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https://www.readbyqxmd.com/read/27904650/cabozantinib-in-the-treatment-of-advanced-renal-cell-carcinoma-clinical-trial-evidence-and-experience
#1
REVIEW
Jose Manuel Ruiz-Morales, Daniel Y C Heng
The treatment of metastatic renal cell carcinoma (mRCC) is rapidly changing. During first-line treatment with targeted therapy, patients ultimately develop resistance to therapy and the disease progresses. Recently, cabozantinib has demonstrated a better response rate, progression-free survival and overall survival compared with everolimus after failure of prior targeted therapy in patients with advanced or metastatic renal cell carcinoma (RCC). Cabozantinib is a small-molecule tyrosine kinase inhibitor (TKI)...
December 2016: Therapeutic Advances in Urology
https://www.readbyqxmd.com/read/27883960/a-dual-potential-electrochemiluminescence-ratiometric-sensor-for-sensitive-detection-of-dopamine-based-on-graphene-cdte-quantum-dots-and-self-enhanced-ru-ii-complex
#2
Xiaomin Fu, Xingrong Tan, Ruo Yuan, Shihong Chen
A novel dual-potential ratiometric electrochemiluminescence (ECL) sensor was designed for detecting dopamine (DA) based on graphene-CdTe quantum dots (G-CdTe QDs) as the cathodic emitter and self-enhanced Ru(II) composite (TAEA-Ru) as the anodic emitter. TAEA-Ru was prepared by linking ruthenium(II) tris(2,2'-bipyridyl-4,4'-dicarboxylato) with tris(2-aminoethyl)amine. Firstly, 3-aminopropyltriethoxysilane founctionalized G-CdTe QDs was used as the substrate for capturing target DA via the specific recognition of the diol of DA to the oxyethyl group of APTES...
November 11, 2016: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/27873490/egf-induced-ret-inhibitor-resistance-in-ccdc6-ret-lung-cancer-cells
#3
Hyun Chang, Ji Hea Sung, Sung Ung Moon, Han Soo Kim, Jin Won Kim, Jong Seok Lee
PURPOSE: Rearrangement of the proto-oncogene rearranged during transfection (RET) has been newly identified potential driver mutation in lung adenocarcinoma. Clinically available tyrosine kinase inhibitors (TKIs) target RET kinase activity, which suggests that patients with RET fusion genes may be treatable with a kinase inhibitor. Nevertheless, the mechanisms of resistance to these agents remain largely unknown. Thus, the present study aimed to determine whether epidermal growth factor (EGF) and hepatocyte growth factor (HGF) trigger RET inhibitor resistance in LC-2/ad cells with CCDC6-RET fusion genes...
January 2017: Yonsei Medical Journal
https://www.readbyqxmd.com/read/27872141/differential-roles-of-ret-isoforms-in-medullary-and-papillary-thyroid-carcinomas
#4
Eric Y Lian, Sarah M Maritan, Jessica G Cockburn, Katayoon Kasaian, Mathieu Jf Crupi, David Hurlbut, Steven Jones, Sam Wiseman, Lois M Mulligan
The RET receptor tyrosine kinase mediates cell proliferation, survival and migration in embryogenesis, and is implicated in transformation and tumour progression in multiple cancers. RET is frequently mutated and constitutively activated in familial and sporadic thyroid carcinomas. As a result of alternative splicing, RET is expressed as two protein isoforms, RET9 and RET51, which differ in their unique C-terminal amino acids. These isoforms have distinct intracellular trafficking and associated signaling complexes, but functional differences are not well defined...
November 21, 2016: Endocrine-related Cancer
https://www.readbyqxmd.com/read/27842445/cabozantinib-in-genitourinary-malignancies
#5
Tian Zhang, Se Eun Park, Cierra Hong, Daniel J George
Cabozantinib inhibits a variety of cellular receptors including VEGFR1-3, MET, AXL, RET, FLT3 and KIT. These signaling pathways have been shown to be important in genitourinary malignancies. Along its clinical development, it has shown most activity in advanced renal cell carcinoma; the METEOR study compared cabozantinib to everolimus and showed clinically and statistically significant improvements in both progression-free survival and overall survival. Herein, we review the development of cabozantinib in the genitourinary malignancies of renal cell carcinoma, prostate adenocarcinoma and urothelial carcinoma...
November 15, 2016: Future Oncology
https://www.readbyqxmd.com/read/27826534/fusion-gene-and-splice-variant-analyses-in-liquid-biopsies-of-lung-cancer-patients
#6
REVIEW
Cristina Aguado, Ana Giménez-Capitán, Niki Karachaliou, Ana Pérez-Rosado, Santiago Viteri, Daniela Morales-Espinosa, Rafael Rosell
Obtaining a biopsy of solid tumors requires invasive procedures that strongly limit patient compliance. In contrast, a blood extraction is safe, can be performed at many time points during the course disease and encourages appropriate therapy modifications, potentially improving the patient's clinical outcome and quality of life. Fusion of the tyrosine kinase genes anaplastic lymphoma kinase (ALK), C-ROS oncogen 1 (ROS 1), rearranged during transfection (RET) and neurotrophic tyrosine kinase 1 (NTRK1) occur in 1-5% of lung adenocarcinomas and constitute therapeutic targets for tyrosine kinase inhibitors...
October 2016: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/27825526/electrogenerated-chemiluminescence-of-si-quantum-dots-in-neutral-aqueous-solution-and-its-biosensing-application
#7
Yong-Ping Dong, Jiao Wang, Ying Peng, Jun-Jie Zhu
Electrogenerated chemiluminescence (ECL) of semiconductor quantum dots (QDs) has been considered as a powerful technique in the fabrication of biosensor, however, high-toxicity of heavy metal ion containing in QDs severely limits their further applications, and the search for the alternative benign nanomaterials with high ECL efficiency is urgent. Herein, ECL behavior of eco-friendly silicon quantum dots (SiQDs) was reported in neutral aqueous condition. Stable and intense cathodic ECL emission was obtained in phosphate buffer solution (PBS) with K2S2O8 as coreactant...
October 13, 2016: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/27807062/in-vitro-transforming-potential-intracellular-signaling-properties-and-sensitivity-to-a-kinase-inhibitor-sorafenib-of-ret-proto-oncogene-variants-glu511lys-ser649leu-and-arg886trp
#8
Hugo Prazeres, Joana P Couto, Fernando Rodrigues, João Vinagre, Joana Torres, Vitor Trovisco, Teresa C Martins, Manuel Sobrinho-Simões, Paula Soares
No abstract text is available yet for this article.
December 2016: Endocrine-related Cancer
https://www.readbyqxmd.com/read/27769406/novel-signal-on-electrochemiluminescence-biosensor-for-the-detection-of-psa-based-on-resonance-energy-transfer
#9
Mei-Sheng Wu, Ruo-Nan Chen, Yao Xiao, Zi-Xin Lv
Here, we propose a simple and novel "signal-on" electrochemiluminescence (ECL) biosensor based on resonance energy transfer (RET) for detection of prostate specific antigen (PSA). The system is composed of Multi-walled carbon nanotubes (MWCNT), polyamidoamine (PAMAM) dendrimer and Au nanoparticles (NPs) film on glassy carbon electrode (GCE) to improve the electron transfer, provide abundant amine group for the immobilization of biomolecules, and amplify the ECL signal. After that, Au nanorods (Au NRs) labeled peptide is modified on electrode surface to serve as ECL-RET acceptor due to the excellent overlap between the ECL emission spectrum of Ru(bpy)3(2+) and the absorption spectrum of Au NRs, leading to the significant decrement of ECL signal...
December 1, 2016: Talanta
https://www.readbyqxmd.com/read/27753862/br-02-2-hypertension-management-in-cancer-patients-undergoing-chemotherapy
#10
Naftali Stern
As both the rate of hypertension and cancer rise with age, concomitant hypertension in patients receiving treatment for cancer is very common. Increase in blood pressure during cancer treatment requires careful clinical assessment. Distinction between discontinuation or malabsorption of antihypertensive treatment due to factors such as nausea/vomiting/diarrhea and anti-cancer drug specific effects must be first made. De-novo hypertension during cancer treatment is likely related to anticancer drugs per se. Classical chemotherapeutic agents such as cyclophosphamide, cisplatin and busulfan have been previously linked to rising blood pressure...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27725612/sensitive-impedimetric-immunoassay-of-japanese-encephalitis-virus-based-on-enzyme-biocatalyzed-precipitation-on-a-gold-nanoparticle-modified-screen-printed-carbon-electrode
#11
Xiaohui Geng, Fanglin Zhang, Qiang Gao, Yingfeng Lei
A sensitive and disposable electrochemical impedance biosensor to detect Japanese encephalitis virus (JEV) was developed based on a gold nanoparticle (AuNP)-modified screen-printed carbon electrode (SPCE). A biosensor was fabricated through covalent grafting of a mixed self-assembled monolayer on AuNPs with a specific antibody. To detect JEV and achieve signal amplification, the horseradish peroxidase (HRP)-labeled second antibody was linked to the biosensor through a sandwich immunity reaction. HRP was used to catalyze 4-chloro-1-naphthol oxidation to produce an insoluble precipitate, which introduced a barrier to electron transfer on the electrode...
2016: Analytical Sciences: the International Journal of the Japan Society for Analytical Chemistry
https://www.readbyqxmd.com/read/27723295/dual-signal-amplification-using-gold-nanoparticles-enhanced-zinc-selenide-nanoflakes-and-p19-protein-for-ultrasensitive-photoelectrochemical-biosensing-of-microrna-in-cell
#12
Wenwen Tu, Huijuan Cao, Long Zhang, Jianchun Bao, Xuhui Liu, Zhihui Dai
Using Au nanoparticles (NPs) decorated water-soluble ZnSe-COOH nanoflakes (NFs), an ultrasensitive photoelectrochemical (PEC) biosensing strategy based on the dual signal amplification was proposed. As a result of the localized surface plasmon resonance (SPR) of Au NPs, the ultraviolet-visible absorption spectrum of Au NPs overlapped with emission spectra of ZnSe-COOH NFs, which generated efficient resonant energy transfer (RET) between ZnSe-COOH NFs and Au NPs. The RET improved photoelectric conversion efficiency of ZnSe-COOH NFs and significantly amplified PEC signal...
October 10, 2016: Analytical Chemistry
https://www.readbyqxmd.com/read/27707976/proliferation-and-survival-of-embryonic-sympathetic-neuroblasts-by-mycn-and-activated-alk-signaling
#13
Marco Kramer, Diogo Ribeiro, Marie Arsenian-Henriksson, Thomas Deller, Hermann Rohrer
: Neuroblastoma (NB) is a childhood tumor that arises from the sympathoadrenal lineage. MYCN amplification is the most reliable marker for poor prognosis and MYCN overexpression in embryonic mouse sympathetic ganglia results in NB-like tumors. MYCN cooperates with mutational activation of anaplastic lymphoma kinase (ALK), which promotes progression to NB, but the role of MYCN and ALK in tumorigenesis is still poorly understood. Here, we use chick sympathetic neuroblasts to examine the normal function of MYCN and MYC in the control of neuroblast proliferation, as well as effects of overexpression of MYCN, MYC, and activated ALK, alone and in combination...
October 5, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27707970/a-ret-er81-nrg1-signaling-pathway-drives-the-development-of-pacinian-corpuscles
#14
Michael S Fleming, Jian J Li, Daniel Ramos, Tong Li, David A Talmage, Shin-Ichi Abe, Silvia Arber, Wenqin Luo
: Axon-Schwann cell interactions are crucial for the development, function, and repair of the peripheral nervous system, but mechanisms underlying communication between axons and nonmyelinating Schwann cells are unclear. Here, we show that ER81 is functionally required in a subset of mouse RET(+) mechanosensory neurons for formation of Pacinian corpuscles, which are composed of a single myelinated axon and multiple layers of nonmyelinating Schwann cells, and Ret is required for the maintenance of Er81 expression...
October 5, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27702942/trans-ethnic-meta-analysis-of-genome-wide-association-studies-for-hirschsprung-disease
#15
Clara Sze-Man Tang, Hongsheng Gui, Ashish Kapoor, Jeong-Hyun Kim, Berta Luzón-Toro, Anna Pelet, Grzegorz Burzynski, Francesca Lantieri, Man-Ting So, Courtney Berrios, Hyoung Doo Shin, Raquel M Fernández, Thuy-Linh Le, Joke B G M Verheij, Ivana Matera, Stacey S Cherny, Priyanka Nandakumar, Hyun Sub Cheong, Guillermo Antiñolo, Jeanne Amiel, Jeong-Meen Seo, Dae-Yeon Kim, Jung-Tak Oh, Stanislas Lyonnet, Salud Borrego, Isabella Ceccherini, Robert M W Hofstra, Aravinda Chakravarti, Hyun-Young Kim, Pak Chung Sham, Paul K H Tam, Maria-Mercè Garcia-Barceló
Hirschsprung disease (HSCR) is the most common cause of neonatal intestinal obstruction. It is characterized by the absence of ganglia in the nerve plexuses of the lower gastrointestinal tract. So far, three common disease-susceptibility variants at the RET, SEMA3 and NRG1 loci have been detected through genome-wide association studies (GWAS) in Europeans and Asians to understand its genetic etiologies. Here we present a trans-ethnic meta-analysis of 507 HSCR cases and 1191 controls, combining all published GWAS results on HSCR to fine-map these loci and narrow down the putatively causal variants to 99% credible sets...
October 3, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27683183/ret-aberrations-in-diverse-cancers-next-generation-sequencing-of-4-871-patients
#16
Shumei Kato, Vivek Subbiah, Erica Marchlik, Sheryl K Elkin, Jennifer L Carter, Razelle Kurzrock
PURPOSE: Aberrations in genetic sequences encoding the tyrosine kinase receptor RET lead to oncogenic signaling that is targetable with anti-RET multi-kinase inhibitors. Understanding the comprehensive genomic landscape of RET aberrations across multiple cancers may facilitate clinical trial development targeting RET. EXPERIMENTAL DESIGN: We interrogated the molecular portfolio of 4,871 patients with diverse malignancies for the presence of RET aberrations using Clinical Laboratory Improvement Amendments (CLIA) certified targeted next-generation sequencing (NGS) of 182 or 236 gene panels...
September 28, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27680026/kinase-regulation-of-human-mhc-class-i-molecule-expression-on-cancer-cells
#17
Elliott J Brea, Claire Y Oh, Eusebio Manchado, Sadna Budhu, Ron S Gejman, George Mo, Patrizia Mondello, James E Han, Casey A Jarvis, David Ulmert, Qing Xiang, Aaron Y Chang, Ralph J Garippa, Taha Merghoub, Jedd D Wolchok, Neal Rosen, Scott W Lowe, David A Scheinberg
The major histocompatibility complex I (MHC-1) presents antigenic peptides to tumor-specific CD8(+) T cells. The regulation of MHC-I by kinases is largely unstudied, even though many patients with cancer are receiving therapeutic kinase inhibitors. Regulators of cell-surface HLA amounts were discovered using a pooled human kinome shRNA interference-based approach. Hits scoring highly were subsequently validated by additional RNAi and pharmacologic inhibitors. MAP2K1 (MEK), EGFR, and RET were validated as negative regulators of MHC-I expression and antigen presentation machinery in multiple cancer types, acting through an ERK output-dependent mechanism; the pathways responsible for increased MHC-I upon kinase inhibition were mapped...
November 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27664392/systemic-treatment-and-management-approaches-for-medullary-thyroid-cancer
#18
Vinicius Ernani, Mukesh Kumar, Amy Y Chen, Taofeek K Owonikoko
Although rare, medullary thyroid cancer (MTC) exemplifies the value that ever-expanding knowledge of molecular pathways and mechanisms brings to managing challenging cancers. Although surgery can be curative for MTC in many patients, a substantial proportion of patients present with locoregional or distant metastatic disease. Once distant disease occurs, treatment options are limited, and conventional cancer treatments such as cytotoxic chemotherapy are of minimal benefit. Biomarkers such as calcitonin and carcinoembryonic antigen are important correlates of disease burden as well as predictors of disease progress, including recurrence and survival...
September 10, 2016: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/27643099/br-02-2-hypertension-management-in-cancer-patients-undergoing-chemotherapy
#19
Naftali Stern
As both the rate of hypertension and cancer rise with age, concomitant hypertension in patients receiving treatment for cancer is very common. Increase in blood pressure during cancer treatment requires careful clinical assessment. Distinction between discontinuation or malabsorption of antihypertensive treatment due to factors such as nausea/vomiting/diarrhea and anti-cancer drug specific effects must be first made. De-novo hypertension during cancer treatment is likely related to anticancer drugs per se. Classical chemotherapeutic agents such as cyclophosphamide, cisplatin and busulfan have been previously linked to rising blood pressure...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27633255/mir-449-overexpression-inhibits-papillary-thyroid-carcinoma-cell-growth-by-targeting-ret-kinase-%C3%AE-catenin-signaling-pathway
#20
Zongyu Li, Xin Huang, Jinkai Xu, Qinghua Su, Jun Zhao, Jiancang Ma
Papillary thyroid carcinoma (PTC) is the most common thyroid cancer and represent approximately 80% of all thyroid cancers. The present study is aimed to investigate the role of microRNA (miR)-449 in the progression of PTC. Our results revealed that miR-449 was underexpressed in the collected PTC specimens compared with non-cancerous PTC tissues. Overexpression of miR-449 induced a cell cycle arrest at G0/G1 phase and inhibited PTC cell growth in vitro. Further studies revealed that RET proto-oncogene (RET) is a novel miR-449 target, due to miR-449 bound directly to its 3'-untranslated region and miR-449 mimic reduced the protein expression of RET...
August 18, 2016: International Journal of Oncology
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