Therefore in the present study we looked for a relationship between F3 and HPSE expression in NSCLC tumors and investigated whether TF and heparanase
are regulated by TP53, PTEN, and STK11.
Research teams in Australia and Israel have both found the long-sought gene for heparanase
, an enzyme that cancer cells use to spread through the body.
Cinara Echart, Gentium's Manager of Molecular Biology, at the same meeting, Defibrotide demonstrated the ability to significantly downregulate heparanase
gene expression and activity in myeloma cell lines in a dose dependent manner (p less than 0.
Two posters presented data that suggest that Defibrotide may suppress tumor-associated angiogenesis and tumor dissemination through suppression of heparanase
with a subsequent reduction in the release of stores of growth factors from the extra-cellular matrix.
In summary, following the decisions taken, Progen will: -- Contract out the commercial supply of PI-88 to an established bio-pharmaceutical manufacturing facility that has a long-standing history of producing commercial bio-pharmaceuticals with FDA approvals; -- Downsize its manufacturing facility from 17 to 9 FTE staff; -- Downsize its drug discovery team from 12 to 8 FTE staff; and -- Retain key staff: - For continuing development of Progen's discovery heparanase
inhibitor program; - For biological assessment of the expanded Progen portfolio of preclinical compounds; and - To manage the transfer of manufacturing know-how and the submission of, amongst others, the Chemistry, Manufacturing and Controls (CMC) parts of the New Drug Application (NDA).
Continued to present data in support of Defibrotide's mechanisms of action at numerous prestigious medical meetings, most recently at the American Association of Cancer Research (AACR), where pre-clinical data was presented showing Defibrotide to modulate heparanase
expression and to prevent angiogenesis both of which have been correlated with advanced progression and metastasis of many tumor types, including multiple myeloma; and at the recent World Congress of Nephrology, pre-clinical data was presented showing Defibrotide to modulate glucose-induced heparanase
expression, representing a potential mechanism of anti-diabetic activity
We are confident that we have the financial resources to drive this new portfolio of assets to the next decision points in the coming 18 months while continuing our development programs for PI-88, PG500 and heparanase
Defibrotide Shown to Modulate Glucose-induced Heparanase
Expression, Representing a Potential Mechanism of Anti-Diabetic Activity
PI-88 is part of a new class of multi-targeted cancer therapeutics inhibiting both angiogenesis (or tumour promoting) factors such as Vascular Endothelial Growth Factor (FEGF), Fibroblast Growth Factors (FGF) 1 and 2, and heparanase
, a degrading enzyme implicated in metastasis (tumour spread).
Defibrotide Shown to Modulate Heparanase
Expression and Prevent Angiogenesis
Abstracts selected for poster presentation include the following: Saturday, June 23, 2007 (12:30pm-2:30pm): 0733 - Role of Reactive Oxygen Species in High Glucose-Induced Heparanase
Expression and Heparan Sulfate Proteoglycan Degradation in the Human Endothelial Cells XIULONG XU, GEETHA RAO, WENDY HUANG, RICHARD A.
Rather than relying on a single mode of action to induce an anticancer response, its anti-angiogenic properties derive from inhibiting multiple growth factors, including Fibroblast Growth Factors (FGFs) and VEGF, as well as inhibiting other angiogenic agents, including heparanase