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https://www.readbyqxmd.com/read/28512242/a-systematic-analysis-of-oncogenic-gene-fusions-in-primary-colon-cancer
#1
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
#2
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
#3
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...
May 15, 2017: Development
https://www.readbyqxmd.com/read/28502721/met-exon-14-skipping-mutations-in-lung-adenocarcinoma-clinicopathologic-implications-and-prognostic-values
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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/a-high-efficient-electrochemiluminescence-resonance-energy-transfer-system-in-one-nanostructure-its-application-for-ultrasensitive-detection-of-microrna-in-cancer-cells
#10
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)32+) and the acceptor of CdSe@ZnS quantum dots (QDs) for acting as the ECL emitter (QDs-Ru(dcbpy)32+), which significantly reduced the energy loss and improved the ECL efficiency of QDs because of the short path of energy transmission...
May 10, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28476040/efficacy-of-a-hsp90-inhibitor-ganetespib-in-preclinical-thyroid-cancer-models
#11
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)...
April 18, 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
#12
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
https://www.readbyqxmd.com/read/28467503/zebrafish-gdnf-and-its-co-receptor-gfr%C3%AE-1-activate-the-human-ret-receptor-and-promote-the-survival-of-dopaminergic-neurons-in-vitro
#13
Tuulia Saarenpää, Konstantin Kogan, Yulia Sidorova, Arun Kumar Mahato, Igor Tascón, Heidi Kaljunen, Liying Yu, Jukka Kallijärvi, Jaana Jurvansuu, Mart Saarma, Adrian Goldman
Glial cell line-derived neurotrophic factor (GDNF) is a ligand that activates, through co-receptor GDNF family receptor alpha-1 (GFRα1) and receptor tyrosine kinase "RET", several signaling pathways crucial in the development and sustainment of multiple neuronal populations. We decided to study whether non-mammalian orthologs of these three proteins have conserved their function: can they activate the human counterparts? Using the baculovirus expression system, we expressed and purified Danio rerio RET, and its binding partners GFRα1 and GDNF, and Drosophila melanogaster RET and two isoforms of co-receptor GDNF receptor-like...
2017: PloS One
https://www.readbyqxmd.com/read/28442998/glial-cell-line-derived-neurotrophic-factor-gene-delivery-in-parkinson-s-disease-a-delicate-balance-between-neuroprotection-trophic-effects-and-unwanted-compensatory-mechanisms
#14
REVIEW
Liliane Tenenbaum, Marie Humbert-Claude
Glial cell line-derived neurotrophic factor (GDNF) and Neurturin (NRTN) bind to a receptor complex consisting of a member of the GDNF family receptor (GFR)-α and the Ret tyrosine kinase. Both factors were shown to protect nigro-striatal dopaminergic neurons and reduce motor symptoms when applied terminally in toxin-induced Parkinson's disease (PD) models. However, clinical trials based on intraputaminal GDNF protein administration or recombinant adeno-associated virus (rAAV)-mediated NRTN gene delivery have been disappointing...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/28428274/egfr-mediates-responses-to-small-molecule-drugs-targeting-oncogenic-fusion-kinases
#15
Aria Vaishnavi, Laura Schubert, Uwe Rix, Lindsay A Marek, Anh T Le, Stephen Keysar, Magdalena J Glogowska, Matthew A Smith, Severine L Kako, Natalia J Sumi, Kurtis D Davies, Kathryn E Ware, Marileila Varella-Garcia, Eric B Haura, Antonio Jimeno, Lynn E Heasley, Dara L Aisner, Robert C Doebele
Oncogenic kinase fusions of ALK, ROS1, RET and NTRK1 act as drivers in human lung and other cancers. Residual tumor burden following treatment of ALK or ROS1+ lung cancer patients with oncogene-targeted therapy ultimately enables the emergence of drug-resistant clones, limiting the long-term effectiveness of these therapies. To determine the signaling mechanisms underlying incomplete tumor cell killing in oncogene-addicted cancer cells, we investigated the role of EGFR signaling in drug-naive cancer cells harboring these oncogene fusions...
April 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28404375/synthesis-and-structure-activity-relationship-study-of-pyrazolo-3-4-d-pyrimidines-as-tyrosine-kinase-ret-inhibitors
#16
Chengyan Wang, Hongchun Liu, Zilan Song, Yinchun Ji, Li Xing, Xia Peng, Xisheng Wang, Jing Ai, Meiyu Geng, Ao Zhang
Three series of pyrazolo[3,4-d]pyrimidine derivatives were synthesized and evaluated as RET kinase inhibitors. Compounds 23a and 23c were identified to show significant activity both in the biochemical and the BaF3/CCDC6-RET cell assays. Compound 23c was found to significantly inhibit RET phosphorylation and down-stream signaling in BaF3/CCDC6-RET cells, confirming its potent cellular RET-targeting profile. Different from other RET inhibitors with equal potency against KDR that associated with severe toxicity, 23c did not show significant KDR-inhibition even at the concentration of 1μM...
March 31, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28382399/ccr5-in-recruitment-and-activation-of-myeloid-derived-suppressor-cells-in-melanoma
#17
REVIEW
Viktor Umansky, Carolin Blattner, Christoffer Gebhardt, Jochen Utikal
Malignant melanoma is characterized by the development of chronic inflammation in the tumor microenvironment, leading to the accumulation of myeloid-derived suppressor cells (MDSCs). Using ret transgenic mouse melanoma model, we found a significant migration of MDSCs expressing C-C chemokine receptor (CCR)5 into primary tumors and metastatic lymph nodes, which was correlated with tumor progression. An increased CCR5 expression on MDSCs was associated with elevated concentrations of CCR5 ligands in melanoma microenvironment...
April 5, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28347966/a-novel-aptasensor-for-lysozyme-based-on-electrogenerated-chemiluminescence-resonance-energy-transfer-between-luminol-and-silicon-quantum-dots
#18
Yong-Ping Dong, Jiao Wang, Ying Peng, Jun-Jie Zhu
In the present work, electrogenerated chemiluminescence (ECL) of luminol was investigated in neutral condition at a gold electrode in the presence of silicon quantum dots (SiQDs). The results revealed that SiQDs can not only greatly enhance luminol ECL, but also act as energy acceptor to construct a novel ECL resonance energy transfer (ECL-RET) system with luminol. As a result, strong anodic ECL signal was obtained in neutral condition at the bare gold electrode, which is suitable for biosensing application...
March 22, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28294980/microrna-146b-a-novel-biomarker-and-therapeutic-target-for-human-papillary-thyroid-cancer
#19
REVIEW
Chen-Kai Chou, Rue-Tusan Liu, Hong-Yo Kang
Papillary thyroid cancer (PTC) is the most common tumor subtype of thyroid cancer. However, not all PTCs are responsive to current surgical and radioiodine treatment. The well-established clinical prognostic factors include tumor size, lymph node/distal metastasis, and extrathyroidal invasion. The RET/PTC-RAS-BRAF linear molecular signaling cascade is known to mediate PTC pathogenesis. However, whether presence of BRAF mutation, the most common genetic alteration in PTC, can affect PTC behavior and prognosis is controversial...
March 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28281264/resonance-energy-transfer-based-nucleic-acid-hybridization-assays-on-paper-based-platforms-using-emissive-nanoparticles-as-donors
#20
Samer Doughan, M Omair Noor, Yi Han, Ulrich J Krull
Quantum dots (QDs) and upconverting nanoparticles (UCNPs) are luminescent nanoparticles (NPs) commonly used in bioassays and biosensors as resonance energy transfer (RET) donors. The narrow and tunable emissions of both QDs and UCNPs make them versatile RET donors that can be paired with a wide range of acceptors. Ratiometric signal processing that compares donor and acceptor emission in RET-based transduction offers improved precision, as it accounts for fluctuations in the absolute photoluminescence (PL) intensities of the donor and acceptor that can result from experimental and instrumental variations...
2017: Methods in Molecular Biology
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