Drug and Alcohol Rehabilitation: Vixapatin (VP12), a C-Type Lectin-Protein From Vipera Xantina Palestinae Venom: Characterization as a Novel Anti-Angiogenic Compound.
Vixapatin (VP12), a C-Type Lectin-Protein from Vipera xantina palestinae Venom: Characterization as a Novel Anti-angiogenic Compound.
Filed under: Drug and Alcohol Rehabilitation
Toxins (Basel). 2012 Oct; 4(10): 862-77
Momic T, Cohen G, Reich R, Arlinghaus FT, Eble JA, Marcinkiewicz C, Lazarovici P
A C-type lectin-like protein (CTL), originally identified as VP12 and lately named Vixapatin, was isolated and characterized from Israeli viper Vipera xantina palestinae snake venom. This CTL was characterized as a selective ?2?1 integrin inhibitor with anti-melanoma metastatic activity. The major aim of the present study was to prove the possibility that this protein is also a potent novel anti-angiogenic compound. Using an adhesion assay, we demonstrated that Vixapatin selectively and potently inhibited the ?2 mediated adhesion of K562 over-expressing cells, with IC(50) of 3 nM. 3 nM Vixapatin blocked proliferation of human dermal microvascular endothelial cells (HDMEC); 25 nM inhibited collagen I induced migration of human fibrosarcoma HT-1080 cells; and 50 nM rat C6 glioma and human breast carcinoma MDA-MB-231 cells. 1 µM Vixapatin reduced HDMEC tube formation by 75% in a Matrigel assay. Furthermore, 1 µM Vixapatin decreased by 70% bFGF-induced physiological angiogenesis, and by 94% C6 glioma-induced pathological angiogenesis, in shell-less embryonic quail chorioallantoic membrane assay. Vixapatin’s ability to inhibit all steps of the angiogenesis process suggest that it is a novel pharmacological tool for studying ?2?1 integrin mediated angiogenesis and a lead compound for the development of a novel anti-angiogenic/angiostatic/anti-cancer drug.
HubMed – drug
Carboplatin and bevacizumab for recurrent malignant glioma.
Filed under: Drug and Alcohol Rehabilitation
Oncol Lett. 2012 Nov; 4(5): 1082-1086
Mrugala MM, Crew LK, Fink JR, Spence AM
Over 65,000 primary brain tumors are diagnosed annually in the US alone. Malignant gliomas represent more than one-third of such cases. Despite advances in neuroimaging, surgical techniques, radiotherapy and chemotherapy, the survival rate of this disease remains poor. The introduction of agents which disrupt the function of vascular endothelial growth factor (VEGF) and its receptors to glioma therapy has resulted in an unusually high percentage of patients experiencing radiographic responses. Bevacizumab, approved by the Food and Drug Administration for the treatment of recurrent glioblastoma in 2009, has changed the field of neuro-oncology. The drug has been utilized as a single agent and in combination with the classic cytotoxic agents typically applied in this setting. Numerous studies have reported high response rates and encouraging extensions of time-to-progression. The optimal schedule and combination of bevacizumab with alternative drugs has not been identified. The current study presents the results of a retrospective analysis of the combination therapy utilizing bevacizumab with the alkylating agent carboplatin in patients with recurrent malignant glioma.
HubMed – drug
Metformin inhibits leptin-induced growth and migration of glioblastoma cells.
Filed under: Drug and Alcohol Rehabilitation
Oncol Lett. 2012 Nov; 4(5): 1077-1081
Ferla R, Haspinger E, Surmacz E
Metformin, a derivative of biguanide, is a first-line therapy for type 2 diabetes mellitus. Since the drug has been shown to significantly reduce the risk of various cancers and cancer mortality in diabetic patients, it is being considered as a potential anticancer therapeutic or preventive agent. In cellular models, metformin inhibits the growth of many types of cancer cells; however, its effects on glioblastoma multi-forme (GBM) are not well characterized. Here, we analyzed the effects of metformin on the growth and migration of LN18 and LN229 GBM cells cultured under basal conditions or exposed to leptin, a cytokine that has recently been implicated in GBM development. We found that 2-16 mM metformin reduced basal and leptin-stimulated growth of GBM cells in a dose-dependent manner. Furthermore, the drug significantly inhibited the migration of GBM cells. The action of metformin was mediated through the upregulation of its main signaling molecule, the adenosine monophosphate-activated protein kinase (AMPK), as well as through the downregulation of the signal transducer and activator of transcription 3 (STAT3) and the Akt/PKB serine/threonine protein kinase. In leptin-treated cells, the drug reversed the effects of the cytokine on the AMPK and STAT3 pathways, but modulated Akt activity in a cell-dependent manner. Our results suggest that metformin or similar AMPK-targeting agents with optimized blood-brain-barrier penetrability could be developed as potential treatments of GBM and could be used in conjunction with other target drugs such as leptin receptor antagonists.
HubMed – drug
Antitumor activity of Endostar combined with radiation against human nasopharyngeal carcinoma in mouse xenograft models.
Filed under: Drug and Alcohol Rehabilitation
Oncol Lett. 2012 Nov; 4(5): 976-980
Zhou J, Wang L, Xu X, Tu Y, Qin S, Yin Y
Radiation treatment for nasopharyngeal carcinoma (NPC) is common and effective. However, local recurrence occurs frequently. Endostar, a novel recombinant human endostatin, is an antiangiogenic drug with a potent antitumor effect. The present study aimed to observe and explore the radiosensitization effects of Endostar on NPC and its underlying mechanism. The NPC subcutaneous transplantation tumor animal model was established to evaluate the antitumor activity of Endostar combined with radiation (Endostar + radiation) treatment compared with monotherapy (Endostar or radiation). Tumor growth and tumor weight were measured to evaluate the antitumor effect. The level of vascular endothelial growth factor (VEGF) and microvessel density (MVD) were measured using immunohistochemical staining of the tumor tissues. Significant antitumor activity was found in the Endostar + radiation group. The tumor inhibition rates of Endostar, radiation and Endostar + radiation were 27.12, 60.45 and 86.11%, respectively. The VEGF levels in the tumor tissue in the Endostar + radiation group were lower than those in the radiation and control groups. The MVD in the tumor tissues in the Endostar + radiation group was 12.2±2.5, lower than that in the Endostar (29.3±3.4), radiation (23.5±3.6) and control (44.7±5.1) groups. These results suggest that Endostar increases the radiation sensitivity of NPC-transplanted tumors in nude mice by lowering VEGF expression. In this study, the NPC animal model was established, which reflects the efficacy of clinical combination therapies and the combination of Endostar and radiation. The mechanisms of the combination therapies should be further investigated using this model.
HubMed – drug
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