Here's the first of several TPI-2 abstracts that I'll upload. TPI-2 is the molecule involved in the CIST cross license with Biotech Australia, the Hoechst venture that has it in a phase I clinical trial. From CIST's 10-K, page 6...... "in May 1993 Cistron entered into the Biotech agreement under which Cistron will receive royalties on the net sales of therapeutic PAI-2 products sold by Biotech or its affiliates in the U.S. Cistron obtained a cross license from Biotech for development of PAI-2 diagnostic products. Cistron has been advised by Biotech that it opened an Australian manufacturing facility in October 1994, has conducted anti-inflammatory animal studies, and initiated a Phase I human clinical trial in Australia in August 1996." As you will see from this post and the next four or so, Aussies are crawling all over this molecule..... TPA, GM-CSF, intraperitoneal adhesions, TNF........ there are many research endeavors for which a TPI-2 test kit might be of interest.......
Plasminogen activator inhibitor type 2 inhibits tumor
necrosis factor alpha-induced apoptosis. Evidence for an
alternate biological function.
Medline. Medlars UID 96070927
J Biol Chem Vol. 270 no. 46 pp. 27894-904
Type: JOURNAL ARTICLE
CAS Registry/EC Number: EC 2.3.1.28 (Chloramphenicol Acetyltransferase)
CAS
Registry/EC Number: 0 (DNA Primers) CAS Registry/EC Number: 0 (Immune
Sera) CAS
Registry/EC Number: 0 (Plasminogen Activator Inhibitor 2) CAS
Registry/EC Number: 0
(Recombinant Proteins) CAS Registry/EC Number: 0 (Tumor Necrosis Factor)
CAS
Registry/EC Number: 66-81-9 (Cycloheximide)
Language: Eng
Country: UNITED STATES
Journal Code: HIV
Indexing Priority: 1
Journal Subset: M Journal Subset: X
MeSH Headings: Amino Acid Sequence Apoptosis/*drug effects Base Sequence
Cell
Line Cell Nucleus/drug effects/physiology/ultrastructure Cell
Survival/drug
effects Chloramphenicol Acetyltransferase/analysis/biosynthesis
Cycloheximide/pharmacology Dose-Response Relationship, Drug DNA Primers
Hela Cells Human Immune Sera Immunoblotting Kinetics Molecular Sequence
Data Mutagenesis, Site-Directed Plasminogen Activator Inhibitor
2/biosynthesis/*physiology Point Mutation Polymerase Chain Reaction
Recombinant Proteins/metabolism/pharmacology Support, Non-U.S. Gov't
Transfection Tumor Necrosis Factor/antagonists &
inhibitors/immunology/*pharmacology
DATE: 1995 Nov 17
Abstract
Plasminogen activator inhibitor type 2 (PAI-2) is a serine proteinase
inhibitor or serpin that is a
major product of macrophages in response to endotoxin and inflammatory
cytokines. We have
explored the role of PAI-2 in apoptotic cell death initiated by tumor
necrosis factor alpha (TNF).
HeLa cells stably transfected with PAI-2 cDNA were protected from
TNF-induced apoptosis,
whereas cells transfected with antisense PAI-2 cDNA, a control gene, or
the plasmid vector alone
remained susceptible. The level of PAI-2 expressed by different HeLa
cell clones was inversely
correlated with their sensitivity to TNF. Loss of TNF sensitivity was
not a result of loss of TNF
receptor binding. In contrast, PAI-2 expression did not confer
protection against apoptosis induced
by ultraviolet or ionizing radiation. The serine proteinase
urokinase-type plasminogen activator was
not demonstrated to be the target of PAI-2 action. The P1-Arg amino acid
residue of PAI-2 was
determined to be required for protection, because cells expressing PAI-2
with an Ala in this position
were not protected from TNF-mediated cell death. The results suggest
that intracellular PAI-2 might
be an important factor in regulating cell death in TNF-mediated
inflammatory processes through
inhibition of a proteinase involved in TNF-induced apoptosis.
Dickinson JL Bates EJ Ferrante
A Antalis TM
Queensland Cancer Fund Experimental Oncology Unit, Queensland
Institute of Medical Research,
Brisbane,
Australia.
1995
960822 |
