pictures at the link:
http://inventorspot.com/articles/sco...cer_98_p_26576
At the University of Washington, where were already studying the effects of venom as a treatment for brain, one group found that they could enhance the effectiveness of the venom by preparing a compound including nanoparticles. This venom/nanoparticle compound cut the cancer spread rate by 98 percent, compared to 45 percent from the venom alone.The lead researcher on this study, Migin Zhang, professor of materials science and engineering, said the results of the study were surprising to everyone. "People talk about he treatment being more effective with nanoparticles, but they [didn't] know how much -- maybe 5 percent or 10 percent."
An almost 100 percent improvement of the scorpion venom treatment alone was quite a bit more than expected.
Scientists have been studying the effects of a peptide called
chlorotoxin that is extracted from scorpion venom to target and treat cancer cells. It binds to certain cancer cells, particularly those with MMP-2 cells.
MMP-2 cells normally spread the cancerous cells to other parts of the body, but when the chlorotoxin attaches itself, it actually causes the MMP-2 to go inside of the cell, keeping the cell from exiting its immediate area.
The nanoparticles intensify the effects of the chlorotoxin because several chlorotoxin cells can bind to one nanoparticle and, as the compound is introduced to the cancer site, the chlorotoxins can attach to several MMP-2s, not just one. Additionally, nanoparticles help keep the chlorotoxins active longer, giving them additional time to do their work.
The following images from thestudy show how the cancer cell is prevented from spreading.
Anticancer Res. 2010 Jan;30(1):39-46.
Potent pleiotropic anti-angiogenic effects of TM601, a synthetic chlorotoxin peptide.
Jacoby DB,
Dyskin E,
Yalcin M,
Kesavan K,
Dahlberg W,
Ratliff J,
Johnson EW,
Mousa SA.
TransMolecular, Inc., 840 Memorial Drive, Cambridge, MA 02139, USA.
jacoby@transmolecular.com
Chemically synthesized chlorotoxin (TM601) has been studied as a tumor targeting peptide. In this study, the anti-angiogenic properties of TM601 are reported. MATERIALS AND METHODS: In vitro and in vivo models of angiogenesis and tumor growth were used to characterize the anti-angiogenic effects of TM601. RESULTS: TM601 bound to proliferating vascular endothelial cells, decreased human umbilical vein endothelial cell (HUVEC) invasion, and reduced secretion of bioactive matrix metalloproteinase-2 (MMP-2). Using the chick chorioallantoic membrane assay (CAM), TM601 inhibited angiogenesis stimulated by any of eight pro-angiogenic factors, and when TM601 was co-administered with bevacizumab, the combination was significantly more potent than a ten-fold increase in bevacizumab dose. TM601 did not alter tumor or vascular endothelial cell growth in vitro, but TM601 treatment of tumors grown on the CAM decreased tumor growth and intra-tumoral hemoglobin levels. Intravenously injected TM601 was also shown to significantly decrease new blood vessel growth in mice. CONCLUSION: TM601 inhibits angiogenesis stimulated by many factors and potentiates the anti-angiogenic effect of bevacizumab.
PMID: 20150615 [PubMed - in process]
J Biol Chem. 2010 Feb 12;285(7):4366-74. Epub 2009 Dec 15.
Annexin A2 is a molecular target for TM601, a peptide with tumor-targeting and anti-angiogenic effects.
Kesavan K,
Ratliff J,
Johnson EW,
Dahlberg W,
Asara JM,
Misra P,
Frangioni JV,
Jacoby DB.
TransMolecular Inc., Cambridge, Massachusetts 02139, USA.
TM601 is a synthetic form of chlorotoxin, a 36-amino acid peptide derived from the venom of the Israeli scorpion, Leirius quinquestriatus, initially found to specifically bind and inhibit the migration of glioma cells in culture. Subsequent studies demonstrated specific in vitro binding to additional tumor cell lines. Recently, we demonstrated that proliferating human vascular endothelial cells are the only normal cell line tested that exhibits specific binding to TM601. Here, we identify annexin A2 as a novel binding partner for TM601 in multiple human tumor cell lines and human umbilical vein endothelial cell (HUVEC). We demonstrate that the surface binding of TM601 to the pancreatic tumor cell line Panc-1 is dependent on the expression of annexin A2. Identification of annexin A2 as a binding partner for TM601 is also consistent with the anti-angiogenic effects of TM601. Annexin A2 functions in angiogenesis by binding to tissue plasminogen activator and regulating plasminogen activation on vascular endothelial cells. We demonstrate that in HUVECs, TM601 inhibits both vascular endothelial growth factor- and basic fibroblast growth factor-induced tissue plasminogen activator activation, which is required for activation of plasminogen to plasmin. Consistent with inhibition of cell surface protease activity, TM601 also inhibits platelet-derived growth factor-C induced trans-well migration of both HUVEC and U373-MG glioma cells.
PMID: 20018898 [PubMed - in process]
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