Scorpion Venom And Nanoparticle Compound Slows Brain Cancer By 98 Percent

[Rich66]

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]

[Rich66]

A taste for scorpion venom could be cancer's undoing

• 02 October 2008
• Magazine issue 2676. Subscribe and get 4 free issues.
• For similar stories, visit the Cancer Topic Guide

RADIOACTIVE scorpion venom sounds like the ultimate doomsday weapon but it is now being tested as a treatment for malignant brain cancer.
The scorpion Leiurus quinquestriatus lives in the Middle East. Among the powerful cocktail of neurotoxins packed into its venom is a peptide that is non-toxic to humans and binds to a receptor found only on some tumour cells. In culture, the peptide has invaded tumours in breast, skin, brain and lung tissue, but left healthy cells untouched. "It's as if the tumours collect it," says Michael Egan of the company TransMolecular in Cambridge, Massachusetts. To see if the peptide could deliver lethal doses of radioactivity to cancer cells, researchers at the company have attached radioactive iodine isotopes to it.
In a trial last year, they injected this agent directly into the tumours of 59 people suffering from inoperable brain cancer. Those receiving a higher dose lived for three months longer, on average.
In recent weeks, researchers at the University of Chicago in Illinois have begun injecting TM601 into the bloodstream of people with different types of malignant brain cancer. This latest trial will allow the company to test whether TM601 can seek out and kill secondary tumours throughout the body, as well as known primary ones.
Cancer - Learn more about one of the world's biggest killers in our comprehensive special report

[Rich66]

Can deliver radiation, chemo, works alone or synergistically with other angiogenesis inhibitors (Avastin etc). Here is the company overview:

http://www.transmolecular.com


2011, transmolecular assets now owned by Morphotek: www.morphotek.com

[Rich66]

FOR IMMEDIATE RELEASE
TransMolecular Announces Presentation of Data Highlighting Anti-angiogenic and Tumor-targeting Properties of TM601 at ASCO Annual Meeting

CAMBRIDGE, MA – May 21, 2009 – TransMolecular, Inc. today announced that new data
highlighting the anti-angiogenic and tumor-targeting properties of TM601 will be discussed in a poster presentation and in a published abstract at the 45th Annual Meeting of the American Society of Clinical Oncology (ASCO), being held May 29-June 2, 2009 in Orlando, FL.
TM601 is a novel, wholly synthetic peptide, found to have robust anti-angiogenic activity in neovascular diseases, including cancer and ophthalmic disease.

Poster presentation #2041 is titled, “A Phase 1 evaluation of intravenous TM601 in recurrent glioblastoma: use of perfusion MRI to monitor anti-angiogenic effects,” and will be presented on Sunday, May 31, in the Central Nervous System Tumors General Poster Session from 8:00 am
- noon ET (Level 2, West Hall C).
Abstract #e14507 titled, “A Phase 1 evaluation of intravenous (IV) 131I-chlorotoxin delivery to solid peripheral and intracranial tumors,” was accepted for publication on the ASCO website and is available at www.asco.org and www.jco.org.

About TM601
TM601 is a novel, wholly synthetic peptide found to have robust anti-angiogenic activity in neovascular diseases, including cancer and ophthalmic disease. For oncology applications, TM601 is highly specific and selective in targeting both primary
tumors and metastases in the periphery and in the central nervous system. TM601 has the unique properties of highly specific tumor cell binding, uptake and internalization. Clinical studies confirm that TM601 targets and binds to a receptor expressed on a wide range of tumor cells, but not on normal, healthy cells. TransMolecular is expanding the TM601 tumor-targeting platform to deliver a range of therapeutic agents, including novel and currently used chemotherapeutic agents, as well as RNAi molecules, to tumor cells.
Most recently, the effects of TM601 on the neovasculature were validated in animal models of ophthalmic disease, including wet age-related macular degeneration (AMD).

About TransMolecular, Inc. TransMolecular, Inc. is committed to discovering and developing novel therapeutic products that help patients combat cancer and neovascular diseases. TransMolecular’s product pipeline is based on the TM601 platform, a novel synthetically derived polypeptide, which has both highly specific tumor binding properties and anti-angiogenic therapeutic properties. More information can be found at www.transmolecular.com.

Contacts:
TransMolecular:
Robert Radie
President and CEO
617-995-3050 x 303
Media:
Jennifer Greenleaf-Conrad
MacDougall Biomedical Communications
(781) 235-3060
jconrad@macbiocom.com
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