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prostate cancer progression

Giorgio Ivan Russo, Simone Bier, Jörg Hennenlotter, Gunthild Beger, Lucretia Pavlenco, Jens van de Flierdt, Siegfried Hauch, Moritz Maas, Simon Walz, Steffen Rausch, Jens Bedke, Giuseppe Morgia, Arnulf Stenzl, Tilman Todenhöfer
OBJECTIVE: To evaluate the presence of circulating tumour cells (CTC) at different stages of prostate cancer (PC) using the ProstateCancerDetect kit. Moreover, we aimed to assess the expression of transcripts that are specific for cancer stem cells (AdnaTest StemCell) and epithelial mesenchymal transition (EMT) in CTC (AdnaTest EMT) as well as additional genes that are known to promote PC progression. PATIENTS AND METHODS: In this prospective study, we included 81 patients who underwent treatment for PC between 07/2014 and 02/2015, including A) 18 patients (22...
March 15, 2018: BJU International
Stephanie N David, Shanna A Arnold Egloff, Rajen Goyal, Peter E Clark, Sharon Phillips, Lan L Gellert, Omar Hameed, Giovanna A Giannico
BACKGROUND: Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (MAGI2) promotes the activity of phosphatase and tensin homolog (PTEN). Recent studies suggest that dysregulation of this signaling pathway has a role in prostate carcinogenesis. Our study aims to determine the prognostic significance of MAGI2 expression in prostate cancer. METHODS: Tissue microarrays from 51 radical prostatectomy cases including benign prostatic tissue, high grade prostatic intraepithelial neoplasia (HGPIN), and adenocarcinoma were constructed...
March 14, 2018: Prostate
Folakemi T Odedina, R R Reams, E Kaninjing, J Nguyen, B Mochona, D E Lyon, N Askins, L S Behar-Horenstein
With the growing burden of cancer in minority populations and limited progress in eliminating cancer disparities, it has become important to develop a diverse oncology workforce in basic, clinical, and behavioral research who will address cancer disparities and increase the participation of minority populations in clinical trials. To address the lack of well-trained underrepresented minority cancer scientists in Florida, the University of Florida collaborated with Florida A&M University in 2012 to establish the Florida Prostate Cancer Research Training Opportunities for Outstanding Leaders (ReTOOL) Program...
March 15, 2018: Journal of Cancer Education: the Official Journal of the American Association for Cancer Education
Muhammad Shuja, Ayman A Elghazaly, Asif Iqbal, Reham Mohamed, Amal Marie, Mutahir A Tunio, Moamen M Aly, Ali Balbaid, Mushabbab Asiri
Introduction Bone metastasis (BM) is a major complication of many solid tumors like breast, prostate, lung and renal cancers. BM leads to serious sequelae of pain, fractures, spinal cord compression and hypercalcemia. Radiotherapy has an established role in relieving pain caused by BM. Worldwide different radiotherapy schedules are being used for BM. The aim of this study is to determine the efficacy of single fraction palliative radiotherapy for painful bone metastases. Methods Between April 2014 and April 2017, single fraction radiotherapy was used to treat 73 patients in our institution...
January 8, 2018: Curēus
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
Peng Hao, Bo Kang, Guoqing Yao, Wenqi Hao, Feihong Ma
Dysregulation of microRNAs (miRNAs/miRs) is frequently associated with cancer progression. Altered expression of miR-211 has been observed in various types of human cancer; however, its expression and role in prostate cancer (PCa) remains unknown. In the present study, the expression of miR-211 in PCa cell lines and tissues was measured by reverse transcription-quantitative PCR (qPCR), revealing that miR-211 was downregulated in PCa cell lines and tissues. Further analysis revealed that low miR-211 was associated with the tumor stage and Gleason score...
April 2018: Oncology Letters
Tong Sun, Shin-Yi Du, Joshua Armenia, Fangfang Qu, Jingyu Fan, Xiaodong Wang, Teng Fei, Kazumasa Komura, Shirley X Liu, Gwo-Shu Mary Lee, Philip W Kantoff
Mechanisms by which non-coding RNAs contribute to the progression of hormone-sensitive prostate cancer (PCa) (HSPC) to castration-resistant PCa (CRPC) remain largely unknown. We previously showed that microRNA-221/222 is up-regulated in CRPC and plays a critical role in modulating androgen receptor function during CRPC development. With further investigation, we characterized a putative promoter region located 23.3 kb upstream of the miR-221/222 gene, and this promoter is differentially activated in CRPC LNCaP-Abl cells, leading to the up-regulation of miR-221/222...
March 13, 2018: Oncogenesis
Kedarlal Sharma, JuhiSingh, Emma E Frost, Prakash P Pillai
MethylCpG binding protein-2 (MeCP2) is an epigenetic regulator and essential for brain development.MeCP2 mutations are associated with a spectrum of neuro-developmental disorders that vary depending on the patient gender, most notably Rett Syndrome. MeCP2 is essential for normal neuronal maturation, and glial cell function in the brain. Besides, its role in neurodevelopmental disorders, MeCP2 is involved in many cancers such as breast, colorectal, lung, liver, and prostate cancer. Glioma is the most lethal form of brain cancer...
March 11, 2018: Neuroscience Letters
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
Juliana Porretti, Guillermo N Dalton, Cintia Massillo, Georgina D Scalise, Paula L Farré, Randolph Elble, Esther N Gerez, Paula Accialini, Ana M Cabanillas, Kevin Gardner, Paola De Luca, Adriana De Siervi
Prostate cancer (PCa) is the most common cancer among men. Metabolic syndrome (MeS) is associated with increased PCa aggressiveness and recurrence. Previously, we proposed C-terminal binding protein 1 (CTBP1), a transcripcional co-repressor, as a molecular link between these two conditions. Notably, CTBP1 depletion decreased PCa growth in MeS mice. The aim of this study was to investigate the molecular mechanisms that explain the link between MeS and PCa mediated by CTBP1. We found that CTBP1 repressed Chloride Channel Accessory 2 (CLCA2) expression in prostate xenografts developed in MeS animals...
March 14, 2018: International Journal of Cancer. Journal International du Cancer
Hiroaki Kobayashi, Takeo Kosaka, Shuji Mikami, Yasumasa Miyazaki, Kazuhiro Matsumoto, Eiji Kikuchi, Akira Miyajima, Kaori Kameyama, Yasufumi Sato, Mototsugu Oya
Background: We previously reported high expression of vasohibin-1 (VASH1), which is specifically expressed in activated vascular endothelial cells, was a prognostic indicator of disease progression in prostate cancer. The aim of this study was to assess whether VASH1 expression at the area of normal prostatic tissue as well as that of intratumoral tissue could reflect the grade of malignancy of prostate cancer. Results: Pathological upgrade of Gleason Score ≥7 by radical prostatectomy was observed in 48 patients (upgraded group)...
February 13, 2018: Oncotarget
Nathalie Harder, Maria Athelogou, Harald Hessel, Nicolas Brieu, Mehmet Yigitsoy, Johannes Zimmermann, Martin Baatz, Alexander Buchner, Christian G Stief, Thomas Kirchner, Gerd Binnig, Günter Schmidt, Ralf Huss
Tissue Phenomics is the discipline of mining tissue images to identify patterns that are related to clinical outcome providing potential prognostic and predictive value. This involves the discovery process from assay development, image analysis, and data mining to the final interpretation and validation of the findings. Importantly, this process is not linear but allows backward steps and optimization loops over multiple sub-processes. We provide a detailed description of the Tissue Phenomics methodology while exemplifying each step on the application of prostate cancer recurrence prediction...
March 13, 2018: Scientific Reports
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
Alicia Bort, Sergio Quesada, Ágata Ramos-Torres, Marta Gargantilla, Eva María Priego, Sophie Raynal, Franck Lepifre, Jose M Gasalla, Nieves Rodriguez-Henche, Ana Castro, Inés Díaz-Laviada
The key metabolic sensor adenosine monophosphate-dependent kinase (AMPK) has emerged as a promising therapeutic target for cancer prevention and treatment. Besides its role in energy homeostasis, AMPK blocks cell cycle, regulates autophagy and suppresses the anabolic processes required for rapid cell growth. AMPK is especially relevant in prostate cancer in which activation of lipogenic pathways correlate with tumor progression and aggressiveness. This study reports the discovery of a new series of 2-oxindole derivatives whose AMPK modulatory ability, as well as the antitumoral profile in prostate cancer cells, was evaluated...
March 12, 2018: Scientific Reports
David P Labbé, Myles Brown
Prostate cancer development involves corruption of the normal prostate transcriptional network, following deregulated expression or mutation of key transcription factors. Here, we provide an overview of the transcription factors that are important in normal prostate homeostasis (NKX3-1, p63, androgen receptor [AR]), primary prostate cancer (ETS family members, c-MYC), castration-resistant prostate cancer (AR, FOXA1), and AR-independent castration-resistant neuroendocrine prostate cancer (RB1, p53, N-MYC). We use functional (in vitro and in vivo) as well as clinical data to discuss evidence that unveils their roles in the initiation and progression of prostate cancer, with an emphasis on results of chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq)...
March 12, 2018: Cold Spring Harbor Perspectives in Medicine
Matthew J Schiewer, Karen E Knudsen
Prostatic adenocarcinoma (PCa) remains a significant health concern. Although localized PCa can be effectively treated, disseminated disease remains uniformly fatal. PCa is reliant on androgen receptor (AR); as such, first-line therapy for metastatic PCa entails suppression of AR signaling. Although initially effective, recurrent tumors reactivate AR function, leading to a lethal stage of disease termed castration-resistant PCa (CRPC). Recent findings implicate AR signaling in control of DNA repair and show that alterations in DNA damage repair pathways are strongly associated with disease progression and poor outcome...
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
Huimin Lu, Nicholas Bowler, Larry A Harshyne, D Craig Hooper, Shiv Ram Krishn, Senem Kurtoglu, Carmine Fedele, Qin Liu, Hsin-Yao Tang, Andrew V Kossenkov, William K Kelly, Kerith Wang, Rhonda B Kean, Paul H Weinreb, Lei Yu, Anindita Dutta, Paolo Fortina, Adam Ertel, Maria Stanczak, Flemming Forsberg, Dmitry I Gabrilovich, David W Speicher, Dario C Altieri, Lucia R Languino
Therapeutic approaches aimed at curing prostate cancer are only partially successful given the occurrence of highly metastatic resistant phenotypes that frequently develop in response to therapies. Recently, we have described αvβ6, a surface receptor of the integrin family as a novel therapeutic target for prostate cancer; this epithelial-specific molecule is an ideal target since, unlike other integrins, it is found in different types of cancer but not in normal tissues. We describe a novel αvβ6-mediated signaling pathway that has profound effects on the microenvironment...
March 9, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
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
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