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Sunitinib

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https://www.readbyqxmd.com/read/28088043/hplc-uv-method-for-simultaneous-determination-of-mk-1775-and-azd-7762-in-both-acetonitrile-aqueous-solution-and-mouse-plasma
#1
REVIEW
Kareem Ebeid, Giang N Ho, Aliasger K Salem
A sensitive and precise method is described for the simultaneous determination of two small molecule kinase inhibitors: MK-1775 (MK) and AZD-7762 (AZD), in acetonitrile (ACN)-aqueous solution and in mouse plasma. A Nova-Pak C18 reversed phase column (3.9mm×150mm, 4μm, 60Å) was utilized in the separation using an isocratic mobile phase of 0.1% v/v triethylamine in phosphate buffer (pH=7.4): acetonitrile (ACN) (60:40, v/v), at a flow rate of 0.8mL/min. Detection wavelength was set at 310nm for both MK and AZD, and 431nm for the internal standard sunitinib (SUN)...
December 30, 2016: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28087600/sunitinib-stimulates-expression-of-vegfc-by-tumor-cells-and-promotes-lymphangiogenesis-in-clear-cell-renal-cell-carcinomas
#2
Maeva Dufies, Sandy Giuliano, Damien Ambrosetti, Audrey Claren, Papa Diogop Ndiaye, Michalis Mastri, Walid Moghrabi, Lindsay S Cooley, Marc Ettaiche, Emmanuel Chamorey, Julien Parola, Valerie Vial, Marilena Lupu-Plesu, Jean-Christophe Bernhard, Alain Ravaud, Delphine Borchiellini, Jean Marc Ferrero, Andreas Bikfalvi, John M L Ebos, Khalid S A Khabar, Renaud Grepin, Gilles Pagès
Sunitinib is an antiangiogenic therapy given as a first-line treatment for renal cell carcinoma (RCC). While treatment improves progression-free survival, most patients relapse. We hypothesized that patient relapse can stem from the development of a lymphatic network driven by the production of the main growth factor for lymphatic endothelial cells, vascular endothelial growth factor C (VEGFC). In this study, we found that sunitinib can stimulate VEGFC gene transcription and increase VEGFC mRNA half-life. Additionally, sunitinib activated p38 MAP kinase, which resulted in the upregulation/activity of HuR and inactivation of tristetraprolin, two AU-rich-element binding proteins...
January 13, 2017: Cancer Research
https://www.readbyqxmd.com/read/28078129/osteonecrosis-of-the-jaw-associated-with-ziv-aflibercept
#3
Hani Mawardi, Peter Enzinger, Nadine McCleary, Reshma Manon, Alessandro Villa, Nathaniel Treister, Sook-Bin Woo
Medication-related osteonecrosis of the jaw (MRONJ) has been associated with medications that include bisphosphonates (BPs), denosumab, bevacizumab and sunitinib. Ziv-aflibercept is a recombinant human vascular endothelial growth factor (VEGF) receptor which has been used to treat patients with various advanced solid tumors. We report three patients without a history of the use of medications known to cause MRONJ presenting with jaw osteonecrosis typical for MRONJ following therapy with ziv-aflibercept. All patients had metastatic gastrointestinal cancer treated with ziv-aflibercept and were evaluated for MRONJ because of exposed bone in the oral cavity...
December 2016: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28077238/patterns-of-care-and-clinical-outcomes-in-patients-with-metastatic-renal-cell-carcinoma-results-from-a-tertiary-cancer-center-in-india
#4
Anant Ramaswamy, Amit Joshi, Vanita Noronha, Vijay M Patil, Rushabh Kothari, Arvind Sahu, Ram Abhinav Kannan, Nilesh Sable, Palak Popat, Santosh Menon, Kumar Prabhash
INTRODUCTION: The current treatment of metastatic renal cell carcinoma (mRCC) revolves around targeted agents, which have resulted in a median overall survival of 22 to 26 months in registration trials. However, the outcomes in a non-trial, real-world Indian population have not yet been evaluated. MATERIALS AND METHODS: The present study was a part of a prospective Clinical Trials Registry-India-registered study, the Kidney Cancer Registry, a prospectively maintained kidney cancer registry...
October 19, 2016: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28075449/construction-of-an-mirna-regulated-drug-pathway-network-reveals-drug-repurposing-candidates-for-myasthenia-gravis
#5
Yuze Cao, Xiaoyan Lu, Jianjian Wang, Huixue Zhang, Zhaojun Liu, Si Xu, Tianfeng Wang, Shangwei Ning, Bo Xiao, Lihua Wang
Myasthenia gravis (MG) is a rare debilitating autoimmune neuromuscular disorder. Many studies have focused on the mechanism and treatment strategies of MG. However, the exact pathogenesis of MG and effective treatment strategies remain unclear. Recent studies have indicated that microRNAs (miRNAs or miRs) can regulate the pathological pathways of MG, suggesting their potential role in novel treatments. In the present study, we created a comprehensive catalog of experimentally confirmed MG risk genes and miRNAs by manually mining published literature and public databases...
January 11, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28070719/sunitinib-paracetamol-sex-divergent-pharmacokinetics-and-tissue-distribution-drug-drug-interaction-in-mice
#6
Ming Hui Liew, Salby Ng, Chii Chii Chew, Teng Wai Koo, Yun Lee Chee, Evelyn Li-Ching Chee, Pilar Modamio, Cecilia Fernández, Eduardo L Mariño, Ignacio Segarra
The sex-divergent pharmacokinetics and interaction of tyrosine kinase inhibitor sunitinib with paracetamol was evaluated in male and female mice. Mice (control groups) were administered 60 mg/kg PO sunitinib alone or with 200 mg/kg PO paracetamol (study groups). Sunitinib concentration in plasma, brain, kidney and liver were determined and non-compartmental pharmacokinetic analysis performed. Female control mice showed 36% higher plasma sunitinib AUC0→∞, 31% and 27% lower liver and kidney AUC0→∞ and 2...
January 9, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28062674/mixed-results-for-sunitinib-in-renal-cancer
#7
(no author information available yet)
Two studies presented at the European Society for Medical Oncology 2016 Congress evaluated sunitinib in patients with renal cell carcinomas. The first found that the drug prevents recurrence in patients who have had their cancerous kidney removed. The second study suggested that cabozantinib, approved for use as a second-line therapy, works better than sunitinib as a first-line treatment in patients with metastatic renal cell carcinoma.
January 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28061498/skull-metastasis-of-gastric-gastrointestinal-stromal-tumor-successfully-managed-by-surgery
#8
Inkeun Park, Dong Hae Chung, Chan Jong Yoo, Dong Bok Shin
Gastrointestinal stromal tumors (GISTs) are rare, but are the most common mesenchymal neoplasm of the gastrointestinal tract. The most common sites of metastasis are liver and peritoneum, while bone metastasis is rare. We report on a patient with skull metastasis after seven years of treatment with imatinib for metastatic GIST. She underwent metastasectomy consisting of craniectomy with excision of the mass, and cranioplasty and continued treatment with imatinib and sunitinib, without evidence of cranial recurrence...
January 1, 2017: Journal of Korean Neurosurgical Society
https://www.readbyqxmd.com/read/28059038/toxicities-of-receptor-tyrosine-kinase-inhibitors-in-cancer-pharmacotherapy-management-with-clinical-pharmacology
#9
Ken-Ichi Fujita, Hiroo Ishida, Yutaro Kubota, Yasutsuna Sasaki
A number of molecularly targeted anticancer drugs that efficiently inhibit receptor tyrosine kinases, so-called receptor tyrosine kinase inhibitors (TKIs), have been developed. Although these receptor TKIs are generally well tolerated, unexpected toxicities sometimes occur in various organs. TKI-induced adverse events not only lower the quality of life of cancer patients but also reduce dose intensity, and sometimes result in treatment discontinuation. To reduce adverse drug events and increase treatment efficacy, oncologists and clinical pharmacologists have made efforts to establish strategies to treat patients via optimal selection and dosing of TKIs...
January 5, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28057423/design-synthesis-and-biological-activities-of-tetrandrine-and-fangchinoline-derivatives-as-antitumer-agents
#10
Dechao Li, Haizheng Liu, Yufa Liu, Qikun Zhang, Chao Liu, Shuhua Zhao, Bo Jiao
The isolation and modification of natural products is always a very important resources to anti-tumor drugs. Therefore, a novel series of tetrandrine and fangchinoline derivatives were designed and synthesized, and their antiproliferative activities against HepG2, MCF-7 cells were evaluated and described. From the activity result obtained, high to very high activity in vitro has been found, one of the tested compounds (compound 5d) exhibited the most significant cytotoxic effects. Compound 5d increased 29.2, 7...
December 23, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28057017/the-brain-penetrating-cxcr4-antagonist-prx177561-increases-the-antitumor-effects-of-bevacizumab-and-sunitinib-in-preclinical-models-of-human-glioblastoma
#11
Giovanni Luca Gravina, Andrea Mancini, Francesco Marampon, Alessandro Colapietro, Simona Delle Monache, Roberta Sferra, Flora Vitale, Peter J Richardson, Lee Patient, Stephen Burbidge, Claudio Festuccia
BACKGROUND: Glioblastoma recurrence after treatment with the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab is characterized by a highly infiltrative and malignant behavior that renders surgical excision and chemotherapy ineffective. It has been demonstrated that anti-VEGF/VEGFR therapies control the invasive phenotype and that relapse occurs through the increased activity of CXCR4. We therefore hypothesized that combining bevacizumab or sunitinib with the novel CXCR4 antagonist, PRX177561, would have superior antitumor activity...
January 5, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28056874/sorafenib-versus-sunitinib-as-first-line-treatment-agents-in-chinese-patients-with-metastatic-renal-cell-carcinoma-the-largest-multicenter-retrospective-analysis-of-survival-and-prognostic-factors
#12
Hai-Liang Zhang, Xi-Nan Sheng, Xue-Song Li, Hong-Kai Wang, Zhi-Hong Chi, Zhi-Song He, Ding-Wei Ye, Jun Guo
BACKGROUND: To compare the efficacy of sorafenib and sunitinib with regard to overall survival (OS) and progression free survival (PFS) in Chinese patients with metastatic renal cell carcinoma (mRCC). METHODS: A multicenter, retrospective study was performed to elucidate the relationship between clinical variables and prognosis comparing sorafenib and sunitinib as first-line treatment agents in Chinese patients with mRCC. Between September 2006 and December 2014, 845 patients received either sorafenib (400 mg bid; n = 483) or sunitinib (50 mg q...
January 5, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28056412/toxicity-of-concurrent-stereotactic-radiotherapy-and-targeted-therapy-or-immunotherapy-a-systematic-review
#13
REVIEW
Stephanie G C Kroeze, Corinna Fritz, Morten Hoyer, Simon S Lo, Umberto Ricardi, Arjun Sahgal, Rolf Stahel, Roger Stupp, Matthias Guckenberger
BACKGROUND AND PURPOSE: Both stereotactic radiotherapy (SRT) and immune- or targeted therapy play an increasingly important role in personalized treatment of metastatic disease. Concurrent application of both therapies is rapidly expanding in daily clinical practice. In this systematic review we summarize severe toxicity observed after concurrent treatment. MATERIAL AND METHODS: PubMed and EMBASE databases were searched for English literature published up to April 2016 using keywords "radiosurgery", "local ablative therapy", "gamma knife" and "stereotactic", combined with "bevacizumab", "cetuximab", "crizotinib", "erlotinib", "gefitinib", "ipilimumab", "lapatinib", "sorafenib", "sunitinib", "trastuzumab", "vemurafenib", "PLX4032", "panitumumab", "nivolumab", "pembrolizumab", "alectinib", "ceritinib", "dabrafenib", "trametinib", "BRAF", "TKI", "MEK", "PD1", "EGFR", "CTLA-4" or "ALK"...
December 19, 2016: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28052652/anti-angiogenic-therapy-in-patients-with-advanced-gastric-and-gastroesophageal-junction-cancer-a-systematic-review
#14
Li-Tzong Chen, Do-Youn Oh, Min-Hee Ryu, Kun-Huei Yeh, Winnie Yeo, Roberto Carlesi, Rebecca Cheng, Jongseok Kim, Mauro Orlando, Yoon-Koo Kang
Despite advancements in therapy for advanced gastric and gastroesophageal junction cancers, their prognosis remains dismal. Tumor angiogenesis plays a key role in cancer growth and metastasis, and recent studies indicate that pharmacologic blockade of angiogenesis is a promising approach to therapy. In this systematic review, we summarize current literature on the clinical benefit of anti-angiogenic agents in advanced gastric cancer. We conducted a systematic search of PubMed and conference proceedings including the American Society of Clinical Oncology, the European Society for Medical Oncology, and the European Cancer Congress...
January 3, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28052007/vhl-missense-mutations-in-the-p53-binding-domain-show-different-effects-on-p53-signaling-and-hif%C3%AE-degradation-in-clear-cell-renal-cell-carcinoma
#15
Caroline Fanja Razafinjatovo, Daniel Stiehl, Eva Deininger, Markus Rechsteiner, Holger Moch, Peter Schraml
Clear cell Renal Cell Carcinoma (ccRCC) formation is connected to functional loss of the von Hippel-Lindau (VHL) gene. Recent data identified its gene product, pVHL, as a multifunctional adaptor protein which interacts with HIFα subunits but also with the tumor suppressor p53. p53 is hardly expressed and rarely mutated in most ccRCC. We showed that low and absent p53 expression correlated with the severity of VHL mutations in 262 analyzed ccRCC tissues. In contrast to nonsense and frameshift mutations which abrogate virtually all pVHL functions, missense mutations may rather influence one or few functions...
December 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/28044472/how-clinical-practice-is-changing-the-rules-the-sunitinib-2-1-schedule-in-metastatic-renal-cell-carcinoma
#16
Sergio Bracarda, Sylvie Negrier, Jochen Casper, Camillo Porta, Manuela Schmidinger, James Larkin, Marine Gross Goupil, Bernard Escudier
Currently, sunitinib is a standard of care in first-line treatment for metastatic renal cell carcinoma (mRCC). However, with the standard 4/2 schedule (sunitinib 50 mg/day; 4 consecutive weeks on treatment; 2 weeks' rest), 50% of patients require dose reductions to mitigate toxicity, highlighting the need to investigate alternative dosing schedules that improve tolerability without compromising efficacy. Areas covered: We present a concise critical review of published studies comparing the efficacy and safety of the 4/2 and 2/1 schedule (2 weeks on treatment; 1 week rest) for sunitinib...
January 3, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28044054/pituitary-metastasis-from-renal-cell-carcinoma-description-of-a-case-report
#17
Chloé Wendel, Marco Campitiello, Francesca Plastino, Nada Eid, Laurent Hennequin, Philippe Quétin, Raffaele Longo
BACKGROUND Pituitary metastasis is uncommon, breast and lung cancers being the most frequent primary tumors. Renal cell carcinoma (RCC) is a rare cause of pituitary metastases, with only a few cases described to date. CASE REPORT We report a case of a 61-year-old man who presented with a progressive deterioration of visual acuity and field associated with a bitemporal hemianopsia. Two years ago, he underwent radical right nephrectomy for a clear cell RCC (ccRCC). The biological tests showed pan-hypopituitarism and diabetes insipidus...
January 3, 2017: American Journal of Case Reports
https://www.readbyqxmd.com/read/28042343/limited-tumor-tissue-drug-penetration-contributes-to-primary-resistance-against-angiogenesis-inhibitors
#18
Szilvia Torok, Melinda Rezeli, Olga Kelemen, Akos Vegvari, Kenichi Watanabe, Yutaka Sugihara, Anna Tisza, Timea Marton, Ildiko Kovacs, Jozsef Tovari, Viktoria Laszlo, Thomas H Helbich, Balazs Hegedus, Thomas Klikovits, Mir Alireza Hoda, Walter Klepetko, Sandor Paku, Gyorgy Marko-Varga, Balazs Dome
Resistance mechanisms against antiangiogenic drugs are unclear. Here, we correlated the antitumor and antivascular properties of five different antiangiogenic receptor tyrosine kinase inhibitors (RTKIs) (motesanib, pazopanib, sorafenib, sunitinib, vatalanib) with their intratumoral distribution data obtained by matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI). In the first mouse model, only sunitinib exhibited broad-spectrum antivascular and antitumor activities by simultaneously suppressing vascular endothelial growth factor receptor-2 (VEGFR2) and desmin expression, and by increasing intratumoral hypoxia and inhibiting both tumor growth and vascularisation significantly...
2017: Theranostics
https://www.readbyqxmd.com/read/28038328/design-synthesis-and-biological-evaluation-of-indolin-2-one-based-derivatives-as-potent-selective-and-efficacious-inhibitors-of-fms-like-tyrosine-kinase3-flt3
#19
Fei Ma, Peng Liu, Min Lei, Jian Liu, Hongtao Wang, Shaohua Zhao, Lihong Hu
Activating mutations of FMS-like tyrosine kinase 3 (FLT3) are present in approximately one third of acute myeloid leukemia (AML) patients, which has been proposed as a promising drug target for AML therapy. A series of indolin-2-one derivatives bearing different groups at the solvent interface position based on sunitinib as FLT3 inhibitors were designed, synthesized and evaluated in FLT3-dependent human AML cell line MV4-11. Structure-activity relationship (SAR)analysis showed that heterocyclic alkane at the solvent interface position could significantly increase the potency for the inhibition of proliferation of MV4-11 cell line...
December 21, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28032146/effects-of-31-fda-approved-small-molecule-kinase-inhibitors-on-isolated-rat-liver-mitochondria
#20
Jun Zhang, Alec Salminen, Xi Yang, Yong Luo, Qiangen Wu, Matthew White, James Greenhaw, Lijun Ren, Matthew Bryant, William Salminen, Thomas Papoian, William Mattes, Qiang Shi
The FDA has approved 31 small-molecule kinase inhibitors (KIs) for human use as of November 2016, with six having black box warnings for hepatotoxicity (BBW-H) in product labeling. The precise mechanisms and risk factors for KI-induced hepatotoxicity are poorly understood. Here, the 31 KIs were tested in isolated rat liver mitochondria, an in vitro system recently proposed to be a useful tool to predict drug-induced hepatotoxicity in humans. The KIs were incubated with mitochondria or submitochondrial particles at concentrations ranging from therapeutic maximal blood concentrations (Cmax) levels to 100-fold Cmax levels...
December 28, 2016: Archives of Toxicology
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