CUTTING OFF BLOOD SUPPLY TO TUMOR

Have been reading about the various new meds out to help us and came across this. It is a year old, and while it would be better to have it mentioned in 2008 (I’ll keep looking), perhaps it might stir some thoughts.

ScienceDaily (Apr. 27, 2007) — Researchers at Johns Hopkins have discovered to their surprise that a drug commonly used to treat toenail fungus can also block angiogenesis, the growth of new blood vessels commonly seen in cancers. The drug, itraconazole, already is FDA approved for human use, which may fast-track its availability as an antiangiogenesis drug.

In mice induced to have excess blood vessel growth, treatment with itraconazole reduced blood vessel growth by 67 percent compared to placebo. “We were surprised, to say the least, that itraconazole popped up as a potential blocker of angiogenesis,” says Jun O. Liu, Ph.D., professor of pharmacology. “We couldn’t have predicted that an antifungal drug would have such a role.”

In their search for antiangiogenesis drugs, the researchers worked with cells from human umbilical cords, a rich source of blood vessels, and exposed them to 2,400 existing drugs - including FDA- and foreign-approved drugs, as well as nonapproved drugs that had passed safety trials - to see which ones could stop the cells from dividing.

“The best outcome was to find an already approved drug that worked, and the fact that we did was very satisfying,” says Liu, whose study appears online in ACS Chemical Biology.

As an antifungal drug, itraconazole blocks a key enzyme for making fungal cholesterol, causing these primitive life forms to become fragile and break apart. It turns out that itraconazole can block the same enzyme in blood vessels, but the researchers aren’t positive if that’s the reason blood vessels stop growing, because related antifungal drugs had much lower inhibitory effect.

“Our screening test did show that cholesterol-lowering statins also appear to stop blood vessel growth,” Liu says, “so there is likely some important connection between cholesterol and angiogenesis.”

While the researchers still must tease out exactly how itraconazole works to stop vessel growth, and test it in animals with cancer, they have high hopes for its use. “Itraconazole can be taken orally for fungal infection, and therefore oral delivery may work for angiogenesis as well,” Liu notes.

The research was funded by the Johns Hopkins School of Medicine, the Johns Hopkins Fund for Medical Discovery, the Johns Hopkins Malaria Research Institute, the Keck Foundation, and the Flight Attendant Medical Research Institute Fund.

Authors on the paper are Curtis Chong, Jing Xu, Jun Lu, Shridhar Bhat, David Sullivan Jr. and Jun O. Liu, all of Johns Hopkins.

Is your news related to this article, or is this another antiangiogenesis drug? This article was published in Nature.

Accidental fungus leads to promising cancer drug By Maggie Fox, Health
and Science Editor - Reuters Sun Jun 29, 6:29 PM ET

A drug developed using nanotechnology and a fungus that contaminated a
lab experiment may be broadly effective against a range of cancers, U.S.
researchers reported on Sunday.

The drug, called lodamin, was improved in one of the last experiments
overseen by Dr. Judah Folkman, a cancer researcher who died in January.
Folkman pioneered the idea of angiogenesis therapy – starving tumors by
preventing them from growing blood supplies.

Lodamin is an angiogenesis inhibitor that Folkman’s team has been
working to perfect for 20 years. Writing in the journal Nature
Biotechnology, his colleagues say they developed a formulation that
works as a pill, without side-effects.

They have licensed it to SynDevRx, Inc, a privately held Cambridge,
Massachusetts biotechnology company that has recruited several prominent
cancer experts to its board.

Tests in mice showed it worked against a range of tumors, including
breast cancer, neuroblastoma, ovarian cancer, prostate cancer, brain
tumors known as glioblastomas and uterine tumors.

It helped stop so-called primary tumors and also prevented their spread,
Ofra Benny of Children’s Hospital Boston and Harvard Medical School and
colleagues reported.

“Using the oral route of administration, it first reaches the liver,
making it especially efficient in preventing the development of liver
metastasis in mice,” they wrote in their report. “Liver metastasis is
very common in many tumor types and is often associated with a poor
prognosis and survival rate,” they added.

‘ALMOST CLEAN’ LIVERS

“When I looked at the livers of the mice, the treated group was almost
clean,” Benny said in a statement. “In the control group you couldn’t
recognize the livers – they were a mass of tumors.”

The drug was known experimentally as TNP-470, and was originally
isolated from a fungus called Aspergillus fumigatus fresenius.

Harvards’s Donald Ingber discovered the fungus by accident while trying
to grow endothelial cells – the cells that line blood vessels. The mold
affected the cells in a way known to prevent the growth of tiny blood
vessels known as capillaries.

Ingber and Folkman developed TNP-470 with the help of Takeda Chemical
Industries in Japan in 1990.

But the drug affected the brain, causing depression, dizziness and other
side-effects. It also did not stay in the body long and required
constant infusions. The lab dropped it.

Efforts to improve it did not work well. Then Benny and colleagues tried
nanotechnology, attaching two “pom-pom”-shaped polymers to TNP-470,
protecting it from stomach acid.

In mice, the altered drug, now named lodamin, went straight to tumor
cells and helped suppress melanoma and lung cancer, with no apparent
side effects, Benny said.

All untreated mice had fluid in the abdominal cavity, and enlarged
livers covered with tumors. Mice treated with lodamin had normal-looking
livers and spleens, the researchers said.

Twenty days after being injected with cancer cells, four out of seven
untreated mice had died, while all treated mice were still alive,
Benny’s team reported.

“I had never expected such a strong effect on these aggressive tumor
models,” she said. The researchers believe lodamin may also be useful in
other diseases marked by abnormal blood vessel growth, such as age-
related macular degeneration.

jenny-
must be related - thanks for the article
its very interesting
and amazing how it was found!

Emily
xxx