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Lindsey E Minion, Krishnansu S Tewari
Introduction Bevacizumab is a recombinant humanized monoclonal antibody against vascular endothelial growth factor (VEGF) (Avastin; Genetech, Inc, San Francisco, CA). Angiogenesis is blocked by the binding of bevacizumab to VEGF, inhibiting the binding of this ligand to the VEGF receptor. On August 14, 2014 the Food and Drug Administration (FDA) approved use of bevacizumab in persistent, recurrent, or metastatic cervical cancer. Areas Covered Herein we review pharmacodynamics and kinetics, clinical data and treatment-related toxicities of bevacizumab in the treatment of metastatic, recurrent or persistent cervical cancer...
October 17, 2016: Expert Review of Anticancer Therapy
Lai Yue Chan, David J Craik, Norelle L Daly
Peptide analogues derived from bioactive hormones such as somatostatin or certain growth factors have great potential as angiogenesis inhibitors for cancer applications. In an attempt to combat emerging drug resistance many FDA-approved anti-angiogenesis therapies are co-administered with cytotoxic drugs as a combination therapy to target multiple signaling pathways of cancers. However, cancer therapies often encounter limiting factors such as high toxicities and side effects. Here, we combined two anti-angiogenic epitopes that act on different pathways of angiogenesis into a single non-toxic cyclic peptide framework, namely MCoTI-II (Momordica cochinchinensis trypsin inhibitor-II), and subsequently assessed the anti-angiogenic activity of the novel compound...
October 13, 2016: Scientific Reports
Yue Xu, Boyu Yang, Yaguang Hu, Lin Lu, Xi Lu, Jiawei Wang, Qinmeng Shu, Qiaochu Cheng, Shanshan Yu, Fan Xu, Jingjing Huang, Xiaoling Liang
Down syndrome candidate region 1 (DSCR1) has two differentially regulated isoforms (DSCR1-1 and DSCR1-4) and is reported to play a role in a number of physiological processes, such as the inhibition of cardiac hypertrophy, attenuation of angiogenesis and carcinogenesis, and protection against neuronal death. However, the function of DSCR1 in the retina is still not clear. Therefore, we analyzed the expression and location of DSCR1 in the retina of neonatal mice with oxygen-induced retinopathy (OIR), and studied its effects on angiogenesis...
October 12, 2016: Molecular Neurobiology
Yi Yang, Jing Lu, Hangfan Liu, Guoguo Jin, Ruihua Bai, Xiang Li, Dongyu Wang, Jimin Zhao, Youtian Huang, Kangdong Liu, Ying Xing, Ziming Dong
Dendritic cells (DC) have been exploited for vaccination against cancer for years. DC loading autologous tumor lysate (ATL-DC) have been assessed in ongoing clinical trials, but frequently do not meet expectation. In this study, we found that mice immunized with ATL-DC induced less protective anti-tumor effect than immunized with DC alone. The percentage of CD8(+) T cells and the lysis efficiency of CTLs to auto tumor cells in ATL-DC vaccination group was less than that of DC group. Moreover, vaccination of mice with ATL-DC also promoted tumor angiogenesis by analyzing the CD31 positive microvessel density and hemoglobin content of tumor specimens...
October 10, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Yuanyuan Liu, Jing Gao, Shuangsheng Huang, Lamei Hu, Zhiqiang Wang, Zheyuan Wang, Xiao Chen, Xiaoyu Zhang, Wenguang Li
Reactive oxygen species (ROS) are involved in the signaling pathway and are triggered by angiogenic factors, including vascular endothelial growth factor and angiopoietins. 4-isothiocyanate-2, 2, 6, 6-tetramethyl piperidinooxyl (4-ISO-Tempo) is one of the nitroxides that exhibits antioxidant activity. However, the anti-angiogenic effect of 4-ISO-Tempo remains unknown. The aim of this study was to investigate the effect of 4-ISO-Tempo on tumor proliferation and angiogenesis as well as its underlying mechanisms...
October 2016: Oncology Letters
Kouichi Itoh, Yasuhiro Ishihara, Rie Komori, Hiromi Nochi, Ruri Taniguchi, Yoichi Chiba, Masaki Ueno, Fuyuko Takata-Tsuji, Shinya Dohgu, Yasufumi Kataoka
Our previous study showed that treatment with levetiracetam (LEV) after status epilepticus (SE) termination by diazepam might prevent the development of spontaneous recurrent seizures via the inhibition of neurotoxicity induced by brain edema events. In the present study, we determined the possible molecular and cellular mechanisms of LEV treatment after termination of SE. To assess the effect of LEV against the brain alterations after SE, we focused on blood-brain barrier (BBB) dysfunction associated with angiogenesis and brain inflammation...
September 27, 2016: Brain Research
Li-Ni Zhao, Ping Wang, Yun-Hui Liu, Heng Cai, Jun Ma, Li-Bo Liu, Zhuo Xi, Zhi-Qing Li, Xiao-Bai Liu, Yi-Xue Xue
Malignant glioma is undoubtedly the most vascularized tumor of central nervous system. Angiogenesis, playing a predominant role in tumor progression, is widely considered as a key point of tumor treatment. The aim of this study was to investigate the potential effects of miR-383 on proliferation, migration, tube formation and angiogenesis of glioma-exposed endothelial cells (GECs) in vitro and to further elucidate its possible molecular mechanisms. The expression of miR-383 in GECs was significantly downregulated compared with that in normal endothelial cells (ECs)...
September 27, 2016: Cellular Signalling
Yuqi Jiang, Jinning Hou, Xiaoyang Li, Yongxue Huang, Xuejian Wang, Jingde Wu, Jian Zhang, Wenfang Xu, Yingjie Zhang
Herein, a novel mutual prodrug BC-A1 was discovered by integrating ubenimex and gemcitabine into one molecule. Biological characterization revealed that compound BC-A1 could maintain both the anti-CD13 activity of ubenimex and the cytotoxic activity of gemcitabine in vitro. Further characterization also demonstrated that compound BC-A1 exhibited significant anti-invasion and anti-angiogenesis effects in vitro. The preliminary stability test of BC-A1 revealed that it could release gemcitabine in vitro. The in vivo anti-tumor results in liver cancer showed that at the same dosage, oral administration of BC-A1 was as potent as intraperitoneal administration of gemcitabine...
September 14, 2016: Bioorganic & Medicinal Chemistry
Roghaye Arezumand, Reza Mahdian, Sirous Zeinali, Gholamreza Hassanzadeh-Ghassabeh, Kamran Mansouri, Hossein Khanahmad, Nabiollah Namvar-Asl, Hamzeh Rahimi, Mahdi Behdani, Reza Ahangari Cohan, Mehdi Eavazalipour, Ali Ramazani, Serge Muyldermans
Placental growth factor (PlGF), a member of vascular endothelial growth factors (VEGF) family, is considered as an important antigen associated with pathological conditions such as cancer cell growth, and metastasis. PlGF-targeting via nanobody (Nb) therefore could be beneficial to modulate these pathologies. In this work, phage-display and computational approach was employed to develop a high affinity PlGF-specific Nb. An Nb library was constructed against human recombinant PlGF (rPlGF). After panning on immobilized rPlGF the periplasmic-extract (PE) of individual colonies were screened by ELISA (PE-ELISA)...
October 2016: Molecular Immunology
Xiuwen Guan, Zhaopei Guo, Lin Lin, Jie Chen, Huayu Tian, Xuesi Chen
A facile strategy is developed to construct an ultrasensitive pH triggered charge/size dual-rebound gene delivery system for efficient tumor treatment. Therapeutic gene is complexed by polyethylenimine (PEI) and poly-L-glutamate (PLG), further in situ tightened by aldehyde modified polyethylene glycol (PEG) via Schiff base reaction. The generated Schiff base bonds are stable in neutral pH but cleavable in tumor extracellular pH. This gene delivery system possesses following favorable properties: (1) the tunable gene delivery system is constructed by chemical bench-free "green" and fast process which is favored by clinician, (2) PEG crosslinking shields the surface positive charges and tightens the complex particles, leading to decreased cytotoxicity, improved stability and prolonged circulation, (3) PEG shielding can be rapidly peeled off by acidic pH as soon as arriving tumors, (4) dual charge/size ultrasensitively rebounding to higher positive potential and bigger size enhances tumor cell uptake efficiency...
September 19, 2016: Nano Letters
Pei-Xin Lai, Chung-Wein Chen, Shih-Chun Wei, Tzu-Yu Lin, Hong-Jyuan Jian, Irving Po-Jung Lai, Ju-Yi Mao, Pang-Hung Hsu, Han-Jia Lin, Wen-Shyong Tzou, Shiow-Yi Chen, Scott G Harroun, Jui-Yang Lai, Chih-Ching Huang
Angiogenesis is the process of formation of new blood vessels, which is essential to human biology, and also plays a crucial role in several pathologies such as tumor growth and metastasis, exudative age-related macular degeneration, and ischemia. Vascular endothelial growth factor (VEGF), in particular, VEGF-A165 is the most important pro-angiogenic factor for angiogenesis. Thus, blocking the interaction between VEGFs and their receptors is considered an effective anti-angiogenic strategy. We demonstrate for that first time that bovine serum albumin-capped graphene oxide (BSA-GO) exhibits high stability in physiological saline solution and possesses ultrastrong binding affinity towards VEGF-A165 [dissociation constant (Kd) ∼3 × 10(-12) M], which is at least five orders of magnitude stronger than that of high-abundant plasma proteins such as human serum albumin, fibrinogen, transferrin, and immunoglobulin G...
December 2016: Biomaterials
Sitelbanat Yassin, Jialiang Hu, Hanmei Xu, Ce Li, Sarra Setrerrahmane
Anti-angiogenesis is an important therapy for cancer treatment. Peptide HM-3 is an integrin antagonist with anti-angiogenic and antitumor activity. Previous research found that HM-3 at an effective dose inhibited tumor growth whereas at higher doses, the inhibitory effect gradually decreased. In the present study, three human tumor cell lines, human colorectal cancer cell (HCT-116) and human hepatic cancer cell (Hep G-2 and SMMC-7721), were selected and their interactions with HM-3 were compared with western blot and flow cytometric assays...
September 9, 2016: Oncology Reports
Bei Xu, Quansheng Jin, Jun Zeng, Ting Yu, Yan Chen, Shuangzhi Li, Daoqiong Gong, Lili He, Xiaoyue Tan, Li Yang, Gu He, Jinhui Wu, Xiangrong Song
A rational combination is critical to achieve efficiently synergistic therapeutic efficacy for tumor treatment. Hence, we designed novel antitumor combinations (T-NPs) by integrating the tumor vascular and tumor cells dual-targeting ligand with antiangiogenesis/antitumor agents. The truncated bFGF peptide (tbFGF), which could effectively bind to FGFR1 overexpressed on tumor neovasculature endothelial cells and tumor cells, was selected to modify PLGA nanoparticles (D/P-NPs) simultaneously loaded with PEDF gene and paclitaxel in this study...
October 5, 2016: ACS Applied Materials & Interfaces
Ruling Shen, Jun Li, Danrong Ye, Qingcheng Wang, Jian Fei
Onconase (Onc) is a cytotoxic ribonuclease derived from leopard frog oocytes or early embryos, and has been applied to the treatment of malignant mesothelioma in clinics. Onc also exhibits effective growth suppression of human non-small-cell lung cancer (NSCLC). Artemisinin (Art) and its derivatives are novel antimalarial drugs that exhibit antitumor and antivirus activities. In this study, we investigated the antitumor effects of combinations of Onc and an Art derivative, dihydroartemisinin (DHA), both in vitro and in vivo Isobologram analyses showed synergistic effects on the proliferation of NSCLC cells under the treatment with Onc and DHA...
October 2016: Acta Biochimica et Biophysica Sinica
Wen-Chin Chiu, Tzeon-Jye Chiou, Meng-Ju Chung, An-Na Chiang
Angiogenesis is the process of new blood vessel formation, and it plays a key role in various physiological and pathological conditions. The β2-glycoprotein I (β2-GPI) is a plasma glycoprotein with multiple biological functions, some of which remain to be elucidated. This study aimed to identify the contribution of 2-GPI on the angiogenesis induced by vascular endothelial growth factor (VEGF), a pro-angiogenic factor that may regulate endothelial remodeling, and its underlying mechanism. Our results revealed that β2-GPI dose-dependently decreased the VEGF-induced increase in endothelial cell proliferation, using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and the bromodeoxyuridine (BrdU) incorporation assays...
2016: PloS One
Hai Tan, Dadong Wang, Rongxin Li, Changming Sun, Ryan Lagerstrom, You He, Yanling Xue, Tiqiao Xiao
The quantification of micro-vasculatures is important for the analysis of angiogenesis on which the detection of tumor growth or hepatic fibrosis depends. Synchrotron-based X-ray computed micro-tomography (SR-µCT) allows rapid acquisition of micro-vasculature images at micrometer-scale spatial resolution. Through skeletonization, the statistical features of the micro-vasculature can be extracted from the skeleton of the micro-vasculatures. Thinning is a widely used algorithm to produce the vascular skeleton in medical research...
September 1, 2016: Journal of Synchrotron Radiation
Qixian Chen, Ruogu Qi, Xiyi Chen, Xi Yang, Xing Huang, Haihua Xiao, Xinhuan Wang, Wenfei Dong
Nucleic acid-based therapy has emerged as a revolutionary methodology for treatment of the diseases related to protein dysfunction; however, lack of systemically applicable synthetic delivery systems limits its current usage in local applications, particularly for DNA-based therapy with regard to the poor bioavailability in the systemic administrations. To overcome this obstacle, we compiled multiple chemistry-based strategies into the manufacture of the gene delivery formulations to pursue improved tolerability of DNA to the enzymatic degradation in the biological milieu and prolonged retention in the systemic circulation...
September 21, 2016: ACS Applied Materials & Interfaces
Junzhong Ruan, Yong Duan, Fugen Li, Zitong Wang
In order to achieve a synergistic effect on anti-tumor and anti-angiogenesis activity, we designed and constructed a DNA vaccine that expresses MUC1and VEGFR2 in the same reading frame. The aim of this study was to investigate the anti-tumor activity of this DNA vaccine. Furthermore, we also investigated the enhanced synergistic anti-Lewis lung carcinoma effect of this DNA vaccine by using GM-CSF as an adjuvant. A series of DNA plasmids encoding MUC1, VEGFR2, GM-CSF, and their conjugates were constructed and injected into mice intramuscularly (i...
August 25, 2016: Clinical and Experimental Pharmacology & Physiology
Lei Shi, Bin Yu, Chun-Hui Cai, Jian-Dong Huang
Despite of a growing number of bacterial species that apparently exhibit intrinsic tumor-targeting properties, no bacterium is able to inhibit tumor growth completely in the immunocompetent hosts, due to its poor dissemination inside the tumors. Oxygen and inflammatory reaction form two barriers and restrain the spread of the bacteria inside the tumors. Here, we engineered a Salmonella typhimurium strain named ST8 which is safe and has limited ability to spread beyond the anaerobic regions of tumors. When injected systemically to tumor-bearing immunocompetent mice, ST8 accumulated in tumors at levels at least 100-fold greater than parental obligate anaerobic strain ST4...
December 2016: AMB Express
Eun Ho Kim, Hyo Sook Song, Seung Hoon Yoo, Myonggeun Yoon
Treatment with alternating electric fields at an intermediate frequency (100-300 kHz), referred to as tumor treating fields (TTF) therapy, inhibits cancer cell proliferation. In the present study, we demonstrated that TTF application suppressed the metastatic potential of U87 and U373 glioblastoma cell lines via the NF-kB, MAPK and PI3K/AKT signaling pathways. Wound-healing and transwell assays showed that TTF suppressed cell migration and invasion compared with controls. Soft agar and three-dimensional culture assays showed that TTF inhibited both anchorage-dependent (cell proliferation) and anchorage-independent (colony formation) GBM cell growth...
August 18, 2016: Oncotarget
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