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Pazopanib

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https://www.readbyqxmd.com/read/29143983/growth-of-doxorubicin-resistant-undifferentiated-spindle-cell-sarcoma-pdox-is-arrested-by-metabolic-targeting-with-recombinant-methioninase
#1
Kentaro Igarashi, Shukuan Li, Qinghong Han, Yuying Tan, Kei Kawaguchi, Takashi Murakami, Tasuku Kiyuna, Kentaro Miyake, Yunfeng Li, Scott D Nelson, Sarah M Dry, Arun S Singh, Irmina A Elliott, Tara A Russell, Mark A Eckardt, Norio Yamamoto, Katsuhiro Hayashi, Hiroaki Kimura, Shinji Miwa, Hiroyuki Tsuchiya, Fritz C Eilber, Robert M Hoffman
Undifferentiated spindle-cell sarcoma (USCS) is a recalcitrant -cancer in need of individualized therapy. A high-grade USCS from a striated muscle of a patient was grown orthotopically in the right biceps femoris muscle of nude mice to establish a patient-derived orthotopic xenograft (PDOX) model. In a previous study, we evaluated the efficacy of standard first-line chemotherapy of doxorubicin (DOX), gemcitabine (GEM) combined with docetaxel (DOC), compared to pazopanib (PAZ), a multi-targeting tyrosine-kinase inhibitor, in an USCS PDOX model...
November 16, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29141209/high-throughput-drug-screening-identifies-pazopanib-and-clofilium-tosylate-as-promising-treatments-for-malignant-rhabdoid-tumors
#2
Céline Chauvin, Amaury Leruste, Arnault Tauziede-Espariat, Mamy Andrianteranagna, Didier Surdez, Aurianne Lescure, Zhi-Yan Han, Elodie Anthony, Wilfrid Richer, Sylvain Baulande, Mylène Bohec, Sakina Zaidi, Marie-Ming Aynaud, Laetitia Maillot, Julien Masliah-Planchon, Stefano Cairo, Sergio Roman-Roman, Olivier Delattre, Elaine Del Nery, Franck Bourdeaut
Rhabdoid tumors (RTs) are aggressive tumors of early childhood characterized by SMARCB1 inactivation. Their poor prognosis highlights an urgent need to develop new therapies. Here, we performed a high-throughput screening of approved drugs and identified broad inhibitors of tyrosine kinase receptors (RTKs), including pazopanib, and the potassium channel inhibitor clofilium tosylate (CfT), as SMARCB1-dependent candidates. Pazopanib targets were identified as PDGFRα/β and FGFR2, which were the most highly expressed RTKs in a set of primary tumors...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/29141017/temozolomide-post-pazopanib-treatment-failure-in-patients-with-advanced-sarcoma-a-case-series
#3
Manojkumar Bupathi, John L Hays, James L Chen
BACKGROUND: Sarcomas are rare, heterogeneous tumors for which prognosis remains dismal in patients with advanced disease. Pazopanib, a vascular endothelial growth factor receptor inhibitor, has shown modest efficacy in patients with soft tissue sarcoma who fail cytotoxic chemotherapy. The cytotoxic agent temozolomide has also demonstrated activity in patients with advanced sarcoma. OBJECTIVE: We performed a retrospective case series to evaluate the feasibility of adding temozolomide to pazopanib in advanced sarcoma patients following single-agent pazopanib failure...
2017: PloS One
https://www.readbyqxmd.com/read/29137331/hdac-inhibitors-enhance-the-immunotherapy-response-of-melanoma-cells
#4
Laurence Booth, Jane L Roberts, Andrew Poklepovic, John Kirkwood, Paul Dent
We focused on the ability of the pan-histone deacetylase (HDAC) inhibitors AR42 and sodium valproate to alter the immunogenicity of melanoma cells. Treatment of melanoma cells with HDAC inhibitors rapidly reduced the expression of multiple HDAC proteins as well as the levels of PD-L1, PD-L2 and ODC, and increased expression of MHCA. In a cell-specific fashion, melanoma isolates released the immunogenic protein HMGB1 into the extracellular environment. Very similar data were obtained in ovarian and H&NSCC PDX isolates, and in established tumor cell lines from the lung and kidney...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29134564/seom-clinical-guideline-for-treatment-of-kidney-cancer-2017
#5
E Gallardo, M J Méndez-Vidal, J L Pérez-Gracia, J M Sepúlveda-Sánchez, M Campayo, I Chirivella-González, X García-Del-Muro, A González-Del-Alba, E Grande, C Suárez
The goal of this article is to provide recommendations about the management of kidney cancer. Based on pathologic and molecular features, several kidney cancer variants were described. Nephron-sparing techniques are the gold standard of localized disease. After a randomized trial, sunitinib could be considered in adjuvant treatment in high-risk patients. Patients with advanced disease constitute a heterogeneous population. Prognostic classification should be considered. Both sunitinib and pazopanib are the standard options for first-line systemic therapy in advanced renal cell carcinoma...
November 13, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/29095301/lingual-alveolar-soft-part-sarcoma-responsive-to-pazopanib-a-case-report
#6
Tomoyasu Yoshihiro, Kenji Tsuchihashi, Kenta Nio, Shuji Arita, Takafumi Nakano, Ryuji Yasumatsu, Rina Jiroumaru, Hiroshi Ariyama, Hitoshi Kusaba, Yoshinao Oda, Koichi Akashi, Eishi Baba
RATIONALE: The multi-targeted tyrosine kinase inhibitors such as cediranib, sunitinib and pazopanib have been reported to be effective for alveolar soft part sarcoma (ASPS). The efficacy of pazopanib for the patient with lingual ASPS has yet to be reported. PATIENT CONCERNS: A 23-year old man presented with articulation disorder and swelling of the tongue. Diagnosis of lingual ASPS was made after incisional biopsy and complete excision of the mass was performed...
November 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29089306/organic-cation-transporter-1-is-responsible-for-hepatocellular-uptake-of-the-tyrosine-kinase-inhibitor-pazopanib
#7
Waleed Elsayed Ahmed Ellawatty, Yusuke Masuo, Ken-Ichi Fujita, Erina Yamazaki, Hiroo Ishida, Hiroshi Arakawa, Noritaka Nakamichi, Ramadan Abdelwahed, Yasutsuna Sasaki, Yukio Kato
Pazopanib is an orally active tyrosine kinase inhibitor that exhibits hepatotoxicity in some patients. Despite the clinical importance of its hepatic distribution, the transporter(s) responsible for hepatic uptake of pazopanib in humans remain undetermined. In order to characterize its hepatic uptake mechanism, we screened the effects of several transporter inhibitors, including tetrapentylammonium (TPeA) for organic cation transporters (OCTs) and cyclosporin A (CsA) for organic anion-transporting polypeptides (OATPs), on both plasma disappearance and hepatic distribution of pazopanib in mice after its intravenous administration...
October 31, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29076108/clinical-and-economic-outcomes-in-elderly-advanced-renal-cell-carcinoma-patients-starting-pazopanib-or-sunitinib-treatment-a-retrospective-medicare-claims-analysis
#8
Nicholas J Vogelzang, Sumanta K Pal, Sameer R Ghate, Elyse Swallow, Nanxin Li, Miranda Peeples, Miriam L Zichlin, Mark K Meiselbach, Jose Ricardo Perez, Neeraj Agarwal
INTRODUCTION: Studies indicate similar survival and toxicity between pazopanib and sunitinib, but few have examined real-world outcomes among elderly patients with advanced renal cell carcinoma (RCC). The purpose of this retrospective claims analysis was to assess real-world overall survival (OS), healthcare resource utilization (HRU), and healthcare costs (both all-cause and associated with RCC diagnosis) among elderly advanced RCC patients starting pazopanib or sunitinib treatment. METHODS: Advanced RCC patients aged 65 years or older who started first-line treatment with pazopanib or sunitinib (index drug; the initiation date was the index date) were identified from the 100% Medicare database plus Part D linkage (January 1, 2006 to December 31, 2014)...
October 26, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/29072563/secondary-polycythemia-due-to-pazopanib-in-patients-with-metastatic-renal-cell-carcinoma
#9
Nedal Bukhari, Eric Winquist
No abstract text is available yet for this article.
November 11, 2017: Canadian Urological Association Journal, Journal de L'Association des Urologues du Canada
https://www.readbyqxmd.com/read/29072336/mechanisms-of-toxicity-associated-with-six-tyrosine-kinase-inhibitors-in-human-hepatocyte-cell-lines
#10
Cécile Mingard, Franziska Paech, Jamal Bouitbir, Stephan Krähenbühl
Tyrosine kinase inhibitors have revolutionized the treatment of certain cancers. They are usually well tolerated, but can cause adverse reactions including liver injury. Currently, mechanisms of hepatotoxicity associated with tyrosine kinase inhibitors are only partially clarified. We therefore aimed at investigating the toxicity of regorafenib, sorafenib, ponatinib, crizotinib, dasatinib and pazopanib on HepG2 and partially on HepaRG cells. Regorafenib and sorafenib strongly inhibited oxidative metabolism (measured by the Seahorse-XF24 analyzer) and glycolysis, decreased the mitochondrial membrane potential and induced apoptosis and/or necrosis of HepG2 cells at concentrations similar to steady-state plasma concentrations in humans...
October 26, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29068785/adjuvant-pazopanib-does-not-protect-against-recurrence-of-high-risk-initially-localized-renal-cell-cancer-but-does-provide-novel-insights
#11
Grant D Stewart, Bradley C Leibovich, Sylvie Negrier, Robert A Figlin
No abstract text is available yet for this article.
October 25, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29067537/posterior-reversible-encephalopathy-syndrome-pres-induced-by-pazopanib-a-multi-targeting-tyrosine-kinase-inhibitor-in-a-patient-with-soft-tissue-sarcoma-case-report-and-review-of-the-literature
#12
Shoichi Deguchi, Koichi Mitsuya, Yoko Nakasu, Nakamasa Hayashi, Hirohisa Katagiri, Hideki Murata, Junji Wasa, Mitsuru Takahashi, Masahiro Endo
Posterior reversible encephalopathy syndrome (PRES) is a clinical entity characterized by acute neurological symptoms such as severe headache, seizures, and visual disturbance, and by typical reversible lesion on brain magnetic resonance (MR) images. Since PRES is thought to be caused by vascular endothelial injury due to cytotoxic agents or acute systemic hypertension, the number of reports on PRES associated with angiogenesis inhibitors has been increasing. Although five cases that developed PRES due to pazopanib for renal cell carcinoma have already been reported, none of PRES due to pazopanib for soft-tissue sarcoma has been reported thus far...
October 25, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/29064751/alternative-response-criteria-and-clinical-risk-factors-for-assessing-tumor-response-in-patients-with-metastatic-renal-cell-carcinoma-who-are-receiving-salvage-therapy
#13
Hyunseon C Kang, Shiva Gupta, Wei Wei, Lina Lu, Marc R Matrana, Nizar M Tannir, Haesun Choi
OBJECTIVE: The purpose of this study is to compare the prognostic value of various solid tumor response criteria as well as the additive value of clinical risk factors in patients with advanced renal cell carcinoma (RCC). MATERIALS AND METHODS: Two sets of CT scans (pretreatment scans and scans obtained 1-3.5 months after treatment) were reviewed for 57 patients with metastatic RCC treated with pazopanib in the salvage setting. Tumor response on the posttherapy scan was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) and Choi, modified Choi (mChoi), MASS (Morphology, Attenuation, Size, and Structure), and 10% threshold criteria...
October 24, 2017: AJR. American Journal of Roentgenology
https://www.readbyqxmd.com/read/29062235/real-world-experience-of-everolimus-as-second-line-treatment-in-metastatic-renal-cell-cancer-after-failure-of-pazopanib
#14
Konstantinos Koutsoukos, Aristotelis Bamias, Kimon Tzannis, Marta Espinosa Montaño, Vasiliki Bozionelou, Christos Christodoulou, Dimitra Stefanou, Haralabos Kalofonos, Ignacio Duran, Konstantinos Papazisis
AIM: We aimed to provide real-life data on the outcomes of metastatic renal cell carcinoma (mRCC) patients treated with everolimus as second-line treatment after failure of first-line pazopanib. PATIENTS AND METHODS: Data from the medical charts of mRCC patients from 8 centers in Greece and Spain were reviewed. All patients had received or were continuing to receive second-line everolimus treatment after failure of first-line treatment with pazopanib. No other previous therapies were allowed...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29054093/the-role-of-pazopanib-on-tumour-angiogenesis-and-in-the-management-of-cancers-a-review
#15
REVIEW
Dinesh Kumar Chellappan, Jestin Chellian, Zhao Yin Ng, Yan Jinn Sim, Chiu Wei Theng, Joyce Ling, Mei Wong, Jia Hui Foo, Goh Jun Yang, Li Yu Hang, Saranyah Nathan, Yogendra Singh, Gaurav Gupta
Pazopanib is a relatively new compound to be introduced into the chemotherapy field. It is thought to have decent anti-angiogenic properties, which gives an additional hope for the treatment of certain types of cancers. A systematic review solely discussing about pazopanib and its anti-angiogenic effect is yet to be published to date, despite several relevant clinical trials being conducted over the recent years. In this review, we aim to investigate the mechanism of pazopanib's anti-angiogenic effect and its effectiveness in treating several cancers...
October 17, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29051995/exposure-survival-analyses-of-pazopanib-in-renal-cell-carcinoma-and-soft-tissue-sarcoma-patients-opportunities-for-dose-optimization
#16
R B Verheijen, L E Swart, J H Beijnen, J H M Schellens, A D R Huitema, N Steeghs
BACKGROUND: Pazopanib is an angiogenesis inhibitor approved for the treatment of renal cell carcinoma and soft tissue sarcoma. Post hoc analysis of a clinical trial demonstrated a relationship between pazopanib trough concentrations (Cmin) and treatment efficacy. The aim of this study was to explore the pharmacokinetics and exposure-survival relationships of pazopanib in a real-world patient cohort. PATIENTS AND METHODS: Renal cell cancer and soft tissue sarcoma patients who had at least one pazopanib plasma concentration available were included...
October 19, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29034773/substrate-dependent-effects-of-molecular-targeted-anticancer-agents-on-activity-of-organic-anion-transporting-polypeptide-1b1
#17
Hiroyoshi Koide, Masayuki Tsujimoto, Ai Takeuchi, Miyu Tanaka, Yoko Ikegami, Mayu Tagami, Syoko Abe, Miki Hashimoto, Tetsuya Minegaki, Kohshi Nishiguchi
1. Organic anion-transporting polypeptide 1B1 (OATP1B1) plays an important role in the hepatic uptake of a broad range of substrate drugs. In vitro experiments show that molecular-targeted agents do not always have similar effects on OATP1B1 activity. 2. The purpose of this study was to clarify whether the effects of molecular-targeted agents on OATP1B1 are substrate-dependent. We used OATP1B1-transfected cells to compare the effects of molecular-targeted agents on OATP1B1-mediated uptake of fluorescein (FL), 2',7'-dichlorofluorescein (DCF), atorvastatin, SN-38, and valsartan...
October 16, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28987881/high-density-lipoprotein-mutant-eye-drops-for-the-treatment-of-posterior-eye-diseases
#18
Kenji Suda, Tatsuya Murakami, Norimoto Gotoh, Ryosuke Fukuda, Yasuhiko Hashida, Mitsuru Hashida, Akitaka Tsujikawa, Nagahisa Yoshimura
Age-related macular degeneration (AMD), in which choroidal neovascularization (CNV) affects the center of the retina (macula), leads to the irreversible visual loss. The intravitreal injection of anti-angiogenesis antibodies improved the prognosis of AMD, but relatively less invasive therapies should be explored. In the present study, we show that a high-density lipoprotein (HDL) mutant is a therapeutically active drug carrier capable of treating a posterior eye disease in mice via instillation. Various HDL mutants were prepared with apoA-I proteins fused with different cell-penetrating peptides (CPPs) and phospholipids with different alkyl chain lengths; their sizes were further controlled in the range of 10-25nm...
October 5, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28983380/acute-pancreatitis-related-to-a-chemotherapy-drug
#19
Ghulam Murtaza, Anadil Faqah, Nicholas Konowitz, Hannah Lu, Aneesh Kuruvilla, Sujeen Adhikari
Drug-induced acute pancreatitis is a rare cause of pancreatitis. We present a case of pancreatitis caused by pazopanib, a tyrosine kinase inhibitor used in the treatment of renal cell carcinoma. A 57-year-old male with no risk factors for pancreatitis and a past medical history of renal cell carcinoma who was being treated with pazopanib presented with epigastric pain with radiation to the back. Lipase was elevated to 7,960 units/L. Pazopanib was discontinued on arrival and his lipase levels decreased from 7,960 to 3,380 units/L one day after discontinuation...
February 2017: World Journal of Oncology
https://www.readbyqxmd.com/read/28981730/establishment-and-proteomic-characterization-of-ncc-lms1-c1-a-novel-cell-line-of-primary-leiomyosarcoma-of-the-bone
#20
Marimu Sakumoto, Mami Takahashi, Rieko Oyama, Yoko Takai, Fusako Kito, Kumiko Shiozawa, Zhiwei Qiao, Akihiko Yoshida, Makoto Endo, Akira Kawai, Tadashi Kondo
Background: Leiomyosarcoma (LMS) is one of most aggressive mesenchymal malignancies that differentiate towards smooth muscle. The clinical outcome of LMS patients is poor; as such, there is an urgent need for novel therapeutic approaches. Experimental models such as patient-derived cell lines are invaluable tools for pre-clinical studies. In the present study, we established a stable cell line from the tumor tissue of a patient with a primary LMS of the bone. Despite the urgent need for novel therapeutic strategies in LMS, there are only a few LMS cell lines available in public cell banks, none of which are primary to the bone...
October 1, 2017: Japanese Journal of Clinical Oncology
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