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Met mutation

Sara K Young-Baird, Byung-Sik Shin, Thomas E Dever
The heterotrimeric eukaryotic translation initiation factor (eIF) 2 plays critical roles in delivering initiator Met-tRNAiMet to the 40S ribosomal subunit and in selecting the translation initiation site. Genetic analyses of patients with MEHMO syndrome, an X-linked intellectual disability syndrome, have identified several unique mutations in the EIF2S3 gene that encodes the γ subunit of eIF2. To gain insights into the molecular consequences of MEHMO syndrome mutations on eIF2 function, we generated a yeast model of the human eIF2γ-I259M mutant, previously identified in a patient with MEHMO syndrome...
December 4, 2018: Nucleic Acids Research
Sied Kebir, Manuel Weber, Lazaros Lazaridis, Cornelius Deuschl, Teresa Schmidt, Christoph Mönninghoff, Kathy Keyvani, Lale Umutlu, Daniela Pierscianek, Michael Forsting, Ulrich Sure, Martin Stuschke, Christoph Kleinschnitz, Björn Scheffler, Patrick M Colletti, Domenico Rubello, Christoph Rischpler, Martin Glas
PURPOSE: With the advent of the revised WHO classification from 2016, molecular features, including isocitrate dehydrogenase (IDH) mutation have become important in glioma subtyping. This pilot trial analyzed the potential for C-methionine (MET) PET/MRI in classifying glioma according to the revised WHO classification using a machine learning model. METHODS: Patients with newly diagnosed WHO grade II-IV glioma underwent preoperative MET-PET/MRI imaging. Patients were retrospectively divided into four groups: IDH wild-type glioblastoma (GBM), IDH wild-type grade II/III glioma (GII/III-IDHwt), IDH mutant grade II/III glioma with codeletion of 1p19q (GII/III-IDHmut1p19qcod) or without 1p19q-codeletion (GII/III-IDHmut1p19qnc)...
December 3, 2018: Clinical Nuclear Medicine
Binliang Liu, Tao An, Meiying Li, Zongbi Yi, Chunxiao Li, Xiaoying Sun, Xiuwen Guan, Lixi Li, Yanfeng Wang, Yuhui Zhang, Binghe Xu, Fei Ma, Yixin Zeng
BACKGROUND: An increasing number of cancer patients die of cardiovascular diseases. The cardiotoxicity of chemotherapy is particularly important in triple-negative breast cancer (TNBC) with limited therapeutic options. Cardiac autophagy is an important mechanism of cardiotoxicity. This research was aimed to investigate the cardiotoxicity of chemotherapy in TNBC, screen the susceptible population, and determine the relationship between cardiotoxicity and autophagy-related polymorphisms...
December 4, 2018: Cancer communications
Sue Zann Lim, Cedric Chuan Young Ng, Vikneswari Rajasegaran, Peiyong Guan, Sathiyamoorthy Selvarajan, Aye Aye Thike, Nur Diyana Binte Md Nasir, Valerie Cui Yun Koh, Benita Kiat Tee Tan, Kong Wee Ong, Bin Tean Teh, Puay Hoon Tan
PURPOSE: We aimed to investigate the genomic profile of breast sarcomas (BS) and compare with that of malignant phyllodes tumours (MPT). METHODS: DNA was extracted from formalin-fixed, paraffin-embedded (FFPE) specimens from 17 cases of BS diagnosed at Singapore General Hospital from January 1991 to December 2014. Targeted deep sequencing and copy number variation (CNV) analysis on 16 genes, which included recurrently mutated genes in phyllodes tumours and genes associated with breast cancer, were performed on these samples...
December 3, 2018: Breast Cancer Research and Treatment
Masanobu Tsubaki
Resistance to the breakpoint cluster region-abelson (BCR-ABL) tyrosine kinase inhibitor (TKI), imatinib, poses a major problem in the treatment of chronic myeloid leukemia (CML). Imatinib resistance often results from a secondary mutation in BCR-ABL1. However, the basis of this BCR-ABL1-independent resistance in the absence of such mutation remains to be elucidated. The aim of the present study is to identify the mechanism of imatinib resistance in CML. To gain insight into BCR-ABL1-independent imatinib resistance mechanisms, we performed an array-based comparative genomic hybridization...
2018: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
Wanhong Xu, Wei Tang, Tingting Li, Xiaoying Zhang, Yi Sun
AC0010 is a pyrrolopyrimidine-based irreversible inhibitor of epidermal growth factor receptor (EGFR), structurally distinct from previously reported pyrimidine-based irreversible EGFR inhibitors such as osimertinib and rociletinib. AC0010 selectively inhibits EGFR T790M mutation in both preclinical and clinical studies. However, AC0010 treatment eventually triggers drug resistance with unknown mechanism. To this end, we established two H1975 NSCLC-derived lines resistant to AC0010 after a series of drug exposure and selection in either nude-mice xenograft tumor (H1975-P) or cell culture (H1975-AVR) settings...
November 29, 2018: Neoplasia: An International Journal for Oncology Research
Birgit Maria Köhler, Hanns-Martin Lorenz, Norbert Blank
OBJECTIVE: Approximately 10%-20% of patients with familial Mediterranean fever (FMF) show an inadequate response to colchicine. In our cohort study, patients with FMF with or without amyloidosis and with an inadequate response to colchicine were treated with anakinra or canakinumab. METHODS: Clinical and laboratory parameters, Mediterranean fever (MEFV) mutations, and patient-reported outcomes were analyzed in 31 patients treated with anakinra or canakinumab. RESULTS: In a cohort of 250 adult patients with FMF, 31 patients were treated with anakinra (n=29) or canakinumab (n=2)...
December 2018: European Journal of Rheumatology
Ramin A Morshed, Seunggu J Han, Shawn L Hervey-Jumper, Melike Pekmezci, Irene Troncon, Susan M Chang, Nicholas A Butowski, Mitchel S Berger
PURPOSE: WHO grade II gliomas are uncommon in patients over the age of 60, and there is a lack in consensus regarding their management. We present molecular tumor characteristics as well as clinical outcomes in patients over the age of 60 undergoing surgical resection of a WHO grade II glioma. METHODS: After receiving IRB approval, patients were identified through the UCSF Brain Tumor Center. Pathologic diagnosis was completed using WHO 2016 grading criteria. RESULTS: Twenty-six patients with a mean age of 66 years met inclusion criteria with a median follow-up of 5...
November 29, 2018: Journal of Neuro-oncology
Darko Castven, Diana Becker, Carolin Czauderna, Diana Wilhelm, Jesper B Andersen, Susanne Strand, Monika Hartmann, Stefanie Heilmann-Heimbach, Wilfried Roth, Nils Hartmann, Beate K Straub, Friederike L Mahn, Sophia Franck, Sharon Pereira, Anna Haupts, Arndt Vogel, Marcus A Wörns, Arndt Weinmann, Stefan Heinrich, Hauke Lang, Snorri S Thorgeirsson, Peter R Galle, Jens U Marquardt
Primary liver cancer (PLC) ranks among the most lethal solid cancers worldwide due to lack of effective biomarkers for early detection and limited treatment options in advanced stages. Development of primary culture models that closely recapitulate phenotypic and molecular diversities of PLC is urgently needed to improve the patient outcome. Long-term cultures of 7 primary liver cancer cell lines of hepatocellular and cholangiocellular origin were established using defined culture conditions. Morphological and histological characteristics of obtained cell lines and xenograft tumors were analyzed and compared to original tumors...
November 28, 2018: International Journal of Cancer. Journal International du Cancer
Christopher D'Avella, Phillip Abbosh, Sumanta K Pal, Daniel M Geynisman
Renal cell carcinoma (RCC) is a commonly diagnosed and histologically diverse urologic malignancy. Clear cell RCC (ccRCC) is by far the most common, followed by the papillary and chromophobe subtypes. Sarcomatoid differentiation is a morphologic change that can be seen in all subtypes that typically portends a poor prognosis. In the past, treatment options for RCC were limited to cytokine-based therapy with a high-toxicity profile and low response rate. An increased understanding of the molecular basis of RCC has led to substantial improvement in treatment options in the form of targeted therapy and immunotherapy...
November 23, 2018: Urologic Oncology
Chiara Cremolini, Daniele Rossini, Emanuela Dell'Aquila, Sara Lonardi, Elena Conca, Marzia Del Re, Adele Busico, Filippo Pietrantonio, Romano Danesi, Giuseppe Aprile, Emiliano Tamburini, Carlo Barone, Gianluca Masi, Francesco Pantano, Francesca Pucci, Domenico C Corsi, Nicoletta Pella, Francesca Bergamo, Eleonora Rofi, Cecilia Barbara, Alfredo Falcone, Daniele Santini
Importance: Based on a small retrospective study, rechallenge with cetuximab-based therapy for patients with KRAS wild-type metastatic colorectal cancer (mCRC) who were previously treated with the same anti-epidermal growth factor receptor-based regimen might be efficacious. Recent data suggest the role of liquid biopsy as a tool to track molecular events in circulating tumor DNA (ctDNA). Objective: To prospectively assess the activity of cetuximab plus irinotecan as third-line treatment for patients with RAS and BRAF wild-type mCRC who were initially sensitive to and then resistant to first-line irinotecan- and cetuximab-based therapy...
November 21, 2018: JAMA Oncology
Sylvie Négrier, Guillaume Moriceau, Valéry Attignon, Véronique Haddad, Daniel Pissaloux, Nicole Guerin, Christian Carrie
BACKGROUND: Renal cell carcinoma represents 3-5% of adult malignant tumors. Metastases are found in 30-40% of patients and brain metastases occurred in more than 10% of them. Despite significant progress in medical treatment, patients with brain metastases still have a limited survival. Cabozantinib, a tyrosine kinase inhibitor directed against vascular endothelial growth factor receptors, was recently registered for the treatment of metastatic renal cell carcinoma. Almost no data are, however, available on patients with brain metastases...
November 25, 2018: Journal of Medical Case Reports
Kazuma Kishi, Hiroshi Sakai, Takashi Seto, Toshiyuki Kozuki, Makoto Nishio, Fumio Imamura, Hiroshi Nokihara, Miyako Satouchi, Shintaro Nakagawa, Takashi Tahata, Kazuhiko Nakagawa
INTRODUCTION: The phase II JO28638 study evaluated first-line onartuzumab plus erlotinib in patients with MET-positive advanced, metastatic, or post-operative recurrent non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. The study was stopped following termination of the global METLung study (OAM4971g), which showed lack of efficacy in the onartuzumab/erlotinib arm. We present immature efficacy and safety data from JO28638. MATERIALS AND METHODS: Chemotherapy-naïve patients aged ≥ 20 years were enrolled...
October 31, 2018: Cancer Treatment and Research Communications
Kyoung-Min Choi, Eunji Cho, Eunjung Kim, Jong Hwan Shin, Minju Kang, Boram Kim, Eun Hee Han, Young-Ho Chung, Jae-Young Kim
Gastric cancer (GC) is one of the most common causes of cancer-associated death. However, traditional therapeutic strategies have failed to significantly improve the survival of patient with advanced GC. While KRAS mutations have been found in some patients with gastric cancer, an effective therapy to treat KRAS-driven gastric cancer has not been established yet. To provide a rationale for clinical application of kinase inhibitors targeting RAS pathways, we first determined the sensitivity of GC cell lines harboring KRAS mutations or amplification to RAS pathway inhibitors...
December 9, 2018: Biochemical and Biophysical Research Communications
H M Gao, C Wang, S S Zhang, D J Xiao, S H Sun, Y S Wang, M X Zhang
OBJECTIVES: To analyse the genetic polymorphism of 21 autosome STR loci in Han population of Shandong Province and the cases with loci mutation or allelic loss typed by Golden e ye® DNA identification system 25A. METHODS: Totally 40 autosome STR loci types of 273 unrelated individuals in Han population of Shandong Province were typed by Golden e ye® DNA identification system 25A and 22NC, and the genetic polymorphism of 21 STR loci in those was analysed. Meanwhile, six cases with loci mutation were analysed by adding the tests with Golden e ye® DNA identification system 22NC, 20Y and 17X...
August 2018: Fa Yi Xue za Zhi
Kei Namba, Kazuhiko Shien, Yuta Takahashi, Hidegiro Torigoe, Hiroki Sato, Takahiro Yoshioka, Tatsuaki Takeda, Eisuke Kurihara, Yusuke Ogoshi, Hiromasa Yamamoto, Junichi Soh, Shuta Tomida, Shinichi Toyooka
Osimertinib (AZD9291) has an efficacy superior to that of standard EGFR-tyrosine kinase inhibitors for the first-line treatment of EGFR-mutant advanced non-small cell lung cancer (NSCLC) patients. However, patients treated with osimertinib eventually acquire drug resistance, and novel therapeutic strategies to overcome acquired resistance are needed. In clinical or preclinical models, several mechanisms of acquired resistance to osimertinib have been elucidated. However, the acquired resistance mechanisms when osimertinib is initially used for EGFR-mutant NSCLC remain unclear...
November 21, 2018: Molecular Cancer Research: MCR
Mirna Perusina Lanfranca, Jenny Lazarus, Xia Shao, Hari Nathan, Marina Pasca Di Magliano, Weiping Zou, Morand Piert, Timothy L Frankel
BACKGROUND: The tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC) contains abundant immunosuppressive tumor-associated macrophages. High level of infiltration is associated with poor outcome and is thought to represent a major roadblock to lymphocyte-based immunotherapy. Efforts to block macrophage infiltration have been met with some success, but noninvasive means to track tumor-associated macrophagess in PDAC are lacking. Translocator protein (TSPO) is a mitochondrial membrane receptor which is upregulated in activated macrophages...
December 2018: Journal of Surgical Research
Roberta Castiglione, Christina Alidousty, Barbara Holz, Svenja Wagener, Till Baar, Carina Heydt, Elke Binot, Susann Zupp, Anna Kron, Jürgen Wolf, Sabine Merkelbach-Bruse, Hans Christian Reinhardt, Reinhard Buettner, Anne Maria Schultheis
Although non-small-cell lung cancer is a leading cause of cancer-related deaths, the molecular characterization and classification of its genetic alterations has drastically changed treatment options and overall survival within the last few decades. In particular, tyrosine kinase inhibitors targeting specific molecular alterations, among other MET, have greatly improved the prognosis of non-small-cell lung cancer patients. Here, we compare the genomic background of a subset of non-small-cell lung cancer cases harboring either a MET high-level amplification (n = 24) or a MET exon 14 skipping mutation (n = 26), using next-generatison sequencing, fluorescence in situ hybridization, immunohistochemistry, and Nanostring nCounter® technology...
November 20, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Wen-Yueh Hung, Jer-Hwa Chang, Yu Cheng, Chi-Kuan Chen, Ji-Qing Chen, Kuo-Tai Hua, Chao-Wen Cheng, Michael Hsiao, Chi-Li Chung, Wei-Jiunn Lee, Ming-Hsien Chien
BACKGROUND/AIMS: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy is a clinical option for non-small cell lung cancer (NSCLC) harboring activating EGFR mutations or for cancer with wild-type (WT) EGFR when chemotherapy has failed. MET receptor activation or MET gene amplification was reported to be a major mechanism of acquired resistance to EGFR-TKI therapy in NSCLC cells. Leukocyte cell-derived chemotaxin 2 (LECT2) is a multifunctional cytokine that was shown to suppress metastasis of hepatocellular carcinoma via inhibiting MET activity...
2018: Cellular Physiology and Biochemistry
Tiffany M Yu, Carl Morrison, Edward J Gold, Alison Tradonsky, Renée J G Arnold
BACKGROUND: Genetic testing for nonsquamous advanced non-small cell lung cancer (aNSCLC) is recommended to guide first-line therapy. Activating mutations can be identified via single-gene testing or next-generation sequencing (NGS). OBJECTIVES: To evaluate the budget impact of NGS instead of single-gene testing for tissue-based molecular assessment of aNSCLC from the US health care payer perspective. METHODS: An annual cohort of newly diagnosed patients with nonsquamous aNSCLC in a hypothetical 1-million-member health care plan was evaluated using a Markov model over 5 years...
November 2018: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
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