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Chisato Tomida, Naoko Yamagishi, Hikaru Nagano, Takayuki Uchida, Ayako Ohno, Katsuya Hirasaka, Takeshi Nikawa, Shigetada Teshima-Kondo
Anti-angiogenic therapies targeting vascular endothelial growth factor (VEGF) and its receptor (VEGF-R) are important treatments for a number of human malignancies, including colorectal cancers. However, there is increasing evidence that VEGF/VEGF-R inhibitors promote the adaptive and evasive resistance of tumor cells to the therapies. The mechanism by which the cancer cells become resistant remains unclear. One potential mechanism is that VEGF/VEGF-R blockers directly act on tumor cells independently of anti-angiogenic effects...
April 2018: International Journal of Oncology
Philip Carter, Costi Alifrangis, Biancastella Cereser, Pramodh Chandrasinghe, Lisa Del Bel Belluz, Thomas Herzog, Joel Levitan, Nina Moderau, Lee Schwartzberg, Neha Tabassum, Jinrui Wen, Jonathan Krell, Justin Stebbing
We evaluated the effect of tailoring treatments based on predictions informed by tumor molecular profiles across a range of cancers, using data from Caris Life Sciences. These included breast carcinoma, colorectal adenocarcinoma, female genital tract malignancy, lung non-small cell lung cancer, neuroendocrine tumors, ovarian surface epithelial carcinomas, and urinary tract cancers. Molecular profiles using mostly immunohistochemistry (IHC) and DNA sequencing for tumors from 841 patients had been previously used to recommend treatments; some physicians followed the suggestions completely while some did not...
February 6, 2018: Oncotarget
Maria Cristina Sini, Valentina Doneddu, Panagiotis Paliogiannis, Milena Casula, Maria Colombino, Antonella Manca, Gerardo Botti, Paolo A Ascierto, Amelia Lissia, Antonio Cossu, Giuseppe Palmieri
Cutaneous melanoma is a common and aggressive human skin cancers. Much is actually known about the molecular mechanisms underlying melanoma pathogenesis. The aim of the study was to evaluate any possible correlation between mutations in main growth-controlling genes ( BRAF, NRAS, CDKN2A ) and copy number variations in frequently amplified candidate genes ( MITF, EGFR, CCND1, cMET, and cKIT ) during melanoma initiation and progression. A large series of primary and secondary melanoma tissue samples ( N = 274) from 232 consecutively-collected patients of Italian origin as well as 32 tumor cell lines derived from primary and metastatic melanomas underwent mutation screening and fluorescence in situ hybridization (FISH) analysis...
February 2, 2018: Oncotarget
Rohini Agrawal, Virendra Nath, Harish Kumar, Vipin Kumar
Cardiometabolic syndrome (CMetS) is a consolidation of metabolic disorders characterized by insulin resistance, dyslipidemia and hypertension. Curcumin, a natural bioactive compound, has been shown to possess notable anti-oxidant activity and it has also been included as a super natural herb in the super natural herbs database. Most of the beneficial effects of Curcumin are possibly due to activation of the nuclear receptor, peroxisome proliferator-activated receptor gamma (PPARγ). The present study investigates molecular interactions of curcumin with PPARγ protein through molecular docking and molecular dynamics (MD) simulation studies...
February 27, 2018: Journal of Receptor and Signal Transduction Research
Chloe Constantinou, Savvas Papadopoulos, Eirini Karyda, Athanasios Alexopoulos, Niki Agnanti, Anna Batistatou, Haris Harisis
BACKGROUND/AIM: To explore the relationship between p53, p63, c-kit, Ki67, cMet, claudin7, CK5/6, CK17, AR, PTEN, EGFR, ALK, PDL-1 and c-MYC expression with the clinicopathological features of triple- negative breast cancer. MATERIALS AND METHODS: Immunohistochemistry was performed in 84 triple-negative breast cancer samples. RESULTS: A statistically significant relationship between tumour grade and claudin-7 (p=0.004) and between protein p53 and positive lymph nodes (p=0...
March 2018: In Vivo
Sugandha Saxena, Yuri Hayashi, Lingyun Wu, Mohammad Awaji, Pranita Atri, Michelle L Varney, Abhilasha Purohit, Satyanarayana Rachagani, Surinder K Batra, Rakesh K Singh
Semaphorin-5A (SEMA5A) has differential cell surface expression between normal and cancer cells and represents an attractive target for therapeutic intervention in pancreatic cancer (PC). In this study, we delineated the pathological expression and significance of SEMA5A during PC progression and metastasis. We utilized human tissue microarrays and different PC mouse models (Pdx1-cre; LSL- Kras(G12D) , Pdx1-Cre; LSL-Kras(G12D) ; LSL-p53(R172H) and RIP1-Tag2) to analyze SEMA5A expression during PC progression...
January 19, 2018: Oncotarget
Yingchao Zhao, Pinan Liu, Na Zhang, Jie Chen, Lukas D Landegger, Limeng Wu, Fu Zhao, Yanxia Zhao, Yanling Zhang, Jing Zhang, Takeshi Fujita, Anat Stemmer-Rachamimov, Gino B Ferraro, Hao Liu, Alona Muzikansky, Scott R Plotkin, Konstantina M Stankovic, Rakesh K Jain, Lei Xu
Neurofibromatosis type II (NF2) is a disease that needs new solutions. Vestibular schwannoma (VS) growth causes progressive hearing loss, and the standard treatment, including surgery and radiotherapy, can further damage the nerve. There is an urgent need to identify an adjunct therapy that, by enhancing the efficacy of radiation, can help lower the radiation dose and preserve hearing. The mechanisms underlying deafness in NF2 are still unclear. One of the major limitations in studying tumor-induced hearing loss is the lack of mouse models that allow hearing testing...
February 9, 2018: Proceedings of the National Academy of Sciences of the United States of America
Deepak K Prusty, Volker Adam, Reza M Zadegan, Stephan Irsen, Michael Famulok
Platforms for targeted drug-delivery must simultaneously exhibit serum stability, efficient directed cell internalization, and triggered drug release. Here, using lipid-mediated self-assembly of aptamers, we combine multiple structural motifs into a single nanoconstruct that targets hepatocyte growth factor receptor (cMet). The nanocarrier consists of lipidated versions of a cMet-binding aptamer and a separate lipidated GC-rich DNA hairpin motif loaded with intercalated doxorubicin. Multiple 2',6'-dimethylazobenzene moieties are incorporated into the doxorubicin-binding motif to trigger the release of the chemotherapeutics by photoisomerization...
February 7, 2018: Nature Communications
Bethany D Williams, Susan B Sisson, Chris A Ardern, Katrina D DuBose, Tammie M Johnson, M Ryan Richardson, James R Churilla
BACKGROUND: While studies to date have shown that children and adolescents who meet the current physical activity (PA) recommendations and maintain a healthy body weight demonstrate significantly lower cardiometabolic risk, there are some studies that suggest that the relationship between PA and metabolic risk may be mediated by adiposity. The aim of the present study was to examine variation in clustered metabolic risk (cMetS) in adolescents classified as not overweight/active (NOA), not overweight/not active (NONA), overweight/active (OA), and overweight/not active (ONA)...
March 2018: Metabolic Syndrome and related Disorders
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
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
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
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
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
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
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
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
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
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
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
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