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Jia Guo, Ming Jiang, Lingjing Jin, Yanxin Yin, Hui Sun, Lihua Yu, Yuting Mao, Jianmin Fang
Objective To construct lentiviral vectors for the expression of monovalent antibody against human c-mesenchymal epithelial transition factor (c-Met) using anti-c-Met chimeric antibody ch3E1D7 plasmid, and test the affinity and neutralizing ability of the purified monovalent antibody in transfected HEK293T cells. Methods The anti-c-Met monovalent antibody was designed, namely mono3E1D7. Three different lentiviral expression vectors of the monovalent antibody were then constructed using genetic engineering technology...
November 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
Richard Wong, Larry Feig
RalGDS is a guanine nucleotide exchange factor that promotes the active GTP-bound form of Ral GTPases, RalA and RalB. GTP-bound Ras has the capacity to activate Ral GTPases at least in part by binding to the C-terminal Ras-binding domain (RBD) of RalGDS and directing the protein to Ral GTPases in the plasma membrane. In many cases, activation of Ral proteins complements other Ras effector pathways to carry out a cell function, but in others it opposes them. Moreover, in many cases activation of Ral proteins contributes to the oncogenic potential of Ras...
October 20, 2016: Biochemical and Biophysical Research Communications
Nando Dulal Das, Guo Nan Yin, Min Ji Choi, Kang-Moon Song, Jin-Mi Park, Anita Limanjaya, Kalyan Ghatak, Nguyen Nhat Minh, Jiyeon Ock, Soo-Hwan Park, Ho Min Kim, Ji-Kan Ryu, Jun-Kyu Suh
INTRODUCTION: Diabetic erectile dysfunction is a disease mostly of vascular origin and men with diabetic erectile dysfunction respond poorly to oral phosphodiesterase-5 inhibitors. Hepatocyte growth factor (HGF) is a pleiotropic factor that plays an essential role in the regulation of cell proliferation, survival, and angiogenesis. AIM: To determine the effectiveness of recombinant human (rh)-HGF in restoring erectile function in diabetic mice. METHODS: Four groups of mice were used: control non-diabetic mice and streptozotocin-induced diabetic mice receiving two successive intracavernous injections of phosphate buffered saline (days -3 and 0), a single intracavernous injection of rh-HGF (day 0), or two successive intracavernous injections of rh-HGF (days -3 and 0)...
November 2016: Journal of Sexual Medicine
Vivek Subbiah, Oliver Holmes, Kyle Gowen, Daniel Spritz, Behrang Amini, Wei-Lien Wang, Alexa B Schrock, Funda Meric-Bernstam, Ralph Zinner, Sarina Piha-Paul, Maria Zarzour, Julia A Elvin, Rachel L Erlich, David L Stockman, Jo-Anne Vergilio, James H Suh, Philip J Stephens, Vincent Miller, Jeffrey S Ross, Siraj M Ali
Malignant gastrointestinal neuroectodermal tumor (GNET) is an aggressive rare tumor, primarily occurring in young adults with frequent local-regional metastases and recurrence after local control. The tumor is characterized by the presence of EWSR1-ATF1 or EWSR1-CREB1 and immunohistochemical positivity for S-100 protein without melanocytic marker positivity. Due to poor responses to standard sarcoma regimens, GNET has a poor prognosis, and development of effective systemic therapy is desperately needed to treat these patients...
October 21, 2016: Oncology
Ying-Chun Lin, Rui-Yun Chen, Shang-Wen Chen, Te-Chun Hsieh, Kuo-Yang Yen, Ji-An Liang, Shih-Neng Yang, Yao-Ching Wang, Ya-Huey Chen, Nan-Haw Chow, Chia-Hung Kao
OBJECTIVES: This study correlated immunohistochemical studies with fluorodeoxyglucose (FDG) uptake on positron emission tomography-computed tomography (PET-CT) and identified prognostic factors for radiotherapy (RT)-based treatment outcomes in patients with squamous cell carcinoma of the oropharynx and hypopharynx. METHODS: Genomic data from pretreatment biopsy specimens (Glut1, CAIX, VEGF, HIF-1α, EGFR, Ki-67, Bcl-2, CLAUDIN-4, YAP-1, c-Met, and p16) of 76 patients were analyzed using tissue microarrays...
October 20, 2016: Clinical Otolaryngology
Jung-Soo Pyo, Guhyun Kang, Hyunjin Cho
PURPOSE: The aim of the present study was to elucidate the clinicopathological significance and diagnostic accuracy of immunohistochemistry (IHC) for determining the mesenchymal epidermal transition (c-MET) expression in patients with gastric cancer (GC). MATERIALS AND METHODS: The present meta-analysis investigated the correlation between c-MET expression as determined by IHC and the clinicopathological parameters in 8,395 GC patients from 37 studies that satisfied the eligibility criteria...
September 2016: Journal of Gastric Cancer
Alice Iezzi, Elisa Caiola, Massimo Broggini
The Phosphatidyl inositol-3 kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) and c-Met signaling pathways are often deregulated in cancer. The two pathways are interconnected and at least c-Met has been implicated in drug resistance. The aim of the study was to assess in ovarian cancer preclinical models, the efficacy and tolerability of a dual PI3K mTOR inhibitor (PF-05212384 or gedatolisib) and a c-Met inhibitor (crizotinib) either as single agents or in combination. In vitro, both PF-05212384 and crizotinib showed a concentration dependent activity in the two ovarian cancer cell lines...
October 2016: Translational Oncology
Hao Xing, Cunling Yan, Liming Cheng, Nianyue Wang, Shuyang Dai, Jianyong Yuan, Wenfeng Lu, Zhouchong Wang, Jun Han, Yijie Zheng, Tian Yang
Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide. Early diagnosis improves the prognosis. Protein induced by vitamin K antagonist-II (PIVKA-II) is an effective serum biomarker for HCC diagnosis and prognosis. Combined with another serum biomarker α-fetoprotein (AFP), the sensitivity and specificity of HCC diagnosis can be improved to a maximum of 94 and 98.5 %, respectively. PIVKA-II alone or in combination with AFP and/or AFP-L3 was effective in predicting the treatment response and clinical outcome of curative hepatic resection, chemotherapy, targeted therapy, radiotherapy, and liver transplantation...
October 13, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Yong-Xu Jia, Teng-Fei Li, Dan-Dan Zhang, Zong-Min Fan, Hui-Jie Fan, Jie Yan, Li-Juan Chen, Hong Tang, Yan-Ru Qin, Xing-Ya Li
Molecular-targeted therapy against tyrosine kinase receptors (RTKs) plays an important role in gastric cancer (GC) treatment. Understanding the correlation between RTK coexpression could better guide clinical drug use. In the present study, the coexpression status of c-MET, fibroblast growth factor receptor 2 (FGFR2), and human epidermal growth factor receptor 2 (HER2) in human GC and their clinical significance in clinical therapy were explored. Immunohistochemical (IHC) staining, quantitative real-time polymerase chain reaction and fluorescent in situ hybridization were performed in 143 cases of GC who had undergone gastrectomy without preoperative chemoradiotherapy...
2016: OncoTargets and Therapy
Ryul Kim, Bhumsuk Keam, Dohee Kwon, Chan-Young Ock, Miso Kim, Tae Min Kim, Hak Jae Kim, Yoon Kyung Jeon, In Kyu Park, Chang Hyun Kang, Dong-Wan Kim, Young Tae Kim, Dae Seog Heo
AIM: To investigate the expression and prognostic role of programmed death ligand-1 (PD-L1) in locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: A total of 200 patients with ESCC who underwent radical esophagectomy with standard lymphadenectomy as the initial definitive treatment in Seoul National University Hospital from December 2000 to April 2013 were eligible for this analysis. Tissue microarrays were constructed by collecting tissue cores from surgical specimens, and immunostained with antibodies directed against PD-L1, p16, and c-Met...
October 7, 2016: World Journal of Gastroenterology: WJG
Jiang-Rui Guo, Wei Li, Yong Wu, Lin-Qing Wu, Xin Li, Ya-Fei Guo, Xiao-Hui Zheng, Xiao-Lan Lian, Hui-Fang Huang, Yuan-Zhong Chen
This study aims to investigate effects of HGF expression on biological behaviors of Kasumi-1 and HL60. Expression of HGF and c-Met gene were detected using qRT-PCR. Short hairpin RNA (shRNA) was used to reduce HGF expression. Silencing effect of shRNA was verified by qRT-PCR and western blot. Cell reproductive capacity, cell clonality and cell cycle (apoptosis) were detected by CCK-8, clone formation, flow cytometry (FCM), respectively. Cell adhesion, cell invasion ability and cell proliferation were also examined...
2016: American Journal of Translational Research
Zhen Qu, Junhua Wu, Junyi Wu, Dongjun Luo, Chunping Jiang, Yitao Ding
BACKGROUND: Exosomes are carriers of intercellular information and regulate the tumor microenvironment. They play an important role in drug resistance by transporting RNA molecules and proteins. However, their effects on sorafenib resistance in hepatocellular carcinoma (HCC) are not completely understood. METHODS: Exosomes were isolated from two invasive hepatoma cell lines (MHCC-97 L and MHCC-97H), and their roles in regulating sorafenib resistance in liver cancer cells as well as the underlying molecular mechanisms were determined...
September 30, 2016: Journal of Experimental & Clinical Cancer Research: CR
Yi Du, Hirohito Yamaguchi, Yongkun Wei, Jennifer L Hsu, Hung-Ling Wang, Yi-Hsin Hsu, Wan-Chi Lin, Wen-Hsuan Yu, Paul G Leonard, Gilbert R Lee, Mei-Kuang Chen, Katsuya Nakai, Ming-Chuan Hsu, Chun-Te Chen, Ye Sun, Yun Wu, Wei-Chao Chang, Wen-Chien Huang, Chien-Liang Liu, Yuan-Ching Chang, Chung-Hsuan Chen, Morag Park, Philip Jones, Gabriel N Hortobagyi, Mien-Chie Hung
No abstract text is available yet for this article.
October 6, 2016: Nature Medicine
Fabio Bozzi, Silvia Brich, Gian Paolo Dagrada, Tiziana Negri, Elena Conca, Barbara Cortelazzi, Antonino Belfiore, Federica Perrone, Ambra Vittoria Gualeni, Annunziata Gloghini, Antonello Cabras, Monica Brenca, Roberta Maestro, Nadia Zaffaroni, Paolo Casali, Rossella Bertulli, Marcello Deraco, Silvana Pilotti
The aim of this study was to reconsider the biological characteristics of epithelioid malignant peritoneal mesothelioma (E-MpM) in the light of new concepts about epithelial mesenchymal transition and mesenchymal epithelial reverse transition (EMT/MErT) and the role of epigenetic reprogramming in this context. To this end we profiled surgical specimens and derived cells cultures by a number of complementary approaches i.e. immunohistochemistry, immunofluorescence, in situ hybridization, biochemistry, pluripotent stem cell arrays, treatments with cytokines, growth factors and specific inhibitors...
September 26, 2016: Oncotarget
Yetkin Yıldız, Cenk Sokmensuer, Suayib Yalcin
BACKGROUND: Met and HER-2 are proto-oncogenes encoding receptor tyrosine kinase c-Met and HER-2, respectively. Hepatocyte growth factor (HGF) is a ligand of c-Met. The frequency of c-Met, HGF, and HER-2 expressions in gastric cancer and their association with other clinicopathological factors have not been fully understood. PATIENTS AND METHODS: Patients with stage 1-4 disease were analyzed. Expressions of c-Met, HGF, and HER-2 were examined using immunohistochemistry...
2016: OncoTargets and Therapy
In-Ho Kim, In Hee Lee, Ji Eun Lee, Sook Hee Hong, Tae-Jung Kim, Kyo-Young Lee, Young Kyoon Kim, Seung Joon Kim, Sook Whan Sung, Jae Kil Park, Ie Ryung Yoo, Yeon Sil Kim, Jung-Oh Kim, Jin Hyoung Kang
PURPOSE: We retrospectively assessed the role of C-MET expression and epidermal growth factor receptor (EGFR) mutation on survival following platinum-based adjuvant chemotherapy. The impact of C-MET on survival was also investigated in relation to EGFR mutation status. METHODS: We enrolled 311 patients with resected lung adenocarcinoma (high-risk stage 1B-3A), and performed immunohistochemistry (IHC) using C-MET- and mutant EGFR (EGFRmut)-specific antibodies in tissue microarrays...
September 30, 2016: Annals of Surgical Oncology
Carolin Sellmann, Achim Doerner, Christine Knuehl, Nicolas Rasche, Vanita Sood, Simon Krah, Laura Rhiel, Annika Messemer, John Wesolowski, Mark Schuette, Stefan Becker, Lars Toleikis, Harald Kolmar, Bjoern Hock
Bispecific antibodies (bsAbs) and antibody-drug conjugates (ADCs), have already demonstrated benefits for the treatment of cancer in several clinical studies, showing improved drug selectivity and efficacy. In particular, simultaneous targeting of prominent cancer antigens, such as EGF receptor (EGFR) and c-MET, by bsAbs has raised increasing interest for potentially circumventing receptor crosstalk and c-MET mediated acquired resistance during anti-EGFR monotherapy. In this study, we combined the selectivity of EGFR x c-MET bsAbs with the potency of cytotoxic agents via bispecific antibody-toxin conjugation...
September 30, 2016: Journal of Biological Chemistry
Jingjin Jiang, Xiaoning Feng, Wenjing Zhou, Yue Wu, Yunmei Yang
Gefitinib is a first line anti-tumor drug used for the treatment of patients with non-small cell lung cancer (NSCLC) harboring EGFR mutations. However, the drug resistance to gefitinib limits its clinical application. Here, we observed the CSCs of PC9 are obviously resistant to gefitinib compared with the non-CSCs. Furthermore, we found the gefitinib failed to suppress the PI3K/AKT pathway in the PC9-CSCs. Mechanically, we showed significant down-regulation of miR-128 in the PC9-CSCs compared with the non-CSCs...
September 27, 2016: Oncotarget
Shuang Li, Haiyang Zhang, Xinyi Wang, Yanjun Qu, Jingjing Duan, Rui Liu, Ting Deng, Tao Ning, Le Zhang, Ming Bai, Likun Zhou, Xia Wang, Shaohua Ge, Guoguang Ying, Yi Ba
MicroRNAs (miRNAs) have been reported to be involved in each stage of tumor development in various types of cancers. We have previously showed that miR-16 is downregulated in cancer and acts as a tumor suppressor. Other studies indicated that hepatocyte growth factor (HGF)/c-Met is implicated in proliferation, migration, and other pathophysiological processes. However, little is known about the relationship between miR-16 and HGF/c-Met in gastric cancer (GC). In the present study, we used bioinformatics tools and related experiments to search for miRNAs targeting HGF...
September 28, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Hassan Y Ebrahim, Mohamed M Mohyeldin, Mohammad M Hailat, Khalid A El Sayed
(1S,2E,4S,6R,7E,11E)-2,7,11-Cembratriene-4,6-diol (1) and its 4-epi-analog (2) are the cembranoid precursors to several key flavor ingredients in most Nicotiana (tobacco) species. Nearly 40-60% of 1 and 2 are purposely degraded during the commercial tobacco fermentation. However, 1 and 2 display promising bioactivities, including anticancer. Breast cancer is the most diagnosed cancer in women and ranked second female disease killer. The receptor tyrosine kinase c-Met correlates with aggressiveness of certain breast cancer phenotypes and thus considered a valid therapeutic target...
September 13, 2016: Bioorganic & Medicinal Chemistry
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