+ + data and comments + +, page-6

re: + + anti-angiogenic drug pi-88 + + A more comprehensive look at PGL's lead drug PI-88:

Refer to the "Cancer dictionary": http://www.cancersource.com/Resources/glossary/index.cfm?DiseaseID=14

The cancers Melanoma, Myeloma an Leukemia can be found here.

The Anti-Angiogenic drug PI-88 is being used in a number of trials. The Phase II trial (Melanoma + Taxotere) has just begun while the drug achieved efficacy endpoint in Phase II Multiple Myeloma ( Refer to the first post of this thread). A reference was also made to PI-88 being a potential leukaemia drug.

These diseases are being feared : Melanoma can travel to other sites of the body (metastasis) and is #1 cause of death in women, aged 25 to 30.

1. Melanoma
When Phase II Melanoma trial was started on Jan. 21, 2004, the following statement was made: "Rob Don, Progen’s VP of R&D commented “PI-88 has been well tolerated by patients in the Phase I trial.

We have also seen positive signs that PI-88 has retarded tumor growth in over 40% of the melanoma patients for periods lasting up to 30 months.

These are particularly encouraging data, as all patients in this trial have advanced cancers, have previously failed to respond to standard surgical, radiation and chemotherapeutic regimens, and they have limited treatment options left available to them.”

2. Myeloma
Myeloma is a cancer arising in the plasma cells in the BONE MARROW. The deathtoll can be high.

July 8, 2003: Progen Industries Ltd (ASX: PGL, Nasdaq: PGLAF) announces the completion of the PI-88 Phase II trial in Multiple Myeloma and achievement of the study’s primary efficacy endpoints.

"The primary endpoint of the study was to investigate clinical efficacy in patients who had exhausted other treatment options.

For the purposes of this study, a clinical response was pre-specified as patients remaining stable or experiencing a decrease in blood levels of paraprotein (a marker of multiple myeloma disease severity). This endpoint was achieved in 39% of patients in the study".

3. Summary of achievements.
Some diseases are very difficult to treat and the primary objective is to lengthen the life span. Any extension of 3 months or more may be deemed highly significant by the FDA.

Patients taking part tend to be "end-stage" patients who may consider this drug as a last resort. Results sofar do show that PI-88 is very promising IMHO.
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Here is a summary of what PI-88 does-Reference PGL's website or reports:

"In preclinical studies, PI-88 has been shown to retard the growth of primary tumors by inhibiting new blood vessel growth (angiogenesis) through two mechanisms:


First; PI-88 inhibits endothelial cell proliferation by preventing the growth factors bFGF and VEGF from binding to the receptors on endothelial cells. ( Endothelial cells form the walls of blood vessels)

Second; PI-88 inhibits the heparanase enzyme secreted by a variety of cells, thus preventing the degradation of the extracellular matrix and the release of growth factors. ( Heparanase degrades the natural "glue" or extracellular matrix which holds cells together in a human body).

Additionally, PI-88 has exhibited the ability to inhibit metastasis in animal models by inactivating heparanase. This prevents the degradation of the extracellular matrix and the basement membrane of blood vessels which would otherwise allow the migration of tumor cells across the basement membrane".

Growth Factors:
BFGF: Basic Fibroblast Growth Factor, one of a family of naturally occurring chemical messengers (cytokines) that stimulate blood vessel growth. Also known as FGF-2.
VEGF: Vascular Endothelial Growth Factor, one of a family of naturally occurring chemical messengers (cytokines) that stimulate blood vessel growth.


Heparanase
An enzyme of the class endoglycosidase which is capable of cleaving heparan sulfate and has been implicated in many important physiological and pathological processes including tumour cell metastasis, angiogenesis and leukocyte migration.

Angiogenesis
The development of new blood vessels. This process is essential for the formation of tumours and metastasis.

"PI-88 is a small molecule with anti-angiogenic, anti-metastatic and anti-thrombotic properties".


Gerry
Readers, please do your own research and you decide if and when to buy, hold or sell any stocks.