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https://www.readbyqxmd.com/read/28915889/anti-fibrotic-efficacy-of-nintedanib-in-pulmonary-fibrosis-via-the-inhibition-of-fibrocyte-activity
#1
Seidai Sato, Shintaro Shinohara, Shinya Hayashi, Shun Morizumi, Shuichi Abe, Hiroyasu Okazaki, Yanjuan Chen, Hisatsugu Goto, Yoshinori Aono, Hirohisa Ogawa, Kazuya Koyama, Haruka Nishimura, Hiroshi Kawano, Yuko Toyoda, Hisanori Uehara, Yasuhiko Nishioka
BACKGROUND: Nintedanib, a tyrosine kinase inhibitor that is specific for platelet-derived growth factor receptors (PDGFR), fibroblast growth factor receptors (FGFR), and vascular endothelial growth factor receptors (VEGFR), has recently been approved for idiopathic pulmonary fibrosis. Fibrocytes are bone marrow-derived progenitor cells that produce growth factors and contribute to fibrogenesis in the lungs. However, the effects of nintedanib on the functions of fibrocytes remain unclear...
September 15, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28914404/development-and-characterization-of-hybrid-tubular-structure-of-plcl-porous-scaffold-with-hmscs-ecs-cell-sheet
#2
Azizah Intan Pangesty, Takaaki Arahira, Mitsugu Todo
Tissue engineering offers an alternate approach to providing vascular graft with potential to grow similar with native tissue by seeding autologous cells into biodegradable scaffold. In this study, we developed a combining technique by layering a sheet of cells onto a porous tubular scaffold. The cell sheet prepared from co-culturing human mesenchymal stem cells (hMSCs) and endothelial cells (ECs) were able to infiltrate through porous structure of the tubular poly (lactide-co-caprolactone) (PLCL) scaffold and further proliferated on luminal wall within a week of culture...
September 15, 2017: Journal of Materials Science. Materials in Medicine
https://www.readbyqxmd.com/read/28904226/tumor-lymphangiogenesis-promotes-t-cell-infiltration-and-potentiates-immunotherapy-in-melanoma
#3
Manuel Fankhauser, Maria A S Broggi, Lambert Potin, Natacha Bordry, Laura Jeanbart, Amanda W Lund, Elodie Da Costa, Sylvie Hauert, Marcela Rincon-Restrepo, Christopher Tremblay, Elena Cabello, Krisztian Homicsko, Olivier Michielin, Douglas Hanahan, Daniel E Speiser, Melody A Swartz
In melanoma, vascular endothelial growth factor-C (VEGF-C) expression and consequent lymphangiogenesis correlate with metastasis and poor prognosis. VEGF-C also promotes tumor immunosuppression, suggesting that lymphangiogenesis inhibitors may be clinically useful in combination with immunotherapy. We addressed this concept in mouse melanoma models with VEGF receptor-3 (VEGFR-3)-blocking antibodies and unexpectedly found that VEGF-C signaling enhanced rather than suppressed the response to immunotherapy. We further found that this effect was mediated by VEGF-C-induced CCL21 and tumor infiltration of naïve T cells before immunotherapy because CCR7 blockade reversed the potentiating effects of VEGF-C...
September 13, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28882731/danggui-buxue-decoction-promotes-angiogenesis-by-up-regulation-of-vegfr1-2-expressions-and-down-regulation-of-svegfr1-2-expression-in-myocardial-infarction-rat
#4
Guanying Hu, Peng Yang, Yu Zeng, Sanyin Zhang, Jiage Song
BACKGROUND: The traditional herbal compound Danggui Buxue decoction (DBD), has long been used for the prevention and treatment of cardiovascular diseases, however, the underlying molecular mechanism for its effect remains still unknown. So this study would to investigate the effect of DBD on cardiac damage induced by myocardial infarction (MI) challenge. METHODS: SD Rats with ligation of left anterior descending (LAD) coronary artery were randomly divided into MI, MI plus Betaloc Zok, MI plus DBD high dose, and MI plus DBD low dose group, together with sham-operated group...
September 4, 2017: Journal of the Chinese Medical Association: JCMA
https://www.readbyqxmd.com/read/28881773/apatinib-inhibits-vegfr-2-and-angiogenesis-in-an-in-vivo-murine-model-of-nasopharyngeal-carcinoma
#5
Qiu-Xia Peng, Yun-Wei Han, Yan-Ling Zhang, Jie Hu, Juan Fan, Shao-Zhi Fu, Shan Xu, Qiang Wan
Angiogenesis is initiated by the activation of the vascular epidermal growth factor receptor-2 (VEGFR-2) by the vascular epidermal growth factor (VEGF) ligand. Overexpression of VEGFR-2 increases the growth of nasopharyngeal carcinomas (NPC). Apatinib (YN968D1) is a highly-selective inhibitor of VEGFR-2, but its effects on NPC have not been hitherto investigated. In the present study, CNE-2 NPC cells were xenografted into 132 nude mice, which were treated with one of 6 drug regimens of apatinib administered alone or in combination with cisplatin (DDP)...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28874077/effects-of-sunitinib-and-bevacizumab-on-vegf-and-mirna-levels-on-corneal-neovascularization
#6
Harun Cakmak, Esra Gokmen, Gokay Bozkurt, Tolga Kocaturk, Kemal Ergin
AIM: To evaluate the effects of sunitinib (0.5mg/ml) and bevacizumab (5mg/ml) on VEGF-A, VEGFR-2 and microRNA (miRNA) levels on corneal neovascularization. METHODS: In this study, corneal neovascularization was induced by silver nitrate application to the cornea, and 40 Albino male rats were equally divided into 4 subgroups: Group 1 (Sunitinib): After silver nitrate application to the cornea, 0.5mg/ml sunitinib eyedrop was administered twice daily for two weeks...
September 5, 2017: Cutaneous and Ocular Toxicology
https://www.readbyqxmd.com/read/28869531/potential-application-of-eicosapentaenoic-acid-monoacylglyceride-in-the-management-of-colorectal-cancer
#7
Caroline Morin, Enrique Rodríguez, Pierre U Blier, Samuel Fortin
BACKGROUND: There is increasing evidence that marine omega-3 oils are involved in the reduction of cancer risk and progression. However, the anticancer effect of omega-3 monoglyceride on colorectal cancer has yet to be assessed. The goal of this study was to evaluate the anti-cancer effects of eicosapentaenoic acid monoglyceride (MAG-EPA) in HCT116 colorectal carcinoma cells. METHODS: The effect of MAG-EPA was evaluated in vitro on HCT116 cells and in vivo on mouse model of HCT116 xenograft...
September 4, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28855350/macrophages-facilitate-resistance-to-anti-vegf-therapy-by-altered-vegfr-expression
#8
Anil K Sood, Heather J Dalton, Sunila Pradeep, Michael McGuire, Yared Hailemichael, Shaolin Ma, Yasmin Lyons, Guillermo N Armaiz-Pena, Rebecca A Previs, Jean M Hansen, Rajesha Rupaimoole, Vianey Gonzalez-Villasana, Min Soon Cho, Sherry Wu, Lingegowda S Mangala, Nicholas B Jennings, Wei Hu, Robert R Langley, Hong Mu, Michael Andreeff, Menashe Bar-Eli, Willem W Overwijk, Prahlad T Ram, Gabriel Lopez-Berestein, Robert L Coleman
PURPOSE: VEGF-targeted therapies have modest efficacy in cancer patients, but acquired resistance is common. The mechanisms underlying such resistance are poorly understood. EXPERIMENTAL DESIGN: To evaluate the potential role of immune cells in the development of resistance to VEGF blockade, we first established a preclinical model of adaptive resistance to anti-VEGF therapy. Additional in vitro and in vivo studies were carried out to characterize the role of macrophages in such resistance...
August 29, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28854900/vegfr2-regulates-endothelial-differentiation-of-colon-cancer-cells
#9
Zhiyong Liu, Lisha Qi, Yixian Li, Xiulan Zhao, Baocun Sun
BACKGROUND: Recent studies suggested that cancer stem-like cells contribute to tumor vasculogenesis by differentiating into endothelial cells. However, such process is governed by still undefined mechanism. METHODS: At varying differentiation levels, three representative colon cancer cells were cultured in endothelial-inducing conditioned medium: human colon cancer cells HCT116 (HCT116) (poorly differentiated), SW480 (moderately differentiated), and HT29 (well differentiated)...
August 30, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28834088/vegf-synthesis-is-induced-by-prostacyclin-and-tgf-%C3%AE-in-distal-lung-fibroblasts-from-copd-patients-and-control-subjects-implications-for-pulmonary-vascular-remodelling
#10
Gunilla Westergren-Thorsson, Mariam Bagher, Annika Andersson-Sjöland, Lena Thiman, Claes-Göran Löfdahl, Oskar Hallgren, Leif Bjermer, Anna-Karin Larsson-Callerfelt
BACKGROUND AND OBJECTIVE: Involvement of pulmonary vascular remodelling is a characteristic sign in COPD. Vascular mediators such as vascular endothelial growth factor (VEGF) and prostacyclin may regulate fibroblast activity. The objective was to study the synthesis of VEGF and interactions with prostacyclin and transforming growth factor (TGF)-β1 in lung fibroblasts from patients with COPD and healthy control subjects. To further explore the autocrine role of synthesized VEGF on fibroblast activity, studies were performed in human lung fibroblasts (HFL-1)...
August 22, 2017: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/28833603/metformin-incombination-with-curcumin-inhibits-the-growth-metastasis-and-angiogenesis-of-hepatocellular-carcinoma-in-vitro-and-in-vivo
#11
Hui-Hui Zhang, Ying Zhang, Yan-Na Cheng, Fu-Lian Gong, Zhan-Qi Cao, Lu-Gang Yu, Xiu-Li Guo
Hepatocellular carcinoma (HCC) has poor prognosis due to the advanced disease stages by the time it is diagnosed, high recurrence rates and metastasis. In the present study, we investigated the effects of metformin (a safe anti-diabetic drug) and curcumin (a turmeric polyphenol extracted from rhizome of Curcuma longa Linn.) on proliferation, apoptosis, invasion, metastasis and angiogenesis of HCC in vitro and in vivo. It was found that co-treatment of metformin and curcumin could not only induce tumor cells into apoptosis through activating the mitochondria pathways, but also suppress the invasion, metastasis of HCC cells and angiogenesis of HUVECs...
August 19, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28833321/population-pharmacokinetic-meta-analysis-of-ramucirumab-in-cancer-patients
#12
Lisa O'Brien, Paul Westwood, Ling Gao, Michael Heathman
AIM: Ramucirumab is a human IgG1 monoclonal antibody that specifically binds vascular endothelial growth factor receptor-2 (VEGFR-2) and blocks binding of VEGF-A, VEGF-C, and VEGF-D. The objective of the analysis was to characterize the clinical pharmacology profile of ramucirumab using a population pharmacokinetic approach. METHODS: A total of 1639 patients with 6427 serum concentrations from 11 Phase 1b, 2, and 3 clinical trials in patients with various cancer indications were included in the analysis...
August 18, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28831181/tibial-dyschondroplasia-is-highly-associated-with-suppression-of-tibial-angiogenesis-through-regulating-the-hif-1%C3%AE-vegf-vegfr-signaling-pathway-in-chickens
#13
Shu-Cheng Huang, Mujeeb Ur Rehman, Yan-Fang Lan, Gang Qiu, Hui Zhang, Muhammad Kashif Iqbal, Hou-Qiang Luo, Khalid Mehmood, Li-Hong Zhang, Jia-Kui Li
Tibial dyschondroplasia (TD) is an intractable poultry problem that is characterized by the appearance of non-vascularized and non-mineralized cartilage masses in tibial growth plates (TGPs). However, the role of angiogenesis inhibition in the occurrence of TD remains unknown. In this study, we found that, compared to low-altitude Arbor Acres chickens (AACs), high-altitude Tibetan chickens showed higher tibial vascular distributions that were accompanied by up-regulation of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor A (VEGFA) and VEGF receptors...
August 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28822888/apatinib-enhances-antitumour-activity-of-egfr-tkis-in-non-small-cell-lung-cancer-with-egfr-tki-resistance
#14
Fang Li, Tengjiao Zhu, Baoshan Cao, Jiadong Wang, Li Liang
BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs)-rechallenged therapy for EGFR-mutant non-small cell lung cancer (NSCLC) patients who acquired resistance showed moderate efficacy. Considering the high interrelation between EGFR and vascular endothelial growth factor/vascular endothelial growth factor receptor (VEGF/VEGFR) pathways, we firstly evaluated EGFR-TKI combined with apatinib (a highly selective VEGFR2 inhibitor) in EGFR-TKI-resistant model and patients...
August 17, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28821104/modulation-of-binding-to-vascular-endothelial-growth-factor-and-receptor-by-heparin-derived-oligosaccharide
#15
Jie-Ru Liu, Hui-Fang Wang, Dan-Feng Yu, Xiao-Yu Chen, Shu-Ying He
We investigated the mechanism of heparin-derived oligosaccharide on the proliferation of vascular smooth muscle cell (VSMC) induced by vascular endothelial growth factor (VEGF). Expression levels of VEGFR 1 and VEGFR 2 were examined by RT-PCR, and the corresponding protein expression levels were detected by Western blotting and immunocytochemistry. Western blotting was taken to identify the expression levels of mechanism proteins. The binding of VEGF and VEGFR 2 was measured by co-IP. Besides, HS competition assay was to detect the ability of HDO to compete with Heparin for VEGF165...
October 15, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28818671/incidence-and-risk-of-cardiotoxicity-in-cancer-patients-treated-with-targeted-therapies
#16
REVIEW
Matteo Santoni, Federico Guerra, Alessandro Conti, Alessandra Lucarelli, Silvia Rinaldi, Laura Belvederesi, Alessandro Capucci, Rossana Berardi
BACKGROUND: Cardiotoxicityis a serious side effect of molecularly targeted agents. The purpose of this study was to evaluate the incidence and Relative Risk (RR) of developing all-grade and high-grade cardiotoxicity in patients with solid tumors receiving targeted agents through a revised meta-analysis of available clinical trials. METHODS: The scientific literature regarding cardiotoxicity was extensively analyzed using MEDLINE, PubMed, Embase and Cochrane Central Register of Controlled Trials (CENTRAL)...
September 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28814666/rapamycin-reversal-of-vegf-c-driven-lymphatic-anomalies-in-the-respiratory-tract
#17
Peter Baluk, Li-Chin Yao, Julio C Flores, Dongwon Choi, Young-Kwon Hong, Donald M McDonald
Lymphatic malformations are serious but poorly understood conditions that present therapeutic challenges. The goal of this study was to compare strategies for inducing regression of abnormal lymphatics and explore underlying mechanisms. CCSP-rtTA/tetO-VEGF-C mice, in which doxycycline regulates VEGF-C expression in the airway epithelium, were used as a model of pulmonary lymphangiectasia. After doxycycline was stopped, VEGF-C expression returned to normal, but lymphangiectasia persisted for at least 9 months...
August 17, 2017: JCI Insight
https://www.readbyqxmd.com/read/28812437/autophagy-induced-kdr-vegfr-2-activation-promotes-the-formation-of-vasculogenic-mimicry-by-glioma-stem-cells
#18
Hai-Bo Wu, Shuai Yang, Hai-Yan Weng, Qian Chen, Xi-Long Zhao, Wen-Juan Fu, Qin Niu, Yi-Fang Ping, Ji Ming Wang, Xia Zhang, Xiao-Hong Yao, Xiu-Wu Bian
Antiangiogenesis with bevacizumab, an antibody against vascular endothelial growth factor (VEGF), has been used for devascularization to limit the growth of malignant glioma. However, the benefits are transient due to elusive mechanisms underlying resistance to the antiangiogenic therapy. Glioma stem cells (GSCs) are capable of forming vasculogenic mimicry (VM), an alternative microvascular circulation independent of VEGF-driven angiogenesis. Herein, we report that the formation of VM was promoted by bevacizumab-induced macroautophagy/autophagy in GSCs, which was associated with tumor resistance to antiangiogenic therapy...
August 16, 2017: Autophagy
https://www.readbyqxmd.com/read/28811219/trinucleotide-repeat-containing-6c-tnrc6c-is-essential-for-microvascular-maturation-during-distal-airspace-sacculation-in-the-developing-lung
#19
Hua Guo, Yana Kazadaeva, Fabian E Ortega, Narasimaswamy Manjunath, Tushar J Desai
GW182 (also known asTNRC6) family members are critically involved in the final effector phase of miRNA-mediated mRNA repression. The three mammalian paralogs, TNRC6a, b and c, are thought to be redundant based on Argonaute (Ago) binding, tethering assays, and RNAi silencing of individual members in cell lines. To test this idea, we generated TNRC6a, b and c knockout mice. TNRC6a mutants die at mid-gestation, while b- and c- deleted mice are born at a Mendelian ratio. However, the majority of TNRC6b and all TNRC6c mutants die within 24h after birth, the latter with respiratory failure...
August 12, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28810837/phase-i-dose-escalation-study-of-pazopanib-combined-with-bevacizumab-in-patients-with-metastatic-renal-cell-carcinoma-or-other-advanced-tumors
#20
Sylvie Négrier, David Pérol, Rastislav Bahleda, Antoine Hollebecque, Etienne Chatelut, Helen Boyle, Philippe Cassier, Séverine Metzger, Ellen Blanc, Jean-Charles Soria, Bernard Escudier
BACKGROUND: Vascular endothelial growth factor (VEGF) directed therapies are being used in a large number of advanced tumors. Metastatic renal cell carcinoma (mRCC) is highly dependent on the VEGF pathway; VEGF receptor (VEGFR) tyrosine kinase inhibitors (TKI) and humanized VEGF monoclonal antibody have been registered for clinical use in advanced renal cell carcinoma. The VEGFR TKI, pazopanib, with a rather manageable toxicity profile, was preferred to sunitinib by mRCC patients. We investigate the combination of pazopanib and bevacizumab to determine the maximum tolerated dose (MTD) in mRCC and other advanced solid tumors...
August 15, 2017: BMC Cancer
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