Navigation Links
Experimental anti-cancer drug made from corn lillies kills brain tumor stem cells
Date:8/30/2007

A drug that shuts down a critical cell-signaling pathway in the most common and aggressive type of adult brain cancer successfully kills cancer stem cells thought to fuel tumor growth and help cancers evade drug and radiation therapy, a Johns Hopkins study shows.

In a series of laboratory and animal experiments, Johns Hopkins scientists blocked the signaling system, known as Hedgehog, with an experimental compound called cyclopamine to explore the blockades effect on cancer stem cells that populate glioblastoma multiforme. Cyclopamine has long been known to inhibit Hedgehog signaling.

They reported their findings in the journal Stem Cells published online on July 19.

Our study lends evidence to the idea that the lack of effective therapies for glioblastoma may be due to the survival of a rare population of cancer stem cells that appear immune to conventional radiation and chemotherapy, says Charles G. Eberhart, M.D., Ph.D., associate professor of pathology, ophthalmology and oncology, who led the work. Hedgehog inhibition kills these cancer stem cells and prevents cancer from growing and may thus develop into the first stem cell-directed therapy for glioblastoma.

Eberhart cautioned that while his study appears to prove the principle of Hedgehog blocking, much work remains before cyclopamine or any similar drug can be tested in patients. Scientists must determine whether the drug can be effectively and safely delivered to the whole body or whether it must go into the brain, and what if any adverse impact on normal stem cells the treatment might cause.

Once youve answered those questions in animals, the next step would be starting phase I clinical trials in humans, Eberhart said.

The new study adds to the growing evidence that only a small percentage of cancer cells - in this case stem cells - are capable of unlimited self-renewal and that these cells alone power a tumors growth.

Eberhart focused on two pathways important to the survival of normal brain stem cells-Hedgehog and Notch-suspecting that brain cancer stem cells cannot live without them.

The Hedgehog gene, first studied in fruit flies, got its name because during embryonic development, the mutated version causes flies to resemble a spiky hedgehog. The pathway plays a major role in controlling normal fetal and postnatal development, and, later in life, helping normal adult stem cells function and proliferate.

The Johns Hopkins scientists first tested 19 human glioblastomas removed during surgery and frozen immediately, and found Hedgehog active in five at the time of tumor removal. They also found Hedgehog activity in four of seven glioblastoma cell lines.

Next, the team used cyclopamine, chemically extracted from corn lilies that grow in the Rocky Mountains, to inhibit Hedgehog in cells lines growing on plastic or as neurospheres, round clusters of stems cells that float in liquid nutrients. This reduced tumor growth in the cell-laden plastic by 40 to 60 percent, and caused the neurospheres to fall apart without any new growth of the cell clusters.

The researchers also pretreated mice with cyclopamine before injecting human glioblastoma cells into their brains, resulting in cancer cells that failed to form tumors in the mice.

Other researchers have shown that radiotherapy fails to kill all cancer stem cells in glioblastomas, apparently because many of these cells can repair the DNA damage inflicted by radiation. The Hopkins team suggests that blocking the Hedgehog pathway with cyclopamine kills these radiation-resistant cancer stem cells.

In previous laboratory experiments, Eberhart used cyclopamine to block Hedgehog using medulloblastoma cells, the most common brain cancer occurring in children.

Along with childhood brain cancers, cyclopamine has shown early promise in treating skin cancer; rhabdomyosarcoma, a muscle tumor; and multiple myeloma, a cancer of the white blood cells in bone marrow.

What excites me is that we have taken things we learned about Hedgehog signaling in these relatively rare childhood brain tumors and translated them into an even more aggressive adult tumor, Eberhart said.

More than 10,000 Americans die annually from glioblastomas. Radiation is the standard therapy for the disease, and several years ago, the U.S. Food and Drug Administration approved adding the drug temozolomide to radiotherapy because the combination provided a small survival increase.

This is an incredibly difficult tumor to treat, says first author Eli E. Bar, Ph.D., a postdoctoral fellow. Survival for glioblastoma has not changed much in 30 years. With the addition of temozolomide, survival got bumped from 12 months to 14 or 15 months.


'/>"/>
Contact: Vanessa Wasta
wastava@jhmi.edu
410-955-1287
Johns Hopkins Medical Institutions
Source:Eurekalert

Related medicine news :

1. Experimental treatment for Ebola Virus Shows promising results in mice
2. Experimental drug to fight flu
3. Experimental SARS Vaccine
4. Experimental vaccine for shingles is effective
5. Experimental Blood Test May Spot Heart Attack Risk, Study Says
6. Five AIDS Patients To Receive Experimental Anti-retroviral Drugs
7. TMC 114 and 125 experimental drugs to be tested on four HIV patients
8. FDA approves Phase 0 trial which tests experimental drugs on humans
9. Protection against HIV and Herpes is possible with the Experimental Microbicide
10. Experimental Therapy Effective Against Malignant Melanoma in Horses
11. Experimental Alzheimer’s Drug curbs the disease in mic
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/18/2017)... , ... January 18, 2017 , ... ... asset protection and financial planning services to families and business owners in the ... aimed at supporting children with developmental disabilities. , The Lakemary Center is a ...
(Date:1/18/2017)... ... January 18, 2017 , ... Catalent ... for drugs, biologics and consumer health products, today announced that Mr. Michael Merges, ... upcoming WCBP Conference, to be held at the Mayflower Hotel, Washington DC, on ...
(Date:1/18/2017)... , ... January 18, 2017 , ... ... the revolutionary Active Brake Technology (ABT), an innovative braking system that allows skaters ... Brake Technology addresses one of the biggest concerns of beginner and intermediate skaters ...
(Date:1/17/2017)... Michigan (PRWEB) , ... January 17, 2017 , ... January is National Stalking Awareness ... who choose to lurk in the corners and commit the crime of stalking, a very ... use and addiction, an often overlooked factor in stalking and other crimes. , “Stalking: know ...
(Date:1/17/2017)... , ... January 17, 2017 , ... ... point of difference. Eden Activewear is a stand-out company for several differences from ... online and only manufacture on demand, this is called 'Agile' manufacturing - ...
Breaking Medicine News(10 mins):
(Date:1/18/2017)... , Jan. 18, 2017  Dermata Therapeutics, LLC, ... to treat a variety of dermatological diseases, announces ... DMT210, in a Phase 2 acne rosacea study. ... downregulate the proinflammatory cytokines in the skin responsible ... rosacea. This clinical trial, DMT210-003, ...
(Date:1/18/2017)... Safe Rx LLC and Good Day Pharmacy, ... Loveland, Colorado , today announced the availability ... Day locations.     "Patients with prescriptions prone ... storage," said Milton Cohen , President & CEO ... a cup of coffee, you can protect your children ...
(Date:1/18/2017)... In China , we say Health is ... China,s Healthy Strategy originates. 2016 is ... and Social Development of the People,s Republic of ... council of the People,s Republic of China ... plan, identifying medical devices as one of the main breakthrough ...
Breaking Medicine Technology: