Re: [MOL] Chris [01214] Medicine On Line


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Re: [MOL] Chris



I did resend it; but let me try again here...

Formerly Flawed Cancer Treatment Is Now ResurrectedLast spring, researchers
who had been advancing a promising cancer treatment for years found a new
obstacle looming when the international journal Nature Medicine published a
study that identified a fatal flaw: The anti-cancer protein used in the
treatment destroys healthy human liver cells.
Now researchers at the University of Pennsylvania School of Medicine have
discovered a solution to that crucial problem, re-opening what the lead
scientist in Penn's efforts calls "a window of opportunity" for using this
powerful treatment against colon, breast, lung, ovarian and esophageal
cancers.

"There are only a handful of very promising anti-cancer drugs and this one
is on that list," said Dr. Wafik El-Deiry, MD-PhD, associate professor of
medicine at Penn. "Part of the reason we've been so excited about this
treatment is because it seems to be very effective on a wide range of human
cancers. It was on its way toward clinical trials, and then there was this
setback.

"But now we've solved the toxicity problem. Within the context of clinical
trials, we should be able to protect the liver while still killing cancer
cells," said El-Deiry, who also serves as assistant investigator for the
Howard Hughes Medical Institute. Findings from his recent work are published
in today's issue of Cancer Research.

The therapy consists of injecting a cancer patient with a particular ligand
(a molecule that binds to receptors on the surface of cells) that scientists
identify by the acronym TRAIL -- for Tumor Necrosis Factor-Related Apoptosis
Inducing Ligand.

Although other related proteins such as TNF and FAS have complicated
research histories because of their side-effects, TRAIL has been widely
considered worth serious research efforts because it triggers a sweeping
death response in its target, destroying cancerous and pre-cancerous cells.

After the Nature Medicine study appeared, El-Deiry and his colleagues set
out to find the key to how TRAIL works, in order to establish a method for
using it safely.

That key lies in the enzyme family known as caspases.

Working first with colon cells, the researchers learned that cancerous colon
cells may be destroyed through two separate actions -- one of which is
triggered through a caspase-8-dependent pathway and the other through a
pathway that requires caspase 9.

Then, working with human liver cells, they found the healthy cells were
destroyed mainly through the caspase-9-requiring path. The human liver cells
could be protected from TRAIL if that path were blocked.

"When we realized that the cells have different sensitivities to these
enzymes, it immediately suggested that many malignant tumor cells will be
killed, but healthy cells will be preserved, if we use a combination of
TRAIL plus a caspase 9 inhibitor," El-Deiry said. But there remained the
problem that some cancerous cells may be destroyed only through a caspase
9-requiring pathway.

The researchers suggest solving that problem through timing: "What we are
proposing is a schedule of treatments that would avoid using chemotherapy or
radiation at the same time we use TRAIL with a caspase 9 inhibitor. That
will increase the safety and strength of both therapies," El-Deiry said. "We
think it could be something to add to other research in the setting of
clinical trials. Now, at least, there is a feasible direction for its
study."

He was assisted in the study by Penn collaborators Nesrin Ozoren; Kunhong
Kim, MD-PhD; Timothy F. Burns; David T. Dicker, and A. David Moscioni, PhD.
The study was funded by the Howard Hughes institute. - By Ellen O'Brien



We invite you to take a look at our Album.
www.angelfire.com/sc/molangels/index.html

  ( Very informational, good tips, Molers pictures, art work and much
more....



We invite you to take a look at our Album.
www.angelfire.com/sc/molangels/index.html

  ( Very informational, good tips, Molers pictures, art work and much
more....

----- Original Message -----
From: <CCR417@aol.com>
To: <mol-cancer@lists.meds.com>
Sent: Monday, November 27, 2000 2:53 PM
Subject: Re: [MOL] Subject of Pain/Reply


> Lillian, pls resend it - someone it's GONE!  -chris
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