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Shuai Wang, Li-Jie Zhao, Yi-Chao Zheng, Dan-Dan Shen, Er-Fei Miao, Xue-Peng Qiao, Li-Juan Zhao, Ying Liu, Ruilei Huang, Bin Yu, Hong-Min Liu
A new series of [1,2,4]triazolo[1,5-a]pyrimidine-based LSD1 inhibitors were designed, synthesized, and further evaluated for their cytotoxicity against MGC-803, EC109, A549 and PC-9 cells as well as the ability of inhibiting LSD1. Some of these compounds showed potent inhibition toward LSD1 and selectively inhibited growth of A549 and PC-9 cells. Compound 6l potently inhibited growth of PC-9 cells (IC50 = 0.59 μM), about 4-fold more potent than 5-FU. Further SARs studies led to the identification of compounds 6l-m, which had good growth inhibition against all the tested cancer cell lines and were much more potent than 5-FU and GSK2879552...
October 14, 2016: European Journal of Medicinal Chemistry
E Faghihloo, Y Araei, M Mohammadi, H Mirzaei, H R Mohammadi, T Mokhtari-Azad
Gastric cancer is among the leading causes of cancer-related death, and the symptoms are commonly characterized in advanced stages. Histone acetylation is among the most important epigenetic alterations occurring during cancer development. In addition, reduced E-cadherin expression is a major contributor in the process of tumor cell invasion and metastasis. Oxamflatin is a histone deacetylase inhibitor that has been suggested as a promising anti-tumor agent; yet its effect on the viability and invasion of gastric tumor cells is unclear...
October 21, 2016: Cancer Gene Therapy
Rong-Hua Yang, Shao-Hai Qi, Shu-Bin Ruan, Ze-Peng Lin, Yan Lin, Feng-Gang Zhang, Xiao-Dong Chen, Ju-Lin Xie
Epidermal growth factor (EGF)-like family members mediate a wide range of biological activities including cell proliferation and migration. Increasing evidence indicated that EGF plays an important role in the process of wound healing by stimulating fibroblast motility. The aim of this study was to see whether EGF-like domain 7 (EGFL7)-overexpressing epidermal stem cells (EGFL7-ESCs) would promote fibroblast proliferation and migration. We found that mRNA and protein levels of EGFL7 expression were significantly increased in EGFL7-ESCs...
October 20, 2016: Molecular and Cellular Biochemistry
Xiaoyun Dai, Kwang Seok Ahn, Ling Zhi Wang, Chulwon Kim, Amudha Deivasigamni, Frank Arfuso, Jae-Young Um, Alan Prem Kumar, Young-Chae Chang, Dhiraj Kumar, Gopal C Kundu, Junji Magae, Boon Cher Goh, Kam Man Hui, Gautam Sethi
Increasing evidence(s) have indicated that epithelial to mesenchymal transition (EMT) at the advanced stage of liver cancer, not only has the ability to self-renew and progress cancer, but also enables greater resistance to conventional chemo- and radio-therapies. Here, we report that ascochlorin (ASC), an isoprenoid antibiotic could potentiate the cytotoxic effect of doxorubicin (DOX) on HCCLM3, SNU387, SNU49, and SK-Hep-1 hepatocellular carcinoma (HCC) cells, which had a predominantly mesenchymal signature with low expression of E-cadherin but high expression of N-cadherin...
October 7, 2016: Molecular Cancer Therapeutics
Verena Stahn, Inga Nagel, Susan Fischer-Huchzermeyer, Florian Oyen, Reinhard Schneppenheim, Stefan Gesk, Axel Bohring, Levan Chikobava, Peter Young, Burkhard Gess, Mathias Werner, Volker Senner, Anja Harder
Neurofibromas and schwannomas are benign Schwann cell-derived peripheral nerve sheath tumors arising sporadically and within neurofibromatoses. Multiple tumors are a hallmark of neurofibromatosis type 1 (NF1) and type 2 (NF2) and schwannomatosis. Neurofibromas in NF1 and schwannomas in NF2 or schwannomatosis are defined by distinctive molecular hits. Among these, multiple hybrid neurofibromas/schwannomas may also appear, not yet being defined by a molecular background. We therefore performed molecular analysis of 22 hybrid neurofibromas/schwannomas using array comparative genomic hybridization, immunohistochemistry, quantitative RT-PCR, and functional analyses of cultured Schwann cells...
October 17, 2016: American Journal of Pathology
Hui-Mei Lee, Vyomesh Patel, Lie-Fen Shyur, Wai-Leng Lee
BACKGROUND: Oral cancer is the sixth most common cancer worldwide and 90% of oral malignancies are caused by oral squamous cell carcinoma (OSCC). Curcumin, a phytocompound derived from turmeric (Curcuma longa) was observed to have anti-cancer activity which can be developed as an alternative treatment option for OSCC. However, OSCC cells with various clinical-pathological features respond differentially to curcumin treatment. HYPOTHESIS: Intracellular copper levels have been reported to correlate with tumor pathogenesis and affect the sensitivity of cancer cells to cytotoxic chemotherapy...
November 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Ishita Mukherjee, Abhijit Chakraborty, Saikat Chakrabarti
BACKGROUND: An active immune surveillance and a range of barriers to infection allow the host to effectively eliminate microbial pathogens. However, pathogens may use diverse strategies to subdue such host defences. For instance, one such mechanism is the use of leucine-rich repeat (LRR) proteins by pathogens (microbial) to cause infection. In this study, we aimed at identifying novel virulence factor(s) in Leishmania donovani, based on the possibility of lateral gene transfers of bacterial virulence factor(s) to L...
October 21, 2016: Parasites & Vectors
Vincent Le Coz, Chaobin Zhu, Aurore Devocelle, Aimé Vazquez, Claude Boucheix, Sandy Azzi, Cindy Gallerne, Pierre Eid, Séverine Lecourt, Julien Giron-Michel
Melanoma is a particularly virulent human cancer, due to its resistance to conventional treatments and high frequency of metastasis. Melanomas contain a fraction of cells, the melanoma-initiating cells (MICs), responsible for tumor propagation and relapse. Identification of the molecular pathways supporting MICs is, therefore, vital for the development of targeted treatments. One factor produced by melanoma cells and their microenvironment, insulin-like growth factor-1 (IGF- 1), is linked to epithelial-mesenchymal transition (EMT) and stemness features in several cancers...
October 18, 2016: Oncotarget
Kishore Polireddy, Ruochen Dong, Peter R McDonald, Tao Wang, Brendan Luke, Ping Chen, Melinda Broward, Anuradha Roy, Qi Chen
BACKGROUND: Pancreatic cancer has an enrichment of stem-like cancer cells (CSCs) that contribute to chemoresistant tumors prone to metastasis and recurrence. Drug screening assays based on cytotoxicity cannot identify specific CSC inhibitors, because CSCs comprise only a small portion of cancer cell population, and it is difficult to propagate stable CSC populations in vitro for high-throughput screening (HTS) assays. Based on the important role of cancer cell epithelial-to-mesenchymal transition (EMT) in promoting CSCs, we hypothesized that inhibition of EMT can be a useful strategy for inhibiting CSCs, and therefore a feasible approach for HTS can be built for identification of CSC inhibitors, based on assays detecting EMT inhibition...
2016: PloS One
Bette K Kleinschmidt-DeMasters
PURPOSE OF REVIEW: Most pituitary region masses are pituitary adenomas; however, when other sellar region masses are encountered by clinicians or pathologists, the differential diagnosis can be broad. This review will focus on updates for pituitary adenomas, as well as briefly discuss some of these other entities: Rathke cleft cyst, hypophysitis, craniopharyngioma, pituicytoma, and spindle cell oncocytoma. RECENT FINDINGS: The use of new immunohistochemical (IHC) tools for assessing transcription factors, pituitary transcription factor-1, steroidogenic factor-1, and the not-yet-widely available Tpit IHC have provided insights into origin particularly of clinically silent and even hormone-negative pituitary adenomas...
October 18, 2016: Current Opinion in Endocrinology, Diabetes, and Obesity
Shinnosuke Ikemura, Nao Aramaki, Satoshi Fujii, Keisuke Kirita, Shigeki Umemura, Shingo Matsumoto, Kiyotaka Yoh, Seiji Niho, Hironobu Ohmatsu, Takeshi Kuwata, Motohiro Kojima, Atsushi Ochiai, Tomoko Betsuyaku, Masahiro Tsuboi, Koichi Goto, Genichiro Ishii
Metastasis and growth in neoplastic lesions requires the multi-step regulation of microenvironmental factors. We aimed to elucidate the microenvironmental changes in the process of lymphatic metastasis of lung squamous cell carcinoma. We examined the morphological characteristics of 102 cases of Primary Tumor (PT), 50 of intralymphatic tumor (ILT), 51 of lymph node (LN) micrometastasis (LN-Mic; less than 2 mm in size) and 82 of LN macrometastasis (LN-Mac; greater than 10 mm in size). Afterwards we evaluated the expression of nine molecules (EGFR, FGFR2, CD44, ALDH1, Podoplanin, E-cadherin, S100A4, geminin and ezrin) in matched PT, ILT, LN-Mic and LN-Mac from 23 of these cases...
October 20, 2016: Cancer Science
Mark R Cronan, Rebecca W Beerman, Allison F Rosenberg, Joseph W Saelens, Matthew G Johnson, Stefan H Oehlers, Dana M Sisk, Kristen L Jurcic Smith, Neil A Medvitz, Sara E Miller, Le A Trinh, Scott E Fraser, John F Madden, Joanne Turner, Jason E Stout, Sunhee Lee, David M Tobin
Mycobacterium tuberculosis infection in humans triggers formation of granulomas, which are tightly organized immune cell aggregates that are the central structure of tuberculosis. Infected and uninfected macrophages interdigitate, assuming an altered, flattened appearance. Although pathologists have described these changes for over a century, the molecular and cellular programs underlying this transition are unclear. Here, using the zebrafish-Mycobacterium marinum model, we found that mycobacterial granuloma formation is accompanied by macrophage induction of canonical epithelial molecules and structures...
October 18, 2016: Immunity
Carl Nathan
In tuberculosis, some macrophages in granulomas assume an epitheloid appearance. Using the Mycobacterium marinum-zebrafish model, Cronan et al. (2016) now show that granuloma macrophages undergo reprograming events involving E-cadherin-dependent formation of epithelial-like cell-cell junctions. Interference with the function of E-cadherin in macrophages disorganized the granulomas and protected the fish, introducing new ideas and questions about macrophage function and granulomatous diseases.
October 18, 2016: Immunity
Vivian E Strong, Sepideh Gholami, Manish A Shah, Laura H Tang, Yelena Y Janjigian, Mark Schattner, Luke V Selby, Sam S Yoon, Erin Salo-Mullen, Zsofia K Stadler, David Kelsen, Murray F Brennan, Daniel G Coit
OBJECTIVE: The aim of this study was to describe postoperative outcomes of total gastrectomy at our institution for patients with hereditary diffuse gastric cancer (HDGC). BACKGROUND: HDGC, which is mainly caused by germline mutations in the E-cadherin gene (CDH1), renders a lifetime risk of gastric cancer of up to 70%, prompting a recommendation for prophylactic total gastrectomy. METHODS: A prospective gastric cancer database identified 41 patients with CDH1 mutation who underwent total gastrectomy during 2005 to 2015...
October 17, 2016: Annals of Surgery
Wu-Yi Sun, Shan-Shan Hu, Jing-Jing Wu, Qiong Huang, Yang Ma, Qing-Tong Wang, Jing-Yu Chen, Wei Wei
β-arrestins, including β-arrestin1 and β-arrestin2, are multifunctional adaptor proteins. β-arrestins have recently been found to play new roles in regulating intracellular signalling networks associated with malignant cell functions. Altered β-arrestin expression has been reported in many cancers, but its role in hepatocellular carcinoma (HCC) is not clear. We therefore examined the roles of β-arrestins in HCC using an animal model of progressive HCC, HCC patient samples and HCC cell lines with stepwise metastatic potential...
October 19, 2016: Scientific Reports
Wen-Juan Gan, Jing-Ru Wang, Xiao-Li Zhu, Xiao-Shun He, Peng-Da Guo, Shen Zhang, Xiu-Ming Li, Jian-Ming Li, Hua Wu
BACKGROUND: Aberrant expression of Retinoic acid receptor γ (RARγ) is implicated in cancer development. Our previous study identified that RARγ functions as a tumor promoter to drive hepatocellular carcinoma (HCC) growth. However, its contribution to HCC invasion and metastasis remains unclear. METHODS: RARγ expression in clinical HCC samples was detected by western blot and immunohistochemistry. The relationship between RARγ expression levels and the clinical characteristics were evaluated...
October 19, 2016: Journal of Experimental & Clinical Cancer Research: CR
Yanhui Zhang, Baocun Sun, Xiulan Zhao, Huizhi Sun, Wei Cui, Zhiyong Liu, Xin Yao, Xueyi Dong
BACKGROUND: Recently, tumor initiating cells (TICs), which possess self-renewal and other stem cell properties, are regarded as the cause of tumor initiation, recurrence and metastasis. The isolation and identification of TICs could help to develop novel therapeutic strategies. METHODS: In this study, we isolated spheroid cells from human renal cell carcinoma (RCC) cell line SN12C in stem cell-conditioned medium. The stemness characteristics of spheroid cells, including tumorigenicity, self-renewal, proliferation and aldehyde dehydrogenase (ALDH) activity were evaluated; the expression levels of stemness genes and related proteins were assessed...
October 18, 2016: Journal of Experimental & Clinical Cancer Research: CR
Denghe Liu, Lu Sun, Xue Qin, Tianhua Liu, Shu Zhang, Yinkun Liu, Shan Li, Kun Guo
OBJECTIVE: Reprogramming energy metabolism has been defined as the ninth hallmark of cancer; glucose deprivation might be a novel, feasible and effective approach for cancer treatment. However, the comprehensive illustration of behavior alteration of hepatocellular carcinoma (HCC) cells induced by glucose restriction is lacking and associated molecular mechanism is still unclear. METHODS: Three human HCC cell lines were cultured with normal control (25.0 mM D-glucose) and low glucose (5...
September 2016: Discovery Medicine
Cheng-Chao Ruan, Yan Li, Yu Ma, Ding-Liang Zhu, Ping-Jin Gao
OBJECTIVE: Previous studies have indicated that adiponectin (APN) protects against hypertension-related cardiovascular disease. However, whether APN is involved in the regulation of hypertensive renal damage remains unclear. The present study aimed to elucidate how APN regulates renal epithelial to mesenchymal transdifferentiation (EMT) in desoxycorticosterone (DOCA)-salt hypertensive mice. DESIGN AND METHOD: Male APN knockout (APNKO) mice and wild-type (WT) C57BL/6 littermates were sc infused with DOCA pellet (50 mg for 21 day release)...
September 2016: Journal of Hypertension
Ching-Hao Li, Chen-Wei Liu, Chi-Hao Tsai, Yi-Jen Peng, Yu-Hsuan Yang, Po-Lin Liao, Chen-Chen Lee, Yu-Wen Cheng, Jaw-Jou Kang
Aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, has been studied extensively in carcinogenesis through the genomic pathway. In recent years, AHR has also been reported to exert positive or negative effects on epithelial-mesenchymal transition (EMT), the crucial step in tumor malignant progression. However, the detailed mechanism remains controversial. Analysis of AHR-expression levels in non-small cell lung cancer cell lines and lung cancer tissues revealed an inverse correlation between AHR protein levels and tumor cell invasion and metastasis...
October 17, 2016: Archives of Toxicology
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