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Sunitinib

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https://www.readbyqxmd.com/read/28350788/ldl-cholesterol-counteracts-the-antitumour-effect-of-tyrosine-kinase-inhibitors-against-renal-cell-carcinoma
#1
Sei Naito, Peter Makhov, Igor Astsaturov, Konstantin Golovine, Alexei Tulin, Alexander Kutikov, Robert G Uzzo, Vladimir M Kolenko
BACKGROUND: Treatment with tyrosine kinase inhibitors (TKIs) significantly improves survival of patients with renal cell carcinoma (RCC). However, about one-quarter of the RCC patients are primarily refractory to treatment with TKIs. METHODS: We examined viability of RCC and endothelial cells treated with low-density lipoprotein (LDL) and/or TKIs. Next, we validated the potential role of PI3K/AKT signalling in LDL-mediated TKI resistance. Finally, we examined the effect of a high-fat/high-cholesterol diet on the response of RCC xenograft tumours to sunitinib...
March 28, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28343336/sunitinib-induced-hypothyroidism-predicts-progression-free-survival-in-metastatic-renal-cell-carcinoma-patients
#2
Anna Buda-Nowak, Jakub Kucharz, Paulina Dumnicka, Marek Kuzniewski, Roman Maria Herman, Aneta L Zygulska, Beata Kusnierz-Cabala
Sunitinib is a tyrosine kinase inhibitor (TKI) used in treatment of metastatic renal cell carcinoma (mRCC), gastrointestinal stromal tumors and pancreatic neuroendocrine tumors. One of the most common side effects related to sunitinib is hypothyroidism. Recent trials suggest correlation between the incidence of hypothyroidism and treatment outcome in patients treated with TKI. This study evaluates whether development of hypothyroidism is a predictive marker of progression-free survival (PFS) in patients with mRCC treated with sunitinib...
April 2017: Medical Oncology
https://www.readbyqxmd.com/read/28339142/selective-effects-of-oral-anti-angiogenic-tyrosine-kinase-inhibitors-on-an-animal-model-of-hereditary-hemorrhagic-telangiectasia
#3
Yong Hwan Kim, Mi-Jung Kim, Se-Woon Choe, Dennis Sprecher, Young Jae Lee, S Paul Oh
BACKGROUND: Epistaxis and gastrointestinal (GI) tract hemorrhages are common symptoms of aged hereditary hemorrhagic telangiectasia (HHT) patients that result in anemia. Clinical as well as animal studies have suggested that vascular endothelial growth factor (VEGF) neutralizing antibodies lessen hemorrhage associated with adult onset arteriovenous malformations (AVMs). OBJECTIVES: The goal of this study is to evaluate potential therapeutic effects of oral delivery of four anti-angiogenic tyrosine-kinase inhibitors (TKIs) in the development of adult onset AVMs in a murine model of HHT...
March 24, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28335742/characteristics-of-early-onset-hematotoxicity-of-sunitinib-in-japanese-patients-with-renal-cell-carcinoma
#4
Renpei Kato, Yoichiro Kato, Tomohiko Matsuura, Mitsugu Kanehira, Ryo Takata, Wataru Obara
BACKGROUND: A high incidence of severe hematological adverse events during sunitinib treatment complicates decision making on dose and treatment cycle. We identified the characteristics of early-onset hematotoxicity of sunitinib in Japanese patients with renal cell carcinoma (RCC). METHODS: Seventy-nine patients were treated with sunitinib as 6-week cycles of "4-week on 2-week off" schedule. To evaluate early-onset hematotoxicity, we compared patients with dose reduction during the first cycle (dose-reduced group, n = 57) and those who maintained the initial dose (dose-maintained group, n = 22)...
March 23, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28330808/germline-genetic-biomarkers-of-sunitinib-efficacy-in-advanced-renal-cell-carcinoma-results-from-the-renal-effect-trial
#5
Robert J Motzer, Robert A Figlin, Jean-François Martini, Subramanian Hariharan, Neeraj Agarwal, Chun Xiao Li, J Andrew Williams, Thomas E Hutson
BACKGROUND: Sunitinib, the vascular endothelial growth factor pathway inhibitor, is an established standard-of-care for advanced renal cell carcinoma (RCC). This study aimed to assess correlations between candidate germline single nucleotide polymorphisms (SNPs) and sunitinib efficacy in patients from the RENAL EFFECT trial (NCT00267748), a randomized phase II study in patients with metastatic RCC comparing the 4-weeks-on/2-weeks-off schedule and a continuous daily dosing schedule. PATIENTS AND METHODS: Informed consent for pharmacogenetics research was obtained from 202 out of 289 treated patients in the trial...
February 27, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28330784/vascular-endothelial-growth-factor-vegf-and-vegf-receptor-inhibitors-in-the-treatment-of-renal-cell-carcinomas
#6
REVIEW
Robert Roskoski
One Von Hippel-Lindau (VHL) tumor suppressor gene is lost in most renal cell carcinomas while the nondeleted allele exhibits hypermethylation-induced inactivation or inactivating somatic mutations. As a result of these genetic modifications, there is an increased production of VEGF-A and pro-angiogenic growth factors in this disorder. The important role of angiogenesis in the pathogenesis of renal cell carcinomas and other tumors has focused the attention of investigators on the biology of VEGFs and VEGFR1-3 and to the development of inhibitors of the intricate and multifaceted angiogenic pathways...
March 18, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28327953/final-overall-survival-analysis-for-the-phase-ii-record-3-study-of-first-line-everolimus-followed-by-sunitinib-versus-first-line-sunitinib-followed-by-everolimus-in-metastatic-rcc
#7
J J Knox, C H Barrios, T M Kim, T Cosgriff, V Srimuninnimit, K Pittman, R Sabbatini, S Y Rha, T W Flaig, R D Page, J T Beck, F Cheung, S Yadav, P Patel, L Geoffrois, J Niolat, N Berkowitz, M Marker, D Chen, R J Motzer
Background: RECORD-3 compared everolimus and sunitinib as first-line therapy, and the sequence of everolimus followed by sunitinib at progression compared with the opposite (standard) sequence in patients with metastatic renal cell carcinoma (mRCC). This final overall survival (OS) analysis evaluated mature data for secondary end points. Patients and Methods: : Patients received either first-line everolimus followed by second-line sunitinib at progression ( n =  238) or first-line sunitinib followed by second-line everolimus ( n =  233)...
February 21, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28327411/gas6-axl-signaling-in-presence-of-sunitinib-is-enhanced-diversified-and-sustained-in-renal-tumor-cells-resulting-in-tumor-progressive-advantages
#8
Anna Gustafsson, Helena K M Fritz, Björn Dahlbäck
Clear Cell Renal Cell Carcinoma (CCRCC) is a lethal cancer with bad prognosis due to development of chemoresistance and recurrence of more aggressive tumors. Investigation of Gas6-mediated Axl signaling in CCRCC and endothelial cells reveals a Sunitinib resistant Gas6-Axl signaling that is sustained and enhanced and specifically triggers downstream AKT and PRAS40 activation in an intensified manner. Gas6-induced Axl signaling in presence of Sunitinib is also diversified displaying onset of Axl-dependent EGFR and METR activation and activation of classical MAPK pathways...
March 19, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28321172/gastrointestinal-stromal-tumor-of-the-stomach-with-axillary-lymph-node-metastasis-a-case-report
#9
Naoki Kubo, Nobumichi Takeuchi
Gastrointestinal stromal tumors (GISTs) are the most common type of gastrointestinal mesenchymal tumors, although metastasis to the perigastric lymph nodes is relatively rare, compared with liver or peritoneal metastasis. In this report, we describe a case of stomach GIST with a solitary simultaneous metastasis in the left axillary lymph node. A 68-year-old man was diagnosed with a large upper-stomach GIST, and computed tomography and positron emission tomography revealed masses in the left axilla and right mediastinum...
March 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28320855/salt-sensitivity-of-angiogenesis-inhibition-induced-blood-pressure-rise-role-of-interstitial-sodium-accumulation
#10
Stephanie Lankhorst, David Severs, Lajos Markó, Natalia Rakova, Jens Titze, Dominik N Müller, A H Jan Danser, Anton H van den Meiracker
In response to salt loading, Na(+) and Cl(-) accumulate in the skin in excess of water, stimulating skin lymphangiogenesis via activation of the mononuclear phagocyte system cell-derived vascular endothelial growth factor-C-vascular endothelial growth factor type 3 receptor signaling pathway. Inhibition of this pathway results in salt-sensitive hypertension. Sunitinib is an antiangiogenic, anticancer agent that blocks all 3 vascular endothelial growth factor receptors and increases blood pressure. We explored the salt dependency of sunitinib-induced hypertension and whether impairment of skin lymphangiogenesis is an underlying mechanism...
March 20, 2017: Hypertension
https://www.readbyqxmd.com/read/28301826/a-multicenter-phase-ii-study-of-sunitinib-in-patients-with-locally-advanced-or-metastatic-differentiated-anaplastic-or-medullary-thyroid-carcinomas-mature-data-from-the-thysu-study
#11
Alain Ravaud, Christelle de la Fouchardière, Philippe Caron, Adelaïde Doussau, Christine Do Cao, Julien Asselineau, Patrice Rodien, Damien Pouessel, Patricia Nicolli-Sire, Marc Klein, Claire Bournaud-Salinas, Jean-Louis Wemeau, Anne Gimbert, Marie-Quitterie Picat, Delphine Pedenon, Laurence Digue, Amaury Daste, Bogdan Catargi, Jean-Pierre Delord
PURPOSE: Patients with advanced radioactive iodine resistant differentiated (MDTC) or medullary (MMTC) thyroid cancer had an unmet need. Early data showed promising efficacy of vascular endothelial growth factor receptor inhibitors. We investigated sunitinib in this setting. PATIENTS AND METHODS: This phase 2 trial enrolled MDTC, anaplastic (MATC) and MMTC patients in 1st line anti-angiogenic therapy with sunitinib at 50 mg/d, 4/6w. Objective response rate was the primary end-point...
March 13, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28298652/patient-specific-blood-pressure-correction-technique-for-arterial-stiffness-evaluation-in-a-cohort-on-anti-angiogenic-medication
#12
Bart Spronck, Tammo Delhaas, Anouk Gw De Lepper, Julie Giroux, François Goldwasser, Pierre Boutouyrie, Maureen Alivon, Koen D Reesink
Arterial pulse wave velocity (PWV) depends on blood pressure (BP). Correction of PWV for BP is commonly performed using a statistical approach, requiring a patient cohort. We recently developed a mechanistic, model-predictive approach to assess BP-independent changes in carotid PWV (cPWV) at the level of the individual. The goal of the present study is to compare our novel technique to conventional statistical correction, in the context of anti-cancer therapy using anti-angiogenic drugs (AADs). AADs frequently lead to a PWV increase, but also to hypertension, underlining the need for BP correction of PWV measurements...
March 16, 2017: Hypertension Research: Official Journal of the Japanese Society of Hypertension
https://www.readbyqxmd.com/read/28291905/long-term-results-of-therapy-with-sunitinib-in-metastatic-alveolar-soft-part-sarcoma
#13
Paulina Jagodzińska-Mucha, Tomasz Świtaj, Katarzyna Kozak, Hanna Koseła-Paterczyk, Anna Klimczak, Iwona Ługowska, Pawel Rogala, Michał Wągrodzki, Sławomir Falkowski, Piotr Rutkowski
BACKGROUND: Alveolar soft part sarcoma (ASPS) is a rare, highly vascularized soft tissue sarcoma characterized by a high frequency of metastatic disease and resistance to classical chemotherapy. The purpose of our analysis was to assess long-term sunitinib activity in the treatment of metastatic ASPS. PATIENTS AND METHODS: Between 2009 and 2015, 15 patients were diagnosed with metastatic ASPS and received therapy with sunitinib at initial continuous daily dosing of 37...
March 8, 2017: Tumori
https://www.readbyqxmd.com/read/28287633/increased-vasohibin-1-expression-is-associated-with-metastasis-and-poor-prognosis-of-renal-cell-carcinoma-patients
#14
Shuji Mikami, Mototsugu Oya, Takeo Kosaka, Ryuichi Mizuno, Yasumasa Miyazaki, Yasufumi Sato, Yasunori Okada
The microvascular density detected by markers of endothelial cells (ECs), such as CD31 and CD34, is considered to be a biomarker for angiogenesis, and it is generally associated with the malignant potential of solid tumors. However, there is a conflicting relationship between the microvascular density and prognosis in clear-cell renal cell carcinoma (ccRCC) patients. It may be explained by the suggestion that the microvascular density cannot fully reflect the angiogenic activity in ccRCC, as the markers of ECs are expressed by both quiescent and activated ECs...
March 13, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28286925/cabozantinib-for-renal-cell-carcinoma-current-and-future-paradigms
#15
REVIEW
Ahmed Abdelaziz, Ulka Vaishampayan
Cabozantinib was approved by the FDA in April 2016 for the treatment of advanced renal cancer, pretreated with at least one prior antiangiogenic therapy. This is the first agent in the therapy of kidney cancer to show a statistically significant improvement in all three endpoints of clinical efficacy, response rate, progression free survival, and overall survival (OS), in a phase III randomized trial. The reporting of METEOR coincided with that of the Checkmate 025 study which randomized similarly eligible patients to receive nivolumab or everolimus 10 mg daily...
March 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28286921/treatment-strategies-for-metastatic-neuroendocrine-tumors-of-the-gastrointestinal-tract
#16
REVIEW
Mauro Cives, Jonathan Strosberg
The therapeutic landscape of gastroenteropancreatic-neuroendocrine tumors (GEP-NETs) has evolved significantly in recent years. Current and emerging treatment options include somatostatin analogs, radiolabeled somatostatin analogs, the mTOR inhibitor everolimus, and the tyrosine kinase inhibitor sunitinib. Although high-quality data from phase III trials are lacking, cytotoxic agents are commonly used for the treatment of poorly differentiated neuroendocrine carcinomas and well-differentiated NETs originating in the pancreas...
March 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28285369/diclofenac-sex-divergent-drug-drug-interaction-with-sunitinib-pharmacokinetics-and-tissue-distribution-in-male-and-female-mice
#17
Chii Chii Chew, Salby Ng, Yun Lee Chee, Teng Wai Koo, Ming Hui Liew, Evelyn Li-Ching Chee, Pilar Modamio, Cecilia Fernández, Eduardo L Mariño, Ignacio Segarra
Coadministration of diclofenac and sunitinib, tyrosine kinase inhibitor, led to sex-divergent pharmacokinetic drug-drug interaction outcomes. Male and female mice were administered 60 mg/kg PO sunitinib alone (control groups) or with 30 mg/kg PO diclofenac. Sunitinib concentration in plasma, brain, kidney and liver were determined by HPLC and non-compartmental pharmacokinetic parameters calculated. In male mice, diclofenac decreased AUC0→∞ 38% in plasma (p < 0.05) and 24% in liver (p < 0.001) and 23% in kidney (p < 0...
March 11, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28278333/adjuvant-treatment-for-high-risk-clear-cell-renal-cancer-updated-results-of-a-high-risk-subset-of-the-assure-randomized-trial
#18
Naomi B Haas, Judith Manola, Janice P Dutcher, Keith T Flaherty, Robert G Uzzo, Michael B Atkins, Robert S DiPaola, Toni K Choueiri
Importance: Given recently published results of a 750-patient adjuvant sunitinib trial showing improved disease-free survival (DFS), the appropriate strategy for treating high-risk patients is unclear. We sought to determine whether there is improved disease-free survival benefit to taking the active drug in patients with high-risk (pT3, pT4, node-positive) clear cell renal cancer (ccRCC) in the ASSURE trial (adjuvant sunitinib or sorafenib vs placebo in resected unfavorable renal cell carcinoma [RCC]), the largest adjuvant trial published to date...
March 9, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28278077/anti-angiogenic-treatment-promotes-triple-negative-breast-cancer-invasion-via-vasculogenic-mimicry
#19
Huizhi Sun, Danfang Zhang, Zhi Yao, Xian Lin, Jiameng Liu, Qiang Gu, Xueyi Dong, Fang Liu, Yi Wang, Nan Yao, Siqi Cheng, Linqi Li, Shuya Sun
Agents that target angiogenesis have shown limited efficacy for human triple-negative breast cancer (TNBC) in clinical trials. Along with endothelium-dependent vessels, there is also vasculogenic mimicry (VM) in the microcirculation of malignant tumors. The role of VM is not completely understood regarding anti-angiogenic treatment. In this study, human TNBC MDA-MB-231 and Hs578T and non-TNBC MCF-7 and BT474 tumor-bearing mice were treated with sunitinib, an anti-angiogenic drug, using a clinically relevant schedule...
February 21, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28276433/renal-cell-carcinoma
#20
REVIEW
James J Hsieh, Mark P Purdue, Sabina Signoretti, Charles Swanton, Laurence Albiges, Manuela Schmidinger, Daniel Y Heng, James Larkin, Vincenzo Ficarra
Renal cell carcinoma (RCC) denotes cancer originated from the renal epithelium and accounts for >90% of cancers in the kidney. The disease encompasses >10 histological and molecular subtypes, of which clear cell RCC (ccRCC) is most common and accounts for most cancer-related deaths. Although somatic VHL mutations have been described for some time, more-recent cancer genomic studies have identified mutations in epigenetic regulatory genes and demonstrated marked intra-tumour heterogeneity, which could have prognostic, predictive and therapeutic relevance...
March 9, 2017: Nature Reviews. Disease Primers
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