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Vandetanib

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https://www.readbyqxmd.com/read/28740542/vandetanib-eluting-radiopaque-beads-in-vivo-pharmacokinetics-safety-and-toxicity-evaluation-following-swine-liver-embolization
#1
Alban Denys, Peter Czuczman, David Grey, Zainab Bascal, Rhys Whomsley, Hugh Kilpatrick, Andrew L Lewis
PURPOSE: To evaluate the plasma and tissue pharmacokinetics, safety and toxicity following intra-arterial hepatic artery administration of Vandetanib (VTB)-eluting Radiopaque Beads (VERB) in healthy swine. MATERIALS AND METHODS: In a first phase, healthy swine were treated with hepatic intra-arterial administration of VERB at target dose loading strengths of 36 mg/mL (VERB36), 72 mg/mL (VERB72) and 120 mg/mL (VERB120). Blood and tissue samples were taken and analysed for VTB and metabolites to determine pharmacokinetic parameters for the different dose forms over 30 days...
2017: Theranostics
https://www.readbyqxmd.com/read/28733794/fatigue-associated-with-newly-approved-vascular-endothelial-growth-factor-receptor-tyrosine-kinase-inhibitors-in-cancer-patients-an-up-to-date-meta-analysis
#2
REVIEW
Jing Li, Jian Gu
The fatigue associated with five newly approved vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) (regorafenib, vandetanib, cabozantinib, lenvatinib, axitinib) is poorly understood. We conducted this systematic review to fully investigate the fatigue associated with these VEGFR-TKIs in cancer patients. Relevant studies of randomized controlled trials in cancer patients treated with the five VEGFR-TKIs were retrieved and a systematic evaluation was conducted. EMBASE, MEDLINE, and PubMed were searched for articles published until March 2017...
July 21, 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28710508/risk-of-gastrointestinal-events-with-newly-approved-after-2011-vascular-endothelial-growth-factor-receptor-tyrosine-kinase-inhibitors-in-cancer-patients-a-meta-analysis-of-randomized-controlled-trials
#3
REVIEW
Jing Li, Jian Gu
PURPOSE: We performed a meta-analysis to systematically review the gastrointestinal (GI) events (diarrhea, nausea, vomiting, anorexia) of five newly approved (after 2011) VEGFR-TKIs in cancer patients. METHODS: The relevant studies of the randomized controlled trials (RCTs) in cancer patients treated with cabozantinib, vandetanib, lenvatinib, regorafenib, and axitinib were retrieved and the systematic evaluation was conducted. RESULTS: Forty-one randomized controlled trials and 10,860 patients were included...
July 15, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28698976/medullary-thyroid-cancer-clinical-characteristics-and-new-insights-into-therapeutic-strategies-targeting-tyrosine-kinases
#4
REVIEW
Sadegh Rajabi, Mehdi Hedayati
Medullary thyroid carcinoma (MTC) is a hyperplasia of thyroid C-cells, accounting for 5-10% of all thyroid cancers. MTCs may appear as sporadic or hereditary forms, and several molecules and signaling pathways have been found to function defectively in MTC cells. Tyrosine kinases are the most well-studied molecules that have abnormal function in these tumor cells. Due to their limited response, chemotherapeutic agents and radiation therapy are not effective in treating patients with advanced metastatic MTC...
July 11, 2017: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/28658345/medullary-thyroid-carcinoma-adverse-events-during-systemic-treatment-risk-benefit-ratio
#5
Léa Maria Zanini Maciel, Patrícia Künzle Ribeiro Magalhães
Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor originating from parafollicular C cells of the thyroid and associated with mutations in the proto-oncogene REarranged during Transfection (RET). The prognosis of MTC depends on clinical stage, with a 95.6% 10-year survival rate among patients with localized disease and 40% among patients with advanced disease. Standard chemotherapy and radiotherapy have no significant impact on the overall survival of these patients and two tyrosine kinase receptor inhibitors (TKIs), vandetanib and cabozantinib, have been recently approved for the systemic treatment of locally advanced or metastatic MTC...
June 26, 2017: Archives of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28635560/sorafenib-in-japanese-patients-with-locally-advanced-or-metastatic-medullary-thyroid-carcinoma-and-anaplastic-thyroid-carcinoma
#6
Yasuhiro Ito, Naoyoshi Onoda, Ken-Ichi Ito, Iwao Sugitani, Shunji Takahashi, Iku Yamaguchi, Koki Kabu, Katsuya Tsukada
BACKGROUND: Therapeutic options for treating advanced or metastatic medullary thyroid carcinoma (MTC) and anaplastic thyroid carcinoma (ATC) are still limited in Japan, even though vandetanib for MTC and lenvatinib for MTC and ATC have been approved. Sorafenib is an oral multikinase inhibitor approved for the treatment of patients with radioactive iodine-refractory differentiated thyroid cancer (DTC). An uncontrolled, open-label, multicenter, single-arm, Phase 2 clinical study was conducted to evaluate the safety and efficacy of sorafenib in Japanese patients with MTC and ATC...
July 24, 2017: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/28602103/advances-in-small-molecule-therapy-for-treating-metastatic-thyroid-cancer
#7
Jolanta Krajewska, Tomasz Gawlik, Barbara Jarzab
Multi kinase inhibitors (MKIs) are new drugs, which show activity against receptors of different growth factors leading to the inhibition of tumor cells growth and proliferation. This review summarizes a 10-year experience with the use of MKIs in thyroid cancer (TC). It focuses not only on sorafenib, lenvatinib, vandetanib and cabozantinib, already approved in TC, but also presents an overview of the results of different trials with distinct MKIs so far carried out in TC. Areas covered: Published results of phase I, II and III studies and other reports evaluated the efficacy of different targeted drugs in TC...
August 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28575860/in-vitro-and-in-vivo-anti-tumor-activity-of-alectinib-in-tumor-cells-with-ncoa4-ret
#8
Sachiko Arai, Kenji Kita, Azusa Tanimoto, Shinji Takeuchi, Koji Fukuda, Hiroshi Sato, Seiji Yano
Rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC) accounts for approximately 1-2% of all NSCLCs. To date, RET fusions that involve at least six fusion partners in NSCLC, such as KIF5B, CCDC6, NCOA4, TRIM33, CLIP1, and ERC1, have been identified. Recent clinical trials for RET fusion-positive NSCLC using vandetanib or cabozantinib demonstrated positive clinical response and considerable differential activities for RET inhibitors among fusion partners. Alectinib, an approved ALK inhibitor, is reported to inhibit KIF5B-RET and CCDC6-RET...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28559461/the-hgf-c-met-pathway-is-a-driver-and-biomarker-of-vegfr-inhibitor-resistance-and-vascular-remodeling-in-non-small-cell-lung-cancer
#9
Tina Cascone, Li Xu, Heather Y Lin, Wenbin Liu, Hai T Tran, Yuan Liu, Kathryn J Howells, Vincent Haddad, Emer O Hanrahan, Monique Nilsson, Maria Angelica Cortez, Uma Giri, Humam Kadara, Babita Saigal, Yun-Yong Park, Weiyi Peng, Ju-Seog Lee, Anderson J Ryan, Juliane M Juergensmeier, Roy S Herbst, Jing Wang, Robert R Langley, Ignacio I Wistuba, J Jack Lee, John Heymach
Resistance to vascular endothelial growth factor receptor (VEGFR) inhibitors is a major obstacle in the treatment of non-small cell lung cancer (NSCLC). We investigated the cellular mechanisms mediating resistance of NSCLCs to VEGFR tyrosine kinase inhibitors.<br /><br />Experimental Design: We generated murine models of human NSCLC and performed targeted inhibition studies with the VEGFR TKIs cediranib and vandetanib. We used species-specific hybridization of microarrays to compare cancer (human) and stromal (mouse) cell transcriptomes of TKI-sensitive and -resistant tumors...
May 30, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28506408/genetics-of-medullary-thyroid-cancer-an-overview
#10
REVIEW
Giacomo Accardo, Giovanni Conzo, Daniela Esposito, Claudio Gambardella, Marco Mazzella, Filomena Castaldo, Carlo Di Donna, Andrea Polistena, Nicola Avenia, Vittorio Colantuoni, Dario Giugliano, Daniela Pasquali
Medullary thyroid carcinoma (MTC) represents 3-5% of thyroid cancers. 75% is sporadic and 25% is the dominant component of the hereditary multiple endocrine neoplasia (MEN) type 2 syndromes. Three different subtypes of MEN2, such as MEN2A, MEN2B, and Familial MTC (FMTC) have been defined, based on presence or absence of hyperparathyroidism, pheocromocytoma and characteristic clinical features. Mutations of the RET proto-oncogene are implicated in the pathogenesis of MTC, but there are many other mutational patterns involved...
May 2017: International Journal of Surgery
https://www.readbyqxmd.com/read/28475408/vandetanib-and-cabozantinib-potentiate-mitochondria-targeted-agents-to-suppress-medullary-thyroid-carcinoma-cells
#11
Dmytro Starenki, Seung-Keun Hong, Pui-Kei Wu, Jong-In Park
Although the FDA-approved receptor tyrosine kinases inhibitors, vandetanib and cabozantinib, are used to treat surgically inoperable progressive medullary thyroid carcinoma (MTC), not all patients are responsive while the disease sometimes progresses after an initial response. To better understand MTC drug resistance at molecular and biochemical levels, we have generated drug-resistant subpopulations of the human MTC cell lines, TT and MZ-CRC-1, via prolonged exposure to vandetanib and cabozantinib. These drug-resistant progenies exhibited substantial cross-resistance to vandetanib and cabozantinib, suggesting that these inhibitors may invoke an overlapping resistance mechanism(s) in MTC cells...
May 5, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28447912/targeting-ret-in-patients-with-ret-rearranged-lung-cancers-results-from-the-global-multicenter-ret-registry
#12
Oliver Gautschi, Julie Milia, Thomas Filleron, Juergen Wolf, David P Carbone, Dwight Owen, Ross Camidge, Vignhesh Narayanan, Robert C Doebele, Benjamin Besse, Jordi Remon-Masip, Pasi A Janne, Mark M Awad, Nir Peled, Chul-Cho Byoung, Daniel D Karp, Michael Van Den Heuvel, Heather A Wakelee, Joel W Neal, Tony S K Mok, James C H Yang, Sai-Hong Ignatius Ou, Georg Pall, Patrizia Froesch, Gérard Zalcman, David R Gandara, Jonathan W Riess, Vamsidhar Velcheti, Kristin Zeidler, Joachim Diebold, Martin Früh, Sebastian Michels, Isabelle Monnet, Sanjay Popat, Rafael Rosell, Niki Karachaliou, Sacha I Rothschild, Jin-Yuan Shih, Arne Warth, Thomas Muley, Florian Cabillic, Julien Mazières, Alexander Drilon
Purpose In addition to prospective trials for non-small-cell lung cancers (NSCLCs) that are driven by less common genomic alterations, registries provide complementary information on patient response to targeted therapies. Here, we present the results of an international registry of patients with RET-rearranged NSCLCs, providing the largest data set, to our knowledge, on outcomes of RET-directed therapy thus far. Methods A global, multicenter network of thoracic oncologists identified patients with pathologically confirmed NSCLC that harbored a RET rearrangement...
May 1, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28435794/cushing-disease-in-a-patient-with-multiple-endocrine-neoplasia-type-2b
#13
Kannan Kasturi, Lucas Fernandes, Martha Quezado, Mary Eid, Leigh Marcus, Prashant Chittiboina, Mark Rappaport, Constantine A Stratakis, Brigitte Widemann, Maya Lodish
CONTEXT: Multiple endocrine neoplasia type 2B (MEN2B) is a rare autosomal-dominant cancer syndrome characterized in part by metastatic medullary thyroid cancer (MTC) and pheochromocytoma. Cushing disease is a rare cause of endogenous hypercortisolism in children. CASE DESCRIPTION: We describe a 21-year-old African-American male who was diagnosed at age 10 with an ACTH-secreting pituitary microadenoma. At age 16 he developed medullary thyroid cancer and was found to have multiple endocrine neoplasia type 2B with the characteristic M918T mutation of the RET proto-oncogene...
June 2017: Journal of clinical and translational endocrinology case reports
https://www.readbyqxmd.com/read/28428205/measurable-supratentorial-white-matter-volume-changes-in-patients-with-diffuse-intrinsic-pontine-glioma-treated-with-an-anti-vascular-endothelial-growth-factor-agent-steroids-and-radiation
#14
P Svolos, W E Reddick, A Edwards, A Sykes, Y Li, J O Glass, Z Patay
BACKGROUND AND PURPOSE: Assessing the response to treatment in infiltrative brain tumors by using lesion volume-based response criteria is challenging. We hypothesized that in such tumors, volume measurements alone may not accurately capture changes in actual tumor burden during treatment. We longitudinally evaluated volume changes in both normal-appearing supratentorial white matter and the brain stem lesions in patients treated for diffuse intrinsic pontine glioma to determine to what extent adjuvant systemic therapies may skew the accuracy of tumor response assessments based on volumetric analysis...
June 2017: AJNR. American Journal of Neuroradiology
https://www.readbyqxmd.com/read/28413487/vandetanib-and-adam-inhibitors-synergistically-attenuate-the-pathological-migration-of-ebv-infected-retinal-pigment-epithelial-cells-by-regulating-the-vegf-mediated-mapk-pathway
#15
Daejin Kim, Hyun-Suk Ko, Ga Bin Park, Dae Young Hur, Yeong Seok Kim, Jae Wook Yang
The extracellular signals induced by vascular endothelial growth factor (VEGF) are implicated in choroidal neovascularization (CNV) and thus, are associated with vision-limiting complications in the human retina. Vandetanib is an oral anticancer drug that selectively inhibits the activities of VEGF receptor and epidermal growth factor receptor tyrosine kinase; however, the effects of vandetanib on VEGF in retinal pigment epithelial (RPE) cells have not yet been studied. In the present study, a combined treatment of vandetanib and a disintegrin and metalloproteinase (ADAM) protein inhibitors were used to assess the regulation of Epstein-Barr virus (EBV)-infected ARPE19 cells (ARPE19/EBV) migration as a model of CNV...
April 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28413233/an-alternative-synthesis-of-vandetanib-caprelsa%C3%A2-via-a-microwave-accelerated-dimroth-rearrangement
#16
Kayleigh L Brocklesby, Jennifer S Waby, Chris Cawthorne, Graham Smith
Vandetanib is an orally available tyrosine kinase inhibitor used in the treatment of cancer. The current synthesis proceeds via an unstable 4-chloroquinazoline, using harsh reagents, in addition to requiring sequential protection and deprotection steps. In the present work, use of the Dimroth rearrangement in the key quinazoline forming step enabled the synthesis of Vandetanib in nine steps (compared to the previously reported 12-14).
April 12, 2017: Tetrahedron Letters
https://www.readbyqxmd.com/read/28392095/real-time-analysis-of-the-binding-of-fluorescent-vegf165a-to-vegfr2-in-living-cells-effect-of-receptor-tyrosine-kinase-inhibitors-and-fate-of-internalized-agonist-receptor-complexes
#17
Laura E Kilpatrick, Rachel Friedman-Ohana, Diana C Alcobia, Kristin Riching, Chloe J Peach, Amanda J Wheal, Stephen J Briddon, Matthew B Robers, Kris Zimmerman, Thomas Machleidt, Keith V Wood, Jeanette Woolard, Stephen J Hill
Vascular endothelial growth factor (VEGF) is an important mediator of angiogenesis. Here we have used a novel stoichiometric protein-labeling method to generate a fluorescent variant of VEGF (VEGF165a-TMR) labeled on a single cysteine within each protomer of the antiparallel VEGF homodimer. VEGF165a-TMR has then been used in conjunction with full length VEGFR2, tagged with the bioluminescent protein NanoLuc, to undertake a real time quantitative evaluation of VEGFR2 binding characteristics in living cells using bioluminescence resonance energy transfer (BRET)...
July 15, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28345929/utility-of-cyp3a4-and-pxr-car-cyp3a4-3a7-transgenic-mouse-models-to-assess-the-magnitude-of-cyp3a4-mediated-drug-drug-interactions
#18
Justin Q Ly, Kirsten Messick, Ann Qin, Ryan H Takahashi, Edna F Choo
Species differences in the expression, activity, regulation, and substrate specificity of metabolizing enzymes preclude the use of animal models to predict clinical drug-drug interactions (DDIs). The objective of this work is to determine if the transgenic (Tg) Cyp3a(-/-)Tg-3A4Hep/Int and Nr1i2/Nr1i3(-/-)-Cyp3a(-/-)Tg-PXR-CAR-3A4/3A7Hep/Int (PXR-CAR-CYP3A4/3A7) mouse models could be used to predict in vivo DDI of 10 drugs; alprazolam, bosutinib, crizotinib, dasatinib, gefitinib, ibrutinib, regorafenib, sorafenib, triazolam, and vandetinib (as victims); with varying magnitudes of reported CYP3A4 clinical DDI...
April 7, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28318881/targeted-therapy-in-thyroid-cancer-state-of-the-art
#19
REVIEW
L Valerio, L Pieruzzi, C Giani, L Agate, V Bottici, L Lorusso, V Cappagli, L Puleo, A Matrone, D Viola, C Romei, R Ciampi, E Molinaro, R Elisei
Thyroid cancer typically has a good outcome following standard treatments, which include surgery, radioactive iodine ablation for differentiated tumours and treatment with thyrotropine hormone-suppressive levothyroxine. Thyroid cancers that persist or recur following these therapies have a poorer prognosis. Cytotoxic chemotherapy or external beam radiotherapy has a low efficacy in these patients. 'Target therapy' with tyrosine kinase inhibitors (TKIs) represent an important therapeutic option for the treatment of advanced cases of radioiodine refractory (RAI-R) differentiated thyroid cancer (DTC), medullary thyroid cancer (MTC) and possibly for cases of poorly differentiated (PDTC) and anaplastic thyroid cancer (ATC)...
May 2017: Clinical Oncology: a Journal of the Royal College of Radiologists
https://www.readbyqxmd.com/read/28259610/vandetanib-plus-gemcitabine-versus-placebo-plus-gemcitabine-in-locally-advanced-or-metastatic-pancreatic-carcinoma-vip-a-prospective-randomised-double-blind-multicentre-phase-2-trial
#20
RANDOMIZED CONTROLLED TRIAL
Gary Middleton, Daniel H Palmer, William Greenhalf, Paula Ghaneh, Richard Jackson, Trevor Cox, Anthony Evans, Victoria E Shaw, Jonathan Wadsley, Juan W Valle, David Propper, Harpreet Wasan, Stephen Falk, David Cunningham, Fareeda Coxon, Paul Ross, Srinivasan Madhusudan, Nick Wadd, Pippa Corrie, Tamas Hickish, Eithne Costello, Fiona Campbell, Charlotte Rawcliffe, John P Neoptolemos
BACKGROUND: Erlotinib is an EGFR tyrosine kinase inhibitor that has shown a significant but only marginally improved median overall survival when combined with gemcitabine in patients with locally advanced and metastatic pancreatic cancer. Vandetanib is a novel tyrosine kinase inhibitor of VEGFR2, RET, and EGFR, all of which are in involved in the pathogenesis of pancreatic cancer. We investigated the clinical efficacy of vandetanib when used in combination with gemcitabine in patients with advanced pancreatic cancer...
April 2017: Lancet Oncology
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