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https://www.readbyqxmd.com/read/28174388/-a-case-of-renal-cell-carcinoma-with-high-everolimus-blood-concentrations-and-hyperglycemia-due-to-everolimus-induced-hepatic-dysfunction
#1
Shinya Takasaki, Masafumi Kikuchi, Yoshihide Kawasaki, Akihiro Ito, Yoichi Arai, Hiroaki Yamaguchi, Nariyasu Mano
We report the case of a patient who had renal cell carcinoma with high everolimus blood concentrations and hyperglycemia due to everolimus-induced hepatic dysfunction. A 74-year-old man who underwent right nephrectomy for renal cell carcinoma was administered everolimus for multiple lung metastases. Everolimus caused grade 3 hepatic dysfunction and hyperglycemia; hence, high blood levels of everolimus were observed. Although the patient was re-administrated everolimus after recovering from hepatic dysfunction, hepatic function test values worsened again...
January 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28161830/combined-vegf-and-pdgf-inhibition-for-neovascular-amd-anti-angiogenic-properties-of-axitinib-on-human-endothelial-cells-and-pericytes-in-vitro
#2
Jakob Siedlecki, Christian Wertheimer, Armin Wolf, Raffael Liegl, Claudia Priglinger, Siegfried Priglinger, Kirsten Eibl-Lindner
PURPOSE: Drugs currently approved for neovascular age-related macular degeneration (nAMD) offer anti-VEGF monotherapy only. Platelet-derived growth factor (PDGF) signaling is pivotal to pericyte-induced stabilization of choroidal neovascularizations (CNV), and causes partial anti-VEGF resistance. No combination therapy for VEGF and PDGF has been approved yet. Axitinib is a tyrosine kinase inhibitor interfering with VEGF and PDGF signaling, and has been approved for the treatment of renal cell carcinoma...
February 4, 2017: Graefe's Archive for Clinical and Experimental Ophthalmology
https://www.readbyqxmd.com/read/28153029/new-treatment-options-for-metastatic-renal-cell-carcinoma-with-prior-anti-angiogenesis-therapy
#3
REVIEW
Kevin Zarrabi, Chunhui Fang, Shenhong Wu
Angiogenesis is a critical process in the progression of advanced renal cell carcinoma. Agents targeting angiogenesis have played a primary role in the treatment of metastatic renal cell carcinoma. However, resistance to anti-angiogenesis therapy almost always occurs, and major progress has been made in understanding its underlying molecular mechanism. Axitinib and everolimus have been used extensively in patients whom have had disease progression after prior anti-angiogenesis therapy. Recently, several new agents have been shown to improve overall survival in comparison with everolimus...
February 2, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28143997/targeted-therapy-for-metastatic-renal-cell-carcinoma
#4
REVIEW
Andika Afriansyah, Agus Rizal Ah Hamid, Chaidir A Mochtar, Rainy Umbas
In the past 10 years, recent development of targeted therapy in metastatic renal cell carcinoma (mRCC) has provided a new hope and significantly enhanced the prognosis of the disease. Three class of targeted therapy were developed, including multi-targeted tyrosine kinase inhibitors (TKI), the mammalian target of rapamycin (mTOR) complex-1 kinase inhibitors, and the humanized antivascular endothelial growth factor (VEGF) monoclonal antibody. Hence, the objective of this article was to critically examine the current evidence of targeted therapy treatment for patients with mRCC...
October 2016: Acta Medica Indonesiana
https://www.readbyqxmd.com/read/28108609/visualization-and-quantification-of-browning-using-a-ucp1-2a-luciferase-knock-in-mouse-model
#5
Liufeng Mao, Baoming Nie, Tao Nie, Xiaoyan Hui, Xuefei Gao, Xiaoliang Lin, Xin Liu, Yong Xu, Xiaofeng Tang, Ran Yuan, Kuai Li, Peng Li, Ke Ding, Yu Wang, Aimin Xu, Jian Fei, Weiping Han, Pentao Liu, Lise Madsen, Karsten Kristiansen, Zhiguang Zhou, Sheng Ding, Donghai Wu
Both mammals and adult humans possess classic brown adipocytes and beige adipocytes, and the amount and activity of these adipocytes are considered key factors in combating obesity and its associated metabolic diseases. Uncoupling protein 1 (Ucp1) is the functional marker of both brown and beige adipocytes. To facilitate a reliable, easy, and sensitive measurement of Ucp1 expression both in vivo and in vitro, we generated a Ucp1-2A-luciferase knock-in mouse by deleting the stop codon for the mouse Ucp1 gene and replacing it with a 2A peptide...
February 2017: Diabetes
https://www.readbyqxmd.com/read/28106614/study-of-intrapatient-variability-and-reproducibility-of-quantitative-tumor-perfusion-parameters-evaluated-with-dynamic-contrast-enhanced-ultrasonography
#6
Nathalie Lassau, Bénédicte Coiffier, Laura Faivre, Baya Benatsou, Sophie Bidault, Elizabeth Girard, Bernard Asselain, Stéphanie Pitre-Champagnat, Serge Koscielny
OBJECTIVES: Dynamic contrast-enhanced (DCE) ultrasonography (US) is a functional imaging technique enabling quantitative assessment of solid tumor perfusion in metastatic patients treated with antiangiogenic therapies.The objective of this prospective single-center study was to evaluate in real-life conditions (in routine clinical practice) the intrapatient variability and reproducibility of DCE-US parameters. MATERIALS AND METHODS: Each patient provided written informed consent and had 2 DCE-US examinations (preprandial and postprandial) at baseline, day 15, and 1 month after treatment initiation...
March 2017: Investigative Radiology
https://www.readbyqxmd.com/read/28098949/identification-of-cellular-targets-involved-in-cardiac-failure-caused-by-pki-in-oncology-an-approach-combining-pharmacovigilance-and-pharmacodynamics
#7
E Patras de Campaigno, E Bondon-Guitton, G Laurent, F Montastruc, J L Montastruc, M Lapeyre-Mestre, F Despas
AIMS: To evaluate the risk of cardiac failure (CF) of 15 anticancer protein kinase inhibitors (PKIs) through a case/non-case analysis and to identify which PK(s) and pathways are involved in PKI-induced CF. METHODS: To evaluate the risk of CF, adjusted reporting odds ratios (aRORs) were calculated for the 15 anticancer PKIs in the WHO safety report database (VigiBase®). We realised a literature review to identify 21 PK possibly involved in CF caused by PKIs. Pearson's correlation coefficients (r) between aROR and affinity data of the 15 PKIs for the 21 PKs were calculated to identify the cellular target most likely involved in PKI-induced CF...
January 18, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28096936/treatment-options-in-advanced-renal-cell-carcinoma-after-first-line-treatment-with-vascular-endothelial-growth-factor-receptor-tyrosine-kinase-inhibitors
#8
REVIEW
Naveen S Basappa
Targeted therapy for metastatic renal cell carcinoma (mRCC) was introduced a decade ago and since then, a number of therapeutic options have been developed. Vascular endothelial growth factor-targeted therapy is the widely accepted first-line option for mRCC. After progression, treatment in the second-line setting has typically been with either axitinib or everolimus. However, with the advent of several new agents demonstrating efficacy in the second-line setting, including nivolumab, cabozantinib, and the combination of lenvatinib and everolimus, the treatment paradigm has shifted toward these novel therapies with improved patient outcomes...
November 2016: Canadian Urological Association Journal, Journal de L'Association des Urologues du Canada
https://www.readbyqxmd.com/read/28093138/re-efficacy-and-safety-of-axitinib-in-elderly-patients-with-metastatic-renal-cell-carcinoma
#9
Tomas L Griebling
No abstract text is available yet for this article.
February 2017: Journal of Urology
https://www.readbyqxmd.com/read/28052652/anti-angiogenic-therapy-in-patients-with-advanced-gastric-and-gastroesophageal-junction-cancer-a-systematic-review
#10
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/28044054/pituitary-metastasis-from-renal-cell-carcinoma-description-of-a-case-report
#11
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/28039049/axitinib-induced-pneumatosis-intestinalis-and-acute-acalculous-cholecystitis-in-a-patient-with-renal-cell-carcinoma
#12
Tomohiro Kameda, Kazuhiko Nakano, Masahiro Yamazaki, Takeshi Koshimizu, Tatsuo Morita
A 71-year-old man with metastatic renal cell carcinoma presented with abdominal pain during treatment with axitinib. The diagnoses were axitinib-induced pneumatosis intestinalis (PI) and acute acalculous cholecystitis (AC). The patient's condition improved with antibiotics, bowel rest, and discontinuation of the axitinib therapy. This is the first case report in the literature. PI and AC induced by other vascular endothelial growth factor receptor tyrosine kinase inhibitors are usually self-limiting upon discontinuation of those uses, but can be life-threatening in some cases...
December 27, 2016: Urology
https://www.readbyqxmd.com/read/28031424/the-dart-study-results-from-the-dose-escalation-and-expansion-cohorts-evaluating-the-combination-of-dalantercept-plus-axitinib-in-advanced-renal-cell-carcinoma
#13
Martin H Voss, Rupal S Bhatt, Elizabeth R Plimack, Brian I Rini, Robert S Alter, J Thaddeus Beck, Dawn Wilson, Xiaosha Zhang, Musa Mutyaba, Chad Glasser, Kenneth M Attie, Matthew L Sherman, Shuchi S Pandya, Michael Atkins
PURPOSE: Activin receptor-like kinase 1 (ALK1) is a novel target in angiogenesis. Concurrent targeting of ALK1 and vascular endothelial growth factor (VEGF) signaling results in augmented inhibition of tumor growth in renal cell carcinoma (RCC) xenograft models. Dalantercept is an ALK1 receptor-fusion protein that acts as a ligand trap for bone morphogenetic proteins (BMP) 9 and 10. The DART Study evaluated the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of dalantercept plus axitinib in patients with advanced RCC and determined the optimal dose for further testing...
December 28, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27980109/folate-hapten-mediated-immunotherapy-synergizes-with-vascular-endothelial-growth-factor-receptor-inhibitors-in-treating-murine-models-of-cancer
#14
N Achini Bandara, Cody D Bates, Yingjuan Lu, Emily K Hoylman, Philip S Low
The over-expression of folate receptors (FR) on many human cancers has led to the development of folate-linked drugs for the imaging and therapy of FR-expressing cancers. In a recent phase 1 clinical trial of late stage renal cell carcinoma patients, folate was exploited to deliver an immunogenic hapten, fluorescein, to FR+ tumor cells in an effort to render the cancer cells more immunogenic. Although >50% of the patients showed prolonged stable disease, all patients eventually progressed, suggesting that the folate-hapten immunotherapy was insufficient by itself to treat the cancer...
December 15, 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27972532/cost-effectivness-analysis-of-axitinib-in-the-treatment-of-metastatic-renal-cell-carcinoma-clinical-data-vs-rwe
#15
M Karbusicka, L Losenicky, P Mazan, J Doleckova, J Duba, M Kolek
No abstract text is available yet for this article.
November 2016: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/27972530/cost-effectiveness-analysis-of-using-everolimus-or-axitinib-in-patients-with-metastatic-renal-cell-carcinoma-who-have-failed-to-use-of-pazopanib-or-sunitinib-in-first-line-treatment
#16
M E Romero Prada, L M Huerfano, N C Roa Cardenas
No abstract text is available yet for this article.
November 2016: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/27936296/antiangiogenic-and-toxic-effects-of-genistein-usnic-acid-and-their-copper-complexes-in-zebrafish-embryos-at-different-developmental-stages
#17
Heidrun Draut, Tobias Rehm, Gerrit Begemann, Rainer Schobert
Angiogenesis plays a major role in the normal embryonic development and in diseases such as cancer. Drugs that control angiogenesis are an alternative way to tackle this disease. The polyphenols usnic acid 3, genistein 5, and daidzein 6 were tested for antiangiogenic and unwanted effects in zebrafish embryos whose blood vessel system resembles that of mammals. The established tyrosine kinase inhibitors axitinib 1 and tyrphostin AG490 2 were included for comparison. All compounds except 6 caused distinct antiangiogenic effects such as a concentration-dependent reduction of intersegmental vessels, dorsal longitudinal anastomotic vessels, subintestinal veins and secondary sprouts...
December 9, 2016: Chemistry & Biodiversity
https://www.readbyqxmd.com/read/27936076/angiogenic-capacity-of-periodontal-ligament-stem-cells-pretreated-with-deferoxamine-and-or-fibroblast-growth-factor-2
#18
Jessica Ratajczak, Petra Hilkens, Pascal Gervois, Esther Wolfs, Reinhilde Jacobs, Ivo Lambrichts, Annelies Bronckaers
Periodontal ligament stem cells (PDLSCs) represent a good source of multipotent cells for cell-based therapies in regenerative medicine. The success rate of these treatments is severely dependent on the establishment of adequate vasculature in order to provide oxygen and nutrients to the transplanted cells. Pharmacological preconditioning of stem cells has been proposed as a promising method to augment their therapeutic efficacy. In this study, the aim was to improve the intrinsic angiogenic properties of PDLSCs by in vitro pretreatment with deferoxamine (DFX; 100μM), fibroblast growth factor-2 (FGF-2; 10ng/mL) or both substances combined...
2016: PloS One
https://www.readbyqxmd.com/read/27926485/axitinib-induces-senescence-associated-cell-death-and-necrosis-in-glioma-cell-lines-the-proteasome-inhibitor-bortezomib-potentiates-axitinib-induced-cytotoxicity-in-a-p21-waf-cip1-dependent-manner
#19
Maria Beatrice Morelli, Consuelo Amantini, Massimo Nabissi, Claudio Cardinali, Matteo Santoni, Giovanni Bernardini, Angela Santoni, Giorgio Santoni
Glioblastoma is associated with a poor overall survival despite new treatment advances. Antiangiogenic strategies targeting VEGF based on tyrosine kinase inhibitors (TKIs) are currently undergoing extensive research for the treatment of glioma.Herein we demonstrated that the TKI axitinib induces DNA damage response (DDR) characterized by γ-H2AX phosphorylation and Chk1 kinase activation leading to G2/M cell cycle arrest and mitotic catastrophe in U87, T98 and U251 glioma cell lines. Moreover, we found that p21(Waf1/Cip1) increased levels correlates with induction of ROS and senescence-associated cell death in U87 and T98 cell lines, which are reverted by N-acetyl cysteine pretreatment...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/27922668/dual-inhibition-using-cabozantinib-overcomes-hgf-met-signaling-mediated-resistance-to-pan-vegfr-inhibition-in-orthotopic-and-metastatic-neuroblastoma-tumors
#20
Estelle Daudigeos-Dubus, Ludivine Le Dret, Olivia Bawa, Paule Opolon, Albane Vievard, Irène Villa, Jacques Bosq, Gilles Vassal, Birgit Geoerger
MET is expressed on neuroblastoma cells and may trigger tumor growth, neoangiogenesis and metastasis. MET upregulation further represents an escape mechanism to various anticancer treatments including VEGF signaling inhibitors. We developed in vitro a resistance model to pan-VEGFR inhibition and explored the simultaneous inhibition of VEGFR and MET in neuroblastoma models in vitro and in vivo using cabozantinib, an inhibitor of the tyrosine kinases including VEGFR2, MET, AXL and RET. Resistance in IGR-N91-Luc neuroblastoma cells under continuous in vitro exposure pressure to VEGFR1-3 inhibition using axitinib was associated with HGF and p-ERK overexpression...
January 2017: International Journal of Oncology
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