Metabolic Imaging Allows Early Prediction of Response to Vandetanib
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SRC Antibody - N-Terminal Region (ARP32476 P050) Data Sheet
SRC antibody - N-terminal region (ARP32476_P050) Data Sheet Product Number ARP32476_P050 Product Name SRC antibody - N-terminal region (ARP32476_P050) Size 50ug Gene Symbol SRC Alias Symbols ASV; SRC1; c-SRC; p60-Src Nucleotide Accession# NM_005417 Protein Size (# AA) 536 amino acids Molecular Weight 60kDa Product Format Lyophilized powder NCBI Gene Id 6714 Host Rabbit Clonality Polyclonal Official Gene Full Name V-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) Gene Family SH2D This is a rabbit polyclonal antibody against SRC. It was validated on Western Blot by Aviva Systems Biology. At Aviva Systems Biology we manufacture rabbit polyclonal antibodies on a large scale (200-1000 Description products/month) of high throughput manner. Our antibodies are peptide based and protein family oriented. We usually provide antibodies covering each member of a whole protein family of your interest. We also use our best efforts to provide you antibodies recognize various epitopes of a target protein. For availability of antibody needed for your experiment, please inquire (). Peptide Sequence Synthetic peptide located within the following region: QTPSKPASADGHRGPSAAFAPAAAEPKLFGGFNSSDTVTSPQRAGPLAGG This gene is highly similar to the v-src gene of Rous sarcoma virus. This proto-oncogene may play a role in the Description of Target regulation of embryonic development and cell growth. SRC protein is a tyrosine-protein kinase whose activity can be inhibited by phosphorylation by c-SRC kinase. Mutations in this gene could be involved in the -
Chemoresistance in Human Ovarian Cancer: the Role of Apoptotic
Reproductive Biology and Endocrinology BioMed Central Review Open Access Chemoresistance in human ovarian cancer: the role of apoptotic regulators Michael Fraser1, Brendan Leung1, Arezu Jahani-Asl1, Xiaojuan Yan1, Winston E Thompson2 and Benjamin K Tsang*1 Address: 1Department of Obstetrics & Gynecology and Cellular & Molecular Medicine, University of Ottawa, Ottawa Health Research Institute, Ottawa, Canada K1Y 4E9, Canada and 2Department of Obstetrics & Gynecology and Cooperative Reproductive Science Research Center, Morehouse School of Medicine, Atlanta, GA 30310, USA Email: Michael Fraser - [email protected]; Brendan Leung - [email protected]; Arezu Jahani-Asl - [email protected]; Xiaojuan Yan - [email protected]; Winston E Thompson - [email protected]; Benjamin K Tsang* - [email protected] * Corresponding author Published: 07 October 2003 Received: 26 June 2003 Accepted: 07 October 2003 Reproductive Biology and Endocrinology 2003, 1:66 This article is available from: http://www.RBEj.com/content/1/1/66 © 2003 Fraser et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL. Abstract Ovarian cancer is among the most lethal of all malignancies in women. While chemotherapy is the preferred treatment modality, chemoresistance severely limits treatment success. Recent evidence suggests that deregulation of key pro- and anti-apoptotic pathways is a key factor in the onset and maintenance of chemoresistance. Furthermore, the discovery of novel interactions between these pathways suggests that chemoresistance may be multi-factorial. Ultimately, the decision of the cancer cell to live or die in response to a chemotherapeutic agent is a consequence of the overall apoptotic capacity of that cell. -
Potential High-Impact Interventions Report Priority Area 02: Cancer
AHRQ Healthcare Horizon Scanning System – Potential High-Impact Interventions Report Priority Area 02: Cancer Prepared for: Agency for Healthcare Research and Quality U.S. Department of Health and Human Services 540 Gaither Road Rockville, MD 20850 www.ahrq.gov Contract No. HHSA290201000006C Prepared by: ECRI Institute 5200 Butler Pike Plymouth Meeting, PA 19462 December 2012 Statement of Funding and Purpose This report incorporates data collected during implementation of the Agency for Healthcare Research and Quality (AHRQ) Healthcare Horizon Scanning System by ECRI Institute under contract to AHRQ, Rockville, MD (Contract No. HHSA290201000006C). The findings and conclusions in this document are those of the authors, who are responsible for its content, and do not necessarily represent the views of AHRQ. No statement in this report should be construed as an official position of AHRQ or of the U.S. Department of Health and Human Services. This report’s content should not be construed as either endorsements or rejections of specific interventions. As topics are entered into the System, individual topic profiles are developed for technologies and programs that appear to be close to diffusion into practice in the United States. Those reports are sent to various experts with clinical, health systems, health administration, and/or research backgrounds for comment and opinions about potential for impact. The comments and opinions received are then considered and synthesized by ECRI Institute to identify interventions that experts deemed, through the comment process, to have potential for high impact. Please see the methods section for more details about this process. This report is produced twice annually and topics included may change depending on expert comments received on interventions issued for comment during the preceding 6 months. -
Vandetanib (ZD6474), an Inhibitor of VEGFR and EGFR Signalling, As a Novel Molecular-Targeted Therapy Against Cholangiocarcinoma
British Journal of Cancer (2009) 100, 1257 – 1266 & 2009 Cancer Research UK All rights reserved 0007 – 0920/09 $32.00 www.bjcancer.com Vandetanib (ZD6474), an inhibitor of VEGFR and EGFR signalling, as a novel molecular-targeted therapy against cholangiocarcinoma 1,2 3 1 4 2 3 ,1,3 D Yoshikawa , H Ojima , A Kokubu , T Ochiya , S Kasai , S Hirohashi and T Shibata* 1 2 Cancer Genomics Project, National Cancer Center Research Institute, Tokyo, Japan; Division of Gastroenterological and General Surgery, Department of Surgery, Asahikawa Medical College, Asahikawa, Japan; 3Pathology Division, National Cancer Center Research Institute, Tokyo, Japan; 4Section for Studies on Metastasis, National Cancer Center Research Institute, Tokyo, Japan Cholangiocarcinoma is an intractable cancer, with no effective therapy other than surgical resection. Elevated vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) expressions are associated with the progression of cholangiocarcinoma. We therefore examined whether inhibition of VEGFR and EGFR could be a potential therapeutic target for cholangiocarcinoma. Vandetanib (ZD6474, ZACTIMA), a VEGFR-2/EGFR inhibitor, was evaluated. Four human cholangiocarcinoma cell lines were molecularly characterised and investigated for their response to vandetanib. In vitro, two cell lines (OZ and HuCCT1), both of which harboured KRAS mutation, were refractory to vandetanib, one cell line (TGBC24TKB) was somewhat resistant, and another cell line (TKKK) was sensitive. The most sensitive cell line (TKKK) had EGFR amplification. Vandetanib significantly À1 À1 À1 À1 inhibited the growth of TKKK xenografts at doses X12.5 mg kg day (Po0.05), but higher doses (50 mg kg day , Po0.05) of À1 À1 vandetanib were required to inhibit the growth of OZ xenografts. -
Epha Receptors and Ephrin-A Ligands Are Upregulated by Monocytic
Mukai et al. BMC Cell Biology (2017) 18:28 DOI 10.1186/s12860-017-0144-x RESEARCHARTICLE Open Access EphA receptors and ephrin-A ligands are upregulated by monocytic differentiation/ maturation and promote cell adhesion and protrusion formation in HL60 monocytes Midori Mukai, Norihiko Suruga, Noritaka Saeki and Kazushige Ogawa* Abstract Background: Eph signaling is known to induce contrasting cell behaviors such as promoting and inhibiting cell adhesion/ spreading by altering F-actin organization and influencing integrin activities. We have previously demonstrated that EphA2 stimulation by ephrin-A1 promotes cell adhesion through interaction with integrins and integrin ligands in two monocyte/ macrophage cell lines. Although mature mononuclear leukocytes express several members of the EphA/ephrin-A subclass, their expression has not been examined in monocytes undergoing during differentiation and maturation. Results: Using RT-PCR, we have shown that EphA2, ephrin-A1, and ephrin-A2 expression was upregulated in murine bone marrow mononuclear cells during monocyte maturation. Moreover, EphA2 and EphA4 expression was induced, and ephrin-A4 expression was upregulated, in a human promyelocytic leukemia cell line, HL60, along with monocyte differentiation toward the classical CD14++CD16− monocyte subset. Using RT-PCR and flow cytometry, we have also shown that expression levels of αL, αM, αX, and β2 integrin subunits were upregulated in HL60 cells along with monocyte differentiation while those of α4, α5, α6, and β1 subunits were unchanged. Using a cell attachment stripe assay, we have shown that stimulation by EphA as well as ephrin-A, likely promoted adhesion to an integrin ligand- coated surface in HL60 monocytes. Moreover, EphA and ephrin-A stimulation likely promoted the formation of protrusions in HL60 monocytes. -
CRKL As a Lung Cancer Oncogene and Mediator Of
views in The spotliGhT CRKL as a Lung Cancer Oncogene and Mediator of Acquired Resistance to eGFR inhibitors: is it All That it is Cracked Up to Be? Marc Ladanyi summary: Cheung and colleagues demonstrate that amplified CRKL can function as a driver oncogene in lung adeno- carcinoma, activating both RAS and RAP1 to induce mitogen-activated protein kinase signaling. In addition, they show that CRKL amplification may be another mechanism for primary or acquired resistance to epidermal growth factor re- ceptor kinase inhibitors. Cancer Discovery; 1(7); 560–1. ©2011 AACR. Commentary on Cheung et al., p. 608 (1). In this issue of Cancer Discovery, Cheung and colleagues (1) mutual exclusivity. Cheung and colleagues (1) report that present extensive genomic and functional data supporting focal CRKL amplification is mutually exclusive with EGFR focal amplification of the CRKL gene at 22q11.21 as a driver mutation and EGFR amplification. However, of the 6 lung oncogene in lung adenocarcinoma. The report expands on cancer cell lines found in this study to have focal gains of data previously presented by Kim and colleagues (2). CRKL CRKL, 2 contain other major driver oncogenes (KRAS G13D is a signaling adaptor protein that contains SH2 and SH3 in HCC515, BRAF G469A in H1755; refs. 7, 8). Interestingly, domains that mediate protein–protein interactions linking both cell lines demonstrated clear dependence on CRKL in tyrosine-phosphorylated upstream signaling molecules (e.g., functional assays. Perhaps CRKL amplification is more akin BCAR1, paxillin, GAB1) to downstream effectors (e.g., C3G, to PIK3CA mutations, which often, but not always, are con- SOS) (3). -
Gefitinib and Afatinib Show Potential Efficacy for Fanconi Anemia−Related Head and Neck Cancer
Published OnlineFirst January 31, 2020; DOI: 10.1158/1078-0432.CCR-19-1625 CLINICAL CANCER RESEARCH | TRANSLATIONAL CANCER MECHANISMS AND THERAPY Gefitinib and Afatinib Show Potential Efficacy for Fanconi Anemia–Related Head and Neck Cancer Helena Montanuy1, Agueda Martínez-Barriocanal2,3, Jose Antonio Casado4,5, Llorenc¸ Rovirosa1, Maria Jose Ramírez1,4,6, Rocío Nieto2, Carlos Carrascoso-Rubio4,5, Pau Riera6,7, Alan Gonzalez 8, Enrique Lerma7, Adriana Lasa4,6, Jordi Carreras-Puigvert9, Thomas Helleday9, Juan A. Bueren4,5, Diego Arango2,3, Jordi Minguillon 1,4,5, and Jordi Surralles 1,4,5 ABSTRACT ◥ Purpose: Fanconi anemia rare disease is characterized by bone two best candidates, gefitinib and afatinib, EGFR inhibitors marrow failure and a high predisposition to solid tumors, especially approved for non–small cell lung cancer (NSCLC), displayed head and neck squamous cell carcinoma (HNSCC). Patients with nontumor/tumor IC50 ratios of approximately 400 and approx- Fanconi anemia with HNSCC are not eligible for conventional imately 100 times, respectively. Neither gefitinib nor afatinib therapies due to high toxicity in healthy cells, predominantly activated the Fanconi anemia signaling pathway or induced hematotoxicity, and the only treatment currently available is sur- chromosomal fragility in Fanconi anemia cell lines. Importantly, gical resection. In this work, we searched and validated two already both drugs inhibited tumor growth in xenograft experiments in approved drugs as new potential therapies for HNSCC in patients immunodeficient mice using two Fanconi anemia patient– with Fanconi anemia. derived HNSCCs. Finally, in vivo toxicity studies in Fanca- Experimental Design: We conducted a high-content screening deficient mice showed that administration of gefitinib or afatinib of 3,802 drugs in a FANCA-deficient tumor cell line to identify was well-tolerated, displayed manageable side effects, no toxicity nongenotoxic drugs with cytotoxic/cytostatic activity. -
Evidence for an Interaction Between the Insulin Receptor and Grb7. a Role for Two of Its Binding Domains, PIR and SH2
Oncogene (2000) 19, 2052 ± 2059 ã 2000 Macmillan Publishers Ltd All rights reserved 0950 ± 9232/00 $15.00 www.nature.com/onc Evidence for an interaction between the insulin receptor and Grb7. A role for two of its binding domains, PIR and SH2 Anne Kasus-Jacobi1,2,3,Ve ronique Be re ziat1,3, Dominique Perdereau1, Jean Girard1 and Anne-FrancËoise Burnol*,1 1Endocrinologie MeÂtabolisme et DeÂveloppement, CNRS, UPR 1524, 9 rue Jules Hetzel, 92190 Meudon, France The molecular adapter Grb7 is likely to be implicated in new family of adapters has recently emerged, the Grb7 the development of certain cancer types. In this study we family of proteins, comprising Grb7, Grb10 and show that Grb7 binds the insulin receptors, when they Grb14. The members of this family were originally are activated and tyrosine phosphorylated. This interac- cloned by interaction with EGF receptor, using the tion is documented by two-hybrid experiments, GST CORT (cloning of receptor target) system (Daly et al., pull-down assays and in vivo coimmunoprecipitations. In 1996; Margolis, 1994; Ooi et al., 1995), and the use of addition, our results argue in favor of a preferential the yeast two-hybrid technology has emphasized their association between Grb7 and the insulin receptors when implication in signal transduction (Daly, 1998). These compared to other tyrosine kinase receptors like the adapters bind also other tyrosine kinase receptors, like EGF receptor, the FGF receptor and Ret. Interestingly, erbB2, Ret, Elk, PDGF receptors, insulin receptors and Grb7 is not a substrate of the insulin receptor tyrosine IGF-1 receptors (Daly et al., 1996; Dey et al., 1996; kinase activity. -
Crosstalk Between Integrin and Receptor Tyrosine Kinase Signaling in Breast Carcinoma Progression
BMB reports Mini Review Crosstalk between integrin and receptor tyrosine kinase signaling in breast carcinoma progression Young Hwa Soung, John L. Clifford & Jun Chung* Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130 This review explored the mechanism of breast carcinoma pro- cancer originates from breast epithelial cells that are trans- gression by focusing on integrins and receptor tyrosine kinases formed into metastatic carcinomas. Metastatic potential and re- (or growth factor receptors). While the primary role of integrins sponsiveness to treatment vary depending on the expression of was previously thought to be solely as mediators of adhesive hormone receptors such as estrogen receptor and progesterone interactions between cells and extracellular matrices, it is now receptor (5), RTKs such as ErbB-2, epidermal growth factor re- believed that integrins also regulate signaling pathways that ceptor (EGFR), and hepatocyte growth factor receptor, c-Met control cancer cell growth, survival, and invasion. A large (6), and integrins (7). Major integrins expressed on breast epi- body of evidence suggests that the cooperation between in- thelial cells include α2β1, α3β1, αvβ3, αvβ5, αvβ6, α5β1, tegrin and receptor tyrosine kinase signaling regulates certain α6β1, and α6β4 (7). Among these, this review focuses on signaling functions that are important for cancer progression. αvβ3, α5β1, and α6β4, all of which are upregulated in in- Recent developments on the crosstalk between integrins and vasive breast carcinoma and have well established relation- receptor tyrosine kinases, and its implication in mammary tu- ships with RTKs (8). These integrins serve as receptors for vi- mor progression, are discussed. -
A Retrospective Analysis of RET Translocation, Gene Copy Number
Platt et al. BMC Cancer (2015) 15:171 DOI 10.1186/s12885-015-1146-8 RESEARCH ARTICLE Open Access A retrospective analysis of RET translocation, gene copy number gain and expression in NSCLC patients treated with vandetanib in four randomized Phase III studies Adam Platt1*, John Morten2, Qunsheng Ji3, Paul Elvin2, Chris Womack2, Xinying Su3, Emma Donald2, Neil Gray2, Jessica Read2, Graham Bigley2, Laura Blockley2, Carl Cresswell2, Angela Dale2, Amanda Davies2, Tianwei Zhang3, Shuqiong Fan3, Haihua Fu3, Amanda Gladwin2, Grace Harrod2, James Stevens2, Victoria Williams2, Qingqing Ye3, Li Zheng3, Richard de Boer4, Roy S Herbst5, Jin-Soo Lee6 and James Vasselli7,8 Abstract Background: To determine the prevalence of RET rearrangement genes, RET copy number gains and expression in tumor samples from four Phase III non-small-cell lung cancer (NSCLC) trials of vandetanib, a selective inhibitor of VEGFR, RET and EGFR signaling, and to determine any association with outcome to vandetanib treatment. Methods: Archival tumor samples from the ZODIAC (NCT00312377, vandetanib ± docetaxel), ZEAL (NCT00418886, vandetanib ± pemetrexed), ZEPHYR (NCT00404924, vandetanib vs placebo) and ZEST (NCT00364351, vandetanib vs erlotinib) studies were evaluated by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) in 944 and 1102 patients. Results: The prevalence of RET rearrangements by FISH was 0.7% (95% CI 0.3–1.5%) among patients with a known result. Seven tumor samples were positive for RET rearrangements (vandetanib, n = 3; comparator, n = 4). 2.8% (n =26) of samples had RET amplification (innumerable RET clusters, or ≥7 copies in > 10% of tumor cells), 8.1% (n = 76) had low RET gene copy number gain (4–6copiesin≥40% of tumor cells) and 8.3% (n = 92) were RET expression positive (signal intensity ++ or +++ in >10% of tumor cells). -
Stimulation of Endogenous GH and Interleukin-6 Receptors Selectively Activates Different Jaks and Stats, with a Stat5 Specific Synergistic Effect of Dexamethasone
301 Stimulation of endogenous GH and interleukin-6 receptors selectively activates different Jaks and Stats, with a Stat5 specific synergistic effect of dexamethasone S von Laue1, J Finidori3, M Maamra1, X-Y Shen1, S Justice1, P R M Dobson2 and R J M Ross1 1Division of Clinical Sciences, University of Sheffield, UK 2Institute for Cancer Studies, University of Sheffield, UK 3INSERM, Unité 344, Faculté de Médecine Necker, Paris, France (Requests for offprints should be addressed to S von Laue, INSERM U344, Laboratoire d’Endocrinologie Moléculaire, Faculté de Médecine Necker-Enfants Malades, 156, rue de Vaugirard, 75 730 Paris cedex 15, France; Email: [email protected]) Abstract The interaction of GH, interleukin (IL)-6 and glucocorti- Stat3 activation. In contrast, the reporter gene containing coids is likely to be important in regulating the GH- the Stat3 responsive element (SIE) was IL-6 specific. The insulin-like growth factor (IGF)-I axis. The signalling levels of gene induction by GH and IL-6 were not altered cascades activated by GH and IL-6 appear to be very by the co-stimulation with GH and IL-6, suggesting that similar, as demonstrated by studies using overexpression of there is little cross-talk at the Jak–Stat activation level the receptor and other components of the Jak-Stat and between the two cytokines. Neither GH nor IL-6 acti- mitogen-activated protein (MAP) kinase pathways. Here vated the MAP-kinase responsive serum response element we show that the human embryonic kidney cell line 293 (SRE), unless GH receptors or gp130 were overexpressed. (HEK293) expresses GH and IL-6 receptors endogenously. -
Increased in Vivo Phosphorylation of Ret Tyrosine 1062 Is a Potential Pathogenetic Mechanism of Multiple Endocrine Neoplasia Type 2B1
[CANCER RESEARCH 61, 1426–1431, February 15, 2001] Increased in Vivo Phosphorylation of Ret Tyrosine 1062 Is a Potential Pathogenetic Mechanism of Multiple Endocrine Neoplasia Type 2B1 Domenico Salvatore, Rosa Marina Melillo, Carmen Monaco, Roberta Visconti, Gianfranco Fenzi, Giancarlo Vecchio, Alfredo Fusco, and Massimo Santoro2 Centro di Endocrinologia ed Oncologia Sperimentale del CNR, c/o Dipartimento di Biologia e Patologia Cellulare e Molecolare [D. S., R. M. M., C. M., R. V., G. V., M. S.], and Dipartimento di Endocrinologia ed Oncologia Molecolare e Clinica, Facolta` di Medicina e Chirurgia [G. F.], Universita` di Napoli “Federico II,” Naples, Italy; and Dipartimento di Medicina Sperimentale e Clinica, Facolta`di Medicina e Chirurgia di Catanzaro, Universita`di Catanzaro, Catanzaro [A. F], Italy ABSTRACT are responsible for the inheritance of MEN2A and MEN2B and FMTC. Each disease has a distinct phenotype: MEN2A is associated Mutations of the Ret receptor tyrosine kinase are responsible for with MTC, pheochromocytoma, and parathyroid hyperplasia. The inheritance of multiple endocrine neoplasia (MEN2A and MEN2B) and MEN2B phenotype is more severe, being characterized by an earlier familial medullary thyroid carcinoma syndromes. Although several famil- ial medullary thyroid carcinoma and most MEN2A mutations involve occurrence of more aggressive MTC. Unlike MEN2A patients, substitutions of extracellular cysteine residues, in most MEN2B cases MEN2B patients develop multiple mucosal neuromas and several there is a methionine-to-threonine substitution at position 918 (M918T) of skeletal abnormalities. Finally, FMTC consists only of an inherited the Ret kinase domain. The mechanism by which the MEN2B mutation predisposition to MTC (3). Involvement of different tissues corre- converts Ret into a potent oncogene is poorly understood.