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https://www.readbyqxmd.com/read/29778948/bioisosteres-of-ethyl-8-ethynyl-6-pyridin-2-yl-4h-benzo-f-imidazo-1-5-a-1-4-diazepine-3-carboxylate-hz-166-as-novel-alpha-2-3-selective-potentiators-of-gaba-a-receptors-improved-bioavailability-enhances-anticonvulsant-efficacy
#1
J M Witkin, J L Smith, X Ping, S D Gleason, M M Poe, G Li, X Jin, J Hobbs, J M Schkeryantz, J S McDermott, A I Alatorre, J N Siemian, J W Cramer, D C Airey, K R Methuku, V V N P B Tiruveedhula, T M Jones, J Crawford, M J Krambis, J L Fisher, J M Cook, R Cerne
HZ-166 has previously been characterized as an α2,3-selective GABAA receptor modulator with anticonvulsant, anxiolytic, and anti-nociceptive properties but reduced motor effects. We discovered a series of ester bioisosteres with reduced metabolic liabilities, leading to improved efficacy as anxiolytic-like compounds in rats. In the present study, we evaluated the anticonvulsant effects KRM-II-81 across several rodent models. In some models we also evaluated key structural analogs. KRM-II-81 suppressed hyper-excitation in a network of cultured cortical neurons without affecting the basal neuronal activity...
May 3, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29778349/a-contemporary-prostate-biopsy-risk-calculator-based-on-multiple-heterogeneous-cohorts
#2
Donna P Ankerst, Johanna Straubinger, Katharina Selig, Lourdes Guerrios, Amanda De Hoedt, Javier Hernandez, Michael A Liss, Robin J Leach, Stephen J Freedland, Michael W Kattan, Robert Nam, Alexander Haese, Francesco Montorsi, Stephen A Boorjian, Matthew R Cooperberg, Cedric Poyet, Emily Vertosick, Andrew J Vickers
BACKGROUND: Prostate cancer prediction tools provide quantitative guidance for doctor-patient decision-making regarding biopsy. The widely used online Prostate Cancer Prevention Trial Risk Calculator (PCPTRC) utilized data from the 1990s based on six-core biopsies and outdated grading systems. OBJECTIVE: We prospectively gathered data from men undergoing prostate biopsy in multiple diverse North American and European institutions participating in the Prostate Biopsy Collaborative Group (PBCG) in order to build a state-of-the-art risk prediction tool...
May 16, 2018: European Urology
https://www.readbyqxmd.com/read/29776408/pre-and-intra-operative-predictors-of-postoperative-hospital-length-of-stay-in-patients-undergoing-radical-prostatectomy-for-prostate-cancer-in-china-a-retrospective-observational-study
#3
Qingmei Huang, Ping Jiang, Lina Feng, Liping Xie, Shuo Wang, Dan Xia, Baihua Shen, Baiye Jin, Li Zheng, Wei Wang
BACKGROUND: Hospital length of stay (LOS) has recently been receiving increasing attention as a marker of medical resource consumption. Identifying predictors of longer LOS can better equip doctors to counsel patients and facilitate more efficient patient flow and utilization of medical resources. The objective of this study was to identify pre- and intra-operative risk factors for postoperative hospital LOS in patients who had undergone radical prostatectomy in China. METHODS: We retrospectively analyzed data of 793 eligible patients with prostate cancer who had undergone radical prostatectomy in our institution between January 2011 and March 2016...
May 18, 2018: BMC Urology
https://www.readbyqxmd.com/read/29775158/microrna-expression-in-tumour-tissue-and-plasma-in-patients-with-newly-diagnosed-metastatic-prostate-cancer
#4
Ahmed Hussein Zedan, Torben Frøstrup Hansen, Jannie Assenholt, Mindaugas Pleckaitis, Jonna Skov Madsen, Palle Jörn Sloth Osther
Prostate cancer is the most common cancer among men in the western world. Clinical practice is continuously challenged by the pitfalls of the available diagnostic tools. microRNAs may represent promising biomarkers in many types of human cancers, including prostate cancer. The aim of this study was to investigate microRNA expression in tumour tissue and matched plasma in a cohort of patients with primary metastatic prostate cancer. The relative expression of 12 microRNAs was assessed in diagnostic needle biopsies from the prostate and matched plasma samples in two prospective cohorts (screening cohorts) comprising 21 patients with metastatic prostate cancer and 25 control patients...
May 2018: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/29773955/survival-outcomes-of-radical-prostatectomy-and-external-beam-radiotherapy-in-clinically-localized-high-risk-prostate-cancer-a-population-based-propensity-score-matched-study
#5
Xiaobin Gu, Xianshu Gao, Ming Cui, Mu Xie, Mingwei Ma, Shangbin Qin, Xiaoying Li, Xin Qi, Yun Bai, Dian Wang
Objective: This study was aimed to compare survival outcomes in high-risk prostate cancer (PCa) patients receiving external beam radiotherapy (EBRT) or radical prostatectomy (RP). Materials and methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify PCa patients with high-risk features who received RP alone or EBRT alone from 2004 to 2008. Propensity-score matching (PSM) was performed. Kaplan-Meier survival analysis was used to compare cancer-specific survival (CSS) and overall survival (OS)...
2018: Cancer Management and Research
https://www.readbyqxmd.com/read/29773186/association-between-cadmium-and-androgen-receptor-protein-expression-differs-in-prostate-tumors-of-african-american-and-european-american-men
#6
Christine M Neslund-Dudas, Russell B McBride, Ashoka Kandegedara, Benjamin A Rybicki, Oleksandr N Kryvenko, Dhananjay Chitale, Nilesh Gupta, Sean R Williamson, Craig G Rogers, Carlos Cordon-Cardo, Andrew G Rundle, Albert M Levin, Q Ping Dou, Bharati Mitra
Cadmium is a known carcinogen that has been implicated in prostate cancer, but how it affects prostate carcinogenesis in humans remains unclear. Evidence from basic science suggests that cadmium can bind to the androgen receptor causing endocrine disruption. The androgen receptor is required for normal prostate development and is the key driver of prostate cancer progression. In this study, we examined the association between cadmium content and androgen receptor protein expression in prostate cancer tissue of African American (N = 22) and European American (N = 30) men...
July 2018: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/29772102/novel-nomograms-for-castration-resistant-prostate-cancer-and-survival-outcome-in-patients-with-de-novo-bone-metastatic-prostate-cancer
#7
Jinge Zhao, Guangxi Sun, Banghua Liao, Xingming Zhang, Cameron M Armstrong, Xiaoxue Yin, Jiandong Liu, Junru Chen, Yaojing Yang, Peng Zhao, Qidun Tang, Zhenghao Wang, Zhibin Chen, Xiong Li, Qiang Wei, Xiang Li, Ni Chen, Allen C Gao, Pengfei Shen, Hao Zeng
OBJECTIVES: To develop nomograms predicting the incidence of castration resistant prostate cancer (CRPC) and overall survival (OS) for de novo metastatic prostate cancer (mPCa). MATERIALS AND METHODS: Data from 449 de novo mPCa patients were retrospectively analyzed. Patients were randomly divided into the training (n=314, 70%) and validation cohort (n=135, 30%). Predictive factors were selected by Cox-proportional model and further used for building predictive models...
May 17, 2018: BJU International
https://www.readbyqxmd.com/read/29769196/an-in-vivo-screen-identifies-pygo2-as-a-driver-for-metastatic-prostate-cancer
#8
Xin Lu, Xiaolu Pan, Chang-Jiun Wu, Di Zhao, Shan Feng, Yong Zang, Rumi Lee, Sunada Khadka, Samirkumar B Amin, Eun-Jung Jin, Xiaoying Shang, Pingna Deng, Yanting Luo, William R Morgenlander, Jacqueline Weinrich, Xuemin Lu, Shan Jiang, Qing Chang, Nora M Navone, Patricia Troncoso, Ronald A DePinho, Y Alan Wang
Advanced prostate cancer displays conspicuous chromosomal instability and rampant copy number aberrations, yet the identity of functional drivers resident in many amplicons remain elusive. Here, we implemented a functional genomics approach to identify new oncogenes involved in prostate cancer progression. Through integrated analyses of focal amplicons in large prostate cancer genomic and transcriptomic datasets as well as genes upregulated in metastasis, 276 putative oncogenes were enlisted into an in vivo gain-of-function tumorigenesis screen...
May 16, 2018: Cancer Research
https://www.readbyqxmd.com/read/29764515/long-term-outcome-of-a-moderately-hypofractionated-intensity-modulated-radiotherapy-approach-using-an-endorectal-balloon-for-patients-with-localized-prostate-cancer
#9
Bin S Teh, Gary D Lewis, Weiyuan Mai, Ramiro Pino, Hiromichi Ishiyama, Edward Brian Butler
BACKGROUND: Technical advances in radiotherapy delivery have simultaneously enabled dose escalation and enhanced bladder and rectal sparing. However, the optimal radiation fractionation regimen for localized prostate cancer is unclear. Laboratory and clinical evidence suggest that hypofractionation may improve the therapeutic ratio of radiotherapy. We report our institutional outcomes using moderately hypofractionated, intensity-modulated radiotherapy (IMRT), and an endorectal balloon, with emphasis on long-term biochemical control and treatment-related adverse events in patients with localized prostate cancer...
April 17, 2018: Cancer communications
https://www.readbyqxmd.com/read/29762048/theranostics-of-prostate-cancer-from-molecular-imaging-to-precision-molecular-radiotherapy-targeting-the-prostate-specific-membrane-antigen
#10
Harshad R Kulkarni, Aviral Singh, Thomas Langbein, Christiane Schuchardt, Dirk Mueller, Jingjing Zhang, Coline Lehmann, Richard P Baum
Alterations at the molecular level are a hallmark of cancer. Prostate cancer is associated with the overexpression of prostate specific membrane antigen (PSMA) in a majority of cases, predominantly in advanced tumors, increasing with the grade or Gleason's score. PSMA can be selectively targeted using radiolabelled PSMA ligands. These small molecules binding the PSMA can be radiolabelled with gamma-emitters like 99m Tc and 111 In or positron emitters like 68 Ga and 18 F for diagnosis as well as with their theranostic pairs such as 177 Lu (beta-emitter) or 225 Ac (alpha-emitter) for therapy...
May 15, 2018: British Journal of Radiology
https://www.readbyqxmd.com/read/29762037/growth-rate-and-cross-linking-kinetics-of-poly-divinyl-benzene-thin-films-formed-via-initiated-chemical-vapor-deposition
#11
Priya Moni, Alan C Mohr, Karen K Gleason
Initiated chemical vapor deposition (iCVD) allows for the formation of highly cross-linked, polymer thin films on a variety of substrates. Here we study the impact of substrate stage temperature and filament temperature on the deposition and crosslinking characteristics of iCVD from divinyl benzene (DVB). Maintaining a constant monomer surface concentration reveals that deposition rates upwards of 15 nm/min can be achieved at substrate stage temperatures of 50 °C. The degree-of-crosslinking is limited by the rate of initiation of the pendant vinyl bonds...
May 15, 2018: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/29761841/prkar2b-promotes-prostate-cancer-metastasis-by-activating-wnt-%C3%AE-catenin-and-inducing-epithelial-mesenchymal-transition
#12
Jianjun Sha, Qing Han, Chenfei Chi, Yinjie Zhu, Jiahua Pan, Baijun Dong, Yiran Huang, Weiliang Xia, Wei Xue
Castration-resistant prostate cancers (CRPC) that occur after the failure of androgen-blocking therapies cause most of the deaths in prostate cancer (PCa) patients. In a previous study we identified that PRKAR2B expression is upregulated in CRPC and possesses potentials to develop CRPC. Here we further investigated the underlying mechanism of PRKAR2B in regulating prostate cancer metastasis. We established an androgen-independent LNCaPcell line (LNCaP-AI), and investigated the function of PRKAR2B on regulating cell invasion in vitro and in vivo...
May 15, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29761525/ets2-is-a-prostate-basal-cell-marker-and-is-highly-expressed-in-prostate-cancers-aberrantly-expressing-p63
#13
Alba Torres, Mohammed Alshalalfa, Elai Davicioni, Anuj Gupta, Srinivasan Yegnasubramanian, Sarah J Wheelan, Jonathan I Epstein, Angelo M De Marzo, Tamara L Lotan
BACKGROUND: Rare prostate carcinomas aberrantly express p63 and have an immunophenotype intermediate between basal and luminal cells. Here, we performed gene expression profiling on p63-expressing prostatic carcinomas and compared them to usual-type adenocarcinoma. We identify ETS2 as highly expressed in p63-expressing prostatic carcinomas and benign prostate basal cells, with lower expression in luminal cells and primary usual-type adenocarcinomas. METHODS: A total of 8 p63-expressing prostate carcinomas at radical prostatectomy were compared to 358 usual-type adenocarcinomas by gene expression profiling performed on formalin fixed paraffin embedded tumor tissue using Affymetrix 1...
May 15, 2018: Prostate
https://www.readbyqxmd.com/read/29760417/ndrg3-lowers-the-metastatic-potential-in-prostate-cancer-as-a-feedback-controller-of-hypoxia-inducible-factors
#14
Ga Young Lee, Seung-Hyun Shin, Hyun-Woo Shin, Yang-Sook Chun, Jong-Wan Park
Expression of hypoxia-inducible factors (HIFs) and N-myc downstream-regulated gene 3 (NDRG3) are oxygen-dependently regulated by prolyl hydroxylase domain (PHD) enzymes. Little is known about the role of NDRG3 in the cellular adaptation to hypoxia, whereas the roles of HIFs are well understood. In this study, we investigated how NDRG3 affects the hypoxic response in prostate cancer cells. Compared with HIF-1α, hypoxic induction of NDRG3 was observed at a later phase. NDRG3 reduced hypoxic expression of HIF-1α by inhibiting AKT-driven translation of HIF1A mRNA...
May 14, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29758220/evaluation-of-an-aggressive-prostate-biopsy-strategy-in-men-younger-than-50-years-of-age
#15
Hanan Goldberg, Zachary Klaassen, Thenappan Chandrasekar, Christopher J D Wallis, Ants Toi, Rashid Sayyid, Bimal Bhindi, Michael Nesbitt, Andrew Evans, Theo van der Kwast, Joan Sweet, Nathan Perlis, Robert J Hamilton, Girish S Kulkarni, Antonio Finelli, Alexandre Zlotta, Neil Fleshner
INTRODUCTION: Longitudinal cohort studies and guidelines demonstrate that PSA ≥1 ng/mL in younger patients confer an increased risk of delayed prostate cancer (PC) death. In our institution we have used an aggressive biopsy strategy among younger patients with PSA of>1 ng/ml. Our objective was to determine the proportion of detected cancer and specifically, clinical significant cancer, with this strategy. METHODS: The prostate biopsy (PB) database at Princess Margaret Cancer Centre was queried for patients younger than 50 who underwent a first PB between 2000 and 2016...
May 11, 2018: Journal of Urology
https://www.readbyqxmd.com/read/29756850/search-for-invisible-axion-dark-matter-with-the-axion-dark-matter-experiment
#16
N Du, N Force, R Khatiwada, E Lentz, R Ottens, L J Rosenberg, G Rybka, G Carosi, N Woollett, D Bowring, A S Chou, A Sonnenschein, W Wester, C Boutan, N S Oblath, R Bradley, E J Daw, A V Dixit, J Clarke, S R O'Kelley, N Crisosto, J R Gleason, S Jois, P Sikivie, I Stern, N S Sullivan, D B Tanner, G C Hilton
This Letter reports the results from a haloscope search for dark matter axions with masses between 2.66 and 2.81  μeV. The search excludes the range of axion-photon couplings predicted by plausible models of the invisible axion. This unprecedented sensitivity is achieved by operating a large-volume haloscope at subkelvin temperatures, thereby reducing thermal noise as well as the excess noise from the ultralow-noise superconducting quantum interference device amplifier used for the signal power readout...
April 13, 2018: Physical Review Letters
https://www.readbyqxmd.com/read/29756298/primary-whole-gland-ablation-for-localized-prostate-cancer-with-high-intensity-focused-ultrasound-the-important-predictors-of-biochemical-recurrence
#17
Po Yen Chen, Po Hui Chiang, Yi Yang Liu, Yao Chi Chuang, Yuan Tso Cheng
OBJECTIVES: To identify predictive factors of biochemical recurrence for patients undergoing high-intensity focused ultrasound treatment for localized prostate cancer. METHODS: We retrospectively identified patients receiving whole-gland prostate ablation with high-intensity focused ultrasound for localized prostate cancer from 2009 to 2015. All the patients received pre-high-intensity focused ultrasound radical transurethral resection of the prostate. We included perioperative parameters as follows: age, preoperative prostate volume, stage of operation, initial prostate-specific antigen, T stage, postoperative prostate-specific antigen nadir, Gleason score, time to prostate-specific antigen nadir and the presence of prostate-specific antigen biochemical recurrence...
May 13, 2018: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/29755715/a-deep-belief-network-and-dempster-shafer-based-multiclassifier-for-the-pathology-stage-of-prostate-cancer
#18
Jae Kwon Kim, Mun Joo Choi, Jong Sik Lee, Jun Hyuk Hong, Choung-Soo Kim, Seong Il Seo, Chang Wook Jeong, Seok-Soo Byun, Kyo Chul Koo, Byung Ha Chung, Yong Hyun Park, Ji Youl Lee, In Young Choi
Object: Pathologic prediction of prostate cancer can be made by predicting the patient's prostate metastasis prior to surgery based on biopsy information. Because biopsy variables associated with pathology have uncertainty regarding individual patient differences, a method for classification according to these variables is needed. Method: We propose a deep belief network and Dempster-Shafer- (DBN-DS-) based multiclassifier for the pathologic prediction of prostate cancer...
2018: Journal of Healthcare Engineering
https://www.readbyqxmd.com/read/29755671/should-reporting-of-peri-neural-invasion-and-extra-prostatic-extension-be-mandatory-in-prostate-cancer-biopsies-correlation-with-outcome-in-biopsy-cases-treated-conservatively
#19
Amar S Ahmad, Vishnu Parameshwaran, Luis Beltran, Gabrielle Fisher, Bernard V North, David Greenberg, Geraldine Soosay, Henrik Møller, Peter Scardino, Jack Cuzick, Daniel M Berney
The identification of perineural invasion (PNI) and extraprostatic extension (ECE) in prostate cancer (PC) biopsies is time consuming and can be difficult. Although this is required information in many datasets, there is little evidence on their effect on outcome in patients treated conservatively. Cases of PC were identified from three cancer registries in the UK from men with clinically localized prostate cancer diagnosed by needle biopsy from 1990-2003. The endpoint was prostate cancer death (DOD). Patients treated radically within 6 months, those with objective evidence of metastases or who had prior hormone therapy were excluded...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29754790/aortic-clamping-strategy-and-postoperative-stroke
#20
Mohamad Alaeddine, Vinay Badhwar, Maria V Grau-Sepulveda, Lawrence M Wei, Chris C Cook, Michael E Halkos, Vinod H Thourani, Jeffrey P Jacobs, Roland Matsouaka, James Meza, Matthew Brennan, Thomas G Gleason, Danny Chu
OBJECTIVE: The effect of aortic clamping strategy on short-term stroke during proximal graft construction for coronary artery bypass grafting (CABG) remains undefined. The aim of this study was to test the hypothesis that partial occluding clamp (POC) technique does not increase incidence of postoperative stroke compared with single clamp (SC) technique for performing proximal coronary anastomoses. METHODS: We identified 52,611 patients who underwent on-pump CABG in the Society of Thoracic Surgeons Adult Cardiac Surgery Database from July 1, 2014 to March 31, 2015...
April 13, 2018: Journal of Thoracic and Cardiovascular Surgery
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