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https://www.readbyqxmd.com/read/28719152/a-first-in-human-phase-i-multicenter-open-label-dose-escalation-study-of-the-oral-raf-vegfr-2-inhibitor-raf265-in-locally-advanced-or-metastatic-melanoma-independent-from-braf-mutation-status
#1
Benjamin Izar, William Sharfman, F Stephen Hodi, Donald Lawrence, Keith T Flaherty, Ravi Amaravadi, Kevin B Kim, Igor Puzanov, Jeffrey Sosman, Reinhard Dummer, Simone M Goldinger, Lyhping Lam, Shefali Kakar, Zhongwen Tang, Oliver Krieter, David F McDermott, Michael B Atkins
To establish the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), safety profile, and anti-tumor efficacy of RAF265. We conducted a multicenter, open-label, phase-I, dose-escalation trial of RAF265, an orally available RAF kinase/VEGFR-2 inhibitor, in patients with advanced or metastatic melanoma. Pharmacokinetic (PK) analysis, pharmacodynamics (PD) and tumor response assessment were conducted. We evaluated metabolic tumor response by 18[F]-fluorodeoxyglucose-positron-emission tomography (FDG-PET), tissue biomarkers using immunohistochemistry (IHC), and modulators of angiogenesis...
July 18, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28718364/evaluation-of-epigenetic-inactivation-of-vascular-endothelial-growth-factor-receptors-in-head-and-neck-squamous-cell-carcinoma
#2
Yuki Misawa, Kiyoshi Misawa, Hideya Kawasaki, Atsushi Imai, Daiki Mochizuki, Ryuji Ishikawa, Shiori Endo, Masato Mima, Takeharu Kanazawa, Toshihide Iwashita, Hiroyuki Mineta
The aim of this study was to determine the methylation status of the genes encoding the vascular endothelial growth factor receptors and to evaluate the usefulness of VEGFR methylation as a prognostic indicator in head and neck squamous cell carcinoma. VEGFR messenger RNA expression and promoter methylation were examined in a panel of cell lines via quantitative reverse transcription and methylation-specific polymerase chain reaction, respectively. Promoter methylation was compared with clinical characteristics in 128 head and neck squamous cell carcinoma samples...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28718185/congenital-pulmonary-lymphangiectasia-a-disorder-not-only-of-fetoneonates
#3
Shi-Min Yuan
Congenital pulmonary lymphangiectasia (CPL) is a rare developmental disorder of the lung, characterized by dilation of pulmonary subpleural, interlobar, perivascular and peribronchial lymphatics. The incidence of CPL among stillborn and neonates was estimated to be <1%. The etiology of CPL is unknown. However, it has been suspected to be of a genetic background. Recent basic studies revealed that it might be caused by the FOXC2, Vegfr-3 and integrin α9β1gene mutations. A clinical diagnosis of CPL can be made much easier in full-term neonates who present with respiratory distress, pleural (especially chylous) effusions with or without generalized edema...
July 2017: Klinische Pädiatrie
https://www.readbyqxmd.com/read/28717175/snake-venom-vegf-vammin-induces-a-highly-efficient-angiogenic-response-in-skeletal-muscle-via-vegfr-2-nrp-specific-signaling
#4
Pyry I Toivanen, Tiina Nieminen, Johanna P Laakkonen, Tommi Heikura, Minna U Kaikkonen, Seppo Ylä-Herttuala
Vascular Endothelial Growth Factors (VEGFs) are promising molecules for the treatment of ischemic diseases by pro-angiogenic therapy. Snake venom VEGFs are a novel subgroup with unique receptor binding profiles and as such are potential new therapeutic agents. We determined the ligand-receptor interactions, gene regulation and angiogenic properties of Vipera ammodytes venom VEGF, Vammin, and compared it to the canonical angiogenic factor VEGF-A to evaluate the use of Vammin for therapeutic angiogenesis. Vammin efficiently induced VEGFR-2 mediated proliferation and expression of genes associated with proliferation, migration and angiogenesis...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28714017/targeting-vegfr-and-fgfr-in-head-and-neck-squamous-cell-carcinoma-in-vitro
#5
Roman C Brands, Luise M Knierim, Francesco De Donno, Valentin Steinacker, Stefan Hartmann, Axel Seher, Alexander C Kübler, Urs D A Müller-Richter
Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease characterized by a tumor microenvironment (TME) that overexpresses vascular endothelial growth factor receptor (VEGFR) and fibroblast growth factor receptor (FGFR), which can lead to neovascularization, tumor growth and metastasis. Therapeutic strategies inhibiting these signaling pathways might lead to innovative HNSCC treatments. Five HNSCC cell lines were characterized based on VEGFR1-3 and FGFR1-4 expression by sqRT-PCR and treated with three different tyrosine kinase inhibitors (TKIs) (nintedanib, dovitinib and pazopanib), all of which are effective against VEGFR and FGFR family members...
July 10, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28713958/lipo%C3%A2-prostaglandin-e1-modifies-cognitive-impairment-in-rats-with-vascular-cognitive-impairment-by-promoting-angiogenesis-via-the-vegf-vegfr-pathway
#6
Bohui Liu, Suping Zhang, Xifeng Xiong, Li Ling, Rui He, Muzhen Wang, Wanqing Deng, Zhihe Liu, Yi Li
The pathological mechanism of vascular cognitive impairment (VCI) involves ischemic lesions in the hippocampus. Prostaglandin E1 (PGE1) serves roles in the promotion of vascular endothelial growth factor (VEGF) expression, angiogenesis and enhances blood flow to ischemic regions. However, the effect of PGE1 on cognitive function in VCI rats and the underlying mechanism are unknown. In the current study, learning and memory function in VCI rats treated by lipo‑PGE1 injection was assessed through Morris Water Maze test...
July 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28712573/ve-cadherin-phosphorylation-regulates-endothelial-fluid-shear-stress-responses-through-the-polarity-protein-lgn
#7
Daniel E Conway, Brian G Coon, Madhusuthan Budatha, Paul T Arsenovic, Fabrizio Orsenigo, Florian Wessel, Jiasheng Zhang, Zhenwu Zhuang, Elisabetta Dejana, Dietmar Vestweber, Martin A Schwartz
Fluid shear stress due to blood flow on the vascular endothelium regulates blood vessel development, remodeling, physiology, and pathology [1, 2]. A complex consisting of PECAM-1, VE-cadherin, and vascular endothelial growth factor receptors (VEGFRs) that resides at endothelial cell-cell junctions transduces signals important for flow-dependent vasodilation, blood vessel remodeling, and atherosclerosis. PECAM-1 transduces forces to activate src family kinases (SFKs), which phosphorylate and transactivate VEGFRs [3-5]...
July 10, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28710508/risk-of-gastrointestinal-events-with-newly-approved-after-2011-vascular-endothelial-growth-factor-receptor-tyrosine-kinase-inhibitors-in-cancer-patients-a-meta-analysis-of-randomized-controlled-trials
#8
REVIEW
Jing Li, Jian Gu
PURPOSE: We performed a meta-analysis to systematically review the gastrointestinal (GI) events (diarrhea, nausea, vomiting, anorexia) of five newly approved (after 2011) VEGFR-TKIs in cancer patients. METHODS: The relevant studies of the randomized controlled trials (RCTs) in cancer patients treated with cabozantinib, vandetanib, lenvatinib, regorafenib, and axitinib were retrieved and the systematic evaluation was conducted. RESULTS: Forty-one randomized controlled trials and 10,860 patients were included...
July 15, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28707601/potential-role-of-natural-compounds-as-anti-angiogenic-agents-in-cancer
#9
Muthu K Shanmugam, Sudha Warrier, Alan Prem Kumar, Gautam Sethi, Frank Arfuso
BACKGROUND: Neovascularization, also known as angiogenesis, is the process of capillary sprouting from pre-existing blood vessels. This physiological process is a hallmark event in normal embryonic development as blood vessels generally supply both oxygen and nutrients to the cells of the body. Any disruption in this process can lead to the development of various chronic diseases, including cancer. In cancer, aberrant angiogenesis plays a prominent role in maintaining sustained tumor growth to malignant phenotypes and promoting metastasis...
July 12, 2017: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/28707479/axitinib-in-metastatic-renal-cell-carcinoma-beyond-the-second-line-setting
#10
Yoshiko Umeyama, Yoshiyuki Shibasaki, Hideyuki Akaza
Treatment options for advanced and metastatic renal cell carcinoma have advanced considerably in the past decade with the approval of several targeted agents, including axitinib. Axitinib is a potent and selective inhibitor of VEGFRs 1-3, and is well established as second-line treatment. This article summarizes factors to be considered when administering axitinib, such as individualized dose titration and axitinib-associated adverse events, in order to retain patients longer on treatment, which would likely lead to improved efficacy outcomes...
July 14, 2017: Future Oncology
https://www.readbyqxmd.com/read/28706139/a-phase-i-study-of-foretinib-plus-erlotinib-in-patients-with-previously-treated-advanced-non-small-cell-lung-cancer-canadian-cancer-trials-group-ind-196
#11
Natasha B Leighl, Ming-Sound Tsao, Geoffrey Liu, Dongsheng Tu, Cheryl Ho, Frances A Shepherd, Nevin Murray, John R Goffin, Garth Nicholas, Shingo Sakashita, Zhuo Chen, Lucia Kim, Jean Powers, Lesley Seymour, Glenwood Goss, Penelope A Bradbury
PURPOSE: MET and AXL mediate resistance to EGFR TKI in NSCLC. Foretinib, a MET/RON/AXL/TIE-2/VEGFR kinase inhibitor may overcome EGFR kinase resistance. This dose escalation study combined foretinib and erlotinib in advanced pretreated NSCLC patients. EXPERIMENTAL DESIGN: The primary endpoint was to define the RP2D of foretinib plus erlotinib as continuous oral daily dosing. Secondary objectives included safety, pharmacokinetics, response and potential biomarkers of response including EGFR, KRAS genotype, MET, AXL expression, and circulating HGF levels...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28700345/platelet-derived-growth-factor-c-promotes-human-melanoma-aggressiveness-through-activation-of-neuropilin-1
#12
Federica Ruffini, Lauretta Levati, Grazia Graziani, Simona Caporali, Maria Grazia Atzori, Stefania D'Atri, Pedro M Lacal
Despite recent progress in advanced melanoma therapy, identification of signalling pathways involved in melanoma switch from proliferative to invasive states is still crucial to uncover new therapeutic targets for improving the outcome of metastatic disease. Neuropilin-1 (NRP-1), a co-receptor for vascular endothelial growth factor-A (VEGF-A) tyrosine kinase receptors (VEGFRs), has been suggested to play a relevant role in melanoma progression. NRP-1 can be activated by VEGF-A also in the absence of VEGFRs, triggering specific signal transduction pathways (e...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28695268/risk-of-venous-and-arterial-thromboembolic-events-associated-with-vegfr-tkis-a-meta-analysis
#13
Bo Liu, Fengxia Ding, Deying Zhang, Guang-Hui Wei
The reported incidence of arterial and venous thromboembolic events varies markedly between VEGFR-TKI-related clinical trials. Here, we performed a meta-analysis to determine the incidence and the relative risk (RR) of venous thromboembolism events (VTEs) and arterial thromboembolic events (ATEs) associated with these agents. Databases (PubMed, Web of Science) were searched for relevant studies. Statistical analyses were conducted to calculate the summary incidences, RRs and 95% confidence intervals (CIs) using either random-effects or fixed-effects models according to the heterogeneity of the included studies...
July 10, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28687807/efficient-activation-of-the-lymphangiogenic-growth-factor-vegf-c-requires-the-c-terminal-domain-of-vegf-c-and-the-n-terminal-domain-of-ccbe1
#14
Sawan Kumar Jha, Khushbu Rauniyar, Terhi Karpanen, Veli-Matti Leppänen, Pascal Brouillard, Miikka Vikkula, Kari Alitalo, Michael Jeltsch
The collagen- and calcium-binding EGF domains 1 (CCBE1) protein is necessary for lymphangiogenesis. Its C-terminal collagen-like domain was shown to be required for the activation of the major lymphangiogenic growth factor VEGF-C (Vascular Endothelial Growth Factor-C) along with the ADAMTS3 (A Disintegrin And Metalloproteinase with Thrombospondin Motifs-3) protease. However, it remained unclear how the N-terminal domain of CCBE1 contributed to lymphangiogenic signaling. Here, we show that efficient activation of VEGF-C requires its C-terminal domain both in vitro and in a transgenic mouse model...
July 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28687044/dual-modified-liposome-codelivery-of-doxorubicin-and-vincristine-improve-targeting-and-therapeutic-efficacy-of-glioma
#15
Yue Zhang, Meifang Zhai, Zhijiang Chen, Xiaoyang Han, Fanglin Yu, Zhiping Li, Xiangyang Xie, Cuiyan Han, Lian Yu, Yang Yang, Xingguo Mei
Therapeutic outcome for the treatment of glioma was often limited due to drug resistance and low permeability of drug across the multiple physiological barriers, including the blood-brain barrier (BBB), and the blood-tumor barrier (BTB). In order to overcome these hurdles, we designed T7 and (D)A7R dual peptides-modified liposomes (abbreviated as T7/(D)A7R-LS) to efficiently co-delivery doxorubicin (DOX) and vincristine (VCR) to glioma in this study. T7 is a seven-peptide ligand of transferrin receptors (TfR) capable of circumventing the BBB and then targeting glioma...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28686443/identification-of-peptidic-antagonists-of-vascular-endothelial-growth-factor-receptor-1-by-scanning-the-binding-epitopes-of-its-ligands
#16
Lei Wang, Lingyu Zhou, Marie Reille-Seroussi, Nathalie Gagey-Eilstein, Sylvain Broussy, Tianyu Zhang, Lili Ji, Michel Vidal, Wang-Qing Liu
Cancer angiogenesis is mainly initiated by the vascular endothelial growth factors (VEGFs). Based on the reported crystal structures of three natural ligands (VEGF-A, -B and PlGF) with the major receptors VEGFR-1 and VEGFR-2, we scanned receptor-binding epitopes of these ligands by designing linear and cyclic peptides in aim to disrupt the VEGF-A/VEGFR-1 interaction, which is implicated in cancer development. The ability of peptides to inhibit this interaction was evaluated by an ELISA-based assay. Several peptides, especially those mimicking loop one (L1) of these ligands that binds primarily to domain D3 of VEGFRs, have demonstrated higher inhibition for VEGF-A/VEGFR-1 binding...
July 7, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28685689/arylurea-derivatives-a-class-of-potential-cancer-targeting-agents
#17
Jia-Nian Chen, De-Wen Wu, Ting Li, Kang-Jian Yang, Li Cheng, Zu-Ping Zhou, Shi-Ming Pu, Wan-Hua Lin
Arylurea derivatives, an important class of small molecules, have received considerable attention in recent years due to their wide range of biological applications. Various molecular targeted agents with arylurea scaffold as potential enzyme/receptor inhibitors were constructed with the successful development of sorafenib and regorafenib. This review focuses on those arylureas possessing anti-cancer activities from 2010 to date. According to their different mechanisms of action, these arylureas are divided into the following six categories: (1) Ras/Raf/MEK/ERK signaling pathway inhibitors; (2) tumor angiogenesis inhibitors, their targets include vascular endothelial growth factor receptors (VEGFRs), fibroblast growth factor receptors (FGFRs), platelet-derived growth factor receptors (PDGFRs), epidermal growth factor receptors (EGFRs), insulin-like growth factor 1 receptor (IGF-1R), Fms-like tyrosine kinase 3 (FLT3), c-Kit, MET, and Smoothened (Smo); (3) PI3K/AKT/mTOR signaling pathway inhibitors; (4) cell cycle inhibitors, their targets include checkpoint kinases (Chks), cyclin-dependent kinases (CDKs), Aurora, SUMO activating enzyme 1 (SUMO E1), tubulin, and DNA; (5) tumor differentiation, migration, and invasion inhibitors, their targets include matrix metalloproteinases (MMPs), LIM kinase (Limk), nicotinamide phosphoribosyltransferase (Nampt), and histone deacetylase (HDAC); (6) arylureas from the rational modification of natural products...
July 7, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28680747/arginase-inhibition-suppresses-lung-metastasis-in-the-4t1-breast-cancer-model-independently-of-the-immunomodulatory-and-anti-metastatic-effects-of-vegfr-2-blockade
#18
Chiara Secondini, Oriana Coquoz, Lorenzo Spagnuolo, Thibaud Spinetti, Sanam Peyvandi, Laura Ciarloni, Francesca Botta, Carole Bourquin, Curzio Rüegg
Tumor angiogenesis promotes tumor growth and metastasis. Anti-angiogenic therapy in combination with chemotherapy is used for the treatment of metastatic cancers, including breast cancer but therapeutic benefits are limited. Mobilization and accumulation of myeloid-derived suppressor cells (MDSC) during tumor progression and therapy have been implicated in metastasis formation and resistance to anti-angiogenic treatments. Here, we used the 4T1 orthotopic syngenic mouse model of mammary adenocarcinoma to investigate the effect of VEGF/VEGFR-2 axis inhibition on lung metastasis, MDSC and regulatory T cells (Tregs)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28679123/advanced-alveolar-soft-part-sarcoma-responds-to-apatinib
#19
Yong Zhou, Fan Tang, Yiying Wang, Li Min, Yi Luo, Wenli Zhang, Rui Shi, Hong Duan, Chongqi Tu
Alveolar soft part sarcoma (ASPS) is a rare, hypervascular soft tissue sarcoma with a low chemotherapy response rate. Here, we report an ASPS case with multiple lung metastases on initial presentation. The primary tumor, a hypervascular soft tissue mass 4.1×3.2×2.0 cm, located in the right thigh, was resected prior to chemotherapy. The patient suffered disease progression after two cycles of gemcitabine-docetaxel treatment. Immunohistochemical examination of the tumor tissue revealed strong positive staining for vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR-2)...
June 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28678611/successful-treatment-of-advanced-pancreatic-liposarcoma-with-apatinib-a-case-report-and-literature-review
#20
Tao Han, Yuting Luan, Ying Xu, Xiaodan Yang, Jing Li, Ran Liu, Qing Li, Zhendong Zheng
Pancreatic liposarcoma is a malignant tumor originated from the pancreas mesenchymal tissue and mostly presented in skin, subcutaneous, periosteum, and long bone on both sides. Both conventional chemotherapy and radiotherapy have limited efficacy and poor prognosis for advanced pancreatic liposarcoma. Here, we reported a case of advanced pancreatic liposarcoma and reviewed the literature specific for liposarcoma of the pancreas and discuss the emerging options of treatment. The patient was treated with apatinib and a cross-line rescue therapy combined with paclitaxel after progressive disease...
July 5, 2017: Cancer Biology & Therapy
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