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Philip Lazarovici, Adi Lahiani, Galit Gincberg, Dikla Haham, Cezary Marcinkiewicz, Peter I Lelkes
The avian chorioallantoic membrane (CAM) is a simple, highly vascularized extraembryonic membrane, which performs multiple functions during embryonic development. Therefore, the models of chicken and quail assays represent robust experimental platforms to study angiogenesis, which reflects perturbation of the entire vascular tree. This experimental approach, when combined with fractal morphometry, is sensitive to changes in vascular branching pattern and density. Nerve growth factor is a neurotrophin promoting angiogenesis in CAM models...
2018: Methods in Molecular Biology
Philip Lazarovici, Adi Lahiani, Galit Gincberg, Dikla Haham, Arnon Fluksman, Ofra Benny, Cezary Marcinkiewicz, Peter I Lelkes
Nerve growth factor (NGF) is a neurotrophin promoting survival, proliferation, differentiation, and neuroprotection in the embryonal and adult nervous system. NGF also induces angiogenic effects in the cardiovascular system, which may be beneficial in engineering new blood vessels and for developing novel anti-angiogenesis therapies for cancer. Angiogenesis is a cellular process characterized by a number of events, including endothelial cell migration, invasion, and assembly into capillaries. In vitro endothelial tube formation assays are performed using primary human umbilical vein endothelial cells, human aortic endothelial cells, and other human or rodent primary endothelial cells isolated from the vasculature of both tumors and normal tissues...
2018: Methods in Molecular Biology
Kyunghee Noh, Lingegowda S Mangala, Hee-Dong Han, Ningyan Zhang, Sunila Pradeep, Sherry Y Wu, Shaolin Ma, Edna Mora, Rajesha Rupaimoole, Dahai Jiang, Yunfei Wen, Mian M K Shahzad, Yasmin Lyons, MinSoon Cho, Wei Hu, Archana S Nagaraja, Monika Haemmerle, Celia S L Mak, Xiuhui Chen, Kshipra M Gharpure, Hui Deng, Wei Xiong, Charles V Kingsley, Jinsong Liu, Nicholas Jennings, Michael J Birrer, Richard R Bouchard, Gabriel Lopez-Berestein, Robert L Coleman, Zhiqiang An, Anil K Sood
Angiogenesis inhibitors are important for cancer therapy, but clinically approved anti-angiogenic agents have shown only modest efficacy and can compromise wound healing. This necessitates the development of novel anti-angiogenesis therapies. Here, we show significantly increased EGFL6 expression in tumor versus wound or normal endothelial cells. Using a series of in vitro and in vivo studies with orthotopic and genetically engineered mouse models, we demonstrate the mechanisms by which EGFL6 stimulates tumor angiogenesis...
December 5, 2017: Cell Reports
A Jain, A Tiwari, A Verma, S K Jain
Over a few decades a strong interlink between oxidative damage and cancer has been investigated by various scientists across the world on the basis of epidemiological observations of the effects of fruits and vegetables used in the diet for cancer patients. Primarily, Vitamin C, Vitamin D and Vitamin E are reported to be involved in the amelioration of side effects which occur in chemotherapy and radiation therapy of lungs, stomach, prostate, colorectal, gastric head and neck cancers. The vitamins acting as antioxidant adjuvants are found to have apoptotic and anti-angiogenesis potential as well as inhibitory effects against metastasis in cancer cells...
December 4, 2017: Current Molecular Medicine
Meiya Chen, Mengjie Lin, Xiaozhong Wang
The microRNA miR-19a is closely related to tumor formation and development and is a key oncogene. Previous studies have demonstrated that miR-19a is upregulated in multiple cancer types, including colorectal cancer (CRC). However, most of these experiments were performed in vitro, and consequently, the mechanisms underlying the effects of miR-19a on CRC are still unclear. Therefore, in the present study, we investigated the role of miR-19a in the development of solid CRC tumors. We generated KRAS 3'UTR-Mut by deleting the predicted binding site for miR-19a in KRAS, and observed that the expression of a reporter gene containing the KRAS 3'UTR in HCT116 cells was suppressed by miR-19a, while that of a reporter gene with mutant KRAS 3'UTR was unaffected by miR-19a...
November 24, 2017: Oncology Reports
Yuqi Jiang, Xiaoyang Li, Jinning Hou, Yongxue Huang, Xuejian Wang, Yuping Jia, Qingwei Wang, Wenfang Xu, Jian Zhang, Yingjie Zhang
Previously a novel ubenimex-fluorouracil (5-FU) conjugate, BC-01 was identified and validated as a potent CD13 inhibitor with marked in vitro and in vivo antitumor potency. Herein, further structural modifications of the linker part of BC-01 was carried out to get more potent and stable ubenimex-fluorouracil conjugates. It was striking that most of these conjugates showed even more potent CD13 inhibitory activities than BC-01 and the approved CD13 inhibitor ubenimex. One representative compound 12a displayed significant in vitro anti-proliferation, pro-apoptosis, anti-metastasis, anti-angiogenesis and CD13+ cell elimination effects...
November 30, 2017: European Journal of Medicinal Chemistry
Kai Zhao, Yang Yuan, Binyan Lin, Zhaorui Miao, Zhiyu Li, Qinglong Guo, Na Lu
LW-215 is a newly synthesized flavonoid, which is the derivative of wogonin. Our group has previously confirmed that wogonin has an anti-angiogenic activity, while the anti-angiogenic effect of LW-215 is unclear. In this study, we explored whether LW-215 can inhibit angiogenesis and further probed the potential molecular mechanisms. We found that LW-215 inhibited migration and tube formation in human umbilical vein endothelial cells (HUVECs) and immortalized endothelial EA.hy926 cells without a significant decrease in cell viability...
November 28, 2017: Gene
Xiang Zou, Li Zhang, Jie Yuan, Chunjie Yang, Zehan Wu, Jianping Song, Wei Zhu, Ying Mao, Liang Chen
Brain arteriovenous malformations (AVMs) which associate with angiogenesis due to local hypertension, chronic cerebral ischaemia and tissue hypoxia usually lead to haemorrhage, however, the therapeutic medicine for the disease is still lacking. 2-methoxyestradiol (2-ME) has been shown effective in the anti-angiogenic treatment. This study was conducted to examine whether and how 2-ME could improve the vascular malformations. Intracranial venous hypertension (VH) model produced in adult male Sprague-Dawley rats and culture of human umbilical vein endothelial cells (HUVECs) at the anoxia condition were used to induce in vivo and in vitro angiogenesis, respectively...
November 29, 2017: Journal of Cellular and Molecular Medicine
Eric Block, Benjamin Bechand, Sivaji Gundala, Abith Vattekkatte, Kai Wang, Shaymaa S Mousa, Kavitha Godugu, Murat Yalcin, Shaker A Mousa
We describe the synthesis, reactivity, and antithrombotic and anti-angiogenesis activity of difluoroallicin (S-(2-fluoroallyl) 2-fluoroprop-2-ene-1-sulfinothioate) and S-2-fluoro-2-propenyl-l-cysteine, both easily prepared from commercially available 3-chloro-2-fluoroprop-1-ene, as well as the synthesis of 1,2-bis(2-fluoroallyl)disulfane, 5-fluoro-3-(1-fluorovinyl)-3,4-dihydro-1,2-dithiin, trifluoroajoene ((E,Z)-1-(2-fluoro-3-((2-fluoroallyl)sulfinyl)prop-1-en-1-yl)-2-(2-fluoroallyl)disulfane), and a bis(2-fluoroallyl)polysulfane mixture...
November 28, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Huixia Lu, Xunian Zhou, Hoi-Hin Kwok, Mei Dong, Zhaoqiang Liu, Po-Ying Poon, Xiaorong Luan, Ricky Ngok-Shun Wong
Angiogenesis is the formation of new blood vessels from the existing vasculature, which is involved in multiple biological processes, including atherosclerosis, ischemic heart disease, and cancer. Ginsenoside-Rb1 (Rb1), the most abundant ginsenoside isolated form Panax ginseng, has been identified as a promising anti-angiogenic agent via the up-regulation of PEDF. However, the underlying molecular mechanisms still unknown. In the present study, human umbilical vein endothelial cells (HUVECs) were selected to perform in vitro assays...
2017: Frontiers in Pharmacology
Lewis A Quayle, Maria G Pereira, Gerjan Scheper, Tammy Wiltshire, Ria E Peake, Issam Hussain, Carol A Rea, Timothy E Bates
Components of the mitochondrial electron transport chain have recently gained much interest as potential therapeutic targets. Since mitochondria are essential for the supply of energy that is required for both angiogenic and tumourigenic activity, targeting the mitochondria represents a promising potential therapeutic approach for treating cancer. Here we investigate the established anti-angiogenesis drugs combretastatin A4, thalidomide, OGT 2115 and tranilast that we hypothesise are able to exert a direct anti-cancer effect in the absence of vasculature by targeting the mitochondria...
October 24, 2017: Oncotarget
Wen-Sen Lee, Yi-Chen Lu, Chun-Ting Kuo, Chiung-Tong Chen, Pei-Hua Tang
AIM: Pregnant women have been recommended to take FA daily to prevent birth defects in the brain and spinal cord. We previously showed that folic acid (FA) exerts an anti-angiogenic activity. Since angiogenesis is important for endometrial reorganization and embryonic development, there should be some mechanisms to allow the pregnant mother and the fetus to escape from the FA-induced anti-angiogenesis. The present study was designed to investigate the effect of female sex hormones on the FA-induced anti-angiogenic activity...
November 25, 2017: Acta Physiologica
Anne Steins, Eva A Ebbing, Marcel C M Pistorius, Cynthia Waasdorp, Kausilia K Krishnadath, Jan Paul Medema, Johanna W Wilmink, Ron A A Mathôt, Maarten F Bijlsma, Hanneke W M van Laarhoven
Angiogenesis is critical to the growth of tumors. Vascularization-targeting agents, with or without cytotoxic drugs, are widely used for the treatment of several solid tumors including esophagogastric adenocarcinoma. However, little is known about the systemic effects of anti-angiogenic therapies and how this affects the pharmacokinetics and intratumoral delivery of cytotoxic agents. In this study, patient-derived xenograft mouse models of esophageal adenocarcinoma were used to identify the effects of DC101, a murine vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor, on the pharmacokinetics and the intratumoral uptake of nab-paclitaxel (NPTX)...
November 2017: Drug Delivery
Shaodan Chen, Tianqiao Yong, Yifang Zhang, Jiyan Su, Chunwei Jiao, Yizhen Xie
This study was carried out to isolate chemical constituents from the lipid enriched fraction of Ganoderma lucidum extract and to evaluate their anti-proliferative effect on tumor cells and human umbilical vein endothelial cells (HUVECs). Ergosterol derivatives (1-14) were isolated and purified from the lipid enriched fraction of G. lucidum. Their chemical structures were established by spectroscopic analyses or by comparison of mass and NMR spectral data with those reported previously. Amongst, compound 1 was purified and identified as a new one...
2017: Frontiers in Chemistry
Xinghua Han, Zhanggui Wang, Bin Hu, Jianming Xu
Endostar is a novel artificially-synthesized anti-angiogenesis drug, and has been approved for clinical use. Previous studies have indicated that patients with esophageal cancer could benefit from Endostar combined with chemotherapy or chemoradiotherapy. However, the most advantageous use of this drug remains to be elucidated. The role of autophagy in cancer treatment remains controversial. The results of the present study demonstrated that Endostar promotes autophagy activation, which is regulated via phosphorylation inhibition of the downstream signaling molecules of the vascular endothelial growth factor, AKT serine/threonine kinase and mechanistic target of rapamycin signaling pathways...
December 2017: Oncology Letters
Shao-Jung Hsu, Jing-Yi Lee, Te-Yueh Lin, Yu-Hsin Hsieh, Hui-Chun Huang, Fa-Yauh Lee, Han-Chieh Lin, Ming-Chih Hou, Shou-Dong Lee
In liver cirrhosis with portal hypertension, the uneven distribution of vasoactive substances leads to increased intrahepatic vascular resistance and splanchnic vasodilatation. Angiogenesis also induces increased portal inflow and portosystemic collaterals. The collaterals may induce lethal complications such as gastroesophageal variceal hemorrhage, but the therapeutic effect of vasoconstrictors is still suboptimal due to poor collateral vasoresponsivenss. Curcumin has aroused much attention for its anti-fibrosis, vasoactive and anti-angiogenesis actions...
November 21, 2017: Bioscience Reports
Mani Divya, Baskaralingam Vaseeharan, Muthukumar Abinaya, Sekar Vijayakumar, Marimuthu Govindarajan, Naiyf S Alharbi, Shine Kadaikunnan, Jamal M Khaled, Giovanni Benelli
The use of natural polymers in drug design plays an important role in biomedical applications. Combinations of nanoparticles (NPs) and biopolymers have been shown to be useful for many purposes. This study focused on gelatin-coated zinc oxide NPs synthesized by co-precipitation. The particles were characterized by UV-Vis spectrum, showing a main peak at 375nm. The stability and crystalline nature of the particles was evaluated by Zeta potential and X-ray diffraction analysis. Fourier transform infrared spectroscopy (FTIR) revealed the possible functional groups of Ge-ZnO NPs, with strong bands at 3851, 3447, and 2923cm(-1)...
November 10, 2017: Journal of Photochemistry and Photobiology. B, Biology
Kjartan Moe, Harald Heidecke, Ralf Dechend, Anne Cathrine Staff
OBJECTIVES: Preeclampsia is a state of antiangiogenesis, with high levels of maternal circulating sVEGFR-1 (soluble vascular endothelial growth factor receptor 1, also named sFlt1) and low levels of PlGF (placenta growth factor). Various autoantibodies have been detected in preeclamptic patients. We hypothesize that circulating autoantibodies against VEGF-A (AA-VEGF-A), VEGFR-1 (AA-VEGFR-1) and PlGF (AA-PlGF) are present in preeclamptic women, with different levels from pregnant women with normotensive pregnancies...
October 2017: Pregnancy Hypertension
Cheng-Ming Li, Zhi-Chao Liu, You-Ting Bao, Xin-Dong Sun, Lin-Lin Wang
Chemotherapy has limited efficacy in the treatment of advanced and metastatic pancreatic cancer (PC), and has serious side effects. The development of novel effective agents, especially targeted therapy, is essential for patients with PC. We present a 58-year-old Chinese woman initially diagnosed with locally advanced PC. As the disease progressed to Stage IV, the patient was unable to tolerate chemotherapy after the fourth-line treatment. She was then treated with apatinib, a novel and highly selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2 and achieved a progression-free-survival of 7 mo...
November 7, 2017: World Journal of Gastroenterology: WJG
Yi-Fang Chen, Ang Yuan, Kuan-Hung Cho, Yi-Chien Lu, Mark Yen-Ping Kuo, Jyh-Horng Chen, Yeun-Chung Chang
This study aimed to investigate the therapeutic responses of lung cancer mice models with adenocarcinoma HCC827 (gefitinib sensitive) and HCC827R (gefitinib resistant) to the epidermal growth factor receptor-tyrosine kinase inhibitor erlotinib alone and in combination with the anti-angiogenesis agent bevacizumab using dynamic contrast enhanced (DCE) and diffusion-weighted MRI. In the HCC827 model, temporal changes in DCE-MRI derived parameters (Ktrans, kep, and iAUC90) and apparent diffusion coefficient (ADC) were significantly correlated with tumor size...
2017: PloS One
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