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https://www.readbyqxmd.com/read/29243324/validation-of-histone-deacetylase-3-as-a-therapeutic-target-in-castration-resistant-prostate-cancer
#1
Abigail B McLeod, James P Stice, Suzanne E Wardell, Holly M Alley, Ching-Yi Chang, Donald P McDonnell
BACKGROUND: Whereas the androgen receptor (AR) signaling axis remains a therapeutic target in castration-resistant prostate cancer (CRPC), the emergence of AR mutations and splice variants as mechanisms underlying resistance to contemporary inhibitors of this pathway highlights the need for new therapeutic approaches to target this disease. Of significance in this regard is the considerable preclinical data, indicating that histone deacetylase (HDAC) inhibitors may have utility in the treatment of CRPC...
December 15, 2017: Prostate
https://www.readbyqxmd.com/read/29238201/diagnostic-significance-of-circulating-long-noncoding-rna-pcat6-in-patients-with-non-small-cell-lung-cancer
#2
Li Wan, Lin Zhang, Kai Fan, Jian-Jun Wang
Aim: We have previously shown that the long noncoding RNA prostate cancer-associated transcript 6 (PCAT6) promoted the proliferation and invasion of lung adenocarcinoma (LUAD) cells. In this study, the diagnostic significance of tissue and serum PCAT6 was evaluated in non-small cell lung cancer (NSCLC). Materials and methods: Tissue expression of PCAT6 was systematically evaluated in five Gene Expression Omnibus datasets (GSE19804, GSE18842, GSE30219, GSE19188, and GSE27262)...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29236331/reduction-of-histone-marks-h3k9me3-and-h3k27me3-by-epidrug-induces-neuroendocrine-differentiation-in-prostate-cancer
#3
Eunsohl Lee, Jingcheng Wang, Younghun Jung, Frank C Cackowski, Russell S Taichman
Neuroendocrine prostate cancer (NE PCa) is an aggressive malignancy, often presenting with advanced metastasis. We previously reported that reduction of histone marks regulated by DNMT1 following epidrug (5-Azacitidine, 5-Aza) treatment controls induction of epithelial to mesenchymal (EMT) and a cancer stem cell (CSC) phenotype, which facilitates tumorigenesis in PCa cells. Here, we use the epidrug 5-Aza as a model for how histone marks may regulate the reprogramming of prostate adenocarcinoma into NE phenotypic cells...
December 13, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29232796/-four-cases-of-bacteremia-caused-by-helicobacter-cinaedi-in-the-urological-ward-at-about-the-same-time
#4
Yoshiki Hiyama, Satoshi Takahashi, Naotaka Nishiyama, Mami Nakae, Satoshi Fujii, Masaaki Shinagawa, Naoya Masumori
Here we report the outbreak of bacteremia caused by Helicobacter cinaedi (H. cinaedi) in the urology ward. Case 1 was a man in his seventies with prostate cancer. Bacteremia caused by H. cinaedi developed 6 days after robot-assisted radical prostatectomy. Case 2 was a man in his sixties with small cell carcinoma of the prostate. Bacteremia developed at 5 days of docetaxel therapy. Case 3 was a man in his fifties with left renal pelvis carcinoma. Bacteremia developed 3 days after laparoscopic left nephroureterectomy...
November 2017: Hinyokika Kiyo. Acta Urologica Japonica
https://www.readbyqxmd.com/read/29230043/nanoparticle-orientation-to-control-rna%C3%A2-loading-and-ligand-display-on-extracellular-vesicles-for-cancer-regression
#5
Fengmei Pi, Daniel W Binzel, Tae Jin Lee, Zhefeng Li, Meiyan Sun, Piotr Rychahou, Hui Li, Farzin Haque, Shaoying Wang, Carlo M Croce, Bin Guo, B Mark Evers, Peixuan Guo
Nanotechnology offers many benefits, and here we report an advantage of applying RNA nanotechnology for directional control. The orientation of arrow-shaped RNA was altered to control ligand display on extracellular vesicle membranes for specific cell targeting, or to regulate intracellular trafficking of small interfering RNA (siRNA) or microRNA (miRNA). Placing membrane-anchoring cholesterol at the tail of the arrow results in display of RNA aptamer or folate on the outer surface of the extracellular vesicle...
December 11, 2017: Nature Nanotechnology
https://www.readbyqxmd.com/read/29230006/platinum-sensitivity-in-metastatic-prostate-cancer-does-histology-matter
#6
Michael S Humeniuk, Rajan T Gupta, Patrick Healy, Megan McNamara, Sundhar Ramalingam, Michael Harrison, Daniel George, Tian Zhang, Yuan Wu, Andrew J Armstrong
BACKGROUND: Platinum-based chemotherapy is effective in men with neuroendocrine prostate cancer (NEPC), but it is unclear whether histology (adenocarcinoma vs. non-adenocarcinoma NEPC variants) is predictive of platinum sensitivity. Given that NEPC exists as a spectrum, there may be men with adenocarcinoma who might benefit from platinum chemotherapy, particularly those men with DNA repair defects. METHODS: This was a retrospective study of all of the men seen at Duke University since 2005 who had metastatic castration-resistant prostate cancer (mCRPC) and were treated with a platinum agent...
December 11, 2017: Prostate Cancer and Prostatic Diseases
https://www.readbyqxmd.com/read/29229583/integrative-genomic-analysis-of-coincident-cancer-foci-implicates-ctnnb1-and-pten-alterations-in-ductal-prostate-cancer
#7
Marc Gillard, Justin Lack, Andrea Pontier, Divya Gandla, David Hatcher, Adam G Sowalsky, Jose Rodriguez-Nieves, Donald Vander Griend, Gladell Paner, David VanderWeele
BACKGROUND: Ductal adenocarcinoma of the prostate is an aggressive subtype, with high rates of biochemical recurrence and overall poor prognosis. It is frequently found coincident with conventional acinar adenocarcinoma. The genomic features driving evolution to its ductal histology and the biology associated with its poor prognosis remain unknown. OBJECTIVE: To characterize genomic features distinguishing ductal adenocarcinoma from coincident acinar adenocarcinoma foci from the same patient...
December 8, 2017: European Urology Focus
https://www.readbyqxmd.com/read/29228680/long-noncoding-rna-miat-promotes-non-small-cell-lung-cancer-proliferation-and-metastasis-through-mmp9-activation
#8
I-Lu Lai, Chin-An Yang, Pei-Chin Lin, Wen-Ling Chan, Ya-Ting Lee, Ju-Chen Yen, Ya-Sian Chang, Jan-Gowth Chang
Long noncoding RNAs (lncRNAs) play crucial roles in carcinogenesis. Myocardial infarction-associated transcript (MIAT), originally isolated as a candidate gene for myocardial infarction, has been found to act as an oncogene in chronic lymphocytic leukaemias and neuroendocrine prostate cancer (NEPC); however, little is known about its expression pattern, biological function, and underlying mechanism in non-small cell lung cancer (NSCLC). In this study, we observed that MIAT expression was upregulated in NSCLC, and its overexpression was associated with advanced tumor stage...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228644/exosomes-in-diagnosis-and-therapy-of-prostate-cancer
#9
REVIEW
Jun Pan, Meng Ding, Kai Xu, Chunhua Yang, Li-Jun Mao
Exosomes are small vesicular bodies released by a variety of cells. Exosomes contain miRNAs, mRNAs and proteins with the potential to regulate signaling pathways in recipient cells. Exosomes deliver nucleic acids and proteins to mediate the communication between cancer cells and stroma cells. In this review, we summarize recent progress in our understanding of the role of exosomes in prostate cancer. The tumorigenesis, metastasis and drug resistance of prostate cancer are associated with the cargos of exosomes such as miRNAs, lncRNAs and proteins...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29223029/design-synthesis-and-evaluation-of-novel-n-hydroxybenzamides-n-hydroxypropenamides-incorporating-quinazolin-4-3h-ones-as-histone-deacetylase-inhibitors-and-antitumor-agents
#10
Doan Thanh Hieu, Duong Tien Anh, Nguyen Minh Tuan, Pham-The Hai, Le-Thi-Thu Huong, Jisung Kim, Jong Soon Kang, Tran Khac Vu, Phan Thi Phuong Dung, Sang-Bae Han, Nguyen-Hai Nam, Nguyen-Dang Hoa
In our search for novel small molecules targeting histone deacetylases, we have designed and synthesized several series of novel N-hydroxybenzamides/N-hydroxypropenamides incorporating quinazolin-4(3H)-ones (4a-h, 8a-d, 10a-d). Biological evaluation showed that these hydroxamic acids were generally cytotoxic against three human cancer cell lines (SW620, colon; PC-3, prostate; NCI-H23, lung cancer). It was found that the N-hydroxypropenamides (10a-d) were the most potent, both in term of HDAC inhibition and cytotoxicity...
December 5, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/29221985/hotair-mediated-reciprocal-regulation-of-ezh2-and-dnmt1-contribute-to-polyphyllin-i-inhibited-growth-of-castration-resistant-prostate-cancer-cells-in-vitro-and-in-vivo
#11
SongTao Xiang, PeiLiang Zou, Qing Tang, Fang Zheng, JingJing Wu, ZhiQiang Chen, Swei Sunny Hann
BACKGROUND: Polyphyllin I (PPI), one of the steroidal saponins in paris polyphylla, has been reported to exhibit antitumor effects. However, the detailed molecular mechanism underlying this has not been elucidated. METHODS: Cell viability and cell cycle distribution were measured using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and Flow cytometry assays, respectively. Cell invasion and migration were examined by Transwell invasion and wound healing assays...
December 5, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29206995/concordance-of-circulating-tumor-dna-and-matched-metastatic-tissue-biopsy-in-prostate-cancer
#12
Alexander W Wyatt, Matti Annala, Rahul Aggarwal, Kevin Beja, Felix Feng, Jack Youngren, Adam Foye, Paul Lloyd, Matti Nykter, Tomasz M Beer, Joshi J Alumkal, George V Thomas, Robert E Reiter, Matthew B Rettig, Christopher P Evans, Allen C Gao, Kim N Chi, Eric J Small, Martin E Gleave
Background: Real-time knowledge of the somatic genome can influence management of patients with metastatic castration-resistant prostate cancer (mCRPC). While routine metastatic tissue biopsy is challenging in mCRPC, plasma circulating tumor DNA (ctDNA) has emerged as a minimally invasive tool to sample the tumor genome. However, no systematic comparisons of matched "liquid" and "solid" biopsies have been performed that would enable ctDNA profiling to replace the need for direct tissue sampling...
December 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29196555/ral-gtpases-biology-and-potential-as-therapeutic-targets-in-cancer
#13
REVIEW
Chao Yan, Dan Theodorescu
More than a hundred proteins comprise the RAS superfamily of small GTPases. This family can be divided into RAS, RHO, RAB, RAN, ARF, and RAD subfamilies, with each shown to play distinct roles in human cells in both health and disease. The RAS subfamily has a well-established role in human cancer with the three genes, HRAS, KRAS, and NRAS being the commonly mutated in tumors. These RAS mutations, most often functionally activating, are especially common in pancreatic, lung, and colorectal cancers. Efforts to inhibit RAS and related GTPases have produced inhibitors targeting the downstream effectors of RAS signaling, including inhibitors of the RAF-mitogen-activated protein kinase/extracellular signal-related kinase (ERK)-ERK kinase pathway and the phosphoinositide-3-kinase-AKT-mTOR kinase pathway...
January 2018: Pharmacological Reviews
https://www.readbyqxmd.com/read/29189002/discovery-of-novel-potent-vegfr-2-inhibitors-exerting-significant-antiproliferative-activity-against-cancer-cell-lines
#14
Yanmin Zhang, Yadong Chen, Danfeng Zhang, Lu Wang, Tao Lu, Yu Jiao
Computational and experimental studies were applied to the discovery of a series of novel vascular endothelial growth factor receptor 2 (VEGFR-2) inhibitors. Eight compounds exhibited nanomolar IC50 values against VEGFR-2 and compounds 1, 3, 8 and 9 showed potent antiproliferative effects against several cell lines. Particularly, compound 9 behaved better than FDA approved drugs, sorafenib and sunitinib, in antiproliferative activity against cell lines related to all nine tumor types tested (GI50 values), and it was better or comparable in safety (LC50 values)...
November 30, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29184058/doxycycline-induces-apoptosis-via-er-stress-selectively-to-cells-with-a-cancer-stem-cell-like-properties-importance-of-stem-cell-plasticity
#15
Takashi Matsumoto, Takeshi Uchiumi, Keisuke Monji, Mikako Yagi, Daiki Setoyama, Rie Amamoto, Yuichi Matsushima, Masaki Shiota, Masatoshi Eto, Dongchon Kang
Tumor heterogeneity can be traced back to a small subset of cancer stem cells (CSCs), which can be derived from a single stem cell and show chemoresistance. Recent studies showed that CSCs are sensitive to mitochondrial targeting antibiotics such as doxycycline. However, little is known about how cancer cells undergo sphere formation and how antibiotics inhibit CSC proliferation. Here we show that under sphere-forming assay conditions, prostate cancer cells acquired CSC-like properties: promoted mitochondrial respiratory chain activity, expression of characteristic CSC markers and resistance to anticancer agents...
November 29, 2017: Oncogenesis
https://www.readbyqxmd.com/read/29181435/organoid-culture-of-human-prostate-cancer-cell-lines-lncap-and-c4-2b
#16
Lin Ma, Jingwu Li, Qiang Nie, Qiuyang Zhang, Sen Liu, Dongxia Ge, Zongbing You
Organoids mimic the architecture and functions of a small organ. Organoid culture technique has been rapidly accepted by all research communities during the past decade to study stem cells, organ development and function, and patient-specific diseases. A protocol for organoid culture of human and mouse prostate epithelial and cancer tissues has been reported. However, organoid culture of the commonly used human prostate cancer cell lines has yet to be established. We followed the published protocol and performed organoid culture of LNCaP and C4-2B cells in MatrigelTM and organoid culture medium for 14 days...
2017: American Journal of Clinical and Experimental Urology
https://www.readbyqxmd.com/read/29180476/a-potent-metabolically-stable-tubulin-inhibitor-targets-the-colchicine-binding-site-and-overcomes-taxane-resistance
#17
Kinsie E Arnst, Yuxi Wang, Dong-Jin Hwang, Yi Xue, Terry Costello, David Hamilton, Qiang Chen, Jinliang Yang, Frank Park, James T Dalton, Duane D Miller, Wei Li
Antimitotics that target tubulin are among the most useful chemotherapeutic drugs, but their clinical activity is often limited by the development of multidrug resistance. We recently discovered the novel small molecule DJ101 as a potent and metabolically stable tubulin inhibitor that can circumvent the drug efflux pumps responsible for multidrug resistance of existing tubulin inhibitors. In this study, we determined the mechanism of action of this drug. The basis for its activity was illuminated by solving the crystal structure of DJ101 in complex with tubulin at a resolution of 2...
November 27, 2017: Cancer Research
https://www.readbyqxmd.com/read/29167690/synchronous-gists-associated-with-multiple-sporadic-tumors-a-case-report
#18
Danila Comandini, Azzurra Damiani, Alessandro Pastorino
Gastrointestinal stromal tumors (GISTs) are rare neoplasms, but they also represent the most common mesenchymal tumors of the gastrointestinal tract originating from the cell of Cajal. GIST incidence ranges around 1% of all gastrointestinal malignancies. Approximately 5% of all GISTs have a hereditary etiology. The remaining 95% of GISTs are considered sporadic events, with up to 75% of cases driven by a constitutional activation of the c-KIT proto-oncogene. GISTs are generally solitary lesions. Nonetheless, multiple sporadic GISTs can occur and present as synchronous or metachronous tumors, usually associated with familial GIST...
2017: Drugs in Context
https://www.readbyqxmd.com/read/29163708/mir-20b-promotes-cellular-proliferation-and-migration-by-directly-regulating-phosphatase-and-tensin-homolog-in-prostate-cancer
#19
Ju Guo, Zewen Xiao, Xingwei Yu, Runfu Cao
MicroRNAs are small non-coding RNAs, which are critical regulators of carcinogenesis and tumor progression. Previous studies have identified that microRNA-20b (miR-20b) acts as an oncogene in numerous cancers. However, the role of miR-20b in prostate cancer remains unclear. The present study aimed to investigate the expression of miR-20b in prostate cancer and to examine whether modulating miR-20b expression impacts prostate cancer cellular proliferation and migration. It was revealed that miR-20b was strongly expressed in prostate cancer tissues compared with adjacent normal prostate tissues (P<0...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29163701/high-levels-of-depdc1b-predict-shorter-biochemical-recurrence-free-survival-of-patients-with-prostate-cancer
#20
Shoumin Bai, Ting Chen, Tao Du, Xianju Chen, Yiming Lai, Xiaoming Ma, Wanhua Wu, Chunhao Lin, Leyuan Liu, Hai Huang
DEP domain-containing protein 1B (DEPDC1B) has been reported to serve important functions in breast cancer and non-small cell lung cancer. However, its involvement in the development of prostate cancer (PCa) remains unclear. Therefore, the present study aimed to investigate the expression and clinical significance of DEPDC1B in tumor tissues from patients diagnosed with PCa. A total of 80 prostate tissue samples were collected following prostatectomy to generate a tissue microarray for immunohistochemical analysis of DEPDC1B protein expression...
December 2017: Oncology Letters
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