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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/27904768/combined-vegfr-and-ctla-4-blockade-increases-the-antigen-presenting-function-of-intratumoral-dcs-and-reduces-the-suppressive-capacity-of-intratumoral-mdscs
#2
Stephanie Du Four, Sarah K Maenhout, Simone P Niclou, Kris Thielemans, Bart Neyns, Joeri L Aerts
Melanoma brain metastases (MBM) occur in 10% to 50% of melanoma patients. They are often associated with a high morbidity and despite the improvements in the treatment of advanced melanoma, including immunotherapy, patients with MBM still have a poor prognosis. Antiangiogenic treatment was shown to reduce the immunosuppressive tumor microenvironment. Therefore we investigated the effect of the combination of VEGFR- and CTLA-4 blockade on the immune cells within the tumor microenvironment. In this study we investigated the effect of the combination of axitinib, a TKI against VEGFR-1, -2 and -3, with therapeutic inhibition of CTLA-4 in subcutaneous and intracranial mouse melanoma models...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27904651/sunitinib-in-the-treatment-of-metastatic-renal-cell-carcinoma
#3
REVIEW
Thomas A Schmid, Martin E Gore
Sunitinib is an oral multi-targeted tyrosine kinase inhibitor (TKI) that targets various receptors, including vascular endothelial growth factor receptors (VEGFRs). Sunitinib received approval in 2006 and became a standard treatment option in the first-line treatment of metastatic renal cell cancer (mRCC) after a phase III trial showed superiority compared with interferon alpha (IFN-α). Sunitinib has also shown activity in second-line treatment in several trials. Most of the combination trials with sunitinib with various agents have led to considerable toxicity without improving efficacy...
December 2016: Therapeutic Advances in Urology
https://www.readbyqxmd.com/read/27904083/novel-sulfonamide-derivatives-carrying-a-biologically-active-3-4-dimethoxyphenyl-moiety-as-vegfr-2-inhibitors
#4
Mostafa Mohammed Ghorab, Mansour Sulaiman Alsaid, Yassin Mohammed Nissan, Abdelkader Elbadawy Ashour, Abdullah Abdulalrahman Al-Mishari, Ashok Kumar, Sheikh Fayaz Ahmed
Novel sulfonamides 3-19 with a biologically active 3,4-dimethoxyphenyl moiety were designed and synthesized. The structures of the synthesized compounds were established using elemental analyses, IR, (1)H-NMR, (13)C-NMR spectral data and mass spectroscopy. All the synthesized compounds were evaluated for their in vitro anticancer activity against four cancer cell lines, namely human hepatocellular carcinoma (HepG2), human medulloblastoma (Daoy), human cervical cancer (HeLa), and human colon cancer (HT-29), by using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and dasatinib as the reference drug...
2016: Chemical & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/27902583/adverse-events-risk-associated-with-anti-vegfr-agents-in-the-treatment-of-advanced-nonsmall-cell-lung-cancer-a-meta-analysis
#5
Biao Gu, WenChuang Gao, HongJun Chu, Jian Gao, Zhi Fu, Hui Ding, JunJie Lv, QingQuan Wu
To perform this meta-analysis, we investigated the risk of the most clinically relevant adverse events related to antivascular endothelial growth factor receptor (VEGFR) agents in advanced nonsmall-cell lung cancer (NSCLC).A comprehensive literature search for studies published up to October 2015 was performed. Prospective randomized controlled phase II/III clinical trials that comparing therapy with or without anti-VEGFR agents for advanced NSCLC were included for analysis. Summary relative risk (RR) and 95% confidence intervals (CIs) were calculated using random effects or fixed effects according to the heterogeneity among included trials...
November 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27894589/discovery-and-preclinical-evaluation-of-7-benzyl-n-substituted-pyrrolo-3-2-d-pyrimidin-4-amines-as-single-agents-with-microtubule-targeting-effects-along-with-triple-acting-angiokinase-inhibition-as-antitumor-agents
#6
Roheeth Kumar Pavana, Shruti Choudhary, Anja Bastian, Michael A Ihnat, Ruoli Bai, Ernest Hamel, Aleem Gangjee
The utility of cytostatic antiangiogenic agents (AA) in cancer chemotherapy lies in their combination with cytotoxic chemotherapeutic agents. Clinical combinations of AA with microtubule targeting agents (MTAs) have been particularly successful. The discovery, synthesis and biological evaluations of a series of 7-benzyl-N-substituted-pyrrolo[3,2-d]pyrimidin-4-amines are reported. Novel compounds which inhibit proangiogenic receptor tyrosine kinases (RTKs) including vascular endothelial growth factor receptor-2 (VEGFR-2), platelet-derived growth factor receptor-β (PDGFR-β) and epidermal growth factor receptor (EGFR), along with microtubule targeting in single molecules are described...
November 15, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27894090/gremlin-promotes-retinal-pigmentation-epithelial-rpe-cell-proliferation-migration-and-vegf-production-via-activating-vegfr2-akt-mtorc2-signaling
#7
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
#8
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/27889393/triple-amirna-vegfrs-inhibition-in-pancreatic-cancer-improves-the-efficacy-of-chemotherapy-through-emt-regulation
#9
Jianfei Huang, Haijun Mei, Zhiyuan Tang, Jieying Li, Xiaojing Zhang, Yixiang Lu, Fang Huang, Qin Jin, Zhiwei Wang
Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with dismal outcome. Both novel prognostic markers and therapeutic targets are needed to improve the overall outcome of patients. Although single or double VEGFRs have been studied in PDAC, little is known about the role of triple combination of VEGFRs (VEGFR1, 2, and 3) in prognosis and therapy. We determined VEGFRs protein expression in 241 pancreatic tissues by tissue microarray immunohistochemistry (TMA-IHC), and correlated with patients' clinical characteristics and overall survival...
November 23, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/27884759/heterodimerisation-between-vegfr-1-and-vegfr-2-and-not-the-homodimers-of-vegfr-1-inhibit-vegfr-2-activity
#10
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
#11
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
#12
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
#13
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/27870831/asymmetric-division-coordinates-collective-cell-migration-in-angiogenesis
#14
Guilherme Costa, Kyle I Harrington, Holly E Lovegrove, Donna J Page, Shilpa Chakravartula, Katie Bentley, Shane P Herbert
The asymmetric division of stem or progenitor cells generates daughters with distinct fates and regulates cell diversity during tissue morphogenesis. However, roles for asymmetric division in other more dynamic morphogenetic processes, such as cell migration, have not previously been described. Here we combine zebrafish in vivo experimental and computational approaches to reveal that heterogeneity introduced by asymmetric division generates multicellular polarity that drives coordinated collective cell migration in angiogenesis...
November 21, 2016: Nature Cell Biology
https://www.readbyqxmd.com/read/27861852/phase-ii-clinical-trial-using-novel-peptide-cocktail-vaccine-as-a-postoperative-adjuvant-treatment-for-surgically-resected-pancreatic-cancer-patients
#15
Motoki Miyazawa, Masahiro Katsuda, Hiroyuki Maguchi, Akio Katanuma, Hiroshi Ishii, Masato Ozaka, Kenji Yamao, Hiroshi Imaoka, Manabu Kawai, Seiko Hirono, Ken-Ichi Okada, Hiroki Yamaue
We investigated peptide cocktail vaccine OCV-C01 containing epitope peptides derived from KIF20A, vascular endothelial growth factor receptor (VEGFR)1 and VEGFR2 combined with gemcitabine in the adjuvant treatment for resected pancreatic cancer patients. A single-arm multicenter phase II study was performed on 30 patients with pancreatic ductal carcinoma who underwent pancreatectomy. At each 28-day treatment cycle, patients received weekly subcutaneous injection of OCV-C01 for 48 weeks and gemcitabine was administered intravenously at 1,000 mg/m(2) on days 1, 8 and 15 for 24 weeks...
November 8, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27855622/the-role-of-the-antiangiogenetic-ramucirumab-in-the-treatment-of-advanced-non-small-cell-lung-cancer
#16
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
#17
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
#18
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
#19
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
#20
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
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