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Axitinib

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https://www.readbyqxmd.com/read/29128510/enzymes-involved-in-tumor-driven-angiogenesis-a-valuable-target-for-anticancer-therapy
#1
REVIEW
Biagio Ricciuti, Jennifer Foglietta, Vanessa Bianconi, Amirhossein Sahebkar, Matteo Pirro
Angiogenesis plays a pivotal role in cancer progression and is required for tissue invasion and metastasis. Starting with Folkman's initial observations in 1971, basic research continued to shed new molecular insight into this multifaceted process, leading to the development of several anti-angiogenic drugs. To date, anti-vascular endothelial growth factor monoclonal antibodies, such as bevacizumab and ramucirumab, and receptor tyrosine kinase inhibitors (e.g., sorafenib, sunitinib, regorafenib and axitinib) have had a profound impact on the way we treat patients with advanced cancer, providing in some cases unprecedented clinical benefit...
November 8, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29109792/mir-205-yap1-in-activated-fibroblasts-of-breast-tumor-promotes-vegf-independent-angiogenesis-through-stat3-signaling
#2
Yan-E Du, Gang Tu, Guanglun Yang, Genyou Li, Dan Yang, Lei Lang, Lei Xi, Kexin Sun, Yanlin Chen, Kunxian Shu, Huadong Liao, Manran Liu, Yixuan Hou
Tumor microenvironment contributes to tumor angiogenesis. However, the role of the activated cancer associated-fibroblasts (CAFs) in angiogenesis is still unclear. Here we report that miR-205/YAP1 signaling in the activated stromal fibroblasts plays a critical role in VEGF-independent angiogenesis in breast tumor. Methods: miR-205 expression was assessed by quantitative real-time polymerase chain reaction (qRT-PCR); YAP1 expression by qRT-PCR, western blotting and immunohistochemistry; IL11 and IL15 expression by qRT-PCR, western blotting and ELISA...
2017: Theranostics
https://www.readbyqxmd.com/read/29079346/axitinib-attenuates-intraplaque-angiogenesis-haemorrhages-and-plaque-destabilization-in-mice
#3
Bieke Van der Veken, Guido R Y De Meyer, Wim Martinet
AIM: An increased density of intraplaque (IP) microvessels in ruptured versus nonruptured human plaques suggests that IP neovascularization has a major causative effect on plaque development and instability. Possibly, vascular endothelial growth factor (VEGF) or other angiogenic factors mediate IP microvessel growth and plaque destabilization. Because apolipoprotein deficient mice with a heterozygous mutation (C1039G+/-) in the fibrillin-1 gene (ApoE(-/-)Fbn1(C1039G+/-)) manifest substantial IP neovascularization, they represent a unique tool to further investigate angiogenesis and its role in atherosclerosis...
October 24, 2017: Vascular Pharmacology
https://www.readbyqxmd.com/read/29046793/updated-recommendation-on-molecular-targeted-therapy-for-metastatic-renal-cell-cancer
#4
Senji Hoshi, Kenji Numahata, Hidenori Kanno, Masahiko Sato, Akihito Kuromoto, Kunihisa Nezu, Takanari Sakai, Chihito Konno, Yuichi Ishizuka, Hideaki Izumi, Katsuyuki Taguchi, Kunio Ono, Kiyotsugu Hoshi, Satoshi Kanto, Rika Takahashi, Bilim Vladimir, Naoe Akimoto, Isoji Sasagawa, Shoichiro Ohta
Molecular-targeted therapy was recommended for the systemic therapy of renal cell cancer (RCC) in the RCC guidelines, but these guidelines do not address the order of administration of the multiple presently available agents. There are several aspects that remain unknown regarding the optimal administration order and combination of molecular-targeted drugs. Until the optimal treatment sequence is determined by clinical trials, treatment individualization is required for each patient based on patient and disease characteristics...
October 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29033542/axitinib-in-the-treatment-of-renal-cell-carcinoma-design-development-and-place-in-therapy
#5
REVIEW
Audrey Bellesoeur, Edith Carton, Jerome Alexandre, Francois Goldwasser, Olivier Huillard
Since 2005, the approved first-line treatment of metastatic renal cell carcinoma consists in tyrosine kinase inhibitors (TKIs) targeting the vascular endothelial growth factor receptors (VEGFRs). Axitinib is an oral second-generation TKI and a potent VEGFR inhibitor with a half maximal inhibitory concentration for the VEGF family receptors 10-fold lower than other TKIs. Axitinib activity in renal cell carcinoma (RCC) patients has been studied in various settings and particularly as second-line treatment. In this setting, axitinib with clinically based dose escalation compared to sorafenib has demonstrated an improvement in progression-free survival in a randomized Phase III trial leading to US Food and Drug Administration approval...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28988341/randomized-phase-ii-trial-comparing-axitinib-with-the-combination-of-axitinib-and-lomustine-in-patients-with-recurrent-glioblastoma
#6
J Duerinck, S Du Four, F Bouttens, C Andre, V Verschaeve, F Van Fraeyenhove, C Chaskis, N D'Haene, M Le Mercier, A Rogiers, A Michotte, I Salmon, B Neyns
Axitinib is a small molecule tyrosine kinase inhibitor with high affinity and specificity for the family of vascular endothelial growth factor receptors. It has previously demonstrated anti-tumor activity in a small cohort of patients with recurrent glioblastoma (rGB). We conducted a non-comparative randomized phase II clinical trial investigating axitinib monotherapy versus axitinib plus lomustine (LOM) in patients with rGB. Primary endpoint was 6 month progression-free survival (6mPFS). Patients who progressed on axitinib-monotherapy were allowed to cross-over...
October 7, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28977627/baseline-risk-stratification-or-duration-of-prior-therapy-predicts-prognosis-in-patients-with-metastatic-renal-cell-carcinoma-treated-with-axitinib
#7
Ryuichi Mizuno, Shuji Mikami, Kimiharu Takamatsu, Toshiaki Shinojima, Eiji Kikuchi, Mototsugu Oya
Background: To elucidate the clinical prognostic factors in patients with metastatic renal cell carcinoma (mRCC) treated with axitinib. Methods: A total of 58 patients were retrospectively analyzed. All patients received axitinib treatment for mRCC at Keio University hospital in Japan. Baseline clinical factors and on treatment adverse events were assessed to predict survival. Results: The median progression free survival (PFS) for axitinib treatment was 10...
September 18, 2017: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28973155/high-throughput-screening-uncovers-mirnas-enhancing-glioblastoma-cell-susceptibility-to-tyrosine-kinase-inhibitors
#8
Pedro P Cunha, Pedro M Costa, Catarina M Morais, Inês R Lopes, Ana M Cardoso, Ana L Cardoso, Miguel Mano, Amália S Jurado, Maria C Pedroso de Lima
Glioblastoma (GBM) is a deadly and therapy resistant malignant brain tumour, characterized by an aggressive and diffuse growth pattern, which prevents complete surgical resection. Despite advances in the identification of genomic and molecular alterations that fuel the tumour, average patient survival post-diagnosis remains very low (∼14.6-months). In addition to being highly heterogeneous, GBM tumour cells exhibit high adaptive capacity to targeted molecular therapies owing to an established network of signalling cascades with functional redundancy, which provides them with robust compensatory survival mechanisms...
November 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28965046/development-and-validation-of-a-sensitive-lc-ms-ms-method-for-simultaneous-determination-of-eight-tyrosine-kinase-inhibitors-and-its-application-in-mice-pharmacokinetic-studies
#9
Yu He, Lei Zhou, Song Gao, Taijun Yin, Yifan Tu, Robert Rayford, Xiaoqiang Wang, Ming Hu
The purpose of this study was to develop and validate a robust and sensitive LC-MS/MS method for simultaneous determinations of various tyrosine kinase inhibitors (TKIs) in biological samples and to apply the method to their pharmacokinetic studies. Processed samples were injected into the UHPLC system coupled to an ESI-triple quadrupole mass spectrometer. The compounds were separated on an AcQuity UHPLC BEH C18 column (50mm×2.1mm ID, 1.7μm) using a gradient elution of acetonitrile/0.1% formic acid in water...
September 11, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28950297/a-randomized-phase-ii-trial-of-crlx101-in-combination-with-bevacizumab-versus-standard-of-care-in-patients-with-advanced-renal-cell-carcinoma
#10
M H Voss, A Hussain, N Vogelzang, J L Lee, B Keam, S Y Rha, U Vaishampayan, W B Harris, S Richey, J M Randall, D Shaffer, A Cohn, T Crowell, J Li, A Senderowicz, E Stone, R Figlin, R J Motzer, N B Haas, T Hutson
Background: Nanoparticle-drug conjugates enhance drug delivery to tumors. Gradual payload release inside cancer cells augments antitumor activity while reducing toxicity. CRLX101 is a novel nanoparticle-drug conjugate containing camptothecin, a potent inhibitor of topoisomerase I and the hypoxia-inducible factors 1α and 2α. In a phase Ib/2 trial, CRLX101 + bevacizumab was well tolerated with encouraging activity in metastatic renal cell carcinoma (mRCC). We conducted a randomized phase II trial comparing CRLX101 + bevacizumab versus standard of care (SOC) in refractory mRCC...
November 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28918879/axitinib-related-osteonecrosis-of-the-jaw
#11
Vinod Patel, Chris Sproat, Jerry Kwok, Nikki Tanna
Tyrosine kinase inhibitors (TKIs) are oral chemotherapy drugs used primarily to treat leukemias, renal cell carcinomas, gastrointestinal stromal tumors, and neuroendocrine tumors. Within this group, a number of drugs have already been implicated in jaw necrosis. Axitinib (Inlyta) is a novel TKI currently licensed for the treatment of renal cell carcinoma. We report the first case, to our knowledge, of jaw necrosis solely related to this medication and review the literature surrounding TKIs and their implication in osteonecrosis of the jaw...
August 18, 2017: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
https://www.readbyqxmd.com/read/28911730/management-of-tyrosine-kinase-inhibitors-tki-side-effects-in-differentiated-and-medullary-thyroid-cancer-patients
#12
REVIEW
C Resteghini, S Cavalieri, D Galbiati, R Granata, S Alfieri, C Bergamini, P Bossi, L Licitra, L D Locati
Four tyrosine kinase inhibitors (TKIs) have been recently licensed in thyroid cancer (TC), sorafenib and lenvatinib for differentiated TC, vandetanib and cabozantinib for medullary TC. Others TKIs such as axitinib, pazopanib, sunitinib, have been tested within phase II trials. The toxicity burden associated to TKIs is not negligible. Drug reductions and interruptions are common, definitive drug withdrawals have also been reported as well as toxic deaths in more rare cases. In this context, the prevention of toxicities is mandatory to allow patients to stay on treatment as long as possible without dose and schedule modifications...
June 2017: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/28891933/tyrosine-kinase-inhibitors-therapies-with-mainly-anti-angiogenic-activity-in-advanced-renal-cell-carcinoma-value-of-pet-ct-in-response-evaluation
#13
REVIEW
Girolamo Ranieri, Ilaria Marech, Artor Niccoli Asabella, Alessandra Di Palo, Mariangela Porcelli, Valentina Lavelli, Giuseppe Rubini, Cristina Ferrari, Cosmo Damiano Gadaleta
Renal cell carcinoma (RCC) is the most frequent renal tumor and the majority of patients are diagnosed with advanced disease. Tumor angiogenesis plays a crucial role in the development and progression of RCC together with hypoxia and glucose metabolism. These three pathways are strictly connected to the cell growth and proliferation, like a loop that is self-feeding. Over the last few years, the ever-deeper knowledge of its contribution in metastatic RCC led to the discovery of numerous tyrosine kinase inhibitors (TKIs) targeting pro-angiogenic receptors at different levels such as sunitinib, sorafenib, pazopanib, axitinib, tivozanib, and dovitinib...
September 9, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28888866/everolimus-versus-axitinib-as-second-line-therapy-in-metastatic-renal-cell-carcinoma-experience-from-institut-gustave-roussy
#14
Annalisa Guida, Laurence Albiges, Lisa Derosa, Yohann Loriot, Christophe Massard, Karim Fizazi, Bernard Escudier
BACKGROUND: Everolimus (E) and axitinib (A) have been standard treatments for patients with metastatic renal cell carcinoma after failure of first-line therapy (1L) with vascular endothelial growth factor-targeted therapy. This study aims to compare both drugs in a large comprehensive cancer center. METHODS: Patient characteristics and outcome data from all patients with metastatic renal cell carcinoma who received E or A as second-line therapy at Gustave Roussy from April 2007 to May 2015 have been recorded...
August 12, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28887097/second-line-systemic-therapy-in-metastatic-renal-cell-carcinoma-a-review
#15
REVIEW
Rohit K Jain, Shipra Gandhi, Saby George
Treatment in metastatic renal-cell carcinoma (mRCC) has evolved tremendously in the last decade. The development of newer targeted agents, like vascular endothelial growth factor inhibitors and immunotherapy have changed the treatment paradigm in mRCC patients. Axitinib and everolimus have been used extensively in patients who progressed on prior antiangiogenic therapy. The newer agents including nivolumab, cabozantinib, and lenvatinib in combination with everolimus have all demonstrated overall survival benefit over everolimus...
November 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28886476/phase-i-study-of-axitinib-and-everolimus-in-metastatic-solid-tumours-and-extension-to-metastatic-renal-cell-carcinoma-results-of-evax-study
#16
MULTICENTER STUDY
Alain Ravaud, Carlos Gomez-Roca, Marie-Quitterie Picat, Laurence Digue, Christine Chevreau, Anne Gimbert, Emmanuelle Chauzit, Rémi Sitta, François Cornelis, Julien Asselineau, Richard Aziza, Amaury Daste, Cathy Quemener, Jessica Baud, Andréas Bikfalvi, Delphine Pedenon-Périchout, Adelaïde Doussau, Mathieu Molimard, Jean-Pierre Delord
PURPOSE: Anti-angiogenic and mammalian target of rapamycin inhibitors have shown efficacy in solid tumours. Reported combination of both drugs was deemed to be too toxic. Due to a potential favourable safety profile of axitinib (AX), a phase I study combining everolimus (EV) and AX for solid tumours was explored. EXPERIMENTAL DESIGN: Patients (pts) with advanced cancers were enrolled in an escalation phase I study to investigate the safety of the combination. Pharmacokinetic profile and functional vascular imaging were performed...
November 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28886175/cabozantinib-versus-everolimus-nivolumab-axitinib-sorafenib-and-best-supportive-care-a-network-meta-analysis-of-progression-free-survival-and-overall-survival-in-second-line-treatment-of-advanced-renal-cell-carcinoma
#17
Billy Amzal, Shuai Fu, Jie Meng, Johanna Lister, Helene Karcher
BACKGROUND: Relative effect of therapies indicated for the treatment of advanced renal cell carcinoma (aRCC) after failure of first line treatment is currently not known. The objective of the present study is to evaluate progression-free survival (PFS) and overall survival (OS) of cabozantinib compared to everolimus, nivolumab, axitinib, sorafenib, and best supportive care (BSC) in aRCC patients who progressed after previous VEGFR tyrosine-kinase inhibitor (TKI) treatment. METHODOLOGY & FINDINGS: Systematic literature search identified 5 studies for inclusion in this analysis...
2017: PloS One
https://www.readbyqxmd.com/read/28879167/vascular-endothelial-growth-factor-irradiation-and-axitinib-have-diverse-effects-on-motility-and-proliferation-of-glioblastoma-multiforme-cells
#18
Reinhardt Krcek, Veronika Matschke, Verena Theis, Irenäus Anton Adamietz, Helmut Bühler, Carsten Theiss
Glioblastoma multiforme (GBM) is the most common primary brain tumor. It is highly aggressive with an unfavorable prognosis for the patients despite therapies including surgery, irradiation, and chemotherapy. One important characteristic of highly vascularized GBM is the strong expression of vascular endothelial growth factor (VEGF). VEGF has become a new target in the treatment of GBM, and targeted therapies such as the VEGF-receptor blocker axitinib are in clinical trials. Most studies focus on VEGF-induced angiogenesis, but only very few investigations analyze autocrine or paracrine effects of VEGF on the tumor cells...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28808717/the-opening-closure-of-the-p-loop-and-hinge-of-bcr-abl1-decodes-the-low-high-bioactivities-of-dasatinib-and-axitinib
#19
Jianyi Wang, Qing Chen, Mian Wang, Cheng Zhong
To obtain new insights into the resistance caused by T315I and the differential selectivities of dasatinib and axitinib against BCR-ABL1(WT) and BCR-ABL1(T315), molecular dynamics simulations and free energy calculations were performed. A rule is summarized that the opening/closure of the P-loop and hinge of BCR-ABL1 could reflect the low/high bioactivities of dasatinib and axitinib. This may be because strong interactions of the ligands with key residues induce the P-loop and hinge of BCR-ABL1 to close, being favorable for the retention of the ligand in the binding site...
August 23, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28807653/the-effects-of-neoadjuvant-axitinib-on-anthropometric-parameters-n-patients-with-locally-advanced-non-metastatic-renal-cell-carcinoma
#20
Shivashankar Damodaran, E Jason Abel
No abstract text is available yet for this article.
August 11, 2017: Urology
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