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https://www.readbyqxmd.com/read/28428707/advanced-pancreatic-ductal-adenocarcinoma-complexities-of-treatment-and-emerging-therapeutic-options
#1
REVIEW
Chandra Diwakarla, Katherine Hannan, Nadine Hein, Desmond Yip
Pancreatic ductal adenocarcinoma is a devastating disease with a poor prognosis regardless of stage. To date the mainstay of therapy for advanced disease has been chemotherapy with little incremental improvements in outcome. Despite extensive research investigating new treatment options the current practices continue to utilise fluorouracil or gemcitabine containing combinations. The need for novel therapeutic approaches is mandated by the ongoing poor survival rates associated with this disease. One such approach may include manipulation of ribosome biogenesis and the nucleolar stress response, which has recently been applied to haematological malignancies such as lymphoma and prostate cancer with promising results...
April 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28428441/selective-glucocorticoid-receptor-modulators-sgrms-delay-castrate-resistant-prostate-cancer-growth
#2
Jacob Kach, Tiha M Long, Phillip Selman, Eva Y Tonsing-Carter, Maria A Bacalao, Ricardo R Lastra, Larischa de Wet, Shane Comiskey, Marc Gillard, Calvin VanOpstall, Diana C West, Wen-Ching Chan, Donald Vander Griend, Suzanne D Conzen, Russell Z Szmulewitz
Increased glucocorticoid receptor (GR) expression and activity following androgen blockade can contribute to castration-resistant prostate cancer (CRPC) progression. Therefore, we hypothesized that GR antagonism will have therapeutic benefit in CRPC. However, the FDA-approved nonselective, steroidal GR antagonist, mifepristone, lacks GR specificity, reducing its therapeutic potential. Here we report that two novel non-steroidal and highly selective GR modulators (SGRMs), CORT118335 and CORT108297, have the ability to block GR activity in prostate cancer (PC) and slow CRPC progression...
April 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28425029/comparison-of-a-novel-formulation-of-abiraterone-acetate-vs-the-originator-formulation-in-healthy-male-subjects-two-randomized-open-label-crossover-studies
#3
Ronald Goldwater, Azra Hussaini, Bill Bosch, Paul Nemeth
BACKGROUND AND OBJECTIVE: Abiraterone acetate is approved for the treatment of metastatic castration-resistant prostate cancer. The originator abiraterone acetate (OAA) formulation is poorly absorbed and exhibits large pharmacokinetic variability in abiraterone exposure. Abiraterone acetate fine particle (AAFP) is a proprietary formulation (using SoluMatrix Fine Particle Technology™) designed to increase the oral bioavailability of abiraterone acetate. Here, we report on two phase I studies in healthy male subjects aged 18-50 years...
April 19, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28424220/gababr-induced-egfr-transactivation-promotes-migration-of-human-prostate-cancer-cells
#4
Shuai Xia, Cong He, Yini Zhu, Suyun Wang, Huiping Li, Zhongling Zhang, Xinnong Jiang, Jianfeng Liu
G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs) act in concert to regulate cell growth, proliferation, survival, and migration. Metabotropic GABAB receptor (GABABR) is the GPCR for the main inhibitory neurotransmitter GABA in the central nervous system. Increased expression of GABABR has been detected in human cancer tissues and cancer cell lines, but the role of GABABR in these cells is controversial and the underlying mechanism remains poorly understood. Here, we investigated whether GABABR hijacks RTK signaling to modulate the fates of human prostate cancer cells...
April 19, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28417057/evaluation-of-shla-g-levels-in-serum-of-patients-with-prostate-cancer-identify-as-a-potential-of-tumor-marker
#5
Mohammad Hassan Heidari, Abolfazl Movafagh, Mohammad-Amin Abdollahifar, Shabnam Abdi, Mohamadreza Mashhoudi Barez, Hadi Azimi, Afshin Moradi, Amin Bagheri, Matineh Heidari, Jafar Hessam Mohseni, Maryam Tadayon, Hoda Mirsafian, Mahdi Ghatrehsamani
Prostate cancer is the most common cancer type in men and is the second cause of death, due to cancer, in patients over 50, after lung cancer. Prostate specific antigen (PSA) is a widely used tumor marker for prostate cancer. Recently, PSA is discovered in non-prostatic cancer tissues in men and women raising doubts about its specificity for prostatic tissues. PSA exists in low serum level in healthy men and in higher levels in many prostate disorders, including prostatitis and prostate cancer. Thus, a supplementary tumor marker is needed to accurately diagnose the cancer and to observe the patient after treatment...
March 2017: Anatomy & Cell Biology
https://www.readbyqxmd.com/read/28416823/-identification-of-a-new-pro-invasion-factor-in-tumor-microenvironment-progress-in-function-and-mechanism-of-extracellular-atp
#6
W G Fang, X X Tian
Up to 90% of all cancer related morbidity and mortality can be attributed to metastasis. In recent years the study of tumor microenvironment, its cellular and molecular components, and how they can affect neoplastic progression toward metastasis, has become a hot focus in cancer research. Accumulated evidence shows that the formation of metastasis is a multi-step sequential process, in which, the tumor cells continuously interact with the host microenvironment. Host derived factors, i.e. growth factors/inhibitors, angiogenic factors, chemokines, etc...
April 18, 2017: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
https://www.readbyqxmd.com/read/28416734/the-angiotensin-receptor-blocker-losartan-inhibits-mammary-tumor-development-and-progression-to-invasive-carcinoma
#7
Rhiannon Coulson, Seng H Liew, Angela A Connelly, Nicholas S Yee, Siddhartha Deb, Beena Kumar, Ana C Vargas, Sandra A O'Toole, Adam C Parslow, Ashleigh Poh, Tracy Putoczki, Riley J Morrow, Mariah Alorro, Kyren A Lazarus, Evie F W Yeap, Kelly L Walton, Craig A Harrison, Natalie J Hannan, Amee J George, Colin D Clyne, Matthias Ernst, Andrew M Allen, Ashwini L Chand
Drugs that target the Renin-Angiotensin System (RAS) have recently come into focus for their potential utility as cancer treatments. The use of Angiotensin Receptor Blockers (ARBs) and Angiotensin-Converting Enzyme (ACE) Inhibitors (ACEIs) to manage hypertension in cancer patients is correlated with improved survival outcomes for renal, prostate, breast and small cell lung cancer. Previous studies demonstrate that the Angiotensin Receptor Type I (AT1R) is linked to breast cancer pathogenesis, with unbiased analysis of gene-expression studies identifying significant up-regulation of AGTR1, the gene encoding AT1R in ER+ve/HER2-ve tumors correlating with poor prognosis...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415742/androgen-receptor-amplification-is-concordant-between-circulating-tumor-cells-and-biopsies-from-men-undergoing-treatment-for-metastatic-castration-resistant-prostate-cancer
#8
Jennifer Podolak, Kristi Eilers, Timothy Newby, Rachel Slottke, Erin Tucker, Susan B Olson, Hui-Wen Lue, Jack Youngren, Rahul Aggarwal, Eric J Small, Julie N Graff, Joshi J Alumkal, Tomasz M Beer, George V Thomas
Increased AR activity has been shown to be preserved in spatially distinct metastatic tumors from the same patient suggesting the requirement for lineage-specific dependencies for metastatic castration resistant prostate cancer (mCRPC). Amplification of the AR gene is a common mechanism by which mCRPC increase AR activity. To determine whether AR amplification in circulating tumor cells (CTC) could complement metastatic tissue biopsies in men undergoing treatment for mCRPC, we developed a novel two-step assay to isolate CTCs and subsequently analyzed AR amplification status in CTCs and matched biopsy tissue from the same patient by fluorescence in situ hybridization (FISH)...
March 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415688/inhibitor-sbfi26-suppresses-the-malignant-progression-of-castration-resistant-pc3-m-cells-by-competitively-binding-to-oncogenic-fabp5
#9
Waseem Al-Jameel, Xiaojun Gou, Shiva S Forootan, Majed Saad Al Fayi, Philip S Rudland, Farzad S Forootan, Jiacheng Zhang, Philip A Cornford, Syed A Hussain, Youqiang Ke
Castration resistant-prostate cancer is largely impervious to feather hormonal therapy and hence the outlook for patients is grim. Here we use an approach to attach the recently discovered Achilles heel. The experimental treatment established in this study is based on the recent discovery that it is the FABP5-PPARγ-VEGF signalling axis, rather than the androgen receptor pathway, played a dominant role in promoting the malignant progression of castration resistant prostate cancer cells. Treatments have been established in mice by suppressing the biological activity of FABP5 using a chemical inhibitor SBFI26...
March 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415632/the-combined-effect-of-usp7-inhibitors-and-parp-inhibitors-in-hormone-sensitive-and-castration-resistant-prostate-cancer-cells
#10
Francesco Morra, Francesco Merolla, Virginia Napolitano, Gennaro Ilardi, Caterina Miro, Simona Paladino, Stefania Staibano, Aniello Cerrato, Angela Celetti
PURPOSE OF THE STUDY: Reduced levels of the tumor suppressor protein CCDC6 sensitize cancer cells to the treatment with PARP-inhibitors. The turnover of CCDC6 protein is regulated by the de-ubiquitinase USP7, which also controls the androgen receptor (AR) stability. Here, we correlated the expression levels of CCDC6 and USP7 proteins in primary prostate cancers (PC). Moreover, we tested the efficacy of the USP7 inhibitors, in combination with PARP-inhibitors as a novel therapeutic option in advanced prostate cancer...
March 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415604/inhibiting-g-protein-%C3%AE-%C3%AE-signaling-blocks-prostate-cancer-progression-and-enhances-the-efficacy-of-paclitaxel
#11
Prakash Paudyal, Qing Xie, Prasanna Kuma Vaddi, Michael D Henry, Songhai Chen
Aberrant activation of G protein-coupled receptors (GPCRs) is implicated in prostate cancer progression, but targeting them has been challenging because multiple GPCRs are involved in cancer progression. In this study, we tested the effect of blocking signaling via a hub through which multiple GPCRs converge - the G-protein Gβγ subunits. Inhibiting Gβγ signaling in several castration-resistant prostate cancer cell lines (i.e. PC3, DU145 and 22Rv1), impaired cell growth and migration in vitro, and halted tumor growth and metastasis in nude mice...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414074/a-novel-chemotherapy-drug-free-delivery-system-composed-of-three-therapeutic-aptamers-for-the-treatment-of-prostate-and-breast-cancers-in-vitro-and-in-vivo
#12
Khalil Abnous, Noor Mohammad Danesh, Mohammad Ramezani, Rezvan Yazdian-Robati, Mona Alibolandi, Seyed Mohammad Taghdisi
In this study, a novel chemotherapy drug-free DNA nanocomplex composed of three therapeutic aptamers (IDA, AS1411 and apMNK2F) was designed for treatment of cancer cells. For MTT assay, PC-3 and 4T1 cells (target cells) and CHO cells (nontarget cells) were treated with apMNK2F-AS1411-IDA complex (DNA nanocomplex), as well as AS1411, IDA and apMNK2F alone. Internalization of apMNK2F-AS1411-IDA complex was analyzed by fluorescence imaging and flow cytometry analysis. In the last step, the presented DNA nanocomplex was applied for prohibition of tumor growth in vivo...
April 13, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28412354/role-of-gpr30-in-estrogen-induced-prostate-epithelial-apoptosis-and-benign-prostatic-hyperplasia
#13
Deng-Liang Yang, Jia-Wen Xu, Jianguo Zhu, Yi-Lin Zhang, Jian-Bang Xu, Qing Sun, Xiao-Nian Cao, Wu-Lin Zuo, Ruo-Shui Xu, Jiehong Huang, Fu-Neng Jiang, Yang-Jia Zhuo, Bai-Quan Xiao, Yun-Zhong Liu, Dongbo Yuan, Zhaolin Sun, Hui-Chan He, Zhao-Rong Lun, Wei-De Zhong, Wen-Liang Zhou
Several studies have implicated estrogen and the estrogen receptor (ER) in the pathogenesis of benign prostatic hyperplasia (BPH); however, the mechanism underlying this effect remains elusive. In the present study, we demonstrated that estrogen (17β-estradiol, or E2)-induced activation of the G protein-coupled receptor 30 (GPR30) triggered Ca(2+) release from the endoplasmic reticulum, increased the mitochondrial Ca(2+) concentration, and thus induced prostate epithelial cell (PEC) apoptosis. Both E2 and the GPR30-specific agonist G1 induced a transient intracellular Ca(2+) release in PECs via the phospholipase C (PLC)-inositol 1, 4, 5-triphosphate (IP3) pathway, and this was abolished by treatment with the GPR30 antagonist G15...
April 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28411207/transdifferentiation-as-a-mechanism-of-treatment-resistance-in-a-mouse-model-of-castration-resistant-prostate-cancer
#14
Min Zou, Roxanne Toivanen, Antonina Mitrofanova, Nicolas Floc'h, Sheida Hayati, Yanping Sun, Clementine Le Magnen, Daniel Chester, Elahe A Mostaghel, Andrea Califano, Mark A Rubin, Michael M Shen, Cory Abate-Shen
Current treatments for castration-resistant prostate cancer (CPRC) that target androgen receptor (AR) signaling improve patient survival, yet ultimately fail. Here we provide novel insights into treatment response for the anti-androgen abiraterone by analyses of a genetically-engineered mouse model (GEMM) with combined inactivation of Trp53 and Pten, which are frequently co-mutated in human CRPC. These NPp53 mice fail to respond to abiraterone, and display accelerated progression to tumors resembling treatment-related CRPC with neuroendocrine differentiation (CRPC-NE) in humans...
April 14, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28410543/probing-the-prostate-tumour-microenvironment-ii-impact-of-hypoxia-on-a-cell-model-of-prostate-cancer-progression
#15
Claire Tonry, John Armstrong, Stephen Pennington
Approximately one in six men are diagnosed with Prostate Cancer every year in the Western world. Although it can be well managed and non-life threatening in the early stages, over time many patients cease to respond to treatment and develop castrate resistant prostate cancer (CRPC). CRPC represents a clinically challenging and lethal form of prostate cancer. Progression of CRPC is, in part, driven by the ability of cancer cells to alter their metabolic profile during the course of tumourgenesis and metastasis so that they can survive in oxygen and nutrient-poor environments and even withstand treatment...
February 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28410139/exosomes-based-biomarker-discovery-for-diagnosis-and-prognosis-of-prostate-cancer
#16
Gati Krushna Panigrahi, Gagan Deep
African American men in the United States have higher incidence and mortality rates due to prostate cancer (PCa) compared to other races. In 2016 alone, nearly 30,000 cases of PCa in African American men were diagnosed and 4,450 men died from PCa. The underlying reasons for this health disparity in PCa are complex and include social, economic, and biologic determinants. To reduce or eliminate this health disparity, we must better understand the biology of the disease in African Americans and then develop novel diagnostic and prognostic biomarkers useful for timely and effective treatment decisions...
June 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28406576/antitumor-activity-and-pharmacologic-characterization-of-the-depsipeptide-analog-as-a-novel-hdac-pi3k-dual-inhibitor
#17
Ken Saijo, Hiroo Imai, Sonoko Chikamatsu, Koichi Narita, Tadashi Katoh, Chikashi Ishioka
Histone deacetylase (HDAC)/phosphatidylinositol 3-kinase (PI3K) dual inhibition is a promising strategy for the treatment of intractable cancers because of the advantages of overcoming potential resistance and exhibiting synergistic effects. Therefore, development of an HDAC/PI3K dual inhibitor is reasonably attractive. Romidepsin (FK228, depsipeptide) is a potent HDAC inhibitor. We have previously reported that depsipeptide and its analogs have an additional activity as PI3K inhibitors and are defined as HDAC/PI3K dual inhibitors...
April 12, 2017: Cancer Science
https://www.readbyqxmd.com/read/28404896/retargeting-of-t-lymphocytes-to-psca-or-psma-positive-prostate-cancer-cells-using-the-novel-modular-chimeric-antigen-receptor-platform-technology-unicar
#18
Anja Feldmann, Claudia Arndt, Ralf Bergmann, Simon Loff, Marc Cartellieri, Dominik Bachmann, Roberta Aliperta, Mirjam Hetzenecker, Florian Ludwig, Susann Albert, Pauline Ziller-Walter, Alexandra Kegler, Stefanie Koristka, Sebastian Gärtner, Marc Schmitz, Armin Ehninger, Gerhard Ehninger, Jens Pietzsch, Jörg Steinbach, Michael Bachmann
New treatment options especially of solid tumors including for metastasized prostate cancer (PCa) are urgently needed. Recent treatments of leukemias with chimeric antigen receptors (CARs) underline their impressive therapeutic potential. However CARs currently applied in the clinics cannot be repeatedly turned on and off potentially leading to severe life threatening side effects. To overcome these problems, we recently described a modular CAR technology termed UniCAR: UniCAR T cells are inert but can be turned on by application of one or multiple target modules (TMs)...
February 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28403781/design-synthesis-and-biological-evaluation-of-novel-1-3-thiazolidine-2-4-diones-as-anti-prostate-cancer-agents
#19
Ramakrishnan Elancheran, Kuppusamy Saravanan, Selvaraj Divakar, Sima Kumari, V Lenin Maruthanila, Senthamarikannan Kabilan, Muthaiah Ramanathan, Rajlakshmi Devi, Jibon Kotoky
Androgen receptor (AR) is an attractive target for the treatment of prostate cancer. Structural modification and molecular docking-based virtual screening approaches were imposed to identify the novel 1,3-thiazolidine-2,4-diones (TZDs) by using Schrödinger (Maestro 9.5). The best fit molecules (3-12 & 23-31) were synthesized and characterized using spectroscopic techniques, then in vitro antioxidant and anti-prostate cancer activities were evaluated. Further, the structure of the intermediate (18) was confirmed by single crystal XRD analysis...
April 12, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28391357/phase-i-iia-clinical-trial-of-a-novel-htert-peptide-vaccine-in-men-with-metastatic-hormone-naive-prostate-cancer
#20
Wolfgang Lilleby, Gustav Gaudernack, Paal F Brunsvig, Ljiljana Vlatkovic, Melanie Schulz, Kate Mills, Knut Håkon Hole, Else Marit Inderberg
In newly diagnosed metastatic hormone-naive prostate cancer (mPC), telomerase-based immunotherapy with the novel hTERT peptide vaccine UV1 can induce immune responses with potential clinical benefit. This phase I dose escalation study of UV1 evaluated safety, immune response, effects on prostate-specific antigen (PSA) levels, and preliminary clinical outcome. Twenty-two patients with newly diagnosed metastatic hormone-naïve PC (mPC) were enrolled; all had started androgen deprivation therapy and had no visceral metastases...
April 8, 2017: Cancer Immunology, Immunotherapy: CII
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