expression in hormone-dependent prostate cancer cells and increased estrogen receptor β (ERβ) protein expression in both hormone-dependent and castration-resistant prostate cancer cell lines. Combining RO with an ERβ agonist increased its ability to reduce castration-resistant prostate cancer cell viability. In addition, RO effectively suppressed the growth of aggressive castration-resistant human prostate cancer cell xenografts in vivo without any signs of toxicity to experimental animals. Importantly, RO did not reduce the viability of normal prostate cells in vitro. Our study is the first to demonstrate that the cholesterol biosynthesis inhibitor RO effectively suppresses growth of human prostate cancer cells

  2. Cholesterol biosynthesis inhibitor RO 48-8071 suppresses growth of hormone-dependent and castration-resistant prostate cancer cells.

    PubMed

    Liang, Yayun; Mafuvadze, Benford; Aebi, Johannes D; Hyder, Salman M

    2016-01-01

    Standard treatment for primary prostate cancer includes systemic exposure to chemotherapeutic drugs that target androgen receptor or antihormone therapy (chemical castration); however, drug-resistant cancer cells generally emerge during treatment, limiting the continued use of systemic chemotherapy. Patients are then treated with more toxic standard therapies. Therefore, there is an urgent need for novel and more effective treatments for prostate cancer. The cholesterol biosynthetic pathway is an attractive therapeutic target for treating endocrine-dependent cancers because cholesterol is an essential structural and functional component of cell membranes as well as the metabolic precursor of endogenous steroid hormones. In this study, we have examined the effects of RO 48-8071 (4'-[6-(allylmethylamino)hexyloxy]-4-bromo-2'-fluorobenzophenone fumarate; Roche Pharmaceuticals internal reference: RO0488071) (RO), which is an inhibitor of 2, 3-oxidosqualene cyclase (a key enzyme in the cholesterol biosynthetic pathway), on prostate cancer cells. Exposure of both hormone-dependent and castration-resistant human prostate cancer cells to RO reduced prostate cancer cell viability and induced apoptosis in vitro. RO treatment reduced androgen receptor protein expression in hormone-dependent prostate cancer cells and increased estrogen receptor β (ERβ) protein expression in both hormone-dependent and castration-resistant prostate cancer cell lines. Combining RO with an ERβ agonist increased its ability to reduce castration-resistant prostate cancer cell viability. In addition, RO effectively suppressed the growth of aggressive castration-resistant human prostate cancer cell xenografts in vivo without any signs of toxicity to experimental animals. Importantly, RO did not reduce the viability of normal prostate cells in vitro. Our study is the first to demonstrate that the cholesterol biosynthesis inhibitor RO effectively suppresses growth of human prostate cancer cells. Our

  3. Effects of afala and antiestrogen ICI 182,780 in the model of hormone-dependent prostate inflammation.

    PubMed

    Bernoulli, J; Konkol, Y; Vuorikoski, H; Yatkin, E

    2014-04-01

    In the hormone-dependent prostate inflammation model induced by implantation of slow-releasing pellets (50 mg testosterone and 5 mg estradiol) to Noble male rats, intragastric administration of Afala at a dose of 7.5 ml/kg for 18 weeks reduced the number of inflamed prostatic acini. The effect of afala was comparable with that of antiestrogen ICI 182,780 (3 mg/kg subcutaneously twice a week for 18 weeks). Prolonged treatment with hormones in high doses induced severe inflammation of the prostate tissue, which was not terminated by the test preparations. As differentiated from the antiestrogen ICI 182,780, afala did not induce body weight gain and decrease in pituitary weight in experimental animals in comparison with the control group. PMID:24824703

  4. Vitamin K2, a Naturally Occurring Menaquinone, Exerts Therapeutic Effects on Both Hormone-Dependent and Hormone-Independent Prostate Cancer Cells

    PubMed Central

    Samykutty, Abhilash; Shetty, Aditya V.; Dakshinamoorthy, Gajalakshmi; Zheng, Gouxing; Chen, Aoshuang; Bosland, Maarten C.; Kajdacsy-Balla, André; Gnanasekar, Munirathinam

    2013-01-01

    In recent years, several studies have shown that vitamin k2 (VK2) has anticancer activity in a variety of cancer cells. The antitumor effects of VK2 in prostate cancer are currently not known. In the present study, we sought to characterize the anticancer potential of VK2 in both androgen-dependent and -independent prostate cancer cells. Our investigations show that VK2 is able to suppress viability of androgen-dependent and androgen-independent prostate cancer cells via caspase-3 and -8 dependent apoptosis. We also show that VK2 treatment reduces androgen receptor expression and PSA secretion in androgen-dependent prostate cancer cells. Our results also implicate VK2 as a potential anti-inflammatory agent, as several inflammatory genes are downregulated in prostate cancer cells following treatment with VK2. Additionally, AKT and NF-kB levels in prostate cancer cells are reduced significantly when treated with VK2. These findings correlated with the results of the Boyden chamber and angiogenesis assay, as VK2 treatment reduced cell migration and angiogenesis potential of prostate cancer cells. Finally, in a nude mice model, VK2 administration resulted in significant inhibition of both androgen-dependent and androgen-independent tumor growth. Overall, our results suggest that VK2 may be a potential therapeutic agent in the treatment of prostate cancer. PMID:24062781

  5. Prostate Cancer Stem Cells: Research Advances

    PubMed Central

    Jaworska, Dagmara; Król, Wojciech; Szliszka, Ewelina

    2015-01-01

    Cancer stem cells have been defined as cells within a tumor that possesses the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor. Experimental evidence showed that these highly tumorigenic cells might be responsible for initiation and progression of cancer into invasive and metastatic disease. Eradicating prostate cancer stem cells, the root of the problem, has been considered as a promising target in prostate cancer treatment to improve the prognosis for patients with advanced stages of the disease. PMID:26593898

  6. Prostate Cancer Stem Cells: Research Advances.

    PubMed

    Jaworska, Dagmara; Król, Wojciech; Szliszka, Ewelina

    2015-01-01

    Cancer stem cells have been defined as cells within a tumor that possesses the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor. Experimental evidence showed that these highly tumorigenic cells might be responsible for initiation and progression of cancer into invasive and metastatic disease. Eradicating prostate cancer stem cells, the root of the problem, has been considered as a promising target in prostate cancer treatment to improve the prognosis for patients with advanced stages of the disease.

  7. Recent advances in imaging-guided interventions for prostate cancers

    PubMed Central

    Wu, Xia; Zhang, Feng; Chen, Ran; Zheng, Weiliang; Yang, Xiaoming

    2014-01-01

    The numbers of patients diagnosed with prostate cancers is increasing due to the widespread application of prostate-specific antigen screening and subsequent prostate biopsies. The methods of systemic administration of therapeutics are not target-specific and thus cannot efficiently destroy prostate tumour cells while simultaneously sparing the surrounding normal tissues and organs. Recent advances in imaging-guided minimally invasive therapeutic techniques offer considerable potential for the effective management of prostate cancers. An objective understanding of the feasibility, effectiveness, morbidity, and deficiencies of these interventional techniques is essential for both clinical practice and scientific progress. This review presents the recent advances in imaging-guided interventional techniques for the diagnosis and treatment of prostate cancers. PMID:24769076

  8. Extracts from Epilobium sp. herbs, their components and gut microbiota metabolites of Epilobium ellagitannins, urolithins, inhibit hormone-dependent prostate cancer cells-(LNCaP) proliferation and PSA secretion.

    PubMed

    Stolarczyk, Magdalena; Piwowarski, Jakub P; Granica, Sebastian; Stefańska, Joanna; Naruszewicz, Marek; Kiss, Anna K

    2013-12-01

    Extracts from Epilobium sp. herbs have been traditionally used in the treatment of prostate-associated ailments. Our studies demonstrated that the extracts from Epilobium angustifolium, Epilobium parviflorum and Epilobium hirsutum herbs are potent prostate cancer cells (LNCaP) proliferation inhibitors with IC50 values around 35 µg/ml. The tested extracts reduced prostate specific antigen (PSA) secretion (from 325.6 ± 25.3 ng/ml to ~90 ng/ml) and inhibited arginase activity (from 65.2 ± 1.1 mUnits of urea/mg of protein to ~40 mUnits of urea/mg protein). Selected constituents of extracts (oenothein B, quercetin-3-O-glucuronide, myricetin-3-O-rhamnoside) were proven to be active in relation to LNCaP cells. However, oenothein B was the strongest inhibitor of cells proliferation (IC50  = 7.8 ± 0.8 μM), PSA secretion (IC50  = 21.9 ± 3.2 μM) and arginase activity (IC50 = 19.2 ± 2.0 μM). Additionally, ellagitannins from E. hirustum extract were proven to be transformed by human gut microbiota into urolithins. Urolithin C showed the strongest activity in the inhibition of cell proliferation (IC50  = 35.2 ± 3.7 μM), PSA secretion (reduced PSA secretion to the level of 100.7 ± 31.0 ng/ml) and arginase activity (reduced to the level of 27.9 ± 3.3 mUnits of urea/mg of protein). Results of the work offer an explanation of the activity of Epilobium extracts and support the use of Epilobium preparations in the treatment of prostate diseases. PMID:23436427

  9. Extracts from Epilobium sp. herbs, their components and gut microbiota metabolites of Epilobium ellagitannins, urolithins, inhibit hormone-dependent prostate cancer cells-(LNCaP) proliferation and PSA secretion.

    PubMed

    Stolarczyk, Magdalena; Piwowarski, Jakub P; Granica, Sebastian; Stefańska, Joanna; Naruszewicz, Marek; Kiss, Anna K

    2013-12-01

    Extracts from Epilobium sp. herbs have been traditionally used in the treatment of prostate-associated ailments. Our studies demonstrated that the extracts from Epilobium angustifolium, Epilobium parviflorum and Epilobium hirsutum herbs are potent prostate cancer cells (LNCaP) proliferation inhibitors with IC50 values around 35 µg/ml. The tested extracts reduced prostate specific antigen (PSA) secretion (from 325.6 ± 25.3 ng/ml to ~90 ng/ml) and inhibited arginase activity (from 65.2 ± 1.1 mUnits of urea/mg of protein to ~40 mUnits of urea/mg protein). Selected constituents of extracts (oenothein B, quercetin-3-O-glucuronide, myricetin-3-O-rhamnoside) were proven to be active in relation to LNCaP cells. However, oenothein B was the strongest inhibitor of cells proliferation (IC50  = 7.8 ± 0.8 μM), PSA secretion (IC50  = 21.9 ± 3.2 μM) and arginase activity (IC50 = 19.2 ± 2.0 μM). Additionally, ellagitannins from E. hirustum extract were proven to be transformed by human gut microbiota into urolithins. Urolithin C showed the strongest activity in the inhibition of cell proliferation (IC50  = 35.2 ± 3.7 μM), PSA secretion (reduced PSA secretion to the level of 100.7 ± 31.0 ng/ml) and arginase activity (reduced to the level of 27.9 ± 3.3 mUnits of urea/mg of protein). Results of the work offer an explanation of the activity of Epilobium extracts and support the use of Epilobium preparations in the treatment of prostate diseases.

  10. Advances in genetics: widening our understanding of prostate cancer

    PubMed Central

    Pine, Angela C.; Fioretti, Flavia F.; Brooke, Greg N.; Bevan, Charlotte L.

    2016-01-01

    Prostate cancer is a leading cause of cancer-related death in Western men. Our understanding of the genetic alterations associated with disease predisposition, development, progression, and therapy response is rapidly improving, at least in part, owing to the development of next-generation sequencing technologies. Large advances have been made in our understanding of the genetics of prostate cancer through the application of whole-exome sequencing, and this review summarises recent advances in this field and discusses how exome sequencing could be used clinically to promote personalised medicine for prostate cancer patients. PMID:27408704

  11. Recent advances in image-guided targeted prostate biopsy.

    PubMed

    Brown, Anna M; Elbuluk, Osama; Mertan, Francesca; Sankineni, Sandeep; Margolis, Daniel J; Wood, Bradford J; Pinto, Peter A; Choyke, Peter L; Turkbey, Baris

    2015-08-01

    Prostate cancer is a common malignancy in the United States that results in over 30,000 deaths per year. The current state of prostate cancer diagnosis, based on PSA screening and sextant biopsy, has been criticized for both overdiagnosis of low-grade tumors and underdiagnosis of clinically significant prostate cancers (Gleason score ≥7). Recently, image guidance has been added to perform targeted biopsies of lesions detected on multi-parametric magnetic resonance imaging (mpMRI) scans. These methods have improved the ability to detect clinically significant cancer, while reducing the diagnosis of low-grade tumors. Several approaches have been explored to improve the accuracy of image-guided targeted prostate biopsy, including in-bore MRI-guided, cognitive fusion, and MRI/transrectal ultrasound fusion-guided biopsy. This review will examine recent advances in these image-guided targeted prostate biopsy techniques. PMID:25596716

  12. Radium-223 for Advanced Prostate Cancer

    Cancer.gov

    A summary of results from a phase III trial that compared radium-223 dichloride plus the best standard of care versus a placebo plus the best standard of care in men with metastatic, castration-resistant prostate cancer.

  13. [Treatment strategy for advanced prostate cancer with bone metastases].

    PubMed

    Sugimoto, Mikio; Kakehi, Yoshiyuki

    2006-08-01

    The introduction of PSA screening has led to confirming a shift towards an earlier pathological stage in the diagnosis of prostate cancer. Consequently, the proportion of detecting early stage prostate cancer has clearly been increasing. On the other hand, progressive cancers in the form of distant metastases and locally advanced ones that have been confirmed at the initial diagnosis exhibit a constant rate. In addition, there have been a lot of cases where hormonal resistance was acquired during hormonal therapy which resulted in advanced metastases of the prostate. Prostate cancer has a tendency to be metastatic to bones. Combining the fact that the survival period of patients undergoing treatment is prolonged after metastases, the length of suffering caused by complications, such as ostealgia, pathological fracture and myelopathy, becomes an issue in which QOL and ADL of the patient are sacrificed for a long time. As for treatment of prostate cancer with metastases, a palliative treatment is common in the clinical scene. However, we can extend a life prognosis with use of radiotherapy and surgical treatment in addition to the palliative treatment at an appropriate time. It appears that a combination of new chemotherapy and hormonal therapy will be promising. In the future, we believe that the appearance of new anticancer drugs, endocrine therapies, bisphosphonates and strontium treatment could be used as a part of the treatment strategy for prostate cancer with bone metastases. PMID:16912523

  14. Advanced prostate cancer: Every Voice Matters.

    PubMed

    Payne, Heather; Westcott, Gemma

    2015-01-01

    Heather Payne speaks to Gemma Westcott, Commissioning Editor: Heather Payne was appointed as a consultant in Clinical Oncology at University College Hospital (London, UK) in 1997. Following her training at St Mary's Hospital London Medical School and after qualifying, she spent time working in general medicine in both London and Haiti. Currently, she specializes in the management of urological malignancies, and is actively involved in clinical research as well as being the principal investigator in a number of international multicenter and local studies. She enjoys helping patients with quality of life and decision-making issues with regard to their treatment options. In addition, she is the chairman of the British Uro-oncology Group, and is a member of the Department of Health Prostate Cancer Advisory Group. Further to this, she is a trustee of the Prostate Cancer Research Centre and clinical lead for the National Prostate Cancer Audit. PMID:26075438

  15. Recent advances in magnetic resonance imaging of prostate cancer

    PubMed Central

    Lawrentschuk, Nathan

    2010-01-01

    This concise review attempts to highlight the recent advances in magnetic resonance imaging (MRI) in relation to all the different aspects of prostate cancer (PCa), and outlines future implications of MRI in the diagnosis, treatment, and surveillance of PCa. PMID:21283654

  16. The association between metabolic syndrome and the risk of prostate cancer, high-grade prostate cancer, advanced prostate cancer, prostate cancer-specific mortality and biochemical recurrence

    PubMed Central

    2013-01-01

    Background Although a previous meta-analysis reported no association between metabolic syndrome (MetS) and prostate cancer risk, a number of studies suggest that MetS may be associated with the aggressiveness and progression of prostate cancer. However, these results have been inconsistent. This systematic review and meta-analysis investigated the nature of this association. Methods We systematically searched MEDLINE, EMBASE and bibliographies of retrieved studies up to January 2013 using the keywords “metabolic syndrome” and “prostate cancer”. We assessed relative risks (RRs) of the prostate cancer, several parameters of prostate cancer aggressiveness and progression associated with MetS using 95% confidence intervals (95% CIs). Results The literature search produced 547 hits from which 19 papers were extracted for the meta-analysis. In cancer-free population with and without MetS, the combined adjusted RR (95% CI) of prostate cancer risk and prostate cancer-specific mortality in longitudinal cohort studies is 0.96 (0.85 ~ 1.09) and 1.12 (1.02 ~ 1.23) respectively. In the prostate cancer patients with and without MetS, the combined unadjusted OR (95% CI) of high grade Gleason prostate cancer is 1.44 (1.20 ~ 1.72), the OR of advanced prostate cancer is 1.37 (1.12 ~ 1.68) and the OR of biochemical recurrence is 2.06 (1.43 ~ 2.96). Conclusions The overall analyses revealed no association between MetS and prostate cancer risk, although men with MetS appear more likely to have high-grade prostate cancer and more advanced disease, were at greater risk of progression after radical prostatectomy and were more likely to suffer prostate cancer-specific death. Further primary studies with adjustment for appropriate confounders and larger, prospective, multicenter investigations are required. PMID:23406686

  17. Management of patients with advanced prostate cancer: recommendations of the St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) 2015

    PubMed Central

    Gillessen, S.; Omlin, A.; Attard, G.; de Bono, J. S.; Efstathiou, E.; Fizazi, K.; Halabi, S.; Nelson, P. S.; Sartor, O.; Smith, M. R.; Soule, H. R.; Akaza, H.; Beer, T. M.; Beltran, H.; Chinnaiyan, A. M.; Daugaard, G.; Davis, I. D.; De Santis, M.; Drake, C. G.; Eeles, R. A.; Fanti, S.; Gleave, M. E.; Heidenreich, A.; Hussain, M.; James, N. D.; Lecouvet, F. E.; Logothetis, C. J.; Mastris, K.; Nilsson, S.; Oh, W. K.; Olmos, D.; Padhani, A. R.; Parker, C.; Rubin, M. A.; Schalken, J. A.; Scher, H. I.; Sella, A.; Shore, N. D.; Small, E. J.; Sternberg, C. N.; Suzuki, H.; Sweeney, C. J.; Tannock, I. F.; Tombal, B.

    2015-01-01

    The first St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) Expert Panel identified and reviewed the available evidence for the ten most important areas of controversy in advanced prostate cancer (APC) management. The successful registration of several drugs for castration-resistant prostate cancer and the recent studies of chemo-hormonal therapy in men with castration-naïve prostate cancer have led to considerable uncertainty as to the best treatment choices, sequence of treatment options and appropriate patient selection. Management recommendations based on expert opinion, and not based on a critical review of the available evidence, are presented. The various recommendations carried differing degrees of support, as reflected in the wording of the article text and in the detailed voting results recorded in supplementary Material, available at Annals of Oncology online. Detailed decisions on treatment as always will involve consideration of disease extent and location, prior treatments, host factors, patient preferences as well as logistical and economic constraints. Inclusion of men with APC in clinical trials should be encouraged. PMID:26041764

  18. Recent advances in treatment for Benign Prostatic Hyperplasia.

    PubMed

    van Rij, Simon; Gilling, Peter

    2015-01-01

    Clinical benign prostatic hyperplasia (BPH), often identified as a worsening ability of a male to pass urine, is a significant problem for men in our society. In 2015, the use of personalised medicine is tailoring treatment to individual patient needs and to genetic characteristics. Technological advances in surgical treatment are changing the way BPH is treated and are resulting in less morbidity. The future of BPH treatments is exciting, and a number of novel techniques are currently under clinical trial.

  19. Recent advances in treatment for Benign Prostatic Hyperplasia.

    PubMed

    van Rij, Simon; Gilling, Peter

    2015-01-01

    Clinical benign prostatic hyperplasia (BPH), often identified as a worsening ability of a male to pass urine, is a significant problem for men in our society. In 2015, the use of personalised medicine is tailoring treatment to individual patient needs and to genetic characteristics. Technological advances in surgical treatment are changing the way BPH is treated and are resulting in less morbidity. The future of BPH treatments is exciting, and a number of novel techniques are currently under clinical trial. PMID:26918132

  20. Recent advances in treatment for Benign Prostatic Hyperplasia

    PubMed Central

    van Rij, Simon; Gilling, Peter

    2015-01-01

    Clinical benign prostatic hyperplasia (BPH), often identified as a worsening ability of a male to pass urine, is a significant problem for men in our society. In 2015, the use of personalised medicine is tailoring treatment to individual patient needs and to genetic characteristics. Technological advances in surgical treatment are changing the way BPH is treated and are resulting in less morbidity. The future of BPH treatments is exciting, and a number of novel techniques are currently under clinical trial. PMID:26918132

  1. Dural Metastases in Advanced Prostate Cancer: A Case Report and Review of the Literature

    PubMed Central

    Weiner, A.B.; Cortes-Mateus, S.; De Luis, E.; Durán, I.

    2014-01-01

    Dural metastases from advanced prostate cancer are considered an uncommon diagnosis. However, autopsy studies show a high association between advanced prostate cancer and metastases to the meninges. Because the overall survival of advanced prostate cancer patients is expected to improve with the advent of new therapies, the incidence of clinically relevant dural metastases from prostate cancer will likely increase. We present a case of a heavily pre-treated castration-resistant prostate cancer patient who developed metastases to the duramater. This entity should be considered in the differential diagnosis of any patient with advanced castration-resistant prostate cancer and neurological symptoms. Clinicians should also be aware of the poor prognosis and survival rates associated with the condition. PMID:24917781

  2. Recent Advances in Metabolic Profiling And Imaging of Prostate Cancer

    PubMed Central

    Thapar, Roopa; Titus, Mark A

    2015-01-01

    Cancer is a metabolic disease. Cancer cells, being highly proliferative, show significant alterations in metabolic pathways such as glycolysis, respiration, the tricarboxylic acid (TCA) cycle, oxidative phosphorylation, lipid metabolism, and amino acid metabolism. Metabolites like peptides, nucleotides, products of glycolysis, the TCA cycle, fatty acids, and steroids can be an important read out of disease when characterized in biological samples such as tissues and body fluids like urine, serum, etc. The cancer metabolome has been studied since the 1960s by analytical techniques such as mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy. Current research is focused on the identification and validation of biomarkers in the cancer metabolome that can stratify high-risk patients and distinguish between benign and advanced metastatic forms of the disease. In this review, we discuss the current state of prostate cancer metabolomics, the biomarkers that show promise in distinguishing indolent from aggressive forms of the disease, the strengths and limitations of the analytical techniques being employed, and future applications of metabolomics in diagnostic imaging and personalized medicine of prostate cancer. PMID:25632377

  3. The Endocannabinoid System and Sex Steroid Hormone-Dependent Cancers

    PubMed Central

    Taylor, Anthony H.; Marczylo, Timothy H.; Willets, Jonathon M.; Konje, Justin C.

    2013-01-01

    The “endocannabinoid system (ECS)” comprises the endocannabinoids, the enzymes that regulate their synthesis and degradation, the prototypical cannabinoid receptors (CB1 and CB2), some noncannabinoid receptors, and an, as yet, uncharacterised transport system. Recent evidence suggests that both cannabinoid receptors are present in sex steroid hormone-dependent cancer tissues and potentially play an important role in those malignancies. Sex steroid hormones regulate the endocannabinoid system and the endocannabinoids prevent tumour development through putative protective mechanisms that prevent cell growth and migration, suggesting an important role for endocannabinoids in the regulation of sex hormone-dependent tumours and metastasis. Here, the role of the endocannabinoid system in sex steroid hormone-dependent cancers is described and the potential for novel therapies assessed. PMID:24369462

  4. Prostate Radiotherapy in the Era of Advanced Imaging and Precision Medicine

    PubMed Central

    Dulaney, Caleb R.; Osula, Daniel O.; Yang, Eddy S.; Rais-Bahrami, Soroush

    2016-01-01

    Tremendous technological advancements in prostate radiotherapy have decreased treatment toxicity and improved clinical outcomes for men with prostate cancer. While these advances have allowed for significant treatment volume reduction and whole-organ dose escalation, further improvement in prostate radiotherapy has been limited by classic techniques for diagnosis and risk stratification. Developments in prostate imaging, image-guided targeted biopsy, next-generation gene expression profiling, and targeted molecular therapies now provide information to stratify patients and select treatments based on tumor biology. Image-guided targeted biopsy improves detection of clinically significant cases of prostate cancer and provides important information about the biological behavior of intraprostatic lesions which can further guide treatment decisions. We review the evolution of prostate magnetic resonance imaging (MRI) and MRI-ultrasound fusion-guided prostate biopsy. Recent advancements in radiation therapy including dose escalation, moderate and extreme hypofractionation, partial prostate radiation therapy, and finally dose escalation by simultaneous integrated boost are discussed. We also review next-generation sequencing and discuss developments in targeted molecular therapies. Last, we review ongoing clinical trials and future treatment paradigms that integrate targeted biopsy, molecular profiling and therapy, and prostate radiotherapy. PMID:27022486

  5. Association of the Innate Immunity and Inflammation Pathway with Advanced Prostate Cancer Risk

    PubMed Central

    Kazma, Rémi; Mefford, Joel A.; Cheng, Iona; Plummer, Sarah J.; Levin, Albert M.; Rybicki, Benjamin A.; Casey, Graham; Witte, John S.

    2012-01-01

    Prostate cancer is the most frequent and second most lethal cancer in men in the United States. Innate immunity and inflammation may increase the risk of prostate cancer. To determine the role of innate immunity and inflammation in advanced prostate cancer, we investigated the association of 320 single nucleotide polymorphisms, located in 46 genes involved in this pathway, with disease risk using 494 cases with advanced disease and 536 controls from Cleveland, Ohio. Taken together, the whole pathway was associated with advanced prostate cancer risk (P = 0.02). Two sub-pathways (intracellular antiviral molecules and extracellular pattern recognition) and four genes in these sub-pathways (TLR1, TLR6, OAS1, and OAS2) were nominally associated with advanced prostate cancer risk and harbor several SNPs nominally associated with advanced prostate cancer risk. Our results suggest that the innate immunity and inflammation pathway may play a modest role in the etiology of advanced prostate cancer through multiple small effects. PMID:23272139

  6. Avoiding obsolescence in advanced prostate cancer management: a guide for urologists.

    PubMed

    Shore, Neal D; Karsh, Lawrence; Gomella, Leonard G; Keane, Thomas E; Concepcion, Raoul S; Crawford, E David

    2015-02-01

    Prostate cancer is one of the most common cancers diagnosed in men in the USA and 20–30% of men treated for localised prostate cancer will fail therapy and develop advanced prostate cancer. More drugs have been approved for the treatment of advanced prostate cancer in the past 3 years than in the past three decades, and each drug has its own mechanism of action and, often, unique monitoring requirements. As the treatment landscape for men with advanced prostate cancer is undergoing significant expansion, the roles of both oncologists and urologists are shifting, and the decision for the urologist to treat vs refer requires early assessment to identify which patients are candidates for these novel treatments and the monitoring of patients for tolerability, response, and potential side-effects. Given these rapid changes, the authors of this review met in January 2013 and again in April 2013 to discuss the current challenges facing urologists in adopting these new treatments into their own practices. Here, we provide a brief overview of advanced prostate cancer medical therapies approved in the past decade, the necessary monitoring procedures and early detection methods needed to safely and effectively manage patients receiving these therapies, and our recommendations for applying these new therapies within different models of urology practice, such that urologists can remain an integral component of their patient's care once he has transitioned into advanced prostate cancer

  7. Avoiding obsolescence in advanced prostate cancer management: a guide for urologists.

    PubMed

    Shore, Neal D; Karsh, Lawrence; Gomella, Leonard G; Keane, Thomas E; Concepcion, Raoul S; Crawford, E David

    2015-02-01

    Prostate cancer is one of the most common cancers diagnosed in men in the USA and 20–30% of men treated for localised prostate cancer will fail therapy and develop advanced prostate cancer. More drugs have been approved for the treatment of advanced prostate cancer in the past 3 years than in the past three decades, and each drug has its own mechanism of action and, often, unique monitoring requirements. As the treatment landscape for men with advanced prostate cancer is undergoing significant expansion, the roles of both oncologists and urologists are shifting, and the decision for the urologist to treat vs refer requires early assessment to identify which patients are candidates for these novel treatments and the monitoring of patients for tolerability, response, and potential side-effects. Given these rapid changes, the authors of this review met in January 2013 and again in April 2013 to discuss the current challenges facing urologists in adopting these new treatments into their own practices. Here, we provide a brief overview of advanced prostate cancer medical therapies approved in the past decade, the necessary monitoring procedures and early detection methods needed to safely and effectively manage patients receiving these therapies, and our recommendations for applying these new therapies within different models of urology practice, such that urologists can remain an integral component of their patient's care once he has transitioned into advanced prostate cancer PMID:25756134

  8. Locally Advanced Prostate Cancer: Three-Dimensional Magnetic Resonance Spectroscopy to Monitor Prostate Response to Therapy

    SciTech Connect

    Valentini, Anna Lia; Gui, Benedetta; D'Agostino, Giuseppe Roberto; Mattiucci, Giancarlo; Clementi, Valeria; Di Molfetta, Ippolita Valentina; Bonomo, Pierluigi; Mantini, Giovanna

    2012-11-01

    Purpose: To correlate results of three-dimensional magnetic resonance spectroscopic imaging (MRSI) with prostate-specific antigen (PSA) levels and time since external beam irradiation (EBRT) in patients treated with long-term hormone therapy (HT) and EBRT for locally advanced disease to verify successful treatment by documenting the achievement of metabolic atrophy (MA). Methods and Materials: Between 2006 and 2008, 109 patients were consecutively enrolled. MA was assessed by choline and citrate peak area-to-noise-ratio <5:1. Cancerous metabolism (CM) was defined by choline-to-creatine ratio >1.5:1 or choline signal-to-noise-ratio >5:1. To test the strength of association between MRSI results and the time elapsed since EBRT (TEFRT), PSA levels, Gleason score (GS), and stage, logistic regression (LR) was performed. p value <0.05 was statistically significant. The patients' outcomes were verified in 2011. Results: MRSI documented MA in 84 of 109 and CM in 25 of 109 cases. LR showed that age, GS, stage, and initial and recent PSA had no significant impact on MRSI results which were significantly related to PSA values at the time of MRSI and to TEFRT. Patients were divided into three groups according to TEFRT: <1 year, 1-2 years, and >2 years. MA was detected in 54.1% of patients of group 1, 88.9% of group 2, and in 94.5% of group 3 (100% when PSA nadir was reached). CM was detected in 50% of patients with reached PSA nadir in group 1. Local relapse was found in 3 patients previously showing CM at long TEFRT. Conclusion: MA detection, indicative of successful treatment because growth of normal or abnormal cells cannot occur without metabolism, increases with decreasing PSA levels and increasing time on HT after EBRT. This supports long-term HT in advanced prostate cancer. Larger study series are needed to assess whether MRSI could predict local relapse by detecting CM at long TEFRT.

  9. Frequently rearranged in advanced T-cell lymphomas-1 demonstrates oncogenic properties in prostate cancer

    PubMed Central

    Zhang, Wei; Xiong, Hua; Zou, Yanmei; Xu, Sanpeng; Quan, Lanping; Yuan, Xianglin; Xu, Ningzhi; Wang, Yihua

    2016-01-01

    Prostate cancer is the fifth most common cause of cancer-associated mortality for males worldwide. Although dysregulation of the β-catenin/T-cell factor (TCF) pathway has been previously reported in prostate cancer, the mechanisms underlying this process remain unknown. Frequently rearranged in advanced T-cell lymphomas-1 (FRAT1) functions as a positive regulator of the β-catenin/TCF signaling pathway. However, to the best of our knowledge, the molecular association between FRAT1 and the β-catenin/TCF pathway in prostate cancer has not been investigated. In the present study, FRAT1 expression was analyzed in normal prostate tissues and prostate adenocarcinoma samples using publicly available databases, a commercial tissue microarray and immunohistochemistry techniques. In addition, FRAT1 expression levels were altered by overexpression or RNA interference-mediated depletion in prostate cancer cells. The effects of FRAT1 expression on tumor growth were determined using cell growth curves in vitro and xenografts in nude mice in vivo. The effects of FRAT1 on β-catenin/TCF activity were measured using the TOPFLASH reporter assay. FRAT1 was expressed exclusively in the nuclei of normal prostate basal cells, and nuclear FRAT1 was detected in 68% (40/59) of prostate adenocarcinoma samples. In addition, FRAT1 activated the TCF luciferase reporter gene promoter in prostate cancer cells, and was observed to promote the growth of prostate cancer cells in vitro. Furthermore, FRAT1 expression was sufficient to transform NIH3T3 mouse embryonic fibroblast cells and lead to tumor formation in vivo. These results suggest that FRAT1 demonstrates oncogenic properties in prostate cancer, potentially by suppressing the inhibitory effect of nuclear glycogen synthase 3β against β-catenin/TCF activity, thus activating the Wnt/β-catenin signaling pathway and promoting cell growth. PMID:27599661

  10. Targeting receptor for advanced glycation end products (RAGE) expression induces apoptosis and inhibits prostate tumor growth

    SciTech Connect

    Elangovan, Indira; Thirugnanam, Sivasakthivel; Chen, Aoshuang; Zheng, Guoxing; Bosland, Maarten C.; Kajdacsy-Balla, Andre; Gnanasekar, Munirathinam

    2012-01-27

    Highlights: Black-Right-Pointing-Pointer Targeting RAGE by RNAi induces apoptosis in prostate cancer cells. Black-Right-Pointing-Pointer Silencing RAGE expression abrogates rHMGB1 mediated cell proliferation. Black-Right-Pointing-Pointer Down regulation of RAGE by RNAi inhibits PSA secretion of prostate cancer cells. Black-Right-Pointing-Pointer Knock down of RAGE abrogates prostate tumor growth in vivo. Black-Right-Pointing-Pointer Disruption of RAGE expression in prostate tumor activates death receptors. -- Abstract: Expression of receptor for advanced glycation end products (RAGE) plays a key role in the progression of prostate cancer. However, the therapeutic potential of targeting RAGE expression in prostate cancer is not yet evaluated. Therefore in this study, we have investigated the effects of silencing the expression of RAGE by RNAi approach both in vitro and in vivo. The results of this study showed that down regulation of RAGE expression by RNAi inhibited the cell proliferation of androgen-dependent (LNCaP) and androgen-independent (DU-145) prostate cancer cells. Furthermore, targeting RAGE expression resulted in apoptotic elimination of these prostate cancer cells by activation of caspase-8 and caspase-3 death signaling. Of note, the levels of prostate specific antigen (PSA) were also reduced in LNCaP cells transfected with RAGE RNAi constructs. Importantly, the RAGE RNAi constructs when administered in nude mice bearing prostate tumors, inhibited the tumor growth by targeting the expression of RAGE, and its physiological ligand, HMGB1 and by up regulating death receptors DR4 and DR5 expression. Collectively, the results of this study for the first time show that targeting RAGE by RNAi may be a promising alternative therapeutic strategy for treating prostate cancer.

  11. Frequently rearranged in advanced T‑cell lymphomas‑1 demonstrates oncogenic properties in prostate cancer.

    PubMed

    Zhang, Wei; Xiong, Hua; Zou, Yanmei; Xu, Sanpeng; Quan, Lanping; Yuan, Xianglin; Xu, Ningzhi; Wang, Yihua

    2016-10-01

    Prostate cancer is the fifth most common cause of cancer‑associated mortality for males worldwide. Although dysregulation of the β‑catenin/T‑cell factor (TCF) pathway has been previously reported in prostate cancer, the mechanisms underlying this process remain unknown. Frequently rearranged in advanced T‑cell lymphomas‑1 (FRAT1) functions as a positive regulator of the β‑catenin/TCF signaling pathway. However, to the best of our knowledge, the molecular association between FRAT1 and the β‑catenin/TCF pathway in prostate cancer has not been investigated. In the present study, FRAT1 expression was analyzed in normal prostate tissues and prostate adenocarcinoma samples using publicly available databases, a commercial tissue microarray and immunohistochemistry techniques. In addition, FRAT1 expression levels were altered by overexpression or RNA interference‑mediated depletion in prostate cancer cells. The effects of FRAT1 expression on tumor growth were determined using cell growth curves in vitro and xenografts in nude mice in vivo. The effects of FRAT1 on β‑catenin/TCF activity were measured using the TOPFLASH reporter assay. FRAT1 was expressed exclusively in the nuclei of normal prostate basal cells, and nuclear FRAT1 was detected in 68% (40/59) of prostate adenocarcinoma samples. In addition, FRAT1 activated the TCF luciferase reporter gene promoter in prostate cancer cells, and was observed to promote the growth of prostate cancer cells in vitro. Furthermore, FRAT1 expression was sufficient to transform NIH3T3 mouse embryonic fibroblast cells and lead to tumor formation in vivo. These results suggest that FRAT1 demonstrates oncogenic properties in prostate cancer, potentially by suppressing the inhibitory effect of nuclear glycogen synthase 3β against β‑catenin/TCF activity, thus activating the Wnt/β‑catenin signaling pathway and promoting cell growth. PMID:27599661

  12. [Prostate cancer stem cells: advances in current research].

    PubMed

    Wu, Gang; Wu, Deng-long

    2015-02-01

    Prostate cancer is one of the most common malignancies threatening men's health, and the mechanisms underlying its initiation and progression are poorly understood. Last decade has witnessed encouraging progress in the studies of prostate cancer stem cells (PCSCs), which are considered to play important roles in tumor initiation, recurrence and metastasis, castration resistance, and drug resistance. Therefore, a deeper insight into PCSCs is of great significance for the successful management of prostate cancer. This article presents an overview on the location, origin, and markers of PCSCs as well as their potential correlation with tumor metastasis and castration resistance.

  13. Dietary flavonoid intake, black tea consumption, and risk of overall and advanced stage prostate cancer.

    PubMed

    Geybels, Milan S; Verhage, Bas A J; Arts, Ilja C W; van Schooten, Frederik J; Goldbohm, R Alexandra; van den Brandt, Piet A

    2013-06-15

    Flavonoids are natural antioxidants found in various foods, and a major source is black tea. Some experimental evidence indicates that flavonoids could prevent prostate cancer. We investigated the associations between flavonoid intake, black tea consumption, and prostate cancer risk in the Netherlands Cohort study, which includes 58,279 men who provided detailed baseline information on several cancer risk factors. From 1986 to 2003, 3,362 prostate cancers were identified, including 1,164 advanced (stage III/IV) cancers. Cox proportional hazards regression using the case-cohort approach was used to estimate hazard ratios and 95% confidence intervals. Intake of total catechin, epicatechin, kaempferol, and myricetin and consumption of black tea were associated with a decreased risk of stage III/IV or stage IV prostate cancer. Hazard ratios of stage III/IV and stage IV prostate cancer for the highest versus the lowest category of black tea consumption (≥5 versus ≤1 cups/day) were 0.75 (95% confidence interval: 0.59, 0.97) and 0.67 (95% confidence interval: 0.50, 0.91), respectively. No associations were observed for overall and nonadvanced prostate cancer. In conclusion, dietary flavonoid intake and black tea consumption were associated with a decreased risk of advanced stage prostate cancer.

  14. A profile of enzalutamide for the treatment of advanced castration resistant prostate cancer

    PubMed Central

    Greasley, Rosa; Khabazhaitajer, Mohammad; Rosario, Derek J

    2015-01-01

    Recent advances in understanding the mechanisms underlying the development and progression of castration resistant prostate cancer from androgen-sensitive prostate cancer have provided new avenues exploring efficacious therapies in a disease which is the second leading cause of cancer deaths among men in the western world. In the evolution of second generation anti-androgens, enzalutamide, a novel androgen-receptor signaling inhibitor, has emerged targeting multiple steps within the androgenic stimulation pathway. This review discusses what is currently known of the mechanisms surrounding castration resistant prostate cancer development and the current human clinical trials to determine whether enzalutamide presents a new hope for men with advanced prostate cancer. The issues of therapy resistance, withdrawal effects and cross-resistance are briefly touched upon. PMID:26109877

  15. Intraductal Carcinoma of the Prostate Gland: Recent Advances

    PubMed Central

    Divatia, Mukul K.

    2016-01-01

    Intraductal carcinoma of the prostate (IDC-P) is characterized by prostatic carcinoma involving ducts and/or acini. The presence of IDC-P is usually associated with a high-grade Gleason score, large tumor volume, and adverse prognostic parameters, including extraprostatic extension and seminal vesicle invasion. When present, IDC-P is associated with worse outcomes, regardless of treatment status. IDC-P is included in a broader diagnostic category of atypical cribriform lesions of the prostate gland. This category of lesions also includes high-grade prostatic intraepithelial neoplasia (HGPIN), urothelial carcinoma involving prostatic ducts or acini, and prostatic ductal adenocarcinoma, amongst other intraductal proliferations. Differentiating between these entities is important as they have differing therapeutic and prognostic implications for patients, although differential diagnosis thereof is not always straightforward. The present review discusses IDC-P in regards to its morphological characteristics, molecular features, and clinical outcomes. Given the current state of knowledge, the presence of IDC-P should be evaluated and documented correctly in both radical prostatectomy and needle biopsy specimens, and the clinical implications thereof should be taken into consideration during treatment and follow up. PMID:27401634

  16. New Players for Advanced Prostate Cancer and the Rationalisation of Insulin-Sensitising Medication

    PubMed Central

    Gunter, Jennifer H.; Sarkar, Phoebe L.; Lubik, Amy A.; Nelson, Colleen C.

    2013-01-01

    Obesity and type 2 diabetes are recognised risk factors for the development of some cancers and, increasingly, predict more aggressive disease, treatment failure, and cancer-specific mortality. Many factors may contribute to this clinical observation. Hyperinsulinaemia, dyslipidaemia, hypoxia, ER stress, and inflammation associated with expanded adipose tissue are thought to be among the main culprits driving malignant growth and cancer advancement. This observation has led to the proposal of the potential utility of “old players” for the treatment of type 2 diabetes and metabolic syndrome as new cancer adjuvant therapeutics. Androgen-regulated pathways drive proliferation, differentiation, and survival of benign and malignant prostate tissue. Androgen deprivation therapy (ADT) exploits this dependence to systemically treat advanced prostate cancer resulting in anticancer response and improvement of cancer symptoms. However, the initial therapeutic response from ADT eventually progresses to castrate resistant prostate cancer (CRPC) which is currently incurable. ADT rapidly induces hyperinsulinaemia which is associated with more rapid treatment failure. We discuss current observations of cancer in the context of obesity, diabetes, and insulin-lowering medication. We provide an update on current treatments for advanced prostate cancer and discuss whether metabolic dysfunction, developed during ADT, provides a unique therapeutic window for rapid translation of insulin-sensitising medication as combination therapy with antiandrogen targeting agents for the management of advanced prostate cancer. PMID:23573093

  17. Advancements in MR Imaging of the Prostate: From Diagnosis to Interventions

    PubMed Central

    Bonekamp, David; Jacobs, Michael A.; El-Khouli, Riham; Stoianovici, Dan

    2011-01-01

    Prostate cancer is the most frequently diagnosed cancer in males and the second leading cause of cancer-related death in men. Assessment of prostate cancer can be divided into detection, localization, and staging; accurate assessment is a prerequisite for optimal clinical management and therapy selection. Magnetic resonance (MR) imaging has been shown to be of particular help in localization and staging of prostate cancer. Traditional prostate MR imaging has been based on morphologic imaging with standard T1-weighted and T2-weighted sequences, which has limited accuracy. Recent advances include additional functional and physiologic MR imaging techniques (diffusion-weighted imaging, MR spectroscopy, and perfusion imaging), which allow extension of the obtainable information beyond anatomic assessment. Multiparametric MR imaging provides the highest accuracy in diagnosis and staging of prostate cancer. In addition, improvements in MR imaging hardware and software (3-T vs 1.5-T imaging) continue to improve spatial and temporal resolution and the signal-to-noise ratio of MR imaging examinations. Another recent advancement in the field is MR imaging guidance for targeted prostate biopsy, which is an alternative to the current standard of transrectal ultrasonography–guided systematic biopsy. © RSNA, 2011 PMID:21571651

  18. Advances in biomarkers for the early diagnosis of prostate cancer.

    PubMed

    Cao, Da-Long; Yao, Xu-Dong

    2010-02-01

    More and more studies have revealed that the level of serum prostate specific antigen(PSA) has little value for early diagnosis of prostate cancer (PCa). For example, negative prostate biopsies are as high as 70%-80% for patients with serum PSA ranging between 4 ng/mL and 10 ng/mL. However, the negative results cannot exclude the existence of cancer. In the studies of the early diagnosis of PCa, investigators focused on seeking biomarkers that have higher sensitivity and specificity. Recently, PSA derivatives, HPC1, PCA3, TMPRSS2: ETS, GSTP1, AMACR, GOLPH2, EPCA, sarcosine, and the combination of multiple biomarkers are widely discussed. In this article, we have reviewed their recent development and the prospective value of the combination of multiple biomarkers, which may be helpful for the early diagnosis and the prognostic monitoring of patients with PCa.

  19. Recent advancements in toxicity prediction following prostate cancer radiotherapy.

    PubMed

    Ospina, J D; Fargeas, A; Dréan, G; Simon, A; Acosta, O; de Crevoisier, R

    2015-01-01

    In external beam radiotherapy for prostate cancer limiting toxicities for dose escalation are bladder and rectum toxicities. Normal tissue complication probability models aim at quantifying the risk of developping adverse events following radiotherapy. These models, originally proposed in the context of uniform irradiation, have evolved to implementations based on the state-of-the-art classification methods which are trained using empirical data. Recently, the use of image processing techniques combined with population analysis methods has led to a new generation of models to understand the risk of normal tissue complications following radiotherapy. This paper overviews those methods in the case of prostate cancer radiation therapy and propose some lines of future research.

  20. Prostate-specific antigen doubling time and survival in patients with advanced metastatic prostate cancer.

    PubMed

    Loberg, Robert D; Fielhauer, Jeffery R; Pienta, Brian A; Dresden, Scott; Christmas, Patty; Kalikin, Linda M; Olson, Karin B; Pienta, Kenneth J

    2003-12-29

    The relation between tumor kinetics and disease progression in patients with hormone-refractory prostate cancer (HRPC) has not been well described. Biochemical recurrence of prostate cancer is characterized by detectable prostate-specific antigen (PSA) levels after treatment and occurs in approximately 30% of patients after therapy for apparent localized disease. An increase in PSA almost always occurs before clinical evidence of disease. The ability to identify early biochemical failure in patients to assess disease aggressiveness and guide changes in treatment needs to be examined. We examined serial PSA data from 249 patients with metastatic disease to assess PSA doubling time (PSADT) in hormone-naive prostate cancer (HNPC) and HRPC states. In a subset of patients, the relation of PSADT to Gleason score and survival was studied. PSADT decreased from 37.5 +/- 4.5 weeks to 15.6 +/- 1.6 weeks (mean +/- SEM) in patients with HNPC versus HRPC. In this small study, PSADT did not correlate with Gleason score, survival from start of hormonal treatment, length of time receiving hormone therapy, or survival in the HRPC state. The decrease in PSADT with disease state may help provide insight into understanding the biology of late-stage disease.

  1. [Endocrine disruptors, reproduction and hormone-dependent cancers].

    PubMed

    Fenichel, Patrick; Brucker-Davis, Françoise; Chevalier, Nicolas

    2016-01-01

    Endocrine disruptors are natural or synthetic chemical compounds which are present in the environment and which are able to interfere with hormonal regulation pathways and to induce human health deleterious effects. While their precise implication in human health and diseases is still matter of debates, it becomes likely that they have to be considered as risk factors in numerous chronic diseases: developmental and reproductive defects and hormone dependent cancers (present review), metabolic diseases (obesity and type 2 diabetes), neurodevelopmental or neurodegenerative diseases. Low doses exposure during critical windows of exposure such as foetal, perinatal and peri-pubertal periods, or chronic exposure with bioaccumulation in the adipose tissue, and possible synergic effects of several compounds ("cocktail effect") may participate to the genetic/environment interface suspected to participate to the pathophysiology of many diseases. PMID:26655259

  2. Testosterone supports hormone-dependent aggression in female rats.

    PubMed

    Albert, D J; Jonik, R H; Walsh, M L; Petrovic, D M

    1989-08-01

    Female hooded rats were ovariectomized and implanted with a single testosterone-filled Silastic tube or an empty tube. The tube size was one which allowed a release of testosterone at the high end of the mean normal serum testosterone concentration for intact females. Following a 7-day recovery period, all rats were placed on a 23-hr food-deprivation schedule and adapted to a highly palatable liquid food over a 5-day period. Each animal with a testosterone implant was then housed with an animal of similar weight but an empty implant. The pairs were subjected to a series of 3 restricted-access competition tests (1/day) followed 4 days later by a series of 3 free-access competition tests. The animals were then separated, adapted to a bland liquid food, and paired with new partners. They were then subjected to the restricted- and free-access food-competition tests but with bland food as the incentive. During the first 6 competition tests there were no significant differences between groups in aggression or in time spent licking at the food spout. During the second series of tests, females with testosterone implants were more aggressive and more successful at maintaining access to the food than were their competitors with empty implants. The difference between groups occurred during the free- as well as the restricted-access tests. The effectiveness of physiological levels of testosterone in supporting aggression is attributed to the use of a test situation that activates as well as elicits hormone-dependent aggression. These results suggest that testosterone may be the hormonal substrate for hormone-dependent aggression in female rats.

  3. Urate calculi complicating orchidectomy in a patient with advanced prostatic cancer. Case report.

    PubMed

    Roosen, J U; Rungby, J A; Hvidt, V

    1991-01-01

    A patient passed 11 urate calculi after palliative orchidectomy for advanced prostatic cancer, and there was a simultaneous rise in urinary urate excretion. We believe that this rise could be the result of increased purine metabolism from lysis of tumour cells. To our knowledge this has not previously been reported.

  4. Value of nuclear bone imaging in advanced prostatic cancer

    SciTech Connect

    Pollen, J.J.; Gerber, K.; Ashburn, W.L.; Schmidt, J.D.

    1981-02-01

    The nuclear bone scan is a highly sensitive means of detecting skeletal metastasis in patients with prostatic cancer. Serial bone imaging provides an accurate method to follow the response of osseous metastases to treatment and to detect relapsing disease in the skeleton. In selected instances the nuclear bone scan can provide information about vertebral metastases that can be important for planning palliative treatment of pain.

  5. [Bisphenol A and hormone-dependent cancers: potential risk and mechanism].

    PubMed

    Rochefort, Henri

    2013-05-01

    Being concerned by the increasing incidence of breast, prostate and testicular cancers, we overviewed the literature on the potential carcinogenic effect of endocrine disruptors (ED). It is extremely difficult to obtain the epidemiological proof of a carcinogenic effect of one ED in human for multi-factorial diseases and the high number of confusing factors. However, many experimental studies in rodents on bis-phenol A (BPA) and its assay in human blood and urine, strongly suggest that BPA might increase the risk of hormone dependant cancers. Contrary to the mitogenic effect of estradiol, directly mediated in mammary cells by the classical nuclear estrogen receptor α, the mechanisms of the deleterious effect of BPA at low doses and in utero remain unknown since the molecular and cellular target(s) have not been defined. Based on all deleterious effects of BPA, France has banned the use of BPA in all food packaging. This should force the food industry to collaborate with members of public research to rapidly find safer substitutes to BPA. PMID:23732105

  6. Rooster feathering, androgenic alopecia, and hormone dependent tumor growth: What is in common?

    PubMed Central

    Mayer, Julie Ann; Chuong, Cheng-Ming; Widelitz, Randall

    2015-01-01

    Different epithelial organs form as a result of epithelial - mesenchymal interactions and share a common theme modulated by variations (Chuong edit. In Molecular Basis of Epithelial Appendage Morphogenesis, 1998). One of the major modulators is the sex hormone pathway that acts on the prototype signaling pathway to alter organ phenotypes. Here we focus on how the sex hormone pathway interfaces with epithelia morphogenesis related signaling pathways. We first survey these sex hormone regulated morphogenetic processes in various epithelial organs. Sexual dimorphism of hairs and feathers has implications in sexual selection. Diseases of these pathways result in androgenic alopecia, hirsutism, henny feathering, etc. The growth and development of mammary glands, prostate glands and external genitalia essential for reproductive function are also dependent on sex hormones. Diseases affecting these organs include congenital anomalies and hormone dependent type of breast and prostate cancers. To study the role of sex hormones in new growth in the context of system biology / pathology, an in vivo model in which organ formation starts from stem cells is essential. With recent developments (Yu et al., The morphogenesis of feathers. Nature 420:308–312, 2002), the growth of tail feathers in roosters and hens has become a testable model in which experimental manipulations are possible. We show exemplary data of differences in their growth rate, proliferative cell population and signaling molecule expression. Working hypotheses are proposed on how the sex hormone pathways may interact with growth pathways. It is now possible to test these hypotheses using the chicken model to learn fundamental mechanisms on how sex hormones affect organogenesis, epithelial organ cycling, and growth related tumorigenesis. PMID:15617560

  7. Endorectal MRI of Prostate Cancer: Incremental Prognostic Importance of Gross Locally Advanced Disease

    PubMed Central

    Muglia, Valdair F.; Westphalen, Antonio C.; Wang, Zhen J.; Kurhanewicz, John; Carroll, Peter R.; Coakley, Fergus V.

    2013-01-01

    OBJECTIVE The purpose of this study was to determine the frequency and incremental prognostic importance of gross locally advanced disease seen at endorectal MRI in patients with prostate cancer. MATERIALS AND METHODS We retrospectively identified the cases of all patients with biopsy-proven prostate cancer who underwent pretreatment endorectal MRI over a 6-year period (n = 1777). Three experienced radiologists identified by consensus patients with gross locally advanced disease, defined as unequivocal extracapsular extension or unequivocal seminal vesicle invasion. Outcome among these patients was compared with that in a control group without gross locally advanced disease matched by D'Amico risk stratification. RESULTS Sixty-six of 1777 (3.7%) patients had gross locally advanced disease. One of 1085 (0.1%) patients had low-risk disease, 25 of 489 (5.1%) had intermediate-risk disease, and 40 of 203 (19.7%) had high-risk disease. Follow-up data were available for 44 of these 66 patients. During a median follow-up period of 79 months, biochemical failure and metastasis had developed in 17 and 6 of these 44 patients compared with 9 and none of the 65 patients in the control group (p < 0.001). CONCLUSION Almost 4% of patients with prostate cancer, particularly those with intermediate- and high-risk disease, have gross locally advanced disease at endorectal MRI and have a significantly worse prognosis than matched controls. These patients may be candidates for more aggressive treatment. PMID:22109291

  8. Abiraterone for the Treatment of Advanced Prostate Cancer.

    PubMed

    Forde, Patrick M; Antonarakis, Emmanuel S

    2012-09-01

    Until recently, treatment options for castration-resistant prostate cancer (CRPC) were limited to only the chemotherapeutic agent docetaxel which demonstrated a survival advantage over palliative chemotherapy. Abiraterone acetate (AA) is an orally available, potent irreversible inhibitor of the adrenal microsomal enzyme cytochrome P450-17 (CYP17). In a large phase III study of AA in docetaxel-pretreated patients, AA demonstrated excellent tolerance and a 4-month survival advantage over placebo, leading to the approval of AA for docetaxel-pretreated patients by the FDA in 2011. More recently, phase III data in docetaxel-naïve patients have become available, showing clear clinical benefits in this population as well, and it is likely that the label for AA will soon be expanded to include men with CRPC who have not yet received chemotherapy. This article summarizes clinical studies of AA in CRPC patients and discusses the emerging treatment paradigm in this rapidly evolving area.

  9. [Prognostic factors of localised, locally advanced or metastatic prostate cancer].

    PubMed

    Joly, Florence; Henry-Amar, Michel

    2007-07-01

    In prostate cancer, whatever the stage of the disease, the selection of a treatment strategy is based on prognostic factors. Clinical stage, serum PSA concentration and Gleason score are among the most recognised factors. A combination of these three parameters leads to a score used to define prognostic groups that are routinely used in daily practice. More recently, predictive statistical models have been developed that were associated with nomograms. The objective of nomograms is, for a given patient, to calculate his probability to develop disease extension or relapse based on clinical, biological, histological and therapeutic (radiotherapy, hormonotherapy) data. Such nomograms are not all validated and their application in daily practice is more difficult than that of classical prognostic classifications. Nowadays, the progress and accessibility to novel technologies applied to biology will make possible in the near future the assessment of new prognostic profiles based on genetic and/or proteomic tumour characteristics.

  10. Prostate cancer is not breast cancer

    PubMed Central

    Venniyoor, Ajit

    2016-01-01

    Cancers of the prostate and breast are hormone dependent cancers. There is a tendency to equate them and apply same algorithms for treatment. It is pointed out that metastatic prostate cancer with bone-only disease is a potentially fatal condition with a much poorer prognosis than metastatic breast cancer and needs a more aggressive approach. PMID:27051149

  11. Sun exposure, vitamin D receptor gene polymorphisms, and risk of advanced prostate cancer.

    PubMed

    John, Esther M; Schwartz, Gary G; Koo, Jocelyn; Van Den Berg, David; Ingles, Sue A

    2005-06-15

    Substantial experimental evidence indicates that the hormonal form of vitamin D promotes the differentiation and inhibits the proliferation, invasiveness, and metastasis of human prostatic cancer cells. Results from epidemiologic studies of vitamin D status and/or vitamin D receptor (VDR) polymorphisms and prostate cancer risk have been mixed. We conducted a population-based, case-control study of advanced prostate cancer among men ages 40 to 79 years from the San Francisco Bay area. Interview data on lifetime sun exposure and other risk factors were collected for 905 non-Hispanic White men (450 cases and 455 controls). Using a reflectometer, we measured constitutive skin pigmentation on the upper underarm (a sun-protected site) and facultative pigmentation on the forehead (a sun-exposed site) and calculated a sun exposure index from these measurements. Biospecimens were collected for 426 cases and 440 controls. Genotyping was done for VDR polymorphisms in the 5' regulatory region (Cdx-2), exon 2 (FokI), and the 3' region (TaqI and BglI). Reduced risk of advanced prostate cancer was associated with high sun exposure determined by reflectometry [odds ratio (OR), 0.51; 95% confidence interval (95% CI), 0.33-0.80] and high occupational outdoor activity (OR, 0.73; 95% CI, 0.48-1.11). Significant risk reductions with the high-activity alleles FokI FF or Ff, TaqI tt, and BglI BB genotypes and a nonsignificant reduction with Cdx-2 AG or AA genotype were observed in the presence of high sun exposure, with ORs ranging from 0.46 to 0.67. Our findings support the hypothesis that sun exposure and VDR polymorphisms together play important roles in the etiology of prostate cancer.

  12. Advances in prostate cancer chemoprevention: a translational perspective.

    PubMed

    Nambiar, Dhanya; Singh, Rana P

    2013-01-01

    Chemopreventive interventions are steadily emerging as an important aspect of cancer management and control. Herein, we have discussed the major epidemiological and clinical studies advocating the role of androgen inhibitors, flavonoids and antioxidants in preventing prostate cancer (PCa). Androgen inhibitors have lately been discussed not only in treatment of PCa, but also as preventive agents especially after trials with Finasteride and Dutasteride. Flavonoids such as silibinin, green tea polyphenols, genistein, curcumin have shown great promise, but avenues to improve their bioavailability are requisite. Agents with antioxidant potentials like lycopene, selenium, and vitamin E have also been explored. Antioxidant trials have yielded mixed results or benefitted only a subgroup of population, although further studies are needed to establish them as preventive agent. Although a majority of the trials resulted in positive outcomes supporting their role as preventive agents; one should be cautious of neutral or negative results as well. For clinical applicability of these agents, we need to identify the ideal target population, time of intervention, appropriate dosage, and extent of intervention required. Incoherency of data with these agents urges for a stringent study design and thorough interpretation to accurately judge the necessity and feasibility of the preventive measures. PMID:23682779

  13. [Staging Based Strategies and Practice for Prostate Cancer].

    PubMed

    Chen, Zhi-qiang; Wang, Shu-sheng; Bai, Zun-guang; Wang, Zhao-hui; Lv, Li-guo; Gu, Chi-ming; Xiang, Song-tao; Dai, Rui-xin; Zhu, Shou-lun

    2016-06-01

    Authors raised that staging based strategies and practice of integrative medicine (IM) by combining syndrome typing and disease identification, and choosing suitable measures in accordance with different persons and seasonal conditions after more than ten years' clinical practice and researches. Radical operation as prior (as evil eliminating) and strengthening vital qi in perioerative period are best strategy for promoting rapid rehabilitation of early stage prostate cancer patients. Strengthening body resistance to eliminate evil was used in treating advanced prostate cancer patients. For example, a comprehensive treatment program for hormone-dependent patients was combined with endocrinotherapy and Chinese herbs for synergisic efficacy-enhancing actions. In this way, these patients' quality of life (QOL) were improved and time to castration resistant prostate cancer (CRPC) was delayed, even some patients were clinically cured. There are lack of effective medicines and methods for CRPC patients. Greatly tonifying original qi is mainly used for improving their clinical symptoms and prolonging survivals. Practice has proved staging based strategies and practice of IM has favorable advantages in treating prostate cancer, especially showing prospect in prolonging survival and postponing progression of advanced prostate cancer patients. Besides, it also could provide beneficial considerations and inspiration for combination of syndrome typing and disease identification. PMID:27491237

  14. Strategies to Circumvent Testosterone Surge and Disease Flare in Advanced Prostate Cancer: Emerging Treatment Paradigms.

    PubMed

    Pokuri, Venkata K; Nourkeyhani, Houman; Betsy, Bodie; Herbst, Laurie; Sikorski, Marcus; Spangenthal, Edward; Fabiano, Andrew; George, Saby

    2015-07-01

    The testosterone surge and disease flare is a feared complication from initiation of gonadotropin-releasing hormone (GnRH) agonist treatment in advanced prostate adenocarcinoma. It is a common practice to start an average 7-day pretreatment regimen with an antiandrogen agent before initiating GnRH agonist therapy, to circumvent disease flare from testosterone surge. However, this might not be the best strategy and can be harmful, especially in patients at high risk of imminent organ damage from minimal testosterone surge. Surgical castration is a simple and cost-effective method that should be considered in these scenarios. But most patients refuse this procedure because of the permanent and psychologic impact of surgery. Novel GnRH antagonists, such as degarelix, and cytochrome P450 17 (CYP17) enzyme inhibitors, such as ketoconazole, achieve castrate-equivalent serum testosterone levels much faster than traditional GnRH agonists without the need for coadministration of antiandrogens. This article reports on 3 cases of impending oncologic emergencies in advanced prostate adenocarcinoma treated promptly with degarelix and ketoconazole without any disease flare related to testosterone surge. In the setting of symptomatic hormone-naïve metastatic prostate cancer, the authors suggest clinical trials using abiraterone, orteronel, and other newer agents that target the CYP17 axis (eg, ketoconazole) for fine-tuning the emergent medical castration methods and avoiding the dangers from the flare phenomenon.

  15. Plasma genetic and genomic abnormalities predict treatment response and clinical outcome in advanced prostate cancer

    PubMed Central

    Du, Meijun; Dittmar, Rachel L.; Lee, Adam; Nandy, Debashis; Yuan, Tiezheng; Guo, Yongchen; Wang, Yuan; Tschannen, Michael R.; Worthey, Elizabeth; Jacob, Howard; See, William; Kilari, Deepak; Wang, Xuexia; Hovey, Raymond L.; Huang, Chiang-Ching; Wang, Liang

    2015-01-01

    Liquid biopsies, examinations of tumor components in body fluids, have shown promise for predicting clinical outcomes. To evaluate tumor-associated genomic and genetic variations in plasma cell-free DNA (cfDNA) and their associations with treatment response and overall survival, we applied whole genome and targeted sequencing to examine the plasma cfDNAs derived from 20 patients with advanced prostate cancer. Sequencing-based genomic abnormality analysis revealed locus-specific gains or losses that were common in prostate cancer, such as 8q gains, AR amplifications, PTEN losses and TMPRSS2-ERG fusions. To estimate tumor burden in cfDNA, we developed a Plasma Genomic Abnormality (PGA) score by summing the most significant copy number variations. Cox regression analysis showed that PGA scores were significantly associated with overall survival (p < 0.04). After androgen deprivation therapy or chemotherapy, targeted sequencing showed significant mutational profile changes in genes involved in androgen biosynthesis, AR activation, DNA repair, and chemotherapy resistance. These changes may reflect the dynamic evolution of heterozygous tumor populations in response to these treatments. These results strongly support the feasibility of using non-invasive liquid biopsies as potential tools to study biological mechanisms underlying therapy-specific resistance and to predict disease progression in advanced prostate cancer. PMID:25915538

  16. Technological advances in transurethral resection of the prostate: bipolar versus monopolar TURP.

    PubMed

    Issa, Muta M

    2008-08-01

    One of the most significant recent advancements in transurethral resection of the prostate (TURP) is the incorporation of bipolar technology. Bipolar circuitry allows TURP to be performed in a normal saline environment, which addresses a fundamental concern of conventional monopolar TURP (i.e., the use of hypo-osmolar irrigation). As a result, the risks of dilutional hyponatremia and transurethral resection (TUR) syndrome are eliminated, allowing for longer and safer resection. This review discusses the principles and applications of electrosurgery in conventional monopolar as well as new bipolar saline-based TURP systems. This review also addresses the positive impact on patient safety and resident training.

  17. Serum Prosaposin Levels Are Increased in Patients with Advanced Prostate Cancer

    PubMed Central

    Koochekpour, Shahriar; Hu, Siyi; Vellasco-Gonzalez, Cruz; Bernardo, Ruiz; Azabdaftari, Gissue; Dalin, Guo-xiang; Zhau, Haiyen E.; Chung, Leland W.; Vessella, Robert L.

    2012-01-01

    BACKGROUND We previously cloned prosaposin (PSAP) from metastatic castrate-resistant prostate cancer (mCRPCa) cells and demonstrated its genomic amplification and/or overexpression in metastatic PCa cell lines, xenografts, and lymph node metastases. The clinicohistopathological significance of serum-PSAP levels and its tissue expression and association with predictive or prognostic variable in primary or advanced PCa are not known. METHODS We examined PSAP expression by immunohistochemical staining during early embryogenic development of the prostate and within a large tissue microarray which included 266 benign and malignant prostate tissues. In addition, serum PSAP levels in the age-adjusted normal male population and in 154 normal individuals and patients with primary or mCRPCa were measured by an ELISA assay. RESULTS Univariate and multivariate analyses revealed a significant and inverse association between PSAP expression and clinical stage II and III tumors, dominant Gleason patterns 3 and 4, and seminal vesicle invasion. In the normal male population, the lowest serum-PSAP level was detected before puberty, peaked at the most reproductive age group (20–39 years old), and then, decreased to a range between the two groups for men above 40 years old. Regardless of age and when compared with normal individuals, serum-PSAP levels significantly decreased in primary organ-confined PCa, but increased in those with mCRPCa. CONCLUSION Our results show that PSAP has the potential to differentiate between primary and advanced PCa. Additional large-scale studies are needed to define the usefulness of tissue expression or serum-PSAP levels as a diagnostic or prognostic marker or as a therapeutic target in PCa. PMID:21630292

  18. Oxidized low-density lipoprotein is associated with advanced-stage prostate cancer.

    PubMed

    Wan, Fangning; Qin, Xiaojian; Zhang, Guiming; Lu, Xiaolin; Zhu, Yao; Zhang, Hailiang; Dai, Bo; Shi, Guohai; Ye, Dingwei

    2015-05-01

    Clinical and epidemiological data suggest coronary artery disease shares etiology with prostate cancer (PCa). The aim of this work was to assess the effects of several serum markers reported in cardiovascular disease on PCa. Serum markers (oxidized low-density lipoprotein [ox-LDL], apolipoprotein [apo] B100, and apoB48) in peripheral blood samples from 50 patients from Fudan University Shanghai Cancer Center (FUSCC) with localized or lymph node metastatic PCa were investigated in this study. Twenty-five samples from normal individuals were set as controls. We first conducted enzyme-linked immunosorbent assay analysis to select candidate markers that were significantly different between these patients and controls. Then, the clinical relevance between OLR1 (the ox-LDL receptor) expression and PCa was analyzed in The Cancer Genome Atlas (TCGA) cohort. We also investigated the function of ox-LDL in PCa cell lines in vitro. Phosphorylation protein chips were used to analyze cell signaling pathways in ox-LDL-treated PC-3 cells. The ox-LDL level was found to be significantly correlated with N stage of prostate cancer. OLR1 expression was correlated with lymph node metastasis in the TCGA cohort. In vitro, ox-LDL stimulated the proliferation, migration, and invasion of LNCaP and PC-3 in a dose-dependent manner. The results of phosphoprotein microarray illustrated that ox-LDL could influence multiple signaling pathways of PC-3. Activation of proliferation promoting signaling pathways (including β-catenin, cMyc, NF-κB, STAT1, STAT3) as well as apoptosis-associating signaling pathways (including p27, caspase-3) demonstrated that ox-LDL had complicated effects on prostate cancer. Increased serum ox-LDL level and OLR1 expression may indicate advanced-stage PCa and lymph node metastasis. Moreover, ox-LDL could stimulate PCa proliferation, migration, and invasion in vitro.

  19. Intraoperative Radiotherapy During Radical Prostatectomy for Locally Advanced Prostate Cancer: Technical and Dosimetric Aspects

    SciTech Connect

    Krengli, Marco; Terrone, Carlo; Ballare, Andrea; Loi, Gianfranco; Tarabuzzi, Roberto; Marchioro, Giansilvio; Beldi, Debora; Mones, Eleonora; Bolchini, Cesare R.T.; Volpe, Alessandro; Frea, Bruno

    2010-03-15

    Purpose: To analyze the feasibility of intraoperative radiotherapy (IORT) in patients with high-risk prostate cancer and candidates for radical prostatectomy. Methods and Materials: A total of 38 patients with locally advanced prostate cancer were enrolled. No patients had evidence of lymph node or distant metastases, probability of organ-confined disease >25%, or risk of lymph node involvement >15% according to the Memorial Sloan-Kettering Cancer Center Nomogram. The IORT was delivered after exposure of the prostate by a dedicated linear accelerator with beveled collimators using electrons of 9 to 12 MeV to a total dose of 10-12 Gy. Rectal dose was measured in vivo by radiochromic films placed on a rectal probe. Administration of IORT was followed by completion of radical prostatectomy and regional lymph node dissection. All cases with extracapsular extension and/or positive margins were scheduled for postoperative radiotherapy. Patients with pT3 to pT4 disease or positive nodes received adjuvant hormonal therapy. Results: Mean dose detected by radiochromic films was 3.9 Gy (range, 0.4-8.9 Gy) to the anterior rectal wall. The IORT procedure lasted 31 min on average (range, 15-45 min). No major intra- or postoperative complications occurred. Minor complications were observed in 10/33 (30%) of cases. Of the 27/31 patients who completed the postoperative external beam radiotherapy, 3/27 experienced Grade 2 rectal toxicity and 1/27 experienced Grade 2 urinary toxicity. Conclusions: Use of IORT during radical prostatectomy is feasible and allows safe delivery of postoperative external beam radiotherapy to the tumor bed without relevant acute rectal toxicity.

  20. Galeterone for the treatment of advanced prostate cancer: the evidence to date

    PubMed Central

    Bastos, Diogo A; Antonarakis, Emmanuel S

    2016-01-01

    Major advances have been achieved recently in the treatment of metastatic castration-resistant prostate cancer, resulting in significant improvements in quality of life and survival with the use of several new agents, including the next-generation androgen receptor (AR)-targeted drugs abiraterone and enzalutamide. However, virtually all patients will eventually progress on these therapies and most will ultimately die of treatment-refractory metastatic disease. Recently, several mechanisms of resistance to AR-directed therapies have been uncovered, including the AR splice variant 7 (AR-V7), which is a ligand-independent constitutionally-active form of the AR that has been associated with poor outcomes to abiraterone and enzalutamide. Galeterone, a potent anti-androgen with three modes of action (CYP17 lyase inhibition, AR antagonism, and AR degradation), is a novel agent under clinical development that could potentially target both full-length AR and aberrant AR, including AR-V7. In this manuscript, we will first discuss the biological mechanisms of action of galeterone and then review the safety and efficacy data from Phase I and II clinical studies of galeterone in patients with metastatic castration-resistant prostate cancer. A Phase III study of galeterone (compared against enzalutamide) in AR-V7-positive patients is currently underway, and represents the first pivotal trial using a biomarker-selection design in this disease. PMID:27486306

  1. The Importance of Supportive Care in Optimizing Treatment Outcomes of Patients with Advanced Prostate Cancer

    PubMed Central

    2012-01-01

    Optimal oncologic care of older men with prostate cancer, including effective prevention and management of the disease and treatment side effects (so-called best supportive care measures) can prolong survival, improve quality of life, and reduce depressive symptoms. In addition, the proportion of treatment discontinuations can be reduced through early reporting and management of side effects. Pharmacologic care may be offered to manage the side effects of androgen-deprivation therapy and chemotherapy, which may include hot flashes, febrile neutropenia, fatigue, and diarrhea. Nonpharmacologic care (e.g., physical exercise, acupuncture, relaxation) has also been shown to benefit patients. At the Georges Pompidou European Hospital, the Program of Optimization of Chemotherapy Administration has demonstrated that improved outpatient follow-up by supportive care measures can reduce the occurrence of chemotherapy-related side effects, reduce cancellations and modifications of treatment, reduce chemotherapy wastage, and reduce the length of stay in the outpatient unit. The importance of supportive care measures to optimize management and outcomes of older men with advanced prostate cancer should not be overlooked. PMID:23015682

  2. Cancer Related Fatigue and Quality of Life in Patients with Advanced Prostate Cancer Undergoing Chemotherapy

    PubMed Central

    Charalambous, Andreas; Kouta, Christiana

    2016-01-01

    Cancer related fatigue (CRF) is a common and debilitating symptom that can influence quality of life (QoL) in cancer patients. The increase in survival times stresses for a better understanding of how CRF affects patients' QoL. This was a cross-sectional descriptive study with 148 randomly recruited prostate cancer patients aiming to explore CRF and its impact on QoL. Assessments included the Cancer Fatigue Scale, EORTC QLQ-C30, and EORTC QLQ-PR25. Additionally, 15 in-depth structured interviews were performed. Quantitative data were analyzed with simple and multiple regression analysis and independent samples t-test. Qualitative data were analyzed with the use of thematic content analysis. The 66.9% of the patients experienced CRF with higher levels being recorded for the affective subscale. Statistically significant differences were found between the patients reporting CRF and lower levels of QoL (mean = 49.1) and those that did not report fatigue and had higher levels of QoL (mean = 72.1). The interviews emphasized CRF's profound impact on the patients' lives that was reflected on the following themes: “dependency on others,” “loss of power over decision making,” and “daily living disruption.” Cancer related fatigue is a significant problem for patients with advanced prostate cancer and one that affects their QoL in various ways. PMID:26981530

  3. Xanthohumol Impairs Human Prostate Cancer Cell Growth and Invasion and Diminishes the Incidence and Progression of Advanced Tumors in TRAMP Mice

    PubMed Central

    Venè, Roberta; Benelli, Roberto; Minghelli, Simona; Astigiano, Simonetta; Tosetti, Francesca; Ferrari, Nicoletta

    2012-01-01

    Despite recent advances in understanding the biological basis of prostate cancer, management of the disease, especially in the phase resistant to androgen ablation, remains a significant challenge. The long latency and high incidence of prostate carcinogenesis provides the opportunity to intervene with chemoprevention to prevent or eradicate prostate malignancies. In this study, we have used human hormone-resistant prostate cancer cells, DU145 and PC3, as an in vitro model to assess the efficacy of xanthohumol (XN) against cell growth, motility and invasion. We observed that treatment of prostate cancer cells with low micromolar doses of XN inhibits proliferation and modulates focal adhesion kinase (FAK) and AKT phosphorylation leading to reduced cell migration and invasion. Oxidative stress by increased production of reactive oxygen species (ROS) was associated with these effects. Transgenic adenocarcinoma of the mouse prostate (TRAMP) transgenic mice were used as an in vivo model of prostate adenocarcinoma. Oral gavage of XN, three times per week, beginning at 4 wks of age, induced a decrease in the average weight of the urogenital (UG) tract, delayed advanced tumor progression and inhibited the growth of poorly differentiated prostate carcinoma. The ability of XN to inhibit prostate cancer in vitro and in vivo suggests that XN may be a novel agent for the management of prostate cancer. PMID:22952060

  4. Prostate biopsy

    MedlinePlus

    ... prostate biopsy; Fine needle biopsy of the prostate; Core biopsy of the prostate; Targeted prostate biopsy; Prostate biopsy - transrectal ultrasound (TRUS); Stereotactic transperineal prostate biopsy (STPB)

  5. GnRH antagonists in the treatment of advanced prostate cancer.

    PubMed

    Pommerville, Peter J; de Boer, Johan G

    2010-04-01

    Analogues of the gonadotropin releasing hormone (GnRH) inhibit the hypothalamic-pituitary-gonadal axis. This has provided treatment modalities for advanced and metastatic prostate cancer. The latest group of analogues, the GnRH antagonists, make promising treatments available that avoid the transient surge in testosterone that occurs with the use of GnRH agonists. Such surges may stimulate tumor growth, causing patients to experience new or worsening cancer symptoms and potential serious adverse effects, including increased bone pain, urinary retention, and spinal cord compression and consequently delay the therapeutic benefits of agonist therapy. Degarelix, an antagonist, recently approved in the United States and Europe, achieves faster, more profound and sustained testosterone suppression and with fewer adverse effects when compared with agonists and other antagonists. This review discusses and compares the compounds degarelix, abarelix, and cetrorelix.

  6. Advanced image reconstruction strategies for 4D prostate DCE-MRI: steps toward clinical practicality

    NASA Astrophysics Data System (ADS)

    Stinson, Eric G.; Borisch, Eric A.; Froemming, Adam T.; Kawashima, Akira; Young, Phillip M.; Warndahl, Brent A.; Grimm, Roger C.; Manduca, Armando; Riederer, Stephen J.; Trzasko, Joshua D.

    2015-09-01

    Dynamic contrast-enhanced (DCE) MRI is an important tool for the detection and characterization of primary and recurring prostate cancer. Advanced reconstruction strategies (e.g., sparse or low-rank regression) provide improved depiction of contrast dynamics and pharmacokinetic parameters; however, the high computation cost of reconstructing 4D (3D+time, 50+ frames) datasets typically inhibits their routine clinical use. Here, a novel alternating direction method-of-multipliers (ADMM) optimization strategy is described that enables these methods to be executed in ∠5 minutes, and thus within the standard clinical workflow. After overviewing the mechanics of this approach, high-performance implementation strategies will be discussed and demonstrated through clinical cases.

  7. Vaccine Treatment for Prostate Cancer

    MedlinePlus

    ... Preventing and treating prostate cancer spread to bones Vaccine treatment for prostate cancer Sipuleucel-T (Provenge) is ... less advanced prostate cancer. Possible side effects of vaccine treatment Side effects from the vaccine tend to ...

  8. Hormone-dependent aggression in male and female rats: experiential, hormonal, and neural foundations.

    PubMed

    Albert, D J; Jonik, R H; Walsh, M L

    1992-01-01

    Hormone-dependent aggression in both male and female rats includes the distinctive behavioral characteristics of piloerection and lateral attack. In males the aggression is dependent on testicular testosterone and is commonly known as intermale aggression. In females, the aggression is most commonly observed as maternal aggression and is dependent on hormones whose identity is only beginning to emerge. The present review examines the experiential events which activate hormone-dependent aggression, the relation of the aggression to gonadal hormones, and the neural structures that participate in its modulation. In males and females, the aggression is activated by cohabitation with a conspecific of the opposite sex, by competitive experience, and by repeated exposure to unfamiliar conspecifics. In the female, the presence of pups also activates aggression. In both males and females, hormones are necessary for the full manifestation of the aggression. The essential hormone appears to be testosterone in males and a combination of testosterone and estradiol in females. The information available suggests the neural control systems for hormone-dependent aggression may be similar in males and females. It is argued that hormone-dependent aggression is behaviorally and biologically homologous in male and female rats.

  9. EMP combination chemotherapy and low-dose monotherapy in advanced prostate cancer.

    PubMed

    Kitamura, Tadaichi; Nishimatsu, Hiroaki; Hamamoto, Toshiaki; Tomita, Kyoichi; Takeuchi, Takumi; Ohta, Nobutaka

    2002-02-01

    Many chemotherapeutic regimens combined with estramustine phosphate (EMP) have been elaborated for the treatment of hormone-refractory prostate cancer over 30 years. However, older EMP-based combination chemotherapies with vinblastine, vinorelbine, doxorubicin or cyclophosphamide showed relatively low PSA response rate (25-58%) accompanied with high toxicities. On the other hand, newly developed EMP-based combination regimens with etoposide, pacitaxel, carboplatin or docetaxel demonstrated promising PSA response rate (43-77%) with moderate to severe toxicity in the rate of thromboembolic event (5-18%) and of neutropenia (9-41%). Treatment-related death was less in the latter combination group (5/615, 0.8%) than that in the former group (3/234, 1.3%). Of note, in the docetaxel combination with EMP, PSA response rate is as high as 77% with high rate (41%) of neutropenia but no treatment-related death was observed. Docetaxel combination with EMP seems to be the best regimen, though not completely justified by randomized trials, to be selected in the modern era, which will be followed by paclitaxel, carboplatin and EMP combination with PSA response rate of 71%. In addition, an interim report in 83 patients was presented. They were not consecutively enrolled but were treated on low-dose EMP monotherapy for previously untreated advanced prostate cancer in Department of Urology of Tokyo University and our 21 affiliated hospitals. Overall PSA response rate was as high as 93.4% out of 76 assessable patients. However, overall toxicity rate was abnormally high (39.5%) with drug discontinuation rate of 32.1%. The reason of low drug compliance may be attributed to gastrointestinal symptoms. To overcome the low drug compliance, appropriate patients for EMP administration should be selected by using gene analysis on the basis of sophisticated tailor-made medicine.

  10. Sulforaphane and TRAIL induce a synergistic elimination of advanced prostate cancer stem-like cells

    PubMed Central

    LABSCH, SABRINA; LIU, LI; BAUER, NATHALIE; ZHANG, YIYAO; ALEKSANDROWICZ, EWA; GLADKICH, JURY; SCHÖNSIEGEL, FRANK; HERR, INGRID

    2014-01-01

    Advanced androgen-independent prostate cancer (AIPC) is an aggressive malignancy with a poor prognosis. Apoptosis-resistant cancer stem cells (CSCs) have been identified in AIPC and are not eliminated by current therapeutics. Novel therapeutic options, which are currently being evaluated in patient studies, include TRAIL and the broccoli-derived isothiocyanate sulforaphane. Although neither agent targets normal cells, TRAIL induces apoptosis in most cancer cells, and sulforaphane eliminates CSCs. In this study, the established AIPC cell lines DU145 and PC3, with enriched CSC features, and primary patient-derived prostate CSCs were treated with sulforaphane and recombinant soluble TRAIL. We examined the effects of these drugs on NF-κB activity, self-renewal and differentiation potential, and stem cell signaling via spheroid- and colony-forming assays, FACS and western blot analyses, immunohistochemistry, and an antibody protein array in vitro and after xenotransplantation. We largely found a stronger effect of sulforaphane on CSC properties compared to TRAIL, though the agents acted synergistically when applied in combination. This was associated with the inhibition of TRAIL-induced NF-κB binding; CXCR4, Jagged1, Notch 1, SOX 2, and Nanog expression; ALDH1 activity inhibition; and the elimination of differentiation and self-renewal potential. In vivo, tumor engraftment and tumor growth were strongly inhibited, without the induction of liver necrosis or other obvious side effects. These findings suggest that sulforaphane shifts the balance from TRAIL-induced survival signals to apoptosis and thus explains the observed synergistic effect. A nutritional strategy for high sulforaphane intake may target the cancer-specific activity of TRAIL in CSCs. PMID:24626333

  11. Intermittent hormone therapy versus continuous hormone therapy for locally advanced prostate cancer: a meta-analysis.

    PubMed

    Dong, ZhiLong; Wang, Hanzhang; Xu, MengMeng; Li, Yang; Hou, MingLi; Wei, YanLing; Liu, Xingchen; Wang, ZhiPing; Xie, XiaoDong

    2015-01-01

    Few randomized studies have compared intermittent hormone therapy (IHT) with continuous hormone therapy (CHT) for the treatment of locally advanced prostate cancer (PCa). Here, we report the results of a meta-analysis of a randomized controlled trial, evaluating the effectiveness of IHT versus CHT for patients with locally advanced PCa. Types of intervention were IHT versus CHT. The primary endpoint of this study is overall mortality and the secondary endpoints are any progression of disease, quality of life (QOL) and adverse effects between two groups. Six randomized controlled trials totaling 2996 patients were included. Results are as follows: after hormone therapy, patients undergoing IHT demonstrated no significant difference from those undergoing CHT in terms of the overall mortality (OR = 1.0, 95% CI [0.86, 1.17]) and disease progression (OR = 1.16, 95% CI [0.86, 1.57]). Men treated with IHT also reported better QOL, fewer adverse effects and considerable economic benefit for the individual and the community. With no difference in overall mortality and incidence of progression, current clinical studies confirm that both therapeutic methods were safe and effective. However, our study also takes into account QOL. When these secondary measures are considered, IHT may be a better option over CHT as patients report a more affordable treatment with improved QOL and fewer adverse effects.

  12. Cost-effectiveness analysis comparing degarelix with leuprolide in hormonal therapy for patients with locally advanced prostate cancer.

    PubMed

    Hatoum, Hind T; Crawford, E David; Nielsen, Sandy Kildegaard; Lin, Swu-Jane; Marshall, Dennis C

    2013-04-01

    Degarelix, approved in the USA in 2008, is a gonadotropin-releasing hormone antagonist, representing one of the latest additions to androgen deprivation therapy (ADT). ADT is used as first-line therapy for locally advanced or metastatic prostate cancer with the aim to reduce testosterone to castrate levels. Like other gonadotropin-releasing hormone-antagonists, degarelix treatment results in rapid decrease in luteinizing hormone, follicle-stimulating hormone and testosterone levels without the associated risk of flare. Using one registration trial for degarelix with leuprolide as the active control, a cost-effectiveness analysis with a Markov model and a 20-year time horizon found the incremental cost-effectiveness ratio for degarelix to be US$245/quality-adjusted life years. Degarelix provides a cost-effective treatment for ADT among patients with locally advanced prostate cancer.

  13. Tobacco smoking, polymorphisms in carcinogen metabolism enzyme genes, and risk of localized and advanced prostate cancer: results from the California Collaborative Prostate Cancer Study

    PubMed Central

    Shahabi, Ahva; Corral, Román; Catsburg, Chelsea; Joshi, Amit D; Kim, Andre; Lewinger, Juan Pablo; Koo, Jocelyn; John, Esther M; Ingles, Sue A; Stern, Mariana C

    2014-01-01

    The relationship between tobacco smoking and prostate cancer (PCa) remains inconclusive. This study examined the association between tobacco smoking and PCa risk taking into account polymorphisms in carcinogen metabolism enzyme genes as possible effect modifiers (9 polymorphisms and 1 predicted phenotype from metabolism enzyme genes). The study included cases (n = 761 localized; n = 1199 advanced) and controls (n = 1139) from the multiethnic California Collaborative Case–Control Study of Prostate Cancer. Multivariable conditional logistic regression was performed to evaluate the association between tobacco smoking variables and risk of localized and advanced PCa risk. Being a former smoker, regardless of time of quit smoking, was associated with an increased risk of localized PCa (odds ratio [OR] = 1.3; 95% confidence interval [CI] = 1.0–1.6). Among non-Hispanic Whites, ever smoking was associated with an increased risk of localized PCa (OR = 1.5; 95% CI = 1.1–2.1), whereas current smoking was associated with risk of advanced PCa (OR = 1.4; 95% CI = 1.0–1.9). However, no associations were observed between smoking intensity, duration or pack-year variables, and advanced PCa. No statistically significant trends were seen among Hispanics or African-Americans. The relationship between smoking status and PCa risk was modified by the CYP1A2 rs7662551 polymorphism (P-interaction = 0.008). In conclusion, tobacco smoking was associated with risk of PCa, primarily localized disease among non-Hispanic Whites. This association was modified by a genetic variant in CYP1A2, thus supporting a role for tobacco carcinogens in PCa risk. PMID:25355624

  14. Tobacco smoking, polymorphisms in carcinogen metabolism enzyme genes, and risk of localized and advanced prostate cancer: results from the California Collaborative Prostate Cancer Study.

    PubMed

    Shahabi, Ahva; Corral, Román; Catsburg, Chelsea; Joshi, Amit D; Kim, Andre; Lewinger, Juan Pablo; Koo, Jocelyn; John, Esther M; Ingles, Sue A; Stern, Mariana C

    2014-12-01

    The relationship between tobacco smoking and prostate cancer (PCa) remains inconclusive. This study examined the association between tobacco smoking and PCa risk taking into account polymorphisms in carcinogen metabolism enzyme genes as possible effect modifiers (9 polymorphisms and 1 predicted phenotype from metabolism enzyme genes). The study included cases (n = 761 localized; n = 1199 advanced) and controls (n = 1139) from the multiethnic California Collaborative Case-Control Study of Prostate Cancer. Multivariable conditional logistic regression was performed to evaluate the association between tobacco smoking variables and risk of localized and advanced PCa risk. Being a former smoker, regardless of time of quit smoking, was associated with an increased risk of localized PCa (odds ratio [OR] = 1.3; 95% confidence interval [CI] = 1.0-1.6). Among non-Hispanic Whites, ever smoking was associated with an increased risk of localized PCa (OR = 1.5; 95% CI = 1.1-2.1), whereas current smoking was associated with risk of advanced PCa (OR = 1.4; 95% CI = 1.0-1.9). However, no associations were observed between smoking intensity, duration or pack-year variables, and advanced PCa. No statistically significant trends were seen among Hispanics or African-Americans. The relationship between smoking status and PCa risk was modified by the CYP1A2 rs7662551 polymorphism (P-interaction = 0.008). In conclusion, tobacco smoking was associated with risk of PCa, primarily localized disease among non-Hispanic Whites. This association was modified by a genetic variant in CYP1A2, thus supporting a role for tobacco carcinogens in PCa risk. PMID:25355624

  15. Prostate cancer patients may have an increased risk of coexisting advanced colorectal neoplasms

    PubMed Central

    Ko, Sun-Hye; Baeg, Myong Ki; Bae, Woong Jin; Kim, Pumsoo; Choi, Myung-Gyu

    2016-01-01

    Background/aims Patients being treated for prostate cancer (PCa) have an increased risk of developing colorectal cancer. However, whether PCa patients are inherently at a higher risk of colorectal neoplasms (CRNs) is unknown. We aimed to investigate the risk of CRNs in PCa patients. Materials and methods Patients who had been diagnosed with PCa at a tertiary medical center and had colonoscopy within 1 year of the PCa diagnosis were investigated. Patients were propensity-matched 1:2 by age and body mass index to asymptomatic control subjects who had undergone colonoscopy for routine health screening. CRN was defined as histological confirmation of an adenoma or adenocarcinoma component. Advanced CRN was defined as any of the following: 1) histological findings of high-grade dysplasia, 2) inclusion of villous features, 3) tumor ≥1 cm in size, or 4) presence of an adenocarcinoma. Risk factors for CRN and advanced CRN were evaluated by univariate and multivariate analysis. Results A total of 191 patients diagnosed with PCa had colonoscopies within 1 year of PCa diagnosis. Of these, 23 patients with a history of previous malignancy and seven with incomplete colonoscopies were excluded, leaving 161 patients in the PCa group. Although presence of PCa was not a significant risk factor for CRN by multivariate analysis, PCa was a significant risk factor for advanced CRN (odds ratio [OR] 3.300; 95% confidence interval [CI] 1.766–6.167; P<0.001). Other significant risk factors for advanced CRN were age (OR 1.050; 95% CI 1.003–1.009; P=0.036) and body mass index (OR 1.205; 95% CI 1.067–1.361; P=0.003), whereas aspirin use (OR 0.414; 95% CI 0.173–0.990; P=0.047) was a preventive factor. Conclusion The risk of advanced CRN may be significantly increased in patients with PCa. Patients with PCa should have a colonoscopy at the time of PCa diagnosis.

  16. Prostate cancer patients may have an increased risk of coexisting advanced colorectal neoplasms

    PubMed Central

    Ko, Sun-Hye; Baeg, Myong Ki; Bae, Woong Jin; Kim, Pumsoo; Choi, Myung-Gyu

    2016-01-01

    Background/aims Patients being treated for prostate cancer (PCa) have an increased risk of developing colorectal cancer. However, whether PCa patients are inherently at a higher risk of colorectal neoplasms (CRNs) is unknown. We aimed to investigate the risk of CRNs in PCa patients. Materials and methods Patients who had been diagnosed with PCa at a tertiary medical center and had colonoscopy within 1 year of the PCa diagnosis were investigated. Patients were propensity-matched 1:2 by age and body mass index to asymptomatic control subjects who had undergone colonoscopy for routine health screening. CRN was defined as histological confirmation of an adenoma or adenocarcinoma component. Advanced CRN was defined as any of the following: 1) histological findings of high-grade dysplasia, 2) inclusion of villous features, 3) tumor ≥1 cm in size, or 4) presence of an adenocarcinoma. Risk factors for CRN and advanced CRN were evaluated by univariate and multivariate analysis. Results A total of 191 patients diagnosed with PCa had colonoscopies within 1 year of PCa diagnosis. Of these, 23 patients with a history of previous malignancy and seven with incomplete colonoscopies were excluded, leaving 161 patients in the PCa group. Although presence of PCa was not a significant risk factor for CRN by multivariate analysis, PCa was a significant risk factor for advanced CRN (odds ratio [OR] 3.300; 95% confidence interval [CI] 1.766–6.167; P<0.001). Other significant risk factors for advanced CRN were age (OR 1.050; 95% CI 1.003–1.009; P=0.036) and body mass index (OR 1.205; 95% CI 1.067–1.361; P=0.003), whereas aspirin use (OR 0.414; 95% CI 0.173–0.990; P=0.047) was a preventive factor. Conclusion The risk of advanced CRN may be significantly increased in patients with PCa. Patients with PCa should have a colonoscopy at the time of PCa diagnosis. PMID:27672332

  17. Autoimmune etiology in chronic prostatitis syndrome: an advance in the understanding of this pathology.

    PubMed

    Rivero, Virginia Elena; Motrich, Ruben Darío; Maccioni, Mariana; Riera, Clelia María

    2007-01-01

    The prostate is the target of many inflammatory and neoplastic disorders that affect men of all ages. Pathological conditions of the prostate gland range from infection of this organ by ascending bacteria from infected urine, to chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) of a still unknown etiology (accompanied with inflammation and lymphocyte infiltration of the gland), to benign hyperplasia and cancer. Patients under 50 years of age usually suffer from CP/CPPS, a chronic inflammatory syndrome characterized by pelvic pain, irritative voiding symptoms, and sexual dysfunction complaints. In this review, we summarize the current knowledge regarding immunological alterations present in CP/ CPPS patients. Remarkably, an inflammation state, in the absence of an invading infectious agent, is established in these patients, suggesting that an autoimmune process could be involved. In fact, specific autoimmune response to prostate antigens has recently been reported in CP/CPPS patients. Autoimmune response to prostate gland affects the seminal quality reported in these patients and may have critical consequences in their fertility. It is anticipated that preclinical studies in experimental models for CP/CPSS will provide important insights into the etiopathogenic mechanisms involved in this disease. We discuss here the similarities and the differences between human disease and experimental models and argue for the importance of the prostate gland in male reproductive function. Ultimately, we suggest that a state of inflammation, originally incited by an autoimmune response within the prostate, together with a diminished prostate functionality, may compromise male fertility.

  18. Therapeutic Rationales, Progresses, Failures, and Future Directions for Advanced Prostate Cancer

    PubMed Central

    Wadosky, Kristine M; Koochekpour, Shahriar

    2016-01-01

    Patients with localized prostate cancer (PCa) have several therapeutic options with good prognosis. However, survival of patients with high-risk, advanced PCa is significantly less than patients with early-stage, organ-confined disease. Testosterone and other androgens have been directly linked to PCa progression since 1941. In this review, we chronicle the discoveries that led to modern therapeutic strategies for PCa. Specifically highlighted is the biology of androgen receptor (AR), the nuclear receptor transcription factor largely responsible for androgen-stimulated and castrate-recurrent (CR) PCa. Current PCa treatment paradigms can be classified into three distinct but interrelated categories: targeting AR at pre-receptor, receptor, or post-receptor signaling. The continuing challenge of disease relapse as CR and/or metastatic tumors, destined to occur within three years of the initial treatment, is also discussed. We conclude that the success of PCa therapies in the future depends on targeting molecular mechanisms underlying tumor recurrence that still may affect AR at pre-receptor, receptor, and post-receptor levels. PMID:27019626

  19. Case-Matched comparison of contemporary radiation therapy to surgery in patients with locally advanced prostate cancer

    SciTech Connect

    Fletcher, Sophie G.; Mills, Stacey E.; Smolkin, Mark E.; Theodorescu, Dan . E-mail: dt9d@virginia.edu

    2006-11-15

    Purpose: Few studies critically compare current radiotherapy techniques to surgery for patients with locally advanced prostate cancer, despite an urgent need to determine which approach offers superior cancer control. Our objective was to compare rates of biochemical relapse-free survival (BFS) and surrogates of disease specific survival among men with high risk adenocarcinoma of the prostate as a function of treatment modality. Methods and Materials: Retrospective data from 409 men with prostate-specific antigen (PSA) {>=}10 or Gleason 7-10 or Stage {>=}T2b cancer treated uniformly at one university between March 1988 and December 2000 were analyzed. Patients had undergone radical prostatectomy (RP), brachytherapy implant alone (BTM), or external beam radiotherapy with brachytherapy boost with short-term neoadjuvant and adjuvant androgen deprivation therapy (BTC). From the total study population a 1:1 matched-cohort analysis (208 patients matched via prostate-specific antigen, Gleason score) comparing RP with BTC was performed as well. Results: Estimated 4-year BFS rates were superior for patients treated with BTC (BTC 72%, BTM 25%, RP 53%; p < 0.001). Matched analysis of BTC vs. RP confirmed these results (BTC 73%, BTM 55%; p = 0.010). Relative risk (RR) of biochemical relapse for BTM and BTC compared with RP were 2.92 (1.95-4.36) and 0.56 (0.36-0.87) (p < 0.001, p = 0.010). RR for BTC from the matched cohort analysis was 0.44 (0.26-0.74; p = 0.002). Conclusions: High-risk prostate cancer patients receiving multimodality radiation therapy (BTC) display apparently superior BFS compared with those receiving surgery (RP) or brachytherapy alone (BTM)

  20. Understanding the Racial and Ethnic Differences in Cost and Mortality Among Advanced Stage Prostate Cancer Patients (STROBE).

    PubMed

    Chhatre, Sumedha; Bruce Malkowicz, Stanley; Sanford Schwartz, J; Jayadevappa, Ravishankar

    2015-08-01

    The aims of the study were to understand the racial/ethnic differences in cost of care and mortality in Medicare elderly with advanced stage prostate cancer.This retrospective, observational study used SEER-Medicare data. Cohort consisted of 10,509 men aged 66 or older and diagnosed with advanced-stage prostate cancer between 2001and 2004. The cohort was followed retrospectively up to 2009. Racial/ethnic variation in cost was analyzed using 2 part-models and quantile regression. Step-wise GLM log-link and Cox regression was used to study the association between race/ethnicity and cost and mortality. Propensity score approach was used to minimize selection bias.Pattern of cost and mortality varies between racial/ethnic groups. Compared with other racial/ethnic groups, non-Hispanic white patients had higher unadjusted costs in treatment and follow-up phases. Quintile regression results indicated that in treatment phase, Hispanics had higher costs in the 95th quantile and non-Hispanic blacks had lower cost in the 95th quantile, compared with non-Hispanic white men. In terminal phase non-Hispanic blacks and Hispanics had higher cost. After controlling for treatment, all-cause and prostate cancer-specific mortality was not significant for non-Hispanic black men, compared with non-Hispanic white men. However, for Asians, mortality remained significantly lower compared with non-Hispanic white men.In conclusion, relationship between race/ethnicity, cost of care, and mortality is intricate. For non-Hispanic black men, disparity in mortality can be attributed to treatment differences. To reduce racial/ethnic disparities in prostate cancer care and outcomes, tailored policies to address underuse, overuse, and misuse of treatment and health services are necessary. PMID:26266389

  1. Denosumab Reduces Risk of Bone Side Effects in Advanced Prostate Cancer

    Cancer.gov

    The biological agent denosumab (Xgeva) is more effective than zoledronic acid at decreasing the risk of bone fractures and other skeletal-related events (SRE) in men with castration-resistant metastatic prostate cancer, according to results from a randomi

  2. [Characteristics of polyamine biosynthesis regulation and tumor growth rate in hormone-dependant grafted breast tumors of mice and rats].

    PubMed

    Orlovskiĭ, A A

    2007-01-01

    Effect of the inhibitors of polyamines biosynthesis on completely or partially hormone-dependant breast tumors (mouse Ca755 carcinoma and Walker W-256 carcinosarcoma) is essentially special: in contrary to hormone-dependant tumors, this effect may be not only breaking but stimulating as well. Change-over from one to another mode of reaction is conditioned, most probable, by hormonal status, which is determined by one or another estral cycle phase. Biochemical mechanisms of this change-over are closely connected with polyamines metabolism, namely the degree of polyamines (especially spermine) interconvertion and physiological reactivity level of the system controlling expression of ornithin-decarboxilase. At that, the first of these pathways is predominant for completely hormone-dependant Ca755 and the second one -for partially hormone-dependant W-256.

  3. Is whole gland salvage cryotherapy effective as palliative treatment of haematuria in patients with locally advanced prostate cancer? Results of a preliminary case series

    PubMed Central

    Mucciardi, Giuseppe; Galì, Alessandro; Pappalardo, Rosa; Lembo, Francesco; Anastasi, Giuseppina; Butticè, Salvatore; Ascenti, Giorgio; Lugnani, Franco

    2015-01-01

    Objectives: Locally advanced prostate cancer may cause several complications such as haematuria, bladder outlet obstruction, and renal failure due to the ureteral obstruction. Various treatments have been suggested, including radiotherapy, antifibrinolytics, bladder irrigation with alum solution, transurethral surgery and angioembolization, none of which have proven effectiveness. In the last years cryoablation has become a valid therapeutic option for prostate cancer. In our experience we used this ‘new’ technique as haemostatic therapy. Methods: We selected four patients with gross haematuria affected by locally advanced hormone refractory prostate cancer, who had already been treated with primary radiotherapy. We used third-generation cryotherapy: under ultrasonographic guidance, we inserted six cryoprobes, two in each of the vascular pedicles reaching at least −60°C, and three thermometers. We then induced two freeze–thaw cycles. Results: After the operation the haematuria stopped in all patients and at 9-month follow up we observed a mean of four red cells (range three to five) in the urinary sediment with no evidence of bacteriuria. Prostate volume, prostate-specific antigen and postmicturition residue were significantly reduced. Qmax improved significantly too. Conclusion: Our experience has given us good results with minimal intra- and postoperative complications. We think that haemostatic cryotherapy as a palliative approach for locally advanced prostate cancer could represent a valid treatment option and more consideration could be given to its use. PMID:26425138

  4. Intensity-Modulated Radiotherapy of Pelvic Lymph Nodes in Locally Advanced Prostate Cancer: Planning Procedures and Early Experiences

    SciTech Connect

    Muren, Ludvig Paul Wasbo, Ellen; Helle, Svein Inge; Hysing, Liv Bolstad; Karlsdottir, Asa; Odland, Odd Harald; Valen, Harald; Ekerold, Randi; Johannessen, Dag Clement

    2008-07-15

    Purpose: We present planning and early clinical outcomes of a study of intensity-modulated radiotherapy (IMRT) for locally advanced prostate cancer. Methods and Materials: A total of 43 patients initially treated with an IMRT plan delivering 50 Gy to the prostate, seminal vesicles, and pelvic lymph nodes, followed by a conformal radiotherapy (CRT) plan delivering 20 Gy to the prostate and seminal vesicles, were studied. Dose-volume histogram (DVH) data for the added plans were compared with dose-volume histogram data for the sum of two CRT plans for 15 cases. Gastrointestinal (GI) and genitourinary (GU) toxicity, based on the Radiation Therapy Oncology Group scoring system, was recorded weekly throughout treatment as well as 3 to 18 months after treatment and are presented. Results: Treatment with IMRT both reduced normal tissue doses and increased the minimum target doses. Intestine volumes receiving more than 40 and 50 Gy were significantly reduced (e.g., at 50 Gy, from 81 to 19 cm{sup 3}; p = 0.026), as were bladder volumes above 40, 50, and 60 Gy, rectum volumes above 30, 50, and 60 Gy, and hip joint muscle volumes above 20, 30, and 40 Gy. During treatment, Grade 2 GI toxicity was reported by 12 of 43 patients (28%), and Grade 2 to 4 GU toxicity was also observed among 12 patients (28%). With 6 to 18 months of follow-up, 2 patients (5%) experienced Grade 2 GI effects and 7 patients (16%) experienced Grade 2 GU effects. Conclusions: Use of IMRT for pelvic irradiation in prostate cancer reduces normal tissue doses, improves target coverage, and has a promising toxicity profile.

  5. Role of the Androgen-Androgen Receptor Axis in the Treatment Resistance of Advanced Prostate Cancer: From Androgen-Dependent to Castration Resistant and Further.

    PubMed

    Fujimoto, Naohiro

    2016-06-01

    After the introduction of prostate-specific antigen (PSA) screening, prostate cancer diagnosis has shifted to early and curative stages, although 10-20% of patients still present with metastatic and incurable cancer. Prostate cancer is androgen-dependent, and most patients with prostate cancer initially respond to androgen deprivation therapy (ADT). After 1-2 years of the treatment, advanced prostate cancer eventually progresses to castration resistant prostate cancer (CRPC). A variety of mechanisms of progression from androgen-dependent prostate cancer to CRPC under ADT have been postulated, and the key pathway is re-activation of the androgen-androgen receptor (AR) axis, for example, caused by AR mutation/overexpression/splice variants, altered expression of AR cofactors, and increased production of androgens. Recently approved new agents, such as the hormonal agents abiraterone and enzalutamide and the chemotherapeutic agent cabazitaxel, have demonstrated survival benefit in men with CRPC. However, the prolongation of survival times provided with these agents is limited because of the treatment resistance. Androgen-AR axis still plays a pivotal role in the resistance to the new agents for CRPC. To improve the prognosis of patients with CRPC, intensive research to identify effective agents, treatment strategies, and useful predictive biomarkers to select the patients who can benefit from such treatments are required. Additional clinical data, with a better understanding of the biology of CRPC, may provide better CRPC treatment outcomes. This article reviews the underlying mechanisms of treatment resistance and future direction of CRPC treatments.

  6. Advances in bi-modal optical and ultrasound detection of prostate cancer diagnosis

    NASA Astrophysics Data System (ADS)

    Boutet, Jerome; Guyon, Laurent; Debourdeau, Mathieu; Dinten, Jean-Marc; Vray, Didier; Rizo, Philippe

    2009-02-01

    Prostate cancer diagnosis is based on PSA dosage and digital rectal examination. In case of positive test, a biopsy is conducted and guided by ultrasound imaging. Today, however, as ultrasound imaging is not able to precisely detect tumors, some biopsies have to be performed in the prostate and the only way to improve detection is to increase the number of those uncomfortable biopsies. In order to decrease this number and to improve the patient wellness, we are studying a way to couple ultrasound and fluorescence optical imaging on an endorectal probe. The ultrasounds are used to get morphological information on the prostate and the optical system to detect and to localize fluorophore marked tumors. To support the development of such a system, we have carried out a new tissue-mimicking phantom which represents the three different kind of tissue concerned during prostate endorectal examination: prostate, rectum, surrounding tissues. It was imaged by ultrasound and by fluorescence diffuse optical imaging. We have proved that the optical system is able to detect and to localize a fluorescing inclusion at different depth inside the phantom which has then been superimposed to the morphological image provided by the ultrasounds.

  7. The Emerging Role of Extracellular Vesicle-Mediated Drug Resistance in Cancers: Implications in Advanced Prostate Cancer

    PubMed Central

    Soekmadji, Carolina; Nelson, Colleen C.

    2015-01-01

    Emerging evidence has shown that the extracellular vesicles (EVs) regulate various biological processes and can control cell proliferation and survival, as well as being involved in normal cell development and diseases such as cancers. In cancer treatment, development of acquired drug resistance phenotype is a serious issue. Recently it has been shown that the presence of multidrug resistance proteins such as Pgp-1 and enrichment of the lipid ceramide in EVs could have a role in mediating drug resistance. EVs could also mediate multidrug resistance through uptake of drugs in vesicles and thus limit the bioavailability of drugs to treat cancer cells. In this review, we discussed the emerging evidence of the role EVs play in mediating drug resistance in cancers and in particular the role of EVs mediating drug resistance in advanced prostate cancer. The role of EV-associated multidrug resistance proteins, miRNA, mRNA, and lipid as well as the potential interaction(s) among these factors was probed. Lastly, we provide an overview of the current available treatments for advanced prostate cancer, considering where EVs may mediate the development of resistance against these drugs. PMID:26587537

  8. Triptorelin in the Relief of Lower Urinary Tract Symptoms in Advanced Prostate Cancer Patients: The RESULT Study.

    PubMed

    Peltier, Alexandre; Aoun, Fouad; De Ruyter, Vincent; Cabri, Patrick; Van Velthoven, Roland

    2015-01-01

    This prospective, noninterventional, open-label, multicentre, Belgian study assessed the prevalence of moderate to severe lower urinary tract symptoms (LUTS) in patients with locally advanced or metastatic prostate cancer scheduled to receive triptorelin therapy and its effects on LUTS were evaluated focusing on symptom relief and changes in quality of life (QOL) related to urinary symptoms (November 2006 to May 2010). Inclusion criteria were age >18 years, histologically confirmed advanced or metastatic prostate cancer, and life expectancy ≥12 months. Exclusion criteria were treatment with any LHRH analogue within the last 6 months or any other investigational agent within the last 3 months before study entry. Patients who received one or more triptorelin doses and had one or more efficacy assessments were evaluated. In total, 325 patients were included with a median age of 74 years (50 to 95 years). Mean age at first diagnosis was 73 ± 8 years. Moderate (IPSS 8-19) to severe (IPSS ≥ 20) LUTS were observed in 62% of patients. Triptorelin reduced LUTS severity. This improvement was perceived within the first 24 weeks of treatment and was maintained after 48 weeks. A decrease in PSA level was also observed. PMID:25694830

  9. Protective effect of carboxymethyl-glucan (CM-G) against DNA damage in patients with advanced prostate cancer.

    PubMed

    Magnani, Marciane; Castro-Gomez, Raul Jorge Hernan; Mori, Mateus Prates; Kuasne, Hellen; Gregório, Emerson Pereira; Libos, Farid; de Syllos Cólus, Ilce Mara

    2011-01-01

    Carboxymethyl-glucan (CM-G) is a soluble derivative from Saccharomyces cerevisiae (1 → 3)(1 → 6)-β-D-glucan. The protective efficiency of CM-G against DNA damage in cells from patients with advanced prostate cancer (PCa), and undergoing Androgen Deprivation Therapy (ADT), was evaluated. DNA damage scores were obtained by the comet assay, both before and after treatment with CM-G. The reduction in DNA damage, ranging from 18% to 87%, with an average of 59%, was not related to the increased number of leukocytes in peripheral blood. The results demonstrate for the first time the protective effect of CM-G against DNA damage in patients with advanced PCa. Among smokers, three presented the highest reduction in DNA damage after treatment with CM-G. There was no observable relationship between DNA damage scores before and after treatment, and age, alcoholism and radiotherapy.

  10. Protective effect of carboxymethyl-glucan (CM-G) against DNA damage in patients with advanced prostate cancer

    PubMed Central

    Magnani, Marciane; Castro-Gomez, Raul Jorge Hernan; Mori, Mateus Prates; Kuasne, Hellen; Gregório, Emerson Pereira; Libos, Farid; de Syllos Cólus, Ilce Mara

    2011-01-01

    Carboxymethyl-glucan (CM-G) is a soluble derivative from Saccharomyces cerevisiae (1 → 3)(1 → 6)-β-D-glucan. The protective efficiency of CM-G against DNA damage in cells from patients with advanced prostate cancer (PCa), and undergoing Androgen Deprivation Therapy (ADT), was evaluated. DNA damage scores were obtained by the comet assay, both before and after treatment with CM-G. The reduction in DNA damage, ranging from 18% to 87%, with an average of 59%, was not related to the increased number of leukocytes in peripheral blood. The results demonstrate for the first time the protective effect of CM-G against DNA damage in patients with advanced PCa. Among smokers, three presented the highest reduction in DNA damage after treatment with CM-G. There was no observable relationship between DNA damage scores before and after treatment, and age, alcoholism and radiotherapy. PMID:21637556

  11. First Report: Robot-Assisted Total Pelvic Exenteration for Locally Advanced Prostate Cancer.

    PubMed

    Castillo, Octavio A; Vidal-Mora, Ivar; Rodriguez-Carlin, Arquimedes; Silva, Andres; Schatloff, Oscar

    2015-07-01

    Pelvic exenteration is used in the treatment of several pelvic cancers, including those of the rectum, uterus, and bladder. We report the first case of robotic pelvic exenteration for the treatment of symptomatic prostate cancer involving the rectum and bladder. A six-port transperitoneal robotic approach was used. Bilateral extended lymphadenectomy up to the inferior mesenteric artery was performed. The rectum and bladder were removed en bloc, and a double-barrel anastomosis was then performed with both ureters being connected to the lower opening of the colostomy. Operative time was 249 minutes, and estimated blood loss was 600 mL. No intraoperative or postoperative complications were recorded. Biopsy of the rectum and bladder showed prostatic adenocarcinoma with a Gleason score of 9 (5+4), and 1 of 17 nodes was positive for cancer. Postoperative prostate-specific antigen level was 1.24 ng/mL. The patient is already 19 months after surgery with optimal quality of life. Thus pelvic exenteration is a feasible alternative for highly symptomatic prostate cancer involving adjacent pelvic organs. PMID:26134069

  12. Target Definition in Salvage Radiotherapy for Recurrent Prostate Cancer: The Role of Advanced Molecular Imaging

    PubMed Central

    Amzalag, Gaël; Rager, Olivier; Tabouret-Viaud, Claire; Wissmeyer, Michael; Sfakianaki, Electra; de Perrot, Thomas; Ratib, Osman; Miralbell, Raymond; Giovacchini, Giampiero; Garibotto, Valentina; Zilli, Thomas

    2016-01-01

    Salvage radiotherapy (SRT) represents the main treatment option for relapsing prostate cancer in patients after radical prostatectomy. Several open questions remain unanswered in terms of target volumes definition and delivered doses for SRT: the effective dose necessary to achieve biochemical control in the SRT setting may be different if the tumor recurrence is micro- or macroscopic. At the same time, irradiation of only the prostatic bed or of the whole pelvis will depend on the localization of the recurrence, local or locoregional. In the “theragnostic imaging” era, molecular imaging using positron emission tomography (PET) constitutes a useful tool for clinicians to define the site of the recurrence, the extent of disease, and individualize salvage treatments. The best option currently available in clinical routine is the combination of radiolabeled choline PET imaging and multiparametric magnetic resonance imaging (MRI), associating the nodal and distant metastases identification based on PET with the local assessment by MRI. A new generation of targeted tracers, namely, prostate-specific membrane antigen, show promising results, with a contrast superior to choline imaging and a higher detection rate even for low prostate-specific antigen levels; validation studies are ongoing. Finally, imaging targeting bone remodeling, using whole-body SPECT–CT, is a relevant complement to molecular/metabolic PET imaging when bone involvement is suspected. PMID:27065024

  13. Benefits of intermittent/continuous androgen deprivation in patients with advanced prostate cancer

    PubMed Central

    MURESANU, HORIA

    2016-01-01

    Background and aims In 1941 Huggins described the effect of castration on prostate cancer. gonadotropin-releasing hormone (GNRH) analogues were introduced in 1985. Complete androgen blockade (association of GNRH analogue with antiandrogen) was introduced by Fernand Labrie to achieve suppression of suprarenal testosterone. Long time androgen deprivation lead to androgen independence of the prostate cancer cell. Our principal aim was to demonstrate longer survival rates on prostate cancer patients with intermittent androgen deprivation. Methods 82 patients in the Urology Department of Vasile Goldis West University Arad were included into two groups, with continuous and intermittent androgen deprivation. Treatment efficiency was assessed by the level of testosterone and PSA. Adverse events (AE) and serious adverse events were reported according to Common Terminology Criteria of Adverse Events (CTCAE) of the National Cancer Institute (NCI). Results Evolution towards castrate resistant prostate cancer: 12.5% from the intermittent androgen deprivation group and 23.8% from the continuous androgen deprivation group Mortality rate: 15% of patients from the intermittent androgen deprivation group; 19% of patients from the continuous androgen deprivation group Conclusions Better quality of life (Qol) in periods without treatment due to testosteron recovery; Less AE’s and metabolic syndrome (MS) related complications; Better survival and longer time of disease control and Cost reduction. PMID:27547063

  14. Advancements in Magnetic Resonance–Guided Robotic Interventions in the Prostate

    PubMed Central

    Macura, Katarzyna J.; Stoianovici, Dan

    2011-01-01

    Magnetic resonance imaging (MRI) provides more detailed anatomical images of the prostate compared with the transrectal ultrasound imaging. Therefore, for the purpose of intervention in the prostate gland, diagnostic or therapeutic, MRI guidance offers a possibility of more precise targeting that may be crucial to the success of prostate interventions. However, access within the scanner is limited for manual instrument handling and the MR environment is most demanding among all imaging equipment with respect to the instrumentation used. A solution to this problem is the use of MR-compatible robots purposely designed to operate in the space and environmental restrictions inside the MR scanner allowing real-time interventions. Building an MRI-compatible robot is a very challenging engineering task because, in addition to the material restrictions that MRI instruments have, the robot requires actuators and sensors that limit the type of energies that can be used. Several important design problems have to be overcome before a successful MR-compatible robot application can be built. A number of MR-compatible robots, ranging from a simple manipulator to a fully automated system, have been developed, proposing ingenious solutions to the design challenge. Several systems have been already tested clinically for prostate biopsy and brachytherapy. As technology matures, precise image guidance for prostate interventions performed or assisted by specialized MR-compatible robotic devices may provide a uniquely accurate solution for guiding the intervention directly based on MR findings and feedback. Such an instrument would become a valuable clinical tool for biopsies directly targeting imaged tumor foci and delivering tumor-centered focal therapy. PMID:19512852

  15. Advances in sentinel node dissection in prostate cancer from a technical perspective.

    PubMed

    Acar, Cenk; Kleinjan, Gijs H; van den Berg, Nynke S; Wit, Esther Mk; van Leeuwen, Fijs Wb; van der Poel, Henk G

    2015-10-01

    The most important feature of sentinel node biopsy for prostate cancer procedure is that staging can be improved. Sentinel nodes might be found outside the extended pelvic lymph node dissection template what renders the sentinel node additive of extended pelvic lymph node dissection. At the same time, staging within the template can be further refined. We reviewed the literature regarding the sentinel node biopsy procedure for prostate cancer. PubMed and Embase were searched for all English-language publications from January 1999 to September 2014 by using the keywords as "prostate cancer" and "sentinel lymph node" plus "biopsy" "dissection" and/or "procedure." The present review discusses step-by-step sentinel node biopsy for prostate cancer. Topics of discussion are: (i) preoperative sentinel node mapping (tracers and imaging); (ii) intraoperative sentinel node identification (surgical procedure and outcome); and (iii) novelties to improve sentinel node identification (pre- and intraoperative approaches). Conventional sentinel node mapping is carried out after the injection of a (99m) Tc-based tracer and subsequent preoperative imaging; for example, lymphoscintigraphy and single-photon emission computed tomography/computed tomography. This approach allowed the detection of sentinel nodes outside the extended lymph node dissection template in 3.6-36% of men with intermediate- and high-risk prostate cancer. Hereby, an overall false negative rate of sentinel nodes was reported between 0% and 24.4%. To further refine the intraoperative sampling procedure, novel imaging methods such as fluorescence imaging have been introduced. Prospective randomized comparison studies are required to confirm the added benefit of sentinel template directed nodal dissection. A proper and obtainable end-point of such a study could be the number of removed positive nodes for carrying out nodal dissection with or without sentinel template directed dissection. Similarly, the clinical

  16. New Prostate Cancer Treatment Target

    Cancer.gov

    Researchers have identified a potential alternative approach to blocking a key molecular driver of an advanced form of prostate cancer, called androgen-independent or castration-resistant prostate cancer.

  17. Opioid requirement, opioid receptor expression, and clinical outcomes in patients with advanced prostate cancer

    PubMed Central

    Zylla, Dylan; Gourley, Brett L.; Vang, Derek; Jackson, Scott; Boatman, Sonja; Lindgren, Bruce; Kuskowski, Michael A.; Le, Chap; Gupta, Kalpna; Gupta, Pankaj

    2013-01-01

    Background Preclinical studies show that opioids stimulate angiogenesis and tumor progression through the mu opioid receptor (MOR). Although MOR is over-expressed in several human malignancies, the effect of chronic opioid requirement on cancer progression or survival has not been examined in humans. Methods We performed a retrospective analysis on 113 patients identified in the Minneapolis VA Tumor Registry (test cohort) and 480 patients from the national VA Central Cancer Registry (validation cohort) diagnosed with stage IV prostate cancer between 1995 and 2010, to examine whether MOR expression or opioid requirement is associated with disease progression and survival. All opioids were converted to oral morphine equivalents (OME) for comparison. Laser scanning confocal microscopy was used to analyze MOR-immunoreactivity in prostate cancer biopsies. The effects of variables on outcomes were analyzed in univariable and multivariable models. Results In patients with metastatic prostate cancer, MOR expression and opioid requirement were independently associated with inferior progression-free survival (PFS) (HR 1.65, 1.33–2.07; p<0.001 and HR 1.08, 1.03–1.13; p<0.001, respectively) and overall survival (OS; HR 1.55, 1.20–1.99; p<0.001 and HR 1.05, 1.00–1.10; p=0.031, respectively). The validation cohort confirmed that increasing opioid requirement was associated with worse OS (HR 1.005, 1.002–1.008, p=0.001). Conclusion Higher MOR expression and greater opioid requirement are associated with shorter PFS and OS in patients with metastatic prostate cancer. Nevertheless, clinical practice should not be changed until prospective randomized trials show that opioid use is associated with inferior clinical outcomes, and that abrogation of the peripheral activities of opioids ameliorates this effect. PMID:24104703

  18. Marital Satisfaction of Advanced Prostate Cancer Survivors and Their Spousal Caregivers: The Dyadic Effects of Physical and Mental Health

    PubMed Central

    Zhou, Eric S.; Kim, Youngmee; Rasheed, Mikal; Benedict, Catherine; Bustillo, Natalie E.; Soloway, Mark; Kava, Bruce R.; Penedo, Frank J.

    2010-01-01

    Objective Coping with the physical and mental side effects of diagnosis and treatment for advanced prostate cancer (APC) is a challenge for both survivors and their spousal caregivers. There is a gap in our current understanding of the dyadic adjustment process on marital satisfaction in this population. The current study sought to: 1) document levels of physical and mental health, and marital satisfaction and 2) evaluate the relationship between physical and mental health with marital satisfaction in this understudied population. Methods APC survivors who had undergone hormonal therapy within the past year and their spousal caregiver participated in the study (N=29 dyads). Physical and mental health was assessed using the MOS SF-36 Health Survey and marital satisfaction was evaluated using the Dyadic Adjustment Scale. Results The Actor-Partner Interdependence Model revealed strong relations between physical and mental health with marital satisfaction for both survivor and caregiver (actor effects). Furthermore, caregiver physical and mental health was related with the survivor's marital satisfaction (partner effect). Conclusions Levels of mental health and marital satisfaction were comparable to community-based or prostate cancer samples, while physical health was higher. Marital satisfaction between APC survivors and their spousal caregivers may be influenced by both physical and mental health functioning. In particular, APC survivor functioning may affect both his marital satisfaction as well as his spousal caregiver's. This has implications for psychosocial interventions for APC dyads. Further evaluation of the complex nature of survivor/caregiver dyadic adjustment in dealing with APC is necessary. PMID:20925137

  19. Final Report of the Intergroup Randomized Study of Combined Androgen-Deprivation Therapy Plus Radiotherapy Versus Androgen-Deprivation Therapy Alone in Locally Advanced Prostate Cancer

    PubMed Central

    Mason, Malcolm D.; Parulekar, Wendy R.; Sydes, Matthew R.; Brundage, Michael; Kirkbride, Peter; Gospodarowicz, Mary; Cowan, Richard; Kostashuk, Edmund C.; Anderson, John; Swanson, Gregory; Parmar, Mahesh K.B.; Hayter, Charles; Jovic, Gordana; Hiltz, Andrea; Hetherington, John; Sathya, Jinka; Barber, James B.P.; McKenzie, Michael; El-Sharkawi, Salah; Souhami, Luis; Hardman, P.D. John; Chen, Bingshu E.; Warde, Padraig

    2015-01-01

    Purpose We have previously reported that radiotherapy (RT) added to androgen-deprivation therapy (ADT) improves survival in men with locally advanced prostate cancer. Here, we report the prespecified final analysis of this randomized trial. Patients and Methods NCIC Clinical Trials Group PR.3/Medical Research Council PR07/Intergroup T94-0110 was a randomized controlled trial of patients with locally advanced prostate cancer. Patients with T3-4, N0/Nx, M0 prostate cancer or T1-2 disease with either prostate-specific antigen (PSA) of more than 40 μg/L or PSA of 20 to 40 μg/L plus Gleason score of 8 to 10 were randomly assigned to lifelong ADT alone or to ADT+RT. The RT dose was 64 to 69 Gy in 35 to 39 fractions to the prostate and pelvis or prostate alone. Overall survival was compared using a log-rank test stratified for prespecified variables. Results One thousand two hundred five patients were randomly assigned between 1995 and 2005, 602 to ADT alone and 603 to ADT+RT. At a median follow-up time of 8 years, 465 patients had died, including 199 patients from prostate cancer. Overall survival was significantly improved in the patients allocated to ADT+RT (hazard ratio [HR], 0.70; 95% CI, 0.57 to 0.85; P < .001). Deaths from prostate cancer were significantly reduced by the addition of RT to ADT (HR, 0.46; 95% CI, 0.34 to 0.61; P < .001). Patients on ADT+RT reported a higher frequency of adverse events related to bowel toxicity, but only two of 589 patients had grade 3 or greater diarrhea at 24 months after RT. Conclusion This analysis demonstrates that the previously reported benefit in survival is maintained at a median follow-up of 8 years and firmly establishes the role of RT in the treatment of men with locally advanced prostate cancer. PMID:25691677

  20. Akt Inhibitor MK2206 and Hydroxychloroquine in Treating Patients With Advanced Solid Tumors, Melanoma, Prostate or Kidney Cancer

    ClinicalTrials.gov

    2016-02-05

    Adult Solid Neoplasm; Hormone-Resistant Prostate Cancer; Recurrent Melanoma; Recurrent Prostate Carcinoma; Recurrent Renal Cell Carcinoma; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Prostate Cancer; Stage IV Renal Cell Cancer; Stage IV Skin Melanoma

  1. Possible relationship between endocrine disrupting chemicals and hormone dependent gynecologic cancers.

    PubMed

    Dogan, Selen; Simsek, Tayup

    2016-07-01

    The effects of the natural and synthetic estrogens have been studied for a long time but the data regarding estrogen related chemicals (endocrine disrupting chemicals, EDCs) and their effects on reproductive system are scarce. EDCs are hormone like agents that are readily present in the environment, which may alter the endocrine system of humans and animals. Approximately 800 chemicals are known or suspected to have the potential to function as EDC. Potential role of EDCs on reproductive disease has gained attention in medical literature in recent years. We hypothesize that exposure to low doses of EDCs in a chronic manner could cause hormone dependent genital cancers including ovarian and endometrial cancer. Long term exposure to low concentrations of EDCs may exert potentiation effect with each other and even with endogenous estrogens and could inhibit enzymes responsible for estrogen metabolism. Exposure time to these EDCs is essential as we have seen from Diethylstilbestrol experience. Dose-response curves of EDCs are also unpredictable. Hence mode of action of EDCs are more complex than previously thought. In the light of these controversies lower doses of EDCs in long term exposure is not harmless. Possibility of this relationship and this hypothesis merit further investigation especially through in vivo studies that could better show the realistic environmental exposure. With the confirmation of our hypothesis, possible EDCs could be identified and eliminated from general use as a public health measure. PMID:27241264

  2. Hormone-dependent aggression in female rats: testosterone implants attenuate the decline in aggression following ovariectomy.

    PubMed

    Albert, D J; Jonik, R H; Walsh, M L

    1990-04-01

    Female rats were individually housed with a sterile male for a 4- to 5-week period. Each female was then tested for aggression toward an unfamiliar female intruder at weekly intervals. Those females that displayed a high level of aggression on each of three weekly tests were ovariectomized and given subcutaneous implants of testosterone-filled tubes, ovariectomized and given subcutaneous implants of empty tubes, or sham-ovariectomized and implanted with empty tubes. These implants should produce a serum testosterone concentration of about 0.6 ng/ml, compared to 0.17 ng/ml in intact females. Beginning 1 week postoperatively, the aggression of each female was tested weekly for 4 weeks. Ovariectomized females with testosterone implants displayed a level of aggression significantly higher than that of ovariectomized females with empty implants on 3 of 4 weekly tests. The level of aggression by females with testosterone implants was not significantly different from that of sham-ovariectomized females on the first postoperative test. Additional observations showed that testosterone implants did not produce an increase in aggression in females whose preoperative level of aggression was low. Further, Silastic implants containing estrogen (1 to 2 mm long) sufficient to maintain a serum estrogen level of 20 to 30 pg/ml also attenuated the decline of aggression following ovariectomy. These results suggest that testosterone and estrogen may both contribute to the biological substrate of hormone-dependent aggression in female rats.

  3. Long-term cancer-related fatigue outcomes in patients with locally advanced prostate cancer after intensity-modulated radiotherapy combined with hormonal therapy

    PubMed Central

    Luo, Hua-Chun; Lei, Yong; Cheng, Hui-Hua; Fu, Zhi-Chao; Liao, Shao-Guang; Feng, Jing; Yin, Qin; Chen, Qun-Hua; Lin, Gui-Shan; Zhu, Jin-Feng; Xu, Jian-Feng; Wang, Dian

    2016-01-01

    Abstract The aim of our study was to investigate the relationship between cancer-related fatigue and clinical parameters, and the effect factors of fatigue for the prostate cancer patients. Long-term follow-up is performed using the Fatigue Symptom Inventory before treatment (A), at the end of intensity-modulated radiotherapy (B), and 3 months (C), 12 months (D), 24 months (E), 36 months (F), and 48 months (G) after the end of intensity-modulated radiotherapy. Three dimensions of fatigue are assessed during follow-up: severity, perceived interference with quality of life, and duration in the past week. In all, 97 patients with locally advanced prostate cancer were enrolled in the study. Median follow-up time was 43.9 months. The fatigue index was significantly higher in the prostate-specific antigen >20 ng/mL, Gleason score >8, the Eastern Cooperative Oncology Group scores, and the higher education. The most severe fatigue occurred at time points B and C. The score for duration of fatigue fluctuated across the time points, with significantly increased scores at time points D, E, and F. In conclusion, we show that cancer-related fatigue is the important symptom which affects the quality of life for the prostate cancer patients. For patients with locally advanced prostate cancer with a high Eastern Cooperative Oncology Group score, a Gleason score of >8 points, prostate-specific antigen levels of >20 ng/mL, and high education, attention should be paid to the interference of fatigue with quality of life, especially general level of activity, ability to concentrate, and mood, after radiotherapy combined with hormonal therapy. PMID:27336890

  4. The Present and Future of Biomarkers in Prostate Cancer: Proteomics, Genomics, and Immunology Advancements

    PubMed Central

    Gaudreau, Pierre-Olivier; Stagg, John; Soulières, Denis; Saad, Fred

    2016-01-01

    Prostate cancer (PC) is the second most common form of cancer in men worldwide. Biomarkers have emerged as essential tools for treatment and assessment since the variability of disease behavior, the cost and diversity of treatments, and the related impairment of quality of life have given rise to a need for a personalized approach. High-throughput technology platforms in proteomics and genomics have accelerated the development of biomarkers. Furthermore, recent successes of several new agents in PC, including immunotherapy, have stimulated the search for predictors of response and resistance and have improved the understanding of the biological mechanisms at work. This review provides an overview of currently established biomarkers in PC, as well as a selection of the most promising biomarkers within these particular fields of development. PMID:27168728

  5. Gonadal hormone-dependent and -independent regulation of immune function by photoperiod in Siberian hamsters.

    PubMed

    Prendergast, Brian J; Baillie, Scott R; Dhabhar, Firdaus S

    2008-02-01

    Siberian hamsters (Phodopus sungorus) exhibit changes in reproductive and immune function in response to seasonal variations in day length. Exposure to short days induces gonadal regression and inhibits testosterone secretion. In parallel, short days enhance immune function: increasing leukocyte numbers and attenuating cytokine and behavioral responses to infection. We examined whether photoperiodic changes in leukocyte phenotypes and sickness behaviors are dependent on concurrent photoperiodic changes in gonadal function. Male hamsters were gonadectomized or sham-gonadectomized and either exposed to short days (9 h light/day; SD) or kept in their natal long-day (15 h light/day; LD) photoperiod for 10-13 wk. Blood samples were obtained for leukocyte enumeration, and hamsters were challenged with bacterial LPS, which induced behavioral (anorexia, reductions in nest building) and somatic (weight loss) sickness responses. Among gonad-intact hamsters, exposure to SD increased total and CD62L+ lymphocytes and CD3+ T lymphocytes in blood and significantly attenuated LPS-induced sickness responses. Independent of photoperiod, castration alone increased total and CD62L+ lymphocyte and CD3+ T lymphocyte numbers and attenuated somatic and anorexic sickness responses. Among castrated hamsters, SD exposure increased lymphocyte numbers and suppressed sickness behaviors. In castrated hamsters, the magnitude of most immunological effects of SD were diminished relative to those evident in gonad-intact hamsters. The SD phenotype in several measures of immunity can be instated via elimination of gonadal hormones alone; however, photoperiodic effects on immune function persist even in castrated hamsters. Thus, photoperiod affects the immune system and neural-immune interactions underlying sickness behaviors via gonadal hormone-dependent and -independent mechanisms.

  6. Correlation between hormone dependency and the regulation of epidermal growth factor receptor by tumor promoters in human mammary carcinoma cells.

    PubMed Central

    Roos, W; Fabbro, D; Küng, W; Costa, S D; Eppenberger, U

    1986-01-01

    The effects of the tumor promoter phorbol 12-tetradecanoate 13-acetate (TPA) on the epidermal growth factor (EGF) receptor levels were investigated in hormone-dependent (MCF-7, T-47-D, and ZR-75-1) and hormone-independent (MDA-MB-231, HBL-100, and BT-20) human mammary carcinoma cell lines. In the absence of TPA, hormone-independent cell lines contained high concentrations of low-affinity EGF receptors (apparent Kd = 8 X 10(-10) M), whereas hormone-dependent cell lines exhibited low concentrations of high-affinity receptors (apparent Kd = 1 X 10(-10) M). TPA causes a change of the receptor from a high- to the low-affinity state in hormone-dependent cell lines (MCF-7, T-47-D, and ZR-75-1), as well as in the hormone-independent HBL-100, whereas the affinity remained unchanged in MDA-MB-231 and BT-20 cells. In addition, progesterone receptor levels are decreased after TPA treatment in the hormone-dependent cell lines MCF-7, T-47-D, and ZR-75-1, whereas the estrogen receptor levels remained unchanged. Tumor promoters such as TPA or teleocidin inhibited the proliferation of these cell lines at concentrations above 10 microM with the exception of the T-47-D cells. The most sensitive cell line towards growth inhibition by tumor promoter was the hormone-dependent MCF-7 cell line. Evaluation of different TPA analogs indicated a positive correlation between the growth-inhibitory effects and their ability to stimulate the subcellular redistribution of protein kinase C activity in MCF-7 cells. These data suggest a protein kinase C-mediated down-regulation of the progesterone receptor concentration and of the EGF receptor affinity, which is supposed to mediate the mitogenic response. Furthermore, these results support the hypothesis that the tumor-derived growth factors induced by estradiol act via the EGF receptor in hormone-dependent mammary carcinoma cells. PMID:3006036

  7. Prostate Cancer

    MedlinePlus

    ... version of this page please turn Javascript on. Prostate Cancer What is Prostate Cancer? How Tumors Form The body is made up ... the Escape (Esc) button on your keyboard.) How Prostate Cancer Occurs Prostate cancer occurs when a tumor forms ...

  8. High-Intensity Focused Ultrasound for the Treatment of Localized and Locally Advanced Hormone-Resistant Prostate Cancer: 2,5 Year Outcome

    NASA Astrophysics Data System (ADS)

    Solovov, V. A.; Dvoynikov, S. Y.; Vozdvizhenskiy, M. O.

    2011-09-01

    Introduction & Objectives: High-Intensity Focused Ultrasound (HIFU) has been shown to be a successful treatment for localised prostate cancer (PC). Here we have explored the effectiveness of the HIFU treatment for hormone-resistant prostate cancer (HRPC). Materials & Methods: 341 patients were treated in our center between September 2007 and December 2009; all of them showed treatment failure following hormone ablation. The median time before hormone-resistance was 20 (3-48) months. In the group with localised PC: number of patients 237, Gleason score ≤7, stage T1-2N0M0, age 69 (60-89) years, mean PSA before treatment 40,0 (5,8-92,9) ng/ml, mean prostate volume—39,3 (28-92) cc; in the group with locally advanced PC: number of patients 104, Gleason score ≤9, stage T2-3N0M0, age 72 (52-83) years, PSA before treatment 30,3 (20,1-60) ng/ml, mean prostate volume—41,2 (25-198) cc. HIFU was delivered under spinal anesthesia using the Ablatherm HIFU device (EDAP, France). Pre HIFU transurethral resection of the prostate (TURP) was performed for all patients. Mean follow-up time 18 months (3-30). Results: The median PSA level 12 months after HIFU treatment was 0,04 (0-2,24) ng/ml—localised PC, and for locally advanced disease—0,05 (0-48,4) ng/ml, at 18 months after HIFU treatment this was 0,2 (0,02-2,0) ng/ml for localised PC, and for locally advanced disease 0,18 (0,04-7,45) ng/ml. Patients with localised PC has 4,5% recurrence, those with locally advanced PC 20%. Kaplan-Meir analyses of the total group indicated that the risk of recurrence after 1 year follow-up was 10%, the risk of recurrence was 19% after 2 years of follow-up. Conclusions: Our initial experience shows that ultrasound ablation is safe, minimally invasive and effective as a treatment for localised and locally advanced hormone-resistant prostate cancer.

  9. Screening for prostate cancer

    NASA Technical Reports Server (NTRS)

    Weirich, Stephen A.

    1993-01-01

    Despite recent advances in both the survival and cure rates for many forms of cancer, unfortunately the same has not been true for prostate cancer. In fact, the age-adjusted death rate from prostate cancer has not significantly improved since 1949, and prostate cancer remains the most common cancer in American men, causing the second highest cancer mortality rate. Topics discussed include the following: serum testosterone levels; diagnosis; mortality statistics; prostate-sppecific antigen (PSA) tests; and the Occupational Medicine Services policy at LeRC.

  10. Novel actions of next-generation taxanes benefit advanced stages of prostate cancer

    PubMed Central

    de Leeuw, Renée; Berman-Booty, Lisa D; Schiewer, Matthew J; Ciment, Stephen J; Den, Robert B; Dicker, Adam P; Kelly, William K; Trabulsi, Edouard J; Lallas, Costas D; Gomella, Leonard G; Knudsen, Karen E

    2014-01-01

    Purpose To improve the outcomes of patients with castrate resistant prostate cancer (CRPC), there is an urgent need for more effective therapies and approaches that individual specific treatments for patients with CRPC. The current studies compared the novel taxane, cabazitaxel with the previous generation docetaxel, and aimed to determine which tumors are most likely to respond. Experimental design Cabazitaxel (CBTX) and docetaxel (DCTX) were compared via in vitro modeling to determine molecular mechanism, biochemical and cell biological impact, and cell proliferation, which was further assessed ex vivo in human tumor explants. Isogenic pairs of RB knockdown and control cells were interrogated in vitro, and in xenograft tumors for cabazitaxel response. Results The data herein show that i. CBTX exerts stronger cytostatic and cytotoxic response compared to DCTX, especially in CRPC; ii. CBTX induces aberrant mitosis, leading to pyknotic and multinucleated cells; iii. taxanes do not act through the androgen receptor (AR); iv. Gene expression profiling reveals distinct molecular actions for CBTX v. tumors that have progressed to castration resistance via loss of RB show enhanced sensitivity to CBTX. Conclusions CBTX not only induces improved cytostatic and cytotoxic effects, but also impacts distinct molecular pathways, compared to DCTX, which could underlie its efficacy after DCTX treatment has failed in CRPC patients. Finally, RB is identified as the first potential biomarker that could define the therapeutic response to taxanes in metastatic CRPC. This would suggest that loss of RB function induces sensitization taxanes, which could benefit up to 50% of CRPC cases. PMID:25691773

  11. Long-term aspirin use and the risk of total, high-grade, regionally advanced and lethal prostate cancer in a prospective cohort of health professionals, 1988–2006

    PubMed Central

    Dhillon, Preet K.; Kenfield, Stacey A.; Stampfer, Meir J; Giovannucci, Edward L.

    2012-01-01

    Experimental studies suggest a role for aspirin in the chemoprevention of prostate cancer and epidemiological evidence supports a modest inverse association between regular aspirin use and prostate cancer risk, especially for advanced disease. In a prospective cohort study of 51,529 health professionals aged 40–75 years at baseline, we evaluated long-term aspirin use and the incidence of total, high-grade (Gleason 8–10, n=488), regionally advanced (T3b-T4 or N1, n=228) and lethal prostate cancer (M1, bony metastases or prostate cancer death, n=580) from 1988–2006. We used Cox proportional hazards regression to evaluate risk associated with frequency (days/week), quantity (tablets/week), recency and duration of aspirin use after multivariable adjustment for confounders and other predictors of prostate cancer risk. A total of 4,858 men were diagnosed with prostate cancer during the 18-year study period. Men taking ≥ 2 adult-strength aspirin tablets a week had a 10% lower risk of prostate cancer (p-for-trend=0.02). For regionally advanced cancer, we observed no significant associations with aspirin use. For high-grade and lethal disease, men taking ≥ 6 adult-strength tablets/week experienced similar reductions in risk (HR=0.72 (95% CI: 0.54, 0.96) and HR=0.71 (95% CI: 0.50, 1.00)). Analytical approaches to address bias from more frequent PSA screening among aspirin users did not yield different conclusions. We observed reductions in the risk of high-grade and lethal prostate cancer associated with higher doses of aspirin, but not with greater frequency or duration, in a large, prospective cohort of health professionals. Our data support earlier observations of modest inverse associations with advanced prostate cancer. PMID:21128233

  12. Development and exploitation of a novel mutant androgen receptor modelling strategy to identify new targets for advanced prostate cancer therapy.

    PubMed

    O'Neill, Daniel; Jones, Dominic; Wade, Mark; Grey, James; Nakjang, Sirintra; Guo, Wenrui; Cork, David; Davies, Barry R; Wedge, Steve R; Robson, Craig N; Gaughan, Luke

    2015-09-22

    The persistence of androgen receptor (AR) signalling in castrate-resistant prostate cancer (CRPC) highlights the unmet clinical need for the development of more effective AR targeting therapies. A key mechanism of therapy-resistance is by selection of AR mutations that convert anti-androgens to agonists enabling the retention of androgenic signalling in CRPC. To improve our understanding of these receptors in advanced disease we developed a physiologically-relevant model to analyse the global functionality of AR mutants in CRPC. Using the bicalutamide-activated AR(W741L/C) mutation as proof of concept, we demonstrate that this mutant confers an androgenic-like signalling programme and growth promoting phenotype in the presence of bicalutamide. Transcriptomic profiling of AR(W741L) highlighted key genes markedly up-regulated by the mutant receptor, including TIPARP, RASD1 and SGK1. Importantly, SGK1 expression was found to be highly expressed in the KUCaP xenograft model and a CRPC patient biopsy sample both of which express the bicalutamide-activated receptor mutant. Using an SGK1 inhibitor, AR(W741L) transcriptional and growth promoting activity was reduced indicating that exploiting functional distinctions between receptor isoforms in our model may provide new and effective therapies for CRPC patients.

  13. Intermittent versus continuous total androgen blockade in the treatment of patients with advanced hormone-naive prostate cancer: results of a prospective randomized multicenter trial.

    PubMed

    de Leval, Jean; Boca, Philippe; Yousef, Enis; Nicolas, Hubert; Jeukenne, Michel; Seidel, Laurence; Bouffioux, Christian; Coppens, Luc; Bonnet, Pierre; Andrianne, Robert; Wlatregny, David

    2002-12-01

    The aim of this study was to compare the efficacy of total intermittent androgen deprivation (IAD) versus total continuous androgen deprivation (CAD) for treating patients with advanced prostate cancer in a phase III randomized trial. A total of 68 evaluable patients with hormone-naive advanced or relapsing prostate cancer were randomized to receive combined androgen blockade according to a continuous (n = 33) or intermittent (n = 35) regimen. Therapeutic monitoring was assessed by use of serum prostate-specific antigen (PSA) measurements. Patients in the CAD and IAD groups were equally stratified for age, biopsy Gleason score, and baseline serum PSA levels. The outcome variable was time to androgen-independence of the tumor, which was defined as increasing serum PSA levels despite androgen blockade. Mean follow-up was 30.8 months. The 35 IAD-treated patients completed 91 cycles, and 19 of them (54.3%) completed > or = 3 cycles. Median cycle length and percentage of time off therapy were 9.0 months and 59.5, respectively. The estimated 3-year progression rate was significantly lower in the IAD group (7.0% +/- 4.8%) than in the CAD group (38.9% +/- 11.2%, P = 0.0052). Our data suggest that IAD treatment may maintain the androgen-dependent state of advanced human prostate cancer, as assessed by PSA measurements, at least as long as CAD treatment. Further studies with longer follow-up times and larger patient cohorts are needed to determine the comparative impacts of CAD and IAD on survival.

  14. Necessity of re-evaluation of estramustine phosphate sodium (EMP) as a treatment option for first-line monotherapy in advanced prostate cancer.

    PubMed

    Kitamura, T

    2001-02-01

    Estramustine phosphate sodium (EMP) was first introduced in the early 1970s for the treatment of prostate cancer, when EMP was supposed to have the dual effect of estrogenic activity and cytotoxicity. For the following decades, it was used mainly in hormone-refractory cases, with a conventional dosage of 4-9 capsules/day, which showed a 30-35% objective response rate. However, a very limited number of cases have been reported that used EMP as a first-line monotherapy in the conventional dosage. One study showed a response rate of 82%, which is at least as effective as conventional estrogen (diethylstilbestrol; DES) monotherapy. Nevertheless, EMP was almost abandoned for the treatment of prostate cancer because of severe adverse side-effects, especially in the cardiovascular system and gastrointestinal tract. Recently, two facts have become evident. First, EMP interferes with cellular microtubule dynamics but does not show alkylating effects. Second, EMP is able to produce a complex with calcium when dairy products are taken concomitantly with EMP, resulting in a decrease in the absorption rate of EMP from the gut. Many clinical trials have been undertaken without warning against concomitant dairy product intake since the introduction of EMP. This fact will jeopardize almost all the clinical trials performed before 1990. It is considered that response rates have been underestimated and better results could have been obtained because side-effects decrease dose-dependently. Low-dose EMP monotherapy (2 capsules/day) has been performed infrequently in previously untreated advanced prostate cancer. The only large trial by the European Organization for Research and Treatment of Cancer in 1984 was biased in selecting patients. Nevertheless, the response rate of EMP is comparable to that of DES. In this study, the adverse side-effects of EMP were less than that of DES. Recently, a study was conducted at the University of Tokyo of 11 patients with advanced prostate cancer on

  15. Cabozantinib in Patients With Advanced Prostate Cancer: Results of a Phase II Randomized Discontinuation Trial

    PubMed Central

    Smith, David C.; Smith, Matthew R.; Sweeney, Christopher; Elfiky, Aymen A.; Logothetis, Christopher; Corn, Paul G.; Vogelzang, Nicholas J.; Small, Eric J.; Harzstark, Andrea L.; Gordon, Michael S.; Vaishampayan, Ulka N.; Haas, Naomi B.; Spira, Alexander I.; Lara, Primo N.; Lin, Chia-Chi; Srinivas, Sandy; Sella, Avishay; Schöffski, Patrick; Scheffold, Christian; Weitzman, Aaron L.; Hussain, Maha

    2013-01-01

    Purpose Cabozantinib (XL184) is an orally bioavailable tyrosine kinase inhibitor with activity against MET and vascular endothelial growth factor receptor 2. We evaluated the activity of cabozantinib in patients with castration-resistant prostate cancer (CRPC) in a phase II randomized discontinuation trial with an expansion cohort. Patients and Methods Patients received 100 mg of cabozantinib daily. Those with stable disease per RECIST at 12 weeks were randomly assigned to cabozantinib or placebo. Primary end points were objective response rate at 12 weeks and progression-free survival (PFS) after random assignment. Results One hundred seventy-one men with CRPC were enrolled. Random assignment was halted early based on the observed activity of cabozantinib. Seventy-two percent of patients had regression in soft tissue lesions, whereas 68% of evaluable patients had improvement on bone scan, including complete resolution in 12%. The objective response rate at 12 weeks was 5%, with stable disease in 75% of patients. Thirty-one patients with stable disease at week 12 were randomly assigned. Median PFS was 23.9 weeks (95% CI, 10.7 to 62.4 weeks) with cabozantinib and 5.9 weeks (95% CI, 5.4 to 6.6 weeks) with placebo (hazard ratio, 0.12; P < .001). Serum total alkaline phosphatase and plasma cross-linked C-terminal telopeptide of type I collagen were reduced by ≥ 50% in 57% of evaluable patients. On retrospective review, bone pain improved in 67% of evaluable patients, with a decrease in narcotic use in 56%. The most common grade 3 adverse events were fatigue (16%), hypertension (12%), and hand-foot syndrome (8%). Conclusion Cabozantinib has clinical activity in men with CRPC, including reduction of soft tissue lesions, improvement in PFS, resolution of bone scans, and reductions in bone turnover markers, pain, and narcotic use. PMID:23169517

  16. Impact of comorbidity on the outcome in men with advanced prostate cancer treated with docetaxel

    PubMed Central

    Zist, Andrej; Amir, Eitan; Ocana, Alberto F.; Seruga, Bostjan

    2015-01-01

    Background Men with metastatic castrate-resistant prostate cancer (mCRPC) may not receive docetaxel in everyday clinical practice due to comorbidities. Here we explore the impact of comorbidity on outcome in men with mCRPC treated with docetaxel in a population-based outcome study. Methods Men with mCRPC treated with docetaxel at the Institute of Oncology Ljubljana between 2005 and 2012 were eligible. Comorbidity was assessed by the age-adjusted Charlson comorbidity index (aa-CCI) and adult comorbidity evaluation (ACE-27) index. Hospital admissions due to the toxicity and deaths during treatment with docetaxel were used as a measure of tolerability. Association between comorbidity and overall survival (OS) was tested using the Cox proportional hazards analysis. Results Two hundred and eight men were treated with docetaxel. No, mild, moderate and severe comorbidity was present in 2%, 32%, 53% and 13% using aa-CCI and in 27%, 35%, 29% and 8% when assessed by ACE-27. A substantial dose reduction of docetaxel occurred more often in men with moderate or severe comorbidity as compared to those with no or mild comorbidity. At all comorbidity levels about one-third of men required hospitalization or died during treatment with docetaxel. In univariate analysis a higher level of comorbidity was not associated with worse OS (aa-CCI HR 0.99; [95% CI 0.87–1.13], p = 0.93; ACE-27: HR 0.96; [95% CI 0.79–1.17], p = 0.69). Conclusions Men with mCRPC, who have comorbidities may benefit from treatment with docetaxel. PMID:26834528

  17. Evidence-based recommendations on androgen deprivation therapy for localized and advanced prostate cancer

    PubMed Central

    Belsey, Jonathan; Drewa, Tomasz; Kołodziej, Anna; Skoneczna, Iwona; Milecki, Piotr; Dobruch, Jakub; Słojewski, Marcin; Chłosta, Piotr L.

    2016-01-01

    Introduction The management of prostate cancer (PC) is still evolving. Although, androgen deprivation therapy (ADT) is an established treatment option, particularly in patients with disseminated disease, important data regarding hormonal manipulation have recently emerged. The aim of this paper is to review the evidence on ADT, make recommendations and address areas of controversy associated with its use in men with PC. Material and methods An expert panel was convened. Areas related to the hormonal management of patients with PC requiring evidence review were identified and questions to be addressed by the panel were determined. Appropriate literature review was performed and included a search of online databases, bibliographic reviews and consultation with experts. Results The panel was able to provide recommendations on: 1) which patients with localised PC should receive androgen deprivation in conjunction with radiotherapy (RT); 2) what standard initial treatment should be used in metastatic hormone-naïve PC (MHNPC); 3) efficacy of androgen deprivation agents; 4) whether ADT should be continued in patients with castration resistant PC (CRPC). However, no recommendations could be made for combined ADT and very high-dose RT in patients with an intermediate-risk disease. Conclusions ADT remains the cornerstone of treatment for both metastatic hormone-naïve and castration-resistant PC. According to the expert panel's opinion, based on the ERG report, luteinizing hormone-releasing hormone agonists might not be equivalent but this needs to be confirmed in long-term data. The combined use of ADT and RT improves outcome and survival in men with high-risk localised disease. The benefits in patients with intermediate-risk disease, particularly those subject to escalated dose RT are controversial. PMID:27551549

  18. The Enzymatic Activity of Apoptosis-inducing Factor Supports Energy Metabolism Benefiting the Growth and Invasiveness of Advanced Prostate Cancer Cells*

    PubMed Central

    Lewis, Eric M.; Wilkinson, Amanda S.; Jackson, Jacqueline S.; Mehra, Rohit; Varambally, Sooryanarayana; Chinnaiyan, Arul M.; Wilkinson, John C.

    2012-01-01

    Apoptosis-inducing factor (AIF) promotes cell death yet also controls mitochondrial homeostasis and energy metabolism. It is unclear how these activities are coordinated, and the impact of AIF upon human disease, in particular cancer, is not well documented. In this study we have explored the contribution of AIF to the progression of prostate cancer. Analysis of archival gene expression data demonstrated that AIF transcript levels are elevated in human prostate cancer, and we found that AIF protein is increased in prostate tumors. Suppression of AIF expression in the prostate cancer cell lines LNCaP, DU145, and PC3 demonstrated that AIF does not contribute to cell toxicity via a variety of chemical death triggers, and growth under nutrient-rich conditions is largely unaffected by AIF ablation. However, under growth stress conditions, AIF depletion from DU145 and PC3 cell lines led to significant reductions in cell survival and growth that were not observed in LNCaP cells. Moreover AIF-deficient PC3 cells exhibited substantial reduction of tumorigenic growth in vivo. This reduced survival correlated with decreased expression of mitochondrial complex I protein subunits and concomitant changes in glucose metabolism. Finally, restoration of AIF-deficient PC3 cells with AIF variants demonstrated that the enzymatic activity of AIF is required for aggressive growth. Overall these studies show that AIF is an important factor for advanced prostate cancer cells and that through control of energy metabolism and redox balance, the enzymatic activity of AIF is critical for this support. PMID:23118229

  19. Simultaneous integrated boost plan comparison of volumetric-modulated arc therapy and sliding window intensity-modulated radiotherapy for whole pelvis irradiation of locally advanced prostate cancer.

    PubMed

    Riou, Olivier; Regnault de la Mothe, Pauline; Azria, David; Aillères, Norbert; Dubois, Jean-Bernard; Fenoglietto, Pascal

    2013-07-08

    Concurrent radiotherapy to the pelvis plus a prostate boost with long-term androgen deprivation is a standard of care for locally advanced prostate cancer. IMRT has the ability to deliver highly conformal dose to the target while lowering irradiation of critical organs around the prostate. Volumetric-modulated arc therapy is able to reduce treatment time, but its impact on organ sparing is still controversial when compared to static gantry IMRT. We compared the two techniques in simultaneous integrated boost plans. Ten patients with locally advanced prostate cancer were included. The planning target volume (PTV) 1 was defined as the pelvic lymph nodes, the prostate, and the seminal vesicles plus setup margins. The PTV2 consisted of the prostate with setup margins. The prescribed doses to PTV1 and PTV2 were 54 Gy in 37 fractions and 74 Gy in 37 fractions, respectively. We compared simultaneous integrated boost plans by means of either a seven coplanar static split fields IMRT, or a one-arc (RA1) and a two-arc (RA2) RapidArc planning. All three techniques allowed acceptable homogeneity and PTV coverage. Static IMRT enabled a better homogeneity for PTV2 than RapidArc techniques. Sliding window IMRT and VMAT permitted to maintain doses to OAR within acceptable levels with a low risk of side effects for each organ. VMAT plans resulted in a clinically and statistically significant reduction in doses to bladder (mean dose IMRT: 50.1 ± 4.6Gy vs. mean dose RA2: 47.1 ± 3.9 Gy, p = 0.037), rectum (mean dose IMRT: 44± 4.5 vs. mean dose RA2: 41.6 ± 5.5 Gy, p = 0.006), and small bowel (V30 IMRT: 76.47 ± 14.91% vs. V30 RA2: 47.49 ± 16.91%, p = 0.002). Doses to femoral heads were higher with VMAT but within accepted constraints. Our findings suggest that simultaneous integrated boost plans using VMAT and sliding window IMRT allow good OAR sparing while maintaining PTV coverage within acceptable levels.

  20. Stable transfection of protein kinase C alpha cDNA in hormone-dependent breast cancer cell lines

    PubMed Central

    Tonetti, D A; Chisamore, M J; Grdina, W; Schurz, H; Jordan, V C

    2000-01-01

    An inverse relationship between protein kinase C (PKC) activity and oestrogen receptor (ER) expression in human breast cell lines and tumours has been firmly established over the past 10 years. To determine whether specific alterations in PKC expression accompany hormone-independence, we examined the expression of PKC isozymes in the hormone-independent human breast cancer cell clones MCF-7 5C and T47D:C42 compared with their hormone-dependent counterparts, MCF-7 A4, MCF-7 WS8 and T47D:A18 respectively. Both hormone-independent cell clones exhibit elevated PKCα expression and increased basal AP-1 activity compared with the hormone-dependent cell clones. To determine whether PKCα overexpression is sufficient to mediate the hormone-independent phenotype, we stably transfected an expression plasmid containing PKCα cDNA to the T47D:A18 and MCF-7 A4 cell lines. This is the first report of PKCα transfection in T47D cells. In contrast to MCF-7 cells, T47D has the propensity to lose the ER and more readily forms tamoxifen-stimulated tumours in athymic mice. We find that in T47D:A18/PKCα clones, there is concomitant up-regulation of PKC βI and δ, whereas in the MCF-7 A4/PKCα transfectants PKC ɛ is up-regulated. In T47D:A18, but not in MCF-7 A4, PKCα stable transfection is accompanied by down-regulation of ER function whilst basal AP-1 activity is elevated. Our results suggest PKCα overexpression may play a role in growth signalling during the shift from hormone dependent to hormone-independent breast cancers. © 2000 Cancer Research Campaign PMID:10952784

  1. Prostate brachytherapy

    MedlinePlus

    Implant therapy - prostate cancer; Radioactive seed placement; Internal radiation therapy - prostate; High dose radiation (HDR) ... plan and then place the seeds that deliver radiation into your prostate. The seeds are placed with ...

  2. Is there room for combined modality treatments? Dosimetric comparison of boost strategies for advanced head and neck and prostate cancer.

    PubMed

    Góra, Joanna; Hopfgartner, Johannes; Kuess, Peter; Paskeviciute, Brigita; Georg, Dietmar

    2013-07-01

    The purpose of the study was to determine the dosimetric difference between three emerging treatment modalities--volumetric-modulated arc therapy (VMAT), intensity-modulated proton beam therapy (IMPT) and intensity-modulated carbon ion beam therapy (IMIT)--for two tumour sites where selective boosting of the tumour is applied. For 10 patients with locally advanced head and neck (H&N) cancer and 10 with high-risk prostate cancer (PC) a VMAT plan was generated for PTV initial that included lymph node regions, delivering 50 Gy (IsoE) for H&N and 50.4 Gy (IsoE) for PC patients. Furthermore, separate boost plans (VMAT, IMPT and IMIT) were created to boost PTV boost up to 70 Gy (IsoE) and 78 Gy (IsoE) for H&N and PC cases, respectively. Doses to brainstem, myelon, larynx and parotid glands were assessed for H&N cases. Additionally, various OARs (e.g. cochlea, middle ear, masticator space) were evaluated that are currently discussed with respect to quality of life after treatment. For PC cases, bladder, rectum and femoral heads were considered as OARs. For both tumour sites target goals were easily met. Looking at OAR sparing, generally VMAT + VMAT was worst. VMAT + IMIT had the potential to spare some structures in very close target vicinity (such as cochlea, middle ear, masticator space ) significantly better than VMAT + IMPT. Mean doses for rectal and bladder wall were on average 4 Gy (IsoE) and 1.5 Gy (IsoE) higher, respectively, compared to photons plus particles scenarios. Similar results were found for parotid glands and larynx. Concerning target coverage, no significant differences were observed between the three treatment concepts. Clear dosimetric benefits were observed for particle beam therapy as boost modality. However, the clinical benefit of combined modality treatments remains to be demonstrated.

  3. Impact of hormonal treatment duration in combination with radiotherapy for locally advanced prostate cancer: Meta-analysis of randomized trials

    PubMed Central

    2010-01-01

    Background Hormone therapy plus radiotherapy significantly decreases recurrences and mortality of patients affected by locally advanced prostate cancer. In order to determine if difference exists according to the hormonal treatment duration, a literature-based meta-analysis was performed. Methods Relative risks (RR) were derived through a random-effect model. Differences in primary (biochemical failure, BF; cancer-specific survival, CSS), and secondary outcomes (overall survival, OS; local or distant recurrence, LR/DM) were explored. Absolute differences (AD) and the number needed to treat (NNT) were calculated. Heterogeneity, a meta-regression for clinic-pathological predictors and a correlation test for surrogates were conducted. Results Five trials (3,424 patients) were included. Patient population ranged from 267 to 1,521 patients. The longer hormonal treatment significantly improves BF (with significant heterogeneity) with an absolute benefit of 10.1%, and a non significant trend in CSS. With regard to secondary end-points, the longer hormonal treatment significantly decrease both the LR and the DM with an absolute difference of 11.7% and 11.5%. Any significant difference in OS was observed. None of the three identified clinico-pathological predictors (median PSA, range 9.5-20.35, Gleason score 7-10, 27-55% patients/trial, and T3-4, 13-77% patients/trial), did significantly affect outcomes. At the meta-regression analysis a significant correlation between the overall treatment benefit in BF, CSS, OS, LR and DM, and the length of the treatment was found (p≤0.03). Conclusions Although with significant heterogeneity (reflecting different patient' risk stratifications), a longer hormonal treatment duration significantly decreases biochemical, local and distant recurrences, with a trend for longer cancer specific survival. PMID:21143897

  4. PET/CT Dose Planning for Volumetric Modulated Arc Radiation Therapy (VMAT) -Comparison with Conventional Approach in Advanced Prostate Cancer Patients.

    PubMed

    Kairemo, Kalevi; Rasulova, Nigora; Kiljunen, Timo; Partanen, Kaarina; Kangasmäki, Aki; Joensuu, Timo

    2015-01-01

    Molecular imaging is the only way of defining biological target volume (BTV) for externalbeam radiation therapy (EBRT) and may be used for advanced targeting in dose planning and dose painting. There are, however, no reports about the EBRT response when dose planning is based on BTV target definition in advanced prostate cancer. Clinical and biochemical results of two clinically equal group of patients with advanced prostate cancer patients were compared. Both groups were treated with volumetric modulated arc therapy (VMAT) based on target definition by PET/CT (1(st) group) or conventional imaging (2(nd) group). Biochemical relapse occurred in 16.6% (in 1 out of 6) of the patients in the first group and 50% (3 out of 6) patients in the second group during the follow up period. Clinical manifestation of disease occurred in 33% (2 out of 6) patients of the first group and in 5 out of 6 (83,3%) patients in the second one. 4 patients in the first group had no biochemical relapse and no clinical manifestation during the follow up period. The difference in the duration of progression free period was statistically significant between the groups (p<0.010) being in the first group 16.5±5.4 (10-24) months and 4.6±2.9 (2-10) months in the second one. Because patients with PET/CT based VMAT had lower incidence of biochemical relapse, less clinical manifestations and longer, statistically significant duration of progression free period as compared to patients treated with VMAT based on conventional imaging, our preliminary results suggest introducing BTV definition based on PET imaging for VMAT in the EBRT of prostate cancer.

  5. Hormone-dependent aggression in male rats is proportional to serum testosterone concentration but sexual behavior is not.

    PubMed

    Albert, D J; Jonik, R H; Watson, N V; Gorzalka, B B; Walsh, M L

    1990-09-01

    Male hooded rats were castrated and implanted with Silastic capsules (1.57 mm i.d.; 3.18 mm o.d.) having a testosterone-filled space 0, 7, 22, 60, or 90 mm long. All animals were returned to their original group cages for a three-week period to allow hormone concentrations and behavioral tendencies to stabilize. Each male was then housed with an intact female in a large cage. Aggression by the male toward an unfamiliar male was tested at weekly intervals for three weeks. Sexual behavior with an estrogen/progesterone-primed ovariectomized female was tested on each of the subsequent two weeks. Serum testosterone was measured during the following week. The frequency of aggression was correlated with serum testosterone concentration up to the normal level and did not increase with higher serum testosterone concentrations. In contrast, sexual behavior was virtually absent in animals with no testosterone replacement and normal in all other groups. These results demonstrate a clear dissociation in the dependence of hormone-dependent aggression and sexual behavior on serum testosterone concentration. In a male cohabiting with a female, sexual experience activates hormone-dependent aggression toward an unfamiliar male but the level of aggression that develops depends on the serum testosterone concentration in the resident male.

  6. Gonadotropin-releasing hormone antagonists versus standard androgen suppression therapy for advanced prostate cancer A systematic review with meta-analysis

    PubMed Central

    Kunath, Frank; Borgmann, Hendrik; Blümle, Anette; Keck, Bastian; Wullich, Bernd; Schmucker, Christine; Sikic, Danijel; Roelle, Catharina; Schmidt, Stefanie; Wahba, Amr; Meerpohl, Joerg J

    2015-01-01

    Objectives To evaluate efficacy and safety of gonadotropin-releasing hormone (GnRH) antagonists compared to standard androgen suppression therapy for advanced prostate cancer. Setting The international review team included methodologists of the German Cochrane Centre and clinical experts. Participants We searched CENTRAL, MEDLINE, Web of Science, EMBASE, trial registries and conference books for randomised controlled trials (RCT) for effectiveness data analysis, and randomised or non-randomised controlled studies (non-RCT) for safety data analysis (March 2015). Two authors independently screened identified articles, extracted data, evaluated risk of bias and rated quality of evidence according to GRADE. Results 13 studies (10 RCTs, 3 non-RCTs) were included. No study reported cancer-specific survival or clinical progression. There were no differences in overall mortality (RR 1.35, 95% CI 0.63 to 2.93), treatment failure (RR 0.91, 95% CI 0.70 to 1.17) or prostate-specific antigen progression (RR 0.83, 95% CI 0.64 to 1.06). While there was no difference in quality of life related to urinary symptoms, improved quality of life regarding prostate symptoms, measured with the International Prostate Symptom Score (IPSS), with the use of GnRH antagonists compared with the use of standard androgen suppression therapy (mean score difference −0.40, 95% CI −0.94 to 0.14, and −1.84, 95% CI −3.00 to −0.69, respectively) was found. Quality of evidence for all assessed outcomes was rated low according to GRADE. The risk for injection-site events was increased, but cardiovascular events may occur less often by using GnRH antagonist. Available evidence is hampered by risk of bias, selective reporting and limited follow-up. Conclusions There is currently insufficient evidence to make firm conclusive statements on the efficacy of GnRH antagonist compared to standard androgen suppression therapy for advanced prostate cancer. There is need for further high-quality research on

  7. Non-steroidal antiandrogen monotherapy compared with luteinizing hormone-releasing hormone agonists or surgical castration monotherapy for advanced prostate cancer: a Cochrane systematic review.

    PubMed

    Kunath, Frank; Grobe, Henrik R; Rücker, Gerta; Motschall, Edith; Antes, Gerd; Dahm, Philipp; Wullich, Bernd; Meerpohl, Joerg J

    2015-07-01

    To assess the effects of non-steroidal antiandrogen monotherapy compared with luteinizing hormone-releasing hormone agonists or surgical castration monotherapy for treating advanced hormone-sensitive stages of prostate cancer. We searched the Cochrane Prostatic Diseases and Urologic Cancers Group Specialized Register (PROSTATE), the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Web of Science with Conference Proceedings, three trial registries and abstracts from three major conferences to 23 December 2013, together with reference lists, and contacted selected experts in the field and manufacturers. We included randomized controlled trials comparing non-steroidal antiandrogen monotherapy with medical or surgical castration monotherapy for men in advanced hormone-sensitive stages of prostate cancer. Two review authors independently examined full-text reports, identified relevant studies, assessed the eligibility of studies for inclusion, extracted data and assessed risk of bias as well as quality of evidence according to the GRADE working group guidelines. We used Review Manager 5.2 for data synthesis and the fixed-effect model as primary analysis (when heterogeneity was low with I(2) < 50%); we used a random-effects model when confronted with substantial or considerable heterogeneity (when I(2) ≥50%). A total of 11 studies involving 3060 randomly assigned participants were included in the present review. Use of non-steroidal antiandrogens resulted in lower overall survival times (hazard ratio [HR] 1.24, 95% confidence interval [CI] 1.05-1.48, six studies, 2712 participants) and greater clinical progression (1 year: risk ratio [RR] 1.25, 95% CI 1.08-1.45, five studies, 2067 participants; 70 weeks: RR 1.26, 95% CI 1.08-1.45, six studies, 2373 participants; 2 years: RR 1.14, 95% CI 1.04-1.25, three studies, 1336 participants), as well as treatment failure (1 year: RR 1.19, 95% CI 1.02-1.38, four studies, 1539 participants; 70 weeks: RR 1

  8. Race and Survival Following Brachytherapy-Based Treatment for Men With Localized or Locally Advanced Adenocarcinoma of the Prostate

    SciTech Connect

    Winkfield, Karen M.; Chen Minghui; Dosoretz, Daniel E.; Salenius, Sharon A.; Katin, Michael; Ross, Rudi; D'Amico, Anthony V.

    2011-11-15

    Purpose: We investigated whether race was associated with risk of death following brachytherapy-based treatment for localized prostate cancer, adjusting for age, cardiovascular comorbidity, treatment, and established prostate cancer prognostic factors. Methods: The study cohort was composed of 5,360 men with clinical stage T1-3N0M0 prostate cancer who underwent brachytherapy-based treatment at 20 centers within the 21st Century Oncology consortium. Cox regression multivariable analysis was used to evaluate the risk of death in African-American and Hispanic men compared to that in Caucasian men, adjusting for age, pretreatment prostate-specific antigen (PSA) level, Gleason score, clinical T stage, year and type of treatment, median income, and cardiovascular comorbidities. Results: After a median follow-up of 3 years, there were 673 deaths. African-American and Hispanic races were significantly associated with an increased risk of all-cause mortality (ACM) (adjusted hazard ratio, 1.77 and 1.79; 95% confidence intervals, 1.3-2.5 and 1.2-2.7; p < 0.001 and p = 0.005, respectively). Other factors significantly associated with an increased risk of death included age (p < 0.001), Gleason score of 8 to 10 (p = 0.04), year of brachytherapy (p < 0.001), and history of myocardial infarction treated with stent or coronary artery bypass graft (p < 0.001). Conclusions: After adjustment for prostate cancer prognostic factors, age, income level, and revascularized cardiovascular comorbidities, African-American and Hispanic races were associated with higher ACM in men with prostate cancer. Additional causative factors need to be identified.

  9. Risk of Pathologic Upgrading or Locally Advanced Disease in Early Prostate Cancer Patients Based on Biopsy Gleason Score and PSA: A Population-Based Study of Modern Patients

    SciTech Connect

    Caster, Joseph M.; Falchook, Aaron D.; Hendrix, Laura H.; Chen, Ronald C.

    2015-06-01

    Purpose: Radiation oncologists rely on available clinical information (biopsy Gleason score and prostate-specific antigen [PSA]) to determine the optimal treatment regimen for each prostate cancer patient. Existing published nomograms correlating clinical to pathologic extent of disease were based on patients treated in the 1980s and 1990s at select academic institutions. We used the Surveillance, Epidemiology, and End Results (SEER) database to examine pathologic outcomes (Gleason score and cancer stage) in early prostate cancer patients based on biopsy Gleason score and PSA concentration. Methods and Materials: This analysis included 25,858 patients whose cancer was diagnosed between 2010 and 2011, with biopsy Gleason scores of 6 to 7 and clinical stage T1 to T2 disease, who underwent radical prostatectomy. In subgroups based on biopsy Gleason score and PSA level, we report the proportion of patients with pathologically advanced disease (positive surgical margin or pT3-T4 disease) or whose Gleason score was upgraded. Logistic regression was used to examine factors associated with pathologic outcomes. Results: For patients with biopsy Gleason score 6 cancers, 84% of those with PSA <10 ng/mL had surgical T2 disease with negative margins; this decreased to 61% in patients with PSA of 20 to 29.9 ng/mL. Gleason score upgrading was seen in 43% (PSA: <10 ng/mL) to 61% (PSA: 20-29.9 ng/mL) of biopsy Gleason 6 patients. Patients with biopsy Gleason 7 cancers had a one-third (Gleason 3 + 4; PSA: <10 ng/mL) to two-thirds (Gleason 4 + 3; PSA: 20-29.9 ng/mL) probability of having pathologically advanced disease. Gleason score upgrading was seen in 11% to 19% of patients with biopsy Gleason 4 + 3 cancers. Multivariable analysis showed that higher PSA and older age were associated with Gleason score upgrading and pathologically advanced disease. Conclusions: This is the first population-based study to examine pathologic extent of disease and pathologic Gleason score

  10. [Prostate cancer].

    PubMed

    Morote, Joan; Maldonado, Xavier; Morales-Bárrera, Rafael

    2016-02-01

    The Vall d'Hebron multidisciplinary prostate cancer (PC) team reviews recent advances in the management of this neoplasm. Screening studies with long follow-up show a reduction in mortality, whereas active surveillance is emerging as a therapeutic approach of non-aggressive cancers. New markers increase the specificity of PSA and also allow targeting suspected aggressive cancers. Multiparametric magnetic resonance (mMRI) has emerged as the most effective method in the selection of patients for biopsy and also for local tumor staging. The paradigm of random prostatic biopsy is changing through the fusion techniques that allow guiding ultrasonography-driven biopsy of suspicious areas detected in mMRI. Radical prostatectomy (RP) and radiotherapy (RT) are curative treatments of localized PC and both have experienced significant technological improvements. RP is highly effective and the incorporation of robotic surgery is reducing morbidity. Modern RT allows the possibility of high tumor dose with minimal adjacent dose reducing its toxicity. Androgen deprivation therapy with LHRH analogues remains the treatment of choice for advanced PC, but should be limited to this indication. The loss of bone mass and adverse metabolic effects increases the frequency of fractures and cardiovascular morbimortality. After castration resistance in metastatic disease, new hormone-based drugs have demonstrated efficacy even after chemotherapy resistance.

  11. [Prostate cancer].

    PubMed

    Morote, Joan; Maldonado, Xavier; Morales-Bárrera, Rafael

    2016-02-01

    The Vall d'Hebron multidisciplinary prostate cancer (PC) team reviews recent advances in the management of this neoplasm. Screening studies with long follow-up show a reduction in mortality, whereas active surveillance is emerging as a therapeutic approach of non-aggressive cancers. New markers increase the specificity of PSA and also allow targeting suspected aggressive cancers. Multiparametric magnetic resonance (mMRI) has emerged as the most effective method in the selection of patients for biopsy and also for local tumor staging. The paradigm of random prostatic biopsy is changing through the fusion techniques that allow guiding ultrasonography-driven biopsy of suspicious areas detected in mMRI. Radical prostatectomy (RP) and radiotherapy (RT) are curative treatments of localized PC and both have experienced significant technological improvements. RP is highly effective and the incorporation of robotic surgery is reducing morbidity. Modern RT allows the possibility of high tumor dose with minimal adjacent dose reducing its toxicity. Androgen deprivation therapy with LHRH analogues remains the treatment of choice for advanced PC, but should be limited to this indication. The loss of bone mass and adverse metabolic effects increases the frequency of fractures and cardiovascular morbimortality. After castration resistance in metastatic disease, new hormone-based drugs have demonstrated efficacy even after chemotherapy resistance. PMID:25727526

  12. Pharmacotherapy for benign prostatic hyperplasia.

    PubMed Central

    Narayan, P; Indudhara, R

    1994-01-01

    Benign prostatic hyperplasia is a benign neoplasm of the prostate seen in men of advancing age. Microscopic evidence of the disorder is seen in about 70% of men by 70 years of age, whereas symptoms requiring some form of surgical intervention occur in 30% of men during their lifetime. Although the exact cause of benign prostatic hyperplasia is not clear, it is well recognized that high levels of intraprostatic androgens are required for the maintenance of prostatic growth. In recent years, extensive surveys of patients undergoing transurethral resection of the prostate reveal an 18% incidence of morbidity that has essentially not changed in the past 30 years. This procedure is also the second highest reimbursed surgical therapy under Medicare. These findings have resulted in an intensive search for alternative therapies for prostatic hyperplasia. An alternative that has now been well defined is the use of alpha-adrenergic blockers to relax the prostatic urethra. This is based on findings that a major component of benign prostatic hyperplasia symptoms is spasm of the prostatic urethra and bladder neck, which is mediated by the alpha-adrenergic nerves. A second approach is to block androgens involved in maintaining prostate growth. Several such drugs are now available for clinical use, and we discuss their side effects and use. We also include the newer recommendations on evaluating benign prostatic hyperplasia that are cost-effective yet comprehensive. Images PMID:7528957

  13. Prostate Cancer Imaging with Novel PET Tracers.

    PubMed

    Lindenberg, Liza; Choyke, Peter; Dahut, William

    2016-03-01

    Molecular imaging of prostate cancer is in a dynamic phase of development. Currently approved techniques are limited and researchers have been working on novel agents to improve accuracy in targeting and detecting prostate tumors. In addition, the complexity of various prostate cancer states also contributes to the challenges in evaluating suitable radiotracer candidates. We have highlighted nuclear medicine tracers that focus on mechanisms involved in bone metastasis, prostate cancer cell membrane synthesis, amino acid analogs, androgen analogs, and the prostate specific membrane antigen. Encouraging results with many of these innovative radiotracer compounds will not only advance diagnostic capabilities for prostate cancer but open opportunities for theranostic applications to treat this worldwide malignancy.

  14. Degarelix for the treatment of advanced prostate cancer compared with GnRh-Agonists: a systematic review and meta-analysis

    PubMed Central

    Hosseini, Seyed Alireza; Rajabi, Fatemeh; Akbari Sari, Ali; Ayati, Mohsen; Heidari, Saeed; Ghamary, Fawzieh

    2016-01-01

    Background: Hormone therapy is currently the mainstay in the management of locally advanced and metastatic prostate cancer. We performed a systematic review to compare safety, efficacy and effectiveness of degarelix, a new gonadotropin-releasing hormone (GnRH) antagonist (blocker), versus gonadotropin-releasing hormone (GnRH) agonists. Methods: MEDLINE, Web of Science and the Cochrane library were searched to identify all of the published Randomized Controlled Trials (RCTs) that used degarelix versus gonadotropin-releasing hormone agonists with or without anti-androgen therapy for the treatment of prostate cancer. We performed meta-analysis of extracted data on safety and efficacy of the target medication. Results: Six studies were included. They involved a total of 2296 patients which were used in the meta-analysis. Follow-up times after treatment were between 12 weeks and 12 months. Three of six RCTs compared degarelix with goserelin and the others compared it with leuprolide. Meta-analysis on safety outcomes revealed that the only statistically significant difference between the degarelix treated group and GnRH agonists treated group was complication in the injection site which was higher in degarelix-treated group (OR= 46.34, 95% CI: 15.79 to 136, p<0.001). Although general mortality rate was lower in degarelix-treated group (OR= 2.06, 95% CI: 1.08 to 3.93, p=0.03); mortality due to the drug side effects was not different. Meta-analysis of efficacy data also showed that International Prostate Symptom Score (IPSS) reduction at week 12, (MD=-1.85, 95% CI: -2.97 to - 0.72, p=0.001) and Testosterone reduction between day 1-28, (OR=11.58, 95% CI: 5.77 to 23.22, p<0.001) was statistically higher in degarelix-treated group. Testosterone reduction after day 28 and prostate volume reduction did not have significant difference. Conclusion: Our meta-analysis indicates that, compared with GnRH agonists, degarelix has significantly more effects on lower urinary tract

  15. Thyroid hormone dependency in immature but not mature grafted locus coeruleus neurons. Evidence from intraocular innervation of iris transplants.

    PubMed

    Granholm, A C; Seiger, A

    1981-02-01

    Fetal brain tissue pieces containing locus coeruleus noradrenaline neurons were combined with sequentially or simultaneously grafted irides in the anterior eye chamber of thyroidectomized or normal host rats. The aim was to reveal possible morphological alterations in the adrenergic fibres innervating the iris grafts, induced by thyroid hormone deficiency, and to compare that possible hormone dependency with what has been found before in host irides innervated by locus coeruleus neurons. Nerve fibre outgrowth was evaluated in iris whole mounts, using Falck Hillarp fluorescence histochemistry. The distribution of locus-coeruleus-derived fibres on host irides was markedly altered in the thyroidectomized hosts. The number of fluorescent axon bundles was significantly decreased, and the intermingled varicose nerve fibre plexus contained numerous accumulations of fluorescent material. In the iris grafts from normal or thyroidectomized hosts reinnervated by matyured locus coeruleus neurons there was no difference in distribution or morphology between the two groups. This clearly shows that matured locus coeruleus neurons are not thyroid hormone dependent during a reinnervation process, after the stimulus elicited by a sensory denervation of iris. When immature locus coeruleus neurons were made to innervate iris grafts by simultaneous grafting of brain tissue and an iris to the eye a clearly reduced number of axon bundles was formed in the iris grafts of the thyroidectomized group. The morphological discrepancies between the two groups were, however, markedly smaller for iris grafts than for corresponding host irides. This might indicate that the potent growth stimulus elicited by sensory denervation of irides partly counteract the inhibition of axon bundle formation by immature grafted locus coeruleus neurons in irides during thyroid hormone deficiency. PMID:7266087

  16. Increased FOG-2 in failing myocardium disrupts thyroid hormone-dependent SERCA2 gene transcription.

    PubMed

    Rouf, Rosanne; Greytak, Sarah; Wooten, Eric C; Wu, Jing; Boltax, Jay; Picard, Michael; Svensson, Eric C; Dillmann, Wolfgang H; Patten, Richard D; Huggins, Gordon S

    2008-08-29

    Reduced expression of sarcoplasmic reticulum calcium ATPase (SERCA)2 and other genes in the adult cardiac gene program has raised consideration of an impaired responsiveness to thyroid hormone (T3) that develops in the advanced failing heart. Here, we show that human and murine cardiomyopathy hearts have increased expression of friend of GATA (FOG)-2, a cardiac nuclear hormone receptor corepressor protein. Cardiac-specific overexpression of FOG-2 in transgenic mice led to depressed cardiac function, activation of the fetal gene program, congestive heart failure, and early death. SERCA2 transcript and protein levels were reduced in FOG-2 transgenic hearts, and FOG-2 overexpression impaired T3-mediated SERCA2 expression in cultured cardiomyocytes. FOG-2 physically interacts with thyroid hormone receptor-alpha1 and abrogated even high levels of T3-mediated SERCA2 promoter activity. These results demonstrate that SERCA2 is an important target of FOG-2 and that increased FOG-2 expression may contribute to a decline in cardiac function in end-stage heart failure by impaired T3 signaling.

  17. Interplay between steroid signalling and microRNAs: implications for hormone-dependent cancers.

    PubMed

    Fletcher, Claire E; Dart, D Alwyn; Bevan, Charlotte L

    2014-10-01

    Hormones are key drivers of cancer development. To date, interest has largely been focussed on the classical model of hormonal gene regulation, but there is increasing evidence for a role of hormone signalling pathways in post-translational regulation of gene expression. In particular, a complex and dynamic network of bi-directional interactions with microRNAs (miRs) at all stages of biogenesis and during target gene repression is emerging. miRs, which act mainly by negatively regulating gene expression through association with 3'-UTRs of mRNA species, are increasingly understood to be important in development, normal physiology and pathogenesis. Given recent demonstrations of altered miR profiles in a diverse range of cancers, their ability to function as oncogenes or tumour suppressors, and hormonal regulation of miRs, understanding mechanisms by which miRs are generated and regulated is vitally important. miRs are transcribed by RNA polymerase II and then processed in the nucleus by the Drosha-containing Microprocessor complex and in the cytoplasm by Dicer, before mature miRs are incorporated into the RNA-induced silencing complex. It is increasingly evident that multiple cellular signalling pathways converge upon the miR biogenesis cascade, adding further layers of regulatory complexity to modulate miR maturation. This review summarises recent advances in identification of novel components and regulators of the Microprocessor and Dicer complexes, with particular emphasis on the role of hormone signalling pathways in regulating their activity. Understanding hormone regulation of miR production and how this is perturbed in cancer are critical for the development of miR-based therapeutics and biomarkers.

  18. Clinical outcomes of anti-androgen withdrawal and subsequent alternative anti-androgen therapy for advanced prostate cancer following failure of initial maximum androgen blockade

    PubMed Central

    MOMOZONO, HIROYUKI; MIYAKE, HIDEAKI; TEI, HIROMOTO; HARADA, KEN-ICHI; FUJISAWA, MASATO

    2016-01-01

    The present study aimed to investigate the significance of anti-androgen withdrawal and/or subsequent alternative anti-androgen therapy in patients with advanced prostate cancer (PC) who relapsed after initial maximum androgen blockade (MAB). The present study evaluated the clinical outcomes of 272 consecutive advanced PC patients undergoing anti-androgen withdrawal and/or subsequent alternative anti-androgen therapy with flutamide following the failure of initial MAB using bicalutamide. With the exception of 41 patients (15.1%) who did not undergo anti-androgen withdrawal due to the characteristics of PC suggesting aggressive diseases, prostate-specific antigen (PSA) declined from the baseline value in 83 patients (35.9%), including 18 (7.8%) with PSA decline >50%, but not in the remaining 148 (64.1%). No significant difference in the overall survival (OS) or cancer-specific survival (CSS) among the three groups was observed based on the response to anti-androgen withdrawal. Following the introduction of alternative anti-androgen therapy with flutamide, PSA decline was observed in 185 patients (68.0%), including 103 (37.9%) who achieved a PSA reduction of >50%; however, the PSA level continued to elevate in the remaining 87 (32.0%). Furthermore, of the numerous factors examined, only the duration of the initial MAB therapy was shown to be significantly correlated with the PSA decline following alternative anti-androgen therapy. Multivariate analysis of several factors identified revealed that only PSA decline following alternative anti-androgen therapy was an independent predictor of CSS and OS. If initial MAB is effective, the introduction of alternative anti-androgen therapy may be considered; however, anti-androgen withdrawal should be omitted, irrespective of the characteristics of advanced PC. PMID:27123292

  19. New drugs in prostate cancer.

    PubMed

    Yoo, Sangjun; Choi, Se Young; You, Dalsan; Kim, Choung-Soo

    2016-06-01

    The standard primary treatment for advanced prostate cancer has been hormonal therapy since the 1940s. However, prostate cancer inevitably progresses to castration-resistant prostate cancer (CRPC) after a median duration of 18 months of androgen deprivation therapy. In patients with CRPC, docetaxel has been regarded as the standard treatment. However, survival advantages of docetaxel over other treatments are slim, and the need for new agents persists. In recent years, novel agents, including abiraterone, enzalutamide, cabazitaxel, radium-223, and sipuleucel-T, have been approved for the treatment of CRPC, and more such agents based on diverse mechanisms are under investigation or evaluation. In this article, the authors reviewed the current literature on recent advances in medical treatment of prostate cancer, especially CRPC. In addition, the authors elaborated on novel drugs for prostate cancer currently undergoing investigation and their mechanisms. PMID:27358841

  20. BRCA1 loss pre-existing in small subpopulations of prostate cancer is associated with advanced disease and metastatic spread to lymph nodes and peripheral blood

    SciTech Connect

    Bednarz, Natalia; Eltze, Elke; Semjonow, Axel; Rink, Michael; Andreas, Antje; Mulder, Lennart; Hannemann, Juliane; Fisch, Margit; Pantel, Klaus; Weier, Heinz-Ulrich G.; Bielawski, Krzysztof P.; Brandt, Burkhard

    2010-03-19

    A recent study concluded that serum prostate specific antigen (PSA)-based screening is beneficial for reducing the lethality of PCa, but was also associated with a high risk of 'overdiagnosis'. Nevertheless, also PCa patients who suffered from organ confined tumors and had negative bone scans succumb to distant metastases after complete tumor resection. It is reasonable to assume that those tumors spread to other organs long before the overt manifestation of metastases. Our current results confirm that prostate tumors are highly heterogeneous. Even a small subpopulation of cells bearing BRCA1 losses can initiate PCa cell regional and distant dissemination indicating those patients which might be at high risk of metastasis. A preliminary study performed on a small cohort of multifocal prostate cancer (PCa) detected BRCA1 allelic imbalances (AI) among circulating tumor cells (CTCs). The present analysis was aimed to elucidate the biological and clinical role of BRCA1 losses on metastatic spread and tumor progression in prostate cancer patients. Experimental Design: To map molecular progression in PCa outgrowth we used FISH analysis of tissue microarrays (TMA), lymph node sections and CTC from peripheral blood. We found that 14% of 133 tested patients carried monoallelic BRCA1 loss in at least one tumor focus. Extended molecular analysis of chr17q revealed that this aberration was often a part of larger cytogenetic rearrangement involving chr17q21 accompanied by AI of the tumor suppressor gene PTEN and lack of the BRCA1 promoter methylation. The BRCA1 losses correlated with advanced T stage (p < 0.05), invasion to pelvic lymph nodes (LN, p < 0.05) as well as BR (p < 0.01). Their prevalence was twice as high within 62 LN metastases (LNMs) as in primary tumors (27%, p < 0.01). The analysis of 11 matched primary PCa-LNM pairs confirmed the suspected transmission of genetic abnormalities between those two sites. In 4 of 7 patients with metastatic disease, BRCA1 losses

  1. Prostate Cancer

    MedlinePlus

    ... man's bladder that produces fluid for semen. Prostate cancer is common among older men. It is rare ... younger than 40. Risk factors for developing prostate cancer include being over 65 years of age, family ...

  2. 89Zr-huJ591 immuno-PET imaging in patients with advanced metastatic prostate cancer

    PubMed Central

    O’Donoghue, Joseph A.; Beylergil, Volkan; Lyashchenko, Serge; Ruan, Shutian; Solomon, Stephen B.; Durack, Jeremy C.; Carrasquillo, Jorge A.; Lefkowitz, Robert A.; Gonen, Mithat; Lewis, Jason S.; Holland, Jason P.; Cheal, Sarah M.; Reuter, Victor E.; Osborne, Joseph R.; Loda, Massimo F.; Smith-Jones, Peter M.; Weber, Wolfgang A.; Bander, Neil H.; Scher, Howard I.; Morris, Michael J.; Larson, Steven M.

    2015-01-01

    Purpose Given the bone tropism of prostate cancer, conventional imaging modalities poorly identify or quantify metastatic disease. 89Zr-huJ591 positron emission tomography (PET) imaging was performed in patients with metastatic prostate cancer to analyze and validate this as an imaging biomarker for metastatic disease. The purpose of this initial study was to assess safety, biodistribution, normal organ dosimetry, and optimal imaging time post-injection for lesion detection. Methods Ten patients with metastatic prostate cancer received 5 mCi of 89Zr-huJ591. Four whole-body scans with multiple whole-body count rate measurements and serum activity concentration measurements were obtained in all patients. Biodistribution, clearance, and lesion uptake by 89Zr-huJ591 immuno-PET imaging was analyzed and dosimetry was estimated using MIRD techniques. Initial assessment of lesion targeting of 89Zr-huJ591 was done. Optimal time for imaging post-injection was determined. Results The dose was well tolerated with mild chills and rigors seen in two patients. The clearance of 89Zr-huJ591 from serum was bi-exponential with biological half-lives of 7 ± 4.5 h (range 1.1–14 h) and 62 ± 13 h (range 51–89 h) for initial rapid and later slow phase. Whole-body biological clearance was 219 ± 48 h (range 153–317 h). The mean whole-body and liver residence time was 78.7 and 25.6 h, respectively. Dosimetric estimates to critical organs included liver 7.7 ± 1.5 cGy/mCi, renal cortex 3.5 ± 0.4 cGy/mCi, and bone marrow 1.2 ± 0.2 cGy/mCi. Optimal time for patient imaging after injection was 7 ± 1 days. Lesion targeting of bone or soft tissue was seen in all patients. Biopsies were performed in 8 patients for a total 12 lesions, all of which were histologically confirmed as metastatic prostate cancer. One biopsy-proven lesion was not positive on 89Zr-huJ591, while the remaining 11 lesions were 89Zr-huJ591 positive. Two biopsy-positive nodal lesions were noted only on 89Zr-huJ591

  3. Prostate cancer.

    PubMed

    Castillejos-Molina, Ricardo Alonso; Gabilondo-Navarro, Fernando Bernardo

    2016-04-01

    Prostate cancer is the most frequent tumor found in men worldwide and in Mexico in particular. Age and family history are the main risk factors. The diagnosis is made by prostate biopsy in patients with abnormalities detected in their prostate-specific antigen (PSA) levels or digital rectal exam (DRE). This article reviews screening and diagnostic methods as well as treatment options for patients diagnosed with prostate cancer. PMID:27557386

  4. Prostate Diseases

    MedlinePlus

    The prostate is a gland in men. It helps make semen, the fluid that contains sperm. The prostate surrounds the tube that carries urine away from ... and out of the body. A young man's prostate is about the size of a walnut. It ...

  5. Stimulation of cartilage amino acid uptake by growth hormone-dependent factors in serum. Mediation by adenosine 3':5'-monophosphate.

    PubMed

    Drezner, M K; Eisenbarth, G S; Neelon, F A; Lebovitz, H E

    1975-02-13

    The effects of growth hormone-dependent serum factors on amino acid transport and on cartilage cyclic AMP levels in embryonic chicken cartilage were studied in vitro. Cartilages incubated in medium containing rat serum showed a significantly greater uptake of alpha-amino [1-14C] isobutyrate or [1-14C] cycloleucine than control cartilages incubated in medium alone. Normal rat serum (5%) added to the incubation medium also caused an increase in cartilage cyclic AMP content (from as little as 23% to as much as 109%). The factors in serum which increase cartilage cyclic AMP and amino acid uptake are growth hormone dependent, since neither growth hormone itself nor serum from hypophysectomized rats restores these serum factors. Studies comparing the ability of sera with varying amounts of growth hormone-dependent factors to stimulate amino-aminoisobutyrate transport and to increase cartilage cyclic AMP show a striking linear correlation between the two effects (r=0.977). Theophylline and prostaglandin E1, WHICH RAISE CARTILAGE CYCLIC AMP also increase amino-aminoisobutyrate transport. Exogenous cyclic AMP, N6-monobutyryl cyclic AMP and n6, 02'-dibutyryl cyclic AMP increase cartilage amino-aminoisobutyrate transport. The data are compatible with the thesis that growth hormone-dependent serum factors increase cartilage amino acid transport by elevating cartilage cyclic AMP.

  6. GTI-2040 and Docetaxel in Treating Patients With Recurrent, Metastatic, or Unresectable Locally Advanced Non-Small Cell Lung Cancer, Prostate Cancer, or Other Solid Tumors

    ClinicalTrials.gov

    2013-01-23

    Recurrent Non-small Cell Lung Cancer; Recurrent Prostate Cancer; Stage III Prostate Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Prostate Cancer; Unspecified Adult Solid Tumor, Protocol Specific

  7. [Antitumor and antiproliferative action of the steroidal cytostatic antiestrogen cytestrol acetate on hormone-dependent tumor models].

    PubMed

    Smirnova, z S; Rzheznikov, V M; Tolkachev, V N; Borisova, L M; Kiseleva, M P; Semeĭkin, A V; Fedotcheva, T A; Shirokikh, K E; Banin, V V; Shimanovskiĭ, N L

    2014-01-01

    Cytestrole acetate (CA), in the structure of which the steroidal antiestrogen component is associated with bis-β-cloroethylamino group, exhibits a strong cytotoxic activity against hormone-dependent cancer cell lines (CaOV, HeLa, MCF-7). In doxorubicin-resistant MCF-7 cells, CA potentiates the cytotoxic effect of etoposide and doxorubicin, and the IC50 for CA in these cells is 40 times lower than that for tamoxifen (TAM). In transplantable mice breast adenocarcinoma Ca-755, the therapeutic CA dose is 25 mg/kg when administered subcutaneously in oil solution for 5 days. On the DMBA-induced mammary tumors in rats, CA injected subcutaneously led to partial regressions 4 weeks after treatment in 75% of test rats, whereas TAM produced this effect in 43% of rats. Among various drug forms of CA, the most active were oil solution of CA in gelatin capsules for oral use and liposomal emulsion for intravenous administration, since these forms exhibited the highest values of Ca-755 tumor growth inhibition index (TGI = 97 - 98%).

  8. Hormone-dependent neural plasticity in the juvenile and adult song system: what makes a successful male?

    PubMed

    Gahr, Manfred

    2004-06-01

    The sexual quality of adult song is the result of genetic and epigenetic mechanisms shaping the neural song system throughout life. Genetic brain-intrinsic mechanisms determine the neuron pools that develop into forebrain song control areas independent of gonadal steroid hormones, androgens and estrogens. One fate of these neurons is the potential to express sex steroid receptors, such as androgen and estrogen receptors. Genetic brain-intrinsic mechanisms, too, determine the activity of hypothalamic-pituitary-gonad (HPG) axis, i.e., the working range and responsiveness of HPG axis to produce gonadal hormones. The epigenetic action of gonadal steroid hormones (androgens and estrogens) on determined vocal neurons is required to maintain and increase the pool of determined vocal neurons and to complete the connections of the vocal system, i.e., to make it function motorically. The subsequent influence of environmental information, including both external (socio-sexual and physical) and internal (body physiology) signals, specify the further neural phenotype of vocal areas either through acting on the HPG axis and differential release of gonadal hormones or through non-gonadal hormone systems, both of which have target neurons in the functional vocal system. Despite the clear evidence of hormone dependency of the development of both the adult song phenotype and song system phenotype, their causal relation is complex.

  9. Role of SP transcription factors in hormone-dependent modulation of genes in MCF-7 breast cancer cells

    PubMed Central

    Wu, Fei; Ivanov, Ivan; Xu, Rui; Safe, Stephen

    2009-01-01

    17β-Estradiol (E2) binds estrogen receptor α (ESR1) in MCF-7 cells and increases cell proliferation and survival through induction or repression of multiple genes. ESR1 interactions with DNA-bound specificity protein (SP) transcription factors is a nonclassical genomic estrogenic pathway and the role of SP transcription factors in mediating hormone-dependent activation or repression of genes in MCF-7 cells was investigated by microarrays and RNA interference. MCF-7 cells were transfected with a nonspecific oligonucleotide or a cocktail of small inhibitory RNAs (iSP), which knockdown SP1, SP3, and SP4 proteins, and treated with dimethylsulfoxide or 10 nM E2 for 6 h. E2 induced 62 and repressed 134 genes and the induction or repression was reversed in ∼62% of the genes in cells transfected with iSP (ESR1/SP dependent), whereas hormonal activation or repression of the remaining genes was unaffected by iSP (SP independent). Analysis of the ESR1/SP-dependent and SP-independent genes showed minimal overlap with respect to the GO terms (functional processes) in genes induced or repressed, suggesting that the different genomic pathways may contribute independently to the hormone-induced phenotype in MCF-7 cells. PMID:18952783

  10. Hormone-dependent aggression in the female rat: testosterone plus estradiol implants prevent the decline in aggression following ovariectomy.

    PubMed

    Albert, D J; Jonik, R H; Walsh, M L

    1991-04-01

    Female rats were individually housed with a sterile male for the duration of the experiment. Beginning 7 to 10 weeks after the start of cohabitation, each female was tested for aggression toward an unfamiliar female at weekly intervals for 3 weeks. Females that displayed consistent and substantial aggression were given one of the following treatments: ovariectomy followed by both testosterone and estradiol implants, ovariectomy followed by 2 empty implants, or sham ovariectomy followed by 2 empty implants. The implants were subcutaneously placed hormone-filled Silastic capsules. They were expected to produce a serum testosterone concentration of 0.5 ng/ml and an estradiol concentration of 15 pg/ml. Postoperatively, the aggression of each female continued to be assessed on a weekly basis for 3 weeks. Ovariectomized females with hormone implants displayed a level of aggression postoperatively similar to that of sham-ovariectomized females and significantly greater than that of ovariectomized females with empty implants. These results, together with others, suggest that estradiol and testosterone act together to form the hormonal foundation of hormone-dependent aggression by females cohabiting with a sterile male.

  11. Circulating Tumor Cells from Patients with Advanced Prostate and Breast Cancer Display Both Epithelial and Mesenchymal Markers

    PubMed Central

    Armstrong, Andrew J.; Marengo, Matthew S.; Oltean, Sebastian; Kemeny, Gabor; Bitting, Rhonda L.; Turnbull, James; Herold, Christina I.; Marcom, Paul K.; George, Daniel; Garcia-Blanco, Mariano A.

    2011-01-01

    During cancer progression malignant cells undergo epithelial-mesenchymal transitions (EMTs) and mesenchymal-epithelial transitions (METs) as part of a broad invasion and metastasis program. We previously observed MET events among lung metastases in a preclinical model of prostate adenocarcinoma that suggested a relationship between epithelial plasticity and metastatic spread. We thus sought to translate these findings into clinical evidence by examining the existence of EMT in circulating tumor cells (CTCs) from patients with progressive metastatic solid tumors, with a focus on men with castration-resistant prostate cancer (CRPC) and women with metastatic breast cancer (BC). We show that the majority (>80%) of these CTCs in patients with metastatic CRPC co-express epithelial proteins such as EpCAM, CK, and E-cadherin, mesenchymal proteins, including vimentin, N-cadherin, and O-cadherin, and the stem cell marker CD133. Equally, we find that over 75% of CTCs from women with metastatic BC co-express cytokeratin, vimentin, and N-cadherin. The existence and high frequency of these CTCs co-expressing epithelial, mesenchymal, and stem-cell markers in patients with progressive metastases has important implications for the application and interpretation of approved methods to detect CTCs. PMID:21665936

  12. What is Prostate Cancer?

    MedlinePlus

    ... Topic Key statistics for prostate cancer What is prostate cancer? Cancer starts when cells in the body begin ... through the center of the prostate. Types of prostate cancer Almost all prostate cancers are adenocarcinomas . These cancers ...

  13. A Randomised Comparison Evaluating Changes in Bone Mineral Density in Advanced Prostate Cancer: Luteinising Hormone-releasing Hormone Agonists Versus Transdermal Oestradiol

    PubMed Central

    Langley, Ruth E.; Kynaston, Howard G.; Alhasso, Abdulla A.; Duong, Trinh; Paez, Edgar M.; Jovic, Gordana; Scrase, Christopher D.; Robertson, Andrew; Cafferty, Fay; Welland, Andrew; Carpenter, Robin; Honeyfield, Lesley; Abel, Richard L.; Stone, Michael; Parmar, Mahesh K.B.; Abel, Paul D.

    2016-01-01

    Background Luteinising hormone-releasing hormone agonists (LHRHa), used as androgen deprivation therapy (ADT) in prostate cancer (PCa) management, reduce serum oestradiol as well as testosterone, causing bone mineral density (BMD) loss. Transdermal oestradiol is a potential alternative to LHRHa. Objective To compare BMD change in men receiving either LHRHa or oestradiol patches (OP). Design, setting, and participants Men with locally advanced or metastatic PCa participating in the randomised UK Prostate Adenocarcinoma TransCutaneous Hormones (PATCH) trial (allocation ratio of 1:2 for LHRHa:OP, 2006–2011; 1:1, thereafter) were recruited into a BMD study (2006–2012). Dual-energy x-ray absorptiometry scans were performed at baseline, 1 yr, and 2 yr. Interventions LHRHa as per local practice, OP (FemSeven 100 μg/24 h patches). Outcome measurements and statistical analysis The primary outcome was 1-yr change in lumbar spine (LS) BMD from baseline compared between randomised arms using analysis of covariance. Results and limitations A total of 74 eligible men (LHRHa 28, OP 46) participated from seven centres. Baseline clinical characteristics and 3-mo castration rates (testosterone ≤1.7 nmol/l, LHRHa 96% [26 of 27], OP 96% [43 of 45]) were similar between arms. Mean 1-yr change in LS BMD was −0.021 g/cm3 for patients randomised to the LHRHa arm (mean percentage change −1.4%) and +0.069 g/cm3 for the OP arm (+6.0%; p < 0.001). Similar patterns were seen in hip and total body measurements. The largest difference between arms was at 2 yr for those remaining on allocated treatment only: LS BMD mean percentage change LHRHa −3.0% and OP +7.9% (p < 0.001). Conclusions Transdermal oestradiol as a single agent produces castration levels of testosterone while mitigating BMD loss. These early data provide further supporting evidence for the ongoing phase 3 trial. Patient summary This study found that prostate cancer patients treated with transdermal oestradiol

  14. Prognostic Value of Abnormal p53 Expression in Locally Advanced Prostate Cancer Treated With Androgen Deprivation and Radiotherapy: A Study Based on RTOG 9202

    SciTech Connect

    Che Mingxin DeSilvio, Michelle; Pollack, Alan; Grignon, David J.; Venkatesan, Varagur Mohan; Hanks, Gerald E.; Sandler, Howard M.

    2007-11-15

    Purpose: The goal of this study was to verify the significance of p53 as a prognostic factor in Radiation Therapy Oncology Group 9202, which compared short-term androgen deprivation (STAD) with radiation therapy (RT) to long-term androgen deprivation + RT in men with locally advanced prostate cancer (Pca). Methods and Materials: Tumor tissue was sufficient for p53 analysis in 777 cases. p53 status was determined by immunohistochemistry. Abnormal p53 expression was defined as 20% or more tumor cells with positive nuclei. Univariate and multivariate Cox proportional hazards models were used to evaluate the relationships of p53 status to patient outcomes. Results: Abnormal p53 was detected in 168 of 777 (21.6%) cases, and was significantly associated with cause-specific mortality (adjusted hazard ratio [HR] = 1.89; 95% confidence interval (CI) 1.14 - 3.14; p = 0.014) and distant metastasis (adjusted HR = 1.72; 95% CI 1.13-2.62; p = 0.013). When patients were divided into subgroups according to assigned treatment, only the subgroup of patients who underwent STAD + RT showed significant correlation between p53 status and cause-specific mortality (adjusted HR = 2.43; 95% CI = 1.32-4.49; p = 0.0044). When patients were divided into subgroups according to p53 status, only the subgroup of patients with abnormal p53 showed significant association between assigned treatment and cause-specific mortality (adjusted HR = 3.81; 95% CI 1.40-10.37; p = 0.0087). Conclusions: Abnormal p53 is a significant prognostic factor for patients with prostate cancer who undergo short-term androgen deprivation and radiotherapy. Long-term androgen deprivation may significantly improve the cause-specific survival for those with abnormal p53.

  15. Toxicities Following Treatment with Bisphosphonates and Receptor Activator of Nuclear Factor-κB Ligand Inhibitors in Patients with Advanced Prostate Cancer

    PubMed Central

    Gartrell, Benjamin A.; Coleman, Robert E.; Fizazi, Karim; Miller, Kurt; Saad, Fred; Sternberg, Cora N.; Galsky, Matthew D.

    2015-01-01

    Context Advanced prostate cancer(PCa) is associated withskeletal complications, both as a result of bone metastases and because of fractures associated with fragility due to androgen-deprivation therapy (ADT). Osteoclast inhibitors are commonly used to reduce skeletal complications but are associated with a number of potential adverse events. Objective To review clinical trials of osteoclast inhibitors in advanced PCa, to discuss the adverse event profile of these agents, and to discuss strategies to address specific adverse events. Evidence acquisition PubMed was searched for reports of clinical trials of osteoclast inhibitors in advanced PCa. As zoledronic acid and denosumab are used most commonly in this disease, these trials were the focus. The literature was reviewed to identify key publications addressing the prevention and management of adverse events associated with these drugs. Evidence synthesis The major findings of the trials and the adverse events are discussed. Prevention and management of common adverse events are addressed. Conclusions Zoledronic acid prevents loss of bone mineral density associated with ADT and delays skeletal-related events in metastatic castration-resistant PCa (mCRPC). Denosumab reduces the incidence of fragility fractures associated with ADT, delays the onset of bone metastases in nonmetastatic castration-resistant disease, and is superior to zoledronic acid in the prevention of skeletal complications in mCRPC. Adverse events associated with both agents include osteonecrosis of the jaw and hypocalcemia. Hypocalcemia is more common with denosumab. Zoledronic acid requires dose modifications for renal insufficiency, is contraindicated in severe renal insufficiency, and has been associated with deterioration of renal function. Appropriate patient selection with close attention to dental health, supplementation with calcium and vitamin D, and monitoring of laboratory values are effective strategies to minimize the impact of adverse

  16. Circadian Disruption, Sleep Loss and Prostate Cancer Risk: A Systematic Review of Epidemiological Studies

    PubMed Central

    Sigurdardottir, Lara G.; Valdimarsdottir, Unnur A.; Fall, Katja; Rider, Jennifer R.; Lockley, Steven W.; Schernhammer, Eva S.; Mucci, Lorelei A.

    2012-01-01

    Disruption of the circadian system has been hypothesized to increase cancer risk, either due to direct disruption of the molecular machinery generating circadian rhythms or due to disruption of parameters controlled by the clock such as melatonin levels or sleep duration. This hypothesis has been studied in hormone-dependent cancers among women, but data are sparse regarding potential effects of circadian disruption on the risk of prostate cancer. This review systematically examines available data evaluating the effects of light at night, sleep patterns, and night shift work on prostate cancer risk. PMID:22564869

  17. High-Grade Prostatic Intraepithelial Neoplasia

    PubMed Central

    Bostwick, David G; Liu, Lina; Brawer, Michael K; Qian, Junqi

    2004-01-01

    High-grade prostatic intraepithelial neoplasia is considered the most likely precursor of prostatic carcinoma. The only method of detection is biopsy; prostatic intraepithelial neoplasia (PIN) does not significantly elevate serum prostate-specific antigen concentration and cannot be detected by ultra-sonography. The incidence of PIN in prostate biopsies averages 9% (range, 4%–16%), representing 115,000 new cases of PIN diagnosed each year in United States. PIN has a high predictive value as a marker for adenocarcinoma, and its identification warrants repeated biopsy for concurrent or subsequent invasive carcinoma. Carcinoma will develop in most patients with PIN within 10 years. PIN is associated with progressive abnormalities of phenotype and genotype that are intermediate between normal prostatic epithelium and cancer, indicating impairment of cell differentiation and regulatory control with advancing stages of prostatic carcinogenesis. Androgen deprivation therapy decreases the prevalence and extent of PIN, suggesting that this form of treatment may play a role in chemoprevention. PMID:16985598

  18. Precursors of prostate cancer.

    PubMed

    Bostwick, David G; Cheng, Liang

    2012-01-01

    High-grade prostatic intraepithelial neoplasia (PIN) is the only accepted precursor of prostatic adenocarcinoma, according to numerous studies of animal models and man; other proposed precursors include atrophy and malignancy-associated changes (with no morphologic changes). PIN is characterized by progressive abnormalities of phenotype and genotype that are intermediate between benign prostatic epithelium and cancer, indicating impairment of cell differentiation and regulatory control with advancing stages of prostatic carcinogenesis. The only method of detection of PIN is biopsy because it does not significantly elevate serum prostate-specific antigen concentration and cannot be detected by ultrasonography. The mean incidence of PIN in biopsies is 9% (range, 4%-16%), representing about 115,000 new cases of isolated PIN diagnosed each year in the United States. The clinical importance of PIN is its high predictive value as a marker for adenocarcinoma, and its identification warrants repeat biopsy for concurrent or subsequent carcinoma, especially when multifocal or observed in association with atypical small acinar proliferation (ASAP). Carcinoma develops in most patients with PIN within 10 years. Androgen deprivation therapy and radiation therapy decrease the prevalence and extent of PIN, suggesting that these forms of treatment may play a role in prevention of subsequent cancer. Multiple clinical trials to date of men with PIN have had modest success in delaying or preventing subsequent cancer. PMID:22212075

  19. Impact of Radiotherapy When Added to Androgen-Deprivation Therapy for Locally Advanced Prostate Cancer: Long-Term Quality-of-Life Outcomes From the NCIC CTG PR3/MRC PR07 Randomized Trial

    PubMed Central

    Brundage, Michael; Sydes, Matthew R.; Parulekar, Wendy R.; Warde, Padraig; Cowan, Richard; Bezjak, Andrea; Kirkbride, Peter; Parliament, Matthew; Moynihan, Clare; Bahary, Jean-Paul; Parmar, Mahesh K.B.; Sanders, Karen; Chen, Bingshu E.; Mason, Malcolm D.

    2015-01-01

    Purpose The NCIC CTG PR3/MRC PR07 randomized phase III trial compared androgen-deprivation therapy (ADT) alone versus ADT with radiotherapy (RT) for patients with locally advanced prostate cancer. This article reports the health-related quality-of-life (HRQOL) outcomes of this trial. Patients and Methods A total of 1,205 patients were randomly allocated to either ADT alone or ADT with RT. HRQOL was assessed at baseline and every 6 months thereafter using the European Organisation for Research and Treatment of Cancer Core Questionnaire and a prostate cancer–specific checklist or the Functional Assessment of Cancer Therapy–Prostate questionnaire. Mean changes from baseline scores for five function domains and nine symptom domains were analyzed as those most relevant to ADT and RT. The proportions of patients with improved, stable, or worsened HRQOL scores according to instrument-specific minimal important differences were calculated. Results Baseline questionnaires were completed by 1,028 patients (88%). At 6 months, RT had a statistically significant impact on mean score for bowel symptoms (P = .02), diarrhea (P < .001), urinary function (P = .003), and erectile dysfunction (P = .008); by 3 years, however, there were no significant between-group differences in any domain. Generalized linear mixed modeling revealed no significant between-arm differences in any of the function scales but showed significant deterioration in both arms over time for Functional Assessment of Cancer Therapy–Prostate total score, treatment outcome index, and physical and functional well-being. Conclusion The addition of RT to ADT for patients with locally advanced prostate cancer significantly improved overall survival and had only modest and transient negative impact on relevant domains of HRQOL. PMID:26014295

  20. Eosinophilic prostatitis and prostatic specific antigen.

    PubMed

    Liu, S; Miller, P D; Holmes, S A; Christmas, T J; Kirby, R S

    1992-01-01

    Eosinophilic prostatitis is a rare form of abacterial prostatitis with uncertain aetiology. Its clinical presentation, like other types of abacterial prostatitis, commonly mimics carcinoma of the prostate. Transrectal ultrasound may be helpful in the diagnosis of prostatitis but histological confirmation is necessary. Prostatic specific antigen has been widely used in the diagnosis and follow-up of patients with prostatic carcinoma. High levels of this antigen (greater than 30 micrograms/l) have been claimed to be highly specific for prostate cancer, although lesser elevations may also occur in patients with large benign prostate glands and in bacterial prostatitis. We report 3 patients with histologically proven eosinophilic prostatitis and high levels of prostatic specific antigen. This diagnosis may closely mimic carcinoma of the prostate and must be excluded by histological examination of biopsy material before treatment for presumed prostate carcinoma is initiated.

  1. The Role of Positron Emission Tomography With (68)Gallium (Ga)-Labeled Prostate-specific Membrane Antigen (PSMA) in the Management of Patients With Organ-confined and Locally Advanced Prostate Cancer Prior to Radical Treatment and After Radical Prostatectomy.

    PubMed

    Rai, Bhavan Prasad; Baum, Richard Paul; Patel, Amit; Hughes, Robert; Alonzi, Roberto; Lane, Tim; Adshead, Jim; Vasdev, Nikhil

    2016-09-01

    The role of positron emission tomography (PET) with (68)Gallium (Ga)-labeled prostate-specific membrane antigen (PSMA) imaging for prostate cancer is gaining prominence. Current imaging strategies, despite having progressed significantly, have limitations, in particular their ability to diagnose metastatic lymph node involvement. Preliminary results of PET with (68)Ga-labeled PSMA have shown encouraging results, particularly in the recurrent prostate cancer setting. Furthermore, the ability of PET with (68)Ga-labeled PSMA of playing a dual diagnostic and therapeutic setting (theranostics) is currently being investigated as well. PET with (68)Ga-labeled PSMA certainly has a role to play in bridging some of the voids in contemporary prostate cancer imaging tools. PMID:26790588

  2. Molecular Imaging of Prostate Cancer: PET Radiotracers

    PubMed Central

    Jadvar, Hossein

    2012-01-01

    OBJECTIVE Recent advances in the fundamental understanding of the complex biology of prostate cancer have provided an increasing number of potential targets for imaging and treatment. The imaging evaluation of prostate cancer needs to be tailored to the various phases of this remarkably heterogeneous disease. CONCLUSION In this article, I review the current state of affairs on a range of PET radiotracers for potential use in the imaging evaluation of men with prostate cancer. PMID:22826388

  3. Targeting prostate cancer stem cells for cancer therapy

    PubMed Central

    Wang, Guocan; Wang, Zhiwei; Sarkar, Fazlul H.; Wei, Wenyi

    2012-01-01

    Prostate cancer (PCa) is the most common malignant neoplasm in men and the second most frequent cause of cancer death for males in the United States. Recently, emerging evidence suggests that prostate cancer stem cells (CSCs) may play a critical role in the development and progression of PCa. Therefore, targeting prostate CSCs for the prevention of tumor progression and treatment of PCa could become a novel strategy for better treatment of patients diagnosed with PCa. In this review article, we will summarize the most recent advances in the prostate CSCs field, with particular emphasis on targeting prostate CSCs to treat prostate cancer. PMID:22369972

  4. Assessing the Role of Volumetric Modulated Arc Therapy (VMAT) Relative to IMRT and Helical Tomotherapy in the Management of Localized, Locally Advanced, and Post-Operative Prostate Cancer

    SciTech Connect

    Davidson, Melanie T.M.; Blake, Samuel J.; Batchelar, Deidre L.; Cheung, Patrick; Mah, Katherine

    2011-08-01

    Purpose: To quantify differences in treatment delivery efficiency and dosimetry between step-and-shoot intensity-modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT), and helical tomotherapy (HT) for prostate treatment. Methods and Materials: Twenty-five prostate cancer patients were selected retrospectively for this planning study. Treatment plans were generated for: prostate alone (n = 5), prostate + seminal vesicles (n = 5), prostate + seminal vesicles + pelvic lymph nodes (n = 5), prostate bed (n = 5), and prostate bed + pelvic lymph nodes (n = 5). Target coverage, dose homogeneity, integral dose, monitor units (MU), and sparing of organs at risk (OAR) were compared across techniques. Time required to deliver each plan was measured. Results: The dosimetric quality of IMRT, VMAT, and HT plans were comparable for target coverage (planning target volume V95%, clinical target volume V100% all >98.7%) and sparing of organs at risk (OAR) for all treatment groups. Although HT resulted in a slightly higher integral dose and mean doses to the OAR, it yielded a lower maximum dose to all OAR examined. VMAT resulted in reductions in treatment times over IMRT (mean = 75%) and HT (mean = 70%). VMAT required 15-38% fewer monitor units than IMRT over all treatment volumes, with the reduction per fraction ranging from 100-423 MU from the smallest to largest volumes. Conclusions: VMAT improves efficiency of delivery for equivalent dosimetric quality as IMRT and HT across various prostate cancer treatment volumes in the intact and postoperative settings.

  5. Efficacy and tolerability of 1- and 3-month leuprorelin acetate depot formulations (Eligard®/Depo-Eligard®) for advanced prostate cancer in daily practice: a Belgian prospective non-interventional study

    PubMed Central

    Michielsen, Dirk

    2014-01-01

    Introduction The 1-, 3- and 6- month biodegradable polymer matrix depot formulations of leuprorelin acetate (Eligard®/Depo-Eligard®, Astellas Pharma Inc/BV) were shown to reduce testosterone and prostate-specific antigen levels and to be well tolerated in patients with advanced prostate cancer in several clinical trials. This study aimed at evaluating the efficacy, safety and tolerability of the 1- and 3-month leuprorelin acetate depot formulations in daily clinical practice. Material and methods A prospective, open-label, non-interventional, phase IV study (MANTA) was conducted in 243 Belgian prostate cancer patients who had been prescribed the 1-month (7.5 mg) or 3-month (22.5 mg) leuprorelin acetate depot formulation. Patients were followed for at least 3 months. Results Median serum prostate-specific antigen levels were reduced by 95% from 12.0 ng/ml at baseline to 0.60 ng/ml after a median follow-up time of 132 days, while median testosterone levels were reduced by 94% from 360 ng/dl to 20 ng/dl. Partial or complete treatment response was observed in 83% of patients at the final visit (according to the physician's assessment). Ninety-two patients (37.86%) experienced treatment-emergent adverse events, with injection site-related reactions, hot flushes and tumor flare being the most common ones. Overall safety and tolerability of the leuprorelin acetate depot formulation were rated as good or excellent by 90% of physicians. Conclusions These data are consistent with efficacy and tolerability results from clinical trials. They confirm that the 1- and 3-month leuprorelin acetate depot formulations are well tolerated and reliably lower serum prostate-specific antigen and testosterone levels in routine clinical practice. PMID:25097577

  6. Prostatic carcinosarcoma with lung metastases.

    PubMed

    Furlan, Stefanie R; Kang, David J; Armas, Armando

    2013-01-01

    Carcinosarcoma of the prostate is an uncommon malignancy with poor long-term prognosis. The cancer is typically discovered at an advanced stage, and with less than 100 reported cases, there is limited literature concerning treatment options. Our patient presented with a history of benign prostatic hypertrophy, erectile dysfunction, and nocturia. Biopsy of his prostate indicated that the patient had prostatic adenocarcinoma, but histopathology after prostatectomy revealed carcinosarcoma. It has been over six years since this patient's diagnosis of carcinosarcoma. Over this span of time, he has received a radical prostatectomy, radiotherapy, and androgen ablative therapy. The patient also developed multiple lung metastases that have been treated with video-assisted thoracic surgery and stereotactic body radiosurgery. Overall, he has remained unimpaired and in good condition despite his aggressive form of cancer. PMID:24294528

  7. Prostatic carcinosarcoma with lung metastases.

    PubMed

    Furlan, Stefanie R; Kang, David J; Armas, Armando

    2013-01-01

    Carcinosarcoma of the prostate is an uncommon malignancy with poor long-term prognosis. The cancer is typically discovered at an advanced stage, and with less than 100 reported cases, there is limited literature concerning treatment options. Our patient presented with a history of benign prostatic hypertrophy, erectile dysfunction, and nocturia. Biopsy of his prostate indicated that the patient had prostatic adenocarcinoma, but histopathology after prostatectomy revealed carcinosarcoma. It has been over six years since this patient's diagnosis of carcinosarcoma. Over this span of time, he has received a radical prostatectomy, radiotherapy, and androgen ablative therapy. The patient also developed multiple lung metastases that have been treated with video-assisted thoracic surgery and stereotactic body radiosurgery. Overall, he has remained unimpaired and in good condition despite his aggressive form of cancer.

  8. Health-Related Quality of Life in Patients With Locally Advanced Prostate Cancer After 76 Gy Intensity-Modulated Radiotherapy vs. 70 Gy Conformal Radiotherapy in a Prospective and Longitudinal Study

    SciTech Connect

    Lips, Irene Dehnad, Human; Kruger, Arto Boeken; Moorselaar, Jeroen van; Heide, Uulke van; Battermann, Jan; Vulpen, Marco van

    2007-11-01

    Purpose: To compare quality of life (QoL) after 70 Gy conformal radiotherapy with QoL after 76 Gy intensity-modulated radiotherapy (IMRT) in patients with locally advanced prostate carcinoma. Methods and Materials: Seventy-eight patients with locally advanced prostate cancer were treated with 70 Gy three-field conformal radiotherapy, and 92 patients received 76 Gy IMRT with fiducial markers for position verification. Quality of life was measured by RAND-36, the European Organization for Research and Treatment of Cancer core questionnaire (EORTC QLQ-C30(+3)), and the prostate-specific EORTC QLQ-PR25, before radiotherapy (baseline) and 1 month and 6 months after treatment. Quality of life changes in time (baseline vs. 1 month and baseline vs. 6 months) of {>=}10 points were considered clinically relevant. Results: Differences between the treatment groups for QoL changes over time occurred in several QoL domains. The 76-Gy group revealed no significant deterioration in QoL compared with the 70-Gy group. The IMRT 76-Gy group even demonstrated a significantly better change in QoL from baseline to 1 month in several domains. The conformal 70-Gy group revealed temporary deterioration in pain, role functioning, and urinary symptoms; for the IMRT 76-Gy group a better QoL in terms of change in health existed after 1 month, which persisted after 6 months. For both treatment groups temporary deterioration in physical role restriction occurred after 1 month, and an improvement in emotional role restriction occurred after 6 months. Sexual activity was reduced after treatment for both groups and remained decreased after 6 months. Conclusions: Intensity-modulated radiotherapy and accurate position verification seem to provide a possibility to increase the radiation dose for prostate cancer without deterioration in QoL.

  9. Benign prostate hyperplasia (BPH) - resources

    MedlinePlus

    Resources - benign prostatic hyperplasia (BPH); Prostate enlargement resources; BPH resources ... organizations provide information on benign prostatic hyperplasia ( prostate enlargement ): National Kidney and Urologic Diseases Information Clearinghouse -- www. ...

  10. Prostate Cancer

    PubMed Central

    Vickers, Andrew J.; Lilja, Hans

    2010-01-01

    Two groundbreaking trials have this year reported conflicting results as to the benefit of screening for prostate cancer. Careful interpretation in the light of contemporary data might, however, reveal the true value of this intervention. PMID:19498406

  11. Enlarged prostate

    MedlinePlus

    ... Possible side effects include decreased sex drive and impotence . Antibiotics may be prescribed to treat chronic prostatitis ( ... less-invasive procedures carry a lower risk for impotence and incontinence than TURP, although the risk with ...

  12. Prostatitis - bacterial

    MedlinePlus

    ... emptying the bladder Foul-smelling urine Weak urine stream Other symptoms that may occur with this condition: ... the risk of spreading bacteria into the blood stream. The exam may reveal that the prostate is: ...

  13. Current Perspectives in Prostate Cancer Vaccines

    PubMed Central

    Arlen, Philip M.; Gulley, James L.

    2012-01-01

    The use of vaccines as a potential therapeutic modality for the treatment of cancer has been extensively studied. Recent advances include identification and characterization of tumor-associated antigens, novel vaccine delivery systems, and the combination of vaccines with immune stimulants and other therapeutic modalities. Immunotherapy as a modality for treatment of prostate cancer has received significant attention. There are several characteristics of prostate cancer that make it an ideal target for immunotherapy. Prostate cancer’s relative indolence allows sufficient time to generate immune responses, which may take weeks or months to mount. In addition, prostate cancer-associated antigens direct the immune response to prostate cancer cells, thus sparing normal vital tissue. This review focuses on promising new vaccines and novel perspectives in the treatment of prostate cancer. PMID:19719454

  14. Prostate Cancer Imaging with Novel PET Tracers.

    PubMed

    Lindenberg, Liza; Choyke, Peter; Dahut, William

    2016-03-01

    Molecular imaging of prostate cancer is in a dynamic phase of development. Currently approved techniques are limited and researchers have been working on novel agents to improve accuracy in targeting and detecting prostate tumors. In addition, the complexity of various prostate cancer states also contributes to the challenges in evaluating suitable radiotracer candidates. We have highlighted nuclear medicine tracers that focus on mechanisms involved in bone metastasis, prostate cancer cell membrane synthesis, amino acid analogs, androgen analogs, and the prostate specific membrane antigen. Encouraging results with many of these innovative radiotracer compounds will not only advance diagnostic capabilities for prostate cancer but open opportunities for theranostic applications to treat this worldwide malignancy. PMID:26874530

  15. [Chemotherapy for prostate cancer].

    PubMed

    Rauchenwald, Michael; De Santis, Maria; Fink, Eleonore; Höltl, Wolfgang; Kramer, Gero; Marei, Isabella-Carolina; Neumann, Hans-Jörg; Reissigl, Andreas; Schmeller, Nikolaus; Stackl, Walter; Hobisch, Alfred; Krainer, Michael

    2008-01-01

    For many years the benefit of chemotherapy in patients with prostate cancer was thought to be limited to palliation of late-stage disease, and thus this treatment option only became involved in patient care towards the end of the disease process, if at all. However, two landmark phase-III trials with docetaxel-based therapy (TAX 327 and Southwest Oncology Group, SWOG, 9916) have shown a survival benefit for patients with hormone refractory prostate cancer (HRPC) thus prompting a change in patterns of care. With raising interest for chemotherapeutic options and clinical trials for new drugs and new indications (neoadjuvant therapy, adjuvant therapy, increasing PSA levels after local treatment, and hormone sensitive cancer) under way our goal was to review within the context of a multidisciplinary team the available evidence and explore the standard for the medical treatment of prostate cancer outside of clinical trials. We are carefully evaluating the current treatment recommendations based on the available evidence and highlight potential future treatment options but also discuss important clinical topics (treatment until progression versus the advantage of chemo holidays, definition of particular patient subgroups and potential second line options) for which there are no clear cut answers to date. The role and importance of radiotherapy, biphosphonate treatment and the medical management of pain and side effects is also discussed. The multitude of treatment options for patients with advanced prostate cancer clearly asks for a close collaboration between urologists, medical oncologists and radiation therapists. PMID:18726672

  16. Small cell carcinoma of the prostate

    PubMed Central

    Nadal, Rosa; Schweizer, Michael; Kryvenko, Oleksandr N.; Epstein, Jonathan I.; Eisenberger, Mario A.

    2015-01-01

    Pure small-cell carcinoma (SCC) of the prostate is a rare entity and one of the most aggressive malignancies of the prostate. Histologically, prostatic SCCs of the prostate are part of a spectrum of anaplastic tumours of the prostate and are similar to SCCs of the lungs. In most cases, SCC of the prostate is associated with conventional prostatic adenocarcinoma. Both components of these mixed tumours frequently share molecular alterations such as ERG gene rearrangements or AURKA and MYCN amplifications, suggesting a common clonal origin. The clinical behaviour of small-cell prostate carcinomas is characterized by extensive local disease, visceral disease, and low PSA levels despite large metastatic burden. Commonly, the emergence of the SCC occurs in patients with high-grade adenocarcinoma who are often treated with androgen deprivation treatment (ADT). However, SCCs do not usually benefit from ADT. A biopsy of accessible lesions is strongly recommended to identify those with SCC pathological features, as management is undoubtedly affected by this finding. Chemotherapy is the standard approach for treating patients with either localized or advanced prostatic SCC. Despite the emergence of more-aggressive treatment modalities, the prognosis of men with prostatic SCC remains dismal. PMID:24535589

  17. Stokes polarimetry imaging of dog prostate tissue

    NASA Astrophysics Data System (ADS)

    Kim, Jihoon; Johnston, William K., III; Walsh, Joseph T., Jr.

    2010-02-01

    Prostate cancer is the second leading cause of death in the United States in 2009. Radical prostatectomy (complete removal of the prostate) is the most common treatment for prostate cancer, however, differentiating prostate tissue from adjacent bladder, nerves, and muscle is difficult. Improved visualization could improve oncologic outcomes and decrease damage to adjacent nerves and muscle important for preservation of potency and continence. A novel Stokes polarimetry imaging (SPI) system was developed and evaluated using a dog prostate specimen in order to examine the feasibility of the system to differentiate prostate from bladder. The degree of linear polarization (DOLP) image maps from linearly polarized light illumination at different visible wavelengths (475, 510, and 650 nm) were constructed. The SPI system used the polarization property of the prostate tissue. The DOLP images allowed advanced differentiation by distinguishing glandular tissue of prostate from the muscular-stromal tissue in the bladder. The DOLP image at 650 nm effectively differentiated prostate and bladder by strong DOLP in bladder. SPI system has the potential to improve surgical outcomes in open or robotic-assisted laparoscopic removal of the prostate. Further in vivo testing is warranted.

  18. Prostate Cancer Screening (Beyond the Basics)

    MedlinePlus

    ... complications of advanced disease. ● For men with an aggressive prostate cancer, the best chance for curing it ... body. However, many early-stage cancers are not aggressive, and the five-year survival will be nearly ...

  19. A Urologist's Personal View of Prostate Cancer.

    PubMed

    Schellhammer, Paul F

    2016-09-01

    A urologist's personal experience with multiple surgical, hormonal, and radio/immunotherapeutic options for the treatment of advanced prostate cancer and thoughts on the role of old and new therapies. PMID:27635283

  20. New developments in metastatic prostate cancer therapy.

    PubMed

    Manickavasagar, Thubeena; Gilson, Clare; Chowdhury, Simon; Kirby, Roger

    2015-04-01

    Metastatic prostate cancer is still commonly a lethal condition. The concept that 'men with prostate cancer die with rather than of their cancer' has been shown to be false. It is estimated that 10-20% of men in the UK present with locally advanced disease. Median overall survival remains only 3.5 years for men presenting with metastatic disease. The use of LHRH analogues to achieve medical castration has become the gold standard for both locally advanced prostate cancer, combined with radiotherapy, and metastatic disease. Androgen deprivation therapy (ADT) is the standard first-line treatment for advanced disease resulting in improvements in symptoms, radiological findings and PSA levels. Ultimately the majority of men with advanced prostate cancer will develop resistance to ADT Docetaxel is the standard first-line therapy recommended by international guidelines for patients with symptomatic metastatic castrate refractory prostate cancer who are suitable candidates for chemotherapy. More than 90% of patients with castrate refractory prostate cancer have bone metastases. Radium-223 dichloride is a novel alpha-emitting radiopharmaceutical agent, which mimics calcium and therefore targets bone metastases. It is indicated in patients with metastatic castrate refractory prostate cancer who have symptomatic bone metastases without visceral metastases.

  1. Evolution of the concept of focal therapy for prostate cancer.

    PubMed

    Tsivian, Matvey; Abern, Michael R; Polascik, Thomas J

    2013-01-01

    The landscape of prostate cancer has been rapidly evolving, and technological advances in imaging and biopsy tools offer novel approaches to focal therapy. In this dynamic environment, the role of focal therapy for prostate cancer is being shaped both by advances in technology and by reconsidering the epidemiological and outcomes data for available treatments. Here we focus on the evolution of the concept of focal therapy and its potential roles in the management of prostate cancer.

  2. The 21st Annual Prostate Cancer Foundation Scientific Retreat report.

    PubMed

    Miyahira, Andrea K; Simons, Jonathan W; Soule, Howard R

    2015-08-01

    The 21st Annual Prostate Cancer Foundation (PCF) Scientific Retreat was held from October 23-25, 2014, in Carlsbad, CA. This event is the world's foremost scientific meeting focusing on prostate cancer and brings together leading basic, translational and clinical researchers in prostate cancer and other diverse disciplines to discuss the newest findings most likely to advance the understanding of prostate cancer and the clinical care of prostate cancer patients. This year's meeting highlighted themes including: (i) research integrity and standards for scientific reproducibility; (ii) prostate cancer disparities; (iii) mechanisms and models of prostate cancer progression and dormancy; (iv) mechanisms of therapeutic resistance; and (v) advancements in precision medicine treatments, treatment models, and predictive and prognostic biomarkers.

  3. Bisphenol A Promotes Human Prostate Stem-Progenitor Cell Self-Renewal and Increases In Vivo Carcinogenesis in Human Prostate Epithelium

    PubMed Central

    Hu, Wen-Yang; Shi, Guang-Bin; Hu, Dan-Ping; Majumdar, Shyama; Li, Guannan; Huang, Ke; Nelles, Jason L.; Ho, Shuk-Mei; Walker, Cheryl Lyn; Kajdacsy-Balla, Andre; van Breemen, Richard B.

    2014-01-01

    Previous studies in rodent models have shown that early-life exposure to bisphenol A (BPA) reprograms the prostate and enhances its susceptibility to hormonal carcinogenesis with aging. To determine whether the human prostate is similarly sensitive to BPA, the current study used human prostate epithelial stem-like cells cultured from prostates of young, disease-free donors. Similar to estradiol-17β (E2), BPA increased stem-progenitor cell self-renewal and expression of stem-related genes in a dose-dependent manner. Further, 10 nM BPA and E2 possessed equimolar membrane-initiated signaling with robust induction of p-Akt and p-Erk at 15 minutes. To assess in vivo carcinogenicity, human prostate stem-progenitor cells combined with rat mesenchyme were grown as renal grafts in nude mice, forming normal human prostate epithelium at 1 month. Developmental BPA exposure was achieved through oral administration of 100 or 250 μg BPA/kg body weight to hosts for 2 weeks after grafting, producing free BPA levels of 0.39 and 1.35 ng/mL serum, respectively. Carcinogenesis was driven by testosterone plus E2 treatment for 2 to 4 months to model rising E2 levels in aging men. The incidence of high-grade prostate intraepithelial neoplasia and adenocarcinoma markedly increased from 13% in oil-fed controls to 33% to 36% in grafts exposed in vivo to BPA (P < .05). Continuous developmental BPA exposure through in vitro (200 nM) plus in vivo (250 μg/kg body weight) treatments increased high-grade prostate intraepithelial neoplasia/cancer incidence to 45% (P < .01). Together, the present findings demonstrate that human prostate stem-progenitor cells are direct BPA targets and that developmental exposure to BPA at low doses increases hormone-dependent cancer risk in the human prostate epithelium. PMID:24424067

  4. PSA and beyond: alternative prostate cancer biomarkers

    PubMed Central

    2016-01-01

    Background The use of biomarkers for prostate cancer screening, diagnosis and prognosis has the potential to improve the clinical management of the patients. Owing to inherent limitations of the biomarker prostate-specific antigen (PSA), intensive efforts are currently directed towards a search for alternative prostate cancer biomarkers, particularly those that can predict disease aggressiveness and drive better treatment decisions. Methods A literature search of Medline articles focused on recent and emerging advances in prostate cancer biomarkers was performed. The most promising biomarkers that have the potential to meet the unmet clinical needs in prostate cancer patient management and/or that are clinically implemented were selected. Conclusions With the advent of advanced genomic and proteomic technologies, we have in recent years seen an enormous spurt in prostate cancer biomarker research with several promising alternative biomarkers being discovered that show an improved sensitivity and specificity over PSA. The new generation of biomarkers can be tested via serum, urine, or tissue-based assays that have either received regulatory approval by the US Food and Drug Administration or are available as Clinical Laboratory Improvement Amendments-based laboratory developed tests. Additional emerging novel biomarkers for prostate cancer, including circulating tumor cells, microRNAs and exosomes, are still in their infancy. Together, these biomarkers provide actionable guidance for prostate cancer risk assessment, and are expected to lead to an era of personalized medicine. PMID:26790878

  5. Progress in prostate cancer imaging

    PubMed Central

    Gulley, James L.; Emberton, Mark; Kurhanewicz, John; Choyke, Peter

    2013-01-01

    There are multiple new technologies being developed for imaging of advanced prostate cancer. This Seminar article highlights several of these emerging modalities that were discussed at the Society of Urologic Oncology annual meeting in Bethesda, MD. © 2012 Elsevier Inc. All rights reserved. PMID:23218070

  6. Localized Prostate Cancer

    MedlinePlus

    ... a decision aid for men with clinically localized prostate cancer (available at http://effectivehealthcare.ahrq.gov/prostate_da) ... A Decision Aid for Men With Clinically Localized Prostate Cancer Page 1 of 24 Introduction Men with clinically ...

  7. Prostate Cancer Prevention

    MedlinePlus

    ... finasteride who did have prostate cancer had more aggressive tumors . The number of deaths from prostate cancer ... men that did not. The number of less aggressive prostate cancers was lower, but the number of ...

  8. Prostate cancer

    MedlinePlus

    ... spread of the cancer. But it does not cure the cancer. If prostate cancer spreads even after hormone therapy, ... the Gleason score) when you are diagnosed. A cure is possible if the cancer has not spread. Hormone treatment can improve survival, ...

  9. Development of New Treatments for Prostate Cancer

    SciTech Connect

    DiPaola, R. S.; Abate-Shen, C.; Hait, W. N.

    2005-02-01

    The Dean and Betty Gallo Prostate Cancer Center (GPCC) was established with the goal of eradicating prostate cancer and improving the lives of men at risk for the disease through research, treatment, education and prevention. GPCC was founded in the memory of Dean Gallo, a beloved New Jersey Congressman who died tragically of prostate cancer diagnosed at an advanced stage. GPCC unites a team of outstanding researchers and clinicians who are committed to high-quality basic research, translation of innovative research to the clinic, exceptional patient care, and improving public education and awareness of prostate cancer. GPCC is a center of excellence of The Cancer Institute of New Jersey, which is the only NCI-designated comprehensive cancer center in the state. GPCC efforts are now integrated well as part of our Prostate Program at CINJ, in which Dr. Robert DiPaola and Dr. Cory Abate-Shen are co-leaders. The Prostate Program unites 19 investigators from 10 academic departments who have broad and complementary expertise in prostate cancer research. The overall goal and unifying theme is to elucidate basic mechanisms of prostate growth and oncogenesis, with the ultimate goal of promoting new and effective strategies for the eradication of prostate cancer. Members' wide range of research interests collectively optimize the chances of providing new insights into normal prostate biology and unraveling the molecular pathophysiology of prostate cancer. Cell culture and powerful animal models developed by program members recapitulate the various stages of prostate cancer progression, including prostatic intraepithelial neoplasia, adenocarcinoma, androgen-independence, invasion and metastases. These models promise to further strengthen an already robust program of investigator-initiated therapeutic clinical trials, including studies adopted by national cooperative groups. Efforts to translate laboratory results into clinical studies of early detection and chemoprevention

  10. Bone-targeting agents in prostate cancer.

    PubMed

    Suzman, Daniel L; Boikos, Sosipatros A; Carducci, Michael A

    2014-09-01

    Bone metastases are present in the vast majority of men with advanced prostate cancer, representing the main cause for morbidity and mortality. Recurrent or metastatic disease is managed initially with androgen deprivation but the majority of the patients eventually will progress to castration-resistant prostate cancer, with patients developing bone metastases in most of the cases. Survival and growth of the metastatic prostate cancer cells is dependent on a complex microenvironment (onco-niche) that includes the osteoblasts, the osteoclasts, the endothelium, and the stroma. This review summarizes agents that target the pathways involved in this complex interaction between prostate cancer and bone microenvironment and aim to transform lethal metastatic prostate cancer into a chronic disease.

  11. Bone-targeting agents in prostate cancer

    PubMed Central

    Suzman, Daniel L.; Boikos, Sosipatros A.; Carducci, Michael A.

    2014-01-01

    Bone metastases are present in the vast majority of men with advanced prostate cancer, representing the main cause for morbidity and mortality. Recurrent or metastatic disease is managed initially with androgen deprivation but the majority of the patients eventually will progress to castration-resistant prostate cancer, with patients developing bone metastases in most of the cases. Survival and growth of the metastatic prostate cancer cells is dependent on a complex microenvironment (onco-niche) that includes the osteoblasts, the osteoclasts, the endothelium, and the stroma. This review summarizes agents that target the pathways involved in this complex interaction between prostate cancer and bone micro-environment and aim to transform lethal metastatic prostate cancer into a chronic disease. PMID:24398856

  12. Prostatitis and male infertility.

    PubMed

    Alshahrani, Saad; McGill, John; Agarwal, Ashok

    2013-11-01

    The prostate gland plays an important role in male reproduction. Inflammation of the prostate gland (prostatitis) is a common health problem affecting many young and middle aged men. Prostatitis is considered a correctable cause of male infertility, but the pathophysiology and appropriate treatment options of prostatitis in male infertility remain unclear. This literature review will focus on current data regarding prostatitis and its impact on male infertility.

  13. Dietary Antioxidants and Prostate Cancer: A Review

    PubMed Central

    Vance, Terrence M.; Su, Joseph; Fontham, Elizabeth T. H.; Koo, Sung I.; Chun, Ock K.

    2013-01-01

    Prostate cancer is the most common non-cutaneous cancer in men in the United States. Several studies have examined the relationship between prostate cancer and antioxidants; however, the results of these studies are inconsistent. This article provides a systematic review of studies on prostate cancer and antioxidant intake from diet and supplements. Tea and coffee appear to offer protection against advanced prostate cancer. Different forms of vitamin E appear to exert different effects on prostate cancer, with alpha-tocopherol potentially increasing and gamma-tocopherol potentially decreasing risk of the disease. There is no strong evidence for a beneficial effect of selenium, vitamin C, or beta-carotene, while lycopene appears to be negatively associated with risk of the disease. The effect of dietary antioxidants on prostate cancer remains undefined and inconclusive, with different antioxidants affecting prostate cancer risk differentially. Further studies are needed to clarify the relationship between antioxidants and prostate cancer risk and to delineate the underlying mechanisms. PMID:23909722

  14. Glycogen Synthase Kinase-3: A Potential Preventive Target for Prostate Cancer Management

    PubMed Central

    Li, Benyi; Thrasher, J. Brantley; Terranova, Paul

    2016-01-01

    Prostate cancers are the frequently diagnosed cancers in men and patients with metastatic disease only have 28% chance for 5-year survival. Patients with low risk tumors are subjected to active surveillance while high risk cases are actively treated. Unfortunately, there is no cure for late-stage patients. Glycogen synthase kinase-3 (GSK-3, α and β) is a protein serine/threonine kinase and has diverse cellular functions and numerous substrates. Accumulating evidence indicates that GSK-3α is mainly expressed in low-risk prostate cancers and is related to hormone-dependent androgen receptor (AR)-mediated gene expression, while GSK-3β is mainly expressed in high-risk prostate cancers and is related to hormone-independent AR-mediated gene expression. GSK-3 has been demonstrated as a positive regulator in AR transactivation and prostate cancer growth independent of the Wnt/β-catenin pathway. Different types of GSK-3 inhibitors including lithium show promising results in suppressing tumor growth in different animal models of prostate cancer. Importantly, clinical use of lithium is associated with reduced cancer incidence in psychiatric patients. Taken together, GSK-3 inhibition might be implicated in prostate cancer management as a preventive treatment. PMID:26051358

  15. Beyond Prostate Adenocarcinoma: Expanding the Differential Diagnosis in Prostate Pathologic Conditions.

    PubMed

    Li, Yi; Mongan, John; Behr, Spencer C; Sud, Seema; Coakley, Fergus V; Simko, Jeffry; Westphalen, Antonio C

    2016-01-01

    Recent advances in magnetic resonance (MR) imaging of the prostate gland have dramatically improved the ability to detect and stage adenocarcinoma of the prostate, one of the most frequently diagnosed cancers in men and one of the most frequently diagnosed pathologic conditions of the prostate gland. A wide variety of nonadenocarcinoma diseases can also be seen with MR imaging, ranging from benign to malignant diseases, as well as infectious and inflammatory manifestations. Many of these diseases have distinctive imaging features that allow differentiation from prostate acinar adenocarcinoma. Early recognition of these entities produces a more accurate differential diagnosis and may enable more expeditious clinical workup. Benign neoplasms of the prostate include plexiform neurofibroma and cystadenoma, both of which demonstrate distinctive imaging features. Stromal neoplasms of uncertain malignant potential are rare tumors of uncertain malignant potential that are often difficult to distinguish at imaging from more-malignant prostate sarcomas. Other malignant neoplasms of the prostate include urothelial carcinoma, primary prostatic carcinoid, carcinosarcoma, endometrioid or ductal adenocarcinoma, and mucinous adenocarcinoma. Prostatic infections can lead to abscesses of pyogenic, tuberculous, or fungal origins. Finally, miscellaneous idiopathic disorders of the prostate include amyloidosis, exophytic benign prostatic hyperplasia, and various congenital cysts. Considerable overlap can exist in the clinical history and imaging findings associated with these prostate pathologic conditions, and biopsy is often required for ultimate confirmation of the diagnosis. However, many diagnoses, including cystadenoma, mucinous adenocarcinoma, sarcoma, and abscesses, have distinct imaging features, which can enable the informed radiologist to identify the diagnosis and recommend appropriate clinical workup and management. (©)RSNA, 2016. PMID:27315446

  16. Mapping of nodal disease in locally advanced prostate cancer: Rethinking the clinical target volume for pelvic nodal irradiation based on vascular rather than bony anatomy

    SciTech Connect

    Shih, Helen A. . E-mail: hshih@partners.org; Harisinghani, Mukesh; Zietman, Anthony L.; Wolfgang, John A.; Saksena, Mansi; Weissleder, Ralph

    2005-11-15

    Purpose: Toxicity from pelvic irradiation could be reduced if fields were limited to likely areas of nodal involvement rather than using the standard 'four-field box.' We employed a novel magnetic resonance lymphangiographic technique to highlight the likely sites of occult nodal metastasis from prostate cancer. Methods and Materials: Eighteen prostate cancer patients with pathologically confirmed node-positive disease had a total of 69 pathologic nodes identifiable by lymphotropic nanoparticle-enhanced MRI and semiquantitative nodal analysis. Fourteen of these nodes were in the para-aortic region, and 55 were in the pelvis. The position of each of these malignant nodes was mapped to a common template based on its relation to skeletal or vascular anatomy. Results: Relative to skeletal anatomy, nodes covered a diffuse volume from the mid lumbar spine to the superior pubic ramus and along the sacrum and pelvic side walls. In contrast, the nodal metastases mapped much more tightly relative to the large pelvic vessels. A proposed pelvic clinical target volume to encompass the region at greatest risk of containing occult nodal metastases would include a 2.0-cm radial expansion volume around the distal common iliac and proximal external and internal iliac vessels that would encompass 94.5% of the pelvic nodes at risk as defined by our node-positive prostate cancer patient cohort. Conclusions: Nodal metastases from prostate cancer are largely localized along the major pelvic vasculature. Defining nodal radiation treatment portals based on vascular rather than bony anatomy may allow for a significant decrease in normal pelvic tissue irradiation and its associated toxicities.

  17. Systematic Structure Modifications of Multi-target Prostate Cancer Drug Candidate Galeterone to Produce Novel Androgen Receptor Down-regulating Agents as an Approach to Treatment of Advanced Prostate Cancer

    PubMed Central

    Purushottamachar, Puranik; Godbole, Abhijit M.; Gediya, Lalji K.; Martin, Marlena S.; Vasaitis, Tadas S.; Kwegyir-Afful, Andrew K.; Ramalingam, Senthilmurugan; Ates-Alagoz, Zeynep; Njar, Vincent C. O.

    2013-01-01

    As part of our program to explore the influence of small structural modifications of our drug candidate, 3β-(hydroxy)-17-(1H-benzimidazol-1-yl)-androsta-5,16-diene (galeterone, 5) on the modulation of the androgen receptor (AR), we have prepared and evaluated a series of novel C-3, C-16 and C-17 analogs. Using structure activity analysis, we established that the benzimidazole moiety at C-17 is essential and optimal and also that hydrophilic and heteroaromatic groups at C-3 enhance both anti-proliferative (AP) and AR degrading (ARD) activities. The most potent anti-proliferative compounds were 3β-(1H-imidazole-1-carboxylate)- 17-(1H-benzimidazol-1-yl)-androsta-5,16-diene (47), 3-((EZ)-hydroximino)-17-(1Hbenzimidazol- 1-yl)-androsta-4,16-diene (36), 3β-(pyridine-4-carboxylate)-17-(1H-benzimidazol- 1-yl)-androsta-5,16-diene (43), with GI50 values of 0.87, 1.91 and 2.57 μM, respectively. Compared to 5, compound 47 was 4- and 8-fold more potent with respect to AP and ARD activities, respectively. Importantly, we also discovered that our compounds, including 5, 36, 43 and 47 could degrade both full-length and truncated AR in CWR22rv1 human prostate cancer cells. With these activities, their potential for development as new drugs for the treatment of all forms of prostate cancer. PMID:23713567

  18. Chronic administration during early adulthood does not alter the hormonally-dependent disruptive effects of delta-9-tetrahydrocannabinol (Δ9-THC) on complex behavior in female rats.

    PubMed

    Winsauer, Peter J; Sutton, Jessie L

    2014-02-01

    This study examined whether chronic Δ(9)-THC during early adulthood would produce the same hormonally-dependent deficits in learning that are produced by chronic Δ(9)-THC during adolescence. To do this, either sham-operated (intact) or ovariectomized (OVX) female rats received daily saline or 5.6 mg/kg of Δ(9)-THC i.p. for 40 days during early adulthood. Following chronic administration, and a drug-free period to train both a learning and performance task, acute dose-effect curves for Δ(9)-THC (0.56-10 mg/kg) were established in each of the four groups (intact/saline, intact/THC, OVX/saline and OVX/THC). The dependent measures of responding under the learning and performance tasks were the overall response rate and the percentage of errors. Although the history of OVX and chronic Δ(9)-THC in early adulthood did not significantly affect non-drug or baseline behavior under the tasks, acute administration of Δ(9)-THC produced both rate-decreasing and error-increasing effects on learning and performance behavior, and these effects were dependent on their hormone condition. More specifically, both intact groups were more sensitive to the rate-decreasing and error-increasing effects of Δ(9)-THC than the OVX groups irrespective of chronic Δ(9)-THC administration, as there was no significant main effect of chronic treatment and no significant interaction between chronic treatment (saline or Δ(9)-THC) and the dose of Δ(9)-THC administered as an adult. Post mortem examination of 10 brain regions also indicated there were significant differences in agonist-stimulated GTPγS binding across brain regions, but no significant effects of chronic treatment and no significant interaction between the chronic treatment and cannabinoid signaling. Thus, acute Δ(9)-THC produced hormonally-dependent effects on learning and performance behavior, but a period of chronic administration during early adulthood did not alter these effects significantly, which is contrary to what we

  19. Prostate CT segmentation method based on nonrigid registration in ultrasound-guided CT-based HDR prostate brachytherapy

    PubMed Central

    Yang, Xiaofeng; Rossi, Peter; Ogunleye, Tomi; Marcus, David M.; Jani, Ashesh B.; Mao, Hui; Curran, Walter J.; Liu, Tian

    2014-01-01

    Purpose: The technological advances in real-time ultrasound image guidance for high-dose-rate (HDR) prostate brachytherapy have placed this treatment modality at the forefront of innovation in cancer radiotherapy. Prostate HDR treatment often involves placing the HDR catheters (needles) into the prostate gland under the transrectal ultrasound (TRUS) guidance, then generating a radiation treatment plan based on CT prostate images, and subsequently delivering high dose of radiation through these catheters. The main challenge for this HDR procedure is to accurately segment the prostate volume in the CT images for the radiation treatment planning. In this study, the authors propose a novel approach that integrates the prostate volume from 3D TRUS images into the treatment planning CT images to provide an accurate prostate delineation for prostate HDR treatment. Methods: The authors’ approach requires acquisition of 3D TRUS prostate images in the operating room right after the HDR catheters are inserted, which takes 1–3 min. These TRUS images are used to create prostate contours. The HDR catheters are reconstructed from the intraoperative TRUS and postoperative CT images, and subsequently used as landmarks for the TRUS–CT image fusion. After TRUS–CT fusion, the TRUS-based prostate volume is deformed to the CT images for treatment planning. This method was first validated with a prostate-phantom study. In addition, a pilot study of ten patients undergoing HDR prostate brachytherapy was conducted to test its clinical feasibility. The accuracy of their approach was assessed through the locations of three implanted fiducial (gold) markers, as well as T2-weighted MR prostate images of patients. Results: For the phantom study, the target registration error (TRE) of gold-markers was 0.41 ± 0.11 mm. For the ten patients, the TRE of gold markers was 1.18 ± 0.26 mm; the prostate volume difference between the authors’ approach and the MRI-based volume was 7.28% ± 0

  20. Prostate CT segmentation method based on nonrigid registration in ultrasound-guided CT-based HDR prostate brachytherapy

    SciTech Connect

    Yang, Xiaofeng Rossi, Peter; Ogunleye, Tomi; Marcus, David M.; Jani, Ashesh B.; Curran, Walter J.; Liu, Tian; Mao, Hui

    2014-11-01

    Purpose: The technological advances in real-time ultrasound image guidance for high-dose-rate (HDR) prostate brachytherapy have placed this treatment modality at the forefront of innovation in cancer radiotherapy. Prostate HDR treatment often involves placing the HDR catheters (needles) into the prostate gland under the transrectal ultrasound (TRUS) guidance, then generating a radiation treatment plan based on CT prostate images, and subsequently delivering high dose of radiation through these catheters. The main challenge for this HDR procedure is to accurately segment the prostate volume in the CT images for the radiation treatment planning. In this study, the authors propose a novel approach that integrates the prostate volume from 3D TRUS images into the treatment planning CT images to provide an accurate prostate delineation for prostate HDR treatment. Methods: The authors’ approach requires acquisition of 3D TRUS prostate images in the operating room right after the HDR catheters are inserted, which takes 1–3 min. These TRUS images are used to create prostate contours. The HDR catheters are reconstructed from the intraoperative TRUS and postoperative CT images, and subsequently used as landmarks for the TRUS–CT image fusion. After TRUS–CT fusion, the TRUS-based prostate volume is deformed to the CT images for treatment planning. This method was first validated with a prostate-phantom study. In addition, a pilot study of ten patients undergoing HDR prostate brachytherapy was conducted to test its clinical feasibility. The accuracy of their approach was assessed through the locations of three implanted fiducial (gold) markers, as well as T2-weighted MR prostate images of patients. Results: For the phantom study, the target registration error (TRE) of gold-markers was 0.41 ± 0.11 mm. For the ten patients, the TRE of gold markers was 1.18 ± 0.26 mm; the prostate volume difference between the authors’ approach and the MRI-based volume was 7.28% ± 0

  1. [Epidemiology of prostate cancer in China: an overview and clinical implication].

    PubMed

    Ye, Dingwei; Zhu, Yao

    2015-04-01

    Prostate cancer is a currently common disease in Chinese male. The incidence is increasing rapidly in urban area and the mortality is high in rural area. According to characteristics of disease stage, advancement in early diagnosis of prostate cancer is the key to improve prostate cancer survival in China. Because of the remarkable disparity in economic and health care across mainland China, a selective prostate cancer screen approach may be a better alternative to spread. Therefore, indepth researches in optimization of prostate specific antigen screen and validation biomarkers of aggressive prostate cancer should be advocated. Furthermore, physicians should take a more active role in population education.

  2. Hormonal therapy and chemotherapy in hormone-naive and castration resistant prostate cancer

    PubMed Central

    Sternberg, Cora N.

    2015-01-01

    The management of advanced castration resistant prostate cancer (CRPC) has been rapidly changing and is still evolving. In the last years, there has been an increasing knowledge of prostate cancer biology. New therapeutic agents and approaches have been evaluated demonstrating benefits in survival and quality of life in patients with metastatic prostate cancer. PMID:26816835

  3. Evolution of the use of the holmium laser for the treatment of benign prostatic hyperplasia

    NASA Astrophysics Data System (ADS)

    Gilling, Peter J.; Cass, Carol B.; Cresswell, Michael D.; Kennett, Katie M.; Mackey, Michael; Fraundorfer, Mark R.; Kabalin, John N.

    1997-05-01

    The holmium laser is becoming an important tool in the urologists' armamentarium. In this manuscript the evolution of laser resection of the prostate using the holmium wavelength is described. This technique represents a significant advance in the surgical management of benign prostatic hyperplasia and allows even very large prostates to be safely and efficiently managed transurethrally.

  4. Benign Conditions That Mimic Prostate Carcinoma: MR Imaging Features with Histopathologic Correlation.

    PubMed

    Kitzing, Yu Xuan; Prando, Adilson; Varol, Celi; Karczmar, Gregory S; Maclean, Fiona; Oto, Aytekin

    2016-01-01

    Multiparametric magnetic resonance (MR) imaging combines anatomic and functional imaging techniques for evaluating the prostate and is increasingly being used in diagnosis and management of prostate cancer. A wide spectrum of anatomic and pathologic processes in the prostate may masquerade as prostate cancer, complicating the imaging interpretation. The histopathologic and imaging findings of these potential mimics are reviewed. These entities include the anterior fibromuscular stroma, surgical capsule, central zone, periprostatic vein, periprostatic lymph nodes, benign prostatic hyperplasia (BPH), atrophy, necrosis, calcification, hemorrhage, and prostatitis. An understanding of the prostate zonal anatomy is helpful in distinguishing the anatomic entities from prostate cancer. The anterior fibromuscular stroma, surgical capsule, and central zone are characteristic anatomic features of the prostate with associated low T2 signal intensity due to dense fibromuscular tissue or complex crowded glandular tissue. BPH, atrophy, necrosis, calcification, and hemorrhage all have characteristic features with one or more individual multiparametric MR imaging modalities. Prostatitis constitutes a heterogeneous group of infective and inflammatory conditions including acute and chronic bacterial prostatitis, infective and noninfective granulomatous prostatitis, and malacoplakia. These entities are associated with variable clinical manifestations and are characterized by the histologic hallmark of marked inflammatory cellular infiltration. In some cases, these entities are indistinguishable from prostate cancer at multiparametric MR imaging and may even exhibit extraprostatic extension and lymphadenopathy, mimicking locally advanced prostate cancer. It is important for the radiologists interpreting prostate MR images to be aware of these pitfalls for accurate interpretation. Online supplemental material is available for this article.

  5. Stem cell and neurogenic gene-expression profiles link prostate basal cells to aggressive prostate cancer

    PubMed Central

    Zhang, Dingxiao; Park, Daechan; Zhong, Yi; Lu, Yue; Rycaj, Kiera; Gong, Shuai; Chen, Xin; Liu, Xin; Chao, Hsueh-Ping; Whitney, Pamela; Calhoun-Davis, Tammy; Takata, Yoko; Shen, Jianjun; Iyer, Vishwanath R.; Tang, Dean G.

    2016-01-01

    The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. Here we describe a genome-wide transcriptome analysis of human benign prostatic basal and luminal epithelial populations using deep RNA sequencing. Through molecular and biological characterizations, we show that the differential gene-expression profiles account for their distinct functional properties. Strikingly, basal cells preferentially express gene categories associated with stem cells, neurogenesis and ribosomal RNA (rRNA) biogenesis. Consistent with this profile, basal cells functionally exhibit intrinsic stem-like and neurogenic properties with enhanced rRNA transcription activity. Of clinical relevance, the basal cell gene-expression profile is enriched in advanced, anaplastic, castration-resistant and metastatic prostate cancers. Therefore, we link the cell-type-specific gene signatures to aggressive subtypes of prostate cancer and identify gene signatures associated with adverse clinical features. PMID:26924072

  6. Holmium Laser Enucleation of the Prostate in a 400 cc Prostate: Case Report

    PubMed Central

    Hong, Matthew K.H.; Pham, Trung

    2016-01-01

    Abstract The modality of choice in the surgical management of benign prostatic hyperplasia for large prostates has traditionally been open prostatectomy. Advances in minimally invasive techniques have begun to challenge this notion with advantages such as lower bleeding and transfusion rates and shorter hospital stay. In this case report, we illustrate the use of holmium laser enucleation of the prostate (HoLEP) in a gland measuring more than 400 cc. We describe the case of a 71-year-old man with persistent voiding urinary symptoms despite two previous transurethral resections of his prostate. With greater experience in HoLEP and declining experience in open prostatectomy, there may be a shift toward HoLEP as the preferred treatment choice for large prostate glands. PMID:27579406

  7. Holmium Laser Enucleation of the Prostate in a 400 cc Prostate: Case Report.

    PubMed

    Gopee, Esha L; Hong, Matthew K H; Pham, Trung

    2016-01-01

    The modality of choice in the surgical management of benign prostatic hyperplasia for large prostates has traditionally been open prostatectomy. Advances in minimally invasive techniques have begun to challenge this notion with advantages such as lower bleeding and transfusion rates and shorter hospital stay. In this case report, we illustrate the use of holmium laser enucleation of the prostate (HoLEP) in a gland measuring more than 400 cc. We describe the case of a 71-year-old man with persistent voiding urinary symptoms despite two previous transurethral resections of his prostate. With greater experience in HoLEP and declining experience in open prostatectomy, there may be a shift toward HoLEP as the preferred treatment choice for large prostate glands. PMID:27579406

  8. Prostate cancer biomarkers: an update.

    PubMed

    Romero Otero, Javier; Garcia Gomez, Borja; Campos Juanatey, Felix; Touijer, Karim A

    2014-04-01

    Many aspects of prostate cancer diagnosis and treatment could be greatly advanced with new, effective biomarkers. Prostate-specific antigen (PSA) has multiple weaknesses as a biomarker, such as not distinguishing well between cancer and benign prostatic hyperplasia or between indolent and aggressive cancers, thus leading to overtreatment, especially unnecessary biopsies. PSA also often fails to indicate accurately which patients are responding to a given treatment. Yet PSA is the only prostate cancer biomarker routinely used by urologists. Here, we provide updated information on the most relevant of the other biomarkers currently in use or in development for prostate cancer. Recent research shows improvement over using PSA alone by comparing total PSA (tPSA) or free PSA (fPSA) with new, related markers, such as prostate cancer antigen (PCA) 3, the individual molecular forms of PSA (proPSA, benign PSA, and intact PSA), and kallikreins other than PSA. Promising results have also been seen with the use of the fusion gene TMPRSS2:ERG and with various forms of the urokinase plasminogen activation receptor. Initially, there were high hopes for early PCA, but those data were not reproducible and thus research on early PCA has been abandoned. Much work remains to be done before any of these biomarkers are fully validated and accepted. Currently, the only markers discussed in this paper with Food and Drug Administration-approved tests are PCA 3 and an isoform of proPSA, [-2]proPSA. Assays are in development for most of the other biomarkers described in this paper. While the biomarker validation process can be long and filled with obstacles, the rewards will be great-in terms of both patient care and costs to the health care system.

  9. Transurethral resection of the prostate

    MedlinePlus

    TURP; Prostate resection - transurethral ... used to remove the inside part of your prostate gland using electricity. ... if you have benign prostatic hyperplasia ( BPH ). The prostate gland often grows larger as men get older. ...

  10. Economic analysis of a phase III clinical trial evaluating the addition of total androgen suppression to radiation versus radiation alone for locally advanced prostate cancer (Radiation Therapy Oncology Group protocol 86-10)

    SciTech Connect

    Konski, Andre . E-mail: a_konski@fccc.edu; Sherman, Eric; Krahn, Murray; Bremner, Karen; Beck, J. Robert; Watkins-Bruner, Deborah; Pilepich, Michael

    2005-11-01

    Purpose: To evaluate the cost-effectiveness of adding hormone therapy to radiation for patients with locally advanced prostate cancer, using a Monte Carlo simulation of a Markov Model. Methods and Materials: Radiation Therapy Oncology Group (RTOG) protocol 86-10 randomized patients to receive radiation therapy (RT) alone or RT plus total androgen suppression (RTHormones) 2 months before and during RT for the treatment of locally advanced prostate cancer. A Markov model was designed with Data Pro (TreeAge Software, Williamstown, MA). The analysis took a payer's perspective. Transition probabilities from one state of health (i.e., with no disease progression or with hormone-responsive metastatic disease) to another were calculated from published rates pertaining to RTOG 86-10. Patients remained in one state of health for 1 year. Utility values for each health state and treatment were obtained from the literature. Distributions were sampled at random from the treatment utilities according to a second-order Monte Carlo simulation technique. Results: The mean expected cost for the RT-only treatments was $29,240 (range, $29,138-$29,403). The mean effectiveness for the RT-only treatment was 5.48 quality-adjusted life years (QALYs) (range, 5.47-5.50). The mean expected cost for RTHormones was $31,286 (range, $31,058-$31,555). The mean effectiveness was 6.43 QALYs (range, 6.42-6.44). Incremental cost-effectiveness analysis showed RTHormones to be within the range of cost-effectiveness at $2,153/QALY. Cost-effectiveness acceptability curve analysis resulted in a >80% probability that RTHormones is cost-effective. Conclusions: Our analysis shows that adding hormonal treatment to RT improves health outcomes at a cost that is within the acceptable cost-effectiveness range.

  11. Metastasis of Prostate Adenocarcinoma to the Testis

    PubMed Central

    Campara, Zoran; Simic, Dejan; Aleksic, Predrag; Spasic, Aleksandar; Milicevic, Snjezana

    2016-01-01

    Introduction: Prostate carcinoma is the most frequently diagnosed carcinoma in the male population. The most typical places of the metastases are pelvic lymphatic glands, bones and lungs, and very rarely it metastasizes into a testis. The prognostic importance of testicular metastasis of prostate cancer is not yet well-known, due to a very few published cases. According to the known facts, it is certain that a metastasis of the prostate carcinoma into a testis is a sign of an advanced disease. Case report: This work presents a 48-year-old patient, to whom an adenocarcinoma of the prostate has been proven by the pathohistological finding of transrectal biopsy, performed due to the elevated level of prostate-specific antigen (PSA). Nine years after the initial diagnosis, due to a gradual rise of PSA and tumorous enlargement of the left testis, left inguinal orchectomy and right orchectomy were performed. Metastatic dissemination of prostate adenocarcinoma into a testis was determined by a pathohistological analysis of the left testis. Conclusion: The metastasis of the prostate carcinoma into a testis, as a rare localization of the metastatic dissemination, after additionally performed orchectomy along with further oncological therapy, can provide a continuation of a good life quality as well as a control of the disease in a longer time period. PMID:27703299

  12. A Phase 1 Study of a Vaccine Targeting Preferentially Expressed Antigen in Melanoma and Prostate-specific Membrane Antigen in Patients With Advanced Solid Tumors

    PubMed Central

    Weber, Jeffrey S.; Vogelzang, Nicholas J.; Ernstoff, Marc S.; Goodman, Oscar B.; Cranmer, Lee D.; Marshall, John L.; Miles, Sabrina; Rosario, Dar; Diamond, David C.; Qiu, Zhiyong; Obrocea, Mihail; Bot, Adrian

    2013-01-01

    Summary Preferentially expressed antigen in melanoma (PRAME) and prostate-specific membrane antigen (PSMA) are tumor-associated antigens implicated in cellular differentiation, genetic stability, and angiogenesis. MKC1106-PP is an immunotherapeutic regimen cotargeting PRAME and PSMA, comprised of a recombinant plasmid (pPRA-PSM encoding fragments derived from both antigens) and 2 peptides (E-PRA and E-PSM derived from PRAME and PSMA, respectively). This multicenter study evaluated MKC1106-PP with a fixed plasmid dose and 2 different peptide doses, administered by intralymph node injection in a prime-boost sequence in human leukocyte antigen-A*0201 and tumor-antigen-positive patients with progressing metastatic solid tumors who had failed standard therapy. Immune monitoring was done by tetramer and enzymatic-linked immune spot analysis. The treatment was well tolerated, with no significant differences in safety, immune response, and clinical outcome relative to peptide doses. Fifteen of 24 evaluable patients showed an immune response, as defined by the expansion of PRAME-specific or PSMA-specific T cells in the blood. There were no partial or complete responses by the Response Evaluation Criteria in Solid Tumors. Seven patients showed stable disease (SD) for 6 months or longer, or prostate specific antigen decline: 4 of 10 with prostate carcinoma, 2 of 2 with renal clear cell carcinoma, and 1 of 10 with metastatic melanoma. In addition, there was an association between the induction and persistence of antigen-specific T cells in blood above baseline levels and disease control, defined as SD for 6 months or longer. These results support further development of MKC1106-PP in specific clinical indications. PMID:21760528

  13. PDEF in prostate cancer.

    PubMed

    Sood, Ashwani K; Kim, Hyung; Geradts, Joseph

    2012-05-01

    Prostate-derived Ets factor (PDEF) is a relatively recently described member of the Ets family of transcription factors. It differs from other family members in its restricted and epithelial-specific expression in normal tissues and its unique DNA-binding motif that together may impart interesting specificity to its function. This communication reviews our current understanding of the expression characteristics of PDEF in normal prostate and in prostate cancer. Also, the biochemical and genetic evidence relating to the role of this transcription factor in prostate cancer is reviewed. Most evidence is consistent with an oncogenic role for PDEF in prostate cancer. Specific observations about the loss of PDEF expression in prostate tumors and its apparent role as a prostate tumor suppressor are also discussed. PDEF is one of the few transcription factors with potential to have a significant impact on the management of prostate cancer. A better understanding of its biology and its role in prostate cancer is urgently needed.

  14. Characterisation of prostate cancer lesions in heterozygous Men1 mutant mice

    PubMed Central

    2010-01-01

    Background Mutations of the MEN1 gene predispose to multiple endocrine neoplasia type 1 (MEN1) syndrome. Our group and others have shown that Men1 disruption in mice recapitulates MEN1 pathology. Intriguingly, rare lesions in hormone-dependent tissues, such as prostate and mammary glands, were also observed in the Men1 mutant mice. Methods To study the occurrence of prostate lesions, we followed a male mouse cohort of 47 Men1+/- mice and 23 age-matched control littermates, starting at 18 months of age, and analysed the prostate glands from the cohort. Results Six Men1+/- mice (12.8%) developed prostate cancer, including two adenocarcinomas and four in situ carcinomas, while none of the control mice developed cancerous lesions. The expression of menin encoded by the Men1 gene was found to be drastically reduced in all carcinomas, and partial LOH of the wild-type Men1 allele was detected in three of the five analysed lesions. Using immunostaining for the androgen receptor and p63, a basal epithelial cell marker, we demonstrated that the menin-negative prostate cancer cells did not display p63 expression and that the androgen receptor was expressed but more heterogeneous in these lesions. Furthermore, our data showed that the expression of the cyclin-dependent kinase inhibitor CDKN1B (p27), a Men1 target gene known to be inactivated during prostate cell tumorigenesis, was notably decreased in the prostate cancers that developed in the mutant mice. Conclusion Our work suggests the possible involvement of Men1 inactivation in the tumorigenesis of the prostate gland. PMID:20663219

  15. Challenges in Clinical Prostate Cancer: Role of Imaging

    PubMed Central

    Kelloff, Gary J.; Choyke, Peter; Coffey, Donald S.

    2010-01-01

    Objective This article reviews a recent 2-day workshop on prostate cancer and imaging technology that was conducted by the Cancer Imaging Program of the National Cancer Institute. The workshop dealt with research trends and avenues for improving imaging and applications across the clinical spectrum of the disease. Conclusion After a summary of prostate cancer incidence and mortality, four main clinical challenges in prostate cancer treatment and management—diagnostic accuracy; risk stratification, initial staging, active surveillance, and focal therapy; prostate-specific antigen relapse after radiation therapy or radical prostatectomy; and assessing response to therapy in advanced disease—were discussed by the 55-member panel. The overarching issue in prostate cancer is distinguishing lethal from nonlethal disease. New technologies and fresh uses for established procedures make imaging effective in both assessing and treating prostate cancer. PMID:19457806

  16. PET/CT AND RADIOIMMUNOTHERAPY OF PROSTATE CANCER

    PubMed Central

    Bouchelouche, Kirsten; Capala, Jacek; Oehr, Peter

    2009-01-01

    Purpose of review Traditional morphologically based imaging modalities are now being complemented by positron emission tomography (PET)/computerized tomography (CT) in prostate cancer. Metastatic prostate cancer is an attractive target for radioimmunotherapy (RIT) since no effective therapies are available. This review highlights the most important achievements within the last year in PET/CT and RIT of prostate cancer. Recent findings Conflicting results exist on the use of choline for detection of malignant disease in the prostate gland. The role of PET/CT in N-staging remains to be elucidated further. However, 18F-choline and 11C-choline PET/CT have been demonstrated to be useful for detection of recurrence. 18F-choline and 18F-fluoride PET/CT are useful for detection of bone metastases. Prostate tumor antigens may be used as targets for RIT. Prostate specific membrane antigen (PSMA) is currently under focus of a number of diagnostic and therapeutic strategies. J591, a monoclonal antibody, that targets the extracellular domain of PSMA, shows promising results. HER2 receptors may also have a potential as target for PET/CT imaging and RIT of advanced prostate cancer. Summary PET/CT in prostate cancer has proven to play a significant role, in particular for detection of prostate cancer recurrence and bone metastases. Radioimmunotherapy of metastatic prostate cancer warrant further investigations. PMID:19535981

  17. Risk stratification of prostate cancer 2016.

    PubMed

    Reiter, Robert E

    2016-01-01

    Prostate cancer is a common malignancy in men, but its management is fraught with controversy owing to its variable biologic and clinical behavior. Despite evidence that PSA screening reduces prostate cancer specific metastasis and death, it has not gained acceptance by various health authorities. Nevertheless, recent advances in biomarker development potentially address many of the shortcomings of routine PSA testing alone, including improved specificity for the detection of clinically significant cancer, optimized risk stratification to aid clinical management decisions, and discovery of genetic variants that may guide optimized therapy of advanced disease. PMID:27533326

  18. Cholesterol biosynthesis inhibitors as potent novel anti-cancer agents: suppression of hormone-dependent breast cancer by the oxidosqualene cyclase inhibitor RO 48-8071.

    PubMed

    Liang, Yayun; Besch-Williford, Cynthia; Aebi, Johannes D; Mafuvadze, Benford; Cook, Matthew T; Zou, Xiaoqin; Hyder, Salman M

    2014-07-01

    In most human breast cancers, tumor cell proliferation is estrogen dependent. Although hormone-responsive tumors initially respond to anti-estrogen therapies, most of them eventually develop resistance. Our goal was to identify alternative targets that might be regulated to control breast cancer progression. Sulforhodamine B assay was used to measure the viability of cultured human breast cancer cell lines exposed to various inhibitors. Protein expression in whole-cell extracts was determined by Western blotting. BT-474 tumor xenografts in nude mice were used for in vivo studies of tumor progression. RO 48-8071 ([4'-[6-(Allylmethylamino)hexyloxy]-4-bromo-2'-fluorobenzophenone fumarate]; RO), a small-molecule inhibitor of oxidosqualene cyclase (OSC, a key enzyme in cholesterol biosynthesis), potently reduced breast cancer cell viability. In vitro exposure of estrogen receptor (ER)-positive human breast cancer cells to pharmacological levels of RO or a dose close to the IC50 for OSC (nM) reduced cell viability. Administration of RO to mice with BT-474 tumor xenografts prevented tumor growth, with no apparent toxicity. RO degraded ERα while concomitantly inducing the anti-proliferative protein ERβ. Two other cholesterol-lowering drugs, Fluvastatin and Simvastatin, were less effective in reducing breast cancer cell viability and were found not to induce ERβ. ERβ inhibition or knockdown prevented RO-dependent loss of cell viability. Importantly, RO had no effect on the viability of normal human mammary cells. RO is a potent inhibitor of hormone-dependent human breast cancer cell proliferation. The anti-tumor properties of RO appear to be in part due to an off-target effect that increases the ratio of ERβ/ERα in breast cancer cells.

  19. PET/CT imaging and radioimmunotherapy of prostate cancer

    PubMed Central

    Bouchelouche, Kirsten; Tagawa, Scott T.; Goldsmith, Stanley J.; Turkbey, Baris; Capala, Jacek; Choyke, Peter

    2012-01-01

    Prostate cancer is a common cancer in men and continues to be a major health problem. Imaging plays an important role in the clinical management of patients with prostate cancer. An important goal for prostate cancer imaging is more accurate disease characterization through the synthesis of anatomic, functional, and molecular imaging information. Positron emission tomography (PET)/computed tomography (CT) in oncology is emerging as an important imaging tool. The most common radiotracer for PET/CT in oncology, 18F- fluorodeoxyglucose (FDG), is not very useful in prostate cancer. However, in recent years other PET tracers have improved the accuracy of PET/CT imaging of prostate cancer. Among these, choline, labelled with 18F or 11C, 11C-acetate and 18F- fluoride have demonstrated promising results, and other new radiopharmaceuticals are currently under development and evaluation in pre-clinical and clinical studies. Large prospective clinical PET/CT trials are needed to establish the role of PET/CT in prostate cancer patients. Because there are only limited available therapeutic options for advanced metastatic prostate cancer, there is an urgent need for the development of more effective treatment modalities that could improve outcome. Prostate cancer represents an attractive target for radioimmunotherapy (RIT) for several reasons, including pattern of metastatic spread (lymph nodes and bone marrow, sites with good access to circulating antibodies), and small volume disease (ideal for antigen access and antibody delivery). Furthermore, prostate cancer is also radiation sensitive. Prostate-specific membrane antigen (PSMA) is expressed by virtually all prostate cancers, and represents an attractive target for RIT. Anti PSMA RIT demonstrates antitumor activity and is well tolerated. Clinical trials are underway to further improve upon treatment efficacy and patient selection. This review focuses on the recent advances of clinical PET/CT imaging and RIT of prostate

  20. A Urologist’s Personal View of Prostate Cancer

    PubMed Central

    Schellhammer, Paul F.

    2016-01-01

    A urologist’s personal experience with multiple surgical, hormonal, and radio/immunotherapeutic options for the treatment of advanced prostate cancer and thoughts on the role of old and new therapies. PMID:27635283

  1. A Urologist’s Personal View of Prostate Cancer

    PubMed Central

    Schellhammer, Paul F.

    2016-01-01

    A urologist’s personal experience with multiple surgical, hormonal, and radio/immunotherapeutic options for the treatment of advanced prostate cancer and thoughts on the role of old and new therapies.

  2. Prostate resection - minimally invasive

    MedlinePlus

    Laser prostatectomy; Transurethral needle ablation; TUNA; Transurethral incision; TUIP; Holmium laser enucleation of the prostate; HoLep; Interstitial laser coagulation; ILC; Photoselective vaporization of the prostate; PVP; Transurethral ...

  3. Screening for Prostate Cancer

    MedlinePlus

    ... of Internal Medicine Summaries for Patients Screening for Prostate Cancer: A Guidance Statement From the Clinical Guidelines Committee ... Physicians The full report is titled “Screening for Prostate Cancer: A Guidance Statement From the Clinical Guidelines Committee ...

  4. Prostate cancer screenings

    MedlinePlus

    ... not do an accurate job of screening for prostate cancer. ... and anxiety, even if you do not have prostate cancer. Side effects from further testing. If your PSA test is higher than normal, you may need to ...

  5. Enlarged prostate - after care

    MedlinePlus

    BPH - self-care; Benign prostatic hypertrophy - self-care; Benign prostatic hyperplasia - self-care ... Your health care provider may have you take a medicine called alpha-1- blocker. Most people find that these drugs help ...

  6. Prostate Cancer Screening

    MedlinePlus

    ... treat. There is no standard screening test for prostate cancer. Researchers are studying different tests to find those ... PSA level may be high if you have prostate cancer. It can also be high if you have ...

  7. Cryotherapy for prostate cancer

    MedlinePlus

    ... the needles to the prostate gland. Then, very cold gas passes through the needles, creating ice balls that destroy the prostate gland. Warm salt water will flow through the catheter to keep your urethra (the tube from the bladder to ...

  8. Prostate cancer - resources

    MedlinePlus

    Resources - prostate cancer ... The following organizations are good resources for information on prostate cancer : American Cancer Society -- www.cancer.org/cancer/prostatecancer/index National Cancer Institute -- www.cancer.gov/cancertopics/ ...

  9. Clinical experience with radium-223 in the treatment of patients with advanced castrate-resistant prostate cancer and symptomatic bone metastases

    PubMed Central

    Hague, Christina; Logue, John P.

    2016-01-01

    The treatment of metastatic castrate-resistant prostate cancer (mCRPC) has grown over the past decade. The majority of patients develop bone metastases, which pose a significant burden on morbidity and mortality, especially skeletal-related events. Whilst demonstrating a favourable safety profile and improving symptoms, radiopharmaceuticals have until recently failed to show a survival benefit. However, since the large phase III randomized ALSYMPCA trial, the calcium mimetic properties of radium-223 (Ra223) have improved patients’ quality of life and improved survival whilst keeping toxicities to a minimum. This review article summarizes the clinical data including our real life experience on the usage of the alpha emitter Ra223 in mCRPC, paying particular attention to how clinicians should best monitor response. PMID:27247627

  10. Clinical experience with radium-223 in the treatment of patients with advanced castrate-resistant prostate cancer and symptomatic bone metastases.

    PubMed

    Hague, Christina; Logue, John P

    2016-06-01

    The treatment of metastatic castrate-resistant prostate cancer (mCRPC) has grown over the past decade. The majority of patients develop bone metastases, which pose a significant burden on morbidity and mortality, especially skeletal-related events. Whilst demonstrating a favourable safety profile and improving symptoms, radiopharmaceuticals have until recently failed to show a survival benefit. However, since the large phase III randomized ALSYMPCA trial, the calcium mimetic properties of radium-223 (Ra223) have improved patients' quality of life and improved survival whilst keeping toxicities to a minimum. This review article summarizes the clinical data including our real life experience on the usage of the alpha emitter Ra223 in mCRPC, paying particular attention to how clinicians should best monitor response. PMID:27247627

  11. Novel diagnostic biomarkers for prostate cancer

    PubMed Central

    Madu, Chikezie O.; Lu, Yi

    2010-01-01

    Prostate cancer is the most frequently diagnosed malignancy in American men, and a more aggressive form of the disease is particularly prevalent among African Americans. The therapeutic success rate for prostate cancer can be tremendously improved if the disease is diagnosed early. Thus, a successful therapy for this disease depends heavily on the clinical indicators (biomarkers) for early detection of the presence and progression of the disease, as well as the prediction after the clinical intervention. However, the current clinical biomarkers for prostate cancer are not ideal as there remains a lack of reliable biomarkers that can specifically distinguish between those patients who should be treated adequately to stop the aggressive form of the disease and those who should avoid overtreatment of the indolent form. A biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. A biomarker reveals further information to presently existing clinical and pathological analysis. It facilitates screening and detecting the cancer, monitoring the progression of the disease, and predicting the prognosis and survival after clinical intervention. A biomarker can also be used to evaluate the process of drug development, and, optimally, to improve the efficacy and safety of cancer treatment by enabling physicians to tailor treatment for individual patients. The form of the prostate cancer biomarkers can vary from metabolites and chemical products present in body fluid to genes and proteins in the prostate tissues. Current advances in molecular techniques have provided new tools facilitating the discovery of new biomarkers for prostate cancer. These emerging biomarkers will be beneficial and critical in developing new and clinically reliable indicators that will have a high specificity for the diagnosis and prognosis of prostate cancer. The

  12. Novel diagnostic biomarkers for prostate cancer.

    PubMed

    Madu, Chikezie O; Lu, Yi

    2010-10-06

    Prostate cancer is the most frequently diagnosed malignancy in American men, and a more aggressive form of the disease is particularly prevalent among African Americans. The therapeutic success rate for prostate cancer can be tremendously improved if the disease is diagnosed early. Thus, a successful therapy for this disease depends heavily on the clinical indicators (biomarkers) for early detection of the presence and progression of the disease, as well as the prediction after the clinical intervention. However, the current clinical biomarkers for prostate cancer are not ideal as there remains a lack of reliable biomarkers that can specifically distinguish between those patients who should be treated adequately to stop the aggressive form of the disease and those who should avoid overtreatment of the indolent form.A biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. A biomarker reveals further information to presently existing clinical and pathological analysis. It facilitates screening and detecting the cancer, monitoring the progression of the disease, and predicting the prognosis and survival after clinical intervention. A biomarker can also be used to evaluate the process of drug development, and, optimally, to improve the efficacy and safety of cancer treatment by enabling physicians to tailor treatment for individual patients. The form of the prostate cancer biomarkers can vary from metabolites and chemical products present in body fluid to genes and proteins in the prostate tissues.Current advances in molecular techniques have provided new tools facilitating the discovery of new biomarkers for prostate cancer. These emerging biomarkers will be beneficial and critical in developing new and clinically reliable indicators that will have a high specificity for the diagnosis and prognosis of prostate cancer. The

  13. Enlarged Prostate (BPH)

    MedlinePlus

    The prostate is a gland in men. It helps make semen, the fluid that contains sperm. The prostate surrounds the tube that carries urine out of the body. As men age, their prostate grows bigger. If it gets too large, it ...

  14. Therapeutic Strategies for Localized Prostate Cancer

    PubMed Central

    Lynch, John H; Batuello, Joseph T; Crawford, E David; Gomella, Leonard G; Kaufman, Joel; Petrylak, Daniel P; Joel, Andrew B

    2001-01-01

    Prostate-specific antigen determinations for prostate cancer screening have led to a dramatic increase in the number of men who are diagnosed with organ-confined and therefore potentially curable prostate cancer. Advances in predicting outcomes with artificial neural networks may help to recommend one therapy over another. Less invasive forms of treatment, such as high-intensity focused ultrasound, may ultimately give patients additional options for treatment. Furthermore, attempts to better define the role of both neoadjuvant hormonal therapy and chemotherapy may give higher-risk patients better outcomes than with current treatments. These advances as well as continued research will likely lead to a day when more and more men with organ-confined disease will be cured. PMID:16985999

  15. A hormone-dependent feedback-loop controls androgen receptor levels by limiting MID1, a novel translation enhancer and promoter of oncogenic signaling

    PubMed Central

    2014-01-01

    Background High androgen receptor (AR) level in primary tumour predicts increased prostate cancer (PCa)-specific mortality. Furthermore, activations of the AR, PI3K, mTOR, NFκB and Hedgehog (Hh) signaling pathways are involved in the fatal development of castration-resistant prostate cancer during androgen ablation therapy. MID1, a negative regulator of the tumor-suppressor PP2A, is known to promote PI3K, mTOR, NFκB and Hh signaling. Here we investigate the interaction of MID1 and AR. Methods AR and MID1 mRNA and protein levels were measured by qPCR, Western blot and immunohistochemistry. Co-immunoprecipitation followed by PCR and RNA-pull-down followed by Western blot was used to investigate protein-mRNA interaction, chromatin-immunoprecipitation followed by next-generation sequencing for identification of AR chromatin binding sites. AR transcriptional activity and activity of promoter binding sites for AR were analyzed by reporter gene assays. For knockdown or overexpression of proteins of interest prostate cancer cells were transfected with siRNA or expression plasmids, respectively. Results The microtubule-associated MID1 protein complex associates with AR mRNA via purine-rich trinucleotide repeats, expansions of which are known to correlate with ataxia and cancer. The level of MID1 directly correlates with the AR protein level in PCa cells. Overexpression of MID1 results in a several fold increase in AR protein and activity without major changes in mRNA-levels, whereas siRNA-triggered knockdown of MID1 mRNA reduces AR-protein levels significantly. Upregulation of AR protein by MID1 occurs via increased translation as no major changes in AR protein stability could be observed. AR on the other hand, regulates MID1 via several functional AR binding sites in the MID1 gene, and, in the presence of androgens, exerts a negative feedback loop on MID1 transcription. Thus, androgen withdrawal increases MID1 and concomitantly AR-protein levels. In line with this, MID1

  16. 3D-Pharmacophore Mapping Using 4D-QSAR Analysis for the Cytotoxicity of Lamellarins Against Human Hormone-Dependent T47D Breast Cancer Cells

    PubMed Central

    Thipnate, Poonsiri; Liu, Jianzhong; Hannongbua, Supa; Hopfinger, A. J.

    2009-01-01

    4D-QSAR and 3D-pharmacophore models were built and investigated for the cytotoxicity using a training set of 25 lamellarins against human hormone dependent T47D breast cancer cells. Receptor-independent (RI) 4D-QSAR models were first constructed from the exploration of eight possible receptor binding alignments for the entire training set. Since the training set is small (25 compounds), the generality of the 4D-QSAR paradigm was then exploited to devise a strategy to maximize the extraction of binding information from the training set, and to also permit virtual screening of diverse lamellarin chemistry. 4D-QSAR models were sought for only six of the most potent lamellarins of the training set as well as another subset composed of lamellarins with constrained ranges in molecular weight and lipophilicty. This overall modeling strategy has permitted maximizing 3D-pharmacophore information from this small set of structurally complex lamellarins that can be used to drive future analog synthesis and the selection of alternate scaffolds. Overall, it was found that formation of an intermolecular hydrogen bond and hydrophobic interactions for substituents on the E ring most modulate the cytotoxicity against T47D breast cancer cells. Hydrophobic substitutions on the F-ring can also enhance cytotoxic potency. A complementary high throughput virtual screen to the 3D-pharmacophore models, a 4D-fingerprint QSAR model, was constructed using absolute molecular similarity. This 4D-fingerprint virtual high throughput screen permits a larger range of chemistry diversity to be assayed than the 4D-QSAR models. The optimized 4D-QSAR 3D-pharmacophore model has a LOO cross-correlation value of xv-r2 = 0.947, while the optimized 4D-fingerprint virtual screening model has a value of xv-r2 = 0.719. This work reveals that it is possible to develop significant QSAR, 3D-pharmacophore and virtual screening models for a small set of lamellarins showing cytotoxic behavior in breast cancer screens

  17. Biomarkers for prostate cancer.

    PubMed

    Makarov, Danil V; Loeb, Stacy; Getzenberg, Robert H; Partin, Alan W

    2009-01-01

    The development of biomarkers for prostate cancer screening, detection, and prognostication has revolutionized the management of this disease. Prostate-specific antigen (PSA) is a useful, though not specific, biomarker for detecting prostate cancer. We review the literature on prostate cancer biomarkers, including serum markers (PAP, tPSA, fPSA, proPSA, PSAD, PSAV, PSADT, EPCA, and EPCA-2), tissue markers (AMACR, methylated GSTP1, and the TMPRSS2-ETS gene rearrangement), and a urine marker (DD3PCA3/UPM-3). Future research should focus on validation of already existing biomarkers and the discovery of new markers to identify men with aggressive prostate cancer.

  18. Recent developments in prostate cancer biomarker research: therapeutic implications

    PubMed Central

    Detchokul, Sujitra; Frauman, Albert G

    2011-01-01

    This review aims to present an overview of recent clinical trials targeting biomarkers in advanced prostate cancer. We searched ClinicalTrials.gov for early phase clinical trials on treatments of prostate cancer that have been recently completed, are ongoing or are actively recruiting participants. Drug targets and their mechanism of actions were assessed and summarized. Trials were categorized according to prostate cancer biomarkers that have potential as therapeutic targets. A total of 19 new therapeutic agents for the treatment of prostate cancer are included in this review. Trials are summarized according to the targeted biomarkers and are categorized into five therapeutic approaches: prostate cancer vaccine, epigenetic therapy, pro-apoptotic agents, prostate cancer antibodies and anti-angiogenesis approach. Some of the therapeutic agents reviewed showed promising results, warranting further investigation in late phase clinical trials. Recent novel prostate cancer biomarkers that made it through clinical trials and their relevance as drug targets are summarized. This review emphasizes the importance of specific prostate cancer biomarkers and their potentials as targets of the disease. Some clinical trials of targeted treatments in prostate cancer show promising results. Better understanding of disease mechanisms should potentially lead to more specific treatments for individual patients. PMID:21219396

  19. Current state of prostate cancer treatment in Jamaica.

    PubMed

    Morrison, Belinda F; Aiken, William D; Mayhew, Richard

    2014-01-01

    Prostate cancer is the commonest cancer in Jamaica as well as the leading cause of cancer-related deaths. One report suggested that Jamaica has the highest incidence rate of prostate cancer in the world, with an age-standardised rate of 304/100,000 per year. The Caribbean region is reported to have the highest mortality rate of prostate cancer worldwide. Prostate cancer accounts for a large portion of the clinical practice for health-care practitioners in Jamaica. The Jamaica Urological Society is a professional body comprising 19 urologists in Jamaica who provide most of the care for men with prostate cancer in collaboration with medical oncologists, radiation oncologists, and a palliative care physician. The health-care system is structured in two tiers in Jamaica: public and private. The urologist-to-patient ratio is high, and this limits adequate urological care. Screening for prostate cancer is not a national policy in Jamaica. However, the Jamaica Urological Society and the Jamaica Cancer Society work synergistically to promote screening as well as to provide patient education for prostate cancer. Adequate treatment for localised prostate cancer is available in Jamaica in the forms of active surveillance, nerve-sparing radical retropubic prostatectomy, external beam radiation, and brachytherapy. However, there is a geographic maldistribution of centres that provide prostate cancer treatment, which leads to treatment delays. Also, there is difficulty in affording some treatment options in the private health-care sectors. Androgen deprivation therapy is available for treatment of locally advanced and metastatic prostate cancer and is subsidised through a programme called the National Health Fund. Second-line hormonal agents and chemotherapeutic agents are available but are costly to most of the population. The infrastructure for treatment of prostate cancer in Jamaica is good, but it requires additional technological advances as well as additional specialist

  20. Variant Prostate Carcinoma and Elevated Serum CA-125

    PubMed Central

    Bilen, Mehmet Asim; Reyes, Adriana; Bhowmick, Deb; Maa, April; Bast, Robert; Pisters, Louis L.; Lin, Sue-Hwa; Logothetis, Christopher J.; Tu, Shi-Ming

    2015-01-01

    Introduction About 10% of tumors derived from nongynecologic, noncoelomic tissues react with the OC125 antibody. Some patients with advanced prostate cancer were found to have elevated serum CA-125 level. Materials and Methods We examined the clinical history of 11 patients with castration-resistant prostate cancer and an elevated serum CA-125 level. Pathological review and immunohistochemical staining were performed on tumors from 8 of these patients. Results Patients with advanced prostate cancer and an elevated serum CA-125 level responded to androgen ablative therapy (median duration, 27 months). They were predisposed to develop persistent or recurrent urinary symptoms and visceral metastases. Eight of 11 patients had a low or undetectable serum prostate-specific antigen level (≤4 ng/ml) or an elevated serum carcinoembryonic antigen level (>6 ng/ml). In 3 of 7 patients whose specimens were available for further review, the tumors contained histologic features compatible with a diagnosis of ductal or endometrioid adenocarcinoma of the prostate. Conclusions Patients with prostate cancer and an elevated serum CA-125 level have unique clinical and pathologic characteristics. Some of these patients possess tumors compatible with a subtype of prostate cancer known as ductal adenocarcinoma. Additional studies need to be performed to elucidate the biologic basis of the various subtypes of prostate cancer. PMID:25347368

  1. Prostate cancer radiotherapy 2002: the way forward.

    PubMed

    Lukka, Himu; Pickles, Tom; Morton, Gerard; Catton, Charles; Souhami, Luis; Warde, Padraig

    2005-02-01

    In November 2000, the GU Radiation Oncologists of Canada had their first meeting, "Controversies in prostate cancer radiotherapy: consensus development". The success of this meeting prompted a second meeting, held in December 2002 to discuss "The Way Forward" in prostate radiotherapy. Radiation oncologists from across Canada were brought together and integrated with key opinion leaders in prostate cancer treatment from throughout North America. The group debated current controversies including: intensity modulated radiotherapy (IMRT), external beam hypofractionation, high dose-rate brachytherapy, and hormone therapy in the management of prostate cancer. The meeting also sought to identify and prioritize clinical trial opportunities and to highlight steps required to achieve these research goals. In summary, advances involving IMRT have enabled the use of higher radiation doses without increasing morbidity. With renewed interest in hypofractionated radiation schedules, the value of hypofractionation using IMRT was discussed and initial results from ongoing clinical trials were presented. The emerging role for high dose-rate brachytherapy in higher risk patients was also discussed. Based on existing preliminary evidence the group expressed enthusiasm for further investigation of the role for brachytherapy in intermediate to high-risk patients. Despite significant advances in radiotherapy, hormone therapy continues to play an important role in prostate cancer treatment for patients with intermediate and high-risk disease. Although evidence supports the effectiveness of hormone therapy, the optimal timing, and duration of hormonal treatment are unclear. Results from ongoing clinical trials will provide insight into these questions and will assist in the design of future clinical trials.

  2. Do Environmental Factors Modify the Genetic Risk of Prostate Cancer?

    PubMed Central

    Loeb, Stacy; Peskoe, Sarah B.; Joshu, Corinne E.; Huang, Wen-Yi; Hayes, Richard B.; Carter, H. Ballentine; Isaacs, William B.; Platz, Elizabeth A.

    2015-01-01

    Background Many SNPs influence prostate cancer risk. To what extent genetic risk can be reduced by environmental factors is unknown. Methods We evaluated effect modification by environmental factors of the association between susceptibility SNPs and prostate cancer in 1,230 incident prostate cancer cases and 1,361 controls, all white and similar ages, nested in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Trial. Genetic risk scores were calculated as number of risk alleles for 20 validated SNPs. We estimated the association between higher genetic risk (≥ 12 SNPs) and prostate cancer within environmental factor strata and tested for interaction. Results Men with ≥12 risk alleles had 1.98, 2.04, and 1.91 times the odds of total, advanced, and nonadvanced prostate cancer, respectively. These associations were attenuated with the use of selenium supplements, aspirin, ibuprofen, and higher vegetable intake. For selenium, the attenuation was most striking for advanced prostate cancer: compared with <12 alleles and no selenium, the OR for ≥12 alleles was 2.06 [95% confidence interval (CI), 1.67–2.55] in nonusers and 0.99 (0.38–2.58) in users (Pinteraction = 0.031). Aspirin had the most marked attenuation for nonadvanced prostate cancer: compared with <12 alleles and nonusers, the OR for ≥12 alleles was 2.25 (1.69–3.00) in nonusers and 1.70 (1.25–2.32) in users (Pinteraction = 0.009). This pattern was similar for ibuprofen (Pinteraction = 0.023) and vegetables (Pinteraction = 0.010). Conclusions This study suggests that selenium supplements may reduce genetic risk of advanced prostate cancer, whereas aspirin, ibuprofen, and vegetables may reduce genetic risk of nonadvanced prostate cancer. PMID:25342390

  3. Bitter melon extract impairs prostate cancer cell-cycle progression and delays prostatic intraepithelial neoplasia in TRAMP model.

    PubMed

    Ru, Peng; Steele, Robert; Nerurkar, Pratibha V; Phillips, Nancy; Ray, Ratna B

    2011-12-01

    Prostate cancer remains the second leading cause of cancer deaths among American men. Earlier diagnosis increases survival rate in patients. However, treatments for advanced disease are limited to hormone ablation techniques and palliative care. Thus, new methods of treatment and prevention are necessary for inhibiting disease progression to a hormone refractory state. One of the approaches to control prostate cancer is prevention through diet, which inhibits one or more neoplastic events and reduces the cancer risk. For centuries, Ayurveda has recommended the use of bitter melon (Momordica charantia) as a functional food to prevent and treat human health related issues. In this study, we have initially used human prostate cancer cells, PC3 and LNCaP, as an in vitro model to assess the efficacy of bitter melon extract (BME) as an anticancer agent. We observed that prostate cancer cells treated with BME accumulate during the S phase of the cell cycle and modulate cyclin D1, cyclin E, and p21 expression. Treatment of prostate cancer cells with BME enhanced Bax expression and induced PARP cleavage. Oral gavage of BME, as a dietary compound, delayed the progression to high-grade prostatic intraepithelial neoplasia in TRAMP (transgenic adenocarcinoma of mouse prostate) mice (31%). Prostate tissue from BME-fed mice displayed approximately 51% reduction of proliferating cell nuclear antigen expression. Together, our results suggest for the first time that oral administration of BME inhibits prostate cancer progression in TRAMP mice by interfering cell-cycle progression and proliferation. PMID:21911444

  4. Enlarged prostate - what to ask your doctor

    MedlinePlus

    ... body? What does the prostate gland do? What causes the prostate gland to enlarge? Do many other men have prostate problems? How do I know my problem is not prostate cancer? What are the symptoms of an enlarged prostate? ...

  5. The high prevalence of undiagnosed prostate cancer at autopsy: implications for epidemiology and treatment of prostate cancer in the Prostate-specific Antigen-era.

    PubMed

    Jahn, Jaquelyn L; Giovannucci, Edward L; Stampfer, Meir J

    2015-12-15

    Widespread prostate-specific antigen (PSA) screening detects many cancers that would have otherwise gone undiagnosed. To estimate the prevalence of unsuspected prostate cancer, we reviewed 19 studies of prostate cancer discovered at autopsy among 6,024 men. Among men aged 70-79, tumor was found in 36% of Caucasians and 51% of African-Americans. This enormous prevalence, coupled with the high sensitivity of PSA screening, has led to the marked increase in the apparent incidence of prostate cancer. The impact of PSA screening on clinical practice is well-recognized, but its effect on epidemiologic research is less appreciated. Before screening, a larger proportion of incident prostate cancers had lethal potential and were diagnosed at advanced stage. However, in the PSA era, overall incident prostate cancer mainly is indolent disease, and often reflects the propensity to be screened and biopsied. Studies must therefore focus on cancers with lethal potential, and include long follow-up to accommodate the lead time induced by screening. Moreover, risk factor patterns differ markedly for potentially lethal and indolent disease, suggesting separate etiologies and distinct disease entities. Studies of total incident or indolent prostate cancer are of limited clinical utility, and the main focus of research should be on prostate cancers of lethal potential.

  6. 6 Common Cancers - Prostate Cancer

    MedlinePlus

    ... Bar Home Current Issue Past Issues 6 Common Cancers - Prostate Cancer Past Issues / Spring 2007 Table of Contents For ... early screening. Photo: AP Photo/Danny Moloshok Prostate Cancer The prostate gland is a walnut-sized structure ...

  7. The role of PI3K/AKT-related PIP5K1α and the discovery of its selective inhibitor for treatment of advanced prostate cancer

    PubMed Central

    Semenas, Julius; Hedblom, Andreas; Miftakhova, Regina R.; Sarwar, Martuza; Larsson, Rikard; Shcherbina, Liliya; Johansson, Martin E.; Härkönen, Pirkko; Sterner, Olov; Persson, Jenny L.

    2014-01-01

    Nitrogen-containing heterocyclic compounds are an important class of molecules that are commonly used for the synthesis of candidate drugs. Phosphatidylinositol-4-phosphate 5-kinase-α (PIP5Kα) is a lipid kinase, similar to PI3K. However, the role of PIP5K1α in oncogenic processes and the development of inhibitors that selectively target PIP5K1α have not been reported. In the present study we report that overexpression of PIP5K1α is associated with poor prognosis in prostate cancer and correlates with an elevated level of the androgen receptor. Overexpression of PIP5K1α in PNT1A nonmalignant cells results in an increased AKT activity and an increased survival, as well as invasive malignant phenotype, whereas siRNA-mediated knockdown of PIP5K1α in aggressive PC-3 cells leads to a reduced AKT activity and an inhibition in tumor growth in xenograft mice. We further report a previously unidentified role for PIP5K1α as a druggable target for our newly developed compound ISA-2011B using a high-throughput KINOMEscan platform. ISA-2011B was discovered during our synthetic studies of C-1 indol-3-yl substituted 1,2,3,4-tetrahydroisoquinolines via a Pictet-Spengler approach. ISA-2011B significantly inhibits growth of tumor cells in xenograft mice, and we show that this is mediated by targeting PIP5K1α-associated PI3K/AKT and the downstream survival, proliferation, and invasion pathways. Further, siRNA-mediated knockdown of PIP5K1α exerts similar effects on PC3 cells as ISA-2011B treatment, significantly inhibiting AKT activity, increasing apoptosis and reducing invasion. Thus, PIP5K1α has high potential as a drug target, and compound ISA-2011B is interesting for further development of targeted cancer therapy. PMID:25071204

  8. The role of PI3K/AKT-related PIP5K1α and the discovery of its selective inhibitor for treatment of advanced prostate cancer.

    PubMed

    Semenas, Julius; Hedblom, Andreas; Miftakhova, Regina R; Sarwar, Martuza; Larsson, Rikard; Shcherbina, Liliya; Johansson, Martin E; Härkönen, Pirkko; Sterner, Olov; Persson, Jenny L

    2014-09-01

    Nitrogen-containing heterocyclic compounds are an important class of molecules that are commonly used for the synthesis of candidate drugs. Phosphatidylinositol-4-phosphate 5-kinase-α (PIP5Kα) is a lipid kinase, similar to PI3K. However, the role of PIP5K1α in oncogenic processes and the development of inhibitors that selectively target PIP5K1α have not been reported. In the present study we report that overexpression of PIP5K1α is associated with poor prognosis in prostate cancer and correlates with an elevated level of the androgen receptor. Overexpression of PIP5K1α in PNT1A nonmalignant cells results in an increased AKT activity and an increased survival, as well as invasive malignant phenotype, whereas siRNA-mediated knockdown of PIP5K1α in aggressive PC-3 cells leads to a reduced AKT activity and an inhibition in tumor growth in xenograft mice. We further report a previously unidentified role for PIP5K1α as a druggable target for our newly developed compound ISA-2011B using a high-throughput KINOMEscan platform. ISA-2011B was discovered during our synthetic studies of C-1 indol-3-yl substituted 1,2,3,4-tetrahydroisoquinolines via a Pictet-Spengler approach. ISA-2011B significantly inhibits growth of tumor cells in xenograft mice, and we show that this is mediated by targeting PIP5K1α-associated PI3K/AKT and the downstream survival, proliferation, and invasion pathways. Further, siRNA-mediated knockdown of PIP5K1α exerts similar effects on PC3 cells as ISA-2011B treatment, significantly inhibiting AKT activity, increasing apoptosis and reducing invasion. Thus, PIP5K1α has high potential as a drug target, and compound ISA-2011B is interesting for further development of targeted cancer therapy.

  9. The role of PI3K/AKT-related PIP5K1α and the discovery of its selective inhibitor for treatment of advanced prostate cancer.

    PubMed

    Semenas, Julius; Hedblom, Andreas; Miftakhova, Regina R; Sarwar, Martuza; Larsson, Rikard; Shcherbina, Liliya; Johansson, Martin E; Härkönen, Pirkko; Sterner, Olov; Persson, Jenny L

    2014-09-01

    Nitrogen-containing heterocyclic compounds are an important class of molecules that are commonly used for the synthesis of candidate drugs. Phosphatidylinositol-4-phosphate 5-kinase-α (PIP5Kα) is a lipid kinase, similar to PI3K. However, the role of PIP5K1α in oncogenic processes and the development of inhibitors that selectively target PIP5K1α have not been reported. In the present study we report that overexpression of PIP5K1α is associated with poor prognosis in prostate cancer and correlates with an elevated level of the androgen receptor. Overexpression of PIP5K1α in PNT1A nonmalignant cells results in an increased AKT activity and an increased survival, as well as invasive malignant phenotype, whereas siRNA-mediated knockdown of PIP5K1α in aggressive PC-3 cells leads to a reduced AKT activity and an inhibition in tumor growth in xenograft mice. We further report a previously unidentified role for PIP5K1α as a druggable target for our newly developed compound ISA-2011B using a high-throughput KINOMEscan platform. ISA-2011B was discovered during our synthetic studies of C-1 indol-3-yl substituted 1,2,3,4-tetrahydroisoquinolines via a Pictet-Spengler approach. ISA-2011B significantly inhibits growth of tumor cells in xenograft mice, and we show that this is mediated by targeting PIP5K1α-associated PI3K/AKT and the downstream survival, proliferation, and invasion pathways. Further, siRNA-mediated knockdown of PIP5K1α exerts similar effects on PC3 cells as ISA-2011B treatment, significantly inhibiting AKT activity, increasing apoptosis and reducing invasion. Thus, PIP5K1α has high potential as a drug target, and compound ISA-2011B is interesting for further development of targeted cancer therapy. PMID:25071204

  10. Early initiation of salvage hormone therapy influences survival in patients who failed initial radiation for locally advanced prostate cancer: A secondary analysis of RTOG protocol 86-10

    SciTech Connect

    Shipley, William U. . E-mail: wshipley@partners.org; DeSilvio, Michelle; Pilepich, Michael V.; Roach, Mack; Wolkov, Harvey B.; Sause, William T.; Rubin, Philip; Lawton, Colleen A.

    2006-03-15

    Purpose: We examined overall and disease-specific survival outcomes both from the time of initial treatment and from the start of salvage hormone therapy (HT), by the extent of disease progression at the time salvage HT was started in patients treated on RTOG Protocol 86-10. Methods and Materials: With a median follow-up of 9.0 years, 247 patients (54%) had received subsequent salvage HT. The overall survival (OVS) and disease-specific survival (DSS) were compared by the extent of disease progression at the time salvage HT was started. Results: For those patients with distant metastases (DM) present at the start of salvage HT, the OVS and DSS were significantly reduced when compared with those with DM absent at the time salvage HT was started (OVS at 8 years, 31% vs. 58%; DSS at 8 years, 38% vs. 65%). A statistically significant increase in DSS was observed among the 143 patients with DM absent when patients with prostate-specific antigen (PSA) less than 20 were compared with those with PSA greater than 20 at the time salvage HT was started. Conclusions: The DSS and the OVS of the relapsed patient are decreased in those with more extensive disease at the time of salvage HT. However, because this protocol could not evaluate the effect of posttreatment PSA velocity on outcomes, which is likely a better predictor of long-term success with salvage HT, these results cannot be taken to demonstrate that early salvage HT in patients with long posttreatment PSA doubling times is necessary for longer survival.

  11. Imaging techniques for prostate cancer: implications for focal therapy

    PubMed Central

    Turkbey, Baris; Pinto, Peter A.; Choyke, Peter L.

    2012-01-01

    The multifocal nature of prostate cancer has necessitated whole-gland therapy in the past; however, since the widespread use of PSA screening, patients frequently present with less-advanced disease. Many men with localized disease wish to avoid the adverse effects of whole-gland therapy; therefore, focal therapy for prostate cancer is being considered as a treatment option. For focal treatment to be viable, accurate imaging is required for diagnosis, staging, and monitoring of treatment. Developments in MRI and PET have brought more attention to prostate imaging and the possibility of improving the accuracy of focal therapy. In this Review, we discuss the advantages and disadvantages of conventional methods for imaging the prostate, new developments for targeted imaging, and the possible role of image-guided biopsy and therapy for localized prostate cancer. PMID:19352394

  12. Men, food, and prostate cancer: gender influences on men's diets.

    PubMed

    Mróz, Lawrence W; Chapman, Gwen E; Oliffe, John L; Bottorff, Joan L

    2011-03-01

    Although healthy eating might enhance long-term survival, few men with prostate cancer make diet changes to advance their well-being. Men's typically poor diets and uninterest in self-health may impede nutrition interventions and diet change. Food choice behavior is complex involving many determinants, including gender, which can shape men's health practices, diets, and prostate cancer experiences. Developing men-centered prostate cancer nutrition interventions to engage men (and where appropriate their partners) in promoting healthy diets can afford health benefits. This article presents an overview and synthesis of current knowledge about men's food practices and provides an analysis of diet and diet change behaviors for men with prostate cancer. Masculinity and gender relations theory are discussed in the context of men's food practices, and suggestions for future applications to nutrition and prostate cancer research and diet interventions are made. PMID:20798140

  13. Men, food, and prostate cancer: gender influences on men's diets.

    PubMed

    Mróz, Lawrence W; Chapman, Gwen E; Oliffe, John L; Bottorff, Joan L

    2011-03-01

    Although healthy eating might enhance long-term survival, few men with prostate cancer make diet changes to advance their well-being. Men's typically poor diets and uninterest in self-health may impede nutrition interventions and diet change. Food choice behavior is complex involving many determinants, including gender, which can shape men's health practices, diets, and prostate cancer experiences. Developing men-centered prostate cancer nutrition interventions to engage men (and where appropriate their partners) in promoting healthy diets can afford health benefits. This article presents an overview and synthesis of current knowledge about men's food practices and provides an analysis of diet and diet change behaviors for men with prostate cancer. Masculinity and gender relations theory are discussed in the context of men's food practices, and suggestions for future applications to nutrition and prostate cancer research and diet interventions are made.

  14. Reversibility of the inhibitory effect of atrazine and lindane on cytosol 5. alpha. -dihydrotestosterone receptor complex formation in rat prostate

    SciTech Connect

    Simic, B.; Kniewald, Z.; Kniewald, J. ); Davies, J.E. )

    1991-01-01

    Once entering the bloodstream, most toxic substances, including pesticides, can reach organs involved in the reproductive system. They can cross the placenta, as well as the brain barrier, posing various risks to the reproductive processes. The organochlorine insecticide lindane and the s-triazine herbicide atrazine produce changes in hormone-dependent reactions in the rat hypothalamus, anterior pituitary, and prostate. Lindane also causes histological and biochemical alterations in the rat testis. In vivo treatment with atrazine produces a markedly inhibitory influence of 5{alpha}-dihydrotestosterone - receptor complex formation in rat prostate cytosol. Therefore, the aim of this study was to investigate whether such changes in the crucial step in the reproductive process are reversible. A parallel investigation using lindane was also undertaken.

  15. Hormone therapy for prostate cancer

    MedlinePlus

    Androgen deprivation therapy; ADT; Androgen suppression therapy; Combined androgen blockade ... Androgens cause prostate cancer cells to grow. Hormone therapy for prostate cancer lowers the effect level of ...

  16. Anti-prostate-specific membrane antigen-based radioimmunotherapy for prostate cancer.

    PubMed

    Tagawa, Scott T; Beltran, Himisha; Vallabhajosula, Shankar; Goldsmith, Stanley J; Osborne, Joseph; Matulich, Dan; Petrillo, Kristen; Parmar, Sarojben; Nanus, David M; Bander, Neil H

    2010-02-15

    Despite recent advances, advanced prostate cancer is suboptimally responsive to current chemotherapeutic agents. Radiolabeled monoclonal antibody therapy that targets prostate-specific membrane antigen (PSMA) shows promise and is an area of active investigation. J591 is a deimmunized IgG monoclonal antibody developed to target the extracellular domain of PSMA. Preclinical and early phase clinical studies using radiolabeled J591 have demonstrated efficacy in targeting tumor cells and decreasing levels of prostate-specific antigen. Radiolabeled J591 is well-tolerated, nonimmunogenic, and can be administered in multiple doses. The dose-limiting toxicity is reversible myelosuppression with little nonhematologic toxicity. Future studies will include approaches to optimize patient selection and incorporate novel strategies to improve the success of anti-PSMA radioimmunotherapy.

  17. Focal Ablation of Prostate Cancer: Four Roles for MRI Guidance

    PubMed Central

    Sommer, Graham; Bouley, Donna; Gill, Harcharan; Daniel, Bruce; Pauly, Kim Butts; Diederich, Christopher

    2014-01-01

    Introduction There is currently a great deal of interest in the possible use of focal therapies for prostate cancer, since such treatments offer the prospect for control or cure of the primary disease with minimal side effects. Many forms of thermal therapy have been proposed for focal ablation of prostate cancer, including laser, high intensity ultrasound and cryotherapy. This review will demonstrate the important roles that MRI guidance can offer to such focal ablation, focusing on the use of high intensity ultrasonic applicators as an example of one promising technique. Materials and Methods Transurethral and interstitial high intensity ultrasonic applicators, designed specifically for ablation of prostate tissue were tested extensively in vivo in a canine model. The roles of MRI in positioning the devices, monitoring prostate ablation, and depicting ablated tissue were assessed using appropriate MRI sequences. Results MRI guidance provides a very effective tool for the positioning of ablative devices in the prostate, and thermal monitoring successfully predicted ablation of prostate tissue when a threshold of 52°C was achieved. Contrast enhanced MRI accurately depicted the distribution of ablated prostate tissue, which is resorbed at 30 days. Conclusions Guidance of thermal therapies for focal ablation of prostate cancer will likely prove critically dependent on MRI functioning in four separate roles. Our studies indicate that in 3 roles: device positioning; thermal monitoring of prostate ablation; and depiction of ablated prostate tissue, MR techniques are highly accurate and likely to be of great benefit in focal prostate cancer ablation. A fourth critical role, identification of cancer within the gland for targeting of thermal therapy, is more problematic at present, but will likely become practical with further technological advances. PMID:23587506

  18. Current Laser Treatments for Benign Prostatic Hyperplasia

    PubMed Central

    Son, Hwancheol; Song, Sang Hoon

    2010-01-01

    The latest technical improvements in the surgical armamentarium are remarkable. In particular, advancements in the urologic field are so exceptional that we could observe the flare-up of robot-assisted laparoscopic radical prostatectomy for prostate cancer and laser prostatectomy for benign prostatic hyperplasia (BPH). Photoselective vaporization of the prostate (PVP) and holmium laser prostatectomy are the most generalized options for laser surgery of BPH, and both modalities have shown good postoperative results. In comparison to transurethral prostatectomy (TURP), they showed similar efficacy and a much lower complication rate in randomized prospective clinical trials. Even in cases of large prostates, laser prostatectomy showed comparable efficacy and safety profiles compared to open prostatectomy. From a technical point of view, PVP is considered to be an easier technique for the urologist to master. Furthermore, patients can be safely followed up in an outpatient clinic. Holmium laser enucleation of the prostate (HoLEP) mimics open prostatectomy because the adenomatous tissue is peeled off the surgical capsule in both procedures. Therefore, HoLEP shows notable volume reduction of the prostate similar to open prostatectomy with fewer blood transfusions, shorter hospital stay, and cost reduction regardless of prostate size. Outcomes of laser prostatectomy for BPH are encouraging but sometimes are unbalanced because safety and feasibility studies were reported mainly for PVP, whereas long-term data are mostly available for HoLEP. We need longer-term randomized clinical data to identify the reoperation rate of PVP and to determine which procedure is the ideal alternative to TURP and open prostatectomy for each patient. PMID:21165192

  19. Specific Pomegranate Juice Components as Potential Inhibitors of Prostate Cancer Metastasis12

    PubMed Central

    Wang, Lei; Ho, Jeffrey; Glackin, Carlotta; Martins-Green, Manuela

    2012-01-01

    Pomegranate juice (PJ) is a natural product that inhibits prostate cancer progression. A clinical trial on patients with recurrent prostate cancer resulted in none of the patients progressing to a metastatic stage during the period of the trial. We have previously found that, in addition to causing cell death of hormone-refractory prostate cancer cells, PJ also markedly increases adhesion and decreases migration of the cells that do not die. However, because PJ is a very complex mixture of components and is found in many different formulations, it is important to identify specific components that are effective in inhibiting growth and metastasis. Here, we show that the PJ components luteolin, ellagic acid, and punicic acid together inhibit growth of hormone-dependent and hormone-refractory prostate cancer cells and inhibit their migration and their chemotaxis toward stromal cell-derived factor 1α (SDF1α), a chemokine that is important in prostate cancer metastasis to the bone. These components also increase the expression of cell adhesion genes and decrease expression of genes involved in cell cycle control and cell migration. Furthermore, they increase several well-known tumor-suppression microRNAs (miRNAs), decrease several oncogenic miRNAs, and inhibit the chemokines receptor type 4 (CXCR4)/SDF1α chemotaxis axis. Our results suggest that these components may be more effective in inhibiting prostate cancer growth and metastasis than simply drinking the juice. Chemical modification of these components could further enhance their bioavailability and efficacy of treatment. Moreover, because the mechanisms of metastasis are similar for most cancers, these PJ components may also be effective in the treatment of metastasis of other cancers. PMID:23066443

  20. Stromal microcalcification in prostate.

    PubMed

    Muezzinoglu, B; Gurbuz, Y

    2001-06-01

    Prostatic calcification is most commonly encountered as calculus or intraluminal calcifications within atypical small glandular proliferations. This study was undertaken to detect stromal microcalcifications in prostate tissue. All slides from 194 needle biopsies were retrospectively reviewed. Six cases (3.1%) had stromal microcalcifications constantly associated with mononuclear inflammatory infiltrate around the each focus. Association with prostatic glands was not seen in any of the microcalcification foci. Three cases had simultaneous adenocarcinoma and one had high-grade prostatic intraepithelial neoplasia, all of which were apart from the microcalcification foci. In conclusion, stromal microcalcification is a dystrophic, inflammation-mediated, benign process.

  1. FGF signalling in prostate development, tissue homoeostasis and tumorigenesis.

    PubMed

    Lin, Yongshun; Wang, Fen

    2010-04-09

    The FGFs (fibroblast growth factors) regulate a broad spectrum of biological activities by activating transmembrane FGFR (FGF receptor) tyrosine kinases and their coupled intracellular signalling pathways. In the prostate, the mesenchymal-epithelial interactions mediated by androgen signalling and paracrine factors are essential for gland organogenesis, homoeostasis and tumorigenesis. FGFs mediate these mesenchymal-epithelial interactions in the prostate by paracrinal crosstalk through a diverse set of ligands and receptors. Gain- and loss-of-function studies in mouse models have demonstrated the requirement for the FGF signalling axis in prostate development and homoeostasis. The aberrant induction of this axis in either compartment of the prostate results in developmental disorders, disrupts the homoeostatic balance and leads to prostate carcinogenesis. FGFs are also implicated in mediating androgen signalling in the prostate between mesenchymal and epithelial compartments. Therefore studying FGF signalling in the prostate will help us to better understand the underlying molecular mechanisms by which the gland develops, maintains homoeostasis and undergoes carcinogenesis; as well as yield clues on how androgens mediate these processes and how advanced-tumour prostate cells escape strict androgen regulations.

  2. Ductal adenocarcinoma of the prostate: histogenesis, biology and clinicopathological features.

    PubMed

    Seipel, Amanda H; Delahunt, Brett; Samaratunga, Hemamali; Egevad, Lars

    2016-08-01

    Ductal adenocarcinoma of the prostate (DAC) is recognised as a subtype of prostatic adenocarcinoma, but its diagnostic criteria and biology remain controversial. DAC was first thought to stem from Müllerian duct remnants, but further studies suggest a prostatic origin. DAC is composed of tall, columnar, pseudostratified epithelium with a papillary, cribriform, glandular or solid architecture. The diagnosis is based on morphology alone with papillary architecture being the most helpful diagnostic feature. The tumour is rare in a pure form and most cases are combined with acinar adenocarcinoma. The most common differential diagnoses of DAC are intraductal carcinoma of the prostate and high-grade prostatic intraepithelial neoplasia. Patients often present at an advanced clinicopathological stage. High rates of extra-prostatic extension, seminal vesicle invasion, local and regional metastases, and positive surgical margins are seen after radical prostatectomy. DAC metastasises to sites that are less commonly seen for prostate cancer such as lung, brain, testis and penis. The morphology and the unusual metastatic locations make the accurate diagnosis of metastases challenging, but a positive immunostain for prostate specific markers may be helpful. The correct identification of DAC has implications for treatment as well as outcome. PMID:27321992

  3. An Overview of Current Screening and Management Approaches for Prostate Cancer.

    PubMed

    Akram, Omar N; Mushtaq, Gohar; Kamal, Mohammad Amjad

    2015-01-01

    Prostate cancer is the fourth leading cause of mortality in Australian men. The prevalence and incidence is increasing in both developed and developing nations, thus there is a need for better screening and management of this disorder. While there is no direct known cause of prostate cancer, management is largely focused on early detection and treatment strategies. Of particular concern is advanced prostate cancer which can manifest as castrate resistant prostate cancer characterized by therapy resistance. This short review outlines the global epidemiology of prostate cancer, clinical manifestations, risk factors, current screening strategies including first line clinical screening as well as the use of circulating biomarkers, and treatment of prostate cancer through mainstream therapeutics as well as the cutting edge peptide and nano-technology based therapeutics that are being implemented or in the process of development to overcome therapeutic obstacles in the treatment of prostate cancer.

  4. Penile Rehabilitation Strategies Among Prostate Cancer Survivors.

    PubMed

    Aoun, Fouad; Peltier, Alexandre; van Velthoven, Roland

    2015-01-01

    Despite advances in technical and surgical approaches, erectile dysfunction (ED) remains the most common complication among prostate cancer survivors, adversely impacting quality of life. This article analyzes the concept and rationale of ED rehabilitation programs in prostate cancer patients. Emphasis is placed on the pathophysiology of ED after diagnosis and treatment of prostate cancer to understand the efficacy of rehabilitation programs in clinical practice. Available evidence shows that ED is a transient complication following prostate biopsy and cancer diagnosis, with no evidence to support rehabilitation programs in these patients. A small increase in ED and in the use of phosphodiesterase type 5 (PDE5) inhibitors was reported in patients under active surveillance. Patients should be advised that active surveillance is unlikely to severely affect erectile function, but clinically significant changes in sexual function are possible. Focal therapy could be an intermediate option for patients demanding treatment/refusing active surveillance and invested in maintaining sexual activity. Unlike radical prostatectomy, there is no support for PDE5 inhibitor use to prevent ED after highly conformal external radiotherapy or low-dose rate brachytherapy. Despite progress in the understanding of the pathophysiologic mechanisms responsible for ED in prostate cancer patients, the success rates of rehabilitation programs remain low in clinical practice. Alternative strategies to prevent ED appear warranted, with attention toward neuromodulation, nerve grafting, nerve preservation, stem cell therapy, investigation of neuroprotective interventions, and further refinements of radiotherapy dosing and delivery methods. PMID:27222641

  5. Penile Rehabilitation Strategies Among Prostate Cancer Survivors

    PubMed Central

    Aoun, Fouad; Peltier, Alexandre; van Velthoven, Roland

    2015-01-01

    Despite advances in technical and surgical approaches, erectile dysfunction (ED) remains the most common complication among prostate cancer survivors, adversely impacting quality of life. This article analyzes the concept and rationale of ED rehabilitation programs in prostate cancer patients. Emphasis is placed on the pathophysiology of ED after diagnosis and treatment of prostate cancer to understand the efficacy of rehabilitation programs in clinical practice. Available evidence shows that ED is a transient complication following prostate biopsy and cancer diagnosis, with no evidence to support rehabilitation programs in these patients. A small increase in ED and in the use of phosphodiesterase type 5 (PDE5) inhibitors was reported in patients under active surveillance. Patients should be advised that active surveillance is unlikely to severely affect erectile function, but clinically significant changes in sexual function are possible. Focal therapy could be an intermediate option for patients demanding treatment/refusing active surveillance and invested in maintaining sexual activity. Unlike radical prostatectomy, there is no support for PDE5 inhibitor use to prevent ED after highly conformal external radiotherapy or low-dose rate brachytherapy. Despite progress in the understanding of the pathophysiologic mechanisms responsible for ED in prostate cancer patients, the success rates of rehabilitation programs remain low in clinical practice. Alternative strategies to prevent ED appear warranted, with attention toward neuromodulation, nerve grafting, nerve preservation, stem cell therapy, investigation of neuroprotective interventions, and further refinements of radiotherapy dosing and delivery methods. PMID:27222641

  6. Landmarks in prostate cancer diagnosis: the biomarkers.

    PubMed

    Artibani, Walter

    2012-10-01

    • The main diagnostic biomarker in current use is prostate-specific antigen (PSA) and it is one of the recommended diagnostic tools from the European Association of Urology Guidelines on prostate cancer. • One of the challenges with PSA is that men with very low levels of PSA can harbour prostate cancer, making it difficult to set a lower limit. • Several modifications to PSA biomarker detection have been suggested to improve its sensitivity and selectivity including PSA density, free:total PSA, PSA velocity/doubling time and different PSA isoforms. • However, there remains a need to improve accuracy of diagnosis and this has led to research in to a number of promising new biomarkers. • These include genetic and blood or urine based biomarkers. The most advanced of these is prostate cancer gene 3 found in urine and developed into a commercial test in 2006. • Other promising markers include circulating tumour cells (CTC) in blood, which have been correlated with survival in castration-resistant prostate cancer. A system for evaluating CTC was approved by the USA Food and Drug Administration in 2008.

  7. Progress and controversies: Radiation therapy for prostate cancer.

    PubMed

    Martin, Neil E; D'Amico, Anthony V

    2014-01-01

    Radiation therapy remains a standard treatment option for men with localized prostate cancer. Alone or in combination with androgen-deprivation therapy, it represents a curative treatment and has been shown to prolong survival in selected populations. In this article, the authors review recent advances in prostate radiation-treatment techniques, photon versus proton radiation, modification of treatment fractionation, and brachytherapy-all focusing on disease control and the impact on morbidity. Also discussed are refinements in the risk stratification of men with prostate cancer and how these are better for matching patients to appropriate treatment, particularly around combined androgen-deprivation therapy. Many of these advances have cost and treatment burden implications, which have significant repercussions given the prevalence of prostate cancer. The discussion includes approaches to improve value and future directions for research. PMID:25234700

  8. Treatment of Metastatic Prostate Cancer in Older Adults.

    PubMed

    Loh, Kah Poh; Mohile, Supriya G; Kessler, Elizabeth; Fung, Chunkit

    2016-10-01

    The aging of the population, along with rising life expectancy, means that increasing numbers of older men will be diagnosed with prostate cancer, and a large proportion of these men will present with metastatic disease. In this paper, we discuss recent advances in prostate cancer treatment. In particular, we review management approaches for older patients with metastatic prostate cancer based on the decision tree developed by the International Society of Geriatric Oncology, which categorized older men as "fit," "vulnerable," and "frail" according to comprehensive geriatric assessment. PMID:27586377

  9. Androgens and prostate disease

    PubMed Central

    Cooper, Lori A; Page, Stephanie T

    2014-01-01

    A growing body of literature has established the anabolic benefits of testosterone (T) therapy in hypogonadal men. However, there remains a paucity of data regarding the risks of exogenous androgen use in older men and the potential for adverse effects on the prostate gland. Whether T therapy in older, hypogonadal men might worsen lower urinary tract symptoms or exacerbate, unmask, or even incite prostate cancer development has tempered enthusiasm for T therapy, while known prostatic disease has served as a relative contraindication to T therapy. Androgens are necessary for the development and maintenance of the prostate gland. However, epidemiologic studies do not consistently find a positive relationship between endogenous serum androgen concentrations and the risk of prostate disease. Recent data demonstrate that 5α-reductase inhibitors decrease the risk of low-grade prostate cancer, suggesting that modifying androgen metabolism may have beneficial effects on prostate health, yet similar reductions in high-grade disease have not been observed, thereby questioning the true clinical benefits of these agents for chemoprevention. Knowing how to best investigate the relationship between androgens and the development of prostate disease given the lack of large, randomized trials is difficult. Accumulating data challenges the assumption that alterations in serum androgens have parallel effects within the prostate hormonal environment or change androgen-regulated processes within the gland. Long-term intervention studies are needed to truly ascertain the effects of androgen manipulation on prostate tissue and disease risk. However, available data do not support the notion that restoring serum androgens to normal physiologic ranges drives prostate disease. PMID:24407178

  10. Piperine, a Bioactive Component of Pepper Spice Exerts Therapeutic Effects on Androgen Dependent and Androgen Independent Prostate Cancer Cells

    PubMed Central

    Dakshinamoorthy, Gajalakshmi; Bartik, Mary Margaret; Johnson, Gary Leon; Webb, Brian; Zheng, Guoxing; Chen, Aoshuang; Kalyanasundaram, Ramaswamy; Munirathinam, Gnanasekar

    2013-01-01

    Prostate cancer is the most common solid malignancy in men, with 32,000 deaths annually. Piperine, a major alkaloid constituent of black pepper, has previously been reported to have anti-cancer activity in variety of cancer cell lines. The effect of piperine against prostate cancer is not currently known. Therefore, in this study, we investigated the anti-tumor mechanisms of piperine on androgen dependent and androgen independent prostate cancer cells. Here, we show that piperine inhibited the proliferation of LNCaP, PC-3, 22RV1 and DU-145 prostate cancer cells in a dose dependent manner. Furthermore, Annexin-V staining demonstrated that piperine treatment induced apoptosis in hormone dependent prostate cancer cells (LNCaP). Using global caspase activation assay, we show that piperine-induced apoptosis resulted in caspase activation in LNCaP and PC-3 cells. Further studies revealed that piperine treatment resulted in the activation of caspase-3 and cleavage of PARP-1 proteins in LNCaP, PC-3 and DU-145 prostate cancer cells. Piperine treatment also disrupted androgen receptor (AR) expression in LNCaP prostate cancer cells. Our evaluations further show that there is a significant reduction of Prostate Specific Antigen (PSA) levels following piperine treatment in LNCaP cells. NF-kB and STAT-3 transcription factors have previously been shown to play a role in angiogenesis and invasion of prostate cancer cells. Interestingly, treatment of LNCaP, PC-3 and DU-145 prostate cancer cells with piperine resulted in reduced expression of phosphorylated STAT-3 and Nuclear factor-κB (NF-kB) transcription factors. These results correlated with the results of Boyden chamber assay, wherein piperine treatment reduced the cell migration of LNCaP and PC-3 cells. Finally, we show that piperine treatment significantly reduced the androgen dependent and androgen independent tumor growth in nude mice model xenotransplanted with prostate cancer cells. Taken together, these results support

  11. Prevention and management of osteoporosis in women with breast cancer and men with prostate cancer.

    PubMed

    Hershman, Dawn; Narayanan, Rashmi

    2004-07-01

    Advances in cancer treatment have resulted in improved life expectancies for survivors of breast and prostate cancer. As the number of cancer survivors grows, the long-term side effects of treatment play an increasingly prominent role in the routine care of these patients. Due to similar management approaches, survivors of breast and prostate cancer are at increased risk for osteoporosis. This review summarizes the prevention and management of osteoporosis and osteopenia resulting from cancer treatment in survivors of breast and prostate cancer.

  12. Deletion of the Olfactomedin 4 Gene Is Associated with Progression of Human Prostate Cancer

    PubMed Central

    Li, Hongzhen; Rodriguez-Canales, Jaime; Liu, Wenli; Zhu, Jianqiong; Hanson, Jeffrey C.; Pack, Svetlana; Zhuang, Zhengping; Emmert-Buck, Michael R.; Rodgers, Griffin P.

    2014-01-01

    The olfactomedin 4 (OLFM4) gene is located on chromosome 13q14.3, which frequently is deleted in human prostate cancer. However, direct genetic evidence of OLFM4 gene alteration in human prostate cancer has not yet been obtained. In this study, we investigated the genetics, protein expression, and functions of the OLFM4 gene in human prostate cancer. We found overall 25% deletions within the OLFM4 gene in cancerous epithelial cells compared with adjacent normal epithelial cells that were microdissected from 31 prostate cancer specimens using laser-capture microdissection and genomic DNA sequencing. We found 28% to 45% hemizygous and 15% to 57% homozygous deletions of the OLFM4 gene via fluorescence in situ hybridization analysis from 44 different prostate cancer patient samples. Moreover, homozygous deletion of the OLFM4 gene significantly correlated with advanced prostate cancer. By using immunohistochemical analysis of 162 prostate cancer tissue array samples representing a range of Gleason scores, we found that OLFM4 protein expression correlated inversely with advanced prostate cancer, consistent with the genetic results. We also showed that a truncated mutant of OLFM4 that lacks the olfactomedin domain eliminated suppression of PC-3 prostate cancer cell growth. Together, our findings indicate that OLFM4 is a novel candidate tumor-suppressor gene for chromosome 13q and may shed new light on strategies that could be used for the diagnosis, prognosis, and treatment of prostate cancer patients. PMID:24070418

  13. The Prostate Exam

    ERIC Educational Resources Information Center

    Romero, Frederico R.; Romero, Antonio W.; Filho, Thadeu Brenny; Kulysz, David; Oliveira, Fernando C., Jr.; Filho, Renato Tambara

    2012-01-01

    Objective: To help students, residents, and general practitioners to improve the technique, skills, and reproducibility of their prostate examination. Methods: We developed a comprehensive guideline outlining prostate anatomy, indications, patient preparation, positioning, technique, findings, and limitations of this ancient art of urological…

  14. Cryosurgery for prostate cancer.

    PubMed

    Fahmy, W E; Bissada, N K

    2003-01-01

    Choice of management for patients with prostate cancer is influenced by patient and disease characteristics and life expectancy. Management options include expectance (watchful waiting), radical prostatectomy, external beam radiotherapy, brachytherapy, and cryosurgical ablation of the prostate (CSAP). The role of cryotherapy in the management of prostate cancer is still evolving. Continued research has allowed the introduction of efficient and safe cryosurgical equipment exemplified by the current third-generation cryosurgical machines. CSAP can be performed in an ambulatory surgery setting or as inpatient surgery with overnight stay. The procedure is performed under continuous ultrasonic monitoring. Mature data from the use of second-generation cryosurgical equipment indicate that CSAP is an effective therapeutic modality for managing patients with prostate cancer. Current data with the third-generation cryosurgical equipment are not mature. However, the favorable side effect profile and the good early responses seem to indicate that this modality will have a prominent role in the management of patients with prostate cancer.

  15. Vitamin K: the missing link to prostate health.

    PubMed

    Donaldson, Michael S

    2015-03-01

    Though age-related prostate enlargement is very common in Western societies, and the causes of benign prostate hyperplasia, BPH, have been diligently sought after, there is no biological, mechanistic explanation dealing with the root causes and progression of this very common disorder among men. All treatments to date are based on symptomatic relief, not a fundamental understanding of the cause of the disease. However, recent advances have shown that even subclinical varicoceles, which are more common than generally realized, cause retrograde blood flow from the testes past the prostate gland causing over a 130-fold increase in free testosterone in the veins near the prostate. By treating the varicoceles via embolization of the internal spermatic vein and its communicating and connected vessels the prostate enlargement can be reversed with corresponding symptomatic relief. So, varicose veins in the pampiniform venous plexus, varicoceles, are the direct cause of BPH. But what causes varicoceles? Recent research has uncovered the role of vitamin K in the calcification of varicose veins as well as a role in the proliferation of smooth muscle cells in the media layer of the vein wall. Vitamin K is intimately involved in the formation of varicose veins. The hypothesis is that poor prostate health is essentially a vitamin K insufficiency disorder. By providing vitamin K in the right form and quantity, along with other supporting nutrients and phytochemicals, it is likely that excellent prostate health can be extended much longer, and perhaps poor prostate health can be reversed. A protective role for vitamin K with respect to advanced prostate cancer was already found in the Heidelberg cohort of the EPIC study. This hypothesis can be further evaluated in studies examining the connection between vitamin K and varicoceles, and also by examining the connection between varicoceles and benign prostate hyperplasia. If this hypothesis is found to be true, management of prostate

  16. IGFBP-3 is a Metastasis Suppression Gene in Prostate Cancer

    PubMed Central

    Mehta, Hemal H.; Gao, Qinglei; Galet, Colette; Paharkova, Vladislava; Wan, Junxiang; Said, Jonathan; Sohn, Joanne J.; Lawson, Gregory; Cohen, Pinchas; Cobb, Laura J.; Lee, Kuk-Wha

    2011-01-01

    The insulin-like growth factor binding protein IGFBP-3 is a pro-apoptotic and anti-angiogenic protein in prostate cancer (CaP). Epidemiological studies suggest that low IGFBP-3 is associated with greater risk of aggressive, metastatic prostate cancers, but in vivo functional data are lacking. Here we show that mice that are genetically deficient in IGFBP-3 exhibit weaker growth of primary prostate tumors growth but higher incidence of metastatic disease. Prostates in IGFBP-3 knockout mice (IGFBP-3KO mice) failed to undergo apoptosis after castration. Spontaneous prostate tumors did not develop in IGFBP-3KO mice, but splenic lymphomas occured in 23% of female IGFBP-3KO mice by 80 weeks of age. To assess the effects of IGFBP-3 deficiency on prostate cancer development, we crossed IGFBP-3KO mice with a c-Myc-driven model of CaP that develops slow-growing, non-metastatic tumors. By 24 weeks of age, well-differentiated prostate cancers were observed in all mice regardless of IGFBP-3 status. However, by 80 weeks of age IGFBP-3KO mice tended to exhibit larger prostate tumors than control mice. More strikingly, lung metastases were observed at this time in 55% of the IGFBP-3KO mice but none of the control animals. Cell lines established from Myc:IGFBP-3KO tumors displayed more aggressive phenotypes in proliferation, invasion and colony formation assays, relative to control Myc tumor cell lines. In addition, Myc:IGFBP-3KO cells exhibited evidence of epithelial-mesenchymal transition (EMT). Our findings establish a function for IGFBP-3 in suppressing metastasis in prostate cancer, and they also offer the first reported transgenic model of spontaneous metastatic prostate cancer for studies of this advanced stage of disease. PMID:21697285

  17. Olaparib With or Without Cediranib in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer

    ClinicalTrials.gov

    2016-09-08

    Hormone-Resistant Prostate Cancer; Metastatic Prostate Carcinoma; Prostate Adenocarcinoma With Focal Neuroendocrine Differentiation; Prostate Carcinoma Metastatic in the Bone; Prostate Small Cell Carcinoma; Stage IV Prostate Adenocarcinoma

  18. Tocopherols and saponins derived from Argania spinosa exert, an antiproliferative effect on human prostate cancer.

    PubMed

    Drissi, A; Bennani, H; Giton, F; Charrouf, Z; Fiet, J; Adlouni, A

    2006-10-01

    The aim of our study is to evaluate the antiproliferative effect of tocopherols obtained from alimentary virgin argan oil extracted from the endemic argan tree of Morocco and of saponins extracted from argan press cake on three human prostatic cell lines (DU145, LNCaP, and PC3). The results were compared to 2-methoxyestradiol as antiproliferative drug candidates. Cytotoxicity and antiproliferative effects were investigated after cells' treatment with tocopherols and saponins compared to 2-Methoxyoestradiol as the positive control. Tocopherols and saponins extracted from argan tree and 2-methoxyestradiol exhibit a dose-response cytotoxic effect and an antiproliferative action on the tested cell lines. The best antiproliferative effect of tocopherols is obtained with DU145 and LNCaP cell lines (28 microg/ml and 32 microg/ml, respectively, as GI50). The saponins fraction displayed the best antiproliferative effect on the PC3 cell line with 18 microg/ml as GI50. Our results confirm the antiproliferative effect of 2-methoxyestradiol and show for the first time the antiproliferative effect of tocopherols and saponins extracted from the argan tree on hormone-dependent and hormone-independent prostate cancer cell lines. These data suggest that argan oil is of potential interest in developing new strategies for prostate cancer prevention. PMID:16982463

  19. Tocopherols and saponins derived from Argania spinosa exert, an antiproliferative effect on human prostate cancer.

    PubMed

    Drissi, A; Bennani, H; Giton, F; Charrouf, Z; Fiet, J; Adlouni, A

    2006-10-01

    The aim of our study is to evaluate the antiproliferative effect of tocopherols obtained from alimentary virgin argan oil extracted from the endemic argan tree of Morocco and of saponins extracted from argan press cake on three human prostatic cell lines (DU145, LNCaP, and PC3). The results were compared to 2-methoxyestradiol as antiproliferative drug candidates. Cytotoxicity and antiproliferative effects were investigated after cells' treatment with tocopherols and saponins compared to 2-Methoxyoestradiol as the positive control. Tocopherols and saponins extracted from argan tree and 2-methoxyestradiol exhibit a dose-response cytotoxic effect and an antiproliferative action on the tested cell lines. The best antiproliferative effect of tocopherols is obtained with DU145 and LNCaP cell lines (28 microg/ml and 32 microg/ml, respectively, as GI50). The saponins fraction displayed the best antiproliferative effect on the PC3 cell line with 18 microg/ml as GI50. Our results confirm the antiproliferative effect of 2-methoxyestradiol and show for the first time the antiproliferative effect of tocopherols and saponins extracted from the argan tree on hormone-dependent and hormone-independent prostate cancer cell lines. These data suggest that argan oil is of potential interest in developing new strategies for prostate cancer prevention.

  20. Optimization of prostate biopsy

    NASA Astrophysics Data System (ADS)

    Bauer, John J.; Zeng, Jianchao; Weir, James; Zhang, Wei; Sesterhenn, Isabell A.; Connelly, Roger R.; Moul, Judd W.; Mun, Seong K.

    1999-05-01

    Urologists routinely use the systematic sextant needle biopsy technique to detect prostate cancer. However, recent evidence suggests that this technique has a significant sampling error. We have developed a novel 3D computer assisted prostate biopsy simulator based upon 201 whole- mounted step-sectioned radical prostatectomy specimens to compare the diagnostic accuracy of various prostate needle biopsy protocols. Computerized prostate models have been developed to accurately depict the anatomy of the prostate and all individual tumor foci. We obtained 18-biopsies of each prostate model to determine the detection rates of various biopsy protocols. As a result, the 10- and 12- pattern biopsy protocols had a 99.0 percent detection rate, while the traditional sextant biopsy protocol rate was only 72.6 percent. The 5-region biopsy protocol had a 90.5 percent detection rate. the lateral sextant pattern revealed a detection rate of 95.5 percent, whereas the 4-pattern lateral biopsy protocol had a 93.5 percent detection rate. Our results suggest that all the biopsy protocols that use laterally placed biopsies based upon the five region anatomical model are superior to the routinely used sextant prostate biopsy pattern. Lateral biopsies in the mid and apical zones of the gland are the most important.

  1. The Distinct Gene Regulatory Network of Myoglobin in Prostate and Breast Cancer

    PubMed Central

    Bicker, Anne; Brahmer, Alexandra M.; Meller, Sebastian; Kristiansen, Glen; Gorr, Thomas A.; Hankeln, Thomas

    2015-01-01

    Myoglobin (MB) is not only strongly expressed in myocytes, but also at much lower levels in different cancer entities. 40% of breast tumors are MB-positive, with the globin being co-expressed with markers of tumor hypoxia in a proportion of cases. In breast cancer, MB expression is associated with a positive hormone receptor status and patient prognosis. In prostate cancer, another hormone-dependent cancer type, 53% of tumors were recently shown to express MB. Especially in more aggressive prostate cancer specimen MB expression also correlates with increased patient survival rates. Both findings might be due to tumor-suppressing properties of MB in cancer cells. In contrast to muscle, MB transcription in breast and prostate cancer mainly depends on a novel, alternative promoter site. We show here that its associated transcripts can be upregulated by hypoxia and downregulated by estrogens and androgens in MCF7 breast and LNCaP prostate cancer cells, respectively. Bioinformatic data mining of epigenetic histone marks and experimental verification reveal a hitherto uncharacterized transcriptional network that drives the regulation of the MB gene in cancer cells. We identified candidate hormone-receptor binding elements that may interact with the cancer-associated MB promoter to decrease its activity in breast and prostate cancer cells. Additionally, a regulatory element, 250 kb downstream of the promoter, acts as a hypoxia-inducible site within the transcriptional machinery. Understanding the distinct regulation of MB in tumors will improve unraveling the respiratory protein’s function in the cancer context and may provide new starting points for developing therapeutic strategies. PMID:26559958

  2. Organoid culture systems for prostate epithelial and cancer tissue.

    PubMed

    Drost, Jarno; Karthaus, Wouter R; Gao, Dong; Driehuis, Else; Sawyers, Charles L; Chen, Yu; Clevers, Hans

    2016-02-01

    This protocol describes a strategy for the generation of 3D prostate organoid cultures from healthy mouse and human prostate cells (either bulk or FACS-sorted single luminal and basal cells), metastatic prostate cancer lesions and circulating tumor cells. Organoids derived from healthy material contain the differentiated luminal and basal cell types, whereas organoids derived from prostate cancer tissue mimic the histology of the tumor. We explain how to establish these cultures in the fully defined serum-free conditioned medium that is required to sustain organoid growth. Starting with the plating of digested tissue material, full-grown organoids can usually be obtained in ∼2 weeks. The culture protocol we describe here is currently the only one that allows the growth of both the luminal and basal prostatic epithelial lineages, as well as the growth of advanced prostate cancers. Organoids established using this protocol can be used to study many different aspects of prostate biology, including homeostasis, tumorigenesis and drug discovery.

  3. Gonadotrophin releasing hormone-based vaccine, an effective candidate for prostate cancer and other hormone-sensitive neoplasms.

    PubMed

    Junco, Jesús A; Basalto, Roberto; Fuentes, Franklin; Bover, Eddy; Reyes, Osvaldo; Pimentel, Eulogio; Calzada, Lesvia; Castro, Maria D; Arteaga, Niurka; López, Yovisleidis; Hernández, Héctor; Bringas, Ricardo; Garay, Hilda; Peschke, Peter; Bertot, José; Guillén, Gerardo

    2008-01-01

    Prostate growth, development, functions, and neoplastic transformation is androgen dependent. Estrogens have similar effects in the ovary and breast. Previous studies using gonadotrophin releasing hormone (GnRH/LHRH) vaccines have shown the usefulness of immunization against this hormone in prostate (PC) and breast cancer (BC). We have synthesized a peptide mutated at position 6 and attached to the 830-844 tetanic toxoid (TT) helper T cell sequence in the same synthesis process. After repeated pig immunizations, we have demonstrated a vaccine that significantly decreased testes size (p < 0.001), prostate (p < 0.01), seminal vesicles (p < 0.01), and testosterone (T) castration [0.05 nM ml(-1) (p < 0. 01)]. Similar results were obtained in adult male and female healthy dogs and Macaca fascicularis models. These data indicate that this GnRHm1-TT vaccine is safe and able to induce significant tumor growth inhibition in the Dunning R3327-H rat androgen responsive prostate tumor model. In these rats, the immunization induced high anti-GnRH titers concomitant with T castration reduction (p < 0.01) in 90% of the animals tested. In addition, 70% of the responders exhibited tumor growth inhibition (p = 0.02) and a survival rate approximately three times longer that those of untreated rats. These data indicate that GnRHm1-TT vaccine may be a potential candidate in the treatment of PC, BC, and other hormone-dependent cancers. PMID:18497085

  4. Gonadotrophin releasing hormone-based vaccine, an effective candidate for prostate cancer and other hormone-sensitive neoplasms.

    PubMed

    Junco, Jesús A; Basalto, Roberto; Fuentes, Franklin; Bover, Eddy; Reyes, Osvaldo; Pimentel, Eulogio; Calzada, Lesvia; Castro, Maria D; Arteaga, Niurka; López, Yovisleidis; Hernández, Héctor; Bringas, Ricardo; Garay, Hilda; Peschke, Peter; Bertot, José; Guillén, Gerardo

    2008-01-01

    Prostate growth, development, functions, and neoplastic transformation is androgen dependent. Estrogens have similar effects in the ovary and breast. Previous studies using gonadotrophin releasing hormone (GnRH/LHRH) vaccines have shown the usefulness of immunization against this hormone in prostate (PC) and breast cancer (BC). We have synthesized a peptide mutated at position 6 and attached to the 830-844 tetanic toxoid (TT) helper T cell sequence in the same synthesis process. After repeated pig immunizations, we have demonstrated a vaccine that significantly decreased testes size (p < 0.001), prostate (p < 0.01), seminal vesicles (p < 0.01), and testosterone (T) castration [0.05 nM ml(-1) (p < 0. 01)]. Similar results were obtained in adult male and female healthy dogs and Macaca fascicularis models. These data indicate that this GnRHm1-TT vaccine is safe and able to induce significant tumor growth inhibition in the Dunning R3327-H rat androgen responsive prostate tumor model. In these rats, the immunization induced high anti-GnRH titers concomitant with T castration reduction (p < 0.01) in 90% of the animals tested. In addition, 70% of the responders exhibited tumor growth inhibition (p = 0.02) and a survival rate approximately three times longer that those of untreated rats. These data indicate that GnRHm1-TT vaccine may be a potential candidate in the treatment of PC, BC, and other hormone-dependent cancers.

  5. Chemoprevention of prostate cancer.

    PubMed

    Vemana, Goutham; Hamilton, Robert J; Andriole, Gerald L; Freedland, Stephen J

    2014-01-01

    Large prospective randomized trials, such as the Prostate Cancer Prevention Trial (PCPT), Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial, and Selenium and Vitamin E Cancer Prevention Trial (SELECT), have provided practitioners with considerable data regarding methods of treatment and prevention of prostate cancer. The best-studied medications for prevention are 5 alpha-reductase inhibitors. Their efficacy and side effects are well characterized. Other medications, dietary nutrients, and supplements have not been as well studied and generally do not demonstrate efficacy for disease prevention with an acceptable level of evidence. PMID:24188663

  6. Assessment of Prostatism

    PubMed Central

    Barrett, Peter H.

    1978-01-01

    Prostatism is a syndrome associated with outlet obstruction at the bladder neck and the commonest cause is benign prostatic hypertrophy. The main indications for investigation and treatment are these symptoms (especially nocturia). The diagnosis should then be confirmed by the physical signs such as an enlarged gland or palpable bladder. If other causes of these symptoms are eliminated, the patient should be referred to a urologist to confirm, through cystoscopy, signs of an obstructing prostate and bladder trabeculation. The surgery (TUR or open) for benign disease leaves the capsules behind and the patient should still be followed with routine rectal examinations for early detection of malignancy. PMID:21301523

  7. Metformin and prostate cancer stem cells: a novel therapeutic target.

    PubMed

    Mayer, M J; Klotz, L H; Venkateswaran, V

    2015-12-01

    Prostate cancer is the second most frequently diagnosed cancer in the world. Localized disease can be effectively treated with radiation therapy or radical prostatectomy. However, advanced prostate cancer is more difficult to treat and if metastatic, is incurable. There is a need for more effective therapy for advanced prostate cancer. One potential target is the cancer stem cell (CSC). CSCs have been described in several solid tumors, including prostate cancer, and contribute to therapeutic resistance and tumor recurrence. Metformin, a common oral biguanide used to treat type 2 diabetes, has been demonstrated to have anti-neoplastic effects. Specifically, metformin targets CSCs in breast cancer, pancreatic cancer, glioblastoma and colon cancer. Metformin acts directly on the mitochondria to inhibit oxidative phosphorylation and reduce mitochondrial ATP production. This forces tumor cells to compensate by increasing the rate of glycolysis. CSCs rely heavily on mitochondrial oxidative phosphorylation for energy production. The glycolytic switch results in an energy crisis in these cells. Metformin could be used to exploit this metabolic weakness in CSCs. This would increase CSC sensitivity to conventional cancer therapies, circumventing treatment resistance and enhancing treatment efficacy. This review will explore the characteristics of prostate CSCs, their role in tumor propagation and therapeutic resistance and the role of metformin as a potential prostate CSC sensitizer to current anticancer therapies. PMID:26215782

  8. Metformin and prostate cancer stem cells: a novel therapeutic target.

    PubMed

    Mayer, M J; Klotz, L H; Venkateswaran, V

    2015-12-01

    Prostate cancer is the second most frequently diagnosed cancer in the world. Localized disease can be effectively treated with radiation therapy or radical prostatectomy. However, advanced prostate cancer is more difficult to treat and if metastatic, is incurable. There is a need for more effective therapy for advanced prostate cancer. One potential target is the cancer stem cell (CSC). CSCs have been described in several solid tumors, including prostate cancer, and contribute to therapeutic resistance and tumor recurrence. Metformin, a common oral biguanide used to treat type 2 diabetes, has been demonstrated to have anti-neoplastic effects. Specifically, metformin targets CSCs in breast cancer, pancreatic cancer, glioblastoma and colon cancer. Metformin acts directly on the mitochondria to inhibit oxidative phosphorylation and reduce mitochondrial ATP production. This forces tumor cells to compensate by increasing the rate of glycolysis. CSCs rely heavily on mitochondrial oxidative phosphorylation for energy production. The glycolytic switch results in an energy crisis in these cells. Metformin could be used to exploit this metabolic weakness in CSCs. This would increase CSC sensitivity to conventional cancer therapies, circumventing treatment resistance and enhancing treatment efficacy. This review will explore the characteristics of prostate CSCs, their role in tumor propagation and therapeutic resistance and the role of metformin as a potential prostate CSC sensitizer to current anticancer therapies.

  9. Focal Therapy in the Management of Prostate Cancer: An Emerging Approach for Localized Prostate Cancer

    PubMed Central

    Nomura, Takeo; Mimata, Hiromitsu

    2012-01-01

    A widespread screening with prostate-specific antigen (PSA) has led increased diagnosis of localized prostate cancer along with a reduction in the proportion of advanced-stage disease at diagnosis. Over the past decade, interest in focal therapy as a less morbid option for the treatment of localized low-risk prostate cancer has recently been renewed due to downward stage migration. Focal therapy stands midway between active surveillance and radical treatments, combining minimal morbidity with cancer control. Several techniques of focal therapy have potential for isolated ablation of a tumor focus with sparing of uninvolved surround tissue demonstrating excellent short-term cancer control and a favorable patient's quality of life. However, to date, tissue ablation has mostly used for near-whole prostate gland ablation without taking advantage of accompanying the technological capabilities. The available ablative technologies include cryotherapy, high-intensity focused ultrasound (HIFU), and vascular-targeted photodynamic therapy (VTP). Despite the interest in focal therapy, this technology has not yet been a well-established procedure nor provided sufficient data, because of the lack of randomized trial comparing the efficacy and morbidity of the standard treatment options. In this paper we briefly summarize the recent data regarding focal therapy for prostate cancer and these new therapeutic modalities. PMID:22593764

  10. AEG-1 promoter-mediated imaging of prostate cancer

    PubMed Central

    Bhatnagar, Akrita; Wang, Yuchuan; Mease, Ronnie C.; Gabrielson, Matthew; Sysa, Polina; Minn, Il; Green, Gilbert; Simmons, Brian; Gabrielson, Kathleen; Sarkar, Siddik; Fisher, Paul B.; Pomper, Martin G.

    2014-01-01

    We describe a new imaging method for detecting prostate cancer, whether localized or disseminated and metastatic to soft tissues and bone. The method relies on the use of imaging reporter genes under the control of the promoter of AEG-1 (MTDH), which is selectively active only in malignant cells. Through systemic, nanoparticle-based delivery of the imaging construct, lesions can be identified through bioluminescence imaging and single photon emission-computed tomography in the PC3-ML murine model of prostate cancer at high sensitivity. This approach is applicable for the detection of prostate cancer metastases, including bone lesions for which there is no current reliable agent for non-invasive clinical imaging. Further, the approach compares favorably to accepted and emerging clinical standards, including positron emission tomography with [18F]fluorodeoxyglucose and [18F]sodium fluoride. Our results offer a preclinical proof of concept that rationalizes clinical evaluation in patients with advanced prostate cancer. PMID:25145668

  11. Temporal Changes in the Pathologic Assessment of Prostate Cancer

    PubMed Central

    2012-01-01

    Thirty years have witnessed dramatic changes in the manner in which we diagnose and manage prostate cancer. With prostate-specific antigen screening, there was a shift towards smaller, clinically localized tumors. Tumors are often multifocal and display phenotypic and molecular heterogeneity. Pathologic evaluation of tissue obtained by needle biopsy remains the gold standard for the diagnosis and risk assessment of prostate cancer. Years of experience with grading, along with changes in the amount of biopsy tissue obtained and diagnostic tools available, have produced shifts in grading practices among genitourinary pathologists. Trends in Gleason grading and advances in pathological risk assessment are reviewed with particular emphasis on recent Gleason grading modifications of the International Society of Urologic Pathology. Efforts to maximize the amount of information from pathological specimens, whether it be morphometric, histochemical, or molecular, may improve predictive accuracy of prostate biopsies. New diagnostic techniques are needed to optimize management decisions. PMID:23271767

  12. Gastric adenocarcinoma with prostatic metastasis.

    PubMed

    Roshni, S; Anoop, Tm; Preethi, Tr; Shubanshu, G; Lijeesh, Al

    2014-06-01

    Metastasis of gastric adenocarcinoma to the prostate gland is extremely rare. Herein, we report a case of gastric adenocarcinoma in a 56-year-old man with prostatic metastasis diagnosed through the analysis of biopsy specimens from representative lesions in the stomach and prostate gland. Immunohistochemistry of the prostatic tissue showed positive staining for cytokeratin 7 and negative staining for prostate-specific antigen (PSA), whereas the serum PSA level was normal, confirming the diagnosis of prostatic metastasis from carcinoma of the stomach. PMID:25061542

  13. Gastric Adenocarcinoma with Prostatic Metastasis

    PubMed Central

    Roshni, S; Preethi, TR; Shubanshu, G; Lijeesh, AL

    2014-01-01

    Metastasis of gastric adenocarcinoma to the prostate gland is extremely rare. Herein, we report a case of gastric adenocarcinoma in a 56-year-old man with prostatic metastasis diagnosed through the analysis of biopsy specimens from representative lesions in the stomach and prostate gland. Immunohistochemistry of the prostatic tissue showed positive staining for cytokeratin 7 and negative staining for prostate-specific antigen (PSA), whereas the serum PSA level was normal, confirming the diagnosis of prostatic metastasis from carcinoma of the stomach. PMID:25061542

  14. Diabetes Protects from Prostate Cancer by Downregulating Androgen Receptor: New Insights from LNCaP Cells and PAC120 Mouse Model

    PubMed Central

    Barbosa-Desongles, Anna; Hernández, Cristina; De Torres, Ines; Munell, Francina; Poupon, Marie-France; Simó, Rafael; Selva, David M.

    2013-01-01

    Type 2 diabetes has been associated with decreased risk of prostate cancer in observational studies, and this inverse association has been recently confirmed in several large cohort studies. However the mechanisms involved in this protective effect remain to be elucidated. The aim of the present study was to explore whether different features of type 2 diabetes (hyperinsulinemia, hyperglycemia and tumor necrosis factor alpha [TNF-α]) protect against the development of prostate cancer. For this purpose LNCaP cells were used for in vitro experiments and nude mice in which PAC120 (hormone-dependent human prostate cancer) xenografts had been implanted were used for in vivo examinations. We provide evidence that increasing glucose concentrations downregulate androgen receptor (AR) mRNA and protein levels through NF-κB activation in LNCaP cells. Moreover, there was a synergic effect of glucose and TNFα in downregulating the AR in LNCaP cells. By contrast, insulin had no effect on AR regulation. In vivo experiments showed that streptozotocin-induced diabetes (STZ-DM) produces tumor growth retardation and a significant reduction in AR expression in PAC120 prostate cancer mice. In conclusion, our results suggest that hyperglycemia and TNF-α play an important role in protecting against prostate cancer by reducing androgen receptor levels via NF-κB. PMID:24058525

  15. Id-1 expression induces androgen-independent prostate cancer cell growth through activation of epidermal growth factor receptor (EGF-R).

    PubMed

    Ling, Ming-Tat; Wang, Xianghong; Lee, Davy T; Tam, P C; Tsao, Sai-Wah; Wong, Yong-Chuan

    2004-04-01

    The failure of prostate cancer treatment is largely due to the development of androgen independence, since the androgen depletion therapy remains the front-line option for this cancer. Previously, we reported that over-expression of the helix-loop-helix protein Id-1 was associated with progression of prostate cancer and ectopic expression of Id-1 induced serum-independent proliferation in prostate cancer cells. In the present study, we investigated if exogenous Id-1 expression in the androgen sensitive LNCaP cells had any effect on androgen-dependent cell growth and studied the molecular mechanisms involved. Using stable Id-1 transfectants, we found that expression of Id-1 was able to reduce androgen-stimulated growth and S phase fraction of the cell cycle in LNCaP cells, indicating that Id-1 may be involved in the development of androgen independence in these cells. The Id-1-induced androgen-independent prostate cancer cell growth was correlated with up-regulation of EGF-R (epidermal growth factor-receptor) and PSA (prostate specific antigen) expression, as confirmed by western blotting analysis and luciferase assays. In contrast, down-regulation of Id-1 in androgen-independent DU145 cells by its antisense oligonucleotides resulted in suppression of EGF-R expression at both transcriptional and protein levels. In addition, the results from immunohistochemistry study showed that Id-1 expression was significantly elevated in hormone refractory prostate cancer tissues when compared with the hormone-dependent tumours. Our results suggest that up-regulation of Id-1 in prostate cancer cells may be one of the mechanisms responsible for developing androgen independence and this process may be regulated through induction of EGF-R expression. Inactivation of Id-1 may provide a potential therapeutic strategy leading to inhibition of androgen-independent prostate cancer cell growth.

  16. MRI of the Prostate

    MedlinePlus

    ... The images can then be examined on a computer monitor, transmitted electronically, printed or copied to a CD. The prostate gland is part of the male reproductive system. It is located in front of the rectum ...

  17. Prostate Cancer Foundation

    MedlinePlus

    ... Close About Us Our Story A Legacy of Leadership About the Prostate Cancer Foundation CEO Message Why ... Cancer Board of Directors Annual Report & Financials Our Leadership Leadership Team A Legacy of Leadership Featured Take ...

  18. Chemoprevention of prostate cancer.

    PubMed

    Rittmaster, Roger S

    2011-06-01

    Over the past two decades, many more men are diagnosed with prostate cancer then die of the disease. This increase in diagnosis has led to aggressive treatment of indolent disease in many individuals and has been the impetus for finding a means of reducing the risk of prostate cancer. In the past decade, there have been eight large trials of prostate cancer risk reduction using dietary supplements, 5α-reductase inhibitors, or anti-estrogens. The only two trials which have demonstrated efficacy are those involving 5α-reductase inhibitors: the PCPT (finasteride) and REDUCE (dutasteride). This review examines prostate cancer risk reduction, with emphasis on conclusions that can be drawn from these two landmark studies. PMID:21604953

  19. Chemoprevention of prostate cancer.

    PubMed

    Stephenson, Andrew J; Abouassaly, Robert; Klein, Eric A

    2010-02-01

    Prostate cancer is an appropriate target for primary chemoprevention because of its ubiquity, disease-related mortality, treatment-related morbidity, and long latency period. The PCPT and REDUCE trials demonstrate that this cancer can be prevented by a relatively nontoxic oral pharmacologic agent (5alpha-reductase inhibitors). Evidence from the SELECT trial argues against the recommendation of the use of vitamins and micronutrients as chemoprevention of prostate cancer. Dietary modification may substantially alter a man's risk of prostate cancer, but the specific dietary manipulations that are necessary are poorly defined and these may need to be instituted in early adulthood to be successful. 5alpha-reductase inhibitors represent an effective primary prevention strategy, and these agents should be used more liberally for the prevention of prostate cancer, particularly in high-risk patients. PMID:20152515

  20. Chronic prostatitis: management strategies.

    PubMed

    Murphy, Adam B; Macejko, Amanda; Taylor, Aisha; Nadler, Robert B

    2009-01-01

    The National Institutes of Health (NIH) has redefined prostatitis into four distinct entities. Category I is acute bacterial prostatitis. It is an acute prostatic infection with a uropathogen, often with systemic symptoms of fever, chills and hypotension. The treatment hinges on antimicrobials and drainage of the bladder because the inflamed prostate may block urinary flow. Category II prostatitis is called chronic bacterial prostatitis. It is characterized by recurrent episodes of documented urinary tract infections with the same uropathogen and causes pelvic pain, urinary symptoms and ejaculatory pain. It is diagnosed by means of localization cultures that are 90% accurate in localizing the source of recurrent infections within the lower urinary tract. Asymptomatic inflammatory prostatitis comprises NIH category IV. This entity is, by definition, asymptomatic and is often diagnosed incidentally during the evaluation of infertility or prostate cancer. The clinical significance of category IV prostatitis is unknown and it is often left untreated. Category III prostatitis is called chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). It is characterized by pelvic pain for more than 3 of the previous 6 months, urinary symptoms and painful ejaculation, without documented urinary tract infections from uropathogens. The syndrome can be devastating, affecting 10-15% of the male population, and results in nearly 2 million outpatient visits each year. The aetiology of CP/CPPS is poorly understood, but may be the result of an infectious or inflammatory initiator that results in neurological injury and eventually results in pelvic floor dysfunction in the form of increased pelvic muscle tone. The diagnosis relies on separating this entity from chronic bacterial prostatitis. If there is no history of documented urinary tract infections with a urinary tract pathogen, then cultures should be taken when patients are symptomatic. Prostatic localization cultures, called the

  1. Prostate cancer (image)

    MedlinePlus

    Treatment of prostate cancer varies depending on the stage of the cancer (i.e., spread) and may include surgical removal, radiation, chemotherapy, hormonal manipulation or a combination of these treatments.

  2. Prostate cancer staging

    MedlinePlus

    ... test. A faster increase could show a more aggressive tumor. A prostate biopsy is done in your ... suggest the cancer is slow growing and not aggressive. Higher numbers indicate a faster growing cancer that ...

  3. What Is Prostate Cancer?

    MedlinePlus Videos and Cool Tools

    ... the more likely he is to develop the disease. Physician: Come on back, first room. Narrator: Most ... cancer. Prostate cancer is really a spectrum of diseases where on one end of the spectrum there ...

  4. Enlarged prostate gland

    MedlinePlus

    ... enlarges in size in a process called benign hypertrophy, which means that the gland got larger without ... in several of the symptoms of benign prostatic hypertrophy, or BPH. Symptoms may include a slowed or ...

  5. Detecting Prostate Cancer

    MedlinePlus Videos and Cool Tools

    ... abnormal and raises the index of suspicion that cancer may be present. Narrator: While the use of ... examination does not mean that they have prostate cancer. It means that we're concerned about it ...

  6. Nanoparticle therapeutics for prostate cancer treatment.

    PubMed

    Sanna, Vanna; Sechi, Mario

    2012-09-01

    The application of nanotechnology in medicine is offering many exciting possibilities in healthcare. Engineered nanoparticles have the potential to revolutionize the diagnosis and the therapy of several diseases, particularly by targeted delivery of anticancer drugs and imaging contrast agents. Prostate cancer, the second most common cancer in men, represents one of the major epidemiological problems, especially for patients in the advanced age. There is a substantial interest in developing therapeutic options for treatment of prostate cancer based on use of nanodevices, to overcome the lack of specificity of conventional chemotherapeutic agents as well as for the early detection of precancerous and malignant lesions. Herein, we highlight on the recent development of nanotechnology strategies adopted for the management of prostate cancer. In particular, the combination of targeted and controlled-release polymer nanotechnologies has recently resulted in the clinical development of BIND-014, a promising targeted Docetaxel-loaded nanoprototype, which can be validated for use in the prostate cancer therapy. However, several limitations facing nanoparticle delivery to solid tumours, such as heterogeneity of intratumoural barriers and vasculature, cytotoxicity and/or hypersensitivity reactions to currently available cancer nanomedicines, and the difficult in developing targeted nanoparticles with optimal biophysicochemical properties, should be still addressed for a successful tumour eradication.

  7. [Radiotherapy in prostate cancer: data from ASTRO 2008].

    PubMed

    Coquard, R

    2009-05-01

    The annual convention of the American Society for Therapeutic Radiology and Oncology (ASTRO) took place in Boston, MA, 21-25 September 2008. On the occasion of this meeting, in which the past year's main advances in radiation oncology have been highlighted, results from clinical studies that may significantly impact the standard clinical practice were presented, particularly in the fields of locally advanced prostate cancer treated with non surgical approaches, and pT3 and/or R1 prostate cancer managed with radical prostatectomy. Randomized studies that emphasize the role of dose escalation have been updated.

  8. Cultural sensitivity and informed decision making about prostate cancer screening.

    PubMed

    Chan, Evelyn C Y; Haynes, Michelle C; O'Donnell, Frederick T; Bachino, Carolyn; Vernon, Sally W

    2003-12-01

    Because informed consent for prostate cancer screening with prostate specific antigen (PSA) is recommended, we determined how African Americans, Hispanics, and Caucasians want information about screening with PSA and the digital rectal exam (DRE) presented in culturally sensitive brochures specific for each group. We analyzed focus group discussions using content analysis and compared themes across groups in a university outpatient internal medicine practice setting. The participants were twenty couples with men age 50 and older who participated in four focus groups. Main outcome measures were participants' views on the content and graphic design of culturally sensitive brochures promoting informed decision making about prostate cancer screening. There were content and graphic design differences in the way ethnic groups wanted information presented about the prostate, prostate cancer, risk, and screening. Caucasians likened the size of the prostate to a walnut; Hispanics, to a small lime. Hispanics emphasized how advanced prostate cancer can be symptomatic; Caucasians, how early prostate cancer can be asymptomatic. African Americans wanted risk information specific for them and the advantages and disadvantages of a PSA and DRE; Hispanics, did not. Caucasians and African Americans sought a more active role for men in informed decision making than Hispanics. Differences in the way African Americans, Hispanics, and Caucasians want information presented about prostate cancer screening suggest there may be cultural differences in the reasonable person standard of informed consent, in attitudes toward the physician-patient relationship, screening, and informed decision making. Physicians promoting informed decision making about controversial screening tests should take cultural sensitivity into account when designing educational interventions and using them. PMID:14620963

  9. Prostate cancer. Foreword.

    PubMed

    Patel, Hiten R H

    2014-11-01

    Professor Hiten Patel is an expert in Laparoscopic and Robotic Surgery for treating prostate disease. He is also a leading researcher in basic science and `clinical research. His basic science research is focused on studying the pathways for improving prostate cancer diagnosis and prognosis through biomarker application, and his clinical research includes new technology applications for training surgeons and improving patient care outcome. Prof Patel is also Chairman of the Urology group for the Enhanced Recovery after Surgery Society.

  10. Three-dimensional visualization and analysis in prostate cancer.

    PubMed

    Robb, Richard A

    2002-03-01

    Current and emerging three- and four-dimensional medical imaging modalities, along with development of efficient 3-D computer rendering and modeling of multidimensional volume image data and image-guided navigation, are significantly advancing our capabilities for improved and minimally invasive diagnosis and treatment of prostate cancer, obviating the need for exploratory surgery, physical dissection, blind biopsies and mental reconstruction of anatomy and pathology. Currently, both diagnostic and therapeutic procedures require x-ray fluoroscopy, transrectal ultrasound, CT and/or MRI for assessing the condition of the prostate and/or the outcome of any therapeutic procedure. New imaging approaches based on three-dimensional ultrasound transducers placed on catheters for easy insertion into the urethra are demonstrating significant promise for improved diagnosis and treatment of prostate disease. Microwave thermal ablation shows promise for reduction of prostate size and tumor volume, and preliminary data from cryosurgery suggests improvements in tumor reduction and/or management while minimizing the risk of serious complications. Prostate brachytherapy is becoming a more popular and effective alternative to surgery. All of these methods, either independently or combined through image fusion, are providing an exciting and rapid evolution in capabilities for visualizing the prostate and its anatomic environment, extending from physical to functional forms and from macro to micro orders of scale. Traversing the scale distances between these imaged objects within the prostate and its environs will be made automatic and instantaneous in the near future with the expected advances in miniaturization of powerful computing and electronic sensing elements. Imaging devices will continue to improve in resolution, speed and affordability and will be deployed harmlessly within the body, as well as outside of it. Diagnosis and therapy of prostate disease will become fully

  11. Prostate-specific acid phosphatase versus acid phosphatase in monitoring patients with prostate cancer.

    PubMed

    Killian, C S; Vargas, F P; Slack, N H; Murphy, G P; Chu, T M

    1982-01-01

    Serial levels of PAP and AcP activity were compared for their relative values in monitoring 57 early and 33 advanced prostate cancer patients. Several findings regarding the patients' disease status and the enzyme levels have been observed that may be beneficial to therapeutic management of these patients. They are: [1] an elevated PAP activity in disease recurrence and disease progression generally precedes an elevated AcP activity, and thus represents a more sensitive index for patients with early and advanced disease; [2] serial mean levels of PAP activity greater than the mean + 3 SD are more predictive for disease recurrence and progression than are those of AcP activity in both groups of patients; [3] PAP activity is a more sensitive monitor for changes in objective treatment response than is AcP activity; and [4] PAP is more specific than AcP for prostate, thus offering a more reliable marker to identify metastasis of unknown origin, or to confirm metastasis derived from a primary prostate tumor that may have been suggested by other non-prostate-specific marker[s]. In addition, data suggest a favorable prognosis for patients receiving therapy as inferred by a serial mean of PAP activity that is less than mean + 3 SD. PMID:6953924

  12. Drugs Approved for Prostate Cancer

    MedlinePlus

    ... Ask about Your Treatment Research Drugs Approved for Prostate Cancer This page lists cancer drugs approved by the ... that are not listed here. Drugs Approved for Prostate Cancer Abiraterone Acetate Bicalutamide Cabazitaxel Casodex (Bicalutamide) Degarelix Docetaxel ...

  13. Understanding Prostate Cancer: Newly Diagnosed

    MedlinePlus

    ... Wellness PCF Spotlight Glossary African American Men Understanding Prostate Cancer Newly Diagnosed Newly Diagnosed Staging the Disease Issues ... you care about has recently been diagnosed with prostate cancer, this section will help guide you through the ...

  14. Computed tomography of the prostate.

    PubMed

    Van Engelshoven, J M; Kreel, L

    1979-02-01

    The conventional anatomy of the prostate is reviewed and the computed tomography (CT) anatomy described and illustrated. The results of 55 "normal" cases were analyzed for size and relationship to the symphysis pubis, retropubic space, and bladder, as shown on CT sections correlating the features with age and possible urinary symptoms. Attention is also drawn to the differences between phleboliths and prostatic calcification. Computed tomography is an effective method of demonstrating the prostate and surrounding structures and of assessing prostatic enlargement.

  15. Prostatic adenoma of ductal origin.

    PubMed

    Min, K W; Gyorkey, F

    1980-07-01

    A case of prostatic adenoma believed to originate from the prostatic duct is described. There were morphologic similarities to basal cell adenomas of salivary glands, and it was concluded that the tumor is a benign counterpart of "salivary gland" carcinomas, rarely observed in the prostate.

  16. Insights into Chemoresistance of Prostate Cancer

    PubMed Central

    Zhang, Wei; Meng, Yan; Liu, Na; Wen, Xiao-Fei; Yang, Tao

    2015-01-01

    Prostate cancer (PCa) remains the most prevalent malignancy among males in the western world. Though hormonal therapies through chemical or surgical castration have been proposed many years ago, heretofore, such mainstay for the treatment on advanced PCa has not fundamentally changed. These therapeutic responses are temporary and most cases will eventually undergo PCa recurrence and metastasis, or even progress to castration-resistant prostate cancer (CRPC) due to persistent development of drug resistance. Prostate cancer stem cells (PCSCs) are a small population of cells, which possess unlimited self-renewal capacities, and can regenerate tumorigenic progenies, and play an essential role in PCa therapy resistance, metastasis and recurrence. Nowadays advanced progresses have been made in understanding of PCSC properties, roles of androgen receptor signaling and ATP-binding cassette sub-family G member 2 (ABCG2), as well as roles of genomic non-coding microRNAs and key signaling pathways, which have led to the development of novel therapies which are active against chemoresistant PCa and CRPC. Based on these progresses, this review is dedicated to address mechanisms underlying PCa chemoresistance, unveil crosstalks among pivotal signaling pathways, explore novel biotherapeutic agents, and elaborate functional properties and specific roles of chemoresistant PCSCs, which may act as a promising target for novel therapies against chemoresistant PCa. PMID:26327810

  17. Multimodality Therapy: Bone-Targeted Radioisotope Therapy of Prostate Cancer

    PubMed Central

    Tu, Shi-Ming; Lin, Sue-Hwa; Podoloff, Donald A.; Logothetis, Christopher J.

    2016-01-01

    Accumulating data suggest that bone-seeking radiopharmaceuticals can be used to treat prostate cancer bone metastasis and improve the clinical outcome of patients with advanced prostate cancer. It remains to be elucidated whether radiopharmaceuticals enhance the disruption of the onco-niche or the eradication of micrometastatic cells in the bone marrow. The purpose of this review is to investigate the role of bone-targeted radioisotope therapy in the setting of multimodality therapy for advanced prostate cancer. We examine available data and evaluate whether dose escalation, newer generations, or repeated dosing of radiopharmaceuticals enhance their antitumor effects and whether their combination with hormone ablative therapy, chemotherapy, or novel targeted therapy can improve clinical efficacy. PMID:20551894

  18. Intensity-modulated radiation therapy: supportive data for prostate cancer.

    PubMed

    Cahlon, Oren; Hunt, Margie; Zelefsky, Michael J

    2008-01-01

    Since its introduction into clinical use in the mid-1990s, intensity-modulated radiation therapy (IMRT) has emerged as the most effective and widely used form of external-beam radiotherapy for localized prostate cancer. Multiple studies have confirmed the importance of delivering sufficiently high doses to the prostate to achieve cure. The dosimetric superiority of IMRT over conventional techniques to produce conformal dose distributions that allow for organ sparing has been shown. A growing number of reports have confirmed that IMRT is the safest way to deliver high doses of external-beam irradiation to the prostate and the regional lymph nodes. Advances in imaging and onboard verification systems continue to advance the capabilities of IMRT and have potential implications with regards to further dose escalation and hypofractionated regimens. The clinical data in support of IMRT and the associated technical aspects of IMRT treatment planning and implementation are highlighted in this review.

  19. Technological aspects of delivering cryotherapy for prostate cancer.

    PubMed

    Lau, Benjamin; Shah, Taimur Tariq; Valerio, Massimo; Hamid, Sami; Ahmed, Hashim Uddin; Arya, Manit

    2015-03-01

    Since the era of prostate specific antigen (PSA) testing, there has been a stage and grade migration seen with prostate cancer along with a reduction in mortality. Subsequently, concerns have been raised about the over treatment of patients following the diagnosis of localized prostate cancers. Cryotherapy, in which extremely low temperatures induce cell death via multiple mechanisms, has seen a drastic improvement in its technology since the 1800s. Such advances have improved oncological outcomes while reducing complication rates. Furthermore, technological advances have allowed the development of focal cryotherapy which aims to reduce morbidity associated with more radical whole-gland therapies. There is growing evidence that focal cryotherapy provides good oncological and morbidity rates when compared with traditional radical/whole-gland therapies.

  20. Steroid hormone receptors in prostatic hyperplasia and prostatic carcinoma.

    PubMed

    Khalid, B A; Nurshireen, A; Rashidah, M; Zainal, B Y; Roslan, B A; Mahamooth, Z

    1990-06-01

    One hundred and six prostatic tissue samples obtained from transurethral resection were analysed for androgen and estrogen receptors. In 62 of these, progesterone and glucocorticoid receptors were also assayed. Steroid receptors were assayed using single saturation dose 3H-labelled ligand assays. Ninety percent of the 97 prostatic hyperplasia tissues and six of the nine prostatic carcinoma tissues were positive for androgen receptors. Estrogen receptors were only present in 19% and 33% respectively. Progesterone receptors were present in 70% of the tissues, but glucocorticoid receptors were present in only 16% of prostatic hyperplasia and none in prostatic carcinoma. PMID:1725553

  1. Experience with prostate-specific antigen in prostatic carcinoma.

    PubMed

    Romics, I; Bach, D

    1991-01-01

    A total of 71 prostatic tumour patients and 45 prostatic adenoma patients were tested for prostate-specific antigen (PSA), immunological prostatic acid phosphatase (PAP) concentration as well as serum prostatic phosphatase (SPP) and enzymic serum phosphatase. It was found among untreated patients that PSA showed the highest percentage of pathologic affection in each stage. PSA, on the evidence of clearance test in the initial days of therapy and after a follow-up period of several months, gave a good picture of the course that the disease had taken.

  2. Anti-Prostate Specific Membrane Antigen-based Radioimmunotherapy for Prostate Cancer

    PubMed Central

    Tagawa, Scott T.; Beltran, Himisha; Vallabhajosula, Shankar; Goldsmith, Stanley J.; Osborne, Joseph; Matulich, Dan; Petrillo, Kristen; Parmar, Sarojben; Nanus, David M.; Bander, Neil H.

    2009-01-01

    Despite recent advances, advanced prostate cancer is suboptimally responsive to current chemotherapeutic agents. Radiolabeled monoclonal antibody therapy that targets prostate specific membrane antigen (PSMA) shows promise and is an area of active investigation. J591 is a deimmunized IgG monoclonal antibody developed to target the extracellular domain of PSMA. Preclinical and early phase clinical studies utilizing radiolabeled J591 have demonstrated efficacy in targeting tumor cells and decreasing levels of PSA. Radiolabeled J591 is well-tolerated, non-immunogenic, and can be administered in multiple doses. The dose limiting toxicity is reversible myelosuppression with little non-hematologic toxicity. Future studies will include approaches to optimize patient selection and incorporate novel strategies to improve the success of anti-PSMA radioimmunotherapy. PMID:20127956

  3. Prostate Cancer Support Groups

    PubMed Central

    Chambers, Suzanne; Garrett, Bernie; Bottorff, Joan L.; McKenzie, Michael; Han, Christina S.; Ogrodniczuk, John S.

    2015-01-01

    To understand prostate cancer (PCa) specialists’ views about prostate cancer support groups (PCSGs), a volunteer sample of Canada-based PCa specialists (n = 150), including urologists (n = 100), radiation oncologists (n = 40), and medical oncologists (n = 10) were surveyed. The 56-item questionnaire used in this study included six sets of attitudinal items to measure prostate cancer specialists’ beliefs about positive and negative influences of PCSGs, reasons for attending PCSGs, the attributes of effective PCSGs, and the value of face-to-face and web-based PCSGs. In addition, an open-ended question was included to invite additional input from participants. Results showed that PCSGs were positively valued, particularly for information sharing, education and psychosocial support. Inclusivity, privacy, and accessibility were identified as potential barriers, and recommendations were made for better marketing PCSGs to increase engagement. Findings suggest prostate cancer specialists highly valued the role and potential benefits of face-to-face PCSGs. Information provision and an educational role were perceived as key benefits. Some concerns were expressed about the ability of web-based PCSGs to effectively engage and educate men who experience prostate cancer. PMID:25061087

  4. Androgen deprivation therapy for prostate cancer.

    PubMed

    Singer, Eric A; Golijanin, Dragan J; Miyamoto, Hiroshi; Messing, Edward M

    2008-02-01

    Androgen deprivation continues to play a crucial role in the treatment of advanced and metastatic prostate cancer. In the 65 years since its use was first described, urologists and medical oncologists have developed new and innovative ways to manipulate the hypothalamic-pituitary-gonadal axis with the goal of alleviating symptoms and prolonging the life of men with prostate cancer. Despite the successes that androgen deprivation therapy has brought, each method and regimen possesses unique benefits and burdens, of which the clinician and patient must be cognizant. This review discusses the first-line androgen deprivation methods and regimens presently in use with special attention paid to their side effects and the management of them, as well as the question of when to initiate androgen deprivation therapy.

  5. Neuroendocrine prostate cancer: subtypes, biology, and clinical outcomes.

    PubMed

    Aggarwal, Rahul; Zhang, Tian; Small, Eric J; Armstrong, Andrew J

    2014-05-01

    Neuroendocrine prostate cancer (NEPC) encompasses various clinical contexts, ranging from the de novo presentation of small cell prostatic carcinoma to a treatment-emergent transformed phenotype that arises from typical adenocarcinoma of the prostate. The development of resistance to potent androgen receptor signaling inhibition may be associated with the emergence of aggressive phenotype, advanced castration-resistant NEPC. Clinically, small cell prostate cancer and NEPC are often manifested by the presence of visceral or large soft tissue metastatic disease, a disproportionately low serum prostate-specific antigen level relative to the overall burden of disease, and a limited response to targeting of the androgen signaling axis. These tumors are often characterized by loss of androgen receptor expression, loss of retinoblastoma tumor suppressor copy number or expression, amplification of Aurora kinase A and N-Myc, and activation of the PI3K pathway. However, a consensus phenotype-genotype definition of NEPC has yet to emerge, and molecularly based biomarkers are needed to expand on traditional morphologic and immunohistochemical markers of NEPC to fully define the spectrum of this aggressive, androgen receptor-independent disease. Emerging studies implicate a shared clonal origin with prostatic adenocarcinoma in many cases, with the adaptive emergence of unique cellular programming and gene expression profiles. Ongoing clinical studies are focused on developing novel targeted therapeutic approaches for this high-risk, lethal subset of disease, to improve on the limited durations of response often observed with traditional platinum-based chemotherapy.

  6. Influence of the number of elongated fiducial markers on the localization accuracy of the prostate

    NASA Astrophysics Data System (ADS)

    de Boer, Johan; de Bois, Josien; van Herk, Marcel; Sonke, Jan-Jakob

    2012-10-01

    Implanting fiducial markers for localization purposes has become an accepted practice in radiotherapy for prostate cancer. While many correction strategies correct for translations only, advanced correction protocols also require knowledge of the rotation of the prostate. For this purpose, typically, three or more markers are implanted. Elongated fiducial markers provide more information about their orientation than traditional round or cylindrical markers. Potentially, fewer markers are required. In this study, we evaluate the effect of the number of elongated markers on the localization accuracy of the prostate. To quantify the localization error, we developed a model that estimates, at arbitrary locations in the prostate, the registration error caused by translational and rotational uncertainties of the marker registration. Every combination of one, two and three markers was analysed for a group of 24 patients. The average registration errors at the prostate surface were 0.3-0.8 mm and 0.4-1 mm for registrations on, respectively, three markers and two markers located on different sides of the prostate. Substantial registration errors (2.0-2.2 mm) occurred at the prostate surface contralateral to the markers when two markers were implanted on the same side of the prostate or only one marker was used. In conclusion, there is no benefit in using three elongated markers: two markers accurately localize the prostate if they are implanted at some distance from each other.

  7. Benign prostatic hyperplasia.

    PubMed Central

    Simpson, R J

    1997-01-01

    The clinical syndrome of benign prostatic hyperplasia reflects a complex interplay between benign prostatic enlargement, which will affect almost all men by the age of 80, and the resulting outlet obstruction and lower urinary tract symptoms. The disease is now known to adversely affect the quality of life of around one man in three over the age of 50. New medical treatments and new surgical interventions are challenging the previous standard treatment of transurethral resection of prostate, which continues to have a morbidity of 17% and some mortality. Primary care will be increasingly involved in shared care with particular emphasis on monitoring of patients on watchful waiting medical therapy- and following operative intervention. PMID:9196969

  8. Efficacy of targeted AKT inhibition in genetically engineered mouse models of PTEN-deficient prostate cancer.

    PubMed

    De Velasco, Marco A; Kura, Yurie; Yoshikawa, Kazuhiro; Nishio, Kazuto; Davies, Barry R; Uemura, Hirotsugu

    2016-03-29

    The PI3K/AKT pathway is frequently altered in advanced human prostate cancer mainly through the loss of functional PTEN, and presents as potential target for personalized therapy. Our aim was to determine the therapeutic potential of the pan-AKT inhibitor, AZD5363, in PTEN-deficient prostate cancer. Here we used a genetically engineered mouse (GEM) model of PTEN-deficient prostate cancer to evaluate the in vivo pharmacodynamic and antitumor activity of AZD5363 in castration-naïve and castration-resistant prostate cancer. An additional GEM model, based on the concomitant inactivation of PTEN and Trp53 (P53), was established as an aggressive model of advanced prostate cancer and was used to further evaluate clinically relevant endpoints after treatment with AZD5363. In vivo pharmacodynamic studies demonstrated that AZD5363 effectively inhibited downstream targets of AKT. AZD5363 monotherapy significantly reduced growth of tumors in castration-naïve and castration-resistant models of PTEN-deficient prostate cancer. More importantly, AZD5363 significantly delayed tumor growth and improved overall survival and progression-free survival in PTEN/P53 double knockout mice. Our findings demonstrate that AZD5363 is effective against GEM models of PTEN-deficient prostate cancer and provide lines of evidence to support further investigation into the development of treatment strategies targeting AKT for the treatment of PTEN-deficient prostate cancer.

  9. Prostate Cancer in Gay, Bisexual, and Other Men Who Have Sex with Men: A Review

    PubMed Central

    Merengwa, Enyinnaya; Capistrant, Benjamin D.; Iantaffi, Alex; Kilian, Gunna; Kohli, Nidhi; Konety, Badrinath R.; Mitteldorf, Darryl; West, William

    2016-01-01

    Abstract Purpose: Prostate cancer in gay, bisexual, and other men who have sex with men (GBM) is an emerging medical and public health concern. The purpose of this review is to summarize the literature on prostate cancer in GBM, including its epidemiology, clinical studies, and anecdotal reports. Methods: In 2015, we undertook a structured literature review of all studies from 2000 to 2015. Results: Despite prostate cancer being the most common cancer in GBM, the main finding of this review is that prostate cancer in GBM is very under-researched. With only 30 published articles in English (a rate of 1.9 articles per year), most of the literature is limited to case studies or anecdotal reports. There is some evidence of a link between human immunodeficiency virus (HIV)-positive status and prostate cancer, with early studies showing HIV infection as a risk factor and more recent studies as it being protective. Antiretroviral treatment appears protective. Globally, only four quantitative studies have been published. Based on this admittedly limited literature, GBM appear to be screened for prostate cancer less than other men and are diagnosed with prostate cancer at about the same rate, but have poorer sexual function and quality-of-life outcomes. Conclusion: Methodological challenges to advancing research include challenges in subject identification, recruitment, heterocentric definitions of dysfunction based on vaginal intercourse and penetrative sex, and inappropriate measures. Six future directions, to advance the study of the effects of prostate cancer in GBM and to improve treatment, are detailed.

  10. Efficacy of targeted AKT inhibition in genetically engineered mouse models of PTEN-deficient prostate cancer

    PubMed Central

    De Velasco, Marco A.; Kura, Yurie; Yoshikawa, Kazuhiro; Nishio, Kazuto; Davies, Barry R.; Uemura, Hirotsugu

    2016-01-01

    The PI3K/AKT pathway is frequently altered in advanced human prostate cancer mainly through the loss of functional PTEN, and presents as potential target for personalized therapy. Our aim was to determine the therapeutic potential of the pan-AKT inhibitor, AZD5363, in PTEN-deficient prostate cancer. Here we used a genetically engineered mouse (GEM) model of PTEN-deficient prostate cancer to evaluate the in vivo pharmacodynamic and antitumor activity of AZD5363 in castration-naïve and castration-resistant prostate cancer. An additional GEM model, based on the concomitant inactivation of PTEN and Trp53 (P53), was established as an aggressive model of advanced prostate cancer and was used to further evaluate clinically relevant endpoints after treatment with AZD5363. In vivo pharmacodynamic studies demonstrated that AZD5363 effectively inhibited downstream targets of AKT. AZD5363 monotherapy significantly reduced growth of tumors in castration-naïve and castration-resistant models of PTEN-deficient prostate cancer. More importantly, AZD5363 significantly delayed tumor growth and improved overall survival and progression-free survival in PTEN/P53 double knockout mice. Our findings demonstrate that AZD5363 is effective against GEM models of PTEN-deficient prostate cancer and provide lines of evidence to support further investigation into the development of treatment strategies targeting AKT for the treatment of PTEN-deficient prostate cancer. PMID:26910118

  11. Staging of prostate cancer.

    PubMed

    Cheng, Liang; Montironi, Rodolfo; Bostwick, David G; Lopez-Beltran, Antonio; Berney, Daniel M

    2012-01-01

    Prostatic carcinoma (PCa) is a significant cause of cancer morbidity and mortality worldwide. Accurate staging is critical for prognosis assessment and treatment planning for PCa. Despite the large volume of clinical activity and research, the challenge to define the most appropriate and clinically relevant staging system remains. The pathologically complex and uncertain clinical course of prostate cancer further complicates the design of staging classification and a substaging system suitable for individualized care. This review will focus on recent progress and controversial issues related to prostate cancer staging. The 2010 revision of the American Joint Committee on Cancer/Union Internationale Contre le Cancer (AJCC/UICC) tumour, node and metastasis (TNM) system is the most widely used staging system at this time. Despite general acceptance of the system as a whole, there is controversy and uncertainty about its application, particularly for T2 subclassification. The three-tiered T2 classification system for organ-confined prostate cancer is superfluous, considering the biology and anatomy of PCa. A tumour size-based substaging system may be considered in the future TNM subclassification of pT2 cancer. Lymph node status is one of the most important prognostic factors for prostate cancer. Nevertheless, clinical outcomes in patients with positive lymph nodes are variable. Identification of patients at the greatest risk of systemic progression helps in the selection of appropriate therapy. The data suggest that the inherent aggressiveness of metastatic prostate cancer is closely linked to the tumour volume of lymph node metastasis. We recommend that a future TNM staging system should consider subclassification of node-positive cancer on the basis of nodal cancer volume, using the diameter of the largest nodal metastasis and/or the number of positive nodes.

  12. Staging of prostate cancer.

    PubMed

    Cheng, Liang; Montironi, Rodolfo; Bostwick, David G; Lopez-Beltran, Antonio; Berney, Daniel M

    2012-01-01

    Prostatic carcinoma (PCa) is a significant cause of cancer morbidity and mortality worldwide. Accurate staging is critical for prognosis assessment and treatment planning for PCa. Despite the large volume of clinical activity and research, the challenge to define the most appropriate and clinically relevant staging system remains. The pathologically complex and uncertain clinical course of prostate cancer further complicates the design of staging classification and a substaging system suitable for individualized care. This review will focus on recent progress and controversial issues related to prostate cancer staging. The 2010 revision of the American Joint Committee on Cancer/Union Internationale Contre le Cancer (AJCC/UICC) tumour, node and metastasis (TNM) system is the most widely used staging system at this time. Despite general acceptance of the system as a whole, there is controversy and uncertainty about its application, particularly for T2 subclassification. The three-tiered T2 classification system for organ-confined prostate cancer is superfluous, considering the biology and anatomy of PCa. A tumour size-based substaging system may be considered in the future TNM subclassification of pT2 cancer. Lymph node status is one of the most important prognostic factors for prostate cancer. Nevertheless, clinical outcomes in patients with positive lymph nodes are variable. Identification of patients at the greatest risk of systemic progression helps in the selection of appropriate therapy. The data suggest that the inherent aggressiveness of metastatic prostate cancer is closely linked to the tumour volume of lymph node metastasis. We recommend that a future TNM staging system should consider subclassification of node-positive cancer on the basis of nodal cancer volume, using the diameter of the largest nodal metastasis and/or the number of positive nodes. PMID:22212080

  13. [New challenges and earlier approved methods in the laboratory diagnosis of prostate cancer].

    PubMed

    Kovács, Gábor L

    2014-12-01

    Prostate cancer is usually a disease of elderly men, however, over 40 years of age the tumor can appear at any times. PSA is a protein molecule synthesized by prostate cells. Measurement of serum PSA has revolutionized the diagnosis and treatment of prostate cancer. However, PSA is not sufficiently specific for the detection of prostate cancer, since serum PSA might also be elevated in benign prostate diseases, as well as following physical stimulation of the gland (digital rectal examination, biopsy, catheterization, or even ejaculation). To increase the specificity of PSA, different derivative parameters have been developed i.e. PSA density (ratio of PSA to prostate volume), PSA velocity (change of PSA over a time period) or age-specific reference ranges. 65-95% of circulating PSA is bound to different proteins, while the rest of PSA circulates in a non-bound form (free PSA, fPSA). In addition to fPSA, the prostate health index [phi; (-2)proPSA/fPSA×√PSA] is increasingly used to differentiate between carcinoma-induced and non-carcinoma-induced increase in PSA. PCA3 is a non-coding messenger RNA, which is 60-70-fold overexpressed by cancer cells in the prostate. Measurement of urine PCA3 appears to be more sensitive than %tPSA, and is independent of prostate volume, age or tPSA. The author reviews laboratory biomarkers related to prostate cancer, used either in the routine clinical practice, or in research. Laboratory biomarkers seem to be useful tools to reduce the incidence of advanced stage, or metastatic prostate cancer, and the cancer-related death rate. A promising perspective for the future is the detection of circulating prostate cancer cells and the profiling of microRNAs, especially on the field of tumor prognosis. PMID:25517448

  14. Mechanisms of resistance in castration-resistant prostate cancer (CRPC)

    PubMed Central

    Chandrasekar, Thenappan; Yang, Joy C.; Gao, Allen C.

    2015-01-01

    Despite advances in prostate cancer diagnosis and management, morbidity from prostate cancer remains high. Approximately 20% of men present with advanced or metastatic disease, while 29,000 men continue to die of prostate cancer each year. Androgen deprivation therapy (ADT) has been the standard of care for initial management of advanced or metastatic prostate cancer since Huggins and Hodges first introduced the concept of androgen-dependence in 1972, but progression to castration-resistant prostate cancer (CRPC) occurs within 2-3 years of initiation of ADT. CRPC, previously defined as hormone-refractory prostate cancer, is now understood to still be androgen dependent. Multiple mechanisms of resistance help contribute to the progression to castration resistant disease, and the androgen receptor (AR) remains an important driver in this progression. These mechanisms include AR amplification and hypersensitivity, AR mutations leading to promiscuity, mutations in coactivators/corepressors, androgen-independent AR activation, and intratumoral and alternative androgen production. More recently, identification of AR variants (ARVs) has been established as another mechanism of progression to CRPC. Docetaxel chemotherapy has historically been the first-line treatment for CRPC, but in recent years, newer agents have been introduced that target some of these mechanisms of resistance, thereby providing additional survival benefit. These include AR signaling inhibitors such as enzalutamide (Xtandi, ENZA, MDV-3100) and CYP17A1 inhibitors such as abiraterone acetate (Zytiga). Ultimately, these agents will also fail to suppress CRPC. While some of the mechanisms by which these agents fail are unique, many share similarities to the mechanisms contributing to CRPC progression. Understanding these mechanisms of resistance to ADT and currently approved CRPC treatments will help guide future research into targeted therapies. PMID:26814148

  15. What Tests Can Detect Prostate Cancer?

    MedlinePlus

    ... prostate cancer early detection What tests can detect prostate cancer early? The tests discussed below are used to ... also found in the blood. Most men without prostate cancer have PSA levels under 4 nanograms per milliliter ( ...

  16. Survival in prostate cancer prevention trial detailed

    Cancer.gov

    In the NCI-sponsored Prostate Cancer Prevention Trial, initial findings from a decade ago showed that the drug finasteride significantly reduced the risk of prostate cancer, but among those who did develop prostate cancer, paradoxically, the drug was asso

  17. Giant prostatic fossa with misleading radiographic features.

    PubMed

    Stenzl, A; Fuchs, G J

    1989-01-01

    The long-term complication of a perforation of the prostatic capsule during transurethral resection of the prostate is described. Calcifications in a giant prostatic fossa led to initially misleading radiologic findings.

  18. Cancer of the Prostate

    MedlinePlus

    ... at a Glance Show More At a Glance Estimated New Cases in 2016 180,890 % of All New Cancer Cases 10.7% Estimated Deaths in 2016 26,120 % of All Cancer ... of This Cancer : In 2013, there were an estimated 2,850,139 men living with prostate cancer ...

  19. [Grading of prostate cancer].

    PubMed

    Kristiansen, G; Roth, W; Helpap, B

    2016-07-01

    The current grading of prostate cancer is based on the classification system of the International Society of Urological Pathology (ISUP) following a consensus conference in Chicago in 2014. The foundations are based on the frequently modified grading system of Gleason. This article presents a brief description of the development to the current ISUP grading system. PMID:27393141

  20. Bone-targeted agents: preventing skeletal complications in prostate cancer.

    PubMed

    Morgans, Alicia K; Smith, Matthew R

    2012-11-01

    In men, prostate cancer is the most common non-cutaneous malignancy and the second most common cause of cancer death. Skeletal complications occur at various points during the disease course, either due to bone metastases directly, or as an unintended consequence of androgen deprivation therapy (ADT). Bone metastases are associated with pathologic fractures, spinal cord compression, and bone pain and can require narcotics or palliative radiation for pain relief. ADT results in bone loss and fragility fractures. This review describes the biology of bone metastases, skeletal morbidity, and recent advances in bone-targeted therapies to prevent skeletal complications of prostate cancer.

  1. High-performance liquid chromatography-diode array and electrospray-mass spectrometry analysis of non-allowed substances in cosmetic products for preventing hair loss and other hormone-dependent skin diseases.

    PubMed

    De Orsi, Daniela; Pellegrini, Manuela; Pichini, Simona; Mattioli, Donatella; Marchei, Emilia; Gagliardi, Luigi

    2008-11-01

    A simple high-performance liquid chromatography (HPLC) method with ultraviolet diode array (UV-DAD) and electrospray ionisation mass spectrometry (ESI-MS) detection has been developed for the determination of minoxidil, progesterone, estrone, spironolactone, canrenone, hydrocortisone and triamcinolone acetonide in cosmetic products. The presence of these substances in commercial cosmetic samples is prohibited. The compounds were separated by reversed phase chromatography with water (0.1% trifluoroacetic acid) and acetonitrile gradient elution and detected by UV-DAD at 230, 254 and 280 nm and by ESI-MS positive ionisation mode. Benzoic acid was used as internal standard. Linearity was studied with UV-DAD detection from 1.50 to 1,000 microg/ml or mug/g range, depending on the different compounds and type of cosmetic preparation and with ESI-MS in the 50-1,000 ng/ml or ng/g range. Good determination coefficients (r(2)>or=0.99) were found in both UV and ESI-MS. At three concentrations spanning the linear dynamic ranges of both UV-DAD and ESI-MS assay, mean recoveries were always higher than 90% for the different analytes. This method was successfully applied to the analysis of substances under investigations illegally added in cosmetic cream and lotions, sold on internet web sites to prevent hair loss and other hormone-dependent skin diseases, like acne and hirsutism. PMID:18656319

  2. Cabazitaxel Plus Prednisone With Octreotide For Castration-Resistant Prostate Cancer (CRPC) Previously Treated With Docetaxel

    ClinicalTrials.gov

    2014-11-21

    Diarrhea; Hormone-resistant Prostate Cancer; Recurrent Prostate Cancer; Stage I Prostate Cancer; Stage IIA Prostate Cancer; Stage IIB Prostate Cancer; Stage III Prostate Cancer; Stage IV Prostate Cancer

  3. Botanical derivatives for the prostate.

    PubMed

    Cristoni, A; Di Pierro, F; Bombardelli, E

    2000-08-01

    The prostate, after the age of 45 years, may undergo benign hyperplasia (BPH). Its etiology has not yet been completely explained, but different factors play a major role in its occurrence, among them, the sexual hormones (with a fundamental role of 5 alpha reductase). The 5-alpha reductase activity and inflammatory aspects in the prostate tissue can be effectively controlled with the use of highly standardized plant extracts (Pygeum africanum, Serenoa repens, etc.), which yield excellent results in the prophylaxis and treatment of the symptoms linked to prostate hypertrophy. The prostate tissue is not affected only by benign diseases but may also be subject to neoplastic transformation. From an epidemiological point of view, a vegetable derivative, lycopene, was linked with a lower occurrence of prostate carcinoma. A recent clinical study demonstrated that lycopene might not only prevent prostate cancer but also have therapeutic effects.

  4. Prostate cancer markers: An update

    PubMed Central

    PENTYALA, SRINIVAS; WHYARD, TERRY; PENTYALA, SAHANA; MULLER, JOHN; PFAIL, JOHN; PARMAR, SUNJIT; HELGUERO, CARLOS G.; KHAN, SARDAR

    2016-01-01

    As the most common noncutaneous malignancy in American men, prostate cancer currently accounts for 29% of all diagnosed cancers, and ranks second as the cause of cancer fatality in American men. Prostatic cancer is rarely symptomatic early in its course and therefore disease presentation often implies local extension or even metastatic disease. Thus, it is extremely critical to detect and diagnose prostate cancer in its earliest stages, often prior to the presentation of symptoms. Three of the most common techniques used to detect prostate cancer are the digital rectal exam, the transrectal ultrasound, and the use of biomarkers. This review presents an update regarding the field of prostate cancer biomarkers and comments on future biomarkers. Although there is not a lack of research in the field of prostate cancer biomarkers, the discovery of a novel biomarker that may have the advantage of being more specific and effective warrants future scientific inquiry. PMID:26998261

  5. Prostate cancer stem cell biology

    PubMed Central

    Yu, Chunyan; Yao, Zhi; Jiang, Yuan; Keller, Evan. T.

    2012-01-01

    The cancer stem cell (CSC) model provides insights into pathophysiology of cancers and their therapeutic response. The CSC model has been both controversial, yet provides a foundation to explore cancer biology. In this review, we provide an overview of CSC concepts, biology and potential therapeutic avenues. We then focus on prostate CSC including (1) their purported origin as either basal-derived or luminal-derived cells; (2) markers used for prostate CSC identification; (3) alterations of signaling pathways in prostate CSCs (4) involvement of prostate CSCs in metastasis of PCa and (5) microRNA-mediated regulation of prostate CSCs. Although definitive evidence for the identification and characterization of prostate CSCs still remains unclear, future directions pursuing therapeutic targets of CSCs may provide novel insights for the treatment of PCa. PMID:22402315

  6. Sox2 Is an Androgen Receptor-Repressed Gene That Promotes Castration-Resistant Prostate Cancer

    PubMed Central

    Kregel, Steven; Kiriluk, Kyle J.; Rosen, Alex M.; Cai, Yi; Reyes, Edwin E.; Otto, Kristen B.; Tom, Westin; Paner, Gladell P.; Szmulewitz, Russell Z.; Vander Griend, Donald J.

    2013-01-01

    Despite advances in detection and therapy, castration-resistant prostate cancer continues to be a major clinical problem. The aberrant activity of stem cell pathways, and their regulation by the Androgen Receptor (AR), has the potential to provide insight into novel mechanisms and pathways to prevent and treat advanced, castrate-resistant prostate cancers. To this end, we investigated the role of the embryonic stem cell regulator Sox2 [SRY (sex determining region Y)-box 2] in normal and malignant prostate epithelial cells. In the normal prostate, Sox2 is expressed in a portion of basal epithelial cells. Prostate tumors were either Sox2-positive or Sox2-negative, with the percentage of Sox2-positive tumors increasing with Gleason Score and metastases. In the castration-resistant prostate cancer cell line CWR-R1, endogenous expression of Sox2 was repressed by AR signaling, and AR chromatin-IP shows that AR binds the enhancer element within the Sox2 promoter. Likewise, in normal prostate epithelial cells and human embryonic stem cells, increased AR signaling also decreases Sox2 expression. Resistance to the anti-androgen MDV3100 results in a marked increase in Sox2 expression within three prostate cancer cell lines, and in the castration-sensitive LAPC-4 prostate cancer cell line ectopic expression of Sox2 was sufficient to promote castration-resistant tumor formation. Loss of Sox2 expression in the castration-resistant CWR-R1 prostate cancer cell line inhibited cell growth. Up-regulation of Sox2 was not associated with increased CD133 expression but was associated with increased FGF5 (Fibroblast Growth Factor 5) expression. These data propose a model of elevated Sox2 expression due to loss of AR-mediated repression during castration, and consequent castration-resistance via mechanisms not involving induction of canonical embryonic stem cell pathways. PMID:23326489

  7. Prostatic Stromal Hyperplasia with Atypia

    PubMed Central

    Hutchinson, Ryan C.; Wu, Kevin J.; Cheville, John C.; Thiel, David D.

    2013-01-01

    Prostatic stromal hyperplasia with atypia (PSHA) is a rare histologic finding diagnosed incidentally on prostate biopsies, transurethral resection specimens, and radical prostatectomy specimens. PSHA has a bizarre histologic appearance and these lesions often raise concern for sarcoma; however, their clinical course is indolent and does not include extraprostatic progression. We discuss a case of PHSA discovered on prostate biopsy performed for an abnormal digital rectal examination and review the literature on this rare pathologic finding. PMID:23781384

  8. Prostatic stromal hyperplasia with atypia.

    PubMed

    Hutchinson, Ryan C; Wu, Kevin J; Cheville, John C; Thiel, David D

    2013-01-01

    Prostatic stromal hyperplasia with atypia (PSHA) is a rare histologic finding diagnosed incidentally on prostate biopsies, transurethral resection specimens, and radical prostatectomy specimens. PSHA has a bizarre histologic appearance and these lesions often raise concern for sarcoma; however, their clinical course is indolent and does not include extraprostatic progression. We discuss a case of PHSA discovered on prostate biopsy performed for an abnormal digital rectal examination and review the literature on this rare pathologic finding. PMID:23781384

  9. Therapeutic efficacy of nanomedicines for prostate cancer: An update

    PubMed Central

    2016-01-01

    Recent advances in cancer nanomedicine have attracted remarkable attention in medical sectors. Pharmacologic research on nanomedicines, including targeted cancer therapy, has increased dramatically in the past 5 years. The success stories of nanomedicines in the clinical field include the fabrication of nanomedicines that show maximum loading efficiency into carriers, maximal release kinetics, and minimum toxicity to healthy cells. Nanoparticle-mediated medicines have been developed to specifically target prostate cancer tissue by use of aptamers, antibody targeting, and sustained release of nanomedicines in a dose- and time-dependent manner. Nanomedicines have been developed for therapeutic application in combination with image-guided therapy in real time. The scope of one of these nanomedicines, Abraxane (paclitaxel), may be extended to prostate cancer therapeutic applications for better quality of patient life and longer survival. This review provides an update on the latest directions and developments in nanomedicines for prostate cancer. PMID:26966723

  10. Image-guided focal therapy for prostate cancer

    PubMed Central

    Sankineni, Sandeep; Wood, Bradford J.; Rais-Bahrami, Soroush; Diaz, Annerleim Walton; Hoang, Anthony N.; Pinto, Peter A.; Choyke, Peter L.; Türkbey, Barış

    2014-01-01

    The adoption of routine prostate specific antigen screening has led to the discovery of many small and low-grade prostate cancers which have a low probability of causing mortality. These cancers, however, are often treated with radical therapies resulting in long-term side effects. There has been increasing interest in minimally invasive focal therapies to treat these tumors. While imaging modalities have improved rapidly over the past decade, similar advances in image-guided therapy are now starting to emerge—potentially achieving equivalent oncologic efficacy while avoiding the side effects of conventional radical surgery. The purpose of this article is to review the existing literature regarding the basis of various focal therapy techniques such as cryotherapy, microwave, laser, and high intensity focused ultrasound, and to discuss the results of recent clinical trials that demonstrate early outcomes in patients with prostate cancer. PMID:25205025

  11. Model-supported virtual environment for prostate cancer pattern analysis

    NASA Astrophysics Data System (ADS)

    Yu, Ping; McClain, Maxine A.; Xuan, Jianhua; Wang, Yue J.; Sesterhenn, Isabell A.; Moul, Judd W.; Zhang, Wei; Mun, Seong K.

    1999-05-01

    As a step toward understanding complex spatial distribution patterns of prostate cancers, a 3D master model of the prostate, showing major anatomical structures and probability maps of the location of tumors, has been pilot developed. A virtual environment supported by the 3D master model and in vivo imaging features, will be used to evaluate, simulate, and optimize the image guided needle biopsy and radiation therapy, thus potentially improving the efficacy of prostate cancer diagnosis, staging, and treatment. A deformable graphics algorithm has been developed to reconstruct the graphics models from 200 serially sectioned whole mount radical prostatectomy specimens and to support computerized needle biopsy simulations. For the construction of a generic model, a principal-axes 3D registration technique has been developed. Simulated evaluation and real data experiment have shown the satisfactory performance of the method in constructing initial generic model with localized prostate cancer placement. For the construction of statistical model, a blended model registration technique is advanced to perform a non-linear warping of the individual model to the generic model so that the prostate cancer probability distribution maps can be accurately positioned. The method uses a spine- surface model and a linear elastic model to dynamically deform both the surface and volume where object re-slicing is required. For the interactive visualization of the 3D master model, four modes of data display are developed: (1) transparent rendering of the generic model, (2) overlaid rendering of cancer distributions, (3) stereo rendering, and (4) true volumetric display, and a model-to-image registration technique using synthetic image phantoms is under investigation. Preliminary results have shown that use of this master model allows correct understanding of prostate cancer distribution patterns and rational optimization of prostate biopsy and radiation therapy strategies.

  12. Minimally invasive prostate cancer detection test using FISH probes

    PubMed Central

    Tinawi-Aljundi, Rima; Knuth, Shannon T; Gildea, Michael; Khal, Joshua; Hafron, Jason; Kernen, Kenneth; Di Loreto, Robert; Aurich-Costa, Joan

    2016-01-01

    Purpose The ability to test for and detect prostate cancer with minimal invasiveness has the potential to reduce unnecessary prostate biopsies. This study was conducted as part of a clinical investigation for the development of an OligoFISH® probe panel for more accurate detection of prostate cancer. Materials and methods One hundred eligible male patients undergoing transrectal ultrasound biopsies were enrolled in the study. After undergoing digital rectal examination with pressure, voided urine was collected in sufficient volume to prepare at least two slides using ThinPrep. Probe panels were tested on the slides, and 500 cells were scored when possible. From the 100 patients recruited, 85 had more than 300 cells scored and were included in the clinical performance calculations. Results Chromosomes Y, 7, 10, 20, 6, 8, 16, and 18 were polysomic in most prostate carcinoma cases. Of these eight chromosomes, chromosomes 7, 16, 18, and 20 were identified as having the highest clinical performance as a fluorescence in situ hybridization test and used to manufacture the fluorescence in situ hybridization probe panels. The OligoFISH® probes performed with 100% analytical specificity. When the OligoFISH® probes were compared with the biopsy results for each individual, the test results highly correlated with positive and negative prostate biopsy pathology findings, supporting their high specificity and accuracy. Probes for chromosomes 7, 16, 18, and 20 showed in the receiver operator characteristics analysis an area under the curve of 0.83, with an accuracy of 81% in predicting the biopsy result. Conclusion This investigation demonstrates the ease of use with high specificity, high predictive value, and accuracy in identifying prostate cancer in voided urine after digital rectal examination with pressure. The test is likely to have positive impact on clinical practice and advance approaches to the detection of prostate cancer. Further evaluation is warranted. PMID

  13. The DHEA-sulfate depot following P450c17 inhibition supports the case for AKR1C3 inhibition in high risk localized and advanced castration resistant prostate cancer.

    PubMed

    Tamae, Daniel; Mostaghel, Elahe; Montgomery, Bruce; Nelson, Peter S; Balk, Steven P; Kantoff, Philip W; Taplin, Mary-Ellen; Penning, Trevor M

    2015-06-01

    Prostate cancer is the second leading cause of cancer death in the United States. Treatment of localized high-risk disease and de novo metastatic disease frequently leads to relapse. These metastatic castration resistant prostate cancers (mCRPC) claim a high mortality rate, despite the extended survival afforded by the growing armamentarium of androgen deprivation, radiation and immunotherapies. Here, we review two studies of neoadjuvant treatment of high-risk localized prostate cancer prior to prostatectomy, the total androgen pathway suppression (TAPS) trial and the neoadjuvant abiraterone acetate (AA) trial. These two trials assessed the efficacy of the non-specific P450c17 inhibitor, ketoconazole and the specific P450c17 inhibitor, AA, to inhibit tissue and serum androgen levels. Furthermore, a novel and validated stable isotope dilution liquid chromatography electrospray ionization selected reaction monitoring mass spectrometry assay was used to accurately quantify adrenal and gonadal androgens in circulation during the course of these trials. The adrenal androgens, Δ(4)-androstene-3,17-dione, dehydroepiandrosterone and dehydroepiandrosterone sulfate were significantly reduced in the patients receiving ketoconazole or AA compared to those who did not. However, in both trials, a significant amount of DHEA-S (∼20 μg/dL) persists and thus may serve as a depot for intratumoral conversion to the potent androgen receptor ligands, testosterone (T) and 5α-dihydrotestosterone (DHT). The final step in conversion of Δ(4)-androstene-3,17-dione and 5α-androstanedione to T and DHT, respectively, is catalyzed by AKR1C3. We therefore present the case that in the context of the DHEA-S depot, P450c17 and AKR1C3 inhibition may be an effective combinatorial treatment strategy.

  14. Prostatic Leiomyoma: A Case Report

    PubMed Central

    Mellas, Soufiane; Bouchikhi, Ahmed Amine; Tazi, Mohammed-Fadl; Khallouk, Abdelhak; Elammari, Jalal-Eddin; El Fassi, Mohammed-Jamal; Farih, Moulay Hassan

    2012-01-01

    Prostatic enlargement due to benign adenomatous hyperplasia is very common in elderly males. However, benign mesenchymal tumors especially true leiomyoma of the prostate are rare. We describe a 68-year-old male presenting a urinary obstruction lasting more than two years. The patient was referred for an acute urinary retention. The clinical examination was normal. The perrectal examination revealed an enlarged prostate without abnormalities. An endoscopic resection was performed. The histopathological examination revealed a benign smooth muscle tumor with absence of glandular hyperplasia; the result was confirmed by immunohistochemistry. Accordingly, the diagnosis of true leiomyoma of the prostate was made. PMID:23198266

  15. Molecular Imaging of Prostate Cancer.

    PubMed

    Wibmer, Andreas G; Burger, Irene A; Sala, Evis; Hricak, Hedvig; Weber, Wolfgang A; Vargas, Hebert Alberto

    2016-01-01

    Prostate cancer is the most common noncutaneous malignancy among men in the Western world. The natural history and clinical course of prostate cancer are markedly diverse, ranging from small indolent intraprostatic lesions to highly aggressive disseminated disease. An understanding of this biologic heterogeneity is considered a necessary requisite in the quest for the adoption of precise and personalized management strategies. Molecular imaging offers the potential for noninvasive assessment of the biologic interactions underpinning prostate carcinogenesis. Currently, numerous molecular imaging probes are in clinical use or undergoing preclinical or clinical evaluation. These probes can be divided into those that image increased cell metabolism, those that target prostate cancer-specific membrane proteins and receptor molecules, and those that bind to the bone matrix adjacent to metastases to bone. The increased metabolism and vascular changes in prostate cancer cells can be evaluated with radiolabeled analogs of choline, acetate, glucose, amino acids, and nucleotides. The androgen receptor, prostate-specific membrane antigen, and gastrin-releasing peptide receptor (ie, bombesin) are overexpressed in prostate cancer and can be targeted by specific radiolabeled imaging probes. Because metastatic prostate cancer cells induce osteoblastic signaling pathways of adjacent bone tissue, bone-seeking radiotracers are sensitive tools for the detection of metastases to bone. Knowledge about the underlying biologic processes responsible for the phenotypes associated with the different stages of prostate cancer allows an appropriate choice of methods and helps avoid pitfalls. PMID:26587888

  16. Prostate resection - minimally invasive - discharge

    MedlinePlus

    Laser prostatectomy - discharge; Transurethral needle ablation - discharge; TUNA - discharge; Transurethral incision - discharge; TUIP - discharge; Holmium laser enucleation of the prostate - discharge; HoLep - discharge; Interstitial laser ...

  17. Xanthogranulomatous prostatitis with prostato-rectal fistula: a case report and review of the literature

    PubMed Central

    Xing, Liyong; Liu, Zhifei; Deng, Gang; Wang, Huan; Zhu, Yanfeng; Shi, Peng; Huo, Bingyue; Li, Yindong

    2016-01-01

    Purpose Xanthogranulomatous prostatitis (XP) is a rare form of nonspecific granulomatous prostatitis that can clinically mimic high-grade prostatic carcinoma. It is difficult to diagnose it definitely in clinical settings. Methods We report a case of XP with prostate-rectal fistula and review the relevant literatures. Result A 75-year-old man presented with rectal bleeding when he urinated. A locally advanced carcinoma of prostate was suspected initially following the physical, imaging, and hematologic examinations. Subsequently on histopathological and immunohistochemical staining after needle biopsy of the prostate, a diagnosis of XP was made definitely. The patient was catheterized temporarily and treated with tamsulosin and estrogen. The patient underwent uneventful recovery after this conservative therapy. Conclusion Histologic and immunohistochemical analyses are valuable in differentially diagnosing XP from high-grade prostate carcinoma. Treatment strategy of XP in principle is recommended to be the conservative method. Long-term follow-up earns are highly regarded considering the possibility of coexisting prostate cancer. PMID:27695691

  18. Integration of regulatory networks by NKX3-1 promotes androgen-dependent prostate cancer survival.

    PubMed

    Tan, Peck Yean; Chang, Cheng Wei; Chng, Kern Rei; Wansa, K D Senali Abayratna; Sung, Wing-Kin; Cheung, Edwin

    2012-01-01

    The NKX3-1 gene is a homeobox gene required for prostate tumor progression, but how it functions is unclear. Here, using chromatin immunoprecipitation coupled to massively parallel sequencing (ChIP-seq) we showed that NKX3-1 colocalizes with the androgen receptor (AR) across the prostate cancer genome. We uncovered two distinct mechanisms by which NKX3-1 controls the AR transcriptional network in prostate cancer. First, NKX3-1 and AR directly regulate each other in a feed-forward regulatory loop. Second, NKX3-1 collaborates with AR and FoxA1 to mediate genes in advanced and recurrent prostate carcinoma. NKX3-1- and AR-coregulated genes include those found in the "protein trafficking" process, which integrates oncogenic signaling pathways. Moreover, we demonstrate that NKX3-1, AR, and FoxA1 promote prostate cancer cell survival by directly upregulating RAB3B, a member of the RAB GTPase family. Finally, we show that RAB3B is overexpressed in prostate cancer patients, suggesting that RAB3B together with AR, FoxA1, and NKX3-1 are important regulators of prostate cancer progression. Collectively, our work highlights a novel hierarchical transcriptional regulatory network between NKX3-1, AR, and the RAB GTPase signaling pathway that is critical for the genetic-molecular-phenotypic paradigm in androgen-dependent prostate cancer.

  19. Studying circulating prostate cancer cells by in-vivo flow cytometer

    NASA Astrophysics Data System (ADS)

    Guo, Jin; Gu, Zhengqin; Chen, Tong; Wang, Cheng; Wei, Xunbin

    2011-11-01

    Prostate cancer is the most common malignancy in American men and the second leading cause of deaths from cancer, after lung cancer. The tumor usually grows slowly and remains confined to the gland for many years. As the cancer advances, however, it can metastasize throughout other areas of the body, such as the bones, lungs, and liver. Surgical resection, hormonal therapy, chemotherapy and radiation therapy are the foundation of current prostate cancer therapies. Treatments for prostate cause both short- and long-term side effects that may be difficult to accept. Molecular mechanisms of prostate cancer metastasis need to be understood better and new therapies must be developed to selectively target to unique characteristics of cancer cell growth and metastasis. We have developed the "in vivo microscopy" to study the mechanisms that govern prostate cancer cell spread through the microenvironment in vivo in real-time confocal near-infrared fluorescence imaging. A recently developed "in vivo flow cytometer" and optical imaging are used to assess prostate cancer cell spreading and the circulation kinetics of prostate cancer cells. We have measured the depletion kinetics of cancer cells with different metastatic potential. Interestingly, more invasive PC-3 prostate cancer cells are depleted faster from the circulation than LNCaP cells.

  20. Studying depletion kinetics of circulating prostate cancer cells by in vivo flow cytometer

    NASA Astrophysics Data System (ADS)

    Liu, Guangda; Gu, Zhengqin; Guo, Jin; Li, Yan; Chen, Yun; Chen, Tong; Wang, Cheng; Wei, Xunbin

    2011-03-01

    Prostate cancer is the most common malignancy in American men and the second leading cause of deaths from cancer, after lung cancer. The tumor usually grows slowly and remains confined to the gland for many years. During this time, the tumor produces little or no symptoms or outward signs. As the cancer advances, however, it can metastasize throughout other areas of the body, such as the bones, lungs, and liver. Surgical resection, hormonal therapy, chemotherapy and radiation therapy are the foundation of current prostate cancer therapies. Treatments for prostate cause both short- and long-term side effects that may be difficult to accept. Molecular mechanisms of prostate cancer metastasis need to be understood better and new therapies must be developed to selectively target to unique characteristics of cancer cell growth and metastasis. We have developed the "in vivo microscopy" to study the mechanisms that govern prostate cancer cell spread through the microenvironment in vivo in real-time confocal near-infrared fluorescence imaging. A recently developed "in vivo flow cytometer" and optical imaging are used to assess prostate cancer cell spreading and the circulation kinetics of prostate cancer cells. A real- time quantitative monitoring of circulating prostate cancer cells by the in vivo flow cytometer will be useful to assess the effectiveness of the potential therapeutic interventions.

  1. Depletion kinetics of circulating prostate cancer cells studied by in vivo flow cytometer

    NASA Astrophysics Data System (ADS)

    Liu, Guangda; Guo, Jin; Li, Yan; Chen, Yun; Gu, Zhengqin; Chen, Tong; Wang, Cheng; Wei, Xunbin

    2010-11-01

    Prostate cancer is the most common malignancy in American men and the second leading cause of deaths from cancer, after lung cancer. The tumor usually grows slowly and remains confined to the gland for many years. During this time, the tumor produces little or no symptoms or outward signs. As the cancer advances, however, it can metastasize throughout other areas of the body, such as the bones, lungs, and liver. Surgical resection, hormonal therapy, chemotherapy and radiation therapy are the foundation of current prostate cancer therapies. Treatments for prostate cause both short- and long-term side effects that may be difficult to accept. Molecular mechanisms of prostate cancer metastasis need to be understood better and new therapies must be developed to selectively target to unique characteristics of cancer cell growth and metastasis. We have developed the "in vivo microscopy" to study the mechanisms that govern prostate cancer cell spread through the microenvironment in vivo in real-time confocal nearinfrared fluorescence imaging. A recently developed "in vivo flow cytometer" and optical imaging are used to assess prostate cancer cell spreading and the circulation kinetics of prostate cancer cells. A real- time quantitative monitoring of circulating prostate cancer cells by the in vivo flow cytometer will be useful to assess the effectiveness of the potential therapeutic interventions.

  2. Studying circulating prostate cancer cells by in-vivo flow cytometer

    NASA Astrophysics Data System (ADS)

    Guo, Jin; Gu, Zhengqin; Chen, Tong; Wang, Cheng; Wei, Xunbin

    2012-03-01

    Prostate cancer is the most common malignancy in American men and the second leading cause of deaths from cancer, after lung cancer. The tumor usually grows slowly and remains confined to the gland for many years. As the cancer advances, however, it can metastasize throughout other areas of the body, such as the bones, lungs, and liver. Surgical resection, hormonal therapy, chemotherapy and radiation therapy are the foundation of current prostate cancer therapies. Treatments for prostate cause both short- and long-term side effects that may be difficult to accept. Molecular mechanisms of prostate cancer metastasis need to be understood better and new therapies must be developed to selectively target to unique characteristics of cancer cell growth and metastasis. We have developed the "in vivo microscopy" to study the mechanisms that govern prostate cancer cell spread through the microenvironment in vivo in real-time confocal near-infrared fluorescence imaging. A recently developed "in vivo flow cytometer" and optical imaging are used to assess prostate cancer cell spreading and the circulation kinetics of prostate cancer cells. We have measured the depletion kinetics of cancer cells with different metastatic potential. Interestingly, more invasive PC-3 prostate cancer cells are depleted faster from the circulation than LNCaP cells.

  3. Prostate cancer stem cells: the role of androgen and estrogen receptors

    PubMed Central

    Di Zazzo, Erika; Galasso, Giovanni; Giovannelli, Pia; Di Donato, Marzia; Di Santi, Annalisa; Cernera, Gustavo; Rossi, Valentina; Abbondanza, Ciro; Moncharmont, Bruno; Sinisi, Antonio Agostino; Castoria, Gabriella; Migliaccio, Antimo

    2016-01-01

    Prostate cancer is one of the most commonly diagnosed cancers in men, and androgen deprivation therapy still represents the primary treatment for prostate cancer patients. This approach, however, frequently fails and patients develop castration-resistant prostate cancer, which is almost untreatable. Cancer cells are characterized by a hierarchical organization, and stem/progenitor cells are endowed with tumor-initiating activity. Accumulating evidence indicates that prostate cancer stem cells lack the androgen receptor and are, indeed, resistant to androgen deprivation therapy. In contrast, these cells express classical (α and/or β) and novel (GPR30) estrogen receptors, which may represent new putative targets in prostate cancer treatment. In the present review, we discuss the still-debated mechanisms, both genomic and non-genomic, by which androgen and estradiol receptors (classical and novel) mediate the hormonal control of prostate cell stemness, transformation, and the continued growth of prostate cancer. Recent preclinical and clinical findings obtained using new androgen receptor antagonists, anti-estrogens, or compounds such as enhancers of androgen receptor degradation and peptides inhibiting non-genomic androgen functions are also presented. These new drugs will likely lead to significant advances in prostate cancer therapy. PMID:26506594

  4. Activation of Notch1 synergizes with multiple pathways in promoting castration-resistant prostate cancer

    PubMed Central

    Stoyanova, Tanya; Riedinger, Mireille; Lin, Shu; Faltermeier, Claire M.; Smith, Bryan A.; Zhang, Kelvin X.; Going, Catherine C.; Goldstein, Andrew S.; Lee, John K.; Drake, Justin M.; Rice, Meghan A.; Hsu, En-Chi; Nowroozizadeh, Behdokht; Castor, Brandon; Orellana, Sandra Y.; Blum, Steven M.; Cheng, Donghui; Pienta, Kenneth J.; Reiter, Robert E.; Pitteri, Sharon J.; Huang, Jiaoti; Witte, Owen N.

    2016-01-01

    Metastatic castration-resistant prostate cancer (CRPC) is the primary cause of prostate cancer-specific mortality. Defining new mechanisms that can predict recurrence and drive lethal CRPC is critical. Here, we demonstrate that localized high-risk prostate cancer and metastatic CRPC, but not benign prostate tissues or low/intermediate-risk prostate cancer, express high levels of nuclear Notch homolog 1, translocation-associated (Notch1) receptor intracellular domain. Chronic activation of Notch1 synergizes with multiple oncogenic pathways altered in early disease to promote the development of prostate adenocarcinoma. These tumors display features of epithelial-to-mesenchymal transition, a cellular state associated with increased tumor aggressiveness. Consistent with its activation in clinical CRPC, tumors driven by Notch1 intracellular domain in combination with multiple pathways altered in prostate cancer are metastatic and resistant to androgen deprivation. Our study provides functional evidence that the Notch1 signaling axis synergizes with alternative pathways in promoting metastatic CRPC and may represent a new therapeutic target for advanced prostate cancer. PMID:27694579

  5. Xanthogranulomatous prostatitis with prostato-rectal fistula: a case report and review of the literature

    PubMed Central

    Xing, Liyong; Liu, Zhifei; Deng, Gang; Wang, Huan; Zhu, Yanfeng; Shi, Peng; Huo, Bingyue; Li, Yindong

    2016-01-01

    Purpose Xanthogranulomatous prostatitis (XP) is a rare form of nonspecific granulomatous prostatitis that can clinically mimic high-grade prostatic carcinoma. It is difficult to diagnose it definitely in clinical settings. Methods We report a case of XP with prostate-rectal fistula and review the relevant literatures. Result A 75-year-old man presented with rectal bleeding when he urinated. A locally advanced carcinoma of prostate was suspected initially following the physical, imaging, and hematologic examinations. Subsequently on histopathological and immunohistochemical staining after needle biopsy of the prostate, a diagnosis of XP was made definitely. The patient was catheterized temporarily and treated with tamsulosin and estrogen. The patient underwent uneventful recovery after this conservative therapy. Conclusion Histologic and immunohistochemical analyses are valuable in differentially diagnosing XP from high-grade prostate carcinoma. Treatment strategy of XP in principle is recommended to be the conservative method. Long-term follow-up earns are highly regarded considering the possibility of coexisting prostate cancer.

  6. Prostatitis--clinical and bacterial studies.

    PubMed

    Chandiok, S; Fisk, P G; Riley, V C

    1992-01-01

    Forty men with clinical prostatitis were studied to determine the value of symptomatology and categorization and 30 (75%) were classified as having prostatitis on the basis of prostatic localization studies. Of these 3 (10%) had chronic bacterial prostatitis, 18 (60%) had chronic abacterial prostatitis, and 9 (30%) had prostatodynia. No patient had acute bacterial prostatitis. Although Enterobacteriaciae were isolated from the 3 men with chronic bacterial prostatitis, these bacteria along with Staphlococcus aureus, Streptococcus faecalis, and Chlamydia trachomatis were isolated from a further 6 patients. The mean pH of the expressed prostatic secretion was measured for each group and was found to be 7.6 for those with chronic bacterial prostatitis, 7.1 for chronic abacterial prostatitis, 6.5 for prostatodynia, and 6.9 for those with urethritis suggesting that this test may be of value in the diagnosis of chronic bacterial prostatitis.

  7. Treatment and prevention of bone complications from prostate cancer.

    PubMed

    Lee, Richard J; Saylor, Philip J; Smith, Matthew R

    2011-01-01

    Bone metastases and skeletal complications are major causes of morbidity in prostate cancer patients. Despite the osteoblastic appearance of bone metastases on imaging studies, patients have elevated serum and urinary markers of bone resorption, indicative of high osteoclast activity. Increased osteoclast activity is independently associated with higher risk of subsequent skeletal complications, disease progression, and death. Osteoclast-targeted therapies are therefore a rational approach to reduction of risk for disease-related skeletal complications, bone metastases, and treatment-related fractures. This review focuses on recent advances in osteoclast-targeted therapy in prostate cancer. Bisphosphonates have been extensively studied in men with prostate cancer. Zoledronic acid significantly decreased the risk of skeletal complications in men with castration-resistant prostate cancer and bone metastases, and it is FDA-approved for this indication. Denosumab is a human monoclonal antibody that binds and inactivates RANKL, a critical mediator of osteoclast differentiation, activation, and survival. Recent global phase 3 clinic trials demonstrated an emerging role for denosumab in the treatment of prostate cancer bone metastases and prevention of fractures associated with androgen deprivation therapy.

  8. Modeling Prostate Cancer in Mice: Limitations and Opportunities

    PubMed Central

    Hensley, Patrick J.; Kyprianou, Natasha

    2013-01-01

    The complex dynamics of the tumor microenvironment and prostate cancer heterogeneity have confounded efforts to establish suitable preclinical mouse models to represent human cancer progression from early proliferative phenotypes to aggressive, androgen-independent, and invasive metastatic tumors. Current models have been successful in capitulating individual characteristics of the aggressive tumors. However, none of these models comprehensively mimics human cancer progression, establishing the challenge in their exploitation to study human disease. The ability to tailor phenotypic outcomes in mice by compounding mutations to target specific molecular pathways provides a powerful tool toward disruption of signaling pathways contributing to the initiation and progression of castration-resistant prostate cancer. Each model is characterized by unique features contributing to the understanding of prostate tumorigenesis, as well as limitations challenging our knowledge of the mechanisms of cancer development and progression. Emerging strategies utilize genomic manipulation technology to circumvent these limitations toward the formulation of attractive, physiologically relevant models of prostate cancer progression to advanced disease. This review discusses the current value of the widely used and well-characterized mouse models of prostate cancer progression to metastasis, as well as the opportunities begging exploitation for the development of new models for testing the antitumor efficacy of therapeutic strategies and identifying new biomarkers of disease progression. PMID:21680808

  9. Prostate cancer magnetic resonance imaging (MRI): multidisciplinary standpoint

    PubMed Central

    Li, Liang; Feng, Zhaoyan; Hu, Zhiquan; Wang, Guoping; Yuan, Xianglin; Wang, He; Hu, Daoyu

    2013-01-01

    Prostate cancer is the most common cancer diagnosed in men and a leading cause of death. Accurate assessment is a prerequisite for optimal clinical management and therapy selection of prostate cancer. There are several parameters and nomograms to differentiate between patients with clinically insignificant disease and patients in need of treatment. Magnetic resonance imaging (MRI) is a technique which provides more detailed anatomical images due to high spatial resolution, superior contrast resolution, and multiplanar capability. State-of-the-art MRI techniques, such as diffusion weighted imaging (DWI), MR spectroscopic imaging (MRSI), dynamic contrast enhanced MRI (DCE-MRI), improve interpretation of prostate cancer imaging. In this article, we review the major role of MRI in the advanced management of prostate cancer to noninvasively improve tumor staging, biologic potential, treatment planning, therapy response, local recurrence, and to guide target biopsy for clinical suspected cancer with previous negative biopsy. Finally, future challenges and opportunities in prostate cancer management in the area of functional MRI are discussed as well. PMID:23630657

  10. The transcriptional programme of the androgen receptor (AR) in prostate cancer.

    PubMed

    Lamb, Alastair D; Massie, Charlie E; Neal, David E

    2014-03-01

    The androgen receptor (AR) is essential for normal prostate and prostate cancer cell growth. AR transcriptional activity is almost always maintained even in hormone relapsed prostate cancer (HRPC) in the absence of normal levels of circulating testosterone. Current molecular techniques, such as chromatin-immunoprecipitation sequencing (ChIP-seq), have permitted identification of direct AR-binding sites in cell lines and human tissue with a distinct coordinate network evident in HRPC. The effectiveness of novel agents, such as abiraterone acetate (suppresses adrenal androgens) or enzalutamide (MDV3100, potent AR antagonist), in treating advanced prostate cancer underlines the on-going critical role of the AR throughout all stages of the disease. Persistent AR activity in advanced disease regulates cell cycle activity, steroid biosynthesis and anabolic metabolism in conjunction with regulatory co-factors, such as the E2F family, c-Myc and signal transducer and activator of transcription (STAT) transcription factors. Further treatment approaches must target these other factors.

  11. Laser-induced interstitial thermotherapy of benign prostatic hyperplasia and prostate cancer

    NASA Astrophysics Data System (ADS)

    Muschter, Rolf

    1994-12-01

    Urinary outflow obstruction by prostatic enlargement is usually treated by resection or, recently, less invasively by thermal `ablation' of tissue through the urethra. With the latter technique, the amount of tissue that can be removed is limited by the limited penetration depth of suitable radiation sources, e.g. lasers, or conduction of heat. Interstitial thermotherapy was expected to overcome this problem. Our initial in vitro and animal studies with different light guides for interstitial application of Nd:YAG laser radiation showed small carbonized lesions with bare fibers, but large homogeneous coagulation zones with special `ITT' (interstitial thermotherapy) fibers. Further studies using these applicators resulted in a technique to be apt for clinical routine in the treatment of symptomatic prostatic enlargement. The tip of the light guide was repeatedly inserted into the prostate either transurethrally through a cystoscope under direct vision or percutaneously from the perineum under transrectal ultrasound guidance. The number of fiber placements depended on the size and configuration of the gland. Irradiation was performed either for 10 min with 5 or 7 W or in the advanced `turbo'- mode for 5 or 3 min per fiber placement using automatically stepwise reduced power (20 W for 30 s, 15 W for 30 s, 10 W for 30 s, and 7 W for 210 or 90 s). By optical feedback control the laser was switched off automatically in the case of carbonization to avoid fiber damage. From July 15, 1991 to October 1, 1993 239 patients with BPH and 14 patients with advanced prostate cancer, suffering from severe urinary outflow obstruction, were treated by laser induced interstitial thermotherapy. The results and complications of treatment are reported.

  12. [Screening for prostate cancer].

    PubMed

    Koch, Klaus; Büchter, Roland; Lange, Stefan

    2013-04-01

    Prostate cancer screening has been a controversial for decades. The recently published findings of large trials have further intensified the debate. The prospect of reducing mortality from prostate cancer is measured against the risk of over-diagnosing the disease. In individual cases, the trade-off between possible benefits and harms is possible to ascertain, so general recommendations in favor of or against PSA tests for individuals cannot be made. The majority of men, however, are not well-informed on the possible advantages and drawbacks of screening. This situation urgently needs to be corrected. The PSA test is promoted to healthy men, who need to be provided with especially detailed information. If not provided with clear and unbiased information on the risks associated with the test (above all over-diagnosis and over-treatment), these men cannot be considered to be fully informed. PMID:23535548

  13. Prostate Focused Ultrasound Therapy.

    PubMed

    Chapelon, Jean-Yves; Rouvière, Olivier; Crouzet, Sébastien; Gelet, Albert

    2016-01-01

    The tremendous progress in engineering and computing power coupled with ultrasound transducer technology and imaging modalities over the past 20 years have encouraged a revival of clinical interest in ultrasound therapy, mainly in High-Intensity Focused Ultrasound (HIFU). So far, the most extensive results from HIFU obtained in urology involve transrectal prostate ablation, which appears to be an effective therapeutic alternative for patients with malignant prostate tumors. Prostate cancer (PCa) is one of the most frequently diagnosed cancers in men. Several treatment options with different therapeutic approaches exist, including HIFU for localized PCa that has been in use for over 15 years. Since the early 2000s, two systems have been marketed for this application, and other devices are currently in clinical trials. HIFU treatment can be used either alone or in combination with (before- or after-) external beam radiotherapy (EBRT) (before or after HIFU) and can be repeated multiple times. HIFU treatment is performed under real-time monitoring with ultrasound or guided by MRI. Two indications are validated today: Primary care treatment and EBRT failure. The results of HIFU for primary care treatment are similar to standard conformal EBRT, even though no randomized comparative studies have been performed and no 10-year follow up data is yet available for HIFU. Salvage HIFU after EBRT failure is increasing with oncological outcomes, similar to those achieved with surgery but with the advantage of fewer adverse effects. HIFU is an evolving technology perfectly adapted for focal treatment. Thus, HIFU focal therapy is another pathway that must be explored when considering the accuracy and reliability for PCa mapping techniques. HIFU would be particularly suited for such a therapy since it is clear that HIFU outcomes and toxicity are relative to the volume of prostate treated.

  14. Simulated prostate biopsy: prostate cancer distribution and clinical correlation

    NASA Astrophysics Data System (ADS)

    Bauer, John J.; Zeng, Jianchao; Zhang, Wei; Sesterhenn, Isabell A.; Dean, Robert; Moul, Judd W.; Mun, Seong K.

    2000-04-01

    Our group has recently obtained data based upon whole- mounted step-sectioned radical prostatectomy specimens using a 3D computer assisted prostate biopsy simulator that suggests an increased detection rate is possible using laterally placed biopsies. A new 10-core biopsy pattern was demonstrated to be superior to the traditional sextant biopsy. This patter includes the traditional sextant biopsy cores and four laterally placed biopsies in the right and left apex and mid portion of the prostate gland. The objective of this study is to confirm the higher prostate cancer defection rate obtained using our simulated 10-core biopsy pattern in a small clinical trial. We retrospectively reviewed 35 consecutive patients with a pathologic diagnosis of prostate cancer biopsied by a single urologist using the 10-core prostate biopsy patterns were compared with respect to prostate cancer detection rate. Of the 35 patients diagnosed with prostate cancer, 54.3 percent were diagnosed when reviewing the sextant biopsy data only. Review of the 10-core pattern revealed that an additional 45.7 percent were diagnosed when reviewing the sextant biopsy data only. Review of the 10-core pattern revealed that an additional 45.7 percent of patients were diagnosed solely with the laterally placed biopsies. Our results suggest that biopsy protocols that use laterally placed biopsies based upon a five region anatomical model are superior to the routinely used sextant prostate biopsy pattern.

  15. Dickkopf-3 regulates prostate epithelial cell acinar morphogenesis and prostate cancer cell invasion by limiting TGF-β-dependent activation of matrix metalloproteases.

    PubMed

    Romero, Diana; Al-Shareef, Zainab; Gorroño-Etxebarria, Irantzu; Atkins, Stephanie; Turrell, Frances; Chhetri, Jyoti; Bengoa-Vergniory, Nora; Zenzmaier, Christoph; Berger, Peter; Waxman, Jonathan; Kypta, Robert

    2016-01-01

    Dickkopf-3 (Dkk-3) is a secreted protein whose expression is downregulated in many types of cancer. Endogenous Dkk-3 is required for formation of acini in 3D cultures of prostate epithelial cells, where it inhibits transforming growth factor (TGF)-β/Smad signaling. Here, we examined the effects of Dkk-3 on the expression and activity of matrix metalloproteases (MMPs), which mediate the effects of TGF-β on extracellular matrix disassembly during tissue morphogenesis and promote invasion of tumor cells. Silencing of Dkk-3 in prostate epithelial cells resulted in increased expression and enzyme activity of MMP-2 and MMP-9. Inhibition of MMP-9 partially restored normal acinar morphogenesis in Dkk-3-silenced RWPE-1 prostate epithelial cells. In PC3 prostate cancer cells, Dkk-3 inhibited TGF-β-dependent migration and invasion. Inhibition was mediated by the Dkk-3 C-terminal cysteine-rich domain (Cys2), which also inhibited TGF-β-induced expression of MMP9 and MMP13. In contrast, Dkk-3, but not Cys2, increased formation of normal acini in Dkk-3-silenced prostate epithelial cells. These observations highlight a role for Dkk-3 in modulating TGF-β/MMP signals in the prostate, and suggest that the Dkk-3 Cys2 domain can be used as a basis for therapies that target the tumor promoting effects of TGF-β signaling in advanced prostate cancer.

  16. Urinary melatonin-sulfate/cortisol ratio and the presence of prostate cancer: A case-control study

    PubMed Central

    Tai, Shu-Yu; Huang, Shu-Pin; Bao, Bo-Ying; Wu, Ming-Tsang

    2016-01-01

    The circadian-related hormones, melatonin and cortisol, have oncostatic and immunosuppressive properties. This study examined the relationship between these two biomarkers and the presence of prostate cancer. We measured their major metabolites in urine collected from 120 newly diagnosed prostate cancer patients and 240 age-matched controls from January 2011 to April 2014. Compared with patients with lower urinary melatonin-sulfate or melatonin-sulfate/cortisol (MT/C) ratio levels, those with above-median levels were significantly less likely to have prostate cancer (adjusted OR (aOR) = 0.59, 95% CI = 0.35–0.99; aOR = 0.46, 95% CI: 0.27–0.77) or advanced stage prostate cancer (aOR = 0.49, 95% CI = 0.26–0.89; aOR = 0.33, 95% CI = 0.17–0.62). The combined effect of both low MT/C ratios and PSA levels exceeding 10 ng/ml was an 8.82-fold greater likelihood of prostate cancer and a 32.06-fold greater likelihood of advanced stage prostate cancer, compared to those with both high MT/C ratios and PSA levels less than 10 ng/ml. In conclusion, patients with high melatonin-sulfate levels or a high MT/C ratio were less likely to have prostate cancer or advanced stage prostate. Besides, a finding of a low MT/C ratio combined with a PSA level exceeding 10 ng/ml showed the greatest potential in detecting prostate cancer and advanced stage prostate cancer. PMID:27387675

  17. Chronic prostatitis: Current concepts

    PubMed Central

    Vaidyanathan, Ram; Mishra, Vibhash C.

    2008-01-01

    Purpose: Chronic prostatitis (CP) is a common condition. It causes significant suffering to the patients and constitutes a sizeable workload for the urologists. The purpose of this review is to describe the currently accepted concepts regarding the aspects of CP. Materials and Methods: Relevant papers on the epidemiology, etiology, diagnosis, evaluation and management of CP were identified through a search of MEDLINE using text terms “prostatitis”, “chronic prostatitis” and “chronic pelvic pain syndrome”. The list of articles thus obtained was supplemented by manual search of bibliographies of the identified articles and also by exploring the MEDLINE option “Related Articles”. Results: The salient points of the relevant articles on each aspect of CP have been summarized in the form of a non-systematic narrative review. Conclusion: Chronic prostatitis is caused by a variety of infective and non-infective factors and is characterized by a rather long remitting and relapsing clinical course. The diagnosis is based on symptoms comprising pain and nonspecific urinary and/or ejaculatory disturbances and microbiological tests to localize bacteria and/or leucocytes in segmented urinary tract specimens. The contemporary classification was proposed by the National Institutes of Health/National Institute of Diabetes Digestive Kidney Diseases (NIH/NIDDK). National Institutes of Health - Chronic Prostatitis Symptom Index (NIH-CPSI) is the patient evaluation tool used extensively in clinical practice and research. Management should be individualized, multimodal and of an appropriate duration. PMID:19468353

  18. Incidental fleurodeoxyglucose uptake in the prostate

    PubMed Central

    Wong, W L; Moule, R N; Nunan, T

    2010-01-01

    This commentary confirms the rarity of prostatic cancer associated with incidental prostatic fleurodeoxyglucose (FDG) uptake. The study adds to the literature by showing that even if a prostate lesion is FDG avid it is unlikely to be due to cancer. The commentary considers the management of incidental prostate FDG uptake on the basis of the available evidence. PMID:20965899

  19. Prostate-specific antigen (PSA) blood test

    MedlinePlus

    Prostate-specific antigen; Prostate cancer screening test; PSA ... special steps are needed to prepare for this test. ... Reasons for a PSA test: This test may be done to screen for prostate cancer. It is also used to follow people after prostate cancer ...

  20. HUMAN PROSTATE CANCER RISK FACTORS

    EPA Science Inventory

    Prostate cancer has the highest prevalence of any non-skin cancer in the human body, with similar likelihood of neoplastic foci found within the prostates of men around the world regardless of diet, occupation, lifestyle, or other factors. Essentially all men with circulating an...

  1. Vitamin E and Prostate Cancer

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vitamin E, its metabolites or its analogs, might help prevent prostate cancer initiation or progression. Prostate cancer is the most common non-skin malignancy and the second leading cause of cancer deaths among men in the United States, exceeded only by lung cancer. About 218,890 new cases of prost...

  2. Human Prostate Cancer Hallmarks Map.

    PubMed

    Datta, Dipamoy; Aftabuddin, Md; Gupta, Dinesh Kumar; Raha, Sanghamitra; Sen, Prosenjit

    2016-08-01

    Human prostate cancer is a complex heterogeneous disease that mainly affects elder male population of the western world with a high rate of mortality. Acquisitions of diverse sets of hallmark capabilities along with an aberrant functioning of androgen receptor signaling are the central driving forces behind prostatic tumorigenesis and its transition into metastatic castration resistant disease. These hallmark capabilities arise due to an intense orchestration of several crucial factors, including deregulation of vital cell physiological processes, inactivation of tumor suppressive activity and disruption of prostate gland specific cellular homeostasis. The molecular complexity and redundancy of oncoproteins signaling in prostate cancer demands for concurrent inhibition of multiple hallmark associated pathways. By an extensive manual curation of the published biomedical literature, we have developed Human Prostate Cancer Hallmarks Map (HPCHM), an onco-functional atlas of human prostate cancer associated signaling and events. It explores molecular architecture of prostate cancer signaling at various levels, namely key protein components, molecular connectivity map, oncogenic signaling pathway map, pathway based functional connectivity map etc. Here, we briefly represent the systems level understanding of the molecular mechanisms associated with prostate tumorigenesis by considering each and individual molecular and cell biological events of this disease process.

  3. Biomarkers in Prostate Cancer Epidemiology

    PubMed Central

    Verma, Mukesh; Patel, Payal; Verma, Mudit

    2011-01-01

    Understanding the etiology of a disease such as prostate cancer may help in identifying populations at high risk, timely intervention of the disease, and proper treatment. Biomarkers, along with exposure history and clinical data, are useful tools to achieve these goals. Individual risk and population incidence of prostate cancer result from the intervention of genetic susceptibility and exposure. Biochemical, epigenetic, genetic, and imaging biomarkers are used to identify people at high risk for developing prostate cancer. In cancer epidemiology, epigenetic biomarkers offer advantages over other types of biomarkers because they are expressed against a person's genetic background and environmental exposure, and because abnormal events occur early in cancer development, which includes several epigenetic alterations in cancer cells. This article describes different biomarkers that have potential use in studying the epidemiology of prostate cancer. We also discuss the characteristics of an ideal biomarker for prostate cancer, and technologies utilized for biomarker assays. Among epigenetic biomarkers, most reports indicate GSTP1 hypermethylation as the diagnostic marker for prostate cancer; however, NKX2-5, CLSTN1, SPOCK2, SLC16A12, DPYS, and NSE1 also have been reported to be regulated by methylation mechanisms in prostate cancer. Current challenges in utilization of biomarkers in prostate cancer diagnosis and epidemiologic studies and potential solutions also are discussed. PMID:24213111

  4. Human Prostate Cancer Hallmarks Map

    PubMed Central

    Datta, Dipamoy; Aftabuddin, Md.; Gupta, Dinesh Kumar; Raha, Sanghamitra; Sen, Prosenjit

    2016-01-01

    Human prostate cancer is a complex heterogeneous disease that mainly affects elder male population of the western world with a high rate of mortality. Acquisitions of diverse sets of hallmark capabilities along with an aberrant functioning of androgen receptor signaling are the central driving forces behind prostatic tumorigenesis and its transition into metastatic castration resistant disease. These hallmark capabilities arise due to an intense orchestration of several crucial factors, including deregulation of vital cell physiological processes, inactivation of tumor suppressive activity and disruption of prostate gland specific cellular homeostasis. The molecular complexity and redundancy of oncoproteins signaling in prostate cancer demands for concurrent inhibition of multiple hallmark associated pathways. By an extensive manual curation of the published biomedical literature, we have developed Human Prostate Cancer Hallmarks Map (HPCHM), an onco-functional atlas of human prostate cancer associated signaling and events. It explores molecular architecture of prostate cancer signaling at various levels, namely key protein components, molecular connectivity map, oncogenic signaling pathway map, pathway based functional connectivity map etc. Here, we briefly represent the systems level understanding of the molecular mechanisms associated with prostate tumorigenesis by considering each and individual molecular and cell biological events of this disease process. PMID:27476486

  5. Biomarkers in localized prostate cancer.

    PubMed

    Ferro, Matteo; Buonerba, Carlo; Terracciano, Daniela; Lucarelli, Giuseppe; Cosimato, Vincenzo; Bottero, Danilo; Deliu, Victor M; Ditonno, Pasquale; Perdonà, Sisto; Autorino, Riccardo; Coman, Ioman; De Placido, Sabino; Di Lorenzo, Giuseppe; De Cobelli, Ottavio

    2016-02-01

    Biomarkers can improve prostate cancer diagnosis and treatment. Accuracy of prostate-specific antigen (PSA) for early diagnosis of prostate cancer is not satisfactory, as it is an organ- but not cancer-specific biomarker, and it can be improved by using models that incorporate PSA along with other test results, such as prostate cancer antigen 3, the molecular forms of PSA (proPSA, benign PSA and intact PSA), as well as kallikreins. Recent reports suggest that new tools may be provided by metabolomic studies as shown by preliminary data on sarcosine. Additional molecular biomarkers have been identified by the use of genomics, proteomics and metabolomics. We review the most relevant biomarkers for early diagnosis and management of localized prostate cancer.

  6. Genetic Regulation of Prostate Development

    PubMed Central

    Meeks, Joshua; Schaeffer, Edward M

    2011-01-01

    Prostatic development is a dynamic process in which basic mechanisms of epithelial outgrowth and epithelial-mesenchymal interaction are initiated by androgens and androgen receptor signaling. Even in adulthood, the prostate's function remains tightly regulated by androgens--without them, pathologic diseases including hyperplastic and malignant growth which together plague nearly 50% of aging males does not occur. Unraveling the etiology of these pathologic processes is a complex and important goal. In fact, many insights into these processes have come from an intimate understanding of the complex signaling networks that regulate physiologic prostatic growth in development. This review aims to highlight important key molecules such as Nkx3.1, sonic hedgehog and Sox9 as well as key signaling pathways including the Fibroblast growth factor and Wnt pathways. These molecules and pathways are critical for prostate development with both know and postulated roles in prostatic pathology. PMID:20930191

  7. Dietary Fat, Fatty Acids and Risk of Prostate Cancer in the NIH-AARP Diet and Health Study

    PubMed Central

    Pelser, Colleen; Mondul, Alison M.; Hollenbeck, Albert R.; Park, Yikyung

    2013-01-01

    Background Observational studies report inconsistent associations of fat and fatty acids with prostate cancer. Methods We investigated associations between dietary fats and fatty acids and risk of prostate cancer in the National Institutes of Health (NIH)-AARP Diet and Health Study. Diet was assessed at baseline with self-administered food-frequency questionnaires. Cases were determined by linkage with state cancer registries. Hazard ratios (HR) and 95% confidence intervals (CIs) were estimated with Cox proportional hazards models. Results Among 288,268 men with average follow-up of 9 years, 23,281 prostate cancer cases (18,934 non-advanced and 2,930 advanced including 725 fatal cases) were identified. Total fat, and mono- and polyunsaturated fat INTAKES were not associated with incidence of prostate cancer. Saturated fat intake was related to increased risk of advanced prostate cancer (HRQuintile 5 vs. Qunitile 1 (Q1 vs. Q5)1.21; 95% CI 1.00–1.46; p-for-trend=0.03) and fatal prostate cancer (HR Q5 vs. Q1 1.47; 95% CI 1.01–2.15; p-for-trend=0.04). Alpha-linolenic acid (ALA) intake was related to increased risk of advanced prostate cancer (HRQ5 vs. Q1 1.17; 95 % CI:1.04–1.31; p-for-trend 0.01). Eicosapentanoic acid (EPA) intake was related to decreased risk of fatal prostate cancer (HR Q5 vs. Q1 0.82; 95% CI 0.64–1.04; p-for-trend 0.02). Conclusion Our study suggests that the associations of fat and fatty acids differ by prostate cancer severity. Saturated fat, ALA and EPA intakes were related to the risk of advanced or fatal prostate cancer, but not to non-advanced prostate cancer. Impact identifying factors associated with advanced prostate cancer could reduce morbidity and mortality. PMID:23549401

  8. Androgen receptor and gene network: Micromechanics reassemble the signaling machinery of TMPRSS2-ERG positive prostate cancer cells

    PubMed Central

    2014-01-01

    Prostate cancer is a gland tumor in the male reproductive system. It is a multifaceted and genomically complex disease. Transmembrane protease, serine 2 and v-ets erythroblastosis virus E26 homolog (TMPRSS2-ERG) gene fusions are the common molecular signature of prostate cancer. Although tremendous advances have been made in unraveling various facets of TMPRSS2-ERG-positive prostate cancer, many research findings must be sequentially collected and re-interpreted. It is important to understand the activation or repression of target genes and proteins in response to various stimuli and the assembly in signal transduction in TMPRSS2-ERG fusion-positive prostate cancer cells. Accordingly, we divide this multi-component review ofprostate cancer cells into several segments: 1) The role of TMPRSS2-ERG fusion in genomic instability and methylated regulation in prostate cancer and normal cells; 2) Signal transduction cascades in TMPRSS2-ERG fusion-positive prostate cancer; 3) Overexpressed genes in TMPRSS2-ERG fusion-positive prostate cancer cells; 4) miRNA mediated regulation of the androgen receptor (AR) and its associated protein network; 5) Quantitative control of ERG in prostate cancer cells; 6) TMPRSS2-ERG encoded protein targeting; In conclusion, we provide a detailed understanding of TMPRSS2-ERG fusion related information in prostate cancer development to provide a rationale for exploring TMPRSS2-ERG fusion-mediated molecular network machinery. PMID:24739220

  9. Photoacoustic imaging of prostate brachytherapy seeds in ex vivo prostate

    NASA Astrophysics Data System (ADS)

    Kuo, Nathanael; Kang, Hyun Jae; DeJournett, Travis; Spicer, James; Boctor, Emad

    2011-03-01

    The localization of brachytherapy seeds in relation to the prostate is a key step in intraoperative treatment planning (ITP) for improving outcomes in prostate cancer patients treated with low dose rate prostate brachytherapy. Transrectal ultrasound (TRUS) has traditionally been the modality of choice to guide the prostate brachytherapy procedure due to its relatively low cost and apparent ease of use. However, TRUS is unable to visualize seeds well, precluding ITP and producing suboptimal results. While other modalities such as X-ray and magnetic resonance imaging have been investigated to localize seeds in relation to the prostate, photoacoustic imaging has become an emerging and promising modality to solve this challenge. Moreover, photoacoustic imaging may be more practical in the clinical setting compared to other methods since it adds little additional equipment to the ultrasound system already adopted in procedure today, reducing cost and simplifying engineering steps. In this paper, we demonstrate the latest efforts of localizing prostate brachytherapy seeds using photoacoustic imaging, including visualization of multiple seeds in actual prostate tissue. Although there are still several challenges to be met before photoacoustic imaging can be used in the operating room, we are pleased to present the current progress in this effort.

  10. A vaccine strategy with multiple prostatic acid phosphatase-fused cytokines for prostate cancer treatment

    PubMed Central

    FUJIO, KEI; WATANABE, MASAMI; UEKI, HIDEO; LI, SHUN-AI; KINOSHITA, RIE; OCHIAI, KAZUHIKO; FUTAMI, JUNICHIRO; WATANABE, TOYOHIKO; NASU, YASUTOMO; KUMON, HIROMI

    2015-01-01

    Immunotherapy is one of the attractive treatment strategies for advanced prostate cancer. The US Food and Drug Administration (FDA) previously approved the therapeutic vaccine, sipuleucel-T, which is composed of autologous antigen-presenting cells cultured with a fusion protein [prostatic acid phosphatase (PAP) and granulocyte-macrophage colony-stimulating factor (GMCSF)]. Although sipuleucel-T has been shown to prolong the median survival of patients for 4.1 months, more robust therapeutic effects may be expected by modifying the vaccination protocol. In the present study, we aimed to develop and validate a novel vaccination strategy using multiple PAP-fused cytokines for prostate cancer treatment. Using a super gene expression (SGE) system that we previously established to amplify the production of a recombinant protein, significant amounts of PAP-fused cytokines [human GMCSF, interleukin-2 (IL2), IL4, IL7 and mouse GMCSF and IL4] were obtained. We examined the activity of the fusion proteins in vitro to validate their cytokine functions. A significant upregulation of dendritic cell differentiation from monocytes was achieved by PAP-GMCSF when used with the other PAP-fused cytokines. The PAP-fused human IL2 significantly increased the proliferation of lymphocytes, as determined by flow cytometry. We also investigated the in vivo therapeutic effects of multiple PAP-fused cytokines in a mouse prostate cancer model bearing prostate-specific antigen (PSA)- and PAP-expressing tumors. The simultaneous intraperitoneal administration of PAP-GMCSF, -IL2, -IL4 and -IL7 significantly prevented tumor induction and inhibited the tumor growth in the PAP-expressing tumors, yet not in the PSA-expressing tumors. The in vivo therapeutic effects with the multiple PAP-fused cytokines were superior to the effects of PAP-GMCSF alone. We thus demonstrated the advantages of the combined use of multiple PAP-fused cytokines including PAP-GMCSF, and propose a promising prostatic antigen

  11. Prostate MRI can reduce overdiagnosis and overtreatment of prostate cancer.

    PubMed

    Rosenkrantz, Andrew B; Taneja, Samir S

    2015-08-01

    The contemporary management of prostate cancer (PCa) has been criticized as fostering overdetection and overtreatment of indolent disease. In particular, the historical inability to identify those men with an elevated PSA who truly warrant biopsy, and, for those needing biopsy, to localize aggressive tumors within the prostate, has contributed to suboptimal diagnosis and treatment strategies. This article describes how modern multi-parametric MRI of the prostate addresses such challenges and reduces both overdiagnosis and overtreatment. The central role of diffusion-weighted imaging (DWI) in contributing to MRI's current impact is described. Prostate MRI incorporating DWI achieves higher sensitivity than standard systematic biopsy for intermediate-to-high risk tumor, while having lower sensitivity for low-grade tumors that are unlikely to impact longevity. Particular applications of prostate MRI that are explored include selection of a subset of men with clinical suspicion of PCa to undergo biopsy as well as reliable confirmation of only low-risk disease in active surveillance patients. Various challenges to redefining the standard of care to incorporate solely MRI-targeted cores, without concomitant standard systematic cores, are identified. These include needs for further technical optimization of current systems for performing MRI-targeted biopsies, enhanced education and expertise in prostate MRI among radiologists, greater standardization in prostate MRI reporting across centers, and recognition of the roles of pre-biopsy MRI and MRI-targeted biopsy by payers. Ultimately, it is hoped that the medical community in the United States will embrace prostate MRI and MRI-targeted biopsy, allowing all patients with known or suspected prostate cancer to benefit from this approach.

  12. Calcium and phosphorus intake and prostate cancer risk: a 24-y follow-up study123

    PubMed Central

    Shui, Irene M; Mucci, Lorelei A; Giovannucci, Edward

    2015-01-01

    Background: High calcium intake has been associated with an increased risk of advanced-stage and high-grade prostate cancer. Several studies have found a positive association between phosphorus intake and prostate cancer risk. Objective: We investigated the joint association between calcium and phosphorus and risk of prostate cancer in the Health Professionals Follow-Up Study, with a focus on lethal and high-grade disease. Design: In total, 47,885 men in the cohort reported diet data in 1986 and every 4 y thereafter. From 1986 to 2010, 5861 cases of prostate cancer were identified, including 789 lethal cancers (fatal or metastatic). We used Cox proportional hazards models to assess the association between calcium and phosphorus intake and prostate cancer, with adjustment for potential confounding. Results: Calcium intakes >2000 mg/d were associated with greater risk of total prostate cancer and lethal and high-grade cancers. These associations were attenuated and no longer statistically significant when phosphorus intake was adjusted for. Phosphorus intake was associated with greater risk of total, lethal, and high-grade cancers, independent of calcium and intakes of red meat, white meat, dairy, and fish. In latency analysis, calcium and phosphorus had independent effects for different time periods between exposure and diagnosis. Calcium intake was associated with an increased risk of advanced-stage and high-grade disease 12–16 y after exposure, whereas high phosphorus was associated with increased risk of advanced-stage and high-grade disease 0–8 y after exposure. Conclusions: Phosphorus is independently associated with risk of lethal and high-grade prostate cancer. Calcium may not have a strong independent effect on prostate cancer risk except with long latency periods. PMID:25527761

  13. Early prostate-specific antigen changes and the diagnosis and prognosis of prostate cancer

    PubMed Central

    Botchorishvili, George; Matikainen, Mika P.; Lilja, Hans

    2009-01-01

    Purpose of review To delineate how recent findings on prostate-specific antigen (PSA) can improve prediction of risk, detection, and prediction of clinical endpoints of prostate cancer (PCa). Recent findings The widely used PSA cut-point of 4.0 ng/ml increasingly appears arbitrary, but no cut-point achieves both high sensitivity and high specificity. The accuracy of detecting PCa can be increased by additional predictive factors and combinations of markers. Evidence implies that a panel of kallikrein markers improves the specificity and reduces costs by eliminating unnecessary biopsies. Large, population-based studies have provided evidence that PSA can be used to predict PCa risk many years in advance, improve treatment selection and patient care, and predict the risk of complications and disease recurrence. However, definitive evidence is currently lacking as to whether PSA screening lowers PCa -specific mortality. Summary PSA is still the main tool for early detection, risk stratification, and monitoring of PCa. However, PSA values are affected by many technical and biological factors. Instead of using a fixed PSA cut-point, using statistical prediction models and considering the integration additional markers may be able to improve and individualize PCa diagnostics. A single PSA measurement at early middle age can predict risk of advanced PCa decades in advance and stratify patients for intensity of subsequent screening. PMID:19318948

  14. Blood lipids and prostate cancer: a Mendelian randomization analysis.

    PubMed

    Bull, Caroline J; Bonilla, Carolina; Holly, Jeff M P; Perks, Claire M; Davies, Neil; Haycock, Philip; Yu, Oriana Hoi Yun; Richards, J Brent; Eeles, Rosalind; Easton, Doug; Kote-Jarai, Zsofia; Amin Al Olama, Ali; Benlloch, Sara; Muir, Kenneth; Giles, Graham G; MacInnis, Robert J; Wiklund, Fredrik; Gronberg, Henrik; Haiman, Christopher A; Schleutker, Johanna; Nordestgaard, Børge G; Travis, Ruth C; Neal, David; Pashayan, Nora; Khaw, Kay-Tee; Stanford, Janet L; Blot, William J; Thibodeau, Stephen; Maier, Christiane; Kibel, Adam S; Cybulski, Cezary; Cannon-Albright, Lisa; Brenner, Hermann; Park, Jong; Kaneva, Radka; Batra, Jyotsna; Teixeira, Manuel R; Micheal, Agnieszka; Pandha, Hardev; Smith, George Davey; Lewis, Sarah J; Martin, Richard M

    2016-06-01

    Genetic risk scores were used as unconfounded instruments for specific lipid traits (Mendelian randomization) to assess whether circulating lipids causally influence prostate cancer risk. Data from 22,249 prostate cancer cases and 22,133 controls from 22 studies within the international PRACTICAL consortium were analyzed. Allele scores based on single nucleotide polymorphisms (SNPs) previously reported to be uniquely associated with each of low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride (TG) levels, were first validated in an independent dataset, and then entered into logistic regression models to estimate the presence (and direction) of any causal effect of each lipid trait on prostate cancer risk. There was weak evidence for an association between the LDL genetic score and cancer grade: the odds ratio (OR) per genetically instrumented standard deviation (SD) in LDL, comparing high- (≥7 Gleason score) versus low-grade (<7 Gleason score) cancers was 1.50 (95% CI: 0.92, 2.46; P = 0.11). A genetically instrumented SD increase in TGs was weakly associated with stage: the OR for advanced versus localized cancer per unit increase in genetic risk score was 1.68 (95% CI: 0.95, 3.00; P = 0.08). The rs12916-T variant in 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) was inversely associated with prostate cancer (OR: 0.97; 95% CI: 0.94, 1.00; P = 0.03). In conclusion, circulating lipids, instrumented by our genetic risk scores, did not appear to alter prostate cancer risk. We found weak evidence that higher LDL and TG levels increase aggressive prostate cancer risk, and that a variant in HMGCR (that mimics the LDL lowering effect of statin drugs) reduces risk. However, inferences are limited by sample size and evidence of pleiotropy. PMID:26992435

  15. Transurethral resection of the prostate (TURP) - Series (image)

    MedlinePlus

    The prostate gland is an organ that surrounds the urinary urethra in men. It secretes fluid that mixes with ... An enlarged prostate gland compresses the urethra, causing problems with ... is caused by prostate gland overgrowth (benign prostatic ...

  16. A Prospective Randomized Trial of Two Different Prostate Biopsy Schemes

    ClinicalTrials.gov

    2016-07-03

    Prostate Cancer; Local Anesthesia; Prostate-Specific Antigen/Blood; Biopsy/Methods; Image-guided Biopsy/Methods; Prostatic Neoplasms/Diagnosis; Prostate/Pathology; Prospective Studies; Humans; Male; Ultrasonography, Interventional/Methods

  17. Treating Enlarged Prostate (BPH): Which Drugs Work Best

    MedlinePlus

    ... the prostate gets larger. This is called prostate enlargement, or BPH (benign prostatic hyperplasia). Why should I ... alpha-blocker doxazosin for a first treatment. Prostate enlargement affects millions of men, including about half of ...

  18. Definition of a FoxA1 Cistrome that is crucial for G1 to S-phase cell-cycle transit in castration-resistant prostate cancer.

    PubMed

    Zhang, Chunpeng; Wang, Liguo; Wu, Dayong; Chen, Hongyan; Chen, Zhong; Thomas-Ahner, Jennifer M; Zynger, Debra L; Eeckhoute, Jérôme; Yu, Jindan; Luo, Jun; Brown, Myles; Clinton, Steven K; Nephew, Kenneth P; Huang, Tim H-M; Li, Wei; Wang, Qianben

    2011-11-01

    The enhancer pioneer transcription factor FoxA1 is a global mediator of steroid receptor (SR) action in hormone-dependent cancers. In castration-resistant prostate cancer (CRPC), FoxA1 acts as an androgen receptor cofactor to drive G₂ to M-phase cell-cycle transit. Here, we describe a mechanistically distinct SR-independent role for FoxA1 in driving G₁ to S-phase cell-cycle transit in CRPC. By comparing FoxA1 binding sites in prostate cancer cell genomes, we defined a codependent set of FoxA1-MYBL2 and FoxA1-CREB1 binding sites within the regulatory regions of the Cyclin E2 and E2F1 genes that are critical for CRPC growth. Binding at these sites upregulate the Cyclin E2 and Cyclin A2 genes in CRPC but not in earlier stage androgen-dependent prostate cancer, establishing a stage-specific role for this pathway in CRPC growth. Mechanistic investigations indicated that FoxA1, MYBL2, or CREB1 induction of histone H3 acetylation facilitated nucleosome disruption as the basis for codependent transcriptional activation and G₁ to S-phase cell-cycle transit. Our findings establish FoxA1 as a pivotal driver of the cell-cycle in CRPC which promotes G₁ to S-phase transit as well as G₂ to M-phase transit through two distinct mechanisms.

  19. Reimbursement for bone loss prevention is different between women with breast cancer and men with prostate cancer: time for a revision

    PubMed Central

    Tjalma, W.A.A.

    2015-01-01

    The hormone dependent breast and prostate cancers have in general a very good survival, due to the anti-hormonal treatment. A disadvantage of this treatment is the increased risk of osteoporosis and fractures. It is surprisingly to note that denosumab has the same impact on fracture reduction incidence for both sexes, but with different reimbursement criteria. Furthermore there is only reimbursement in case of osteoporosis and not for cancer patients who are at an increased risk of developing osteoporosis. The clinician detects the accelerated bone loss during follow-up, but has to wait until there is osteoporosis. The impact of osteoporosis on the quality of life is severe and underestimated. Management of cancer should not only focus on survival, therefore it is time to reconsider the reimbursement criteria, discuss the willingness of society to pay for bone health and make choices regarding the advice we give to our patients. PMID:26977268

  20. AMR-Me inhibits PI3K/Akt signaling in hormone-dependent MCF-7 breast cancer cells and inactivates NF-κB in hormone-independent MDA-MB-231 cells.

    PubMed

    Rabi, Thangaiyan; Huwiler, Andrea; Zangemeister-Wittke, Uwe

    2014-07-01

    AMR-Me, a C-28 methylester derivative of triterpenoid compound Amooranin isolated from Amoora rohituka stem bark and the plant has been reported to possess multitude of medicinal properties. Our previous studies have shown that AMR-Me can induce apoptosis through mitochondrial apoptotic and MAPK signaling pathways by regulating the expression of apoptosis related genes in human breast cancer MCF-7 cells. However, the molecular mechanism of AMR-Me induced apoptotic cell death remains unclear. Our results showed that AMR-Me dose-dependently inhibited the proliferation of MCF-7 and MDA-MB-231 cells under serum-free conditions supplemented with 1 nM estrogen (E2) with an IC50 value of 0.15 µM, 0.45 µM, respectively. AMR-Me had minimal effects on human normal breast epithelial MCF-10A + ras and MCF-10A cells with IC50 value of 6 and 6.5 µM, respectively. AMR-Me downregulated PI3K p85, Akt1, and p-Akt in an ERα-independent manner in MCF-7 cells and no change in expression levels of PI3K p85 and Akt were observed in MDA-MB-231 cells treated under similar conditions. The PI3K inhibitor LY294002 suppressed Akt activation similar to AMR-Me and potentiated AMR-Me induced apoptosis in MCF-7 cells. EMSA revealed that AMR-Me inhibited nuclear factor-kappaB (NF-κB) DNA binding activity in MDA-MB-231 cells in a time-dependent manner and abrogated EGF induced NF-κB activation. From these studies we conclude that AMR-Me decreased ERα expression and effectively inhibited Akt phosphorylation in MCF-7 cells and inactivate constitutive nuclear NF-κB and its regulated proteins in MDA-MB-231 cells. Due to this multifactorial effect in hormone-dependent and independent breast cancer cells AMR-Me deserves attention for use in breast cancer prevention and therapy. PMID:23475563

  1. Bioenergetic theory of prostate malignancy.

    PubMed

    Costello, L C; Franklin, R B

    1994-09-01

    Normal and benign prostate hyperplasia (BPH) prostate is characterized by the presence of extraordinarily high levels of citrate. Presumably, this results from the inability of the prostate epithelial cells to oxidize citrate due to a limiting mitochondrial (m-) aconitase. In contrast, prostate carcinoma (CA) is not characterized by high citrate levels. Malignant prostate epithelial cells apparently undergo a metabolic transformation from citrate-producing to citrate-oxidizing cells. A consequence of citrate production in normal and BPH cells is an inefficient and low level of ATP production. It is proposed that the process of malignancy necessitates an energy production that cannot be provided by citrate-producing cells. Consequently, the transformation of prostate epithelial cells to citrate-oxidizing cells which increases the energy production capability is essential to the process of malignancy and metastasis. The metabolic transformation likely occurs as a premalignant or early malignant stage. This bioenergetic theory of prostate malignancy, if correct, will provide new approaches to the diagnosis and treatment of CA. PMID:7520580

  2. BCAS2 promotes prostate cancer cells proliferation by enhancing AR mRNA transcription and protein stability

    PubMed Central

    Kuo, P-C; Huang, C-W; Lee, C-I; Chang, H-W; Hsieh, S-W; Chung, Y-P; Lee, M-S; Huang, C-S; Tsao, L-P; Tsao, Y-P; Chen, S-L

    2015-01-01

    Background: We showed previously that breast carcinoma amplified sequence 2 (BCAS2) functions as a negative regulator of p53. We also found that BCAS2 is a potential AR-associated protein. AR is essential for the growth and survival of prostate carcinoma. Therefore we characterised the correlation between BCAS2 and AR. Methods: Protein interactions were examined by GST pull-down assay and co-immunoprecipitation. Clinical prostate cancer (PCa) specimens were evaluated by immunohistochemical assay. AR transcriptional activity and LNCaP cell growth were assessed by luciferase assay and MTT assay, respectively. Results: BCAS2 expression was significantly increased in PCa. BCAS2 stabilised AR protein through both hormone-dependent and -independent manners. There are at least two mechanisms for BCAS2-mediated AR protein upregulation: One is p53-dependent. The p53 is suppressed by BCAS2 that results in increasing AR mRNA and protein expression. The other is via p53-independent inhibition of proteasome degradation. As BCAS2 can form a complex with AR and HSP90, it may function with HSP90 to stabilise AR protein from being degraded by proteasome. Conclusions: In this study, we show that BCAS2 is a novel AR-interacting protein and characterise the correlation between BCAS2 and PCa. Thus we propose that BCAS2 could be a diagnostic marker and therapeutic target for PCa. PMID:25461807

  3. Anatomic imaging of the prostate.

    PubMed

    Bhavsar, Anil; Verma, Sadhna

    2014-01-01

    The important role of magnetic resonance imaging (MRI) in the anatomic evaluation, detection, and staging of prostate cancer is well established. This paper focuses on the pertinent embryologic, anatomic, and imaging facts regarding both the normal prostate and the several examples of prostate cancers as well as staging implications. The discussion primarily includes findings related to T2-weighted imaging as opposed to the other functional sequences, including diffusion weighted imaging (DWI) or dynamic contrast enhanced MRI and MR spectroscopic imaging, respectively. PMID:25243174

  4. Promising Long-Term Health-Related Quality of Life After High-Dose-Rate Brachytherapy Boost for Localized Prostate Cancer

    SciTech Connect

    Wahlgren, Thomas Nilsson, Sten; Lennernaes, Bo; Brandberg, Yvonne

    2007-11-01

    Purpose: To explore the long-term general and disease-specific health-related quality of life (HRQOL) >5 years after combined radiotherapy for localized prostate cancer, including a high-dose-rate brachytherapy boost and hormonal deprivation therapy. Methods and Materials: Of 196 eligible patients with localized prostate cancer (Stage T1-T3a) consecutively treated with curative radiotherapy at our institution between June 1998 and August 2000, 182 (93%) completed the European Organization for Research and Treatment of Cancer Quality of Life questionnaires QLQ-C30 and QLQ-PR25, including specific questions on fecal incontinence >5 years after treatment in September 2005. A comparison with age-matched normative data was done, as well as a longitudinal analysis using HRQOL data from a previous study. Results: The analysis included 158 nonrecurrent patients. Comparisons made with normative data showed that physical and role functioning were significantly better statistically and social functioning was significantly worse. Diarrhea and sleep disturbances were more pronounced and pain less pronounced than in a normal male population. The longitudinal analysis of disease-specific HRQOL showed that urinary urgency and erectile problems persisted 5 years after treatment, and nocturia and hormonally dependent symptoms had declined significantly, with a statistically significant difference. Fecal incontinence was recognized by 25% of patients, of whom 80% considered it a minor problem. Conclusion: More than 5 years after combined radiotherapy, irritative urinary problems and erectile dysfunction remain concerns, although severe bowel disturbance and fecal incontinence seem to be minor problems. Longitudinally, a decline mainly in hormonally dependent symptoms was seen. Minor differences in general HRQOL compared with normative data were observed, possibly including 'response shift' effects.

  5. [Chronic prostatitis with chronic pelvic pain syndrome].

    PubMed

    Balvocius, Antanas

    2002-01-01

    Almost 10% of the adult male population suffer from prostatitis. The International Prostatitis Collaborative Network has devised and validated a clinically useful classification of prostatitis that urologists and primary care clinicians will find helpful. According to this schema, chronic bacterial prostatitis is clearly an infectious disease, and patients with chronic prostatitis associated with chronic pelvic pain syndrome can have either inflammatory or noninflammatory disease. Chronic bacterial prostatitis is uncommon, chronic nonbacterial prostatitis (CPPS) is extremely common. Antibiotic therapy is indicated in management of chronic bacterial prostatitis and inflammatory chronic pelvic pain syndrome. Fluoroquinolones are safe and effective in managing chronic bacterial prostatitis. Based on literature, noninflammatory chronic pelvic pain syndrome can be treated using adrenergic blockade, analgesic, tricyclic antidepressants, benzodiazepie, physical therapy. PMID:12556633

  6. Does Inflammation Mediate the Obesity and BPH Relationship? An Epidemiologic Analysis of Body Composition and Inflammatory Markers in Blood, Urine, and Prostate Tissue, and the Relationship with Prostate Enlargement and Lower Urinary Tract Symptoms

    PubMed Central

    Fowke, Jay H.; Koyama, Tatsuki; Fadare, Oluwole; Clark, Peter E.

    2016-01-01

    The WHR, an estimate of centralized obesity, was associated with the severity of inflammatory regions in prostate tissue and with LUTS severity among men with inflammation. Our results suggest centralized obesity advances prostate tissue inflammation to increase LUTS severity. Clinically targeting centralized fat deposition may reduce LUTS severity. Mechanistically, the lack of a clear relationship between systemic inflammatory or oxidative stress markers in blood or urine with prostate size or LUTS suggests pathways other than systemic inflammatory signaling may link body adiposity to BPH outcomes. PMID:27336586

  7. Building on Prostate Cancer Working Group 2 to change the paradigm from palliation to cure.

    PubMed

    Scher, Howard I

    2014-01-01

    Developing systemic therapies for advanced prostate cancer has significant challenges, including the difficulty of assessing baseline disease status, disease heterogeneity, and the lack of standards for assessing treatment effects that reliably reflect clinical benefit. To address these issues, the Prostate Cancer Working Group (PCWG2) took three actions. First, the Group incorporated a prostate cancer clinical states model framework for patient management and drug development. Second was establishing a two-objective paradigm in which trials are designed to evaluate a drug's ability to either (a) control, relieve, or eliminate present disease manifestations or (b) prevent or delay future disease manifestations. Third was the development of consensus criteria for eligibility, outcomes, and reporting in prostate cancer clinical trials. Now that the molecular interrogation of prostate cancer has led to a more complex understanding of disease biology, drug development has transitioned from evaluating cytotoxic agents with activity in multiple tumor types to the rational development of therapies targeting different aspects of the malignant process. In addition, the current availability of multiple therapies for advanced prostate cancer that prolong life brings a new mandate: that we define, validate, and qualify predictive biomarkers of sensitivity to guide treatment selection and establish endpoints short of survival that can lead to drug approval. Optimization of outcomes in future trials will require revised guidance on how to align clinically relevant objectives and eligibility with an evolving disease framework.

  8. Low Temperature Plasma: A Novel Focal Therapy for Localized Prostate Cancer?

    PubMed Central

    Hirst, Adam M.; Frame, Fiona M.; Maitland, Norman J.; O'Connell, Deborah

    2014-01-01

    Despite considerable advances in recent years for the focal treatment of localized prostate cancer, high recurrence rates and detrimental side effects are still a cause for concern. In this review, we compare current focal therapies to a potentially novel approach for the treatment of early onset prostate cancer: low temperature plasma. The rapidly evolving plasma technology has the potential to deliver a wide range of promising medical applications via the delivery of plasma-induced reactive oxygen and nitrogen species. Studies assessing the effect of low temperature plasma on cell lines and xenografts have demonstrated DNA damage leading to apoptosis and reduction in cell viability. However, there have been no studies on prostate cancer, which is an obvious candidate for this novel therapy. We present here the potential of low temperature plasma as a focal therapy for prostate cancer. PMID:24738076

  9. A comprehensive bone-health management approach for men with prostate cancer receiving androgen deprivation therapy.

    PubMed

    Lee, C E; Leslie, W D; Czaykowski, P; Gingerich, J; Geirnaert, M; Lau, Y K J

    2011-08-01

    For advanced and metastatic prostate cancer, androgen deprivation therapy (adt) is the mainstay of treatment. Awareness of the potential bone-health complications consequent to adt use is increasing. Many studies have shown that prolonged adt leads to significant bone loss and increased fracture risk that negatively affect quality of life. Clinical practice guidelines for preserving bone health in men with prostate cancer on adt vary across Canada. This paper reviews recent studies on bone health in men with prostate cancer receiving adt and the current evidence regarding bone-health monitoring and management in reference to Canadian provincial guidelines. Based on this narrative review, we provide general bone-health management recommendations for men with prostate cancer receiving adt.

  10. Radium-223 dichloride: a new paradigm in the treatment of prostate cancer.

    PubMed

    Anido Herranz, Urbano; Fernández Calvo, Ovidio; Afonso Afonso, Francisco Javier; Rodríguez Martínez de Llano, Sofía; Lázaro Quintela, Martín; León Mateos, Luis; Vázquez Estévez, Sergio; Antón Aparicio, Luis Miguel

    2015-03-01

    Radionuclides have been widely used for cancer treatment. Recently, new research about radium-223 dichloride has been conducted in prostate cancer, which reveals that it is the first radiopharmaceutical to demonstrate an improvement in overall survival and time to first symptomatic skeletal event in patients with castration resistant prostate cancer with symptomatic bone metastases. This fact has created a new paradigm in the treatment of prostate cancer landscape, where only chemotherapy and hormone therapy had a role, while β-emitters had been confined exclusively to the role of pain relief with no impact on survival. The aim of this review is to outline current treatment approaches for advanced prostate cancer with a focus on the role of radium-223 dichloride, reviewing patients' profile that make them suitable to therapy and chances for further studies.

  11. MRI-guided biopsies and minimally invasive therapy for prostate cancer

    PubMed Central

    Ghai, Sangeet; Trachtenberg, John

    2015-01-01

    Recent advances in multiparametric magnetic resonance imaging (mp-MRI) have led to a paradigm shift in the diagnosis and management of prostate cancer (PCa). Its sensitivity in detecting clinically significant cancer and the ability to localize the tumor within the prostate gland has opened up discussion on targeted diagnosis and therapy in PCa. Use of mp-MRI in conjunction with prostate-specific antigen followed by targeted biopsy allows for a better diagnostic pathway than transrectal ultrasound (TRUS) biopsy and improves the diagnosis of PCa. Improved detection of PCa by mp-MRI has also opened up opportunities for focal therapy within the organ while reducing the incidence of side-effects associated with the radical treatment methods for PCa. This review discusses the evidence and techniques for in-bore MRI-guided prostate biopsy and provides an update on the status of MRI-guided targeted focal therapy in PCa. PMID:26166964

  12. Recommended patient-reported core set of symptoms to measure in prostate cancer treatment trials.

    PubMed

    Chen, Ronald C; Chang, Peter; Vetter, Richard J; Lukka, Himansu; Stokes, William A; Sanda, Martin G; Watkins-Bruner, Deborah; Reeve, Bryce B; Sandler, Howard M

    2014-07-01

    The National Cancer Institute (NCI) Symptom Management and Health-Related Quality of Life Steering Committee convened four working groups to recommend core sets of patient-reported outcomes to be routinely incorporated in clinical trials. The Prostate Cancer Working Group included physicians, researchers, and a patient advocate. The group's process included 1) a systematic literature review to determine the prevalence and severity of symptoms, 2) a multistakeholder meeting sponsored by the NCI to review the evidence and build consensus, and 3) a postmeeting expert panel synthesis of findings to finalize recommendations. Five domains were recommended for localized prostate cancer: urinary incontinence, urinary obstruction and irritation, bowel-related symptoms, sexual dysfunction, and hormonal symptoms. Four domains were recommended for advanced prostate cancer: pain, fatigue, mental well-being, and physical well-being. Additional domains for consideration include decisional regret, satisfaction with care, and anxiety related to prostate cancer. These recommendations have been endorsed by the NCI for implementation. PMID:25006192

  13. Novel Tools for Prostate Cancer Prognosis, Diagnosis, and Follow-Up

    PubMed Central

    2014-01-01

    Prostate-specific antigen (PSA) is the main diagnostic tool when it comes to prostate cancer but it possesses serious limitations. Therefore, there is an urgent need for more sensitive and specific biomarkers for prostate cancer prognosis and patient follow-up. Recent advances led to the discovery of many novel diagnostic/prognostic techniques and provided us with many worthwhile candidates. This paper briefly reviews the most promising biomarkers with respect to their implementation in screening, early detection, diagnostic confirmation, prognosis, and prediction of therapeutic response or monitoring disease and recurrence; and their use as possible therapeutic targets. This review also examines the possible future directions in the field of prostate cancer marker research. PMID:24877145

  14. The Role of Cryosurgery of the Prostate for Nonsurgical Candidates

    PubMed Central

    Nayeemuddin, Mohammed; Maddox, Michael; Pareek, Gyan

    2013-01-01

    Introduction: Technological advancements have reduced the morbidity associated with cryosurgery, leading to an increased interest in this modality for the treatment of organ-confined prostate cancer. In this study, we critically examine the current role of cryoablation of the prostate to better understand how to counsel patients regarding this treatment option. Methods: A database was compiled over a 3-year period (2008–2011) of 30 patients who underwent cryoablation for organ-confined prostate cancer. Indications for cryosurgery included primary treatment, focal treatment (institutional review board–approved prospective study), and salvage cryotherapy for radiation failure. The primary outcomes were biochemical response via prostate-specific antigen (PSA) measurement and morbidity associated with cryoablation. Cryotherapy failure was defined as an increasing postcryotherapy PSA level ≥ 2 ng/mL above the post-treatment nadir, a positive prostate biopsy, or radiographic evidence of metastatic disease. Results: Of the 30 patients who underwent cryoablation from 2008 to 2011, 26 patients had complete follow-up data for analysis. Of these patients, 17 (65.38%) had total gland cryotherapy, 5 (19.23%) had salvage cryotherapy for radiation failure, and 4 (15.38%) had focal cryotherapy. The mean patient age was 68 years (54–89); median preoperative PSA was 5.5 ng/mL (1.7–15.9); median prostate volume was 35 mL (15–54); mean Gleason score was 7; and the median PSA at study conclusion was 0.7 (0.02–3.4) ng/mL. Of the 17 patients who had total prostate cryotherapy, 11 (64.7%) had significant factors precluding primary treatment by a surgical and/or radiation approach, including neurological disorders (2), morbid obesity (1), rectal cancer treated with radiation (1), kidney/pancreas transplant (2), ileoanal pouch secondary to inflammatory bowel disease (IBD) (1), renal failure (1), and age (3).There were no intra- or postoperative complications. After a median

  15. Dystrophic calcification of the prostate after cryotherapy.

    PubMed

    Dru, Christopher; Bender, Leon

    2014-01-01

    We present a previously undocumented complication of dystrophic calcification of the prostate after cryotherapy. An 87-year-old male presented with recurrent lower urinary tract infections and was found to have an obstructing large calcified mass in the right lobe of the prostate. Subsequently, he underwent transurethral resection of the prostate (TURP) and bladder neck with laser lithotripsy to remove the calculus. We propose that chronic inflammation and necrosis of the prostate from cryotherapy resulted in dystrophic calcification of the prostate. As the use of cryotherapy for the treatment of localized prostate cancer continues to increase, it is important that clinicians be aware of this scenario and the technical challenges it poses.

  16. Oxidative stress in prostate hyperplasia and carcinogenesis.

    PubMed

    Udensi, Udensi K; Tchounwou, Paul B

    2016-01-01

    Prostatic hyperplasia (PH) is a common urologic disease that affects mostly elderly men. PH can be classified as benign prostatic hyperplasia (BPH), or prostate cancer (PCa) based on its severity. Oxidative stress (OS) is known to influence the activities of inflammatory mediators and other cellular processes involved in the initiation, promotion and progression of human neoplasms including prostate cancer. Scientific evidence also suggests that micronutrient supplementation may restore the antioxidant status and hence improve the clinical outcomes for patients with BPH and PCa. This review highlights the recent studies on prostate hyperplasia and carcinogenesis, and examines the role of OS on the molecular pathology of prostate cancer progression and treatment. PMID:27609145

  17. Contemporary Management of Prostate Cancer

    PubMed Central

    Cotter, Katherine; Konety, Badrinath; Ordonez, Maria A.

    2016-01-01

    Prostate cancer represents a spectrum ranging from low-grade, localized tumors to devastating metastatic disease. We discuss the general options for treatment and recent developments in the field. PMID:26949522

  18. Prostate Cancer Genetics: A Review

    PubMed Central

    Wallis, Christopher J.D.

    2015-01-01

    Over the past decades, research has focussed on identifying the genetic underpinnings of prostate cancer. It has been recognized that a number of forms of genetic changes coupled with epigenetic and gene expression changes can increase the prediction to develop prostate cancer. This review outlines the role of somatic copy number alterations (SCNAs), structural rearrangements, point mutations, and single nucleotide polymorphisms (SNPs) as well as miRNAs. Identifying relevant genetic changes offers the ability to develop novel biomarkers to allow early and accurate detection of prostate cancer as well as provide risk stratification of patients following their diagnosis. The concept of personalized or individualized medicine has gained significant attention. Therefore, a better understanding of the genetic and metabolic pathways underlying prostate cancer development offers the opportunity to explore new therapeutic interventions with the possibility of offering patient-specific targeted therapy.

  19. Autophagy as a Modulator and Target in Prostate Cancer

    PubMed Central

    Farrow, Jason M.; Yang, Joy C.; Evans, Christopher P.

    2015-01-01

    Autophagy, or “self eating,” is an adaptive process that helps cells cope with metabolic, toxic, and even infectious stressors. While the adaptive capability of autophagy is generally beneficial, autophagy can also facilitate enhanced nutrient utilization and improved growth characteristics in cancer cells. Moreover, autophagy can promote greater cellular robustness in the context of therapeutic intervention. This has proven to be the case in advanced prostate cancer, where preclinical data largely supports that autophagy facilitates both disease progression and therapeutic resistance. Notably, androgen deprivation therapy, taxane-based chemotherapy, targeted kinase inhibition, and nutrient restriction all induce significant cellular distress. Autophagy is subsequently up-regulated through core metabolic regulatory signaling cascades (i.e. AMPK, PI3K, and mTOR), and more favorable growth and nutrient conditions are established. Current research also demonstrates that when the autophagic machinery is inhibited, greater cell killing and tumor responsiveness can be obtained. In this review, we will cover current prostate cancer treatments associated with alterations in autophagy; data supporting autophagic modulation with added emphasis on alterations occurring within prostate cancer models; and finally, research supporting adjuvant autophagic modulation with current prostate cancer treatment paradigms. PMID:25134829

  20. Efficient use of continuous, real-time prostate localization

    NASA Astrophysics Data System (ADS)

    Malinowski, Kathleen T.; Noel, Camille; Roy, Meghana; Willoughby, Twyla; Djemi, Toufik; Jani, Shirish; Solberg, Timothy; Liu, David; Levine, Lisa; Parikh, Parag J.

    2008-09-01

    Recent technological advances make it possible to monitor prostate movement during radiation delivery. Using previously published data from 35 patients who underwent continuous localization during prostate cancer treatment, we simulated various interventions to identify the radiation-gating and patient-repositioning strategies that least prolonged the time to complete the daily treatment. Acceptable response protocols were those that resulted in at least 95% of patients' prostates remaining within the planning margins at least 95% of the time. Gating and repositioning were not necessary for margins of 7 or 10 mm because of the rarity of excursions at these margins. However, intervention was routinely necessary for margins of 3 and 5 mm. In simulated interventions for which the therapist could reposition the treatment couch without entering the room, the most time-efficient response protocol was to reposition the couch immediately after the prostate position was outside the treatment margins. In simulations in which the therapist had to enter the room to reposition the couch, overall treatment time could be reduced and accuracy could be increased by manually gating treatment for 11 and 21 s for 3- and 5-mm margins, respectively, before interrupting treatment to reposition the treatment couch.

  1. Formalized prediction of clinically significant prostate cancer: is it possible?

    PubMed Central

    Nguyen, Carvell T; Kattan, Michael W

    2012-01-01

    Greater understanding of the biology and epidemiology of prostate cancer in the last several decades have led to significant advances in its management. Prostate cancer is now detected in greater numbers at lower stages of disease and is amenable to multiple forms of efficacious treatment. However, there is a lack of conclusive data demonstrating a definitive mortality benefit from this earlier diagnosis and treatment of prostate cancer. It is likely due to the treatment of a large proportion of indolent cancers that would have had little adverse impact on health or lifespan if left alone. Due to this overtreatment phenomenon, active surveillance with delayed intervention is gaining traction as a viable management approach in contemporary practice. The ability to distinguish clinically insignificant cancers from those with a high risk of progression and/or lethality is critical to the appropriate selection of patients for surveillance protocols versus immediate intervention. This chapter will review the ability of various prediction models, including risk groupings and nomograms, to predict indolent disease and determine their role in the contemporary management of clinically localized prostate cancer. PMID:22367181

  2. Prostate-Specific Antigen: Nonspecific in Deceased Organ Donors.

    PubMed

    Pabisiak, K; Ostrowski, M; Kram, A; Safranow, K; Myślak, M; Sieńko, J; Sulikowski, T; Ciechanowski, K

    2016-06-01

    Currently, there is no clear position regarding the donation of organs from donors with prostate carcinoma (CaP) in European countries, except Italy. The lengthening of life expectancy increases the probability of prostate cancer among potential organ donors. The concentration of prostate-specific antigen (PSA) >2 ng/mL at 60 years of age is related to the increasing possibility of identifying an advanced form of CaP. In recent years in Poland, the recommendation has been to determine tumor markers in potential donors. In the first year of the recommendation, 10% of potential male cadaveric donors were disqualified in West Pomerania, Poland, on the basis of elevated PSA levels (>10 ng/mL). To avoid reduction of the actual donor pool, each potential male donor reported to the center since January 2010 undergoes a routine histologic evaluation of the whole prostate, regardless of the PSA level, before organ implantation. In the study group (N = 52), histopathologic evaluation revealed 6 cases of CaP (12%). In CaP positive group Gleason score range from 2+2 to 3+4. In CaP donors PSA level have been noticed in range 1.79 ng/mL - 7.66 ng/mL. There was no correlation between histologically confirmed CaP and the PSA level. PMID:27496408

  3. Divergent clonal evolution of castration-resistant neuroendocrine prostate cancer.

    PubMed

    Beltran, Himisha; Prandi, Davide; Mosquera, Juan Miguel; Benelli, Matteo; Puca, Loredana; Cyrta, Joanna; Marotz, Clarisse; Giannopoulou, Eugenia; Chakravarthi, Balabhadrapatruni V S K; Varambally, Sooryanarayana; Tomlins, Scott A; Nanus, David M; Tagawa, Scott T; Van Allen, Eliezer M; Elemento, Olivier; Sboner, Andrea; Garraway, Levi A; Rubin, Mark A; Demichelis, Francesca

    2016-03-01

    An increasingly recognized resistance mechanism to androgen receptor (AR)-directed therapy in prostate cancer involves epithelial plasticity, in which tumor cells demonstrate low to absent AR expression and often have neuroendocrine features. The etiology and molecular basis for this 'alternative' treatment-resistant cell state remain incompletely understood. Here, by analyzing whole-exome sequencing data of metastatic biopsies from patients, we observed substantial genomic overlap between castration-resistant tumors that were histologically characterized as prostate adenocarcinomas (CRPC-Adeno) and neuroendocrine prostate cancer (CRPC-NE); analysis of biopsy samples from the same individuals over time points to a model most consistent with divergent clonal evolution. Genome-wide DNA methylation analysis revealed marked epigenetic differences between CRPC-NE tumors and CRPC-Adeno, and also designated samples of CRPC-Adeno with clinical features of AR independence as CRPC-NE, suggesting that epigenetic modifiers may play a role in the induction and/or maintenance of this treatment-resistant state. This study supports the emergence of an alternative, 'AR-indifferent' cell state through divergent clonal evolution as a mechanism of treatment resistance in advanced prostate cancer.

  4. NMR-based metabolomics of prostate cancer: a protagonist in clinical diagnostics.

    PubMed

    Kumar, Deepak; Gupta, Ashish; Nath, Kavindra

    2016-06-01

    Advances in the application of NMR spectroscopy-based metabolomic profiling of prostate cancer comprises a potential tactic for understanding the impaired biochemical pathways arising due to a disease evolvement and progression. This technique involves qualitative and quantitative estimation of plethora of small molecular weight metabolites of body fluids or tissues using state-of-the-art chemometric methods delivering an important platform for translational research from basic to clinical, to reveal the pathophysiological snapshot in a single step. This review summarizes the present arrays and recent advancements in NMR-based metabolomics and a glimpse of currently used medical imaging tactics, with their role in clinical diagnosis of prostate cancer. PMID:26959614

  5. QUANTITATIVE STUDIES OF PROSTATIC SECRETION

    PubMed Central

    Huggins, Charles; Clark, Philip Johnson

    1940-01-01

    Cystic hyperplasia of the prostate occurs spontaneously in senile dogs only when they possess physiologically effective amounts of androgenic hormone. The cysts are closely grouped and radially arranged in a conical manner with the base of the cone at the periphery of the gland. Flattened and columnar epithelium, varying from about 5 to 25µ are seen in each cyst. The cysts communicate with the urethra by way of ducts. Both normal and cystic prostates undergo marked atrophy when the testes are removed, the chief difference 3 months after orchiectomy being the persistence of slightly dilated clefts and spaces at the site of the former cysts in the senile state. In the castrate dog whose prostate gland is being reconstructed as result of the influence of daily injections of androgen, certain doses of estrogen prevent increase of secretion and still larger doses greatly depress the output of the gland. In dogs so treated by daily injections of testosterone propionate, 10 mg., the amount of secretion is maintained from day to day at a level by daily injections of stilbestrol, 0.4 to 0.6 mg. and greatly depressed by doses of 1 to 1.5 mg. When the larger amounts of estrogen are used, together with androgen, squamous metaplasia occurs in the posterior lobe of the prostate while the epithelium of the acini decreases in height to cuboidal or low columnar form; these histological signs of activity of both androgen and estrogen on the prostate show that inhibition of the male hormone by stilbestrol is incomplete at these ratios. In dogs with either normal or cystic prostate glands, the prostate decreases in size when estrogen is injected in amounts to depress prostatic secretion profoundly. The gland is maintained in an atrophic state and overdosage avoided by controlled periodic injections of stilbestrol until secretion is reduced to the minimum, followed by free intervals, the estrogen being again administered when secretion measurably increases. The shrinkage is related to

  6. Tumor clone dynamics in lethal prostate cancer.

    PubMed

    Carreira, Suzanne; Romanel, Alessandro; Goodall, Jane; Grist, Emily; Ferraldeschi, Roberta; Miranda, Susana; Prandi, Davide; Lorente, David; Frenel, Jean-Sebastien; Pezaro, Carmel; Omlin, Aurelius; Rodrigues, Daniel Nava; Flohr, Penelope; Tunariu, Nina; S de Bono, Johann; Demichelis, Francesca; Attard, Gerhardt

    2014-09-17

    It is unclear whether a single clone metastasizes and remains dominant over the course of lethal prostate cancer. We describe the clonal architectural heterogeneity at different stages of disease progression by sequencing serial plasma and tumor samples from 16 ERG-positive patients. By characterizing the clonality of commonly occurring deletions at 21q22, 8p21, and 10q23, we identified multiple independent clones in metastatic disease that are differentially represented in tissue and circulation. To exemplify the clinical utility of our studies, we then showed a temporal association between clinical progression and emergence of androgen receptor (AR) mutations activated by glucocorticoids in about 20% of patients progressing on abiraterone and prednisolone or dexamethasone. Resistant clones showed a complex dynamic with temporal and spatial heterogeneity, suggesting distinct mechanisms of resistance at different sites that emerged and regressed depending on treatment selection pressure. This introduces a management paradigm requiring sequential monitoring of advanced prostate cancer patients with plasma and tumor biopsies to ensure early discontinuation of agents when they become potential disease drivers.

  7. Big Data Analytics for Prostate Radiotherapy.

    PubMed

    Coates, James; Souhami, Luis; El Naqa, Issam

    2016-01-01

    Radiation therapy is a first-line treatment option for localized prostate cancer and radiation-induced normal tissue damage are often the main limiting factor for modern radiotherapy regimens. Conversely, under-dosing of target volumes in an attempt to spare adjacent healthy tissues limits the likelihood of achieving local, long-term control. Thus, the ability to generate personalized data-driven risk profiles for radiotherapy outcomes would provide valuable prognostic information to help guide both clinicians and patients alike. Big data applied to radiation oncology promises to deliver better understanding of outcomes by harvesting and integrating heterogeneous data types, including patient-specific clinical parameters, treatment-related dose-volume metrics, and biological risk factors. When taken together, such variables make up the basis for a multi-dimensional space (the "RadoncSpace") in which the presented modeling techniques search in order to identify significant predictors. Herein, we review outcome modeling and big data-mining techniques for both tumor control and radiotherapy-induced normal tissue effects. We apply many of the presented modeling approaches onto a cohort of hypofractionated prostate cancer patients taking into account different data types and a large heterogeneous mix of physical and biological parameters. Cross-validation techniques are also reviewed for the refinement of the proposed framework architecture and checking individual model performance. We conclude by considering advanced modeling techniques that borrow concepts from big data analytics, such as machine learning and artificial intelligence, before discussing the potential future impact of systems radiobiology approaches.

  8. New bone formation in nude mouse calvaria induced by canine prostate tissue.

    PubMed

    LeRoy, Bruce E; Bahnson, Robert R; Rosol, Thomas J

    2002-11-29

    Osteoblastic metastases are common in patients with advanced prostate cancer. The pathophysiology of the new bone formation at metastatic sites is not currently known, but it is hypothesized that growth factors secreted by the prostate may be involved. Unfortunately, most rodent models of prostate cancer with metastasis to bone are osteolytic and not osteoblastic. Significant osteolysis by tumor cells at metastatic sites also may lead to fractures or bone instability. Misinterpretation of new periosteal bone due to bone instability as tumor-cell osteo-induction is another disadvantage of the osteolytic models. To circumvent these problems, we have developed a model system of new bone formation in the calvaria of nude mice stimulated by normal canine prostate tissue. Collagenase-digested normal prostate tissue was implanted adjacent to the calvaria of nude mice. Calvaria were examined at 2 weeks post-implantation for changes in the bone microenvironment by histology, calcein uptake at sites of bone mineralization, and tartrate-resistant acid phosphatase staining for osteoclasts. The prostate tissue remained viable and induced abundant new woven bone formation on the adjacent periosteal surface. In some cases new bone formation also was induced on the distant or concave calvarial periosteum. The new bone stained intensely with calcein, which demonstrated mineralization of the bone matrix. The new bone formation on prostate-implanted calvaria significantly increased (1.7-fold) the thickness of the calvaria compared with control calvaria. New bone formation was not induced in calvaria of mice implanted with normal canine kidney, urinary bladder, spleen, or skeletal muscle tissue, or mice with surgically-induced disruption of the periosteum. Osteoclast numbers in the medullary spaces and periosteum of calvaria were mildly increased (61%) in mice with implanted prostate tissue. In conclusion, this animal model will be useful for investigating the roles of prostate

  9. [Prostate cancer external beam radiotherapy].

    PubMed

    de Crevoisier, R; Pommier, P; Latorzeff, I; Chapet, O; Chauvet, B; Hennequin, C

    2016-09-01

    The prostate external beam radiotherapy techniques are described, when irradiating the prostate or after prostatectomy, with and without pelvic lymph nodes. The following parts are presented: indications of radiotherapy, total dose and fractionation, planning CT image acquisition, volume of interest delineation (target volumes and organs at risk) and margins, Intensity modulated radiotherapy planning and corresponding dose-volume constraints, and finally Image guided radiotherapy. PMID:27516051

  10. Common genetic variants in prostate cancer risk prediction – Results from the NCI Breast and Prostate Cancer Cohort Consortium (BPC3)

    PubMed Central

    Lindström, Sara; Schumacher, Fredrick R.; Cox, David; Travis, Ruth C.; Albanes, Demetrius; Allen, Naomi E.; Andriole, Gerald; Berndt, Sonja I.; Boeing, Heiner; Bueno-de-Mesquita, H. Bas; Crawford, E. David; Diver, W. Ryan; Ganziano, J. Michael; Giles, Graham G.; Giovannucci, Edward; Gonzalez, Carlos A.; Henderson, Brian; Hunter, David J.; Johansson, Mattias; Kolonel, Laurence N.; Ma, Jing; Le Marchand, Loic; Pala, Valeria; Stampfer, Meir; Stram, Daniel O.; Thun, Michael J.; Tjonneland, Anne; Trichopoulos, Dimitrios; Virtamo, Jarmo; Weinstein, Stephanie J.; Willett, Walter C.; Yeager, Meredith; Hayes, Richard B.; Severi, Gianluca; Haiman, Christopher A.; Chanock, Stephen J.; Kraft, Peter

    2012-01-01

    Background One of the goals of personalized medicine is to generate individual risk profiles that could identify individuals in the population that exhibit high risk. The discovery of more than two-dozen independent SNP markers in prostate cancer has raised the possibility for such risk stratification. In this study, we evaluated the discriminative and predictive ability for prostate cancer risk models incorporating 25 common prostate cancer genetic markers, family history of prostate cancer and age. Methods We fit a series of risk models and estimated their performance in 7,509 prostate cancer cases and 7,652 controls within the NCI Breast and Prostate Cancer Cohort Consortium (BPC3). We also calculated absolute risks based on SEER incidence data. Results The best risk model (C-statistic=0.642) included individual genetic markers and family history of prostate cancer. We observed a decreasing trend in discriminative ability with advancing age (P=0.009), with highest accuracy in men younger than 60 years (C-statistic=0.679). The absolute ten-year risk for 50-year old men with a family history ranged from 1.6% (10th percentile of genetic risk) to 6.7% (90th percentile of genetic risk). For men without family history, the risk ranged from 0.8% (10th percentile) to 3.4% (90th percentile). Conclusions Our results indicate that incorporating genetic information and family history in prostate cancer risk models can be particularly useful for identifying younger men that might benefit from PSA screening. Impact Although adding genetic risk markers improves model performance, the clinical utility of these genetic risk models is limited. PMID:22237985

  11. Serum Autoantibodies in Chronic Prostate Inflammation in Prostate Cancer Patients

    PubMed Central

    Schlick, Bettina; Massoner, Petra; Lueking, Angelika; Charoentong, Pornpimol; Blattner, Mirjam; Schaefer, Georg; Marquart, Klaus; Theek, Carmen; Amersdorfer, Peter; Zielinski, Dirk; Kirchner, Matthias; Trajanoski, Zlatko; Rubin, Mark A.; Müllner, Stefan; Schulz-Knappe, Peter; Klocker, Helmut

    2016-01-01

    Background Chronic inflammation is frequently observed on histological analysis of malignant and non-malignant prostate specimens. It is a suspected supporting factor for prostate diseases and their progression and a main cause of false positive PSA tests in cancer screening. We hypothesized that inflammation induces autoantibodies, which may be useful biomarkers. We aimed to identify and validate prostate inflammation associated serum autoantibodies in prostate cancer patients and evaluate the expression of corresponding autoantigens. Methods Radical prostatectomy specimens of prostate cancer patients (N = 70) were classified into high and low inflammation groups according to the amount of tissue infiltrating lymphocytes. The corresponding pre-surgery blood serum samples were scrutinized for autoantibodies using a low-density protein array. Selected autoantigens were identified in prostate tissue and their expression pattern analyzed by immunohistochemistry and qPCR. The identified autoantibody profile was cross-checked in an independent sample set (N = 63) using the Luminex-bead protein array technology. Results Protein array screening identified 165 autoantibodies differentially abundant in the serum of high compared to low inflammation patients. The expression pattern of three corresponding antigens were established in benign and cancer tissue by immunohistochemistry and qPCR: SPAST (Spastin), STX18 (Syntaxin 18) and SPOP (speckle-type POZ protein). Of these, SPAST was significantly increased in prostate tissue with high inflammation. All three autoantigens were differentially expressed in primary and/or castration resistant prostate tumors when analyzed in an inflammation-independent tissue microarray. Cross-validation of the inflammation autoantibody profile on an independent sample set using a Luminex-bead protein array, retrieved 51 of the significantly discriminating autoantibodies. Three autoantibodies were significantly upregulated in both screens, MUT

  12. Personalized prostate cancer screening among men with high risk genetic predisposition- study protocol for a prospective cohort study

    PubMed Central

    2014-01-01

    Background Prostate cancer screening among the general population is highly debatable. Nevertheless, screening among high-risk groups is appealing. Prior data suggests that men carrying mutations in the BRCA1& 2 genes may be at increased risk of developing prostate cancer. Additionally, they appear to develop prostate cancer at a younger age and with a more aggressive course. However, prior studies did not systematically perform prostate biopsies and thus cannot determine the true prevalence of prostate cancer in this population. Methods This will be a prospective diagnostic trial of screening for prostate cancer among men with genetic predisposition. The target population is males (40–70 year old) carrying a BRCA1 and/or BRCA2 germ line mutation. They will be identified via our Genetic counseling unit. All men after signing an informed consent will undergo the following tests: PSA, free to total PSA, MRI of prostate and prostate biopsy. The primary endpoint will be to estimate the prevalence, stage and grade of prostate cancer in this population. Additionally, the study aims to estimate the impact of these germ line mutations on benign prostatic hyperplasia. Furthermore, this study aims to create a bio-bank of tissue, urine and serum of this unique cohort for future investigations. Finally, this study will identify an inception cohort for future interventional studies of primary and secondary prevention. Discussion The proposed research is highly translational and focuses not only on the clinical results, but on the future specimens that will be used to advance our understanding of prostate cancer patho-physiology. Most importantly, these high-risk germ-line mutation carriers are ideal candidates for primary and secondary prevention initiatives. Trial registration ClinicalTrials.gov: NCT02053805. PMID:25047061

  13. Emerging Roles of Human Prostatic Acid Phosphatase

    PubMed Central

    Kong, Hoon Young; Byun, Jonghoe

    2013-01-01

    Prostate cancer is one of the most prevalent non-skin related cancers. It is the second leading cause of cancer deaths among males in most Western countries. If prostate cancer is diagnosed in its early stages, there is a higher probability that it will be completely cured. Prostatic acid phosphatase (PAP) is a non-specific phosphomonoesterase synthesized in prostate epithelial cells and its level proportionally increases with prostate cancer progression. PAP was the biochemical diagnostic mainstay for prostate cancer until the introduction of prostate-specific antigen (PSA) which improved the detection of early-stage prostate cancer and largely displaced PAP. Recently, however, there is a renewed interest in PAP because of its usefulness in prognosticating intermediate to high-risk prostate cancers and its success in the immunotherapy of prostate cancer. Although PAP is believed to be a key regulator of prostate cell growth, its exact role in normal prostate as well as detailed molecular mechanism of PAP regulation is still unclear. Here, many different aspects of PAP in prostate cancer are revisited and its emerging roles in other environment are discussed. PMID:24009853

  14. Prostatic Artery Embolization for Enlarged Prostates Due to Benign Prostatic Hyperplasia. How I Do It

    SciTech Connect

    Carnevale, Francisco C.; Antunes, Alberto A.

    2013-12-15

    Prostatic artery embolization (PAE) has emerged as an alternative to surgical treatments for benign prostatic hyperplasia (BPH). Patient selection and refined technique are essential for good results. Urodynamic evaluation and magnetic resonance imaging are very important and technical limitations are related to elderly patients with tortuous and atherosclerotic vessels, anatomical variations, difficulty visualizing and catheterizing small diameter arteries feeding the prostate, and the potential risk of bladder and rectum ischemia. The use of small-diameter hydrophilic microcatheters is mandatory. Patients can be treated safely by PAE with low rates of side effects, reducing prostate volume with clinical symptoms and quality of life improvement without urinary incontinence, ejaculatory disorders, or erectile dysfunction. A multidisciplinary approach with urologists and interventional radiologists is essential to achieve better results.

  15. Review of Prostate Anatomy and Embryology and the Etiology of Benign Prostatic Hyperplasia.

    PubMed

    Aaron, LaTayia; Franco, Omar E; Hayward, Simon W

    2016-08-01

    Prostate development follows a common pattern between species and depends on the actions of androgens to induce and support ductal branching morphogenesis of buds emerging from the urogenital sinus. The human prostate has a compact zonal anatomy immediately surrounding the urethra and below the urinary bladder. Rodents have a lobular prostate with lobes radiating away from the urethra. The human prostate is the site of benign hyperplasia, prostate cancer, and prostatitis. The rodent prostate has little naturally occurring disease. Rodents can be used to model aspects of human benign hyperplasia, but care should be taken in data interpretation and extrapolation to the human condition. PMID:27476121

  16. Highly specific transgene expression mediated by a complex adenovirus vector incorporating a prostate-specific amplification feedback loop

    PubMed Central

    Woraratanadharm, Jan; Rubinchik, Semyon; Yu, Hong; Fan, Fan; Morrow, Scotty M.; Dong., John Y.

    2007-01-01

    Summary Development of novel therapeutic agents is needed to address the problems of locally recurrent, metastatic, and advanced hormone-refractory prostate cancer. We have constructed a novel complex adenovirus (Ad) vector regulation system that incorporates both the prostate-specific ARR2PB promoter and a positive feedback loop using the TRE promoter to enhance gene expression. This regulation strategy involves the incorporation of the TRE upstream of the prostate-specific ARR2PB promoter to enhance its activity with Tet-regulation. The expressions of both GFP and tTA were placed under the control of these TRE-ARR2PB promoters, so that in the cells of prostate origin, a positive feedback loop would be generated. This design greatly enhanced GFP reporter expression in prostate cancer cells, while retaining tight control of expression in non-prostate cancer cells, even at MOI as high as 1000. This novel positive feedback loop with prostate specificity (PFLPS) regulation system we have developed may have broad applications for expressing not only high levels of toxic proteins in cancer cells but alternatively could be manipulated to regulate essential genes in a highly efficient conditionally replicative adenovirus (CRAd) vector specifically directed to prostate cancer cells. The PFLPS regulation system, therefore, serves as a promising new approach in the development of both a specific and effective vector for cancer gene therapy. PMID:15229631

  17. Androgen receptor targeted therapies in castration-resistant prostate cancer: Bench to clinic.

    PubMed

    Imamura, Yusuke; Sadar, Marianne D

    2016-08-01

    The androgen receptor is a transcription factor and validated therapeutic target for prostate cancer. Androgen deprivation therapy remains the gold standard treatment, but it is not curative, and eventually the disease will return as lethal castration-resistant prostate cancer. There have been improvements in the therapeutic landscape with new agents approved, such as abiraterone acetate, enzalutamide, sipuleucel-T, cabazitaxel and Ra-223, in the past 5 years. New insight into the mechanisms of resistance to treatments in advanced disease is being and has been elucidated. All current androgen receptor-targeting therapies inhibit the growth of prostate cancer by blocking the ligand-binding domain, where androgen binds to activate the receptor. Persuasive evidence supports the concept that constitutively active androgen receptor splice variants lacking the ligand-binding domain are one of the resistant mechanisms underlying advanced disease. Transcriptional activity of the androgen receptor requires a functional AF-1 region in its N-terminal domain. Preclinical evidence proved that this domain is a druggable target to forecast a potential paradigm shift in the management of advanced prostate cancer. This review presents an overview of androgen receptor-related mechanisms of resistance as well as novel therapeutic agents to overcome resistance that is linked to the expression of androgen receptor splice variants in castration-resistant prostate cancer.

  18. The relationship between prostate-specific antigen and prostate cancer risk: the Prostate Biopsy Collaborative Group

    PubMed Central

    Vickers, Andrew J.; Cronin, Angel M.; Roobol, Monique J.; Hugosson, Jonas; Jones, J. Stephen; Kattan, Michael W.; Klein, Eric; Hamdy, Freddie; Neal, David; Donovan, Jenny; Parekh, Dipen J.; Ankerst, Donna; Bartsch, George; Klocker, Helmut; Horninger, Wolfgang; Benchikh, Amine; Salama, Gilles; Villers, Arnauld; Freedland, Steve J.; Moreira, Daniel M.; Schröder, Fritz H.; Lilja, Hans

    2010-01-01

    PURPOSE The relationship between prostate specific antigen (PSA) level and prostate cancer risk remains subject to fundamental disagreements. We hypothesize that the risk of prostate cancer on biopsy for a given PSA level is affected by identifiable characteristics of the cohort under study. EXPERIMENTAL DESIGN We used data from 5 European and 3 US cohorts of men undergoing biopsy for prostate cancer; six were population-based studies and two were clinical cohorts. The association between PSA and prostate cancer was calculated separately for each cohort using locally-weighted scatterplot smoothing. RESULTS The final data set included 25,772 biopsies and 8,503 cancers. There were gross disparities between cohorts with respect to both the prostate cancer risk at a given PSA level and the shape of the risk curve. These disparities were associated with identifiable differences between cohorts: for a given PSA level, a greater number of biopsy cores increased risk of cancer (odds ratio for >6 vs. 6 core biopsy 1.35; 95% C.I. 1.18, 1.54; p<0.0005); recent screening led to a smaller increase in risk per unit change in PSA (p=0.001 for interaction term) and US cohorts had higher risk than the European cohorts (2.14; 95% C.I. 1.99, 2.30; p<0.0005). CONCLUSIONS Our results suggest that the relationship between PSA and risk of a positive prostate biopsy varies, both in terms of the probability of prostate cancer at a given PSA value and the shape of the risk curve. This poses challenges to the use of PSA-driven algorithms to determine whether biopsy is indicated. PMID:20736330

  19. Prostate-Specific Antigen (PSA) Test

    MedlinePlus

    ... What are some of the limitations and potential harms of the PSA test for prostate cancer screening? ... has been learned about both the benefits and harms of prostate cancer screening, a number of organizations ...

  20. Selenium level in benign and cancerous prostate.

    PubMed

    Zachara, Bronislaw A; Szewczyk-Golec, Karolina; Wolski, Zbigniew; Tyloch, Janusz; Skok, Zdzislaw; Bloch-Boguslawska, Elzbieta; Wasowicz, Wojciech

    2005-03-01

    The dietary microelement selenium (Se) has been proposed as a potential chemopreventive agent for prostate cancer. This element is present in various amounts in all tissues. Little information is available on Se level in patients with prostate gland disorders. The levels of Se in prostatic gland of patients with prostate cancer, benign prostate hyperplasia, and healthy controls were examined. The Se level for benign prostate hyperplasia (156 +/- 30.6 ng/g) was the same as in the control group (157 +/- 26.0 ng/g), but in the gland of prostate cancer patients (182 +/- 34.1 ng/g wet weight), the Se level was significantly (p < 0.01) higher than in both healthy controls and benign prostate hyperplasia. Thus, the Se level in human healthy controls is lower than in kidney and liver but higher compared with other tissues. PMID:15784953

  1. African American Men and Prostate Cancer

    MedlinePlus Videos and Cool Tools

    ... have one of the highest incidences of prostate cancer in the world, and in this country the ... an epidemic. Winston Dyer: My introduction to prostate cancer started with the death of my 46-year- ...

  2. Hydrodynamic stretching for prostate cancer detection

    NASA Astrophysics Data System (ADS)

    Belotti, Yuri; Conneely, Michael; Palmer, Scott; Huang, Tianjun; Campbell, Paul; McKenna, Stephen; Nabi, Ghulam; McGloin, David

    2015-06-01

    Advances in diagnostic technologies enabled scientists to link a large number of diseases with structural changes of the intracellular organisation. This intrinsic biophysical characteristic opened up the possibility to perform clinical assessments based on the measurement of single-cell mechanical properties. In this work, we combine microfluidics, high speed imaging and computational automatic tracking to measure the single-cell deformability of large samples of prostate cancer cells at a rate of ~ 104cells/s. Such a high throughput accounts for the inherent heterogeneity of biological samples and enabled us to extract statistically meaningful signatures from each cell population. In addition, using our technique we investigate the effect of Latrunculin A to the cellular stiffness.

  3. Holmium laser applications of the prostate.

    PubMed

    Lerner, Lori B; Tyson, Mark D

    2009-11-01

    The high-powered holmium laser is an excellent tool for the surgical treatment of benign prostatic hyperplasia. This article discusses the background of holmium use in the prostate and describes the surgical techniques of holmium laser ablation of the prostate and holmium laser enucleation of the prostate. Operative challenges are reviewed with suggestions as to how to avoid these problems or deal with them when they arise. Surgical outcomes and a thorough literature review are both presented.

  4. Contact laser vaporization of the prostate for benign prostatic hypertrophy

    NASA Astrophysics Data System (ADS)

    Gomella, Leonard G.; Lotfi, M. A.; Milam, Douglas F.; Albala, David; Reagan, Gary

    1994-05-01

    The contact laser applications for the removal of the enlarged prostate are distinctly different than the majority of non-contact Nd:YAG lasers that rely on coagulation necrosis and delayed sloughing. Contact Nd:YAG laser allows cutting, coagulation and vaporization of tissue with minimal penetration beyond the contact surface. Using the contact laser prostatectomy technique, the contact laser probe directly touches and immediately vaporizes the prostatic tissue under the probe. The net result is the immediate removal of the obstructing tissue, in a manner similar to the standard electrosurgical TURP. This immediate removal of tissue offers the patient treated with the contact laser the potential for decreased catheter time and a more rapid resolution of symptoms. Our initial experience suggests that the contact technique may be better suited for the smaller prostate gland (i.e. less than 30 gm). The contact laser may also be used for a procedure termed the `laser assisted TURP': a standard electrosurgical TURP is performed and the contact laser is used for hemostasis. Several investigators have reported non-randomized results of the contact technique with good outcomes. A prospective randomized trial of the contact laser prostatectomy vrs the electrosurgical TURP is underway. The contact laser vaporization of the prostate holds great promise for the treatment of symptomatic benign prostatic hypertrophy: it is virtually bloodless and allows immediate visualization of the TUR defect.

  5. Detection of preneoplasia in histologically normal prostate biopsies.

    PubMed

    Slater, M D; Delprado, W J; Murphy, C R; Barden, J A

    2001-01-01

    P2X immunolabeling of prostate detected preneoplastic changes in apparently normal tissue. Labeling occurred in two well-defined stages before the diagnostic histological markers of cancer were visible. As cancer progressed, the location of P2X expression changed from confinement within individual nuclei in the acini (stage 1) to a cytoplasmic punctate label in the acinal epithelium, with an associated removal of nuclear stain (stage 2). Finally, in advanced cases, where clear morphological evidence of cancer was apparent, the P2X label condensed exclusively on the apical epithelium (stage 3). BPH/normal tissue was entirely devoid of P2X label. Biopsy samples (77) were tested in three categories. One group (35) were diagnosed as normal benign prostatic hyperplasia (BPH) on the basis of haematoxylin and eosin (H&E) stain, although underlying disease was suspected. Of these, 14 (40%) were clearly normal and appeared entirely devoid of label, 13 (37%) exhibited the first stage of P2X receptor labeling and the remaining eight (23%) exhibited second stage labeling. The accompanying H&E-stained sections of all these cases had a normal appearance. Low grade cancer biopsy samples with Gleason scores G4-7 (25) all revealed widespread second stage receptor labeling in areas of both normal and cancerous morphology, while 17 high grade cancer biopsy samples (Gleason G8-10) all showed third stage labeling along with some residual second stage labeling. The features of each P2X labeling stage occupied the entire histological area affected, offering more opportunity to diagnose the tissue than was supplied by the more-localised diagnostic features identified by H&E-stain. Besides detecting cases of preneoplasia in biopsies with a normal H&E appearance, this technique was also able to rule out the presence of neoplasia in purely hyperplasic prostates by the absence of any P2X labeling.Prostate Cancer and Prostatic Diseases (2001) 4, 92-96 PMID:12497044

  6. Counseling the Client with Prostate Cancer.

    ERIC Educational Resources Information Center

    Curtis, Russell C.; Juhnke, Gerald A.

    2003-01-01

    Prostate cancer is prevalent in the United States and has a far-reaching effect on men and their relationships. Being diagnosed with and treated for prostate cancer often causes men to experience side effects that induce physical, emotional, and social change. Counselors need to be aware of prostate cancer's impact on men and their families.…

  7. The many faces of neuroendocrine differentiation in prostate cancer progression.

    PubMed

    Terry, Stéphane; Beltran, Himisha

    2014-01-01

    In normal prostate, neuroendocrine (NE) cells are rare and interspersed among the epithelium. These cells are believed to provide trophic signals to epithelial cell populations through the secretion of an abundance of neuropeptides that can diffuse to influence surrounding cells. In the setting of prostate cancer (PC), NE cells can also stimulate surrounding prostate adenocarcinoma cell growth, but in some cases adenocarcinoma cells themselves acquire NE characteristics. This epithelial plasticity is associated with decreased androgen receptor (AR) signaling and the accumulation of neuronal and stem cell characteristics. Transformation to an NE phenotype is one proposed mechanism of resistance to contemporary AR-targeted treatments, is associated with poor prognosis, and thought to represent up to 25% of lethal PCs. Importantly, the advent of high-throughput technologies has started to provide clues for understanding the complex molecular profiles of tumors exhibiting NE differentiation. Here, we discuss these recent advances, the multifaceted manner by which an NE-like state may arise during the different stages of disease progression, and the potential benefit of this knowledge for the management of patients with advanced PC. PMID:24724054

  8. Hyperspectral imaging and quantitative analysis for prostate cancer detection

    PubMed Central

    Akbari, Hamed; Halig, Luma V.; Schuster, David M.; Osunkoya, Adeboye; Master, Viraj; Nieh, Peter T.; Chen, Georgia Z.

    2012-01-01

    Abstract. Hyperspectral imaging (HSI) is an emerging modality for various medical applications. Its spectroscopic data might be able to be used to noninvasively detect cancer. Quantitative analysis is often necessary in order to differentiate healthy from diseased tissue. We propose the use of an advanced image processing and classification method in order to analyze hyperspectral image data for prostate cancer detection. The spectral signatures were extracted and evaluated in both cancerous and normal tissue. Least squares support vector machines were developed and evaluated for classifying hyperspectral data in order to enhance the detection of cancer tissue. This method was used to detect prostate cancer in tumor-bearing mice and on pathology slides. Spatially resolved images were created to highlight the differences of the reflectance properties of cancer versus those of normal tissue. Preliminary results with 11 mice showed that the sensitivity and specificity of the hyperspectral image classification method are 92.8% to 2.0% and 96.9% to 1.3%, respectively. Therefore, this imaging method may be able to help physicians to dissect malignant regions with a safe margin and to evaluate the tumor bed after resection. This pilot study may lead to advances in the optical diagnosis of prostate cancer using HSI technology. PMID:22894488

  9. Isolation and characterization of circulating tumor cells in prostate cancer

    PubMed Central

    Diamond, Elan; Lee, Guang Yu; Akhtar, Naveed H.; Kirby, Brian J.; Giannakakou, Paraskevi; Tagawa, Scott T.; Nanus, David M.

    2012-01-01

    Circulating tumor cells (CTCs) are tumor cells found in the peripheral blood that putatively originate from established sites of malignancy and likely have metastatic potential. Analysis of CTCs has demonstrated promise as a prognostic marker as well as a source of identifying potential targets for novel therapeutics. Isolation and characterization of these cells for study, however, remain challenging owing to their rarity in comparison with other cellular components of the peripheral blood. Several techniques that exploit the unique biochemical properties of CTCs have been developed to facilitate their isolation. Positive selection of CTCs has been achieved using microfluidic surfaces coated with antibodies against epithelial cell markers or tumor-specific antigens such as EpCAM or prostate-specific membrane antigen (PSMA). Following isolation, characterization of CTCs may help guide clinical decision making. For instance, molecular and genetic characterization may shed light on the development of chemotherapy resistance and mechanisms of metastasis without the need for a tissue biopsy. This paper will review novel isolation techniques to capture CTCs from patients with advanced prostate cancer, as well as efforts to characterize the CTCs. We will also review how these analyzes can assist in clinical decision making. Conclusion: The study of CTCs provides insight into the molecular biology of tumors of prostate origin that will eventually guide the development of tailored therapeutics. These advances are predicated on high yield and accurate isolation techniques that exploit the unique biochemical features of these cells. PMID:23087897

  10. Proapoptotic effect of endocannabinoids in prostate cancer cells

    PubMed Central

    ORELLANA-SERRADELL, O.; POBLETE, C.E.; SANCHEZ, C.; CASTELLÓN, E.A.; GALLEGOS, I.; HUIDOBRO, C.; LLANOS, M.N.; CONTRERAS, H.R.

    2015-01-01

    In the early stages, prostate cancer is androgen- dependent; therefore, medical castration has shown significant results during the initial stages of this pathology. Despite this early effect, advanced prostate cancer is resilient to such treatment. Recent evidence shows that derivatives of Cannabis sativa and its analogs may exert a protective effect against different types of oncologic pathologies. The purpose of the present study was to detect the presence of cannabinoid receptors (CB1 and CB2) on cancer cells with a prostatic origin and to evaluate the effect of the in vitro use of synthetic analogs. In order to do this, we used a commercial cell line and primary cultures derived from prostate cancer and benign prostatic hyperplasia. The presence of the CB1 and CB2 receptors was determined by immunohistochemistry where we showed a higher expression of these receptors in later stages of the disease (samples with a high Gleason score). Later, treatments were conducted using anandamide, 2-arachidonoyl glycerol and a synthetic analog of anandamide, methanandamide. Using the MTT assay, we proved that the treatments produced a cell growth inhibitory effect on all the different prostate cancer cultures. This effect was demonstrated to be dose-dependent. The use of a specific CB1 receptor blocker (SR141716) confirmed that this effect was produced primarily from the activation of the CB1 receptor. In order to understand the MTT assay results, we determined cell cycle distribution by flow cytometry, which showed no variation at the different cell cycle stages in all the cultures after treatment. Treatment with endocannabinoids resulted in an increase in the percentage of apoptotic cells as determined by Annexin V assays and caused an increase in the levels of activated caspase-3 and a reduction in the levels of Bcl-2 confirming that the reduction in cell viability noted in the MTT assay was caused by the activation of the apoptotic pathway. Finally, we observed that

  11. The Influence of Prostate Volume on Outcome After High-Dose-Rate Brachytherapy Alone for Localized Prostate Cancer

    SciTech Connect

    Le, Hien Rojas, Ana; Alonzi, Roberto; Hughes, Robert; Ostler, Peter; Lowe, Gerry; Bryant, Linda; Hoskin, Peter

    2013-10-01

    Objective: To determine whether late genitourinary toxicity, biochemical control of prostate cancer, and dosimetric parameters in patients with large prostate glands is different from those variables in men with smaller glands after treatment with high-dose-rate brachytherapy alone (HDR-BT). Methods: From November 2003 to July 2009, 164 patients with locally advanced prostate carcinoma were sequentially enrolled and treated with 34 or 36 Gy in 4 fractions and 31.5 Gy in 3 fractions of {sup 192}Ir HDR-BT alone. The median follow-up time was 71 months. Gland size was not considered in the selection criteria for this study. Estimates of freedom from biochemical relapse (FFbR) and late morbidity, stratified by median clinical target volume (CTV), were obtained, and differences were compared. Results: The median CTV volume was 60 cc (range, 15-208 cc). Dose–volume parameters D90 and V100 (ie, minimum dose to 90% of the prostate volume and volume receiving 100% of the prescribed isodose) achieved in patients with glands ≥60 cc were not significantly different from those with glands <60 cc (P≥.2). Nonetheless, biochemical control in patients with larger CTV was significantly higher (91% vs 78% at 6 years; P=.004). In univariate and multivariate analysis, CTV was a significant predictor for risk of biochemical relapse. This was not at the expense of an increase in either moderate (P=.6) or severe (P=.3) late genitourinary toxicity. The use of hormonal therapy was 17% lower in the large gland group (P=.01). Conclusions: Prostate gland size does not affect dosimetric parameters in HDR-BT assessed by D90 and V100. In patients with larger glands, a significantly higher biochemical control of disease was observed, with no difference in late toxicity. This improvement cannot be attributed to differences in dosimetry. Gland size should not be considered in the selection of patients for HDR-BT.

  12. Strategies for Online Organ Motion Correction for Intensity-Modulated Radiotherapy of Prostate Cancer: Prostate, Rectum, and Bladder Dose Effects

    SciTech Connect

    Rijkhorst, Erik-Jan; Lakeman, Annemarie; Nijkamp, Jasper; Bois, Josien de; Herk, Marcel van; Lebesque, Joos V.; Sonke, Jan-Jakob

    2009-11-15

    Purpose: To quantify and evaluate the accumulated prostate, rectum, and bladder dose for several strategies including rotational organ motion correction for intensity-modulated radiotherapy (IMRT) of prostate cancer using realistic organ motion data. Methods and Materials: Repeat computed tomography (CT) scans of 19 prostate patients were used. Per patient, two IMRT plans with different uniform margins were created. To quantify prostate and seminal vesicle motion, repeat CT clinical target volumes (CTVs) were matched onto the planning CTV using deformable registration. Four different strategies, from online setup to full motion correction, were simulated. Rotations were corrected for using gantry and collimator angle adjustments. Prostate, rectum, and bladder doses were accumulated for each patient, plan, and strategy. Minimum CTV dose (D{sub min}), rectum equivalent uniform dose (EUD, n = 0.13), and bladder surface receiving >=78 Gy (S78), were calculated. Results: With online CTV translation correction, a 7-mm margin was sufficient (i.e., D{sub min} >= 95% of the prescribed dose for all patients). A 4-mm margin required additional rotational correction. Margin reduction lowered the rectum EUD(n = 0.13) by approx2.6 Gy, and the bladder S78 by approx1.9%. Conclusions: With online correction of both translations and rotations, a 4-mm margin was sufficient for 15 of 19 patients, whereas the remaining four patients had an underdosed CTV volume <1%. Margin reduction combined with online corrections resulted in a similar or lower dose to the rectum and bladder. The more advanced the correction strategy, the better the planned and accumulated dose agreed.

  13. Prevention strategies for prostate cancer.

    PubMed

    Schmitz-Dräger, B J; Lümmen, G; Bismarck, E; Fischer, C

    2012-12-01

    Through the last decade consideration of the role of vitamins and minerals in primary prevention of genitourinary tumors has dramatically changed. Despite all efforts efficacy of a specific compound has not been proven, so far. In consequence, recommendations for a use of vitamins or other supplements with the intention of prostate cancer prevention should be avoided today. In contrast, there is some evidence that life style modification might be helpful: recent investigations suggest that smoking may be involved in prostate cancer carcinogenesis. In addition, there is evidence that moderate food consumption, reduction of dairy products and an Asian or Mediterranean diet might not only prevent prostate cancer but also harbors additional beneficial effects on general health. This move from single compounds to more complex diets can be considered as a change of paradigm in prostate cancer prevention and could be the starting point of future epidemiological research. Disappointing findings with regards to nutritional cancer prevention contrast with a solid evidence concerning the efficacy of chemoprevention using 5a-reductase inhibitors: Long-term use of Finasteride and Dutasteride significantly reduces prostate cancer detection. Further candidate drugs are under investigation. However, translation of these findings into urological practice remains a matter of controversial discussion. PMID:23288209

  14. Active surveillance for prostate cancer.

    PubMed

    Romero-Otero, Javier; García-Gómez, Borja; Duarte-Ojeda, José M; Rodríguez-Antolín, Alfredo; Vilaseca, Antoni; Carlsson, Sigrid V; Touijer, Karim A

    2016-03-01

    It is worth distinguishing between the two strategies of expectant management for prostate cancer. Watchful waiting entails administering non-curative androgen deprivation therapy to patients on development of symptomatic progression, whereas active surveillance entails delivering curative treatment on signs of disease progression. The objectives of the two management strategies and the patients enrolled in either are different: (i) to review the role of active surveillance as a management strategy for patients with low-risk prostate cancer; and (ii) review the benefits and pitfalls of active surveillance. We carried out a systematic review of active surveillance for prostate cancer in the literature using the National Center for Biotechnology Information's electronic database, PubMed. We carried out a search in English using the terms: active surveillance, prostate cancer, watchful waiting and conservative management. Selected studies were required to have a comprehensive description of the demographic and disease characteristics of the patients at the time of diagnosis, inclusion criteria for surveillance, and a protocol for the patients' follow up. Review articles were included, but not multiple papers from the same datasets. Active surveillance appears to reduce overtreatment in patients with low-risk prostate cancer without compromising cancer-specific survival at 10 years. Therefore, active surveillance is an option for select patients who want to avoid the side-effects inherent to the different types of immediate treatment. However, inclusion criteria for active surveillance and the most appropriate method of monitoring patients on active surveillance have not yet been standardized.

  15. Prostate cancer in Asian men.

    PubMed

    Ito, Kazuto

    2014-04-01

    Prostate cancer incidence and mortality in most native Asian populations have gradually increased, but are around one-third lower than in corresponding Asian-American cohorts, which are themselves lower than the rates observed in other American cohorts. Although genetic and environmental factors, particularly a Western diet, could partially explain these differences, lower exposure to PSA screening in Asian individuals might be a major contributing factor. Genetic features and diet are, however, unlikely to differ substantially within the same region of Asia, and age-stratified PSA levels in men from various Asian countries are almost identical; therefore, variation in the epidemiology of prostate cancer among native Asian populations might be attributable to differences in access to PSA testing, urology clinics, and available therapies. Conversely, the proportion of patients with metastatic prostate cancer is substantially higher even in the more developed Asian countries than in migratory Asian populations residing in Western countries and in Westerners. Consequently, the most appropriate approaches to the management of prostate cancer in Asian countries probably also differ, and therefore individualized prostate cancer screening and treatment strategies based on the epidemiological features and socioeconomic status of each country are needed.

  16. Lycopene: Redress for Prostate Cancer

    PubMed Central

    Pisipati, Sai Venkata Vedavyas; Pathapati, Harshavardhan; Bhukya, Ganesh; Nuthakki, Suresh; Chandu, Baburao; Nama, SreeKanth; Adeps, RajDev

    2012-01-01

    Lycopene, a carotenoid is what that gives red colour to some fruits like pomegranate, tomato, papaya etc... People with a sound diet of lycopene may have a less risk of cancers especially prostate cancer which is most impedent for the males of age 40-50 years. So, in countries of north America and Europe food contains much of the lycopene supplements. In accordance with the American journal of epidemiology 2002 studies implies that men with crushed serum lycopene levels are more divulged to prostate cancer and those with sound diet of lycopene have a less risk of prostate cancer. In a care study conveyed by The British journal of urology, men with prostate cancer are subjected to surgery and the tumour is detonated. Amongst the men half a set were supplemented with lycopene supplements and half were not. Those subjected with lycopene supplements have less bone pains and live longer than those not supplemented. This paints a picture about importance of lycopene in treatment of prostate cancer. This article evokes the importance of lycopene and its way of destroying the cancer. Lycopene reduces the risk of cancer by diverging its effect on the plasma Insulin like growth factor, on Connexins , and the most acceptable one, by quench of free radicals. PMID:24826034

  17. Prostate cancer as a model for tumour immunotherapy.

    PubMed

    Drake, Charles G

    2010-08-01

    Advances in basic immunology have led to an improved understanding of the interactions between the immune system and tumours, generating renewed interest in approaches that aim to treat cancer immunologically. As clinical and preclinical studies of tumour immunotherapy illustrate several immunological principles, a review of these data is broadly instructive and is particularly timely now that several agents are beginning to show evidence of efficacy. This is especially relevant in the case of prostate cancer, as recent approval of sipuleucel-T by the US Food and Drug Administration marks the first antigen-specific immunotherapy approved for cancer treatment. Although this Review focuses on immunotherapy for prostate cancer, the principles discussed are applicable to many tumour types, and the approaches discussed are highlighted in that context.

  18. TRPM8 Puts the Chill on Prostate Cancer.

    PubMed

    Grolez, Guillaume P; Gkika, Dimitra

    2016-01-01

    Prostate cancer (PCa) is one of the most frequently diagnosed cancers in developed countries. Several studies suggest that variations in calcium homeostasis are involved in carcinogenesis. Interestingly, (Transient Receptor Potential Melastatin member 8) TRPM8 calcium permeable channel expression is differentially regulated during prostate carcinogenesis, thereby suggesting a potential functional role for this channel in those cell processes, which are important for PCa evolution. Indeed, several studies have shown that TRPM8 plays a key role in processes such as the proliferation, viability and cell migration of PCa cells. Where cell migration is concerned, TRPM8 seems to have a protective anti-invasive effect and could be a particularly promising therapeutic target. The goal of this review is to inventory advances in understanding of the role of TRPM8 in the installation and progression of PCa. PMID:27409624

  19. Circulating tumour cells-monitoring treatment response in prostate cancer.

    PubMed

    Miyamoto, David T; Sequist, Lecia V; Lee, Richard J

    2014-07-01

    The availability of new therapeutic options for the treatment of metastatic castration-resistant prostate cancer (mCRPC) has heightened the importance of monitoring and assessing treatment response. Accordingly, there is an unmet clinical need for reliable biomarkers that can be used to guide therapy. Circulating tumour cells (CTCs) are rare cells that are shed from primary and metastatic tumour deposits into the peripheral circulation, and represent a means of performing noninvasive tumour sampling. Indeed, enumeration of CTCs before and after therapy has shown that CTC burden correlates with prognosis in patients with mCRPC. Moreover, studies have demonstrated the potential of molecular analysis of CTCs in monitoring and predicting response to therapy in patients. This Review describes the challenges associated with monitoring treatment response in mCRPC, and the advancements in CTC-analysis technologies applied to such assessments and, ultimately, guiding prostate cancer treatment.

  20. TRPM8 Puts the Chill on Prostate Cancer

    PubMed Central

    Grolez, Guillaume P.; Gkika, Dimitra

    2016-01-01

    Prostate cancer (PCa) is one of the most frequently diagnosed cancers in developed countries. Several studies suggest that variations in calcium homeostasis are involved in carcinogenesis. Interestingly, (Transient Receptor Potential Melastatin member 8) TRPM8 calcium permeable channel expression is differentially regulated during prostate carcinogenesis, thereby suggesting a potential functional role for this channel in those cell processes, which are important for PCa evolution. Indeed, several studies have shown that TRPM8 plays a key role in processes such as the proliferation, viability and cell migration of PCa cells. Where cell migration is concerned, TRPM8 seems to have a protective anti-invasive effect and could be a particularly promising therapeutic target. The goal of this review is to inventory advances in understanding of the role of TRPM8 in the installation and progression of PCa. PMID:27409624

  1. Immunotherapy of prostate cancer in the Dunning rat model: use of cytokine gene modified tumor vaccines.

    PubMed

    Vieweg, J; Rosenthal, F M; Bannerji, R; Heston, W D; Fair, W R; Gansbacher, B; Gilboa, E

    1994-04-01

    Adenocarcinoma of the prostate is the most common cancer in men. The majority of cancers are discovered once they have already metastasized, and there is no effective therapy for prostatic cancer at this stage. The use of cytokine-secreting tumor cell preparations as therapeutic vaccines for the treatment of advanced prostate cancer was investigated in the Dunning rat R3327-MatLyLu prostatic tumor model. IL-2 secreting, irradiated, tumor cell preparations were capable of curing animals with s.c. established tumors, and induced immunological memory that protected animals from subsequent tumor challenge. Immunotherapy was less effective when tumors were induced orthotopically, but nevertheless led to improved outcome, significantly delaying, and occasionally preventing, recurrence of tumors after resection of the cancerous prostate. Granulocyte-macrophage colony stimulating factor secreting tumor cell preparations were less effective, and interferon-gamma secreting cells had only a marginal effect. Induction of a potent immune response in tumor bearing animals against the nonimmunogenic MatLyLu tumor supports the view that active immunotherapy warrants further investigation as a potential therapeutic approach to prostate cancer. PMID:8137291

  2. Calcium, vitamin D, and dairy product intake and prostate cancer risk: the Multiethnic Cohort Study.

    PubMed

    Park, Song-Yi; Murphy, Suzanne P; Wilkens, Lynne R; Stram, Daniel O; Henderson, Brian E; Kolonel, Laurence N

    2007-12-01

    High intakes of calcium and dairy products have been suggested to be related to prostate cancer risk. Such associations were examined in the Multiethnic Cohort Study (1993-2002) among 82,483 men who completed a detailed quantitative food frequency questionnaire. During a mean follow-up of 8 years, 4,404 total cases of prostate cancer were identified. In Cox proportional hazards models, no association was found between calcium and vitamin D intake and total, advanced, or high-grade prostate cancer risk, whether for total intake, intake from foods, or intake from supplements, among all male participants or among nonusers of supplemental calcium. No association of calcium or vitamin D intake was seen across racial/ethnic groups. In analyses of food groups, dairy product and total milk consumption were not associated with prostate cancer risk. However, low-/nonfat milk was related to an increased risk and whole milk to a decreased risk of total prostate cancer; after stratification, these effects were limited to localized or low-grade tumors. Although the findings from this study do not support an association between the intakes of calcium and vitamin D and prostate cancer risk, they do suggest that an association with milk consumption may vary by fat content, particularly for early forms of this cancer.

  3. Castration Therapy of Prostate Cancer Results in Downregulation of HIF-1{alpha} Levels

    SciTech Connect

    Al-Ubaidi, Firas L.T.; Schultz, Niklas; Egevad, Lars; Granfors, Torvald; Helleday, Thomas

    2012-03-01

    Background and Purpose: Neoadjuvant androgen deprivation in combination with radiotherapy of prostate cancer is used to improve radioresponsiveness and local tumor control. Currently, the underlying mechanism is not well understood. Because hypoxia causes resistance to radiotherapy, we wanted to test whether castration affects the degree of hypoxia in prostate cancer. Methods and Materials: In 14 patients with locally advanced prostate cancer, six to 12 prostatic needle core biopsy specimens were taken prior to castration therapy. Bilateral orchidectomy was performed in 7 patients, and 7 were treated with a GnRH-agonist (leuprorelin). After castrationm two to four prostatic core biopsy specimens were taken, and the level of hypoxia-inducible factor-1{alpha} (HIF-1{alpha}) in cancer was determined by immunofluorescence. Results: Among biopsy specimens taken before castration, strong HIF-1{alpha} expression (mean intensity above 30) was shown in 5 patients, weak expression (mean intensity 10-30) in 3 patients, and background levels of HIF-1{alpha} (mean intensity 0-10) in 6 patients. Downregulation of HIF-1{alpha} expression after castration was observed in all 5 patients with strong HIF-1{alpha} precastration expression. HIF-1{alpha} expression was also reduced in 2 of 3 patients with weak HIF-1{alpha} precastration expression. Conclusions: Our data suggest that neoadjuvant castration decreases tumor cell hypoxia in prostate cancer, which may explain increased radiosensitivity after castration.

  4. Calpain-mediated androgen receptor breakdown in apoptotic prostate cancer cells.

    PubMed

    Yang, Huanjie; Murthy, Shalini; Sarkar, Fazlul H; Sheng, Shijie; Reddy, G Prem-Veer; Dou, Q Ping

    2008-12-01

    Since androgen receptor (AR) plays an important role in prostate cancer development and progression, androgen-ablation has been the frontline therapy for treatment of advanced prostate cancer even though it is rarely curative. A curative strategy should involve functional and structural elimination of AR from prostate cancer cells. We have previously reported that apoptosis induced by medicinal proteasome-inhibitory compound celastrol is associated with a decrease in AR protein levels. However celastrol-stimulated events contributing to this AR decrease have not been elucidated. Here, we report that a variety of chemotherapeutic agents, including proteasome inhibitors, a topoisomerase inhibitor, DNA-damaging agents and docetaxel that cause cell death, decrease AR levels in LNCaP prostate cancer cells. This decrease in AR protein levels was not due to the suppression of AR mRNA expression in these cells. We observed that a proteolytic activity residing in cytosol of prostate cancer cells is responsible for AR breakdown and that this proteolytic activity was stimulated upon induction of apoptosis. Interestingly, proteasome inhibitor celastrol- and chemotherapeutic drug VP-16-stimulated AR breakdown was attenuated by calpain inhibitors calpastatin and N-acetyl-L-leucyl-L-leucyl-L-methioninal. Furthermore, AR proteolytic activity pulled down by calmodulin-agarose beads from celastrol-treated PC-3 cells showed immunoreactivity to a calpain antibody. Taken together, these results demonstrate calpain involvement in proteasome inhibitor-induced AR breakdown, and suggest that AR degradation is intrinsic to the induction of apoptosis in prostate cancer cells.

  5. An integrated computational model of the bone microenvironment in bone-metastatic prostate cancer.

    PubMed

    Araujo, Arturo; Cook, Leah M; Lynch, Conor C; Basanta, David

    2014-05-01

    Bone metastasis will impact most men with advanced prostate cancer. The vicious cycle of bone degradation and formation driven by metastatic prostate cells in bone yields factors that drive cancer growth. Mechanistic insights into this vicious cycle have suggested new therapeutic opportunities, but complex temporal and cellular interactions in the bone microenvironment make drug development challenging. We have integrated biologic and computational approaches to generate a hybrid cellular automata model of normal bone matrix homeostasis and the prostate cancer-bone microenvironment. The model accurately reproduces the basic multicellular unit bone coupling process, such that introduction of a single prostate cancer cell yields a vicious cycle similar in cellular composition and pathophysiology to models of prostate-to-bone metastasis. Notably, the model revealed distinct phases of osteolytic and osteogenic activity, a critical role for mesenchymal stromal cells in osteogenesis, and temporal changes in cellular composition. To evaluate the robustness of the model, we assessed the effect of established bisphosphonate and anti-RANKL therapies on bone metastases. At approximately 100% efficacy, bisphosphonates inhibited cancer progression while, in contrast with clinical observations in humans, anti-RANKL therapy fully eradicated metastases. Reducing anti-RANKL yielded clinically similar results, suggesting that better targeting or dosing could improve patient survival. Our work establishes a computational model that can be tailored for rapid assessment of experimental therapies and delivery of precision medicine to patients with prostate cancer with bone metastases.

  6. Atg7 cooperates with Pten loss to drive prostate cancer tumor growth.

    PubMed

    Santanam, Urmila; Banach-Petrosky, Whitney; Abate-Shen, Cory; Shen, Michael M; White, Eileen; DiPaola, Robert S

    2016-02-15

    Understanding new therapeutic paradigms for both castrate-sensitive and more aggressive castrate-resistant prostate cancer is essential to improve clinical outcomes. As a critically important cellular process, autophagy promotes stress tolerance by recycling intracellular components to sustain metabolism important for tumor survival. To assess the importance of autophagy in prostate cancer, we generated a new autochthonous genetically engineered mouse model (GEMM) with inducible prostate-specific deficiency in the Pten tumor suppressor and autophagy-related-7 (Atg7) genes. Atg7 deficiency produced an autophagy-deficient phenotype and delayed Pten-deficient prostate tumor progression in both castrate-naïve and castrate-resistant cancers. Atg7-deficient tumors display evidence of endoplasmic reticulum (ER) stress, suggesting that autophagy may promote prostate tumorigenesis through management of protein homeostasis. Taken together, these data support the importance of autophagy for both castrate-naïve and castrate-resistant growth in a newly developed GEMM, suggesting a new paradigm and model to study approaches to inhibit autophagy in combination with known and new therapies for advanced prostate cancer. PMID:26883359

  7. Current Approaches, Challenges and Future Directions for Monitoring Treatment Response in Prostate Cancer

    PubMed Central

    Wallace, T.J.; Torre, T.; Grob, M.; Yu, J.; Avital, I.; Brücher, BLDM; Stojadinovic, A.; Man, Y.G.

    2014-01-01

    Prostate cancer is the most commonly diagnosed non-cutaneous neoplasm in men in the United States and the second leading cause of cancer mortality. One in 7 men will be diagnosed with prostate cancer during their lifetime. As a result, monitoring treatment response is of vital importance. The cornerstone of current approaches in monitoring treatment response remains the prostate-specific antigen (PSA). However, with the limitations of PSA come challenges in our ability to monitor treatment success. Defining PSA response is different depending on the individual treatment rendered potentially making it difficult for those not trained in urologic oncology to understand. Furthermore, standard treatment response criteria do not apply to prostate cancer further complicating the issue of treatment response. Historically, prostate cancer has been difficult to image and no single modality has been consistently relied upon to measure treatment response. However, with newer imaging modalities and advances in our understanding and utilization of specific biomarkers, the future for monitoring treatment response in prostate cancer looks bright. PMID:24396494

  8. MOLECULAR IMAGING OF PROSTATE CANCER: translating molecular biology approaches into the clinical realm

    PubMed Central

    Vargas, Hebert Alberto; Grimm, Jan; Donati, Olivio F.; Sala, Evis; Hricak, Hedvig

    2016-01-01

    The epidemiology of prostate cancer has dramatically changed since the introduction of prostate-specific antigen (PSA) screening in the 1980’s. Most prostate cancers today are detected at early stages of the disease and are considered “indolent”, however some patients’ prostate cancers demonstrate a more aggressive behavior which leads to rapid progression and death. Increasing understanding of the biology underlying the heterogeneity that characterizes this disease has lead to a continuously evolving role of imaging in the management of prostate cancer. Functional and metabolic imaging techniques are gaining importance as the impact on the therapeutic paradigm has shifted from structural tumor detection alone to distinguishing patients with indolent tumors that can be managed conservatively (e.g., by active surveillance) from patients with more aggressive tumors that may require definitive treatment with surgery or radiation. In this review, we discuss advanced imaging techniques that allow direct visualization of molecular interactions relevant to prostate cancer and their potential for translation to the clinical setting in the near future. The potential use of imaging to follow molecular events during drug therapy as well as the use of imaging agents for therapeutic purposes will also be discussed. PMID:25693661

  9. Novel agents for castration-resistant prostate cancer: Early experience and beyond.

    PubMed

    Fujimoto, Naohiro

    2016-02-01

    Androgen deprivation therapy is the initial treatment for men with advanced prostate cancer. Almost all these patients eventually develop progressive castration-resistant prostate cancer despite an initial favorable response. Docetaxel was the first agent to show a survival benefit in patients with castration-resistant prostate cancer. After cancer progression on docetaxel, patients with castration-resistant prostate cancer had few therapeutic options. A better understanding of the mechanisms of resistance to androgen deprivation therapy has led to the development of novel agents with distinct mechanisms of action. Prospective, large-scale clinical trials have shown overall survival benefits with the hormonal agents abiraterone acetate and enzalutamide, the immunotherapeutic agent sipuleucel T, the chemotherapeutic agent cabazitaxel, and bone-targeted Ra-223. Although these agents provided clinical benefit, treatment for castration-resistant prostate cancer remains a major clinical challenge. We recognize many questions, such as methods to select patients for specific treatments, optimal sequencing and drug combinations, and means to overcome drug resistance. There is an urgent need to answer these questions and to establish better treatment strategies. The development of biomarkers that are predictive of treatment results is also required. The present article reviews new castration-resistant prostate cancer treatments, and discusses possible resistant mechanisms as well as potential drug combinations and optimal sequencing.

  10. Translationally Controlled Tumor Protein in Prostatic Adenocarcinoma: Correlation with Tumor Grading and Treatment-Related Changes

    PubMed Central

    Rocca, Bruno Jim; Ginori, Alessandro; Barone, Aurora; Calandra, Calogera; Crivelli, Filippo; De Falco, Giulia; Gazaneo, Sara; Tripodi, Sergio; Cevenini, Gabriele; del Vecchio, Maria Teresa; Ambrosio, Maria Raffaella; Tosi, Piero

    2015-01-01

    Prostate cancer is the second leading cause of cancer-related death. The androgen deprivation therapy is the standard treatment for advanced stages. Unfortunately, virtually all tumors become resistant to androgen withdrawal. The progression to castration-resistance is not fully understood, although a recent paper has suggested translationally controlled tumor protein to be implicated in the process. The present study was designed to investigate the role of this protein in prostate cancer, focusing on the correlation between its expression level with tumor differentiation and response to treatment. We retrieved 292 prostatic cancer specimens; of these 153 had been treated only by radical prostatectomy and 139 had undergone radical prostatectomy after neoadjuvant treatment with combined androgen blockade therapy. Non-neoplastic controls were represented by 102 prostatic peripheral zone specimens. In untreated patients, the expression of the protein, evaluated by RT-qPCR and immunohistochemistry, was significantly higher in tumor specimens than in non-neoplastic control, increasing as Gleason pattern and score progressed. In treated prostates, the staining was correlated with the response to treatment. An association between protein expression and the main clinicopathological factors involved in prostate cancer aggressiveness was identified. These findings suggest that the protein may be a promising prognostic factor and a target for therapy. PMID:25667934

  11. Clinical and economic considerations in the treatment of prostate cancer.

    PubMed

    Varenhorst, E; Carlsson, P; Pedersen, K

    1994-08-01

    Prostate cancer is a growing health problem with considerable economic consequences. Despite progress in the management of this disease, few areas in medicine generate greater disagreement. The larger part of healthcare resources are allocated to 'halfway technologies' aimed at palliative intervention to prolong life, while a relatively small part goes to measures aimed at preventing or curing the disease. The aetiology of this cancer is multifactorial and no practical measures for primary prevention are known. The number of patients diagnosed with prostate cancer is increasing steadily. The age-adjusted mortality, however, has increased only slightly. In its early stages, prostate cancer is often asymptomatic and is usually not diagnosed until it has advanced. Programmes for the early detection of prostate cancer (screening) claimed to reduce morbidity and mortality are a matter of controversy. Furthermore, there has been much debate regarding optimal treatment in the early stages of the disease. Economic considerations have not as yet been integrated into studies concerning localised prostate cancer. The routine first-line treatment of advanced prostate cancer usually involves some type of endocrine treatment. The most straightforward technique is surgical castration. Oral estrogens are as effective as castration, but have significant cardiovascular adverse effects. These may possibly be prevented if estrogens are given parenterally. A third principal endocrine treatment is the administration of antiandrogens. Medical castration can be attained by the administration of recently developed synthetic peptides, gonadotrophin-releasing hormone {luteinising hormone-releasing hormone (LHRH)} (GnRH) analogue agonists which are given parenterally. The advantage of this type of medical castration is that the trauma of surgical castration and the adverse effects of oral estrogens are avoided. In an attempt to improve the results obtained with endocrine treatment, the

  12. Two year experience with transrectal prostate ultrasound.

    PubMed

    Badalament, R A; York, J P; Drago, J R

    1990-01-01

    During the last two and a half years, transrectal prostate ultrasound has been used extensively at our institution. Three hundred and twenty patients have been evaluated in a double blind fashion as part of a study comparing digital rectal examination and transrectal prostatic ultrasound. Prostate cancer was detected in twenty three patients (7.2%); 13 had palpable nodules (4.1%) and 10 had non-palpable nodules (3.1%). Of the 23 patients, 19 had clinically localized (Stage B) prostate cancer. Clinical and pathologic staging correlated in 15 patients (79%). This compares favorably to clinical staging accuracy of 55% in patients prior to utilization of transrectal prostatic ultrasound.

  13. PSA, PSA derivatives, proPSA and prostate health index in the diagnosis of prostate cancer

    PubMed Central

    Ayyıldız, Sema Nur; Ayyıldız, Ali

    2014-01-01

    Currently, prostate- specific antigen (PSA) is the most common oncological marker used for prostate cancer screening. However, high levels of PSA in benign prostatic hyperplasia and prostatitis decrease the specificity of PSA as a cancer marker. To increase the specificity of PSA, PSA derivatives and PSA kinetics have been used. However, these new techniques were not able to increase the diagnostic specificity for prostate cancer. Therefore, the search for new molecules and derivatives of PSA continues. With the aim of increasing the specificity of prostate cancer diagnosis, proPSA and the Prostate Health Index have been introduced. In this review, the roles of PSA, PSA derivatives, proPSA and the Prostate Health Index in Prostate Cancer diagnosis are examined. PMID:26328156

  14. Prostate Cancer Detection and Diagnosis: The Role of MR and its Comparison to other Diagnostic Modalities – A Radiologist's Perspective

    PubMed Central

    Penzkofer, Tobias; Tempany-Afdhal, Clare M.

    2013-01-01

    It is now universally recognized that many prostate cancers are over-diagnosed and over-treated. The European Randomized Study of Screening for Prostate Cancer (ERSPC) from 2009 evidenced that, to save one man from death of prostate cancer, over 1,400 men had to be screened, and 48 had to undergo treatment. Detection of prostate cancer is traditionally based upon digital rectal examination (DRE) and measuring serum prostate specific antigen (PSA), followed by ultrasound guided biopsy. The primary role of imaging for the detection and diagnosis of prostate cancer has been transrectal ultrasound (TRUS) guidance during biopsy. MRI has traditionally been used primarily for staging disease in men with biopsy proven cancer. It is has a well-established role in detecting T3 disease, planning radiation therapy, especially 3D conformal or intensity modulated external beam radiation therapy (IMRT), and planning and guiding interstitial seed implant or brachytherapy. New advances have now established prostate MRI can accurately characterize focal lesions within the gland, an ability that has led to new opportunities for improved cancer detection and guidance for biopsy. There are two new approaches to prostate biopsy are under investigation both use pre-biopsy MRI to define potential targets for sampling and then the biopsy is performed either with direct real-time MR guidance (in-bore) or MR fusion/registration with TRUS images (out-of-bore). In-bore or out-of-bore MRI-guided prostate biopsies have the advantage of using the MR target definition for accurate localization and sampling of targets or suspicious lesions. The out-of-bore method uses combined MRI/TRUS with fusion software that provided target localization and increases the sampling accuracy for TRUS-guided biopsies by integrating prostate MRI information with TRUS. Newer parameters for each imaging modality such as sonoelastography or shear wave elastography (SWE), contrast enhanced US (CEUS) and MRI

  15. Expression and Localization of Aquaporins in Benign Prostate Hyperplasia and Prostate Cancer

    PubMed Central

    Hwang, Insang; Hwang, Eu-Chang; Song, Seung Hee; Lee, Hyun-Suk; Kim, Sun-Ouck; Kang, Taek-Won; Kwon, Dongdeuk; Park, Kwangsung

    2012-01-01

    The aquaporin (AQP) families of water channels are intrinsic membrane proteins that facilitate selective water and small solute movement across the plasma membrane. The purposes of this study were to determine the expression and localization of AQPs in benign prostatic hyperplasia and prostate cancer. Prostatic tissue was collected from patients with benign prostatic hyperplasia or prostate cancer by transurethral resection of the prostate. The expression and cellular localization of the AQPs were determined in the human prostate by Western blot and immunohistochemistry. AQP1, 3, and 9 were expressed in the human prostate. Western blot analysis revealed bands at 28-36 kDa for the AQP1, 3, and 9 proteins. Of these proteins, AQP3 and 9 were expressed in the epithelium. Immunolabeling showed that AQP1 was mainly expressed in the capillaries and venules of the prostate, AQP9 was expressed in the cytoplasm of the epithelium, and AQP3 was mainly associated with the plasma membrane of the prostatic epithelium. Only AQP3 expression was localized in the cell membrane, and expressed AQP3 was translocated to the cytoplasm in prostate cancer. The epithelium in the human prostate expresses AQP3 and 9 proteins, and the capillaries and venules of the prostate express AQP1. Characterizing or modifying the expression of AQP3 may lead to an understanding of the role of the AQPs in human prostatic disease. PMID:23323224

  16. Development of a peptide-based vaccine targeting TMPRSS2:ERG fusion positive prostate cancer

    PubMed Central

    Kissick, Haydn Thomas; Sanda, Martin George; Dunn, Laura Kathleen; Arredouani, Mohamed Simo

    2013-01-01

    Identification of novel vaccine targets is critical for the design and advancement of prostate cancer (PCa) immunotherapy. Ideal targets are proteins that are abundant in prostate tumors while absent in extra-prostatic tissues. The fusion of the androgen-regulated TMPRSS2 gene with the ETS transcription factor ERG occurs in approximately 50% of prostate cancer cases and results in aberrant ERG expression. Because expression of ERG is very low in peripheral tissue, we evaluated the suitability of this protein as an antigen target in PCa vaccines. ERG-derived HLA-A*0201-restricted immunogenic epitopes were identified through a 3-step strategy that included in silico, in vitro, and in vivo validation. Algorithms were used to predict potential HLA-A*0201-binding epitopes. High scoring epitopes were tested for binding to HLA-A*0201 using the T2-based stabilization assay in vitro. Five peptides were found to bind HLA-A*0201 and were subsequently tested for immunogenicity in humanized HLA-A*0201 transgenic mice. The in vivo screening identified three immunogenic peptides. One of these peptides, ERG295, overcame peripheral tolerance in HLA-A*0201 mice that expressed prostate restricted ERG. Also, this peptide induced an antigen specific response against ERG-expressing human prostate tumor cells. Finally, tetramer assay showed detectable and responsive ERG295-specific cytotoxic lymphocytes in peripheral blood of HLA-A*0201+ prostate cancer patients. Detection of ERG-specific CTLs in both mice and the blood of prostate cancer patients indicates that ERG-specific tolerance can be overcome. Additionally, these data suggest that ERG is a suitable target antigen for PCa immunotherapy. PMID:24149465

  17. Anti-cancer activity of curcumin loaded nanoparticles in prostate cancer

    PubMed Central

    Yallapu, Murali M.; Khan, Sheema; Maher, Diane M.; Ebeling, Mara C.; Sundram, Vasudha; Chauhan, Neeraj; Ganju, Aditya; Balakrishna, Swati; Gupta, Brij K.; Zafar, Nadeem; Jaggi, Meena; Chauhan, Subhash C.

    2014-01-01

    Prostate cancer is the most commonly diagnosed cancer disease in men in the Unites States and its management remains challenge in everyday oncology practice. Thus, advanced therapeutic strategies are required to treat prostate cancer patients. Curcumin (CUR) is a promising anticancer agent for various cancer types. The objective of this study was to evaluate therapeutic potential of novel poly(lactic-co-glycolic acid)- CUR nanoparticles (PLGA-CUR NPs) for prostate cancer treatment. Our results indicate that PLGA-CUR NPs efficiently internalize in prostate cancer cells and release biologically active CUR in cytosolic compartment of cells for effective therapeutic activity. Cell proliferation (MTS), clonogenic, and Western blot analyses reveal that PLGA-CUR NPs can effectively inhibit proliferation and colony formation ability of prostate cancer cells than free CUR. PLGA-CUR NPs showed superior tumor regression compared to CUR in xenograft mice. Further investigations reveal that PLGA-CUR NPs inhibit nuclear β-catenin and AR expression in cells and in tumor xenograft tissues. It also suppresses STAT3 and AKT phosphorylation and leads to apoptosis via inhibition of key anti-apoptotic proteins, MCL-1, Bcl-xL and caused induction of PARP cleavage. Additionally, PLGA-CUR NPs significant downregulation of oncogenic miR21 and up-regulation of miR-205 was observed with PLGA-CUR NPs treatment as determined by RT-PCR and in situ hybridization analyses. A superior anti-cancer potential was attained with PSMA antibody conjugated PLGA-CUR NPs in prostate cancer cells and a significant tumor targeting of 131I labelled PSMA antibody was achieved with PLGA-CUR NPs in prostate cancer xenograft mice model. In conclusion, PLGA-CUR NPs can significantly accumulate and exhibit superior anticancer activity in prostate cancer. PMID:25028336

  18. Integrative analysis identifies targetable CREB1/FoxA1 transcriptional co-regulation as a predictor of prostate cancer recurrence

    PubMed Central

    Sunkel, Benjamin; Wu, Dayong; Chen, Zhong; Wang, Chiou-Miin; Liu, Xiangtao; Ye, Zhenqing; Horning, Aaron M.; Liu, Joseph; Mahalingam, Devalingam; Lopez-Nicora, Horacio; Lin, Chun-Lin; Goodfellow, Paul J.; Clinton, Steven K.; Jin, Victor X.; Chen, Chun-Liang; Huang, Tim H.-M.; Wang, Qianben

    2016-01-01

    Identifying prostate cancer-driving transcription factors (TFs) in addition to the androgen receptor promises to improve our ability to effectively diagnose and treat this disease. We employed an integrative genomics analysis of master TFs CREB1 and FoxA1 in androgen-dependent prostate cancer (ADPC) and castration-resistant prostate cancer (CRPC) cell lines, primary prostate cancer tissues and circulating tumor cells (CTCs) to investigate their role in defining prostate cancer gene expression profiles. Combining genome-wide binding site and gene expression profiles we define CREB1 as a critical driver of pro-survival, cell cycle and metabolic transcription programs. We show that CREB1 and FoxA1 co-localize and mutually influence each other's binding to define disease-driving transcription profiles associated with advanced prostate cancer. Gene expression analysis in human prostate cancer samples found that CREB1/FoxA1 target gene panels predict prostate cancer recurrence. Finally, we showed that this signaling pathway is sensitive to compounds that inhibit the transcription co-regulatory factor MED1. These findings not only reveal a novel, global transcriptional co-regulatory function of CREB1 and FoxA1, but also suggest CREB1/FoxA1 signaling is a targetable driver of prostate cancer progression and serves as a biomarker of poor clinical outcomes. PMID:26743006

  19. Arachidonic acid pathway members PLA2G7, HPGD, EPHX2, and CYP4F8 identified as putative novel therapeutic targets in prostate cancer.

    PubMed

    Vainio, Paula; Gupta, Santosh; Ketola, Kirsi; Mirtti, Tuomas; Mpindi, John-Patrick; Kohonen, Pekka; Fey, Vidal; Perälä, Merja; Smit, Frank; Verhaegh, Gerald; Schalken, Jack; Alanen, Kalle A; Kallioniemi, Olli; Iljin, Kristiina

    2011-02-01

    The arachidonic acid and prostaglandin pathway has been implicated in prostate carcinogenesis, but comprehensive studies of the individual members in this key pathway are lacking. Here, we first conducted a systematic bioinformatic study of the expression of 36 arachidonic acid pathway genes across 9783 human tissue samples. The results showed that the PLA2G7, HPGD, EPHX2, and CYP4F8 genes are highly expressed in prostate cancer. Functional studies using RNA interference in prostate cancer cells indicated that all four genes are also essential for cell growth and survival. Clinical validation confirmed high PLA2G7 expression, especially in ERG oncogene-positive prostate cancers, and its silencing sensitized ERG-positive prostate cancer cells to oxidative stress. HPGD was highly expressed in androgen receptor (AR)-overexpressing advanced tumors, as well as in metastatic prostate cancers. EPHX2 mRNA correlated with AR in primary prostate cancers, and its inhibition in vitro reduced AR signaling and potentiated the effect of antiandrogen flutamide in cultured prostate cancer cells. In summary, we identified four novel putative therapeutic targets with biomarker potential for different subtypes of prostate cancer. In addition, our results indicate that inhibition of these enzymes may be particularly powerful when combined with other treatments, such as androgen deprivation or induction of oxidative stress. PMID:21281786

  20. Screening spectroscopy of prostate cancer

    NASA Astrophysics Data System (ADS)

    Yermolenko, S. B.; Voloshynskyy, D. I.; Fedoruk, O. S.

    2015-11-01

    The aim of the study was to establish objective parameters of the field of laser and incoherent radiation of different spectral ranges (UV, visible, IR) as a non-invasive optical method of interaction with different samples of biological tissues and fluids of patients to determine the state of prostate cancer and choosing the best personal treatment. The objects of study were selected venous blood plasma of patient with prostate cancer, histological sections of rat prostate gland in the postoperative period. As diagnostic methods have been used ultraviolet spectrometry samples of blood plasma in the liquid state, infrared spectroscopy middle range (2,5-25 microns) dry residue of plasma by spectral diagnostic technique of thin histological sections of biological tissues.

  1. [Castration resistant prostate cancer 2015].

    PubMed

    Merseburger, A S; Böker, A; Kuczyk, M A; von Klot, C-A

    2015-01-01

    Prostate cancer is still the most common urological cancer of the elderly man. In some patients, a metastatic prostate cancer arises which may remain a stable disease for years with palliative antiandrogen therapy. On average, after 3-4 years, affected men develop a PSA rise and disease progression with the formation of a so-called castration-resistant disease. 5 years ago cytotoxic chemotherapy with docetaxel was the only life-prolonging treatment option in this situation. In the last 5 years, the results of randomised phase III studies have led to the approval of 5 new agents for the treatment of metastatic castration resistant prostate cancer (mCRPC). The results and approval status of the substances, Abiraterone, Enzalutamide, Cabazitaxel, Sipuleucel-T and radium-223 are described below. In addition, some aspects of sequential therapy and possible future molecular approaches are discussed. PMID:25658232

  2. The inhibitory effects of AR/miR-190a/YB-1 negative feedback loop on prostate cancer and underlying mechanism.

    PubMed

    Xu, Shaohua; Wang, Tao; Song, Wen; Jiang, Tao; Zhang, Feng; Yin, Yu; Jiang, Shi-Wen; Wu, Kongming; Yu, Zuoren; Wang, Chenguang; Chen, Ke

    2015-08-28

    Prostate cancer at advanced stages including metastatic and castration-resistant cancer remains incurable due to the lack of effective therapies. MiR-190a belongs to the small noncoding RNA family and has an important role in breast cancer metastasis. However, it is still unknown whether miR-190a plays a role in prostate cancer development. Herein, we first observed AR/miR-190a/YB-1 forms an auto-regulatory negative feedback loop in prostate cancer: miR-190a expression was down-regulated by AR activation; YB-1 functions are as an AR activator; miR-190a inhibited AR expression and transactivation through direct binding to 3'UTR of YB-1 gene. MiR-190a contributes the human prostate cancer cell growth through AR-dependent signaling. Moreover, we examined the expression of miR-190a and observed a significant decrease in human prostate cancers. Reduced expression of miR-190a was inversely correlated to AR levels of prostate cancer patients, and patients with higher miR-190a expression in their tumor have improved tumor-free survival. Taken together, our findings identified a biochemical and functional link between miR-190a with reduced expression in advanced prostate cancer, YB-1 and AR signaling in prostate cancer.

  3. Stilbenes inhibit androgen receptor expression in 22Rv1 castrate-resistant prostate cancer cells

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Androgen receptor (AR) signaling plays an important role in the development and progression of prostate cancer (PCa). Importantly, AR continues to be expressed in advanced stages of castrate-resistant PCa (CRPC), where it can have ligand- independent activity. Identification of naturally occurring s...

  4. The role of radiation therapy in the treatment of metastatic castrate-resistant prostate cancer

    PubMed Central

    Rose, Jim N.

    2015-01-01

    In the setting of castrate-resistant prostate cancer, patients present with a variety of symptoms, including bone metastases, spinal cord compression and advanced pelvic disease. Fortunately, a variety of radiotherapeutic options exist for palliation. This article focuses on these options, including both external beam radiotherapy and radiopharmaceuticals. PMID:26161144

  5. Detection of DNA viruses in prostate cancer

    PubMed Central

    Smelov, Vitaly; Bzhalava, Davit; Arroyo Mühr, Laila Sara; Eklund, Carina; Komyakov, Boris; Gorelov, Andrey; Dillner, Joakim; Hultin, Emilie

    2016-01-01

    We tested prostatic secretions from men with and without prostate cancer (13 cases and 13 matched controls) or prostatitis (18 cases and 18 matched controls) with metagenomic sequencing. A large number (>200) of viral reads was only detected among four prostate cancer cases (1 patient each positive for Merkel cell polyomavirus, JC polyomavirus and Human Papillomavirus types 89 or 40, respectively). Lower numbers of reads from a large variety of viruses were detected in all patient groups. Our knowledge of the biology of the prostate may be furthered by the fact that DNA viruses are commonly shed from the prostate and can be readily detected by metagenomic sequencing of expressed prostate secretions. PMID:27121729

  6. Prognostic and predictive factors in prostate cancer: historical perspectives and recent international consensus initiatives.

    PubMed

    Srigley, John R; Amin, Mahul; Boccon-Gibod, Liliane; Egevad, Lars; Epstein, Jonathan I; Humphrey, Peter A; Mikuz, Gregor; Newling, Don; Nilsson, Sten; Sakr, Wael; Wheeler, Thomas M; Montironi, Rodolfo

    2005-05-01

    An understanding of prognosis in cancer medicine is important for patient care, research and cancer control programs. In prostate cancer, prognostic (predictive) factors are particularly important given the marked heterogeneity of this disease at clinical, morphologic and biomolecular levels. Clinical stage and histologic grade have historically played major roles in defining heterogeneity in prostate cancer. More recently, serum prostate-specific antigen measurement has assumed a significant prognostic role. Over the last two decades there has been an explosion of research into biomarkers, many of which have been purported to have prognostic significance. In this paper we present an overview of the various consensus initiatives that have transpired over the last dozen years. Criteria for evaluating prognostic factors and classifications of predictive factors have emerged that have proven useful and advanced our understanding of the biology of prostate cancer. The results of these consensus initiatives form a foundation on which the current international consultation on prognosis (prediction) in prostate cancer is built. Advances in our understanding of the new and promising prognostic factors will require a more rigorous evidence-based approach to the analysis of published studies. Furthermore, appropriate mathematical models for the analysis of the multiple factors that influence a prognostic system will have to be employed.

  7. Prostate Cancer Immunotherapy with Sipuleucel-T: Current Standards and Future Directions.

    PubMed

    Wei, Xiao X; Fong, Lawrence; Small, Eric J

    2015-01-01

    The management of advanced prostate cancer, specifically metastatic castrate-resistant prostate cancer (mCRPC), remains a therapeutic challenge. Sipuleucel-T (Provenge; APC8015) was approved by the FDA in 2010 for the treatment of asymptomatic or minimally symptomatic mCRPC patients, and it remains the only FDA-approved immunotherapy for prostate cancer of any indication to date. Given the continued need to improve therapeutics in patients with advanced prostate cancer, as well as recent enthusiasm for cancer immunotherapy, there is a wide range of ongoing trials evaluating combinations of sipuleucel-T with other therapeutics. Additional trials are aiming to expand the application of sipuleucel-T to prostate cancer patients beyond the mCRPC setting. Ongoing challenges include understanding the full mechanism of action of sipuleucel-T, optimizing the sequence of sipuleucel-T in relation to other therapies for mCRPC in clinical practice, and the identification of surrogate markers to predict survival benefit in clinical trials.

  8. Moving Beyond the Androgen Receptor (AR): Targeting AR-Interacting Proteins to Treat Prostate Cancer.

    PubMed

    Foley, Christopher; Mitsiades, Nicholas

    2016-04-01

    Medical or surgical castration serves as the backbone of systemic therapy for advanced and metastatic prostate cancer, taking advantage of the importance of androgen signaling in this disease. Unfortunately, resistance to castration emerges almost universally. Despite the development and approval of new and more potent androgen synthesis inhibitors and androgen receptor (AR) antagonists, prostate cancers continue to develop resistance to these therapeutics, while often maintaining their dependence on the AR signaling axis. This highlights the need for innovative therapeutic approaches that aim to continue disrupting AR downstream signaling but are orthogonal to directly targeting the AR itself. In this review, we discuss the preclinical research that has been done, as well as clinical trials for prostate cancer, on inhibiting several important families of AR-interacting proteins, including chaperones (such as heat shock protein 90 (HSP90) and FKBP52), pioneer factors (including forkhead box protein A1 (FOXA1) and GATA-2), and AR transcriptional coregulators such as the p160 steroid receptor coactivators (SRCs) SRC-1, SRC-2, SRC-3, as well as lysine deacetylases (KDACs) and lysine acetyltransferases (KATs). Researching the effect of-and developing new therapeutic agents that target-the AR signaling axis is critical to advancing our understanding of prostate cancer biology, to continue to improve treatments for prostate cancer and for overcoming castration resistance.

  9. Gray level entropy matrix is a superior predictor than multiplex ELISA in the detection of reactive stroma and metastatic potential of high-grade prostatic adenocarcinoma.

    PubMed

    Jia, Xiaopeng; Sun, Yanan; Wang, Baozhi

    2014-12-01

    Recent reports have indicated that not only the primary glandular tissue but also the surrounding stromal tissue plays an active role in the progression of carcinoma. Such is true for cancer tissues arising in the prostate. However, the precise role of stromal tissue in benign prostatic hyperplasia (BPH) and prostate adenocarcinoma is not well described. We undertook this current investigation to examine the changes in orientation of the extracellular matrix and correlate with prostatic cancer progression. We used a novel form of image analysis called gray level entropy matrix (GLEM) texture analysis to evaluate morphometric changes in stromal tissues. We used normal prostatic tissue obtained from cadaveric specimen and compared with BPH, prostatic intraepithelium neoplastic, hormone responsive prostatic adenocarcinoma and castration-resistant prostatic adenocarcinoma tissues. GLEM showed higher entropy in disease-resistant prostatic tissues, compared with benign forms of all spectra of pathologically diagnosed prostatic tissues (P < 0.05, ANOVA, between groups). Higher entropy is reflective of the disorganized morphological organization of the stroma, possibly reflecting the reactive matrix. In contrast, ELISA revealed that although individually correlated with the progressive stages of benign and carcinomatous prostatic tissues and trend correlation between groups, intergroup comparisons failed to arrive at statistical significance of comparisons between markers of neovasculogenesis, vascular endothelial growth factor, epithelial-mesenchymal transition (beta1-integrin, E-cadherin, MMP3) and osteogenic metastasis (RANKL and osteoprotegerin). The results of our study demonstrate the potential of GLEM entropy of gray level pixel in providing quasiquantitative estimate of a reactive stroma in advance stages of prostatic adenocarcinoma and thus can be routinely used in clinical decision making.

  10. [Prostatilen treatment of prostatic adenoma].

    PubMed

    Al'-Shukri, S Kh; Gorbachev, A G; Borovets, S Iu; Belousov, V Ia; Kuz'min, I V; Chushkin, K A

    2006-01-01

    We studied efficacy of repeated courses of prostatilen in suppositories with dimexide in prostatic adenoma patients with normal micturition. Rectal suppositories contain 30 mg prostatilen and 90 mg dimexide. The course consisted of 15 suppositories. The treatment reduced clinical symptoms of infravesical obstruction, residual urine volume in administration of prostatilen in 15-day courses each 3 months. This suggests possibility of suppository prostatilen use not only as an alternative for expensive drugs but also in combination with them in treatment of initial prostatic adenoma.

  11. Cryosurgery of the prostate gland.

    PubMed Central

    Green, N. A.

    1977-01-01

    This personal review of the use of cryosurgery in prostatic disorders aims to put in perspective the value of the technique, establishing its place in the urologist's armamentarium mainly in the unfit subject but pointing to other applications as well. "Blind" perurethral cryosurgery has been used and has been shown to be effective in relieving urethral outflow obstruction, particularly in the second series of 178 patients with benign prostatic disease in which a simple "rule of thumb" technique was used. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 PMID:879634

  12. Calcium, dairy foods, and risk of incident and fatal prostate cancer: the NIH-AARP Diet and Health Study.

    PubMed

    Park, Yikyung; Mitrou, Panagiota N; Kipnis, Victor; Hollenbeck, Albert; Schatzkin, Arthur; Leitzmann, Michael F

    2007-12-01

    Calcium and dairy foods in relation to prostate cancer were examined in the National Institutes of Health (NIH)-AARP (formerly known as the American Association of Retired Persons) Diet and Health Study (1995/1996-2001). Diet was assessed with a food frequency questionnaire at baseline. Multivariate relative risks and 95% confidence intervals were estimated by Cox regression. During up to 6 years of follow-up (n = 293,888), the authors identified 10,180 total prostate cancer cases (8,754 nonadvanced, 1,426 advanced, and 178 fatal cases). Total and supplemental calcium were unrelated to total and nonadvanced prostate cancer. However, a statistically nonsignificant positive association with total calcium was observed for advanced (> or = 2,000 vs. 500-<750 mg/day: relative risk (RR) = 1.25, 95% confidence interval (CI): 0.91, 1.71; p(trend) = 0.06) and fatal (> or = 1,000 vs. 500-<750 mg/day: RR = 1.39, 95% CI: 0.92, 2.09; p(trend) = 0.10) prostate cancer. Skim milk, but not other dairy foods, was associated with increased risk of advanced prostate cancer (> or = 2 vs. zero servings/day: RR = 1.23, 95% CI: 0.99, 1.54; p(trend) = 0.01). In contrast, calcium from nondairy foods was associated with lower risk of nonadvanced prostate cancer (> or = 600 vs. < 250 mg/day: RR = 0.82, 95% CI: 0.68, 0.99; p(trend) = 0.04). Although the authors cannot definitively rule out a weak association for aggressive prostate cancer, their findings do not provide strong support for the hypothesis that calcium and dairy foods increase prostate cancer risk.

  13. Non-Prostate-Specific Membrane Antigen-Avid Metastatic Lung Nodule From Primary Prostatic Adenocarcinoma.

    PubMed

    Shetty, Deepa; Loh, Han; Bui, Chuong; Mansberg, Robert; Hadjashrafi, Amirazin; Do, Viet

    2016-10-01

    Ga-prostate-specific membrane antigen (PSMA) PET/CT is increasingly used to evaluate recurrent prostatic malignancy due to its high specificity. A 56-year-old man with previous history of treated prostate cancer 4 years earlier presented with rising prostate-specific antigen level and underwent Ga-PSMA PET/CT, which demonstrated an enlarging pulmonary nodule without PSMA avidity. The pulmonary nodule, however, showed moderate uptake on a corresponding FDG PET/CT study, suspicious of primary lung malignancy. Cytological and histopathological examination of the pulmonary nodule confirmed a metastatic deposit from ductal prostatic adenocarcinoma, an uncommon variant of prostatic malignancy.

  14. Vaccine Therapy and Pembrolizumab in Treating Patients With Hormone-Resistant, Metastatic Prostate Cancer

    ClinicalTrials.gov

    2016-06-22

    Hormone-Resistant Prostate Cancer; Metastatic Malignant Neoplasm in the Bone; Metastatic Malignant Neoplasm in the Soft Tissues; Metastatic Prostate Carcinoma; Prostate Adenocarcinoma; Recurrent Prostate Carcinoma; Stage IV Prostate Cancer

  15. Intrafractional prostate motion during external beam radiotherapy monitored by a real-time target localization system.

    PubMed

    Tong, Xu; Chen, Xiaoming; Li, Jinsheng; Xu, Qianqian; Lin, Mu-Han; Chen, Lili; Price, Robert A; Ma, Chang-Ming

    2015-03-08

    This paper investigates the clinical significance of real-time monitoring of intrafractional prostate motion during external beam radiotherapy using a commercial 4D localization system. Intrafractional prostate motion was tracked during 8,660 treatment fractions for 236 patients. The following statistics were analyzed: 1) the percentage of fractions in which the prostate shifted 2-7 mm for a certain duration; 2) the proportion of the entire tracking time during which the prostate shifted 2-7mm; and 3) the proportion of each minute in which the shift exceeded 2-7 mm. The ten patients exhibiting maximum intrafractional-motion patterns were analyzed separately. Our results showed that the percentage of fractions in which the prostate shifted by > 2, 3, 5, and 7 mm off the baseline in any direction for > 30 s was 56.8%, 27.2%, 4.6%, and 0.7% for intact prostate and 68.7%, 35.6%, 10.1%, and 1.8% for postprostatectomy patients, respectively. For the ten patients, these percentages were 91.3%, 72.4%, 36.3%, and 6%, respectively. The percentage of tracking time during which the prostate shifted > 2, 3, 5, and 7 mm was 27.8%, 10.7%, 1.6%, and 0.3%, respectively, and it was 56.2%, 33.7%, 11.2%, and 2.1%, respectively, for the ten patients. The percentage of tracking time for a > 3 mm posterior motion was four to five times higher than that in other directions. For treatments completed in 5 min (VMAT) and 10 min (IMRT), the proportion for the prostate to shift by > 3mm was 4% and 12%, respectively. Although intrafractional prostate motion was generally small, caution should be taken for patients who exhibit frequent large intrafractional motion. For those patients, adjustment of patient positioning may be necessary or a larger treatment margin may be used. After the initial alignment, the likelihood of prostate motion increases with time. Therefore, it is favorable to use advanced techniques (e.g., VMAT) that require less delivery time in order to reduce the treatment

  16. Magnetic resonance spectroscopic imaging for improved treatment planning of prostate cancer

    NASA Astrophysics Data System (ADS)

    Venugopal, Niranjan

    . Results from the in vivo study were verified with post-histopathological data. Lastly, 1H-MRSI data was incorporated into the radiation treatment planning software and used to assess tumour control by escalating the radiation to prostate lesions that were identified by 1H-MRSI. In summary, this thesis demonstrates the clinical feasibility of using advanced spectroscopic imaging techniques for improved diagnosis and treatment of prostate cancer.

  17. Body size across the life course and prostate cancer in the Health Professionals Follow-up Study.

    PubMed

    Möller, Elisabeth; Wilson, Kathryn M; Batista, Julie L; Mucci, Lorelei A; Bälter, Katarina; Giovannucci, Edward

    2016-02-15

    Current evidence of an association between body size and prostate cancer is conflicting, possibly due to differential effects of body size across the lifespan and the heterogeneity of the disease. We therefore examined childhood and adult body size in relation to total incident prostate cancer and prognostic subtypes in a prospective cohort of 47,491 US men in the Health Professionals Follow-up Study. We assessed adult height, body mass index (BMI) in early and middle-to-late adulthood, adult waist circumference, and body shape at age 10. With follow-up from 1986 to 2010, we estimated the relative risk (RR) of prostate cancer using Cox proportional hazards models. We identified 6,183 incident cases. Tallness was associated with increased risk of advanced-stage tumors, particularly fatal disease (RR = 1.66, 95% CI 1.23-2.23, highest vs. lowest quintile, ptrend < 0.001). High BMI at age 21 was inversely associated with total prostate cancer (RR = 0.89, 95% CI 0.80-0.98, BMI ≥ 26 vs. 20-21.9, ptrend = 0.01) and with fatal and advanced disease. The association for late adult BMI differed by age (pinteraction < 0.001); high BMI was inversely associated with total prostate cancer (RR = 0.64, 95% CI 0.51-0.78, BMI ≥ 30 vs. 21-22.9, ptrend <0.001) and with non-advanced and less aggressive tumors among men ≤ 65 years, whereas no association was seen among men >65 years. Adult waist circumference was weakly inversely associated with less aggressive disease. Childhood obesity was unclearly related to risk. Our study confirms tall men to be at increased risk of fatal and advanced prostate cancer. The influence of adiposity varies by prognostic disease subtype and by age. The relationship between body size and prostate cancer is complex. Body size changes progressively throughout life and consequent effects on prostate cancer risk may be associated with related changes in hormonal and metabolic pathways. This large prospective study examined potential associations

  18. Body size across the life course and prostate cancer in the Health Professionals Follow-up Study.

    PubMed

    Möller, Elisabeth; Wilson, Kathryn M; Batista, Julie L; Mucci, Lorelei A; Bälter, Katarina; Giovannucci, Edward

    2016-02-15

    Current evidence of an association between body size and prostate cancer is conflicting, possibly due to differential effects of body size across the lifespan and the heterogeneity of the disease. We therefore examined childhood and adult body size in relation to total incident prostate cancer and prognostic subtypes in a prospective cohort of 47,491 US men in the Health Professionals Follow-up Study. We assessed adult height, body mass index (BMI) in early and middle-to-late adulthood, adult waist circumference, and body shape at age 10. With follow-up from 1986 to 2010, we estimated the relative risk (RR) of prostate cancer using Cox proportional hazards models. We identified 6,183 incident cases. Tallness was associated with increased risk of advanced-stage tumors, particularly fatal disease (RR = 1.66, 95% CI 1.23-2.23, highest vs. lowest quintile, ptrend < 0.001). High BMI at age 21 was inversely associated with total prostate cancer (RR = 0.89, 95% CI 0.80-0.98, BMI ≥ 26 vs. 20-21.9, ptrend = 0.01) and with fatal and advanced disease. The association for late adult BMI differed by age (pinteraction < 0.001); high BMI was inversely associated with total prostate cancer (RR = 0.64, 95% CI 0.51-0.78, BMI ≥ 30 vs. 21-22.9, ptrend <0.001) and with non-advanced and less aggressive tumors among men ≤ 65 years, whereas no association was seen among men >65 years. Adult waist circumference was weakly inversely associated with less aggressive disease. Childhood obesity was unclearly related to risk. Our study confirms tall men to be at increased risk of fatal and advanced prostate cancer. The influence of adiposity varies by prognostic disease subtype and by age. The relationship between body size and prostate cancer is complex. Body size changes progressively throughout life and consequent effects on prostate cancer risk may be associated with related changes in hormonal and metabolic pathways. This large prospective study examined potential associations

  19. Prostatic and dietary omega-3 fatty acids and prostate cancer progression during active surveillance.

    PubMed

    Moreel, Xavier; Allaire, Janie; Léger, Caroline; Caron, André; Labonté, Marie-Ève; Lamarche, Benoît; Julien, Pierre; Desmeules, Patrice; Têtu, Bernard; Fradet, Vincent

    2014-07-01

    The association between omega-3 (ω-3) fatty acids and prostate cancer has been widely studied. However, little is known about the impact of prostate tissue fatty acid content on prostate cancer progression. We hypothesized that compared with the estimated dietary ω-3 fatty acids intake and the ω-3 fatty acids levels measured in red blood cells (RBC), the prostate tissue ω-3 fatty acid content is more strongly related to prostate cancer progression. We present the initial observations from baseline data of a phase II clinical trial conducted in a cohort of 48 untreated men affected with low-risk prostate cancer, managed under active surveillance. These men underwent a first repeat biopsy session within 6 months after the initial diagnosis of low-risk prostate cancer, at which time 29% of the men had progressed from a Gleason score of 6 to a Gleason score of 7. At the first repeat biopsy session, fatty acid levels were assessed with a food-frequency questionnaire, and determined in the RBC and in the prostate tissue biopsy. We found that eicosapentaenoic acid (EPA) was associated with a reduced risk of prostate cancer progression when measured directly in the prostate tissue. Thus, this initial interim study analysis suggests that prostate tissue ω-3 fatty acids, especially EPA, may be protective against prostate cancer progression in men with low-risk prostate cancer.

  20. Olfactomedin 4 deficiency promotes prostate neoplastic progression and is associated with upregulation of the hedgehog-signaling pathway

    PubMed Central

    Li, Hongzhen; Liu, Wenli; Chen, Weiping; Zhu, Jianqiong; Deng, Chu-Xia; Rodgers, Griffin P.

    2015-01-01

    Loss of olfactomedin 4 (OLFM4) gene expression is associated with the progression of human prostate cancer, but its role and the molecular mechanisms involved in this process have not been completely understood. In this study, we found that Olfm4-knockout mice developed prostatic intraepithelial neoplasia and prostatic adenocarcinoma. Importantly, we found that the hedgehog-signaling pathway was significantly upregulated in the Olfm4-knockout mouse model. We also found that restoration of OLFM4 in human prostate-cancer cells that lack OLFM4 expression significantly downregulated hedgehog signaling-pathway component expression. Furthermore, we demonstrated that the OLFM4 protein interacts with sonic hedgehog protein, as well as significantly inhibits GLI-reporter activity. Bioinformatic and immunohistochemistry analyses revealed that decreased OLFM4 and increased SHH expression was significantly associated with advanced human prostate cancer. Thus, olfactomedin 4 appears to play a critical role in regulating progression of prostate cancer, and has potential as a new biomarker for prostate cancer. PMID:26581960