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https://www.readbyqxmd.com/read/29324814/comprehensive-molecular-profiling-of-advanced-metastatic-olfactory-neuroblastomas
#1
Jasmina Topcagic, Rebecca Feldman, Anatole Ghazalpour, Jeffrey Swensen, Zoran Gatalica, Semir Vranic
Olfactory neuroblastoma (ONB) is a rare, locally aggressive, malignant neoplasm originating in the olfactory epithelium in the nasal vault. The recurrence rate of ONB remains high and there are no specific treatment guidelines for recurrent/metastatic ONBs. This study retrospectively evaluated 23 ONB samples profiled at Caris Life Sciences (Phoenix, Arizona) using DNA sequencing (Sanger/NGS [Illumina], n = 15) and gene fusions (Archer FusionPlex, n = 6), whole genome RNA microarray (HumanHT-12 v4 beadChip, Illumina, n = 4), gene copy number assays (chromogenic and fluorescent in situ hybridization), and immunohistochemistry...
2018: PloS One
https://www.readbyqxmd.com/read/29285843/exosomes-serve-as-nano-particles-to-suppress-tumor-growth-and-angiogenesis-in-gastric-cancer-by-delivering-hgf-sirna
#2
Haiyang Zhang, Yi Wang, Ming Bai, Junyi Wang, Kegan Zhu, Rui Liu, Shaohua Ge, JiaLu Li, Tao Ning, Ting Deng, Qian Fan, Hongli Li, Wu Sun, Guoguang Ying, Yi Ba
Exosomes derived from cells have been found to mediate signal transduction between cells and to act as efficient carriers to deliver drugs and small RNAs. HGF is known to promote the growth of both cancer cells and vascular cells, and the HGF-cMET pathway is a potential clinical target. Here, we characterized the inhibitory effect of HGF siRNA on tumor growth and angiogenesis in gastric cancer. In addition, we showed that HGF siRNA packed in exosomes can be transported into cancer cells, where it dramatically down-regulates HGF expression...
December 29, 2017: Cancer Science
https://www.readbyqxmd.com/read/29285491/detection-of-met-amplification-in-gastroesophageal-tumor-specimens-using-iqfish
#3
Jan Trøst Jørgensen, Karsten Bork Nielsen, Jens Mollerup, Anna Jepsen, Ning Go
Background: The gene mesenchymal epithelial transition factor (MET) is a proto-oncogene that encodes a transmembrane receptor with intrinsic tyrosine kinase activity known as Met or cMet. MET is found to be amplified in several human cancers including gastroesophageal cancer. Methods: Here we report the MET amplification prevalence data from 159 consecutive tumor specimens from patients with gastric (G), gastroesophageal junction (GEJ) and esophageal (E) adenocarcinoma, using a novel fluorescence in situ hybridization (FISH) assay, MET/CEN-7 IQFISH Probe Mix [an investigational use only (IUO) assay]...
December 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29249325/outcomes-in-patients-with-non-small-cell-lung-cancer-and-acquired-thr790met-mutation-treated-with-osimertinib-a-genomic-study
#4
Chia-Chi Lin, Jin-Yuan Shih, Chong-Jen Yu, Chao-Chi Ho, Wei-Yu Liao, Jih-Hsing Lee, Tzu-Hsiu Tsai, Kang-Yi Su, Min-Shu Hsieh, Yih-Leong Chang, Ya-Ying Bai, Derek De-Rui Huang, Kenneth S Thress, James Chih-Hsin Yang
BACKGROUND: Osimertinib is approved for the treatment of non-small-cell lung cancer in patients who develop the EGFR Thr790Met mutation after treatment with epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKIs). We assessed outcomes in patients with non-small-cell lung cancer and the EGFR Thr790Met mutation who were treated with osimertinib, a third-generation EGFR TKI, after previous treatment failure with one or more other EGFR TKIs. METHODS: Eligible patients had been enrolled at one centre in the AURA study, had shown resistance to a previous EGFR TKI, and had EGFR-activating mutations and acquired Thr790Met mutation detectable in tumour tissue or plasma...
December 14, 2017: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/29246028/challenges-and-future-of-biomarker-tests-in-the-era-of-precision-oncology-can-we-rely-on-immunohistochemistry-ihc-or-fluorescence-in-situ-hybridization-fish-to-select-the-optimal-patients-for-matched-therapy
#5
REVIEW
Young Kwang Chae, Ayush Arya, Lauren Chiec, Hiral Shah, Ari Rosenberg, Sandip Patel, Kirtee Raparia, Jaehyuk Choi, Derek A Wainwright, Victoria Villaflor, Massimo Cristofanilli, Francis Giles
Molecular techniques have improved our understanding of the pathogenesis of cancer development. These techniques have also fueled the rational development of targeted drugs for patient populations stratified by their genetic characteristics. These novel methods have changed the classic paradigm of diagnostic pathology; among them are IHC, FISH, polymerase chain reaction (PCR) and microarray technology. IHC and FISH detection methods for human epidermal growth factor receptor-2 (HER2), epidermal growth factor receptor (EGFR) and programmed death ligand-1 (PD-L1) were recently approved by the Food and Drug Administration (FDA) as routine clinical practice for cancer patients...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228696/mp0250-a-vegf-and-hgf-neutralizing-darpin%C3%A2-molecule-shows-high-anti-tumor-efficacy-in-mouse-xenograft-and-patient-derived-tumor-models
#6
Ulrike Fiedler, Savira Ekawardhani, Andreas Cornelius, Pat Gilboy, Talitha R Bakker, Ignacio Dolado, Michael T Stumpp, Keith M Dawson
Background: The VEGF/VEGFR and the HGF/cMET pathways are key mediators of the interplay of tumor cells and their microenvironment. However, inhibition of VEGF has been shown to produce only limited clinical benefit and inhibition of the activation of cMET by HGF has not translated into clinical benefit in pivotal trials. MP0250, a DARPin® molecule that specifically inhibits both VEGF and HGF has been developed to explore the clinical potential of dual inhibition of these pathways. Results: MP0250 binding to VEGF and HGF inhibited downstream signalling through VEGFR2 and cMET resulting in inhibition of proliferation of VEGF- and HGF-dependent cells...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29199685/role-of-crizotinib-in-c-mesenchymal-epidermal-transition-positive-nonsmall-cell-lung-cancer-patients
#7
U Batra, A Jain, M Sharma, R Bajaj, M Suryavanshis
The increasing cases of NSCLC and improved understanding of its molecular biology has lead to identification of its varied driver mutations. cMET amplification has an important role as resistance mechanism for EGFR TKIs. Crizotinib is a drug which shows its anti-tumoral effect in cMET positive cases. Here we present a case series of three such patients who achieved were cMET amplified and showed partial response on Crizotinib.
January 2017: Indian Journal of Cancer
https://www.readbyqxmd.com/read/29151898/validity-of-a-continuous-metabolic-syndrome-score-as-an-index-for-modeling-metabolic-syndrome-in-children-and-adolescents-the-caspian-v-study
#8
Ramin Heshmat, Motahar Heidari, Hanieh-Sadat Ejtahed, Mohammad Esmaeil Motlagh, Armita Mahdavi-Gorab, Hasan Ziaodini, Majzoubeh Taheri, Gita Shafiee, Shaghayegh Beshtar, Mostafa Qorbani, Roya Kelishadi
Background: The purpose of the present study was to assess the validity of continuous metabolic syndrome score (cMetS) for predicting metabolic syndrome (MetS) and to determine the cutoff values in a representative sample of Iranian children and adolescents. Methods: This national study was conducted among 3843 students, aged 7-18 years country during the fifth survey of a national school-based surveillance program. The cMetS was computed by standardizing the residuals of waist circumference, mean arterial blood pressure, high-density lipoprotein cholesterol, triglycerides, and glucose by regressing them according to age and sex and aggregating them...
2017: Diabetology & Metabolic Syndrome
https://www.readbyqxmd.com/read/29094277/association-of-anthropometric-indices-with-continuous-metabolic-syndrome-in-children-and-adolescents-the-caspian-v-study
#9
Hanieh-Sadat Ejtahed, Mostafa Qorbani, Mohammad Esmaeil Motlagh, Pooneh Angoorani, Shirin Hasani-Ranjbar, Hasan Ziaodini, Majzoubeh Taheri, Zeinab Ahadi, Shaghayegh Beshtar, Tahereh Aminaee, Ramin Heshmat, Roya Kelishadi
PURPOSE: This study aims to examine the association of anthropometric indices with continuous metabolic syndrome (cMetS) among Iranian children and adolescents. METHODS: This multicentric study was conducted on 14138 students aged 7-18 years, who participated in a national surveillance program. Fasting blood sample was obtained from a subsample of 3843 randomly selected students. Physical examination including the measurement of anthropometric indices and blood pressure was conducted; fasting blood glucose and lipid profile were measured; and cMetS score was computed...
November 1, 2017: Eating and Weight Disorders: EWD
https://www.readbyqxmd.com/read/29061221/-advances-in-the-transformation-to-small-cell-lung-cancer-from-non-small-cell-lung-cancer-following-acquired-drug-resistance-to-egfr-tyrosine-kinase-inhibitors
#10
Wenqiu Zhang, Yongqi Li, Di Wu
The use of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in the treatment of sensitive EGFR mutation in non-small cell lung cancer (NSCLC) has been proved significant curative effect. However, the acquisition of the drug resistance to EGFR-TKIs is almost inevitable, and common drug resistance mechanisms include T790M mutation, cMET amplification, etc. One of the rare resistance mechanisms of EGFR-TKIs is the transformation from NSCLC into small cell lung cancer (SCLC), which account for about 3%-15%...
October 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28915692/biomarker-analysis-of-the-phase-3-torch-trial-for-first-line-erlotinib-versus-chemotherapy-in-advanced-non-small-cell-lung-cancer-patients
#11
Lucia Kim, Mauro Saieg, Massimo Di Maio, Ciro Gallo, Charles Butts, Fortunato Ciardiello, Ronald Feld, Dengxiao Cheng, Vittorio Gebbia, Marco Angelo Burgio, Yasmin Alam, Simona Signoriello, Antonio Rossi, Natasha Leighl, Paolo Maione, Alessandro Morabito, Geoffrey Liu, Ming-Sound Tsao, Francesco Perrone, Cesare Gridelli
BACKGROUND: The TORCH phase III trial compared the efficacy of first-line erlotinib followed by chemotherapy at progression (experimental arm) with the reverse sequence (standard arm) in unselected advanced non-small cell lung cancer (NSCLC) patients. Here we report biomarker analyses. METHODS: EGFR and KRAS mutation, expression of EGFR family members and of cMET and PTEN and EGFR and ABCG2 germline polymorphisms were tested on tumor tissue or blood samples to either confirm previously proposed predictive role or describe it in an explorative setting...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28757336/double-trouble-a-case-series-on-concomitant-genetic-aberrations-in-nsclc
#12
REVIEW
Nele Van Der Steen, Yves Mentens, Marc Ramael, Leticia G Leon, Paul Germonpré, Jose Ferri, David R Gandara, Elisa Giovannetti, Godefridus J Peters, Patrick Pauwels, Christian Rolfo
Several oncogenic drivers have been identified in non-small cell lung cancer. Targeted therapies for these aberrations have already been successfully developed and implemented in clinical practice. Owing to improved sensitivity in genetic testing, more and more tumors with multiple driver mutations are identified, resulting in dilemmas for treating physicians whether and which targeted therapy to use. In this case series, we provide an overview of patients with intrinsic double mutations in oncogenic drivers and their reported response to targeted therapies, with a focus on epidermal growth factor receptor, anaplastic lymphoma kinase, cMET, and Kirsten rat sarcoma viral oncogene...
July 6, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28714063/microrna-206-prevents-the-pathogenesis-of-hepatocellular-carcinoma-by-modulating-expression-of-met-proto-oncogene-and-cyclin-dependent-kinase-6-in-mice
#13
Heng Wu, Junyan Tao, Xiaolei Li, Tianpeng Zhang, Lei Zhao, Yao Wang, Lei Zhang, Jun Xiong, Zhi Zeng, Na Zhan, Clifford J Steer, Li Che, Mingjie Dong, Xiaomei Wang, Junqi Niu, Zhuoyu Li, Guiqing Yan, Xin Chen, Guisheng Song
Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide, and therapeutic agents for this malignancy are lacking. MicroRNAs play critical roles in carcinogenesis and present tremendous therapeutic potential. Here, we report that microRNA-206 is a robust tumor suppressor that plays important roles in the development of HCC by regulating cell-cycle progression and the cMet signaling pathway. MicroRNA-206 was underexpressed in livers of two HCC mouse models, human individuals bearing HCC, and human HCC cell lines...
December 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28673967/piperlongumine-induces-reactive-oxygen-species-ros-dependent-downregulation-of-specificity-protein-transcription-factors
#14
Keshav Karki, Erik Hedrick, Ravi Kasiappan, Un-Ho Jin, Stephen Safe
Piperlongumine is a natural product found in the plant species Piper longum, and this compound exhibits potent anticancer activity in multiple tumor types and has been characterized as an inducer of reactive oxygen species (ROS). Treatment of Panc1 and L3.6pL pancreatic, A549 lung, 786-O kidney, and SKBR3 breast cancer cell lines with 5 to 15 μmol/L piperlongumine inhibited cell proliferation and induced apoptosis and ROS, and these responses were attenuated after cotreatment with the antioxidant glutathione...
August 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28536037/identification-of-molecular-targets-in-vulvar-cancers
#15
Marguerite L Palisoul, Mary M Mullen, Rebecca Feldman, Premal H Thaker
OBJECTIVES: To identify molecular alterations that contribute to vulvar cancer pathogenesis with the intent of identifying molecular targets for treatment. METHODS: After retrospective analysis of a database of molecularly-profiled gynecologic cancer patients, 149 vulvar cancer patients were included and tested centrally at a CLIA laboratory (Caris Life Sciences, Phoenix, AZ). Tests included one or more of the following: gene sequencing (Sanger or next generation sequencing [NGS]), protein expression (immunohistochemistry [IHC]), and gene amplification (C/FISH)...
August 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28427160/biomarker-analysis-of-the-phase-3-torch-trial-for-first-line-erlotinib-versus-chemotherapy-in-advanced-non-small-cell-lung-cancer-patients
#16
Lucia Kim, Mauro Saieg, Massimo Di Maio, Ciro Gallo, Charles Butts, Fortunato Ciardiello, Ronald Feld, Dengxiao Cheng, Vittorio Gebbia, Marco Angelo Burgio, Yasmin Alam, Simona Signoriello, Antonio Rossi, Natasha Leighl, Paolo Maione, Alessandro Morabito, Geoffrey Liu, Ming-Sound Tsao, Francesco Perrone, Cesare Gridelli
BACKGROUND: The TORCH phase III trial compared the efficacy of first-line erlotinib followed by chemotherapy at progression (experimental arm) with the reverse sequence (standard arm) in unselected advanced non-small cell lung cancer (NSCLC) patients. Here we report biomarker analyses. METHODS: EGFR and KRAS mutation, expression of EGFR family members and of cMET and PTEN and EGFR and ABCG2 germline polymorphisms were tested on tumor tissue or blood samples to either confirm previously proposed predictive role or describe it in an explorative setting...
February 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414564/tivantinib-for-the-treatment-of-hepatocellular-carcinoma
#17
REVIEW
Jan Best, Clemens Schotten, Gregor Lohmann, Guido Gerken, Alexander Dechêne
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide with a poor prognosis due to late diagnosis in the majority of cases. Physicians are frequently confronted with patients who are not eligible for curative or locoregional treatments any more. In this scenario, the multi-tyrosine kinase inhibitor sorafenib remains the only systemic first-line treatment option providing modest survival benefit compared to placebo with significant but for most patients acceptable adverse effects...
May 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28362115/novel-egfr-t790m-cmet-dual-inhibitors-putative-therapeutic-agents-for-non-small-cell-lung-cancer
#18
Pankaj Kumar Singh, Om Silakari
AIM: Different resistance mechanisms, especially, T790M secondary acquired point mutation and in some cases amplification of cMET, have been a major setback for the lung cancer therapies. METHODOLOGY: The current in silico study explored the small molecules which can act as putative EGFR (T790M)-cMET dual inhibitors. Databases were first filtered and subsequently cross filtered, initially by thoroughly validated pharmacophore models for both targets. As per score and interactions obtained in docking, the molecules were subjected to molecular dynamics simulations, to study the stability and binding orientations of their complexes with target proteins...
April 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28336956/preclinical-development-of-a-humanized-neutralizing-antibody-targeting-hgf
#19
Hyori Kim, Sung Hee Hong, Jung Yong Kim, In-Chull Kim, Young-Whan Park, Song-Jae Lee, Seong-Won Song, Jung Ju Kim, Gunwoo Park, Tae Min Kim, Yun-Hee Kim, Jong Bae Park, Junho Chung, In-Hoo Kim
Hepatocyte growth factor (HGF) and its receptor, cMET, play critical roles in cell proliferation, angiogenesis and invasion in a wide variety of cancers. We therefore examined the anti-tumor activity of the humanized monoclonal anti-HGF antibody, YYB-101, in nude mice bearing human glioblastoma xenografts as a single agent or in combination with temozolomide. HGF neutralization, The extracellular signal-related kinases 1 and 2 (ERK1/2) phosphorylation, and HGF-induced scattering were assessed in HGF-expressing cell lines treated with YYB-101...
March 24, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28336955/progress-of-antibody-based-inhibitors-of-the-hgf-cmet-axis-in-cancer-therapy
#20
REVIEW
Ki-Hyun Kim, Hyori Kim
Dysregulated receptor tyrosine kinase signaling in human cancer cells leads to tumor progression, invasion and metastasis. The receptor tyrosine kinase cMET is frequently overexpressed in cancer tissue, and activation of cMET signaling is related to drug resistance and the processes of carcinogenesis, invasion and metastasis. For that reason, cMET and its ligand, hepatocyte growth factor (HGF), are considered prime targets for the development of anticancer drugs. At least eight anti-cMET and four anti-HGF antibodies have been tested or are being tested in clinical trials...
March 24, 2017: Experimental & Molecular Medicine
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