Cell death was once
thought to be a passive non-specific event, but is now
known to be an
active biochemical process. Scientists have discovered that any
cells have the
ability to die by this process, called programmed cell death or
A number of important
human diseases are caused by abnormal apoptosis
which can result in either a pathological increase in the
number of cells
(e.g. cancer) or a damaging loss of cells (e.g. degenerative
data has shown that cells have a discrete cell death pathway
defined by a specific
set of genes. These genes encode proteins that form the
that ultimately invokes cell death.
The key genes that
control the cell death process are the cell death effectors of
the CED-3/ICE ("caspase")
family and the cell death inhibitors of the Bcl-2
family. The caspase
gene family encodes a set of proteases responsible for
carrying out the
death process. In a living cell, these proteases are normally
kept inactive by
proteins encoded by the Bcl-2 family.
The caspases are a
family of proteases responsible for carrying out the cell death
process. In a living
cell, these proteases are kept inactive by proteins on the
surface from the BcL-2 family. When a cell is exposed to cell death
signals such as ischemia,
chemotherapy or radiation, BcL-2 function is blocked and
initiate the cell death cascade.
Small molecule drugs,
like CHML, are able to specifically modulate the activity
of the caspase
family, the Bcl-2 family, or other key points in the apoptotic
pathway, and exert
control over the cell death process and have utility in
by either excessive or insufficient levels of apoptosis.
CHML is able to specifically modulate
key points in the apoptotic pathway.
p53 protein, commonly referred to as "the tumor suppressor
gene," is a key player
in the cellular apoptosis process. Bio-therapeutic
activation of this pathway, has
been a popular target for recent drug discovery technology.
p53, Bax and p21 protein levels were measured by immunoblotting
MCF-7, ML-1, H1299 (human lung carcinoma) and RKO
(human colon cancer,)
cell lines after treatment with CHML. p53 protein
was found to be elevated in
the MCF-7, RKO and ML-1 cells.
As the ability to induce apoptosis is not limited to
p53 positive cell lines, it
appears that CHML is able to provoke apoptosis through
and -independent pathways.
Supporting GLORY's drug discovery
program, is a sophisticated new technology
for drug administration. Arterial
Infusion using DSA*, is a fast developing
science performed by trained
Interventional Radiologists. Formerly used in
the management of Cardiology
related conditions, the technology is capable of
delivering concentrated drugs
to a highly specific site (e.g. tumor) via the
(Real Time DSA) movie of destruction of tumor feeding network.
CHML Arterial Infusion using
Digital Subtraction Angiography.*
DSA is capable of delivering
concurrent imaging of the intricate vasculature of
the tumoral network. This is
used to guide the delivery of CHML, as well as
measure the immediate effects
on the tumors blood supply network.
In recent studies, CHML was able
to effect significant disruptions to the tumoral
vasculature network in a number
of various malignancies. In virtually every
case, marked destruction of
the tumor's feeding system could be observed in
less than 30 minutes.
This information further corroborates
CHML's ability to penetrate a number
of difficult tumors.
Marked reduction can be seen
on the two angiogram sequences below.