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https://www.readbyqxmd.com/read/27909994/cabozantinib-a-review-in-advanced-renal-cell-carcinoma
#1
Zaina T Al-Salama, Gillian M Keating
The multiple tyrosine kinase inhibitor (TKI) cabozantinib (Cabometyx™) is approved in the USA for the treatment of patients with advanced renal cell carcinoma (RCC) who have received prior antiangiogenic therapy. In the EU, cabozantinib is indicated for the treatment of advanced RCC in adults following prior vascular endothelial growth factor (VEGF)-targeted therapy. In adults with advanced or metastatic clear-cell RCC who had previously received VEGF receptor (VEGFR) TKIs, progression-free survival (PFS) and overall survival (OS) were significantly prolonged in patients who received oral cabozantinib versus oral everolimus in the pivotal METEOR trial...
December 1, 2016: Drugs
https://www.readbyqxmd.com/read/27894090/gremlin-promotes-retinal-pigmentation-epithelial-rpe-cell-proliferation-migration-and-vegf-production-via-activating-vegfr2-akt-mtorc2-signaling
#2
Yuan Liu, Zhijun Chen, Haixia Cheng, Juan Chen, Jing Qian
Retinopathy of prematurity (ROP) is characterized by late-phase pathologic retinal vasoproliferation. Gremlin is a novel vascular endothelial growth factors (VEGF) receptor 2 (VEGFR2) agonist and promotes angiogenic response. We demonstrated that gremlin expression was significantly increased in retinas of ROP model mice, which was correlated with VEGF upregulation. In retinal pigmentation epithelial (RPE) cells, gremlin activated VEGFR2-Akt-mTORC2 (mammalian target of rapamycin complex 2) signaling, and promoted cell proliferation, migration and VEGF production...
November 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27891227/society-for-immunotherapy-of-cancer-consensus-statement-on-immunotherapy-for-the-treatment-of-renal-cell-carcinoma
#3
Brian I Rini, David F McDermott, Hans Hammers, William Bro, Ronald M Bukowski, Bernard Faba, Jo Faba, Robert A Figlin, Thomas Hutson, Eric Jonasch, Richard W Joseph, Bradley C Leibovich, Thomas Olencki, Allan J Pantuck, David I Quinn, Virginia Seery, Martin H Voss, Christopher G Wood, Laura S Wood, Michael B Atkins
Immunotherapy has produced durable clinical benefit in patients with metastatic renal cell cancer (RCC). In the past, patients treated with interferon-alpha (IFN) and interleukin-2 (IL-2) have achieved complete responses, many of which have lasted for multiple decades. More recently, a large number of new agents have been approved for RCC, several of which attack tumor angiogenesis by inhibiting vascular endothelial growth factors (VEGF) and VEGF receptors (VEGFR), as well as tumor metabolism, inhibiting the mammalian target of rapamycin (mTOR)...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27884759/heterodimerisation-between-vegfr-1-and-vegfr-2-and-not-the-homodimers-of-vegfr-1-inhibit-vegfr-2-activity
#4
Meng Cai, Keqing Wang, Colin E Murdoch, Yuchun Gu, Asif Ahmed
Vascular endothelial growth factor (VEGF) signaling is tightly regulated by specific VEGF receptors (VEGF-R). Recently, we identified heterodimerisation between VEGFR-1 and VEGFR-2 (VEGFR1-2) to regulate VEGFR-2 function. However, both the mechanism of action and the relationship with VEGFR-1 homodimers remain unknown. The current study shows that activation of VEGFR1-2, but not VEGFR-1 homodimers, inhibits VEGFR-2 receptor phosphorylation under VEGF stimulation in human endothelial cells. Furthermore, inhibition of phosphatidylinositol 3-kinase (PI3K) increases VEGFR-2 phosphorylation under VEGF stimulation...
November 21, 2016: Vascular Pharmacology
https://www.readbyqxmd.com/read/27879653/ellagic-acid-inhibits-bladder-cancer-invasiveness-and-in-vivo-tumor-growth
#5
Claudia Ceci, Lucio Tentori, Maria Grazia Atzori, Pedro M Lacal, Elena Bonanno, Manuel Scimeca, Rosella Cicconi, Maurizio Mattei, Maria Gabriella de Martino, Giuseppe Vespasiani, Roberto Miano, Grazia Graziani
Ellagic acid (EA) is a polyphenolic compound that can be found as a naturally occurring hydrolysis product of ellagitannins in pomegranates, berries, grapes, green tea and nuts. Previous studies have reported the antitumor properties of EA mainly using in vitro models. No data are available about EA influence on bladder cancer cell invasion of the extracellular matrix triggered by vascular endothelial growth factor-A (VEGF-A), an angiogenic factor associated with disease progression and recurrence, and tumor growth in vivo...
November 22, 2016: Nutrients
https://www.readbyqxmd.com/read/27878275/method-for-in%C3%A2-vitro-differentiation-of-bone-marrow-mesenchymal-stem-cells-into-endothelial-progenitor-cells-and-vascular-endothelial-cells
#6
Qihong Wang, Weifeng Zhang, Guifen He, Huifang Sha, Zhe Quan
Vascular development is a regulated process and is dependent on the participation and differentiation of many cell types including the proliferation and migration of vascular endothelial cells and differentiation of endothelial progenitor cells (EPCs) to mesodermal precursor cells. Thus, reconstitution of this process in vitro necessitates providing ambient conditions for generating and culturing EPCs in vitro and differentiating them to vascular endothelial cells. In the present study, we developed methods to differentiate bone marrow mesenchymal stem cells (MSC) into EPCs and to vascular endothelial cells...
November 18, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27878269/marmesin-mediated-suppression-of-vegf-vegfr-and-integrin%C3%A2-%C3%AE-1-expression-its-implication-in-non-small-cell-lung-cancer-cell-responses-and-tumor-angiogenesis
#7
Jae Hyeon Kim, Min Su Kim, Bo Hee Lee, Jin-Kyu Kim, Eun-Kyung Ahn, Hye-Jin Ko, Young-Rak Cho, Sang-Jin Lee, Gyu-Un Bae, Yong Kee Kim, Joa Sub Oh, Dong-Wan Seo
In the present study, we investigated the effects and molecular mechanism of marmesin, a natural coumarin compound isolated from Broussonetia kazinoki, on non-small cell lung cancer (NSCLC) cell responses and tumor angiogenesis. Marmesin abrogated mitogen-stimulated proliferation and invasion in both p53 wild-type A549 and p53-deficient H1299 NSCLC cells. These antitumor activities of marmesin were mediated by the inactivation of mitogenic signaling pathways and downregulation of cell signaling-related proteins including vascular endothelial growth factor receptor-2 (VEGFR-2), integrin β1, integrin-linked kinase and matrix metalloproteinases-2...
November 15, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27855622/the-role-of-the-antiangiogenetic-ramucirumab-in-the-treatment-of-advanced-non-small-cell-lung-cancer
#8
Paolo Maione, Assunta Sgambato, Francesca Casaluce, Paola Claudia Sacco, Giuseppe Santabarbara, Antonio Rossi, Cesare Gridelli
Angiogenesis is one of the most important phenomena sustaining tumor development and metastatization, including for non small cell lung cancer (NSCLC). A dominant role in angiogenesis is played by the vascular endothelial growth factor (VEGF) and its signalling pathway. Ramucirumab, is a fully human immunoglobulin G1 monoclonal antibody that binds to the extracellular domain of the VEGF receptor-2 (VEGFR-2) with high specificity and affinity blocking the interaction of VEGFR-2 and VEGF ligands, thus inhibiting their signaling pathways and the consequential endothelial proliferation and migration...
November 18, 2016: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/27855197/efficacy-of-anti-vegf-vegfr-agents-on-animal-models-of-endometriosis-a-systematic-review-and-meta-analysis
#9
Shuangge Liu, Xiaoyan Xin, Teng Hua, Rui Shi, Shuqi Chi, Zhishan Jin, Hongbo Wang
BACKGROUND/OBJECTIVE: Vascular endothelial growth factor (VEGF) is the most important promotor of angiogenesis. Some studies indicate that anti-angiogenic agents that interfere with VEGF and its receptor (VEGFR), i.e., anti-VEGF/VEGFR agents, may be applied to treat endometriosis. This meta-analysis investigated the efficacy of anti-VEGF/VEGFR agents in animal models of endometriosis. METHODS: A systematic literature search was performed for animal studies published in English or Chinese from January 1995 to June 2016, which evaluated the effect of anti-VEGF/VEGFR agents on endometriosis...
2016: PloS One
https://www.readbyqxmd.com/read/27853960/phase-ii-study-of-tivozanib-an-oral-vegfr-inhibitor-in-patients-with-recurrent-glioblastoma
#10
Jayashree Kalpathy-Cramer, Vyshak Chandra, Xiao Da, Yangming Ou, Kyrre E Emblem, Alona Muzikansky, Xuezhu Cai, Linda Douw, John G Evans, Jorg Dietrich, Andrew S Chi, Patrick Y Wen, Stephen Stufflebeam, Bruce Rosen, Dan G Duda, Rakesh K Jain, Tracy T Batchelor, Elizabeth R Gerstner
Targeting tumor angiogenesis is a potential therapeutic strategy for glioblastoma because of its high vascularization. Tivozanib is an oral pan-VEGF receptor tyrosine kinase inhibitor that hits a central pathway in glioblastoma angiogenesis. We conducted a phase II study to test the effectiveness of tivozanib in patients with recurrent glioblastoma. Ten adult patients were enrolled and treated with tivozanib 1.5 mg daily, 3 weeks on/1 week off in 28-day cycles. Brain MRI and blood biomarkers of angiogenesis were performed at baseline, within 24-72 h of treatment initiation, and monthly thereafter...
November 16, 2016: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/27852824/differential-receptor-binding-and-regulatory-mechanisms-for-the-lymphangiogenic-growth-factors-vegf-c-and-vegf-d
#11
Natalia Davydova, Nicole C Harris, Sally Roufail, Sophie Paquet-Fifield, Musarat Ishaq, Victor A Streltsov, Steven P Williams, Tara Karnezis, Steven A Stacker, Marc G Achen
VEGF-C(2) and VEGF-D are secreted glycoproteins that induce angiogenesis and lymphangiogenesis in cancer, thereby promoting tumor growth and spread. They exhibit structural homology and activate VEGFR-2 and VEGFR-3, receptors on endothelial cells that signal for growth of blood vessels and lymphatics. VEGF-C and VEGF-D were thought to exhibit similar bioactivities, yet recent studies indicated distinct signalling mechanisms, e.g. tumor-derived VEGF-C promoted expression of the prostaglandin biosynthetic enzyme COX-2 in lymphatics, a response thought to facilitate metastasis via the lymphatic vasculature, whereas VEGF-D did not...
November 16, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27852069/acidic-ph-reduces-vegf-mediated-endothelial-cell-responses-by-downregulation-of-vegfr-2-relevance-for-anti-angiogenic-therapies
#12
Seraina Faes, Emilie Uldry, Anne Planche, Tania Santoro, Catherine Pythoud, Nicolas Demartines, Olivier Dormond
Anti-angiogenic treatments targeting the vascular endothelial growth factor or its receptors have shown clinical benefits. However, impact on long-term survival remains limited. Solid tumors display an acidic microenvironment that profoundly influences their biology. Consequences of acidity on endothelial cells and anti-angiogenic therapies remain poorly characterized and hence are the focus of this study. We found that exposing endothelial cells to acidic extracellular pH resulted in reduced cell proliferation and migration...
November 12, 2016: Oncotarget
https://www.readbyqxmd.com/read/27852059/avian-leukosis-virus-subgroup-j-induces-vegf-expression-via-nf-%C3%AE%C2%BAb-pi3k-dependent-il-6-production
#13
Yanni Gao, Yao Zhang, Yongxiu Yao, Xiaolu Guan, Yongzhen Liu, Xiaole Qi, Yongqiang Wang, Changjun Liu, Yanping Zhang, Honglei Gao, Venugopal Nair, Xiaomei Wang, Yulong Gao
Avian leukosis virus subgroup J (ALV-J) is an oncogenic virus causing hemangiomas and myeloid tumors in chickens. Interleukin-6 (IL-6) is a multifunctional pro-inflammatory interleukin involved in many types of cancer. We previously demonstrated that IL-6 expression was induced following ALV-J infection in chickens. The aim of this study is to characterize the mechanism by which ALV-J induces IL-6 expression, and the role of IL-6 in tumor development. Our results demonstrate that ALV-J infection increases IL-6 expression in chicken splenocytes, peripheral blood lymphocytes, and vascular endothelial cells...
November 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/27851787/euterpe-oleracea-extract-a%C3%A3-a%C3%A3-is-a-promising-novel-pharmacological-therapeutic-treatment-for-experimental-endometriosis
#14
Daniel Escorsim Machado, Karina Cristina Rodrigues-Baptista, Jessica Alessandra-Perini, Roberto Soares de Moura, Thiago Alves Dos Santos, Kariny Gomes Pereira, Yasmin Marinho da Silva, Pergentino José Cunha Souza, Luiz Eurico Nasciutti, Jamila Alessandra Perini
This study investigated the therapeutic potential of Euterpe oleracea extract (açaí) on the growth and survival of endometriotic lesions using an experimental model. Twenty female Sprague-Dawley rats were randomized into two groups after the implantation and establishment of autologous endometrium onto the peritoneum abdominal wall and treated with 200 mg/kg hydroalcoholic solution extract from açaí stone or vehicle via gastric tube for 30 consecutive days. Body weight, lesion surface areas, histological and immunohistochemistry analyses of vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR-2), metalloproteinase-9 (MMP-9), cyclooxygenase-2 (COX-2) and F4-80 were performed...
2016: PloS One
https://www.readbyqxmd.com/read/27849428/germline-polymorphisms-of-the-vegf-pathway-predict-recurrence-in-non-advanced-differentiated-thyroid-cancer
#15
Vincenzo Marotta, Concetta Sciammarella, Mario Capasso, Alessandro Testori, Claudia Pivonello, Maria Grazia Chiofalo, Claudio Gambardella, Marica Grasso, Antonio Antonino, Annamaria Annunziata, Paolo Emidio Macchia, Rosario Pivonello, Luigi Santini, Gerardo Botti, Simona Losito, Luciano Pezzullo, Annamaria Colao, Antongiulio Faggiano
CONTEXT: Angiogenesis is an hallmark of cancer and is mainly determined by genetic background, rather than environment. Germline single nucleotide polymorphisms (SNPs) of VEGF-pathway have demonstrated prognostic value in different tumours. OBJECTIVES: Main: testing prognostic value of germline SNPs of VEGF-pathway in non-advanced DTC. Secondary: correlating analyzed SNPs with microvessel density (MVD). DESIGN: Multicenter, retrospective, observational study...
November 16, 2016: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27846380/pulmonary-vasculopathy-associated-with-figf-gene-mutation
#16
Evan Bailey, Ye Cui, Alicia Casey, Joan M Stoler, Xingbin Ai, Dongdong Ma, Robert Handin, Piotr Sliz, Sara O Vargas, Souheil Y El-Chemaly
Vascular endothelial growth factor (VEGF)-D is capable of inducing angiogenesis and lymphangiogenesis through signaling via VEGF receptor (VEGFR)-2 and VEGFR-3, respectively. Mutations in the FIGF (c-fos-induced growth factor) gene encoding VEGF-D have not been reported previously. We describe a young male with a hemizygous mutation in the X-chromosome gene FIGF (c.352 G>A) associated with early childhood respiratory deficiency. Histologically, lungs showed ectatic pulmonary arteries and pulmonary veins...
November 12, 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27835047/cabozantinib-for-the-treatment-of-renal-cell-carcinoma
#17
Bernard Escudier, Julie C Lougheed, Laurence Albiges
Agents that target the vascular endothelial growth factor (VEGF) or mammalian target of rapamycin (mTOR) pathway as well as the PD-1 checkpoint inhibitor nivolumab are standard therapies for advanced renal cell carcinoma (RCC). Recently, cabozantinib, an inhibitor of MET, VEGF receptors, and AXL, was approved by the FDA and European Commission based on improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) compared to standard of care treatment with everolimus in a randomized phase 3 trial in advanced RCC after prior VEGFR-tyrosine kinase inhibitor (TKI) therapy...
November 22, 2016: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/27834196/adenosine-triphosphate-is-a-critical-determinant-for-vegfr-signal-during-hypoxia
#18
Abdullah Al Mamun, Hisaki Hayashi, Miho Sakima, Motohiko Sato
Hypoxia induces angiogenesis through the VEGF signaling pathway; however, signal propagation of VEGF under hypoxia is not understood fully. In this study, we examined alterations of VEGF signaling under hypoxia and its determinant in endothelial cells. To analyze VEGF signaling during hypoxia, human umbilical vein endothelial cells (HUVECs) were exposed to 3 h hypoxia (1% O2), followed by 3 h reoxygenation or 12 h hypoxia. Hypoxia induced the expression of VEGF mRNA; however, it was not associated with an increase of tube formation by HUVECs...
November 9, 2016: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/27833959/ultrastructure-and-histomorphometric-analysis-of-human-umbilical-cord-vessels-in-preeclampsia-a-potential-role-of-vegf-vegfr-1-and-vegfr-2
#19
Shaima M Almasry, Amr K Elfayomy, Hala E Hashem
AIM: This study aimed to analyze the ultrastructure and histomorphometric changes of the human umbilical cord vessels of preeclampsia compared to healthy pregnancies and the possible role of vascular endothelial growth factor (VEGF) and its receptors. MATERIALS AND METHODS: Umbilical cord (UC) specimens were collected between August, 2014 and July, 2015. Histomorphometric analysis of UC vessels was performed utilizing an image analysis system. Cellular localization of VEGF, VEGFR-1 (VEGF receptor-1) and VEGFR-2 (VEGF receptor-2) were examined in immunohistochemically-stained sections of UC from 45 pregnancies with preeclampsia (PE) and 40 healthy pregnancies...
2016: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
https://www.readbyqxmd.com/read/27833450/the-era-of-anti-vascular-endothelial-growth-factor-vegf-drugs-in-ophthalmology-vegf-and-anti-vegf-therapy
#20
REVIEW
Dorota Pożarowska, Piotr Pożarowski
Angiogenesis is a clue process for tissue development and function, both in normal and pathological conditions. This process is regulated by multiple molecular systems. One of the most potent is vascular endothelial growth factor (VEGF) and its receptor (VEGFR) system. Members of this family are involved in new vessel formation in embryogenesis and maturation, as well as in reparative or pathological reactions in later stages. They play a substantial role in regeneration, inflammation, wound healing, as well as in cancer pathology...
2016: Central-European Journal of Immunology
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