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Pazopanib

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https://www.readbyqxmd.com/read/28443292/measurements-of-metastatic-renal-cell-tumours-as-determined-by-diffusion-weighted-imaging-or-computed-tomography-are-in-close-agreement-a-pilot-study
#1
J Farnebo, C Suzuki, R Vargas-Paris, P Sandström, L Blomqvist
BACKGROUND: Diffusion weighted magnetic resonance imaging (DWI) provides both functional and anatomical information regarding tumours but can also be used for tumour detection. Today, tumour treatment response in clinical trials is mainly assessed on Computed Tomography (CT) using established criteria. Despite availability of dedicated software, CT still requires significant manual work for selection and measurement in treatment response evaluation of solid tumours. PURPOSE: To compare the maximum diameter of tumour lesions on CT with the corresponding measurements on diffusion weighted images...
2017: European Journal of Radiology Open
https://www.readbyqxmd.com/read/28441383/the-oral-vegf-receptor-tyrosine-kinase-inhibitor-pazopanib-in-combination-with-the-mek-inhibitor-trametinib-in-advanced-cholangiocarcinoma
#2
Rachna T Shroff, Mark Yarchoan, Ashley O'Connor, Denise Gallagher, Marianna L Zahurak, Gary Rosner, Chimela Ohaji, Susan Sartorius-Mergenthaler, Vivek Subbiah, Ralph Zinner, Nilofer S Azad
BACKGROUND: Cholangiocarcinoma is an aggressive malignancy with limited therapeutic options. MEK inhibition and antiangiogenic therapies have individually shown modest activity in advanced cholangiocarcinoma, whereas dual inhibition of these pathways has not been previously evaluated. We evaluated the safety and efficacy of combination therapy with the oral VEGF receptor tyrosine kinase inhibitor pazopanib plus the MEK inhibitor trametinib in patients with advanced cholangiocarcinoma...
April 25, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28440337/corrigendum-patient-specific-hepatocyte-like-cells-derived-from-induced-pluripotent-stem-cells-model-pazopanib-mediated-hepatotoxicity
#3
Yukti Choudhury, Yi Chin Toh, Jiangwa Xing, Yinghua Qu, Jonathan Poh, Huan Li, Hui Shan Tan, Ravindran Kanesvaran, Hanry Yu, Min-Han Tan
No abstract text is available yet for this article.
April 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28430711/evaluation-of-kdr-rs34231037-as-a-predictor-of-sunitinib-efficacy-in-patients-with-metastatic-renal-cell-carcinoma
#4
María Apellániz-Ruiz, Meta H Diekstra, Juan M Roldán, Epie Boven, Daniel Castellano, Hans Gelderblom, Ron H J Mathijssen, Jesse J Swen, Stefan Böhringer, Jesús García-Donás, Brian I Rini, Henk-Jan Guchelaar, Cristina Rodríguez-Antona
The identification of biomarkers able to predict clinical benefit from vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors is urgently needed. Recently, Maitland and colleagues described an association between KDR-rs34231037 and soluble VEGFR2 levels as well as pazopanib pharmacodynamics. We investigated in a well-characterized series of metastatic clear cell renal cell carcinoma patients whether rs34231037 could influence sunitinib response. Clinical data and DNA were available from an international series of 276 patients...
April 20, 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28430700/prescriber-compliance-with-liver-monitoring-guidelines-for-pazopanib-in-the-postapproval-setting-results-from-a-distributed-research-network
#5
Sumitra Shantakumar, Beth L Nordstrom, Susan A Hall, Luc Djousse, Myrthe P P van Herk-Sukel, Kathy H Fraeman, David R Gagnon, Karen Chagin, Jeanenne J Nelson
OBJECTIVES: Pazopanib received US Food and Drug Administration approval in 2009 for advanced renal cell carcinoma. During clinical development, liver chemistry abnormalities and adverse hepatic events were observed, leading to a boxed warning for hepatotoxicity and detailed label prescriber guidelines for liver monitoring. As part of postapproval regulatory commitments, a cohort study was conducted to assess prescriber compliance with liver monitoring guidelines. METHODS: Over a 4-year period, a distributed network approach was used across 3 databases: US Veterans Affairs Healthcare System, a US outpatient oncology community practice database, and the Dutch PHARMO Database Network...
April 20, 2017: Journal of Patient Safety
https://www.readbyqxmd.com/read/28427506/recent-advances-in-genitourinary-tumors-a-review-focused-on-biology-and-systemic-treatment
#6
REVIEW
Aránzazu González Del Alba, José Ángel Arranz, Javier Puente, María José Méndez-Vidal, Enrique Gallardo, Enrique Grande, Begoña Pérez-Valderrama, Enrique González-Billalabeitia, Martín Lázaro-Quintela, Álvaro Pinto, Nuria Lainez, Josep M Piulats, Emilio Esteban, José Pablo Maroto Rey, Jorge A García, Cristina Suárez
Updated information published up to 2016 regarding major advances in renal cancer, bladder cancer, and prostate cancer is here presented. Based on an ever better understanding of the genetic and molecular alterations that govern the initial pathogenic mechanisms of tumor oncogenesis, an improvement in the characterization and treatment of urologic tumors has been achieved in the past year. According to the Cancer Genome Atlas (ATLAS) project, alterations in the MET pathway are characteristics of type 1 papillary renal cell carcinomas, and activation of NRF2-ARE pathway is associated with the biologically distinct type 2...
May 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28426279/combination-of-gemcitabine-and-docetaxel-regress-both-gastric-leiomyosarcoma-proliferation-and-invasion-in-an-imageable-patient-derived-orthotopic-xenograft-ipdox-model
#7
Kei Kawaguchi, Kentaro Igarashi, Takashi Murakami, Tasuku Kiyuna, Scott D Nelson, Sarah M Dry, Yunfeng Li, Tara A Russell, Arun S Singh, Bartosz Chmielowski, Michiaki Unno, Fritz C Eilber, Robert M Hoffman
Gastric leiomyosarcoma is a recalcitrant cancer and chemotherapy strategy is controversial. The present study used a patient-derived orthotopic xenograft (PDOX) nude mouse model of gastric leiomyosarcoma to identify an effective therapeutic regimen in order to develop individualized precision medicine for this disease. A gastric leiomyosarcoma obtained from a patient was first grown in transgenic nude mice ubiquitously expressing red fluorescent protein (RFP) in order to stably label the tumor stroma. The RFP-expressing tumor was then passaged orthotopically in the gastric wall of non-transgenic nude mice to establish an imageable PDOX (iPDOX) model...
April 20, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28416534/pazopanib-associated-posterior-reversible-encephalopathy-syndrome-with-intracerebral-haemorrhage
#8
Cameron Miller-Patterson, Corey R Fehnel
Pazopanib is a tyrosine kinase receptor antagonist used for renal cell carcinoma and soft tissue sarcoma that inhibits tumour growth and angiogenesis. A common side effect of pazopanib is hypertension. We report a case of a 69-year-old woman with clear cell renal cell carcinoma who developed a large right occipital intracerebral haemorrhage 3 weeks after initiating pazopanib. Although this was initially suspected to be a haemorrhagic metastasis, MRI revealed bi-occipital oedema, supporting a diagnosis of posterior reversible encephalopathy syndrome (PRES)...
April 17, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28413127/evolution-of-circulating-tumor-dna-profile-from-first-line-to-subsequent-therapy-in-metastatic-renal-cell-carcinoma
#9
Sumanta K Pal, Guru Sonpavde, Neeraj Agarwal, Nicholas J Vogelzang, Sandy Srinivas, Naomi B Haas, Sabina Signoretti, Bradley A McGregor, Jeremy Jones, Richard B Lanman, Kimberly C Banks, Toni K Choueiri
BACKGROUND: Treatment of metastatic renal cell carcinoma (mRCC) typically entails mechanistically distinct agents across the first- and second-line setting. Activity of these agents may be predicated on selective pressure that modulates RCC biology. Circulating tumor DNA (ctDNA) is a platform to noninvasively ascertain temporal changes in genomic profile. OBJECTIVE: To assess the ctDNA profile in a large cohort of mRCC patients, and to assess changes across patients receiving first-line and later lines of therapy...
April 13, 2017: European Urology
https://www.readbyqxmd.com/read/28410910/heart-failure-a-paraneoplastic-manifestation-of-renal-cell-carcinoma-reversed-with%C3%A2-pazopanib
#10
Manu Pandey, Shipra Gandhi, Saby George
No abstract text is available yet for this article.
February 27, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28403496/-interdisciplinary-recommendations-for-the-treatment-of-metastatic-renal-cell-carcinoma
#11
Kurt Miller, Lothar Bergmann, Christian Doehn, Jürgen Gschwend, Ulrich Keilholz
Thanks to the use of targeted therapies, the prognosis of patients with metastatic renal cell carcinoma (mRCC) has improved significantly. A median overall survival of more than 2 years is a realistic claim. These improvements are also reflected in recent discussions about 3 and more lines of therapy.Sunitinib, pazopanib, the combination of bevacizumab and interferon alpha, and temsirolimus are approved for first-line therapy of mRCC. Sunitinib and pazopanib are also approved for second-line therapy, which, for pazopanib, is confined to the use after cytokine failure...
February 2017: Aktuelle Urologie
https://www.readbyqxmd.com/read/28402747/randomized-phase-ii-study-investigating-pazopanib-versus-weekly-paclitaxel-in-relapsed-or-progressive-urothelial-cancer
#12
Robert J Jones, Syed A Hussain, Andrew S Protheroe, Alison Birtle, Prabir Chakraborti, Robert A Huddart, Satinder Jagdev, Amit Bahl, Andrew Stockdale, Santhanam Sundar, Simon J Crabb, Judith Dixon-Hughes, Laura Alexander, Anna Morris, Caroline Kelly, Jon Stobo, James Paul, Thomas Powles
Purpose Two previous single-arm trials have drawn conflicting conclusions regarding the activity of pazopanib in urothelial cancers after failure of platinum-based chemotherapy. Patients and Methods This randomized (1:1) open-label phase II trial compared the efficacy of pazopanib 800 mg orally with paclitaxel (80 mg/m(2) days 1, 8, and 15 every 28 days) in the second-line setting. The primary end point was overall survival (OS). Results Between August 2012 and October 2014, 131 patients, out of 140 planned, were randomly assigned...
April 12, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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
#13
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 energy transfer (BRET)...
April 6, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28385611/description-of-the-eurotarget-cohort-a-european-collaborative-project-on-targeted-therapy-in-renal-cell-cancer-genetic-and-tumor-related-biomarkers-for-response-and-toxicity
#14
Loes F M van der Zanden, Sita H Vermeulen, Arna Oskarsdottir, Jake S F Maurits, Meta H M Diekstra, Valentin Ambert, Anne Cambon-Thomsen, Daniel Castellano, Achim Fritsch, Jesus Garcia Donas, Rosa Guarch Troyas, Henk-Jan Guchelaar, Arndt Hartmann, Christina Hulsbergen-van de Kaa, Ulrich Jaehde, Kerstin Junker, Anna Martinez-Cardus, Gisli Masson, Jeannette Oosterwijk-Wakka, Marius T Radu, Thorunn Rafnar, Cristina Rodriguez-Antona, Max Roessler, Rob Ruijtenbeek, Kari Stefansson, Anne Warren, Lodewyk Wessels, Tim Eisen, Lambertus A L M Kiemeney, Egbert Oosterwijk
OBJECTIVE: For patients with metastatic renal cell cancer (mRCC), treatment choice is mainly based on clinical parameters. With many treatments available and the limited response to treatment and associated toxicities, there is much interest in identifying better biomarkers for personalized treatment. EuroTARGET aims to identify and characterize host- and tumor-related biomarkers for prediction of response to tyrosine kinase inhibitor therapy in mRCC. Here, we describe the EuroTARGET mRCC patient cohort...
April 3, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28384659/clinical-response-to-pazopanib-in-a-patient-with-kdr-mutated-metastatic-basal-cell-carcinoma
#15
Todd C Knepper, Morganna L Freeman, Geoffrey T Gibney, Howard L McLeod, Jeffery S Russell
No abstract text is available yet for this article.
April 5, 2017: JAMA Dermatology
https://www.readbyqxmd.com/read/28383677/pazopanib-in-advanced-germ-cell-tumors-after-chemotherapy-failure-results-of-the-open-label-single-arm-phase-2-pazotest-trial
#16
A Necchi, S Lo Vullo, P Giannatempo, D Raggi, G Calareso, E Togliardi, F Crippa, M Pennati, N Zaffaroni, F Perrone, A Busico, M Colecchia, N Nicolai, L Mariani, R Salvioni
BACKGROUND: Therapeutic options for patients with chemoresistant germ cell tumors (GCT) are limited. Pazopanib is a selective tyrosine kinase inhibitor with distinct antiangiogenic activity. We aimed to evaluate pazopanib activity in patients with refractory GCT. PATIENTS AND METHODS: In the open-label, single-arm, phase 2 Pazotest study (NCT01743482), patient eligibility included failure of ≥ 2 platinum-based regimens, and allowed prior high-dose chemotherapy (HDCT) administration...
April 5, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28377484/phase-ib-ii-study-of-safety-efficacy-of-combination-therapy-with-multikinase-vegf-inhibitor-pazopanib-and-mek-inhibitor-trametinib-in-advanced-soft-tissue-sarcoma
#17
Vivek Subbiah, Christian Meyer, Ralph Zinner, Funda Meric-Bernstam, Marianna L Zahurak, Ashley O'Connor, Jason Roszik, Kenna Shaw, Joseph A Ludwig, Razelle Kurzrock, Nilofer A Azad
Purpose: Pazopanib, a multi-receptor tyrosine kinase inhibitor targeting primarily vascular endothelial growth factor receptors 1-3 (VEGFRs1-3), is approved for advanced soft tissue sarcoma and renal cell cancer. Downstream of VEGFR, trametinib is an FDA-approved MEK inhibitor used for melanoma. We hypothesized that vertical pathway inhibition using a trametinib would synergize with pazopanib in advanced soft tissue sarcoma (STS). <p>Experimental Design: In an open-label, multicenter, investigator-initiated NCCN-sponsored trial, patients with metastatic or advanced STS received pazopanib 800 mg and 2 mg of trametinib continuously for 28-day cycles...
April 4, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28350009/activation-of-erk1-2-causes-pazopanib-resistance-via-downregulation-of-dusp6-in-synovial-sarcoma-cells
#18
Nobuhiko Yokoyama, Tomoya Matsunobu, Yoshihiro Matsumoto, Jun-Ichi Fukushi, Makoto Endo, Mihoko Hatano, Akira Nabeshima, Suguru Fukushima, Seiji Okada, Yukihide Iwamoto
Synovial sarcoma (SS) is a rare high-grade malignant mesenchymal tumour with a relatively poor prognosis despite intensive multimodal therapy. Although pazopanib, a multi-kinase inhibitor, is often used for advanced SS, most cases eventually become resistant to pazopanib. In the present study, we investigated the mechanisms of acquired pazopanib resistance in SS. To examine acquired pazopanib resistance, two SS cell lines, SYO-1 and HS-SY-II, were isolated after multiple selection steps with increasing concentrations of pazopanib...
March 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28339142/selective-effects-of-oral-anti-angiogenic-tyrosine-kinase-inhibitors-on-an-animal-model-of-hereditary-hemorrhagic-telangiectasia
#19
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/28330784/vascular-endothelial-growth-factor-vegf-and-vegf-receptor-inhibitors-in-the-treatment-of-renal-cell-carcinomas
#20
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 19, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
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