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https://www.readbyqxmd.com/read/29768367/the-phenotypic-heterogeneity-of-patients-with-marfan-related-disorders-and-their-variant-spectrums
#1
Go Hun Seo, Yoon-Myung Kim, Eungu Kang, Gu-Hwan Kim, Eul-Ju Seo, Beom Hee Lee, Jin-Ho Choi, Han-Wook Yoo
Marfan syndrome (MFS) and Loeys-Dietz syndrome (LDS) are the connective tissue disorders characterized by aortic root aneurysm and/or dissection and various additional features. We evaluated the correlation of these mutations with the phenotypes and determined the clinical applicability of the revised Ghent criteria.The mutation spectrum and phenotypic heterogeneities of the 83 and 5 Korean patients with suspected MFS and LDS were investigated as a retrospective manner. In patients with suspected MFS patients, genetic testing was conducted in half of 44 patients who met the revised Ghent criteria clinically and half of 39 patients who did not meet these criteria...
May 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29767258/pd-l1-mrna-expression-in-egfr-mutant-lung-adenocarcinoma
#2
Kazutoshi Isobe, Atsushi Kakimoto, Tetuo Mikami, Kyohei Kaburaki, Hiroshi Kobayashi, Takahiro Yoshizawa, Yuta Nakano, Takashi Makino, Hajime Otsuka, Go Sano, Keishi Sugino, Susumu Sakamoto, Yujiro Takai, Naobumi Tochigi, Akira Iyoda, Sakae Homma
Molecular mechanisms of programmed death-ligand 1 (PD-L1) mRNA expression and roles of apoptosis and biomarkers are poorly understood in epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma patients. Thirty-three patients with recurrent postoperative EGFR-mutant lung adenocarcinoma (exon 19 deletion in 16, L858R in 15, G719C in 2 patients) treated with gefitinib were studied. PD-L1 mRNA expression of formalin-fixed paraffin-embedded paratumoral and intratumoral tissues was quantified by PCR. Correlations of PD-L1 mRNA expression with BIM, p53 upregulated modular of apoptosis (PUMA), human epidermal growth factor receptor 2 (HER2), mesenchymal-epithelial transition (MET), EGFR, and vascular endothelial growth factor A (VEGFA) were determined...
May 16, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29728634/quantification-and-localization-of-oncogenic-receptor-tyrosine-kinase-variant-transcripts-using-molecular-inversion-probes
#3
Corina N A M van den Heuvel, Arvid I Das, Tessa de Bitter, Femke Simmer, Thomas Wurdinger, Miguel Angel Molina-Vila, William P J Leenders
Oncogenic membrane receptor tyrosine kinases such as MET and EGFR, or auto-active variants thereof, are important targets for cancer precision therapy. Targeted inhibition of these oncogenic receptors however invariably leads to resistance, resulting from acquisition of resistance-inducing mutations or from selective outgrowth of a priori resistant tumour cells. Most applied molecular protocols cannot distinguish between intracellular and intercellular heterogeneity of oncogene (variant) expression, which may lead to misinterpretation of the molecular make-up of a cancer and suboptimal application of targeted therapies...
May 4, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29690664/-clinicopathologic-features-of-gastric-plexiform-fibromyxoma
#4
G M Hu, H P Chen, Q Y Liu, X C Shi, H F Wu, Y K Feng, J L Ren, C F Wang
Objective: To analyse the clinicopathologic features of gastric plexiform fibromyxoma (PF) including diagnosis, differential diagnosis, immunohistochemistry and molecular pathology. Methods: Eight cases of PF were collected from June 2006 to June 2017 at the Second Affiliated Hospital of Zhengzhou University and the First Affiliated Hospital of Zhengzhou University. The clinicopathologic findings of eight cases of PF were retrospectively analyzed, and immunohistochemistry (EnVision method) and molecular detection of glioma-associated oncogene homologue 1 (GLI1) gene translocation were performed...
April 8, 2018: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/29690663/-expression-of-succinate-dehydrogenase-subunit-protein-in-succinate-dehydrogenase-deficient-gastrointestinal-stromal-tumors
#5
Y J Zhang, Y H Cheng, L X Guo, N Q Wang, H Liu
Objective: To investigate the expression of succinate dehydrogenase complex subunit protein in succinate dehydrogenase-deficient gastrointestinal stromal tumors (SDH-deficient GISTs). Methods: Three hundred fifty-two cases of GISTs were collected from January 2003 to January 2017 at the Affiliated Hospital of Guizhou Medical University and West China Hospital of Sichuan University.The expression of succinate dehydrogenase subunit protein was detected by immunohistochemical EnVision technique in 352 cases of GISTs, and the negative cases were analyzed for clinicopathologic features and outcome...
April 8, 2018: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/29621416/c-met-inhibitors-for-advanced-non-small-cell-lung-cancer
#6
REVIEW
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
https://www.readbyqxmd.com/read/29507487/standardizing-biomarker-testing-for-canadian-patients-with-advanced-lung-cancer
#7
B Melosky, N Blais, P Cheema, C Couture, R Juergens, S Kamel-Reid, M-S Tsao, P Wheatley-Price, Z Xu, D N Ionescu
Background: The development and approval of both targeted and immune therapies for patients with advanced non-small cell lung cancer (nsclc) has significantly improved patient survival rates and quality of life. Biomarker testing for patients newly diagnosed with nsclc, as well as for patients progressing after treatment with epidermal growth factor receptor ( EGFR ) inhibitors, is the standard of care in Canada and many parts of the world. Methods: A group of thoracic oncology experts in the field of thoracic oncology met to describe the standard for biomarker testing for lung cancer in the Canadian context, focusing on evidence-based recommendations for standard-of-care testing for EGFR , anaplastic lymphoma kinase ( ALK ), ROS1 , BRAF V600 and programmed death-ligand (PD-L1) at the time of diagnosis of advanced disease and EGFR T790M upon progression...
February 2018: Current Oncology
https://www.readbyqxmd.com/read/29489023/kras-mutation-is-predictive-of-outcome-in-patients-with-pulmonary-sarcomatoid-carcinoma
#8
Mitra Mehrad, Somak Roy, William A LaFramboise, Patti Petrosko, Caitlyn Miller, Pimpin Incharoen, Sanja Dacic
AIMS: Pulmonary sarcomatoid carcinoma (PSC) is a poorly differentiated non-small-cell lung carcinoma (NSCLC) with aggressive behaviour. This study aimed to evaluate the prognostic clinicopathological and genetic characteristics of PSCs. METHODS AND RESULTS: Fifty-three cases of surgically treated PSCs were selected, 23 of which were subjected to mutation and copy number variation analysis using the 50-gene Ion AmpliSeq Cancer Panel. The majority of the patients were male (32 of 53, 60...
February 28, 2018: Histopathology
https://www.readbyqxmd.com/read/29467863/detection-of-egfr-and-braf-mutations-by-competitive-allele-specific-taqman-polymerase-chain-reaction-in-lung-adenocarcinoma
#9
Yang Yang, Yi Meng, Hang Zhang, Xiaoyan Shen, Rutian Li, Lixia Yu, Baorui Liu, Lifeng Wang
Epithelial growth factor receptor (EGFR)-tyrosine kinase inhibitors are the standard first-line treatment for patients with metastatic non-small cell lung cancer (NSCLC) expressing sensitive EGFR-mutants. Other drugs target different driver mutants, including the serine/threonine-protein kinase B-raf (BRAF) inhibitor dabrafenib, which has exhibited promising efficacy for treating patients with metastatic BRAF-mutated NSCLC. Therefore, identifying patients carrying mutations that may be treated using targeted therapies is important...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29456848/survival-associated-factors-of-first-line-egfr-tyrosine-kinase-inhibitor-responders-and-non-responders-in-lung-adenocarcinoma-patients-with-common-egfr-mutations
#10
Ming-Szu Hung, Yu-Hung Fang, Yu-Ching Lin, Jr-Hau Lung, Meng-Jer Hsieh, Ying-Huang Tsai
The aim of the present retrospective cohort study was to elucidate the clinical presentation of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) responders and non-responders in lung adenocarcinoma patients with common EGFR mutations. The cohort included 131 lung adenocarcinoma patients with common exon 19 or exon 21 EGFR mutations, who were receiving first-line EGFR-TKI therapy. The patient characteristics, treatment regimen and outcomes were recorded and analyzed. Of the 131 patients, 104 (79...
March 2018: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29435981/forty-nine-gastric-cancer-cell-lines-with-integrative-genomic-profiling-for-development-of-c-met-inhibitor
#11
Hyun Jeong Kim, Sun Kyoung Kang, Woo Sun Kwon, Tae Soo Kim, Inhye Jeong, Hei-Cheul Jeung, Michael Kragh, Ivan D Horak, Hyun Cheol Chung, Sun Young Rha
Receptor tyrosine kinase MET (c-MET) has received considerable attention as a potential target for gastric cancer (GC) therapy and a number of c-MET inhibitors have been developed. For successful drug development, proper preclinical studies especially using patient derived cancer cell lines are very important. We profiled MET and MET-related characteristics in 49 GC cell lines to utilize them as models in preclinical studies of GC. Forty-nine cell lines were analyzed for genetic, biological, and molecular status to characterize MET and MET-related molecules...
July 1, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29416799/correlation-among-genetic-variations-of-c-met-in-chinese-patients-with-non-small-cell-lung-cancer
#12
Jianchun Duan, Xiaodan Yang, Jun Zhao, Minglei Zhuo, Zhijie Wang, Tongtong An, Hua Bai, Jie Wang
Background: The purpose of our research was to determine the correlation of amplification, protein expression and somatic mutation of c-MET in IIIb-IV stage NSCLC (Non-small cell lung cancer). We also explored correlation of c-MET variation with clinical outcome. Results: c-MET expression was observed in 28.6% (56/196) cases, and among those 13.8% (27/196) were shown to be FISH positive. Only 2.67% patients in this study carried the c-MET mutation. Cases with c-MET FISH positive were all IHC positive ,but in IHC positive cases, only half were FISH positive...
January 5, 2018: Oncotarget
https://www.readbyqxmd.com/read/29381967/responses-to-crizotinib-and-disease-monitoring-with-circulating-tumor-cells-in-lung-adenocarcinoma-patient-with-met-exon-14-skipping-mutation-a-case-report
#13
Xiang Tan, Lei Dai, Yongyong Wang, Guanbiao Liang, Nuo Yang, Mingwu Chen
RATIONALE: Mesenchymal-to-epithelial transition (MET) exon 14 skipping mutation was a targetable alteration in nonsmall-cell lung cancer (NSCLC), and the MET inhibitor of crizotinib had the most efficacy among all the targeted drugs. Most of the cancer-related deaths are associated with metastasis. Circulating tumor cells (CTCs) have been a valuable biomarker in assessing metastasis. Recent experiences suggested that CTCs detection may help improve diagnosis and predict prognosis for patients with NSCLC...
November 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29338938/distinct-met-protein-localization-associated-with-met-exon-14-mutation-types-in-patients-with-non-small-cell-lung-cancer
#14
Tian Qiu, Weihua Li, Tongtong Zhang, Puyuan Xing, Wenting Huang, Bingning Wang, Lixia Chu, Lei Guo, Xiuyun Liu, Yan Li, Jianming Ying, Junling Li
BACKGROUND: The MET gene has been recognized as a potential important therapeutic target in non-small-cell lung cancer (NSCLC). We sought to investigate the MET exon 14 mutations in a cohort of Chinese patients with NSCLC. METHODS: We tested 461 NSCLCs for MET exon 14 mutations by sequencing whole exon 14 and its flanking introns. The protein expression was determined by immunohistochemical analysis. RESULTS: In this study, we identified MET exon 14 mutations in 9 (2...
December 21, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/29217198/clinical-molecular-and-computational-analysis-in-two-cases-with-mitochondrial-encephalomyopathy-associated-with-suclg1-mutation-in-a-consanguineous-family
#15
Marwa Maalej, Amel Tej, Jihène Bouguila, Samia Tilouche, Senda Majdoub, Boudour Khabou, Mouna Tabbebi, Rahma Felhi, Marwa Ammar, Emna Mkaouar-Rebai, Leila Keskes, Lamia Boughamoura, Faiza Fakhfakh
Deficiency of the mitochondrial enzyme succinyl COA ligase (SUCL) is associated with encephalomyopathic mtDNA depletion syndrome and methylmalonic aciduria. This disorder is caused by mutations in both SUCL subunits genes: SUCLG1 (α subnit) and SUCLA2 (β subnit). We report here, two Tunisian patients belonging to a consanguineous family with mitochondrial encephalomyopathy, hearing loss, lactic acidosis, hypotonia, psychomotor retardation and methylmalonic aciduria. Mutational analysis of SUCLG1 gene showed, for the first time, the presence of c...
January 8, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29188469/met-targeting-antibody-emibetuzumab-and-kinase-inhibitor-merestinib-as-single-agent-or-in-combination-in-a-cancer-model-bearing-met-exon-14-skipping
#16
S Betty Yan, Suzane L Um, Victoria L Peek, Jennifer R Stephens, Wei Zeng, Bruce W Konicek, Ling Liu, Jason R Manro, Volker Wacheck, Richard A Walgren
Purpose Approximately 3% of lung cancer bears mutations leading to MET exon 14 skipping, an oncogenic driver which is further evidenced by case reports of patient response to MET kinase inhibitor treatment. Approximately 15% of tumors harboring MET exon14 skipping have concurrent MET amplification. Experimental Design Merestinib is a type II MET kinase inhibitor. Emibetuzumab, a bivalent anti-MET antibody, internalizes MET receptor. Each single agent and the combination were evaluated in the Hs746t gastric cancer line bearing MET exon14 skipping and MET amplification...
November 29, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/29139039/genetic-screening-and-molecular-characterization-of-met-alterations-in-non-small-cell-lung-cancer
#17
M Saigi, A McLeer-Florin, E Pros, E Nadal, E Brambilla, M Sanchez-Cespedes
PURPOSE: Aberrant activation of MET as a result of exon 14-skipping (METex14) mutations or gene amplification is an oncogenic mechanism in non-small cell lung carcinoma (NSCLC) and a potential therapeutic target. The purpose of this study was to characterize MET alterations in a cohort of NSCLC patients treated with surgery. METHODS AND PATIENTS: 157 NSCLCs of various histopathologies, including pulmonary sarcomatoid carcinomas (PSC), were tested for MET alterations...
November 14, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/29066084/comparative-genomic-profiling-of-matched-primary-and-metastatic-tumors-in-renal-cell-carcinoma
#18
Maria F Becerra, Ed Reznik, Almedina Redzematovic, Daniel M Tennenbaum, Mahyar Kashan, Mazyar Ghanaat, Jozefina Casuscelli, Brandon Manley, Philip Jonsson, Renzo G DiNatale, Kyle A Blum, Jeremy C Durack, Stephen B Solomon, Maria E Arcila, Caitlin Bourque, Nick Socci, Maria I Carlo, Chung-Han Lee, Martin H Voss, Darren R Feldman, Robert J Motzer, Jonathan A Coleman, Paul Russo, Emily H Cheng, A Ari Hakimi, James J Hsieh
BACKGROUND: Next-generation sequencing (NGS) studies of matched pairs of primary and metastatic tumors in renal cell carcinoma (RCC) have been limited to small cohorts. OBJECTIVE: To evaluate the discordance in somatic mutations between matched primary and metastatic RCC tumors. DESIGN, SETTING, AND PARTICIPANTS: Primary tumor (P), metastasis (M), and germline DNA from 60 patients with RCC was subjected to NGS with a targeted exon capture-based assay of 341 cancer-associated genes...
October 20, 2017: European Urology Focus
https://www.readbyqxmd.com/read/29063069/targeting-met-in-cancer-therapy
#19
REVIEW
Hong-Nan Mo, Peng Liu
MET encodes a receptor tyrosine kinase c-MET for hepatocyte growth factor (HGF). The specific combination of c-MET and HGF activates downstream signaling pathways to trigger cell migration, proliferation, and angiogenesis. MET exon 14 alterations and MET gene amplification play a critical role in the origin of cancer. Several monoclonal antibodies and small-molecule inhibitors of c-MET have been evaluated in clinical trials. In patients with advanced non-small cell lung cancer, cabozantinib and crizotinib showed clear efficacy with a generally tolerable adverse events profile...
September 2017: Chronic Diseases and Translational Medicine
https://www.readbyqxmd.com/read/29037218/clinicopathologic-features-and-treatment-efficacy-of-chinese-patients-with-braf-mutated-metastatic-colorectal-cancer-a-retrospective-observational-study
#20
Xicheng Wang, Qing Wei, Jing Gao, Jian Li, Jie Li, Jifang Gong, Yanyan Li, Lin Shen
BACKGROUND: The prognostic role of the V600E mutation of v-raf murine sarcoma viral oncogene homolog B1 (BRAF) in metastatic colorectal cancer (mCRC) is well established, but the therapeutic regimen targeting this disease is lacking. This study aimed to analyze the clinicopathologic features of and treatment efficacy of commonly used regimens on BRAF-mutated mCRCs. METHODS: We collected and reviewed the medical records of mCRC patients treated at Peking University Cancer Hospital & Institute (Beijing, China) between July 2011 and July 2016...
October 16, 2017: Chinese Journal of Cancer
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