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Prostate cancer survival

Jeff M Michalski, Jennifer Moughan, James Purdy, Walter Bosch, Deborah W Bruner, Jean-Paul Bahary, Harold Lau, Marie Duclos, Matthew Parliament, Gerard Morton, Daniel Hamstra, Michael Seider, Michael I Lock, Malti Patel, Hiram Gay, Eric Vigneault, Kathryn Winter, Howard Sandler
Importance: Optimizing radiation therapy techniques for localized prostate cancer can affect patient outcomes. Dose escalation improves biochemical control, but no prior trials were powered to detect overall survival (OS) differences. Objective: To determine whether radiation dose escalation to 79.2 Gy compared with 70.2 Gy would improve OS and other outcomes in prostate cancer. Design, Setting, and Participants: The NRG Oncology/RTOG 0126 randomized clinical trial randomized 1532 patients from 104 North American Radiation Therapy Oncology Group institutions March 2002 through August 2008...
March 15, 2018: JAMA Oncology
Masato Yasui, Yoriko Hasegawa, Takashi Kawahara, Yohei Kumano, Yasuhide Miyoshi, Nobuaki Matsubara, Hiroji Uemura
Abiraterone acetate (AA), a CYP17 inhibitor, now has a crucial role in the treatment of castration-resistant prostate cancer (CRPC), and previous studies have reported several prognostic clinical factors for AA treatment. The neutrophil-to-lymphocyte ratio (NLR) has also been investigated for a CRPC treatments in a few reports, however it has not been identified to be a prognostic factor for AA treatment in Japanese patients. The present study aimed to assess the association of the baseline NLR with the overall survival (OS) in CPRC patients treated by AA...
April 2018: Molecular and Clinical Oncology
Tony Tong-Lin Wu, Yat-Ching Tong, I-Hung Chen, Ho-Shan Niu, Yingxiao Li, Juei-Tang Cheng
The therapeutic action of ginsenoside Rh2 on several cancer models has been reported. This study aimed to evaluate its apoptotic effect on prostate cancer and the underlying mechanism. Cultured DU145 cells were treated with Rh2 (5 × 10-5 to 1 × 10-4 M), peroxisome proliferator-activated receptor-delta (PPAR-delta) antagonist GSK0660 (1 × 10-6 to 5 × 10-6 M); or small interfering RNA (siRNA) of PPAR-delta. The treatment effects were evaluated with cell viability assay, life/death staining and flow cytometry for apoptosis...
February 16, 2018: Oncotarget
David W McIlwain, Melissa L Fishel, Alexander Boos, Mark R Kelley, Travis J Jerde
A key feature of prostate cancer progression is the induction and activation of survival proteins, including the Inhibitor of Apoptosis (IAP) family member survivin. Apurinic/apyrimidinic endonuclease 1/redox effector factor 1 (APE1/Ref-1) is a multifunctional protein that is essential in activating oncogenic transcription factors. Because APE1/Ref-1 is expressed and elevated in prostate cancer, we sought to characterize APE1/Ref-1 expression and activity in human prostate cancer cell lines and determine the effect of selective reduction-oxidation (redox) function inhibition on prostate cancer cells in vitro and in vivo ...
February 16, 2018: Oncotarget
Filippo Cortesi, Gloria Delfanti, Andrea Grilli, Arianna Calcinotto, Francesca Gorini, Ferdinando Pucci, Roberta Lucianò, Matteo Grioni, Alessandra Recchia, Fabio Benigni, Alberto Briganti, Andrea Salonia, Michele De Palma, Silvio Bicciato, Claudio Doglioni, Matteo Bellone, Giulia Casorati, Paolo Dellabona
Heterotypic cellular and molecular interactions in the tumor microenvironment (TME) control cancer progression. Here, we show that CD1d-restricted invariant natural killer (iNKT) cells control prostate cancer (PCa) progression by sculpting the TME. In a mouse PCa model, iNKT cells restrained the pro-angiogenic and immunosuppressive capabilities of tumor-infiltrating immune cells by reducing pro-angiogenic TIE2+ , M2-like macrophages (TEMs), and sustaining pro-inflammatory M1-like macrophages. iNKT cells directly contacted macrophages in the PCa stroma, and iNKT cell transfer into tumor-bearing mice abated TEMs, delaying tumor progression...
March 13, 2018: Cell Reports
Erfan Amini, Tracy Campanelli Palmer, Jie Cai, Gary Lieskovsky, Siamak Daneshmand, Hooman Djaladat
PURPOSE: Few studies have evaluated prostate cancer oncologic outcomes in different ethnic groups following radical prostatectomy for clinically organ-confined disease. Existing studies lack long-term outcome data. We conducted this study to assess the impact of racial differences on risk profile and oncologic outcomes in a large cohort of patients with prostate cancer who underwent radical prostatectomy. METHODS: Using our institutional review board-approved prostate cancer database, we retrospectively reviewed the records of 3437 patients who underwent radical prostatectomy with curative intent in our institution between 1987 and 2009...
March 13, 2018: World Journal of Urology
Waiel Abusnina, Eric Yiman Auyoung, Mohammed Megri, Toni Pacioles
Small cell carcinomas (SCCs) are aggressive neoplasms commonly associated with a pulmonary origin. However, albeit rare, extrapulmonary SCC can occur in a variety of sites with an incidence in North America approximated to be 0.1% to 0.4%. Among these sites, approximately 10% of extrapulmonary SCC cases occur in the prostate and are associated with a poor mortality with a median survival of 10 months. Because of the rarity of the prostatic SCC, there is no formal treatment protocol. In this case report, we present a patient who was diagnosed with SCC in the prostate as primary origin...
January 2018: Journal of Investigative Medicine High Impact Case Reports
Donggen Jiang, Chutian Xiao, Tuzeng Xian, Liantao Wang, Yunhua Mao, Junfu Zhang, Jun Pang
Background: Doublecortin-like kinase 1 (DCLK1) has been proven to be involved in numerous tumors, while its role in prostate cancer (PCa) is still unclear. This study aimed at investigating the expression pattern and prognostic value of DCLK1 in PCa. Patients and methods: Real-time polymerase chain reaction and Western blot were employed to determine DCLK1 mRNA and protein levels in 25 paired fresh samples of PCa and benign prostatic hyperplasia (BPH) as well as in PCa cell lines...
2018: OncoTargets and Therapy
Guoyu Yu, Chien-Jui Cheng, Song-Chang Lin, Yu-Chen Lee, Daniel E Frigo, Li-Yuan Yu-Lee, Gary E Gallick, Mark A Titus, Leta K Nutt, Sue-Hwa Lin
Although emerging evidence suggests a potential role of calcium/calmodulin-dependent kinase II (CaMKII) in prostate cancer (PCa), its role in PCa tumorigenesis is largely unknown. Here we examine whether the acetyl CoA-CaMKII pathway, first described in frog oocytes, promotes PCa tumorigenesis. In human PCa specimens, metastatic PCa expressed higher levels of active CaMKII compared to localized PCa. Correspondingly, basal CaMKII activity was significantly higher in the more tumorigenic PC3 and PC3-mm2 cells relative to the less tumorigenic LNCaP and C4-2B4 cells...
March 13, 2018: Cancer Research
Manish K Thakur, Lance Heilbrun, Kimberlee Dobson, Julie Boerner, Karri Stark, Jing Li, Daryn Smith, Elisabeth Heath, Joseph Fontana, Ulka Vaishampayan
BACKGROUND: Pasireotide (SOM230; Novartis Inc, Basel, Switzerland) is a multitargeted somatostatin receptor analogue likely to treat the neuroendocrine, and docetaxel resistant components within metastatic castrate-resistant prostate cancer (mCRPC). This phase I trial tested the combination of pasireotide, docetaxel, and prednisone in pretreated mCRPC. PATIENTS AND METHODS: Chemotherapy naive mCRPC patients received docetaxel 75 mg/m2 intravenously every 21 days and pasireotide intramuscularly every 28 days at escalating dose levels of 40, 60, and 80 mg...
February 13, 2018: Clinical Genitourinary Cancer
Ellen Wargowski, Laura E Johnson, Jens C Eickhoff, Lauren Delmastro, Mary Jane Staab, Glenn Liu, Douglas G McNeel
BACKGROUND: Prostatic acid phosphatase (PAP) is a prostate tumor antigen, and the target of the only FDA-approved anti-tumor vaccine, sipuleucel-T. We have previously reported in two clinical trials that a DNA vaccine encoding PAP (pTVG-HP) could elicit PAP-specific, Th1-biased T cells in patients with PSA-recurrent prostate cancer. In the current pilot trial we sought to evaluate whether this vaccine could augment PAP-specific immunity when used as a booster to immunization with sipuleucel-T in patients with metastatic, castration-resistant prostate cancer (mCRPC)...
March 13, 2018: Journal for Immunotherapy of Cancer
GuangLiang Jiang, QingFeng Hu, Hui Wang, WeiHong Ding, Ning Zhang, YiShuo Wu, QiDong Zhou, ChuanYu Sun, GuoWei Xia, Qiang Ding, Rong Na, Ke Xu
BACKGROUND: Epithelial-mesenchymal transition (EMT) was reported to have an important effect on malignant metastasis; however, it remained largely unknown if EMT marker expression of neoplastic tissue had predictive value for prognosis of prostate cancer. METHODS: We searched for published studies which measured EMT marker expression and analyzed its association with clinical outcomes of patients after Radical Prostatectomy (RP). We reviewed and pooled-analyzed the association of EMT marker expression and biochemical recurrence-free survival (BFS), as well as the difference in strong or weak expression of EMT markers in tumors of high Gleason score (≥8)...
January 2018: Annals of Clinical and Laboratory Science
Margaret M Centenera, Luke A Selth, Esmaeil Ebrahimie, Lisa M Butler, Wayne D Tilley
Recent genomic analyses of metastatic prostate cancer have provided important insight into adaptive changes in androgen receptor (AR) signaling that underpin resistance to androgen deprivation therapies. Novel strategies are required to circumvent these AR-mediated resistance mechanisms and thereby improve prostate cancer survival. In this review, we present a summary of AR structure and function and discuss mechanisms of AR-mediated therapy resistance that represent important areas of focus for the development of new therapies...
March 12, 2018: Cold Spring Harbor Perspectives in Medicine
T Steuber, C Jilg, P Tennstedt, A De Bruycker, K Decaestecker, T Zilli, B A Jereczek-Fossa, U Wetterauer, A L Grosu, W Schultze-Seemann, H Heinzer, M Graefen, A Morlacco, R J Karnes, Piet Ost
BACKGROUND: Most prostate cancer (PCa) patients with a biochemical failure following primary multimodality treatment (surgery and postoperative radiotherapy) relapse in the nodes. OBJECTIVE: To perform a matched-case analysis in men with lymph node recurrent PCa comparing standard of care (SOC) with metastasis-directed therapy (MDT). DESIGN, SETTING, AND PARTICIPANTS: PCa patients with a prostate-specific antigen (PSA) progression following multimodality treatment were included in this retrospective multi-institutional analysis...
March 9, 2018: European Urology Focus
Matthew R Sydes, Melissa R Spears, Malcolm D Mason, Noel W Clarke, David P Dearnaley, Johann S de Bono, Gert Attard, Simon Chowdhury, Bill Cross, Silke Gillessen, Zaf Malik, Rob Jones, Chris Parker, Alastair W S Ritchie, J Martin Russell, Robin Millman, David Matheson, Claire Amos, Clare Gilson, Alison Birtle, Susannah Brock, Lisa Capaldi, Prabir Chakraborti, Ananya Choudhury, Linda Evans, Daniel Ford, Joanna Gale, Stephanie Gibbs, Duncan Gilbert, Robert Hughes, Duncan McLaren, Jason Lester, Ashok Nikapota, Joe O'Sullivan, Omi Parikh, Clive Peedell, Andrew Protheroe, Sarah M Rudman, Richard Shaffer, Denise Sheehan, Matthew Simms, Narayanan Srihari, Räto Strebel, Santhanam Sundar, Shaun Tolan, David Tsang, Mohini Varughese, John Wagstaff, Mahesh K B Parmar, Nicholas D James
Background: Adding abiraterone acetate with prednisolone (AAP) or docetaxel with prednisolone (DocP) to standard-of-care (SOC) each improved survival in STAMPEDE: a multi-arm multi-stage platform randomised controlled protocol recruiting patients with high-risk locally advanced or metastatic PCa starting long-term androgen deprivation therapy (ADT). The protocol provides the only direct, randomised comparative data of SOC+AAP vs SOC+DocP. Method: Recruitment to SOC+DocP and SOC+AAP overlapped Nov-2011─Mar-2013...
February 26, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Shayna E Thomas-Jardin, Mohammed S Kanchwala, Joan Jacob, Sana Merchant, Rachel K Meade, Nagham M Gahnim, Afshan F Nawas, Chao Xing, Nikki A Delk
BACKGROUND: In immunosurveillance, bone-derived immune cells infiltrate the tumor and secrete inflammatory cytokines to destroy cancer cells. However, cancer cells have evolved mechanisms to usurp inflammatory cytokines to promote tumor progression. In particular, the inflammatory cytokine, interleukin-1 (IL-1), is elevated in prostate cancer (PCa) patient tissue and serum, and promotes PCa bone metastasis. IL-1 also represses androgen receptor (AR) accumulation and activity in PCa cells, yet the cells remain viable and tumorigenic; suggesting that IL-1 may also contribute to AR-targeted therapy resistance...
March 11, 2018: Prostate
Alice F Yan, Yang Wang, Alexander V Ng
Multiple chronic conditions in cancer survivors are highly prevalent and may increase health care costs for both patients and the health care system. Studies of cancer survivors reveal positive effects of physical activity (PA) on reducing risk of cancer recurrence, other chronic conditions, and secondary cancer. Few nationally representative studies have examined how physical activity levels have affected survivors' annual economic burden in the United States. Leisure-time physical activity data from the National Health Interview Survey was linked to health care expenditure data from the Medical Expenditure Panel Survey data (2008-2012)...
March 2018: Preventive Medicine Reports
Christoph Oing, Pierre Tennstedt, Ronald Simon, Jennifer Volquardsen, Kerstin Borgmann, Carsten Bokemeyer, Cordula Petersen, Ekkehard Dikomey, Kai Rothkamm, Wael Y Mansour
Here we report that BCL2 blocks DNA double strand break (DSB) repair via nonhomologous end-joining (NHEJ), through sequestration of KU80 protein outside the nucleus. We find that this effect is associated with a repair switch to the error-prone PARP1-dependent end-joining (PARP1-EJ). We present in-vitro proof-of-concept for therapeutic targeting of this switch using PARP inhibitor to specifically enhance the radiosensitivity of BCL2-overexpressing cells. Given its erroneous behavior, PARP1-EJ might allow for the accumulation of genetic alterations and tumor progression...
March 8, 2018: Cancer Letters
Morane Le Hiress, Bernardin Akagah, Guillaume Bernadat, Ly Tu, Raphaël Thuillet, Alice Huertas, Carole Phan, Elie Fadel, Gérald Simonneau, Marc Humbert, Gaël Jalce, Christophe Guignabert
Macrophage migration inhibitory factor (MIF) is a key pleiotropic mediator and a promising therapeutic target in cancer as well as in several inflammatory and cardiovascular diseases including pulmonary arterial hypertension (PAH). Here, a novel series of N-(phenylmethyl)-benzoxazol-2-thiones 5-32 designed to target the MIF tautomerase active site was synthesized and evaluated for its effects on cell survival. Investigation of structure-activity relationship (SAR) particularly at the 5-position of the benzoxazole core led to the identification of 31 that potently inhibits cell survival in DU-145 prostate cancer cells and pulmonary endothelial cells derived from patients with idiopathic PAH (iPAH-ECs), two cell lines for which survival is MIF-dependent...
March 10, 2018: Journal of Medicinal Chemistry
Matthew Utter, Sohag Chakraborty, Limor Goren, Lucas Feuser, Yuan-Shan Zhu, David A Foster
Prostate cells are hormonally driven to grow and divide. Typical treatments for prostate cancer involve blocking activation of the androgen receptor by androgens. Androgen deprivation therapy can lead to the selection of cancer cells that grow and divide independently of androgen receptor activation. Prostate cancer cells that are insensitive to androgens commonly display metastatic phenotypes and reduced long-term survival of patients. In this study we provide evidence that androgen-insensitive prostate cancer cells have elevated PLD activity relative to the androgen-sensitive prostate cancer cells...
March 7, 2018: Cancer Letters
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