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Ret signaling

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https://www.readbyqxmd.com/read/29776413/the-cxcr4-antagonist-plerixafor-amd3100-promotes-proliferation-of-ewing-sarcoma-cell-lines-in-vitro-and-activates-receptor-tyrosine-kinase-signaling
#1
Philipp Berning, Christiane Schaefer, Dagmar Clemens, Eberhard Korsching, Uta Dirksen, Jenny Potratz
BACKGROUND: The CXCR4 receptor antagonist plerixafor (AMD3100) is raising interest as an anti-cancer agent that disrupts the CXCL12-CXCR4 chemokine - receptor interaction between neoplastic cells and their microenvironment in tumor progression and metastasis. Here, we investigated plerixafor for anti-cancer activity in Ewing sarcoma, a rare and aggressive cancer of bone and soft tissues. METHODS: We used a variety of methods such as cell viability and migration assays, flow cytometry, phospho-tyrosine arrays and western blotting to determine plerixafor effects on five characterized Ewing sarcoma cell lines and a low-passage culture in vitro...
May 18, 2018: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29759226/a-novel-electrochemiluminescence-resonance-energy-transfer-system-of-luminol-graphene-quantum-dot-composite-and-its-application-in-h-2-o-2-detection
#2
Kaile Tian, Dejian Li, Tingting Tang, Fei Nie, Yang Zhou, Jianxiu Du, Jianbin Zheng
Luminol-nitrogen doped graphene quantum dot (luminol-NGQDs) nanocomposite was synthesized and a novel electrochemiluminescence resonance energy transfer (ECL-RET) process occurred between luminol as the donor and NGQDs as the acceptor in the composite. This ECL-RET effect helped luminol-NGQDs composite produced an anodic ECL signal without coreactants. The ECL-RET mechanism was also studied based on the fluorescence spectra, the ultraviolet-visible absorption spectra and the electrochemiluminescence (ECL) spectra...
August 1, 2018: Talanta
https://www.readbyqxmd.com/read/29749533/egf-upregulates-rfpl3-and-htert-via-the-mek-signaling-pathway-in-non%C3%A2-small-cell-lung-cancer-cells
#3
Chuan Lin, Yu Qin, Hua Zhang, Ming-Yang Gao, Yan-Fu Wang
Activation of the epidermal growth factor receptor (EGFR) during tumor development can trigger the MEK signaling pathway. In the present study, we investigated the MEK signaling pathway in non‑small cell lung cancer (NSCLC) cells with respect to the effect of epidermal growth factor (EGF) on expression of Ret finger protein like 3 (RFPL3) and human telomerase reverse transcriptase (hTERT), and the effect of RFPL3 overexpression on other MEK signaling proteins. In vitro, A549 and H1299 cells were treated with different concentrations of EGF for 24 h or 48 h...
May 8, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29743240/control-of-mitochondrial-superoxide-production-by-reverse-electron-transport-at-complex-i
#4
Ellen L Robb, Andrew R Hall, Tracy A Prime, Simon Eaton, Marten Szibor, Carlo Viscomi, Andrew M James, Michael P Murphy
The generation of mitochondrial superoxide (O2 •- ) by reverse electron transport (RET) at complex I causes oxidative damage in pathologies such as ischemia reperfusion injury, but also provides the precursor to H2 O2 production in physiological mitochondrial redox signaling. Here, we quantified the factors that determine mitochondrial O2 •- production by RET in isolated heart mitochondria. Measuring mitochondrial H2 O2 production at a range of Δp values and for several CoQ and NADH pool redox states obtained with the uncoupler p-trifluoromethoxyphenylhydrazone, we show that O2 •- production by RET responds to changes in O2 concentration, the magnitude of the proton-motive force (Δp), and the redox states of the coenzyme Q (CoQ) and NADH pools...
May 9, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29689503/electrochemiluminescence-quenching-of-luminol-by-cus-in-situ-grown-on-reduced-graphene-oxide-for-detection-of-n-terminal-pro-brain-natriuretic-peptide
#5
Xiaojian Li, Peng Lu, Bin Wu, Yaoguang Wang, Huan Wang, Bin Du, Xuehui Pang, Qin Wei
A novel electrochemiluminescence (ECL) signal-off strategy based on CuS in situ grown on reduced graphene oxide (CuS-rGO) quenching luminol/H2 O2 system was firstly proposed. Luminol was grafted on the surface of Au@Fe3 O4 -Cu3 (PO4 )2 nanoflowers (Luminol-Au@Fe3 O4 -Cu3 (PO4 )2 ) which exhibited excellent catalytic effect towards the reduction of H2 O2 to enhance the ECL intensity of luminol. Cu3 (PO4 )2 nanoflowers showed large surface area which can immobilize more Fe3 O4 and Au nanoparticles. The quenching mechanism of CuS-rGO was due to ECL resonance energy transfer (RET)...
April 17, 2018: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/29688429/ef24-a-curcumin-analog-and-zstk474-emphasizes-the-effect-of-cabozantinib-in-medullary-thyroid-cancer
#6
Loris Bertazza, Francesca Sensi, Elisabetta Cavedon, Sara Watutantrige-Fernando, Simona Censi, Jacopo Manso, Federica Vianello, Eric Casal Ide, Maurizio Iacobone, Raffaele Pezzani, Caterina Mian, Susi Barollo
XL184 is a small-molecule kinase inhibitor recently included in first-line systemic therapy for patients with advanced, progressive medullary thyroid cancer (MTC). EF24 is a curcumin analog with a high bio-availability, and ZSTK474 is an inhibitor of the PI3K signaling pathway. We investigated the effect of these compounds, alone and in combination, in two RET-mutated TT and MZ-CRC-1 MTC cell lines, and in six mostly RET wild-type human MTC primary cultures. Low IC50 values demonstrated the efficacy of the drugs, while the Combination Index revealed a significant synergistic effect of combinations of XL184+ZSTK474 and XL184+EF24...
April 23, 2018: Endocrinology
https://www.readbyqxmd.com/read/29683733/cep55-overexpression-causes-male-specific-sterility-in-mice-by-suppressing-foxo1-nuclear-retention-through-sustained-activation-of-pi3k-akt-signaling
#7
Debottam Sinha, Murugan Kalimutho, Josephine Bowles, Ai-Leen Chan, D Jo Merriner, Amanda L Bain, Jacinta L Simmons, Raimundo Freire, J Alejandro Lopez, Robin M Hobbs, Moira K O'Bryan, Kum Kum Khanna
Spermatogenesis is a dynamic process involving self-renewal and differentiation of spermatogonial stem cells, meiosis, and ultimately, the differentiation of haploid spermatids into sperm. Centrosomal protein (CEP)-55 is necessary for somatic cell abscission during cytokinesis. It facilitates equal segregation of cytoplasmic contents between daughter cells by recruiting endosomal sorting complex required for transport machinery (ESCRT) at the midbody. In germ cells, CEP55, in partnership with testes expressed-14 protein (TEX14), has also been shown to be an integral component of intercellular bridge before meiosis...
April 17, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29657135/precision-targeted-therapy-with-blu-667-for-ret-driven-cancers
#8
Vivek Subbiah, Justin F Gainor, Rami Rahal, Jason D Brubaker, Joseph L Kim, Michelle Maynard, Wei Hu, Qiongfang Cao, Michael P Sheets, Douglas Wilson, Kevin J Wilson, Lucian DiPietro, Paul Fleming, Michael Palmer, Mimi I Hu, Lori Wirth, Marcia S Brose, Sai-Hong Ignatius Ou, Matthew Taylor, Elena Garralda, Stephen Miller, Beni Wolf, Christoph Lengauer, Timothy Guzi, Erica K Evans
The receptor tyrosine kinase, rearranged during transfection (RET), is an oncogenic driver activated in multiple cancers including non-small cell lung cancer (NSCLC), medullary thyroid cancer (MTC) and papillary thyroid cancer (PTC). No approved therapies have been designed to target RET; treatment has been limited to multi-kinase inhibitors (MKIs) which can have significant off-target toxicities and limited efficacy. BLU-667 is a highly potent and selective RET inhibitor designed to overcome these limitations...
April 15, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29626249/molecular-markers-in-well-differentiated-thyroid-cancer
#9
REVIEW
Anil K D'Cruz, Richa Vaish, Abhishek Vaidya, Iain J Nixon, Michelle D Williams, Vincent Vander Poorten, Fernando López, Peter Angelos, Ashok R Shaha, Avi Khafif, Alena Skalova, Alessandra Rinaldo, Jennifer L Hunt, Alfio Ferlito
PURPOSE: Thyroid nodules are of common occurrence in the general population. About a fourth of these nodules are indeterminate on aspiration cytology placing many a patient at risk of unwanted surgery. The purpose of this review is to discuss various molecular markers described to date and place their role in proper perspective. This review covers the fundamental role of the signaling pathways and genetic changes involved in thyroid carcinogenesis. The current literature on the prognostic significance of these markers is also described...
April 6, 2018: European Archives of Oto-rhino-laryngology
https://www.readbyqxmd.com/read/29608602/er-positive-breast-cancer-cells-are-poised-for-ret-mediated-endocrine-resistance
#10
Sachi Horibata, Edward J Rice, Chinatsu Mukai, Brooke A Marks, Kelly Sams, Hui Zheng, Lynne J Anguish, Scott A Coonrod, Charles G Danko
The RET tyrosine kinase signaling pathway is involved in the development of endocrine resistant ER+ breast cancer. However, we know little about how ER+ cells activate RET signaling and initiate an endocrine resistant phenotype. Here we show that both ER+ endocrine resistant and sensitive breast cancers have a functional RET tyrosine kinase signaling pathway, but that endocrine sensitive breast cancer cells lack RET ligands that are necessary to drive endocrine resistance. Transcription of one RET ligand, GDNF, is necessary and sufficient to confer resistance in the ER+ MCF-7 cell line...
2018: PloS One
https://www.readbyqxmd.com/read/29601828/identification-of-variants-in-ret-and-ihh-pathway-members-in-a-large-family-with-history-of-hirschsprung-disease
#11
Y Sribudiani, R K Chauhan, M M Alves, L Petrova, E Brosens, C Harrison, T Wabbersen, B M de Graaf, T Rügenbrink, G Burzynski, R W W Brouwer, W F J van IJcken, S M Maas, A de Klein, J Osinga, B J L Eggen, A J Burns, A S Brooks, I T Shepherd, R M W Hofstra
BACKGROUND & AIMS: Hirschsprung disease (HSCR) is an inherited congenital disorder characterized by absence of enteric ganglia in the distal part of the gut. Variants in ret proto-oncogene (RET) have been associated with up to 50% of familial and 35% of sporadic cases. We searched for variants that affect disease risk in a large, multi-generational family with history of HSCR in a linkage region previously associated with the disease (4q31.3-q32.3) and exome wide. METHODS: We performed exome sequencing analyses of a family in the Netherlands with 5 members diagnosed with HSCR and 2 members diagnosed with functional constipation...
March 27, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29569362/temporally-restricted-death-and-the-role-of-p75ntr-as-a-survival-receptor-in-the-developing-sensory-nervous-system
#12
Irene Cheng, Lucy Jin, Lucy C Rose, Christopher D Deppmann
The peripheral somatosensory system overproduces neurons early in development followed by a period of cell death during final target innervation. The decision to survive or die in somatosensory neurons of the dorsal root ganglion (DRG) is mediated by target derived neurotrophic factors and their cognate receptors. Subsets of peripheral somatosensory neurons can be crudely defined by the neurotrophic receptors that they express: peptidergic nociceptors (TrkA+), non-peptidergic nociceptors (Ret+), mechanoreceptors (Ret+ or TrkB+), and proprioceptors (TrkC+)...
March 22, 2018: Developmental Neurobiology
https://www.readbyqxmd.com/read/29567567/molecularly-imprinted-sensor-based-on-russian-matryoshka-structured-molecules-for-enhanced-specific-identification-and-double-amplification-in-ultra-trace-tb-3-determination
#13
Jianping Li, Bin Yang, Hongcheng Pan, Guobao Xu
The selective and sensitive detection of rare earth elements is thought to be difficult because the concentration of those elements in the sample is commonly at a low level and they normally have severe mutual interference which is caused by homologous chemical properties. In this study, a novel molecularly imprinted polymer (MIP) sensor was fabricated for highly sensitive and selective determination of ultra-trace Tb3+ . The Tb3+ -ethylenediaminetetraacetic acid complex (Tb-EDTA) as the template molecule was incorporated into mono-6-mercapto-β-cyclodextrin (mono-6-SH-β-CD) to form a Russian Matryoshka (RM)-structured molecule (CD/Tb-EDTA)...
March 14, 2018: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/29563833/evolution-of-regorafenib-from-bench-to-bedside-in-colorectal-cancer-is-it-an-attractive-option-or-merely-a-me-too-drug
#14
REVIEW
Gaurav Goel
Colorectal cancer (CRC) is a major public health problem in the United States with an estimated 50,260 deaths in 2017. Over the past two decades, several agents have been approved by the US Food and Drug Administration (FDA) for the treatment of patients with metastatic CRC (mCRC). Regorafenib (BAY 73-4506) is a small-molecule multikinase inhibitor that was approved for the treatment of mCRC in 2012. This agent is a novel oral diphenylurea-based multikinase inhibitor that is active against several angiogenic receptor tyrosine kinases (RTKs; VEGFR-1, VEGFR-2, VEGFR-3, TIE-2), oncogenic RTKs (c-KIT, RET), stromal RTKs (PDGFR-B, FGFR-1), and intracellular signaling kinases (c-RAF/RAF-1, BRAF, BRAFV600E )...
2018: Cancer Management and Research
https://www.readbyqxmd.com/read/29549897/detection-of-ret-rearranged-during-transfection-variants-and-their-downstream-signal-molecules-in-ret-rearranged-lung-adenocarcinoma-patients
#15
Jeong-Oh Kim, Jung-Young Shin, Min Young Kim, Kyoung Hwa Son, Chan Kwon Jung, Tae-Jung Kim, Su Young Kim, Jae Kil Park, Sook Whan Sung, Sang Ju Bae, Hyun Jung Min, Jin-Hyoung Kang
BACKGROUND: We screened resected tumor tissues from patients with lung cancer for EGFR mutations, ALK rearrangements, and rearranged during transfection (RET) gene variants (including RET rearrangements and the Kinesin Family Member 5B (KIF5B)-RET fusion gene) using various methods including reverse transcription polymerase chain reaction (RT-PCR), transcript assays, fluorescence in situ hybridization (FISH), and immunohistochemistry (IHC). We also examined the protein expression of associated downstream signaling molecules to assess the effect of these variants on patient outcome...
March 2018: Surgical Oncology
https://www.readbyqxmd.com/read/29548890/the-expressional-disorder-of-the-renal-ras-mediates-nephrotic-syndrome-of-male-rat-offspring-induced-by-prenatal-ethanol-exposure
#16
Yanan Zhu, Na Zuo, Bin Li, Ying Xiong, Haiyun Chen, Hangyuan He, Zhaoxia Sun, Shuangshuang Hu, Hui Cheng, Ying Ao, Hui Wang
This study aimed to prove that prenatal ethanol exposure (PEE) can induce nephrotic syndrome in male rat offspring and to explore the underlying intrauterine programming mechanisms. Pregnant Wistar rats were intragastrically administered ethanol (4 g/kg d) from gestational day (GD) 9 to GD 20, and the male fetuses were delivered by cesarean section at GD20 and the male adult offspring were euthanized at postnatal week (PW) 24. In vitro, the primary metanephric mesenchyme cells were treated with ethanol at concentrations of 15-60 mM...
May 1, 2018: Toxicology
https://www.readbyqxmd.com/read/29517106/vandetanib-has-antineoplastic-activity-in-anaplastic-thyroid-cancer-in-vitro-and-in-vivo
#17
Silvia Martina Ferrari, Guido Bocci, Teresa Di Desidero, Ilaria Ruffilli, Giusy Elia, Francesca Ragusa, Anna Fioravanti, Paola Orlandi, Sabrina Rosaria Paparo, Armando Patrizio, Simona Piaggi, Concettina La Motta, Salvatore Ulisse, Enke Baldini, Gabriele Materazzi, Paolo Miccoli, Alessandro Antonelli, Poupak Fallahi
The antitumor activity of vandetanib [a multiple signal transduction inhibitor including the RET tyrosine kinase, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) receptor (VEGFR), ERK and with antiangiogenic activity], in primary anaplastic thyroid cancer (ATC) cells, in the human cell line 8305C [undifferentiated thyroid cancer (TC)] and in an ATC‑cell line (AF), was investigated in the present study. Vandetanib (1 and 100 nM; 1, 10, 25 and 50 µM) was tested by WST‑1, apoptosis, migration and invasion assays: in primary ATC cells, in the 8305C continuous cell line, and in AF cells; and in 8305C cells in CD nu/nu mice...
May 2018: Oncology Reports
https://www.readbyqxmd.com/read/29517103/lenvatinib-exhibits-antineoplastic-activity-in-anaplastic-thyroid-cancer-in-vitro-and-in-vivo
#18
Silvia Martina Ferrari, Guido Bocci, Teresa Di Desidero, Giusy Elia, Ilaria Ruffilli, Francesca Ragusa, Paola Orlandi, Sabrina Rosaria Paparo, Armando Patrizio, Simona Piaggi, Concettina La Motta, Salvatore Ulisse, Enke Baldini, Gabriele Materazzi, Paolo Miccoli, Alessandro Antonelli, Poupak Fallahi
Lenvatinib is an oral, multitargeted tyrosine kinase inhibitor (TKI) of VEGFR1-VEGFR3, FGFR1-FGFR4, PDGFRα, RET and v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) signaling networks involved in tumor angiogenesis. We have evaluated the antitumor activity of lenvatinib in primary anaplastic thyroid cancer (ATC) cells, in the human cell line 8305C (undifferentiated thyroid cancer) and in an ATC-cell line (AF). The AF cell line was obtained from the primary ATC cultures and was the one that grew over 50 passages...
May 2018: Oncology Reports
https://www.readbyqxmd.com/read/29468981/lenvatinib-in-the-therapy-of-aggressive-thyroid-cancer-state-of-the-art-and-new-perspectives-with-patents-recently-applied
#19
Silvia Martina Ferrari, Ilaria Ruffilli, Marco Centanni, Camilla Virili, Gabriele Materazzi, Magdalini Alexopoulou, Mario Miccoli, Alessandro Antonelli, Poupak Fallahi
BACKGROUND AND OBJECTIVE: Lenvatinib is an oral, multitargeted tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor receptors (VEGFR1-VEGFR3), fibroblast growth factor receptors (FGFR1-FGFR4), platelet-derived growth factor receptor (PDGFR)α, rearranged during transfection (RET), and v-kit (KIT) signaling networks implicated in tumor angiogenesis. METHOD: Here we review the scientific literature about lenvatinib in the treatment of thyroid cancer...
February 19, 2018: Recent Patents on Anti-cancer Drug Discovery
https://www.readbyqxmd.com/read/29455670/the-rationale-for-druggability-of-ccdc6-tyrosine-kinase-fusions-in-lung-cancer
#20
REVIEW
Aniello Cerrato, Roberta Visconti, Angela Celetti
Gene fusions occur in up to 17% of solid tumours. Oncogenic kinases are often involved in such fusions. In lung cancer, almost 30% of patients carrying an activated oncogene show the fusion of a tyrosine kinase to an heterologous gene. Several genes are partner in the fusion with the three kinases ALK, ROS1 and RET in lung. The impaired function of the partner gene, in combination with the activation of the kinase, may alter the cell signaling and promote the cancer cell addiction to the oncogene. Moreover, the gene that is partner in the fusion to the kinase may affect the response to therapeutics and/or promote resistance in the cancer cells...
February 19, 2018: Molecular Cancer
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