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https://www.readbyqxmd.com/read/28324113/microrna-expression-patterns-involved-in-amyloid-beta-induced-retinal-degeneration
#1
Peirong Huang, Junran Sun, Fenghua Wang, Xueting Luo, Jingyang Feng, Qing Gu, Te Liu, Xiaodong Sun
Purpose: Dry age-related macular degeneration (AMD) is characterized by the accumulation of drusen under Bruch's membrane, and amyloid beta (Aβ) is speculated to be one of the key pathologic factors. While the detrimental effects of Aβ on retinas have been widely explored, Aβ-induced epigenetic regulatory changes have yet to be fully investigated. We therefore aimed to identify the microRNA (miRNA) expression profiles in an Aβ-induced mouse model of retinal degeneration. Methods: C57BL/6 mice were intravitreally injected with Aβ1-40 or PBS and the eye tissues were collected for hematoxylin and eosin (H&E) staining, apoptosis immunofluorescence staining, and miRNA profiling...
March 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28322831/chemical-inhibitors-of-c-met-receptor-tyrosine-kinase-stimulate-osteoblast-differentiation-and-bone-regeneration
#2
Jung-Woo Kim, Mi Nam Lee, Byung-Chul Jeong, Sin-Hye Oh, Min-Suk Kook, Jeong-Tae Koh
The c-Met receptor tyrosine kinase and its ligand, hepatocyte growth factor (HGF), have been recently introduced to negatively regulate bone morphogenetic protein (BMP)-induced osteogenesis. However, the effect of chemical inhibitors of c-Met receptor on osteoblast differentiation process has not been examined, especially the applicability of c-Met chemical inhibitors on in vivo bone regeneration. In this study, we demonstrated that chemical inhibitors of c-Met receptor tyrosine kinase, SYN1143 and SGX523, could potentiate the differentiation of precursor cells to osteoblasts and stimulate regeneration in calvarial bone defects of mice...
March 16, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28321014/homogeneous-assays-for-ldl-c-and-hdl-c-are-reliable-in-both-the-postprandial-and-fasting-state
#3
Takashi Miida, Kunihiro Nishimura, Satoshi Hirayama, Yoshihiro Miyamoto, Masakazu Nakamura, Daisaku Masuda, Shizuya Yamashita, Masaji Ushiyama, Toshiaki Komori, Naohisa Fujita, Shinji Yokoyama, Tamio Teramoto
AIM: Most epidemiological and clinical studies calculated low-density lipoprotein-cholesterol (LDL-C) by Friedewald's formula which cannot be used in the postprandial samples. Although the homogeneous assays with poor analytical performance were withdrawn from the market, it remained unclear whether the currently available reagents for LDL-C and high-density lipoprotein-cholesterol (HDL-C) are as accurate for postprandial samples as for fasting samples. METHODS: Fresh blood samples were collected from 59 non-diseased and 109 diseased subjects...
March 17, 2017: Journal of Atherosclerosis and Thrombosis
https://www.readbyqxmd.com/read/28315964/biological-predictors-of-radiosensitivity-in-head-and-neck-squamous-cell-carcinoma
#4
Mathias Fiedler, Florian Weber, Matthias G Hautmann, Frank Haubner, Torsten E Reichert, Christoph Klingelhöffer, Stephan Schreml, Johannes K Meier, Arndt Hartmann, Tobias Ettl
OBJECTIVES: The aim of this study is to investigate the influence of prognostic biomarkers on radiosensitivity and survival of advanced head and neck squamous cell carcinomas treated by primary (chemo)radiation. MATERIAL AND METHODS: The clinicopathological data and immunohistochemical staining of p16, c-Met, survivin, PD-1, and PD-L1 of 82 primarily (chemo)irradiated patients with head and neck squamous cell carcinoma were analyzed. Associations with local and locoregional radiation response, overall survival (OS), disease-free (DFS), and disease-specific survival (DSS) were assessed...
March 18, 2017: Clinical Oral Investigations
https://www.readbyqxmd.com/read/28315949/-89-zr-onartuzumab-pet-imaging-of-c-met-receptor-dynamics
#5
Martin Pool, Anton G T Terwisscha van Scheltinga, Arjan Kol, Danique Giesen, Elisabeth G E de Vries, Marjolijn N Lub-de Hooge
PURPOSE: c-MET and its ligand hepatocyte growth factor are often dysregulated in human cancers. Dynamic changes in c-MET expression occur and might predict drug efficacy or emergence of resistance. Noninvasive visualization of c-MET dynamics could therefore potentially guide c-MET-directed therapies. We investigated the feasibility of (89)Zr-labelled one-armed c-MET antibody onartuzumab PET for detecting relevant changes in c-MET levels induced by c-MET-mediated epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib resistance or heat shock protein-90 (HSP90) inhibitor NVP-AUY-922 treatment in human non-small-cell lung cancer (NSCLC) xenografts...
March 19, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28314274/increased-hgf-expression-induces-resistance-to-c-met-tyrosine-kinase-inhibitors-in-gastric-cancer
#6
So Yeong Ahn, Jin Kim, Min A Kim, Jiwoon Choi, Woo Ho Kim
BACKGROUND: Increased expression of hepatocyte growth factor (HGF) and MET proto-oncogene (c-MET) is associated with poor prognosis in various cancer types. Recently, it was reported that the expression of HGF induces resistance to tyrosine kinase inhibitors (TKIs) targeting epidermal growth factor receptor, human epidermal receptor receptor 2, and b-raf proto-oncogene. Here, we investigated the effects of HGF overexpression in gastric cancer cells in the absence or presence of c-MET TKIs...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28291253/mecp2-mediated-epigenetic-silencing-of-mir-137-contributes-to-colorectal-adenoma-carcinoma-sequence-and-tumor-progression-via-relieving-the-suppression-of-c-met
#7
Tao Chen, Shi-Lun Cai, Jian Li, Zhi-Peng Qi, Xu-Quan Li, Le-Chi Ye, Xiao-Feng Xie, Ying-Yong Hou, Li-Qing Yao, Mei-Dong Xu, Ping-Hong Zhou, Jian-Min Xu, Yun-Shi Zhong
The molecular mechanisms underlying colorectal cancer (CRC) development remain elusive. In this study, we examined the miRNA and mRNA expressions in the adenoma-carcinoma sequence (ACS), a critical neoplastic progression in CRC development. We found that miR-137 was down-regulated in all adenoma and carcinoma tissues. Low miR-137 levels were correlated negatively with tumor progression and metastasis. Then we identified the inhibition effect of the miR-137 in CRC development, both in CRC cell lines and mouse models...
March 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28284719/hypoxia-mediated-mechanisms-associated-with-antiangiogenic-treatment-resistance-in-glioblastomas
#8
REVIEW
Sean Mahase, Rachel N Rattenni, Pieter Wesseling, William Leenders, Clarissa Baldotto, Rajan Jain, David Zagzag
Glioblastomas (GBMs) are malignant tumors characterized by their vascularity and invasive capabilities. Antiangiogenic therapy (AAT) is a treatment option that targets GBM-associated vasculature to mitigate the growth of GBMs. However, AAT demonstrates transient effects, because many patients eventually develop resistance to this treatment. Several recent studies attempt to explain the molecular and biochemical basis of resistance to AAT in GBM patients. Experimental investigations suggest that the induction of extensive intratumoral hypoxia plays a key role in GBM escape from AAT...
March 8, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28284101/relationship-between-14-c-meaib-uptake-and-amino-acid-transporter-family-gene-expression-levels-or-proliferative-activity-in-a-pilot-study-in-human-carcinoma-cells-comparison-with-3-h-methionine-uptake
#9
Shinya Kagawa, Ryuichi Nishii, Tatsuya Higashi, Hiroshi Yamauchi, Emi Ogawa, Hiroyuki Okudaira, Masato Kobayashi, Mitsuyoshi Yoshimoto, Naoto Shikano, Keiichi Kawai
INTRODUCTION: To clarify the difference between system A and L amino acid transport imaging in PET clinical imaging, we focused on the use of α-[N-methyl-(11)C]-methylaminoisobutyric acid ([(11)C]MeAIB), and compared it with [S-methyl-(11)C]-L-methionine ([(11)C]MET). The aim of this study was to assess the correlation of accumulation of these two radioactive amino acid analogs with expression of amino acid transporters and cell proliferative activity in carcinoma cells. METHODS: Amino acid uptake inhibitor studies were performed in four human carcinoma cells (epidermal carcinoma A431, colorectal carcinoma LS180, and lung carcinomas PC14/GL and H441/GL) using the radioisotope analogs [(3)H]MET and [(14)C]MeAIB...
January 26, 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/28272703/the-study-of-endogenous-hepatocyte-growth-factor-in-the-pathogenesis-of-intracranial-aneurysms
#10
L-L Yu, Y-J Liu, Z-H Wang, L Shi, L-X Liu
OBJECTIVE: Inflammation as a significant influence factor plays an important role in the formation and rupture of intracranial aneurysms. However, based on plenty of related studies, it is believed that the hepatocyte growth factor (HGF) is able to prevent vascular inflammation. This paper, therefore, explored the role and mechanism of endogenous HGF in the pathogenesis of intracranial aneurysms. MATERIALS AND METHODS: 16 blood samples were collected from the intracranial aneurysms and the lumens of the femoral artery of 16 patients...
February 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28272674/the-role-of-egfr-hepatocyte-growth-factor-receptor-c-met-c-erbb2-her2-neu-and-clinicopathological-parameters-in-the-pathogenesis-and-prognosis-of-chordoma
#11
Zeynep Tosuner, Süheyla Uyar Bozkurt, Türker Kiliç, Baran Yilmaz
OBJECTIVE: Chordoma is a rare malignant bone tumor with a poor outcome. Although radiotherapy and gamma knife surgery have been used for treatment, providing a cure for the tumor is not easy, because of the frequent recurrences. Molecular targeted therapy against tyrosine kinases has been effective in the treatment of malignancies such as breast and lung cancers and brain tumors. We aimed to analyse the histopathological features of chordomas and the immunoexpression profiles of the three receptor tyrosine kinases of EGFR, c-Met and c-Erb-B2 in chordomas...
February 4, 2017: Türk Patoloji Dergisi
https://www.readbyqxmd.com/read/28271563/gastric-cancer-managment-kinases-as-a-target-therapy
#12
Batoul Farran, Susanne Müller, Raquel C Montenegro
The molecular diagnostics revolution has reshaped the practice of oncology by facilitating the identification of genetic, epigenetic and proteomic modifications correlated with cancer, thus delineating 'oncomaps' for various cancer types. These advances have enhanced our understanding of gastric cancer, one of the most fatal diseases worldwide, and culminated in the approval of novel molecular therapies such as trastuzumab. Gastric tumours display recurrent aberrations in key kinase oncogenes such as Her2, EGFR, PI3K, mTOR or c-Met, suggesting that these receptors are amenable to inhibition using specific drug agents...
March 7, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28270618/novel-combinatorial-screening-identifies-neurotrophic-factors-for-selective-classes-of-motor-neurons
#13
Sébastien Schaller, Dorothée Buttigieg, Alysson Alory, Arnaud Jacquier, Marc Barad, Mark Merchant, David Gentien, Pierre de la Grange, Georg Haase
Numerous neurotrophic factors promote the survival of developing motor neurons but their combinatorial actions remain poorly understood; to address this, we here screened 66 combinations of 12 neurotrophic factors on pure, highly viable, and standardized embryonic mouse motor neurons isolated by a unique FACS technique. We demonstrate potent, strictly additive, survival effects of hepatocyte growth factor (HGF), ciliary neurotrophic factor (CNTF), and Artemin through specific activation of their receptor complexes in distinct subsets of lumbar motor neurons: HGF supports hindlimb motor neurons through c-Met; CNTF supports subsets of axial motor neurons through CNTFRα; and Artemin acts as the first survival factor for parasympathetic preganglionic motor neurons through GFRα3/Syndecan-3 activation...
March 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28263602/aldehyde-oxidase-mediated-metabolism-in-drug-like-molecules-a-combined-computational-and-experimental-study
#14
Yuan Xu, Liang Li, Yulan Wang, Jing Xing, Lei Zhou, Dafang Zhong, Xiaomin Luo, Hualiang Jiang, Kaixian Chen, Mingyue Zheng, Pan Deng, Xiaoyan Chen
Aldehyde oxidase (AOX) is an important drug-metabolizing enzyme. However, the current in vitro models for evaluating AOX metabolism are sometimes misleading, and preclinical animal models generally fail to predict human AOX-mediated metabolism. In this study, we report a combined computational and experimental investigation of drug-like molecules that are potential aldehyde oxidase substrates, of which multiple sites of metabolism (SOMs) mediated by AOX and their preferences for the reaction can be unambiguously identified...
March 6, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28260185/-11-c-l-methyl-methionine-dynamic-pet-ct-of-skeletal-muscle-response-to-protein-supplementation-compared-to-l-ring-13-c6-phenylalanine-infusion-with-serial-muscle-biopsy
#15
Emily J Arentson-Lantz, Isra H Saeed, Lynda A Frassetto, Umesh Masharani, Roy J Harnish, Youngho Seo, Henry F VanBrocklin, Randall A Hawkins, Carina Mari-Aparici, Miguel H Pampaloni, James Slater, Douglas Paddon-Jones, Thomas F Lang
OBJECTIVE: The objective of this study was to determine if clinical dynamic PET/CT imaging with (11)C-L-methyl-methionine ((11)C-MET) in healthy older women can provide an estimate of tissue-level post-absorptive and post-prandial skeletal muscle protein synthesis that is consistent with the more traditional method of calculating fractional synthesis rate (FSR) of muscle protein synthesis from skeletal muscle biopsies obtained during an infusion of L-[ring (13)C6] phenylalanine ((13)C6-Phe)...
March 4, 2017: Annals of Nuclear Medicine
https://www.readbyqxmd.com/read/28259294/understanding-c-met-signalling-in-squamous-cell-carcinoma-of-the-head-neck
#16
REVIEW
P Szturz, E Raymond, C Abitbol, S Albert, A de Gramont, S Faivre
c-MET is a membrane spanning receptor tyrosine kinase for hepatocyte growth factor (HGF) also termed scatter factor. Transmitting signals from mesenchymal to epithelial cells, the HGF/c-MET axis mediates a range of biological processes that stimulate proliferation, motility, invasiveness, morphogenesis, apoptosis, and angiogenesis. Aberrant c-MET signal transduction favours tumorigenesis with the acquisition of invasive and metastatic phenotypes. Biological functions of c-MET may strongly vary according to microenvironmental changes, which occur at different stages of tumorigenesis and include also HGF/c-MET activation in stromal cells...
March 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28258248/caf-derived-hgf-promotes-cell-proliferation-and-drug-resistance-by-up-regulating-the-c-met-pi3k-akt-and-grp78-signaling-in-ovarian-cancer-cells
#17
De Ying Wei, Feng Geng, Shu Mei Liang, Hui Zhao, Ming Liu, Hong Qing Wang
The tumor microenvironment which is a highly heterogeneous entity plays crucial roles in cancer progression. As the most prominent stromal cell types, cancer-associated fibroblasts (CAFs) produce a variety of factors into the tumor microenvironment. In this study, we firstly isolated CAFs from tumor tissues of the patients with ovarian cancer and demonstrated that hepatocyte growth factor (HGF) was highly expressed in the supernatant of CAFs. CAF-derived HGF or human recombinant HGF promoted cell proliferation in human ovarian cell lines SKOV3 and HO-8910 cells...
March 3, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28255772/isolation-culture-and-biological-characteristics-of-multipotent-porcine-skeletal-muscle-satellite-cells
#18
Jinjuan Yang, Hao Liu, Kunfu Wang, Lu Li, Hongyi Yuan, Xueting Liu, Yingjie Liu, Weijun Guan
Skeletal muscle has a huge regenerative potential for postnatal muscle growth and repair, which mainly depends on a kind of muscle progenitor cell population, called satellite cell. Nowadays, the majority of satellite cells were obtained from human, mouse, rat and other animals but rarely from pig. In this article, the porcine skeletal muscle satellite cells were isolated and cultured in vitro. The expression of surface markers of satellite cells was detected by immunofluorescence and RT-PCR assays. The differentiation capacity was assessed by inducing satellite cells into adipocytes, myoblasts and osteoblasts...
March 2, 2017: Cell and Tissue Banking
https://www.readbyqxmd.com/read/28253717/pha665752-inhibits-the-hgf-stimulated-migration-and-invasion-of-cells-by-blocking-pi3k-akt-pathway-in-human-cell-line-uveal-melanoma
#19
Z Wang, C He, L Liu, N Ma, X Chen, D Zheng, G H Qiu
HGF/c-MET is frequently associated with tumor metastasis in many cancers, including uveal melanoma (UM). PHA665752, a selective c-MET inhibitor, exhibits anticancer activity through inhibiting cell motility in some cancers. In this study, we investigated the effects of PHA665752 on UM cell lines M17 and SP6.5. Our data show that HGF stimulated the motility of UM cells, and induced the activation of both c-MET and PI3K/AKT, but not ERK1/2. Moreover, consistent with the amount of c-MET within the nucleus, PHA665752 significantly inhibited HGF-promoted cell motility and suppressed the phosphorylation of c-MET and PI3K/AKT, but not ERK1/2 induced by HGF...
March 3, 2017: Neoplasma
https://www.readbyqxmd.com/read/28243120/correlations-of-microvascular-blood-flow-of-contrast-enhanced-ultrasound-and-hgf-c-met-signaling-pathway-with-clinicopathological-features-and-prognosis-of-patients-with-hepatocellular-carcinoma
#20
Peng-Hui Zhuang, Lei Xu, Lu Gao, Wei Lu, Li-Tao Ruan, Jin Yang
The study is designed to explore the correlations of microvascular blood flow of contrast-enhanced ultrasound (CEUS) and hepatocyte growth factor (HGF)/c-Met signaling pathway with clinicopathological features and prognosis of patients with hepatocellular carcinoma (HCC). One hundred and eighteen patients pathologically diagnosed as primary HCC were selected. All HCC patients underwent CEUS examination before operation. HCC tissues and adjacent normal tissue specimens were obtained to detect the protein rates of HGF and c-Met expressions by immunohistochemistry...
2017: OncoTargets and Therapy
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