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Ret signaling

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https://www.readbyqxmd.com/read/28645787/striatal-hypodopamine-phenotypes-found-in-transgenic-mice-that-overexpress-glial-cell-line-derived-neurotrophic-factor
#1
Hidekazu Sotoyama, Yuriko Iwakura, Kanako Oda, Toshikuni Sasaoka, Nobuyuki Takei, Akiyoshi Kakita, Hideki Enomoto, Hiroyuki Nawa
Glial cell line-derived neurotrophic factor (GDNF) positively regulates the development and maintenance of in vitro dopaminergic neurons. However, the in vivo influences of GDNF signals on the brain dopamine system are controversial and not fully defined. To address this question, we analyzed dopaminergic phenotypes of the transgenic mice that overexpress GDNF under the control of the glial Gfap promoter in the brain. Compared with wild-type, the GDNF transgenic mice contained higher levels of GDNF protein and phosphorylated RET receptors in the brain...
June 20, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28637019/clinicopathological-characteristics-of-ros1-and-ret-rearranged-nsclc-in-caucasian-patients-data-from-a-cohort-of-713-non-squamous-nsclc-lacking-kras-egfr-her2-braf-pik3ca-alk-alterations
#2
Frédéric Dugay, Francisco Llamas-Gutierrez, Marjory Gournay, Sarah Medane, François Mazet, Dan Christian Chiforeanu, Emmanuelle Becker, Régine Lamy, Hervé Léna, Nathalie Rioux-Leclercq, Marc-Antoine Belaud-Rotureau, Florian Cabillic
Targeted therapies have substantially changed the management of non-small cell lung cancer (NSCLC) patients with driver oncogenes. Given the high frequency, EGFR and ALK aberrations were the first to be detected and paved the way for tyrosine kinase inhibitor (TKI) treatments. Other kinases such as ROS1 and more recently RET have emerged as promising targets, and ROS1 and RET TKIs are already available for precision medicine.We screened a large cohort of 713 Caucasian non-squamous NSCLC patients lacking EGFR/KRAS/BRAF/HER2/PI3KCA/ALK aberrations for ROS1 and RET rearrangements using fluorescence in situ hybridization to determine the frequency and clinicopathological characteristics of ROS1- and RET-positive patients...
June 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28612612/-molecular-aspects-of-thyroid-tumors-with-emphasis-on-microrna-and-their-clinical-implications
#3
M Ludvíková, I Kholová, D Kalfeřt
BACKGROUND: Central to neoplastic transformation and tumor progression is alteration of the signaling pathways that control cell proliferation and apoptosis. The key mechanisms for this neoplastic process are genetic changes (mutations of cancer-related genes) and recently identified epigenetic changes that involve DNA methylation, chromatin remodeling (which has a profound effect on the control of gene expression), and noncoding, regulatory RNA (notably, microRNA - miRNA). MiRNAs control expression of their target gene post-transcriptionally...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/28598261/neurotoxicity-of-alkylated-polycyclic-aromatic-compounds-in-human-neuroblastoma-cells
#4
Sailendra Nath Sarma, Jules M Blais, Hing Man Chan
Polycyclic aromatic compounds (PAC) are ubiquitous environmental pollutants originating from incomplete combustion processes. While the toxicity of parent PAC such as benzo[a]pyrene (BaP) is well characterized, effects of other alkyl-PAC dibenzothiophene (DBT) and retene (Ret) are not well established. The aim of this study was to examine the underlying relative neurotoxic mechanisms attributed to BaP (parent PAH), DBT and Ret (alkyl-PACs) using human neuroblastoma SK-N-SH cells. The lethal concentrations (LC10 and LC20) were found at approximately 10 µM and 40 µM, respectively after 24-h exposure of SK-N-SH cells...
June 9, 2017: Journal of Toxicology and Environmental Health. Part A
https://www.readbyqxmd.com/read/28598087/-bioinformatic-analysis-of-differentially-expressed-genes-involved-in-the-post-hypoxic-ischemic-brain-damage-of-newborn-rats
#5
Jing Shi, Jun Tang, De-Zhi Mu
OBJECTIVES: To analyze the differentially expressed genes (DEGs) in cerebral cortices of rats which were seven weeks after neonatal hypoxic ischemic brain damage (HIBD) and elucidate the biological significance of the DEGs. METHODS: The gene expression profile of GSE37777, including 4 HI samples subjected to HIBD and 4 normal controls, was downloaded from the Gene Expression Omnibus database (GEO). DEGs were screened using the R package in HIBD groups compared with normal controls...
September 2016: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28591570/compromised-survival-of-cerebellar-molecular-layer-interneurons-lacking-gdnf-receptors-gfr%C3%AE-1-or-ret-impairs-normal-cerebellar-motor-learning
#6
Maria Christina Sergaki, Juan Carlos López-Ramos, Stefanos Stagkourakis, Agnès Gruart, Christian Broberger, José María Delgado-García, Carlos F Ibáñez
The role of neurotrophic factors as endogenous survival proteins for brain neurons remains contentious. In the cerebellum, the signals controlling survival of molecular layer interneurons (MLIs) are unknown, and direct evidence for the requirement of a full complement of MLIs for normal cerebellar function and motor learning has been lacking. Here, we show that Purkinje cells (PCs), the target of MLIs, express the neurotrophic factor GDNF during MLI development and survival of MLIs depends on GDNF receptors GFRα1 and RET...
June 6, 2017: Cell Reports
https://www.readbyqxmd.com/read/28570681/activated-e2f-activity-induces-cell-death-in-papillary-thyroid-carcinoma-k1-cells-with-enhanced-wnt-signaling
#7
Dong Yang, Chuanjiang Wang, Yingwei Luo, Xuan Li, Qingbin Song, Jian Zhang, Shijie Xin
Disruption of Wnt signaling often happens in tumorigenesis, but whether Wnt signaling affects the early stages of thyroid tumor, such as papillary thyroid carcinoma, is still a question, especially in the papillary thyroid carcinoma without genomic RET/PTC mutation. In this study, we demonstrated the important function of Wnt signaling in papillary thyroid carcinoma K1 cells, which have no RET/PTC mutation. We found that K1 cells have enhanced Wnt signaling in comparison to normal thyroid cells. We further demonstrated that K1 cells require the enhanced Wnt signaling for growth and survival...
2017: PloS One
https://www.readbyqxmd.com/read/28560674/detection-of-gene-rearrangements-in-circulating-tumor-cells-examples-of-alk-ros1-ret-rearrangements-in-non-small-cell-lung-cancer-and-erg-rearrangements-in-prostate-cancer
#8
Cyril Catelain, Emma Pailler, Marianne Oulhen, Vincent Faugeroux, Anne-Laure Pommier, Françoise Farace
Circulating tumor cells (CTCs) hold promise as biomarkers to aid in patient treatment stratification and disease monitoring. Because the number of cells is a critical parameter for exploiting CTCs for predictive biomarker's detection, we developed a FISH (fluorescent in situ hybridization) method for CTCs enriched on filters (filter-adapted FISH [FA-FISH]) that was optimized for high cell recovery. To increase the feasibility and reliability of the analyses, we combined fluorescent staining and FA-FISH and developed a semi-automated microscopy method for optimal FISH signal identification in filtration-enriched CTCs ...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28512242/a-systematic-analysis-of-oncogenic-gene-fusions-in-primary-colon-cancer
#9
Wigard P Kloosterman, Robert R J Coebergh van den Braak, Mark Pieterse, Markus J van Roosmalen, Anieta M Sieuwerts, Christina Stangl, Ronne Brunekreef, Zarina S Lalmahomed, Salo Ooft, Anne van Galen, Marcel Smid, Armel Lefebvre, Fried Zwartkruis, John W M Martens, John A Foekens, Katharina Biermann, Marco J Koudijs, Jan N M IJzermans, Emile E Voest
Genomic rearrangements that give rise to oncogenic gene fusions can offer actionable targets for cancer therapy. Here we present a systematic analysis of oncogenic gene fusions among a clinically well-characterized, prospectively collected set of 278 primary colon cancers spanning diverse tumor stages and clinical outcomes. Gene fusions and somatic genetic variations were identified in fresh frozen clinical specimens by Illumina RNA-sequencing, the STAR fusion gene detection pipeline, and GATK RNA-seq variant calling...
May 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28507274/targeted-next-generation-sequencing-identifies-somatic-mutations-and-gene-fusions-in-papillary-thyroid-carcinoma
#10
Zheming Lu, Yujie Zhang, Dongdong Feng, Jindong Sheng, Wenjun Yang, Baoguo Liu
138 papillary thyroid carcinoma (PTC) samples were assessed for somatic mutation profile and fusion genes by targeted resequencing using a cancer panel (ThyGenCapTM) targeting 244 cancer-related genes and 20 potential fusion genes. At least one genetic alteration (including mutations and fusion genes) was observed in 118/138 (85.5%) samples. The most frequently mutated gene was BRAF V600E (57.2%). Moreover, we identified 11 fusion genes including eight previously reported ones and three novel fusion genes, UEVLD-RET, OSBPL9-BRAF, and SQSTM1-NTRK3...
April 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28506996/ret-mediated-glial-cell-line-derived-neurotrophic-factor-signaling-inhibits-mouse-prostate-development
#11
Hyun-Jung Park, Eric C Bolton
In humans and rodents, the prostate gland develops from the embryonic urogenital sinus (UGS). The androgen receptor (AR) is thought to control the expression of morphogenetic genes in inductive UGS mesenchyme, which promotes proliferation and cytodifferentiation of the prostatic epithelium. However, the nature of the AR-regulated morphogenetic genes and the mechanisms whereby AR controls prostate development are not understood. Glial cell line-derived neurotrophic factor (GDNF) binds GDNF family receptor α1 (GFRα1) and signals through activation of RET tyrosine kinase...
June 15, 2017: Development
https://www.readbyqxmd.com/read/28502721/met-exon-14-skipping-mutations-in-lung-adenocarcinoma-clinicopathologic-implications-and-prognostic-values
#12
Geun Dong Lee, Seung Eun Lee, Doo-Yi Oh, Dan-Bi Yu, Hae Min Jeong, Jooseok Kim, Sungyoul Hong, Hun Soon Jung, Ensel Oh, Ji-Young Song, Mi-Sook Lee, Mingi Kim, Kyungsoo Jung, Jhingook Kim, Young Kee Shin, Yoon-La Choi, Hyeong Ryul Kim
INTRODUCTION: Response to MET inhibitors in non-small cell lung cancer with MET exon 14 (METex14) skipping has fueled molecular screening efforts and search for optimal therapies. However, further work is needed to refine the clinicopathologic and prognostic implications of METex14 skipping METHODS: Among 795 East-Asian patients who underwent surgery for non-small cell lung cancer, we screened 45 patients with quintuple-negative (EGFR-/KRAS-/ALK-/ROS1-/RET-) lung adenocarcinomas using RT-PCR, and found 17 patients (37...
May 10, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28502425/resonance-energy-transfer-based-electrochemiluminescence-and-fluorescence-sensing-of-riboflavin-using-graphitic-carbon-nitride-quantum-dots
#13
Huan Wang, Qin Ma, Yanfeng Wang, Caihe Wang, Dongdong Qin, Duoliang Shan, Jing Chen, Xiaoquan Lu
Graphitic carbon nitride quantum dots (g-CNQDs) are rarely used in the field of electrochemiluminescence. In this paper, g-CNQDs have a strong and stable electrochemiluminescence (ECL) signal generated in the presence of co-reactant K2S2O8. The ECL signal of g-CNQDs was quenched by the mechanism of resonance energy transfer (RET) between donor g-CNQDs and receptor riboflavin (RF) that is proved by UV-vis absorption spectroscopy, electrochemiluminescence and fluorescence emission spectroscopy analysis technology...
June 22, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/28500237/resistance-to-ret-inhibition-in-ret-rearranged-nsclc-is-mediated-by-reactivation-of-ras-mapk-signaling
#14
Sarah K Nelson-Taylor, Anh T Le, Minjae Yoo, Laura Schubert, Katie M Mishall, Andrea Doak, Marileila Varella-Garcia, Aik-Choon Tan, Robert C Doebele
Oncogenic rearrangements in RET are present in 1-2% of lung adenocarcinoma (LAD) patients. Ponatinib is a multi-kinase inhibitor with low-nanomolar potency against the RET kinase domain. Here, we demonstrate that ponatinib exhibits potent anti-proliferative activity in RET fusion positive LC-2/ad LAD cells and inhibits phosphorylation of the RET fusion protein and signaling through ERK1/2 and AKT. Using distinct dose-escalation strategies, two ponatinib-resistant LC-2/ad cell lines, PR1 and PR2, were derived...
May 12, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28498409/demonstration-of-a-potent-ret-transcriptional-inhibitor-for-the-treatment-of-medullary-thyroid-carcinoma-based-on-an-ellipticine-derivative
#15
Vishnu Muthuraj Kumarasamy, Daekyu Sun
Dominant-activating mutations in the RET (rearranged during transfection) proto-oncogene, which encodes a receptor tyrosine kinase, is often associated with the development of medullary thyroid carcinoma (MTC). The proximal promoter region of the RET gene consists of a guanine-rich sequence containing five runs of three consecutive guanine residues that serve as the binding site for transcriptional factors. As we have recently shown, this stretch of nucleotides in the promoter region is highly dynamic in nature and tend to form non-B DNA secondary structures called G-quadruplexes, which suppress the transcription of the RET gene...
May 11, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28490466/ret-signaling-in-prostate-cancer
#16
Kechen Ban, Shu Feng, Longjiang Shao, Michael Ittmann
Purpose: Large diameter perineural prostate cancer is associated with poor outcomes. GDNF, with its co-receptor GFRα1, binds RET and activates downstream pro-oncogenic signaling. Since both GDNF and GFRα1 are secreted by nerves, we examined the role of RET signaling in prostate cancer. <p>Experimental Design: Expression of RET, GDNF and/or GFRα1 was assessed. The impact of RET signaling on proliferation, invasion and soft agar colony formation, perineural invasion and growth in vivo was determined...
May 10, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28489587/ngs-based-identification-of-mutational-hotspots-for-targeted-therapy-in-anaplastic-thyroid-carcinoma
#17
Vera Tiedje, Saskia Ting, Thomas Herold, Sarah Synoracki, Soeren Latteyer, Lars C Moeller, Denise Zwanziger, Martin Stuschke, Dagmar Fuehrer, Kurt Werner Schmid
CONTEXT: Anaplastic thyroid carcinoma (ATC) represents one of the most aggressive carcinomas with no consistent survival benefit when treated with conventional radiochemotherapy. Approaches targeting "oncogene addiction" of ATC are increasingly explored and first promising results have been reported in single case studies. OBJECTIVE: To determine the prevalence of mutations in known thyroid oncogenes and signalling pathways amendable to targeted therapy in a large cohort of ATC...
April 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28488439/highly-efficient-electrochemiluminescence-resonance-energy-transfer-system-in-one-nanostructure-its-application-for-ultrasensitive-detection-of-microrna-in-cancer-cells
#18
Zhaoyang Li, Zongfan Lin, Xiaoyu Wu, Haotian Chen, Yaqin Chai, Ruo Yuan
The electrochemiluminesce (ECL) efficiency of luminous emitter can be enhanced by the means of electrochemiluminesce resonance energy transfer (ECL-RET) with a matched donor. However, generally, the donor and acceptor pairs were separated in different independent nanostructures, experiencing the challenging issues of limited energy transfer efficiency and luminous stability. Herein, we designed novel ECL-RET model within one nanostructure containing the donor of tris(4,4'-dicarboxylicacid-2,2'-bipyridyl) ruthenium(II) dichloride (Ru(dcbpy)3(2+)) and the acceptor of CdSe@ZnS quantum dots (QDs) for acting as the ECL emitter (QDs-Ru(dcbpy)3(2+)), which significantly reduced the energy loss and improved the ECL efficiency of QDs because of the short path of energy transmission...
June 6, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28476040/efficacy-of-an-hsp90-inhibitor-ganetespib-in-preclinical-thyroid-cancer-models
#19
Shu-Fu Lin, Jen-Der Lin, Chuen Hsueh, Ting-Chao Chou, Chun-Nan Yeh, Ming-Huang Chen, Richard J Wong
Heat shock protein 90 is a molecular chaperon that maintains the correct folding and function of multiple client proteins. The inhibition of heat shock protein 90, which leads to the simultaneous degradation of multiple proteins involved in oncogenic signaling pathways, has revealed an innovative strategy to treat a variety of cancer types. We evaluated the therapeutic effects of ganetespib, a heat shock protein 90 inhibitor, in treating thyroid cancer. Ganetespib effectively inhibited cell proliferation in a dose-dependent manner in eight cell lines originating from four major histologic types of thyroid cancer (papillary, follicular, anaplastic and medullary)...
June 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28475846/resistance-exercise-attenuates-skeletal-muscle-oxidative-stress-systemic-pro-inflammatory-state-and-cachexia-in-walker-256-tumor-bearing-rats
#20
Camila Souza Padilha, Fernando H Borges, Lilian Eslaine Costa Mendes da Silva, Fernando Tadeu Trevisan Frajacomo, Alceu Afonso Jordao, José Alberto Duarte, Rubens Cecchini, Flávia Alessandra Guarnier, Rafael Deminice
The aim of this study was to investigate the effects of resistance exercise training (RET) on oxidative stress, systemic inflammatory markers and muscle wasting in Walker-256 tumor-bearing rats. Male (Wistar) rats were divided into 4 groups: sedentary controls (n=9); tumor-bearing (n=9); exercised (n=9); and tumor-bearing exercised (n=10). Exercised and tumor-bearing exercised rats were exposed to resistance exercise of climbing a ladder apparatus with weights tied to their tails during 6-wks. The physical activity of control and tumor-bearing rats was confined to the space of the cage...
May 5, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
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