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Advanced prostate cancer

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https://www.readbyqxmd.com/read/28334734/multinucleated-polyploidy-drives-resistance-to-docetaxel-chemotherapy-in-prostate-cancer
#1
Karuna Mittal, Shashi Donthamsetty, Ramneet Kaur, Chunhua Yang, Meenakshi V Gupta, Michelle D Reid, Da Hoon Choi, Padmashree C G Rida, Ritu Aneja
BACKGROUND: Docetaxel is the only FDA-approved first-line treatment for castration-resistant prostate cancer (CRPC) patients. Docetaxel treatment inevitably leads to tumour recurrence after an initial therapeutic response with generation of multinucleated polyploid (MP) cells. Here we investigated role of MP cells in clinical relapse of CRPC. METHODS: Prostate cancer (PC-3) cells were treated with docetaxel (5 nM) for 3 days followed by a washout and samples were collected at close intervals over 35 days post drug washout...
March 23, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28331050/first-in-human-clinical-trial-of-oral-onc201-in-patients-with-refractory-solid-tumors
#2
Mark N Stein, Joseph R Bertino, Howard L Kaufman, Tina Mayer, Rebecca Moss, Ann Silk, Nancy Chan, Jyoti Malhotra, Lorna Rodriguez-Rodriguez, Joseph Aisner, Robert D Aiken, Bruce G Haffty, Robert S DiPaola, Tracie Saunders, Andrew Zloza, Sherri Damare, Yasmeen Beckett, Bangning Yu, Saltanat Najmi, Christian Gabel, Siobhan Dickerson, Ling Zheng, Wafik S El-Deiry, Joshua Allen, Martin Stogniew, Wolfgang Oster, Janice M Mehnert
Purpose ONC201 is a small molecule selective antagonist of the G protein-coupled receptor DRD2 that is the founding member of the imipridone class of compounds. A first-in-human phase I study of ONC201 was conducted to determine its recommended phase II dose (RP2D). Experimental Design This open-label study treated 10 patients during dose escalation with histologically-confirmed advanced solid tumors. Patients received ONC201 orally once every 3 weeks, defined as one cycle, at doses from 125 to 625 mg using an accelerated titration design...
March 22, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28327203/an-appraisal-of-analytical-tools-used-in-predicting-clinical-outcomes-following-radiation-therapy-treatment-of-men-with-prostate-cancer-a-systematic-review
#3
Elspeth Raymond, Michael E O'Callaghan, Jared Campbell, Andrew D Vincent, Kerri Beckmann, David Roder, Sue Evans, John McNeil, Jeremy Millar, John Zalcberg, Martin Borg, Kim Moretti
BACKGROUND: Prostate cancer can be treated with several different modalities, including radiation treatment. Various prognostic tools have been developed to aid decision making by providing estimates of the probability of different outcomes. Such tools have been demonstrated to have better prognostic accuracy than clinical judgment alone. METHODS: A systematic review was undertaken to identify papers relating to the prediction of clinical outcomes (biochemical failure, metastasis, survival) in patients with prostate cancer who received radiation treatment, with the particular aim of identifying whether published tools are adequately developed, validated, and provide accurate predictions...
March 21, 2017: Radiation Oncology
https://www.readbyqxmd.com/read/28326819/inflammation-and-nitrosative-stress-effects-in-ovarian-and-prostate-pathology-and-carcinogenesis
#4
Amy J Burke, Pablo Garrido, Carol Johnson, Francis J Sullivan, Sharon A Glynn
SIGNIFICANCE: Prostate and ovarian cancers are major contributors to cancer-related deaths worldwide. Recently, inflammation and nitrosative stress have been implicated in carcinogenesis, with the overexpression of NOS2 and concomitant release of nitric oxide (NO) associated with cancer initiation and progression. Recent Advances: An increasing body of evidence indicates an association between NOS2 expression and aggressive ovarian cancer. Research also indicates a role for NO in prostate disease pathology and prostate cancer...
March 22, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28324908/-magnetic-sentinel-lymph-node-detection-in-prostate-cancer-after-intraprostatic-injection-of-superparamagnetic-iron-oxide-nanoparticles
#5
Alexander Winter, Svenja Engels, Tobias Kowald, Tina Susanne Paulo, Holger Gerullis, Ajay Chavan, Friedhelm Wawroschek
In prostate cancer, reliable information about the lymph node status is of great importance for accurate staging and the optimal planning of treatment. Despite recent advances in imaging, the histological detection of metastases, or pelvic lymphadenectomy (PLND), continues to be the most reliable method for lymph node staging in clinically localised prostate cancer, especially as this procedure enables the detection of small or micrometastases. Radioisotope-guided sentinel PLND (sPLND) demonstrates high sensitivity in the detection of lymph node metastases as well as low morbidity in prostate cancer because of the targeted removal of a relatively small number of lymph nodes...
March 21, 2017: Aktuelle Urologie
https://www.readbyqxmd.com/read/28323658/changing-face-of-metastatic-prostate-cancer-the-law-of-diminishing-returns-holds-true
#6
Ulka N Vaishampayan
PURPOSE OF REVIEW: Prostate cancer presents with a multitude of faces. It ranges from localized cancers staying quiescent for many years during active surveillance to the raging diffuse liver metastases causing terminal disease. The incidence of metastatic disease is increasing. This review will highlight some of the recent developments as well as ongoing challenges of managing advanced prostate cancer. RECENT FINDINGS: Significant strides are being made in managing metastatic prostate cancer...
March 18, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/28323036/targeting-androgen-receptor-versus-targeting-androgens-to-suppress-castration-resistant-prostate-cancer
#7
Changcheng Guo, Shuyuan Yeh, Yuanjie Niu, Gonghui Li, Junhua Zheng, Lei Li, Chawnshang Chang
Prostate cancer (PCa) is the 2nd leading cause of cancer-related death among men in the United States and its progression is tightly associated with the androgen/androgen receptor (AR) signals. Men castrated before puberty (eunuchs) or men with inherited deficiency of type II 5α-reductase (with failure to convert testosterone to the more potent dihydrotestosterone) (DHT) do not develop PCa. To date, androgen deprivation therapy (ADT) with anti-androgen treatments to reduce or prevent androgens from binding to the AR remains the main therapeutic option for advanced PCa since its discovery by Huggins and Hodges in 1941...
March 18, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28323031/an-anti-prostate-cancer-benzofuran-conjugated-iridium-iii-complex-as-a-dual-inhibitor-of-stat3-and-nf-%C3%AE%C2%BAb
#8
Tian-Shu Kang, Wanhe Wang, Hai-Jing Zhong, Zhen-Zhen Dong, Qi Huang, Simon Wing Fai Mok, Chung-Hang Leung, Vincent Kam Wai Wong, Dik-Lung Ma
Four benzofuran-conjugated iridium(III) or rhodium (III)-based metal complexes are synthesized to screen as an inhibitor of STAT3 activity in prostate cancer cells. All complexes show the high stability and solubility in the biological system. In this study, an iridium(III) complex engages STAT3 and NF-κB to inhibit their translocation and transcriptional activities. Moreover, complex 1 shows more potential antiproliferative activity against DU145 cells and suppresses tumor growth in a prostate cancer xenograft mouse without observable adverse effects...
March 16, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28322234/propsa-and-the-prostate-health-index-as-predictive-markers-for-aggressiveness-in-low-risk-prostate-cancer-results-from-an-international-multicenter-study
#9
I Heidegger, H Klocker, R Pichler, A Pircher, W Prokop, E Steiner, C Ladurner, E Comploj, A Lunacek, D Djordjevic, A Pycha, E Plas, W Horninger, J Bektic
BACKGROUND: One of the major challenges in prostate cancer (PCa) treatment is distinguishing insignificant PCa from those forms that need active treatment. We evaluated the impact of PSA isoforms on risk stratification in patients with low-risk PCa as well as in active surveillance (AS) candidates who underwent radical prostatectomy. METHODS: A total of 112 patients with biopsy confirmed Gleason score (GS) 6 PCa of four different international institutions were prospectively enrolled in the study...
March 21, 2017: Prostate Cancer and Prostatic Diseases
https://www.readbyqxmd.com/read/28321463/-when-is-surgical-resection-of-the-primary-tumor-indicated-in-metastatic-prostate-cancer-and-what-is-the-scientific-rationale
#10
J Noldus
Similar to other tumour entities, analyses of cancer databases giving hope that patients with advanced prostate cancer with osseous metastases benefit from cytoreductive surgery. Prospective clinical trials are in the process of proving this hypothesis. This review article focuses on molecular genetic pathways and clinical data.
March 20, 2017: Der Urologe. Ausg. A
https://www.readbyqxmd.com/read/28321130/effective-combinatorial-immunotherapy-for-castration-resistant-prostate-cancer
#11
Xin Lu, James W Horner, Erin Paul, Xiaoying Shang, Patricia Troncoso, Pingna Deng, Shan Jiang, Qing Chang, Denise J Spring, Padmanee Sharma, John A Zebala, Dean Y Maeda, Y Alan Wang, Ronald A DePinho
A significant fraction of patients with advanced prostate cancer treated with androgen deprivation therapy experience relapse with relentless progression to lethal metastatic castration-resistant prostate cancer (mCRPC). Immune checkpoint blockade using antibodies against cytotoxic-T-lymphocyte-associated protein 4 (CTLA4) or programmed cell death 1/programmed cell death 1 ligand 1 (PD1/PD-L1) generates durable therapeutic responses in a significant subset of patients across a variety of cancer types. However, mCRPC showed overwhelming de novo resistance to immune checkpoint blockade, motivating a search for targeted therapies that overcome this resistance...
March 20, 2017: Nature
https://www.readbyqxmd.com/read/28319070/foxa1-inhibits-prostate-cancer-neuroendocrine-differentiation
#12
J Kim, H Jin, J C Zhao, Y A Yang, Y Li, X Yang, X Dong, J Yu
Neuroendocrine prostate cancer (NEPC) has increasingly become a clinical challenge. The mechanisms by which neuroendocrine (NE) cells arises from prostate adenocarcinoma cells are poorly understood. FOXA1 is a transcription factor of the forkhead family that is required for prostate epithelial differentiation. In this study, we demonstrated that FOXA1 loss drives NE differentiation, demarcated by phenotypical changes and NEPC marker expressions. Mechanistically, this is mediated by FOXA1 binding to the promoter of interleukin 8 (IL-8), a chemokine previously shown elevated in NEPC, to directly inhibit its expression...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28319065/the-drebrin-eb3-pathway-drives-invasive-activity-in-prostate-cancer
#13
A E Dart, D C Worth, G Muir, A Chandra, J D Morris, C McKee, C Verrill, R J Bryant, P R Gordon-Weeks
Prostate cancer is the most common cancer in men and the metastatic form of the disease is incurable. We show here that the drebrin/EB3 pathway, which co-ordinates dynamic microtubule/actin filament interactions underlying cell shape changes in response to guidance cues, plays a role in prostate cancer cell invasion. Drebrin expression is restricted to basal epithelial cells in benign human prostate but is upregulated in luminal epithelial cells in foci of prostatic malignancy. Drebrin is also upregulated in human prostate cancer cell lines and co-localizes with actin filaments and dynamic microtubules in filopodia of pseudopods of invading cells under a chemotactic gradient of the chemokine CXCL12...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28314609/germline-dna-repair-mutations-and-response-to-hormonal-therapy-in-advanced-prostate-cancer
#14
EDITORIAL
Emmanuel S Antonarakis
No abstract text is available yet for this article.
March 14, 2017: European Urology
https://www.readbyqxmd.com/read/28302580/the-role-of-therapeutic-layering-in-optimizing-treatment-for-patients-with-castration-resistant-prostate-cancer-radar-ii
#15
E David Crawford, Daniel P Petrylak, Neal Shore, Fred Saad, Susan F Slovin, Nicholas J Vogelzang, Thomas E Keane, Phillip J Koo, Leonard G Gomella, Joe M O'Sullivan, Bertrand Tombal, Raoul S Concepcion, Paul Sieber, Nelson N Stone, Steven E Finkelstein, Evan Y Yu
OBJECTIVE: To offer recommendations on identification of disease progression, treatment management strategies, and suggestions on timing of initiating and discontinuing specific CRPC treatments. MATERIALS AND METHODS: The RADAR II [Prostate Cancer Radiographic Assessments for Detection of Advanced Recurrence] Working Group convened to provide guidance on sequencing, combination, or layering of approved treatments for mCRPC based on available data and clinical experience...
March 13, 2017: Urology
https://www.readbyqxmd.com/read/28300967/burden-of-cancer-mortality-and-differences-attributable-to-demographic-aging-and-risk-factors-in-argentina-1986-2011
#16
Sonia Alejandra Pou, Natalia Tumas, Julia Becaria Coquet, Camila Niclis, María Dolores Román, María Del Pilar Díaz
The world faces an aging population that implies a large number of people affected with chronic diseases. Argentina has reached an advanced stage of demographic transition and presents a comparatively high rate of cancer mortality within Latin America. The objectives of this study were to examine cancer mortality trends in the province of Córdoba, Argentina, between 1986 and 2011, and to analyze the differences attributable to risk variations and demographic changes. Longitudinal series of age-standardized mortality rates for overall, breast and prostate cancers were modeled by Joinpoint regression to estimate the annual percent change...
March 9, 2017: Cadernos de Saúde Pública
https://www.readbyqxmd.com/read/28300506/adding-celecoxib-with-or-without-zoledronic-acid-for-hormone-na%C3%A3-ve-prostate-cancer-long-term-survival-results-from-an-adaptive-multiarm-multistage-platform-randomized-controlled-trial
#17
Malcolm D Mason, Noel W Clarke, Nicholas D James, David P Dearnaley, Melissa R Spears, Alastair W S Ritchie, Gerhardt Attard, William Cross, Rob J Jones, Christopher C Parker, J Martin Russell, George N Thalmann, Francesca Schiavone, Estelle Cassoly, David Matheson, Robin Millman, Cyrill A Rentsch, Jim Barber, Clare Gilson, Azman Ibrahim, John Logue, Anna Lydon, Ashok D Nikapota, Joe M O'Sullivan, Emilio Porfiri, Andrew Protheroe, Narayanan Nair Srihari, David Tsang, John Wagstaff, Jan Wallace, Catherine Walmsley, Mahesh K B Parmar, Matthew R Sydes
Purpose Systemic Therapy for Advanced or Metastatic Prostate Cancer: Evaluation of Drug Efficacy is a randomized controlled trial using a multiarm, multistage, platform design. It recruits men with high-risk, locally advanced or metastatic prostate cancer who were initiating long-term hormone therapy. We report survival data for two celecoxib (Cel)-containing comparisons, which stopped accrual early at interim analysis on the basis of failure-free survival. Patients and Methods Standard of care (SOC) was hormone therapy continuously (metastatic) or for ≥ 2 years (nonmetastatic); prostate (± pelvic node) radiotherapy was encouraged for men without metastases...
March 13, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28299719/the-non-coding-transcriptome-of-prostate-cancer-implications-for-clinical-practice
#18
REVIEW
Irene V Bijnsdorp, Martin E van Royen, Gerald W Verhaegh, Elena S Martens-Uzunova
Prostate cancer (PCa) is the most common type of cancer and the second leading cause of cancer-related death in men. Despite extensive research, the molecular mechanisms underlying PCa initiation and progression remain unclear, and there is increasing need of better biomarkers that can distinguish indolent from aggressive and life-threatening disease. With the advent of advanced genomic technologies in the last decade, it became apparent that the human genome encodes tens of thousands non-protein-coding RNAs (ncRNAs) with yet to be discovered function...
March 15, 2017: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/28297567/developing-a-novel-two-dimensional-culture-system-to-enrich-human-prostate-luminal-progenitors-that-can-function-as-a-cell-of-origin-for-prostate-cancer
#19
Dingxiao Zhang, Kevin Lin, Yue Lu, Kiera Rycaj, Yi Zhong, Hsueh-Ping Chao, Tammy Calhoun-Davis, Jianjun Shen, Dean G Tang
Elucidating the cell of origin of cancer has great significance in stratifying patients into appropriate treatment groups and for developing novel targeted therapies. Early studies demonstrate that only stem-like basal cells in the normal human prostate (NHP) can function as the cell of origin for prostate cancer (PCa). Here, we show that the organoids derived from bulk NHP luminal cells can also be tumorigenically transformed. We further show that the WIT medium, which is used to culture human mammary epithelial progenitor cells, when combined with the ROCK inhibitor, can readily propagate a population of progenitor-like cells from the primary NHP luminal cell isolates...
March 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28293633/combined-ligand-structure-based-virtual-screening-and-molecular-dynamics-simulations-of-steroidal-androgen-receptor-antagonists
#20
Yuwei Wang, Rui Han, Huimin Zhang, Hongli Liu, Jiazhong Li, Huanxiang Liu, Paola Gramatica
The antiandrogens, such as bicalutamide, targeting the androgen receptor (AR), are the main endocrine therapies for prostate cancer (PCa). But as drug resistance to antiandrogens emerges in advanced PCa, there presents a high medical need for exploitation of novel AR antagonists. In this work, the relationships between the molecular structures and antiandrogenic activities of a series of 7α-substituted dihydrotestosterone derivatives were investigated. The proposed MLR model obtained high predictive ability...
2017: BioMed Research International
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