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Zhan-Peng Yan, Ting-Ting Xu, Zhen-Tao An, Ying Hu, Wan-Zhen Chen, Fang-Shi Zhu
The aim of this study was to investigate the mechanisms of mono-functional alkylating agent MNNG to damage human gastric epithelial GES-1 cells and roles of Wnt/β-catenin signaling pathway in the process. The GES-1 cells were treated with MNNG (2 × 10-5 mol/L) for 24 h. The morphological changes of the GES-1 cells were observed under inverted microscope 2 d after treatment. The cell viability was measured by MTT assay. The apoptosis and cell cycle distribution of the GES-1 cells were analyzed by flow cytometry...
June 25, 2018: Sheng Li Xue Bao: [Acta Physiologica Sinica]
Darren L Lath, Clive H Buckle, Holly R Evans, Matthew Fisher, Jenny M Down, Michelle A Lawson, Andrew D Chantry
The receptor tyrosine kinase c-Met, its ligand HGF, and components of the downstream signalling pathway, have all been implicated in the pathogenesis of myeloma, both as modulators of plasma cell proliferation and as agents driving osteoclast differentiation and osteoblast inhibition thus, all these contribute substantially to the bone destruction typically caused by myeloma. Patients with elevated levels of HGF have a poor prognosis, therefore, targeting these entities in such patients may be of substantial benefit...
2018: PloS One
Sung-Young Shin, Anna-Katharina Müller, Nandini Verma, Sima Lev, Lan K Nguyen
Prediction of drug combinations that effectively target cancer cells is a critical challenge for cancer therapy, in particular for triple-negative breast cancer (TNBC), a highly aggressive breast cancer subtype with no effective targeted treatment. As signalling pathway networks critically control cancer cell behaviour, analysis of signalling network activity and crosstalk can help predict potent drug combinations and rational stratification of patients, thus bringing therapeutic and prognostic values. We have previously showed that the non-receptor tyrosine kinase PYK2 is a downstream effector of EGFR and c-Met and demonstrated their crosstalk signalling in basal-like TNBC...
June 2018: PLoS Computational Biology
Yingbing Wang, Otto Rapalino, Pedram Heidari, Jay Loeffler, Helen A Shih, Kevin Oh, Umar Mahmood
PURPOSE/OBJECTIVES: Response criteria of glioblastoma after chemoradiation do not account for metabolic changes that occur after treatment. The purpose of this study is to evaluate the utility of positron emission tomography imaging with C11 Methionine (MET-PET) for detecting changes that occur after chemoradiation therapy and the value of molecular biomarkers for predicting magnitude of metabolic response. MATERIALS AND METHODS: Newly diagnosed glioblastoma patients undergoing standard chemoradiation treatment were enrolled in this prospective imaging study with MET-PET scan performed within 3 days following surgical resection and again at 4 weeks after completion of chemoradiation...
June 15, 2018: International Journal of Radiation Oncology, Biology, Physics
Khaled AbouAitah, Anna Swiderska-Sroda, Ahmed A Farghali, Jacek Wojnarowicz, Agata Stefanek, Stanislaw Gierlotka, Agnieszka Opalinska, Abdou K Allayeh, Tomasz Ciach, Witold Lojkowski
Naturally derived prodrugs have a wide range of pharmacological activities, including anticancer, antioxidant, and antiviral effects. However, significant barriers inhibit their use in medicine, e.g. their hydrophobicity. In this comprehensive study, we investigated simple and effective nanoformulations consisting of amine-functionalized and conjugated with folic acid (FA) mesoporous silica nanoparticles (MSNs). Two types of MSNs were studied: KCC- 1, with mean size 324 nm and mean pore diameter 3.4 nm, and MCM - 41, with mean size 197 and pore diameter 2 nm...
May 29, 2018: Oncotarget
Elke Tatjana Aristizabal Prada, Gerald Spoettl, Julian Maurer, Michael Lauseker, Eva Koziolek, Jörg Schrader, Ashley B Grossman, Karel Pacak, Felix Beuschlein, Christoph J Auernhammer, Svenja Nölting
Pancreatic neuroendocrine tumors (panNETs) are often inoperable at diagnosis. The mTORC1 inhibitor everolimus has been approved for the treatment of advanced NETs. However, the regular development of resistance to everolimus limits its clinical efficacy. We established two independent everolimus-resistant panNET (BON1) cell lines (BON1 RR1, BON1 RR2) to find potential mechanisms of resistance. After 24 weeks of permanent exposure to 10 nM everolimus, BON1 RR1 and BON1 RR2 showed stable resistance with cellular survival rates of 96...
June 12, 2018: Endocrine-related Cancer
Weihua Li, Hongqun Zheng, Jiankai Xu, Shaodong Cao, Xiuan Xu, Peng Xiao
OBJECTIVES: c-Met is a receptor tyrosine kinase shown inappropriate expression and actively involved in progression and metastasis in most types of human cancer. Development of c-Met-targeted imaging and therapeutic agents would be extremely useful. Previous studies reported that c-Met-binding peptide (Met-pep1, YLFSVHWPPLKA) specifically targets c-Met receptor. Here, we evaluated 18F-labeled Met-pep1 for PET imaging of c-Met positive tumor in human head and neck squamous cell carcinoma (HNSCC) xenografted mice...
2018: PloS One
Chigusa Morizane, Makoto Ueno, Masafumi Ikeda, Takuji Okusaka, Hiroshi Ishii, Junji Furuse
Biliary tract cancer, carcinoma of the extrahepatic bile ducts, carcinoma of the gall bladder, ampullary carcinoma and intrahepatic cholangiocarcinoma are often identified at an advanced stage and have poor prognoses. Although effective chemotherapy regimens are needed, their development remains unsatisfactory. From the results of a phase III clinical trial (ABC-02 trial), gemcitabine plus cisplatin is the standard first-line chemotherapeutic regimen for advanced biliary tract cancer. A phase III trial of gemcitabine plus cisplatin vs...
June 11, 2018: Japanese Journal of Clinical Oncology
Koji Yamasaki, Shoichiro Mukai, Satoru Sugie, Takahiro Nagai, Kozue Nakahara, Toyoharu Kamibeppu, Hiromasa Sakamoto, Noboru Shibasaki, Naoki Terada, Yoshinobu Toda, Hiroaki Kataoka, Toshiyuki Kamoto
MET, a c-met proto-oncogene product and hepatocyte growth factor (HGF) receptor, is known to play an important role in cancer progression, including bone metastasis. In a previous study, we reported increased expression of MET and matriptase, a novel activator of HGF, in bone metastasis. In this study, we employed a mouse model of renal cell carcinoma (RCC) bone metastasis to clarify the significance of the HGF/MET signaling axis and the regulator of HGF activator inhibitor type-2 (HAI-2). Luciferase-transfected 786-O cells were injected into the left cardiac ventricle of mice to prepare the mouse model of bone metastasis...
June 8, 2018: Cancers
S B Cele, F Odun-Ayo, O A Onyangunga, J Moodley, T Naicker
OBJECTIVE: Hepatocyte Growth Factor (HGF) plays a role in the migration and morphogenesis of different cell types and tissues. Preeclampsia (PE) is associated with deficient trophoblast invasion and placental insufficiency; hence HGF production is expected to be compromised. This study therefore aimed to immunolocalize and morphometrically analyse placental HGF in normotensive versus PE pregnancies stratified by HIV status and gestational age. STUDY DESIGN: Normotensive (N; n = 40) and preeclamptic (PE; n = 80) women were stratified by HIV status (HIV- and HIV+), and gestational age i...
June 1, 2018: European Journal of Obstetrics, Gynecology, and Reproductive Biology
Fang Wang, Thomas Bank, Gregory Malnassy, Maribel Arteaga, Na Shang, Annika Dalheim, Xianzhong Ding, Scott J Cotler, Mitchell F Denning, Michael I Nishimura, Peter Breslin, Wei Qiu
Hepatocellular carcinoma (HCC) is the fifth most common primary cancer and second largest cause of cancer-related death worldwide. The first-line oral chemotherapeutic agent sorafenib only increases survival in patients with advanced HCC by less than 3 months. Most patients with advanced HCC have shown limited response rates and survival benefits with sorafenib. Although sorafenib is an inhibitor of multiple kinases, including serine/threonine-protein kinase c-Raf, serine/threonine-protein kinase B-Raf, vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, VEGFR-3, and platelet-derived growth factor receptor β, HCC cells are able to escape from sorafenib treatment using other pathways that the drug insufficiently inhibits...
June 2018: Hepatology Communications
Seo-Yeon Ahn, Seong Young Kwon, Sung-Hoon Jung, Jae-Sook Ahn, Su Woong Yoo, Jung-Joon Min, Hee-Seung Bom, So Yeon Ki, Hyeoung-Joon Kim, Je-Jung Lee, Sang Yun Song, Deok-Hwan Yang
PURPOSE: Primary central nervous system lymphoma (PCNSL) has a poor prognosis. There has been limited study evaluating the role of interim PET/CT in PCNSL. This prospective study investigated the interim response using sequential brain PET/CT with C-methionine (C-MET) to provide prognostic information during the treatment of PCNSL. MATERIALS AND METHODS: A total of 26 immunocompetent patients recently diagnosed with PCNSL were evaluated. Brain MRI and C-MET PET/CT were performed at the time of diagnosis and after 4 cycles of high-dose methotrexate-based induction chemotherapy...
June 5, 2018: Clinical Nuclear Medicine
Yoshifumi Iwagami, Jing Zou, Hongyu Zhang, Kevin Cao, Chengcheng Ji, Miran Kim, Chiung-Kuei Huang
MicroRNAs (miRs) have been recently shown to be heavily involved in the development of alcoholic liver disease (ALD) and suggested as a potential therapeutic target in ALD. The miR-34a was consistently reported to be significantly elevated in several ALD rodent models, but it remains unclear how miR-34a modulates the cellular behaviours of hepatocytes in ALD development and progression. This study aims to characterize alcohol-induced miR-34a impact on hepatocytes growth and apoptosis. The miRNA array was performed to assess changes in miRNA after chronic alcohol feeding...
June 5, 2018: Journal of Cellular and Molecular Medicine
Rafat M Mohareb, Nadia Y Megally Abdo, Karam A El-Sharkawy
BACKGROUND: Among wide range of heterocyclic steroidal derivatives acquired a special attention due to their wide range of pharmacological activities especially the therapeutic activities. Many pharmacological drugs containing the thiophene nucleus were known in the market. METHOD: A series of tetrahydrobenzothienopyridine derivatives were synthesized from the reaction 2-amino-3-benzoyl-4,5-dihydrobenzo[b]thiophen-6(7H)-one were synthesized and used for further heterocyclization reactions through the reaction with different reagent...
June 3, 2018: Anti-cancer Agents in Medicinal Chemistry
Qiang Wu, Xuewei Yi
Epilepsy is a common chronic brain disorder and is characterized by an enduring predisposition to generate seizures. The hippocampus is especially vulnerable to seizure-induced damage. In this study, we explore the ability of long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) to influence the autophagy and apoptosis of hippocampal neurons in epilepsy and the underlying mechanism involving the PI3K/Akt signaling pathway. Seventy-two Sprague-Dawley rats were assigned to normal, sham, Ep, Ep + si-NC, Ep + si-MALAT1, and Ep + si-MALAT1 + LY groups...
June 1, 2018: Journal of Molecular Neuroscience: MN
Peeyush K Lala, Pinki Nandi, Mousumi Majumder
Lymphangiogenesis (formation of new lymphatic vessels), unlike angiogenesis, has been a lesser-focused field in cancer biology, because of earlier controversy regarding whether lymphatic metastasis occurs via pre-existing or newly formed lymphatics. Recent evidence reveals that peri-tumoral or intra-tumoral lymphangiogenesis is a precursor for lymphatic metastasis in most carcinomas and melanomas. Two major lymphangiogenic factors, vascular endothelial growth factor (VEGF)-C and VEGF-D, are produced by cancer cells or immune cells such as macrophages in the tumor-stroma to promote sprouting of lymphatics from lymphatic endothelial cells (LEC) or LEC precursors (LECP) by binding to their primary (high affinity) receptor VEGF-R3 or secondary receptors VEGF-R2, neuropilin (NRP)2 and α9/β1 integrin...
June 1, 2018: Cancer Metastasis Reviews
Juan Zeng, Heying Zhang, Yonggang Tan, Cheng Sun, Yusi Liang, Jinyang Yu, Huawei Zou
BACKGROUND: Activation of c-Met, a receptor tyrosine kinase, induces radiation therapy resistance in non-small cell lung cancer (NSCLC). The activated residual of c-Met is located in lipid rafts (Duhon et al. Mol Carcinog 49:739-49, 2010). Therefore, we hypothesized that disturbing the integrity of lipid rafts would restrain the activation of the c-Met protein and reverse radiation resistance in NSCLC. In this study, a series of experiments was performed to test this hypothesis. METHODS: NSCLC A549 and H1993 cells were incubated with methyl-β-cyclodextrin (MβCD), a lipid raft inhibitor, at different concentrations for 1 h before the cells were X-ray irradiated...
May 30, 2018: BMC Cancer
Camille Emprou, Pauline Le Van Quyen, Jérémie Jégu, Nathalie Prim, Noëlle Weingertner, Eric Guérin, Erwan Pencreach, Michèle Legrain, Anne-Claire Voegeli, Charlotte Leduc, Bertrand Mennecier, Pierre-Emmanuel Falcoz, Anne Olland, Nicolas Santelmo, Elisabeth Quoix, Gilbert Massard, Dominique Guenot, Marie-Pierre Chenard, Michèle Beau-Faller
Lymph node metastasis is an important prognosis factor in non-small cell lung cancer (NSCLC) patients. The aim of this study was to investigate the role of epithelial to mesenchymal transition (EMT) in lymph node progression in the early stages of NSCLC. We studied a retrospective cohort of 160 consecutive surgically treated NSCLC patients with available frozen tumor samples for expression of EMT markers (CDH1, CTNNB1, CDH2, and VIMENTIN), inducers (TGFB1, c-MET, and CAIX), and transcription factors (EMT-TF: SNAI1, SNAI2, ZEB1, TWIST1, and TWIST2)...
May 29, 2018: Cancer Medicine
Kyeong Ryang Ko, Junghun Lee, Deokho Lee, Boram Nho, Sunyoung Kim
During the peripheral nerve regeneration process, a variety of neurotrophic factors play roles in nerve repair by acting on neuronal or non-neuronal cells. In this report, we investigated the role(s) of hepatocyte growth factor (HGF) and its receptor, c-met, in peripheral nerve regeneration. When mice were subjected to sciatic nerve injury, the HGF protein level was highly increased at the injured and distal sites. The level of both total and phosphorylated c-met was also highly upregulated, but almost exclusively in Schwann cells (SCs) distal from the injury site...
May 29, 2018: Scientific Reports
Inan Olmez, Ying Zhang, Laryssa Manigat, Mouadh Benamar, Breanna Brenneman, Ichiro Nakano, Jakub Godlewski, Agnieszka Bronisz, Jeongwu Lee, Tarek Abbas, Roger Abounader, Benjamin Purow
Glioblastoma (GBM) is the most common primary brain malignancy and carries an extremely poor prognosis. Recent molecular studies revealed the CDK4/6-Rb-E2F axis and receptor tyrosine kinase (RTK) signaling to be deregulated in most GBM, creating an opportunity to develop more effective therapies by targeting both pathways. Using a phospho-RTK protein array, we found that both c-Met and TrkA-B pathways were significantly activated upon CDK4/6 inhibition in GBM cells. We therefore investigated the efficacy of combined CDK4/6 and c-Met/TrkA-B inhibition against GBM...
May 29, 2018: Cancer Research
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