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Le Tao, Jianxin Qiu, Spencer Slavin, Zhenyu Ou, Zhihong Liu, Jifu Ge, Elizabeth A Guancial, Edward M Messing, Chawnshang Chang, Shuyuan Yeh
Clinical data indicates that T cells can be recruited to bladder cancer (BCa) tumors, yet the impact of T cells on BCa progression remains unclear. In the present study, we found that T cells were recruited more to BCa tissues than to the surrounding normal bladder tissues. Results from an in vitro co-culture system also found that BCa recruited more CD4+ T cells than did normal bladder cells. The recruiting of T cells to BCa tissues may increase the proliferation and invasion of BCa cells. Mechanistic studies revealed that infiltrating T cells stimulate BCa estrogen receptor beta (ERβ) signaling and consequently increase the expression of MET proto-oncogene, receptor tyrosine kinase (c-MET), through either direct binding to its promoter or via modulation of IL-1 expression...
April 20, 2018: Cancer Letters
Mary Lou Affronti, Jennifer Gamboa Jackman, Frances McSherry, James E Herndon, Elwood C Massey, Eric Lipp, Annick Desjardins, Henry S Friedman, Gordana Vlahovic, James Vredenburgh, Katherine B Peters
LESSONS LEARNED: Due to evolving imaging criteria in brain tumors and variation in magnetic resonance imaging evaluation, it is not ideal to use response rate as a primary objective. Future studies involving antiangiogenic agents should use overall survival.Disease-expected toxicities should be considered when defining the clinical significance of an adverse event. For example, vascular thromboembolic events are common in brain tumor patients and should not be attributed to the study drug in the safety analysis...
April 17, 2018: Oncologist
Demin Jiao, Jun Chen, Yu Li, Xiali Tang, Jian Wang, Wei Xu, Jia Song, You Li, Huimin Tao, Qingyong Chen
Hepatocyte growth factor (HGF) overexpression is an important mechanism in acquired epidermal growth factor receptor (EGFR) kinase inhibitor gefitinib resistance in lung cancers with EGFR activating mutations. MiR-1-3p and miR-206 act as suppressors in lung cancer proliferation and metastasis. However, whether miR-1-3p and miR-206 can overcome HGF-induced gefitinib resistance in EGFR mutant lung cancer is not clear. In this study, we showed that miR-1-3p and miR-206 restored the sensitivities of lung cancer cells PC-9 and HCC-827 to gefitinib in present of HGF...
April 17, 2018: Journal of Cellular and Molecular Medicine
Samira M Sadowski, Marc Pusztaszeri, Marie-Claude Brulhart-Meynet, Volodymyr Petrenko, Claudio De Vito, Jonathan Sobel, Céline Delucinge-Vivier, Electron Kebebew, Romano Regazzi, Jacques Philippe, Frédéric Triponez, Charna Dibner
Context: Hyperparathyroidism is associated with hypercalcemia and the excess of parathyroid hormone secretion. However, the alterations in molecular pattern of functional genes during parathyroid tumorigenesis have not been unraveled. We aimed at establishing transcriptional patterns of normal and pathological parathyroid glands (PG) in sporadic primary and secondary hyperparathyroidism (HPT1, 2). Objective: To evaluate dynamic alterations in molecular patterns as a function of the type of PG pathology, a comparative transcript analysis was conducted in subgroups of healthy samples, sporadic HPT1 adenoma and hyperplasia, and HPT2...
April 5, 2018: Journal of Clinical Endocrinology and Metabolism
Yanying Wang, Pingping Zhu, Jing Wang, Xiaoxiao Zhu, Jianjun Luo, Shu Meng, Jiayi Wu, Buqing Ye, Luyun He, Ying Du, Lei He, Runsheng Chen, Yong Tian, Zusen Fan
BACKGROUND & AIMS: Long noncoding RNAs (lncRNAs) play important roles in various biological processes and regulate gene expression by diverse mechanisms. However, how lncRNAs regulate liver repopulation is unknown. METHODS: Here we identify a divergent lncRNA termed LncHand2 that is highly expressed over liver regeneration after partial hepatectomy (PHx). RESULTS: LncHand2 is constitutively expressed in the nuclei of pericentral hepatocytes in mouse and human livers...
April 10, 2018: Journal of Hepatology
C-H Yang, X-Y Zhang, L-N Zhou, Y Wan, L-L Song, W-L Gu, R Liu, Y-N Ma, H-R Meng, Y-L Tian, Y Zhang
OBJECTIVE: To investigate the possible function and mechanism of lncRNA SNHG8 in the pathogenesis of endometrial carcinoma. PATIENTS AND METHODS: We utilized qRT-PCR to detect the expression of SNHG8 in 60 cases of endometrial carcinoma and 25 cases of normal endometrium; after that, the endometrial carcinoma cell lines were screened. SNHG8 was transfected into endometrial carcinoma cells by Lipofectamine and the proliferative activity of cells was detected by cell counting kit-8 (CCK-8) assay...
March 2018: European Review for Medical and Pharmacological Sciences
Yuxiang Ma, Xin Zheng, Hongyun Zhao, Wenfeng Fang, Yang Zhang, Jieying Ge, Lu Wang, Weicong Wang, Ji Jiang, Shaokun Chuai, Zhou Zhang, Wanhong Xu, Xiao Xu, Pei Hu, Li Zhang
INTRODUCTION: AC0010 is a mutation-selective, third-generation EGFR tyrosine kinase inhibitor (TKI). This first-in-human phase I trial determine the maximum tolerated dose (MTD), recommended phase II dose (RP2D), schedule, safety, pharmacokinetics, pharmacodynamics, and antitumor activity of AC0010 in patients with advanced or recurrent NSCLC and acquired resistance to the first-generation EGFR-TKI. METHODS: Patients received escalating daily doses of AC0010 (50 to 600 mg) throughout 28-day cycles...
April 4, 2018: Journal of Thoracic Oncology
Wei Feng, Qianyi Xie, Suo Liu, Ying Ji, Chunyun Li, Chunle Wang, Longyu Jin
Gefitinib have been widely used in the first-line treatment of advanced EGFR-mutated non-small-cell lung cancer (NSCLC). However, many NSCLC patients will acquire resistance to gefitinib after 9-14 months of treatment. This study revealed that Krüppel-like factor 4 (KLF4) contributes to the formation of gefitinib resistance in c-Met overexpressing NSCLC cells. We observed that KLF4 was overexpressed in c-Met overexpressing NSCLC cells and tissues. Knockdown of KLF4 increased tumorigenic properties in gefitinib-resistant NSCLC cell lines without c-Met overexpression, but it reduced tumorigenic properties and increased gefitinib sensitivity in gefitinib-resistant NSCLC cells with c-Met overexpression, whereas overexpression of KLF4 reduced gefitinib sensitivity in gefitinib-sensitive NSCLC cells...
April 6, 2018: Cancer Science
Giulia Pasquini, Giuseppe Giaccone
The role of the c-mesenchymal-epithelial transition factor (c-MET) signaling pathway in tumor progression and invasion has been extensively studied. C-MET inhibitors have shown anti-tumor activity in NSCLC both in preclinical and in clinical trials. However, given the molecular heterogeneity of NSCLC, it is likely that only a specific subset of NSCLC patients will benefit from c-MET inhibitors. Emerging data also suggest that MET inhibitors in combination with EGFR-TKIs (epidermal growth factor receptor tyrosine kinase inhibitors) may have a role in therapy for both EGFR-TKI resistant and EGFR-TKI naïve patients...
April 2018: Expert Opinion on Investigational Drugs
Noah E Berlow, Matthew N Svalina, Michael J Quist, Teagan P Settelmeyer, Viktor Zherebitskiy, Mari Kogiso, Lin Qi, Yuchen Du, Cynthia E Hawkins, Esther Hulleman, Xiao-Nan Li, Sakir H Gultekin, Charles Keller
Diffuse intrinsic pontine glioma (DIPG) is a universally fatal childhood cancer of the brain. Despite the introduction of conventional chemotherapy and radiotherapy, improvements in survival have been marginal and long-term survivorship is uncommon. Thus, new targets for therapeutics are critically needed. Early phase clinical trials exploring molecularly-targeted therapies against the epidermal growth factor receptor (EGFR) and novel immunotherapies targeting interleukin receptor-13α2 (IL-13Rα2) have demonstrated activity in this disease...
2018: PloS One
Zhen Yang, Juanli Duan, Jianlin Wang, Qi Liu, Runze Shang, Xisheng Yang, Peng Lu, Congcong Xia, Lin Wang, Kefeng Dou
Introduction: A safe and effective in vivo siRNA delivery system is a prerequisite for liver tumor treatment based on siRNA cancer therapeutics. Nanoparticles based on superparamagnetic iron oxide (SPIO) provide a promising delivery system. In this study, we aimed to explore a novel nanoparticle, which is composed of SPIO. Materials and methods: The particles have a core of iron oxide that is modified by galactose (Gal) and polyethylenimine (PEI), which act as shells, providing targeted delivery of therapeutic siRNA to the liver cancer...
2018: International Journal of Nanomedicine
Yi Shao, Hui Lv, Dian-Sheng Zhong, Qing-Hua Zhou
Patients with non-small-cell lung cancer (NSCLC) with sensitive epidermal growth factor receptor (EGFR) mutations generally react well to tyrosine kinase inhibitors (TKIs). However acquired resistance eventually occurs. Several mechanisms contribute to the resistance including T790M mutation, c-Met amplification and PIK3CA mutation. In recent years, cancer stem cells (CSCs) have been suggested to be involved in TKI resistance. MAP17 is aberrantly overexpressed in a number of malignancies. However, the expression pattern and function of MAP17 in CSCs are still unclear...
May 2018: Oncology Letters
Wen Wang, Jing Dong, Maoxiu Wang, Shujuan Yao, Xiangyu Tian, Xiujuan Cui, Shijie Fu, Shiqian Zhang
MicroRNAs (miRNAs) are a group of small non-coding RNAs that modulate post-transcriptional gene expression. It has been demonstrated that various miRNAs may be expressed at different levels in different types of tumors. The present study assessed the role of microRNA-148a-3p (miR-148a-3p) in epithelial ovarian cancer (EOC). The results demonstrated that miR-148a-3p was decreased in EOC tissues and that a lower miRa-148-3p concentration was associated with a higher overall survival rate. Transfection of miR-148a-3p suppressed the invasive and proliferative capacity of SKOV3 cells...
May 2018: Oncology Letters
Leonora Sf Boogerd, Maxime Jm van der Valk, Martin C Boonstra, Hendrica Ajm Prevoo, Denise E Hilling, Cornelis Jh van de Velde, Cornelis Fm Sier, Arantza Fariña Sarasqueta, Alexander L Vahrmeijer
Purpose: Intraoperative identification of rectal cancer (RC) can be challenging, especially because of fibrosis after treatment with preoperative chemo- and radiotherapy (CRT). Tumor-targeted fluorescence imaging can enhance the contrast between tumor and normal tissue during surgery. Promising targets for RC imaging are carcinoembryonic antigen (CEA), epithelial cell adhesion molecule (EpCAM) and the tyrosine-kinase receptor Met (c-Met). The effect of CRT on their expression determines their applicability for imaging...
2018: OncoTargets and Therapy
Tianhui Shi, Menglin Wang, Hao Li, Miao Wang, Xingyu Luo, Yan Huang, Hong-Hui Wang, Zhou Nie, Shouzhuo Yao
Cancer cells contain a unique set of cell surface receptors that provide potential targets for tumor theranostics. Here, we propose an efficient approach to construct G-quadruplex-based aptamers that specifically recognize cell-surface receptors and monitor them in an amplified manner. This designed aptamer combined particular sequence for the c-Met on the cell surface and poly-G-quadruplexes structures that allow a rapid and amplified fluorescent readout upon the binding of thioflavin T (ThT). The poly-G-quadruplexes also function as a carrier for photosensitizers such as TMPyP4 in that, the aptamer further trigger the production of reactive oxygen species (ROS) to commit cells to death...
April 3, 2018: Scientific Reports
Li Zhang, Jingyun Zhao, Beichen Zhang, Tao Lu, Yadong Chen
A series of [1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivatives were designed, synthesized and evaluated for their biological activity. Most of these compounds showed potent activities against c-Met kinase and cell growth inhibition. The most promising compound, 7d, has the IC50 values of 2.02 and 88 nM to inhibit c-Met kinase activity and cell growth in the MKN45 cell line, respectively. In addition, 7d is highly selective to c-Met and exhibits over 2500-fold selective inhibition to 16 tyrosine kinases evaluated...
March 21, 2018: European Journal of Medicinal Chemistry
Paschalis Gavriilidis, Theofilos Poutahidis, Alexander Giakoustidis, Kali Makedou, Katerina Angelopoulou, Alexander Hardas, Paola Andreani, Argyro Zacharioudaki, George Saridis, Athanasios Gargavanis, Eleni Louri, Nikolaos Antoniadis, Eleftheria Karampela, Nikolaos Psychalakis, Antonios Michalopoulos, Apostolos Papalois, Stavros Iliadis, Satvinder Mudan, Daniel Azoulay, Dimitrios Giakoustidis
Background : To elucidate the expression of Aurora kinases (AURK) and the anticancer effects of pan-aurora kinase inhibitor Danusertib in hepatocarcinogenesis model in C56Bl6 mice. Methods : Thirty mice C56Bl6 were randomly divided into Group A or control, Group B animals who underwent experimental hepatocarcinogenesis with diethylnitrosamine (DEN), and Group C animals with DEN-induced hepatocarcinogenenesis that treated with pan-aurora kinase inhibitor Danusertib. Primary antibodies for immunochistochemistry (IHC) included rabbit antibodies against Ki-67, DKK1, INCENP, cleaved caspase-3, NF-κB p65, c-Jun, β-catenin...
2018: Journal of Cancer
Wei Zhou, Congqing Jiang, Nan Zhan, Xiaoguang Lv, Lifang Fan, Maskey Ninu
Background: Tyrosine kinase growth factor receptors (TKGFRs) play an important role in the progression of cancer. A variety of studies have investigated the clinicopathologic correlation of these receptors and their influences on patient survival in different types of cancer. As the members of TKGFRs, the biomarkers c-MET, epidermal growth factor receptor (EGFR), and human epidermal growth factor receptor 2 (HER-2) have been extensively investigated in biliary tract cancer (BTC). However, their prognostic value is still controversial...
2018: Journal of Cancer Research and Therapeutics
Su Jin Lee, Jeeyun Lee, Se Hoon Park, Joon Oh Park, Ho Yeong Lim, Won Ki Kang, Young Suk Park, Seung Tae Kim
INTRODUCTION: Increased mesenchymal-epithelial transition factor gene (c-MET) expression in several human malignancies is related to increased tumor progression and is a new potential drug target for several types of cancers. In the present study, we investigated the incidence of c-MET overexpression and its prognostic significance in patients with colorectal cancer (CRC). PATIENTS AND METHODS: We retrospectively reviewed the data from 255 stage IV CRC patients who had results from a c-MET immunohistochemical test at Samsung Medical Center...
March 2, 2018: Clinical Colorectal Cancer
Linxiao Wang, Xiaobo Liu, Yongli Duan, Xiaojing Li, Bingbing Zhao, Caolin Wang, Zhen Xiao, Pengwu Zheng, Qidong Tang, Wufu Zhu
Six series of pyrrolo[2,3-d]pyrimidine and pyrazolo[3,4-d]pyrimidine derivatives bearing 1,2,3-triazole moiety were designed, synthesized, and some bio-evaluation were also carried out. As a result, four points can be summarized: Firslty, some of compounds exhibited excellent cytotoxicity activity and selectivity with the IC50 values in single-digit μM level. Especially, the most promising compound 16d showed equal activity to lead compound Foretinib against A549, HepG2 and MCF-7 cell lines, with the IC50 values of 4...
March 25, 2018: Chemical Biology & Drug Design
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