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https://www.readbyqxmd.com/read/28346812/identification-of-a-novel-benzimidazole-pyrazolone-scaffold-that-inhibits-kdm4-lysine-demethylases-and-reduces-proliferation-of-prostate-cancer-cells
#1
David M Carter, Edgar Specker, Jessica Przygodda, Martin Neuenschwander, Jens Peter von Kries, Udo Heinemann, Marc Nazaré, Ulrich Gohlke
Human lysine demethylase (KDM) enzymes (KDM1-7) constitute an emerging class of therapeutic targets, with activities that support growth and development of metastatic disease. By interacting with and co-activating the androgen receptor, the KDM4 subfamily (KDM4A-E) promotes aggressive phenotypes of prostate cancer (PCa). Knockdown of KDM4 expression or inhibition of KDM4 enzyme activity reduces the proliferation of PCa cell lines and highlights inhibition of lysine demethylation as a possible therapeutic method for PCa treatment...
March 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28346806/active-surveillance-in-younger-men-with-prostate-cancer
#2
Michael S Leapman, Janet E Cowan, Hao G Nguyen, Katsuto K Shinohara, Nannette Perez, Matthew R Cooperberg, William J Catalona, Peter R Carroll
Purpose The suitability of younger patients with prostate cancer (PCa) for initial active surveillance (AS) has been questioned on the basis of eventual treatment necessity and concerns of safety; however, the role of age on surveillance outcomes has not been well defined. Patients and Methods We identified men managed with AS at our institution with a minimum follow-up of 6 months. The primary study objective was to examine the association of age with risk of biopsy-based Gleason score upgrade during AS. We also examined the association of age with related end points, including overall biopsy-determined progression, definitive treatment, and pathologic and biochemical outcomes after delayed radical prostatectomy (RP), using descriptive statistics, the Kaplan-Meier method, and multivariable Cox proportional hazards regression...
March 27, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28346805/brachytherapy-for-patients-with-prostate-cancer-american-society-of-clinical-oncology-cancer-care-ontario-joint-guideline-update
#3
Joseph Chin, R Bryan Rumble, Marisa Kollmeier, Elisabeth Heath, Jason Efstathiou, Tanya Dorff, Barry Berman, Andrew Feifer, Arthur Jacques, D Andrew Loblaw
Purpose To jointly update the Cancer Care Ontario guideline on brachytherapy for patients with prostate cancer to account for new evidence. Methods An Update Panel conducted a targeted systematic literature review and identified more recent randomized controlled trials comparing dose-escalated external beam radiation therapy (EBRT) with brachytherapy in men with prostate cancer. Results Five randomized controlled trials provided the evidence for this update. Recommendations For patients with low-risk prostate cancer who require or choose active treatment, low-dose rate brachytherapy (LDR) alone, EBRT alone, and/or radical prostatectomy (RP) should be offered to eligible patients...
March 27, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28346770/a-core-outcome-set-for-localised-prostate-cancer-effectiveness-trials
#4
Steven MacLennan, Paula R Williamson, Hanneke Bekema, Marion Campbell, Craig Ramsay, James N'Dow, Sara MacLennan, Luke Vale, Philipp Dahm, Nicolas Mottet, Thomas Lam, Paul Abel, Hashim U Ahmed, Gary Akehurst, Robert Almquist, Karl Beck, David Budd, Steven Canfield, James Catto, Philip Cornford, William Cross, Alexander Ewen, Judith Grant, Rakesh Heer, David Hurst, Rob Jones, Roger Kockelbergh, Andrew Mackie, Graham MacDonald, Alan McNeill, Malcolm Mason, Sam McClinton, Duncan McLaren, Hugh Mostafid, Ian Pearce, Linda Pennet, Justine Royle, Hans Schreuder, Grant D Stewart, Henk van der Poel, Kevin Wardlaw, Thomas Wiegel
OBJECTIVE: To develop a core outcome set (COS) applicable for effectiveness trials of all interventions for localised prostate cancer. BACKGROUND: Many treatments exist for localised prostate cancer, although it is unclear which offers the optimal therapeutic ratio. This is confounded by inconsistencies in the selection, definition, measurement and reporting of outcomes in clinical trials. SUBJECTS AND METHODS: A list of 79 outcomes was derived from a systematic review of published localised prostate cancer effectiveness studies and semi-structured interviews with 15 prostate cancer patients...
March 27, 2017: BJU International
https://www.readbyqxmd.com/read/28346424/skp2-deficiency-restricts-the-progression-and-stem-cell-features-of-castration-resistant-prostate-cancer-by-destabilizing-twist
#5
D Ruan, J He, C-F Li, H-J Lee, J Liu, H-K Lin, C-H Chan
Castration-resistant prostate cancer (CRPC) remains a major clinical challenge because of the lack of effective targeted therapy for its treatment. The mechanism underlying how CRPC gains resistance toward hormone depletion and other forms of chemotherapy is poorly understood. Research on understanding the factors that drive these processes is desperately needed to generate new therapies to cure the disease. Here, we discovered a fundamental role of S-phase protein kinase 2 (Skp2) in the formation and progression of CRPC...
March 27, 2017: Oncogene
https://www.readbyqxmd.com/read/28345847/five-year-survival-is-not-a-useful-measure-for-cancer-control-in-the-population-an-analysis-based-on-uk-data
#6
Si Qi Li, Xiong Fei Pan, Michael Saheb Kashaf, Qing Ping Xue, Hui Jing Luo, Yan Yan Wang, Ying Wen, Chun Xia Yang
Background: Five-year survival is an important metric for progress in cancer control broadly used both in the cancer literature and by the public. In order to assess its validity and relation to other common metrics, we analyzed the relationship between 5-year survival, incidence and mortality using publicly available cancer registry data from England and Wales. Methods: Five-year survival, incidence and mortality data were obtained from the online database of a registered charity, Cancer Research UK. We extracted sex-specific age-standardized mortality, incidence, and 5-year survivalfor16 types of cancer over the period from 1976 to 1995...
February 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28345462/functional-interaction-of-fibroblast-growth-factor-8b-and-androgen-in-prostate-cancer-cell-proliferation
#7
Wen-Jun Xiao, Gui-Ming Zhang, Ding-Wei Ye
Fibroblast growth factor 8b and androgen play important roles in cell proliferation of prostate cancer. We investigated the effects of fibroblast growth factor 8b and androgen on the proliferation of prostate cell lines and the corresponding intracellular mechanisms. It is found that dihydrotestosterone and fibroblast growth factor 8b stimulated Lncap cell mitosis in a concentration-responsive manner, with 30 ng/mL as the most suitable concentration, respectively. Dihydrotestosterone treatment alone did not enhance the expression and phosphorylation level of fibroblast growth factor receptor but significantly enhanced the level of fibroblast growth factor receptor phosphorylation elicited by fibroblast growth factor 8b...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28345444/budgetary-impact-of-cabazitaxel-use-after-docetaxel-treatment-for-metastatic-castration-resistant-prostate-cancer
#8
Kyle Flannery, Ed Drea, Louis Hudspeth, Shelby Corman, Xin Gao, Mei Xue, Raymond Miao
BACKGROUND: With the approval of several new treatments for metastatic castration-resistant prostate cancer (mCRPC), budgetary impact is a concern for health plan decision makers. Budget impact models (BIMs) are becoming a requirement in many countries as part of formulary approval or reimbursement decisions. Cabazitaxel is a second-generation taxane developed to overcome resistance to docetaxel and is approved for the treatment of patients with mCRPC previously treated with a docetaxel-containing regimen...
April 2017: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/28345329/lycopene-extracts-from-different-tomato-based-food-products-induce-apoptosis-in-cultured-human-primary-prostate-cancer-cells-and-regulate-tp53-bax-and-bcl-2-transcript-expression
#9
Nathalia da Costa Pereira Soares, Clara Lima Machado, Bruno Boquimpani Trindade, Ingridy Celestino do Canto Lima, Etel Rodrigues Pereira Gimba, Anderson Junger Teodoro, Christina Takiya, Radovan Borojevic
Carotenoids are the main tomato components, especially lycopene. Lycopene is more bioavailable in tomato processed products than in raw tomatos, since formation of lycopene cis-isomers during food processing and storage may increase its biological activity. In the current study, we evaluated the influence of lycopene extracts (5 mg / mL) from different tomato-based food products (paste, sauce, extract and ketchup) on cell viability and apoptosis on primary human prostate cancer cells (PCa cels) for 96h. Using MTT assay, we observed a significant decrease on primary PCa cell viability upon treatment with lycopene extracted from either 4 tomato-based food products...
February 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28345187/novel-biomarkers-for-prostate-cancer-an-evidence-based-review-for-use-in-clinical-practice
#10
REVIEW
Vikram M Narayan, Badrinath R Konety, Christopher Warlick
Prostate cancer is a heterogeneous disease with disparate outcomes. Traditional clinical parameters are limited in their ability to differentiate between these cases, and there is uncertainty regarding management strategies. A number of novel biomarkers have emerged, but how best to use them at the point of care remains confusing. In the present review, we describe the most common novel biomarkers, their key supporting literature, and propose a meaningful algorithm for their use in clinical practice. To identify commercially available prostate cancer diagnostic tests, we carried out a PubMed literature search (through May 2016)...
March 27, 2017: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/28345023/enhancement-of-psma-directed-car-adoptive-immunotherapy-by-pd-1-pd-l1-blockade
#11
Inna Serganova, Ekaterina Moroz, Ivan Cohen, Maxim Moroz, Mayuresh Mane, Juan Zurita, Larissa Shenker, Vladimir Ponomarev, Ronald Blasberg
Chimeric antigen receptor (CAR) T cell therapy in hematologic malignancies has shown remarkable responses, but the same level of success has not been observed in solid tumors. A new prostate cancer model (Myc-CaP:PSMA(+)) and a second-generation anti-hPSMA human CAR T cells expressing a Click Beetle Red luciferase reporter) were used to study hPSMA targeting and assess CAR T cell trafficking and persistence by bioluminescence imaging (BLI). We investigated the antitumor efficacy of human CAR T cells targeting human prostate-specific membrane antigen (hPSMA), in the presence and absence of the target antigen; first alone and then combined with a monoclonal antibody targeting the human programmed death receptor 1 (anti-hPD1 mAb)...
March 17, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28344814/the-role-of-chemotherapy-and-new-targeted-agents-in-the-management-of-primary-prostate-cancer
#12
Sanjeev Srinivas Kumar, Simon Pacey
While early treatment of primary prostate cancer is very effective, the incidence of primary prostate cancer continues to rise and therefore the detection of men with high-risk non-metastatic prostate cancer and their subsequent management is becoming increasingly important. There continues to be no molecularly-targeted or chemotherapeutic options with proven, statistically significant survival benefit in this setting. However, there are indications that further risk stratification using molecular features could potentially help distinguish indolent from aggressive prostate cancer, ultimately providing biological markers that could guide a more personalised approach to therapy selection...
December 2016: Journal of Clinical Urology
https://www.readbyqxmd.com/read/28344813/the-modern-role-of-androgen-deprivation-therapy-in-the-management-of-localised-and-locally-advanced-prostate-cancer
#13
Charlotte Gunner, Aziz Gulamhusein, Derek J Rosario
INTRODUCTION: Approximately 50% of men diagnosed with prostate cancer will be exposed to androgen deprivation therapy (ADT) at some stage. The role of ADT in the management of metastatic disease has long been recognised, and its place in the management of localised and locally advanced disease has become clearer in the past few years. Nevertheless, concerns remain that some men might not benefit from ADT in earlier-stage disease. The purpose of the current article is to provide a brief narrative review of the role of ADT as part of a strategy of treatment with curative intent, concentrating mainly on key recent developments in the area...
December 2016: Journal of Clinical Urology
https://www.readbyqxmd.com/read/28344812/novel-concepts-for-risk-stratification-in-prostate-cancer
#14
Keval M Patel, Vincent J Gnanapragasam
Since Partin introduced the analysis of prostate-specific antigen, clinical T-stage and Gleason scores to estimate the risk of progression in men with localised prostate cancer, our understanding of factors that modify this risk has changed drastically. There are now multiple risk stratification tools available, including look-up tables, risk stratification/classification analyses, regression-tree analyses, nomograms and artificial neural networks. Concurrently, descriptions of novel biopsy strategies, imaging modalities and biomarkers are frequently published with the aim of improving risk stratification...
December 2016: Journal of Clinical Urology
https://www.readbyqxmd.com/read/28344810/novel-biomarkers-for-the-detection-of-prostate-cancer
#15
Niels Asger Jakobsen, Freddie Charles Hamdy, Richard John Bryant
Prostate-specific antigen (PSA) is widely used as a biomarker in the detection of prostate cancer and for decision making regarding treatment options, response to therapy, and clinical follow-up. Despite its widespread use, it is well recognised that PSA has suboptimal performance as a screening tool due to poor specificity, resulting in high negative biopsy rates and potential 'over-diagnosis' and 'over-treatment' of clinically insignificant cancers. In particular, PSA does not reliably distinguish either cancer from benign prostatic conditions, or 'clinically significant' from 'indolent cancers', and it is inaccurate in predicting disease burden and response to treatment...
December 2016: Journal of Clinical Urology
https://www.readbyqxmd.com/read/28344102/effect-of-visceral-disease-site-on-outcomes-in-patients-with-metastatic-castration-resistant-prostate-cancer-treated-with-enzalutamide-in-the-prevail-trial
#16
Joshi J Alumkal, Simon Chowdhury, Yohann Loriot, Cora N Sternberg, Johann S de Bono, Bertrand Tombal, Joan Carles, Thomas W Flaig, Tanya B Dorff, De Phung, David Forer, Sarah B Noonberg, Hank Mansbach, Tomasz M Beer, Celestia S Higano
BACKGROUND: The Multinational Phase 3, Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study of Oral MDV3100 in Chemotherapy-Naive Patients With Progressive Metastatic Prostate Cancer Who Have Failed Androgen Deprivation Therapy (PREVAIL) trial was unique as it included patients with visceral disease. This analysis was designed to describe outcomes for the subgroup of men from PREVAIL with specific sites of visceral disease to help clinicians understand how these patients responded to enzalutamide prior to chemotherapy...
March 3, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28343795/use-of-mri-in-low-dose-rate-and-high-dose-rate-prostate-brachytherapy-from-diagnosis-to-treatment-assessment-defining-the-knowledge-gaps-technical-challenges-and-barriers-to-implementation
#17
S J Frank, F Mourtada, J Crook, C Ménard
MRI is rapidly evolving as an imaging tool in both low-dose-rate and high-dose-rate brachytherapy for prostate cancer. The ability of MRI to identify intraprostatic tumors and reduce uncertainties in the workflow process should enable a more accurate and precise radiation delivery approach while simultaneously improving the quality assurance process. The ability to identify functional anatomic structures adjacent to the prostate cancer could reduce or eliminate some of the more common side effects of the treatment...
March 23, 2017: Brachytherapy
https://www.readbyqxmd.com/read/28343345/assessment-of-nucleosides-as-putative-tumor-biomarkers-in-prostate-cancer-screening-by-ce-uv
#18
Adriana Zardini Buzatto, Mariana de Oliveira Silva, Ronei Jesus Poppi, Ana Valéria Colnaghi Simionato
Cancer is responsible for millions of deaths worldwide, but most base diseases may be cured if detected early. Screening tests may be used to identify early-stage malignant neoplasms. However, the major screening tool for prostate cancer, the prostate-specific antigen test, has unsuitable sensitivity. Since cancer cells may affect the pattern of consumption and excretion of nucleosides, such biomolecules are putative biomarkers that can be used for diagnosis and treatment evaluation. Using a previously validated method for the analysis of nucleosides in blood serum by capillary electrophoresis with UV-vis spectroscopy detection, we investigated 60 samples from healthy individuals and 42 samples from prostate cancer patients...
March 25, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28343199/-hypogonadism-in-patients-with-testicular-tumors-and-prostate-cancer
#19
Marcin Radko, Tomasz Syryło, Henryk Zieliński
Hypogonadism is defined as an array of symptoms arising from a deficiency of androgens. It is caused by a hormonal and spermatogenic dysfunction of the testes. It results in impaired fertility and has a negative impact on the functions of multiple organs and systems, physical well-being, sexual functions and also mental state. Particularly patients with a history of cancer have a high risk of developing hypogonadism as a result of not only the nature of the disease, but mainly its treatment. While leaving the patient with cancer without treatment does not fall within the concept of the art of medicine and the ethical canon of a physician, the symptoms of hypogonadism are often ignored and left untreated...
2017: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/28343079/population-model-of-bladder-motion-and-deformation-based-on-dominant-eigenmodes-and-mixed-effects-models-in-prostate-cancer-radiotherapy
#20
Richard Rios, Renaud De Crevoisier, Juan D Ospina, Frederic Commandeur, Caroline Lafond, Antoine Simon, Pascal Haigron, Jairo Espinosa, Oscar Acosta
In radiotherapy for prostate cancer irradiation of neighboring organs at risk may lead to undesirable side-effects. Given this setting, the bladder presents the largest inter-fraction shape variations hampering the computation of the actual delivered dose vs. planned dose. This paper proposes a population model, based on longitudinal data, able to estimate the probability of bladder presence during treatment, using only the planning computed tomography (CT) scan as input information. As in previously-proposed principal component analysis (PCA) population-based models, we have used the data to obtain the dominant eigenmodes that describe bladder geometric variations between fractions...
March 8, 2017: Medical Image Analysis
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