Navigation Links
Cancer requires support from immune system to develop, UT Southwestern researchers report
Date:10/30/2008

DALLAS Oct. 30, 2008 Tumors that grow around nerves in a rare genetic disease need cooperation from cells from the immune system in order to grow, reports a team of scientists, including researchers from UT Southwestern Medical Center.

Treating mice with a drug that attacks the immune cells not the tumor greatly reduced the size and metabolism of the tumors, the scientists reported. A clinical trial of the treatment in humans has begun.

"It was not the tumor being treated, but its environment," said Dr. Luis Parada, chairman of developmental biology at UT Southwestern and co-senior author of the study, which appears in the Oct. 31 issue of the journal Cell. "This insight has led to a very promising therapy of a previously untreatable tumor.

"This is the first time a mouse model has been used to gain insight into a cancer that could not be derived from patient studies," said Dr. Parada, director of the Kent Waldrep Center for Basic Research on Nerve Growth and Regeneration.

The researchers were studying tumors called plexiform neurofibromas, which occur around peripheral nerves. In humans, they occur as part of a genetic disease called neurofibromatosis-1. About 25 percent to 40 percent of people with the disease develop the tumors, which are generally benign but can grow large enough to cause disfigurement or disability and can sometimes become malignant.

These tumors are complex structures that include many different types of cells, particularly Schwann cells, which provide a fatty coating that makes nerve cells electrically efficient, and mast cells.

Because of their complexity, plexiform neurofibromas are difficult to remove surgically, and there is currently no cure for them.

Neurofibromatosis-1 is caused by a mutation in a single gene called Nf1. About 250,000 people in the U.S., Europe and Japan have this mutation. The mutation is dominant, meaning that people with one normal gene and one mutated gene develop the disease.

The UT Southwestern researchers had previously found in mice that plexiform neurofibromas develop from Schwann cells that have two mutated copies of Nf1. In addition, they discovered that even before a plexiform neurofibroma begins to form around a nerve, mast cells migrate into the area.

In the current study, the scientists used genetically engineered mice to confirm first that the animals need two mutated copies of Nf1 in their Schwann cells to develop neurofibromas, which the rest of their cells can still have one normal and one mutant Nf1 gene.

In addition, a bone marrow transplant from normal mice with two normal Nf1 genes prevented 90 percent of the engineered mice from developing neurofibromas, confirming that even with two mutated genes in the Schwann cells, a mutated copy must also be present in other cells. Bone marrow is the source of mast cells, blood cells and many other types of cells that circulate through blood vessels.

The researchers then focused on the role of mast cells in tumor formation, particularly a molecule on the cells' surface called c-kit, which controls many functions, including migration and proliferation.

The mice engineered to develop tumors were given the drug imatinib mesylate, also known as Gleevec. The drug, known to inhibit c-kit, currently is used to treat chronic myelogenous leukemia and other cancers.

Positron emission tomography scans showed that Gleevec halved the metabolic activity of the tumors, while later examination confirmed that the tumors were much smaller than in placebo-treated mice.

"We found there was a requirement from the immune system to interact with the tumor for the tumor to grow," Dr. Parada said. "When mast cells are blocked, the tumor cannot grow."

During the course of these experiments, the researchers learned about a girl who had a large neurofibroma that could not be removed surgically because too many blood vessels were involved. Because Gleevec is already approved for other conditions, the girl's doctor treated her under "compassionate use" guidelines.

The girl's tumor shrank by 70 percent with no apparent side effects during the first three months of a six-month treatment under "compassionate use" regulations. The mass has remained dormant in the six months afterward, the researchers reported.

While this was only a single case, it was consistent with the one-year study of the tumor and its action in mice, Dr. Parada said, and the child's treatment was tailored to reflect the findings from the animal study.

A phase 2 clinical trial of this treatment in people with neurofibromatosis has been approved and is under way.

Dr. Parada cautioned, however, that further research is needed. A single human case, while encouraging, is not enough to prove the long-term effectiveness of the treatment, and Gleevec might be exerting other actions in addition to inhibiting mast cells.


'/>"/>

Contact: Aline McKenzie
aline.mckenzie@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center
Source:Eurekalert  

Related medicine news :

1. Conventional prognostic factors fail to explain better prostate cancer survival in most Asian men
2. Survival differences by race most apparent in advanced stages of breast cancer
3. MRI finds breast cancer before it becomes dangerous
4. Investigators uncover intriguing clues to why persistent acid reflux sometimes turns into cancer
5. Pathway links inflammation, angiogenesis and breast cancer
6. Radiologists encouraged to look beyond cancer for clinically unseen diseases
7. Diet high in meat, fat and refined grains linked to risk for colon cancer recurrence, death
8. Immune deficiency linked to a type of eye cancer
9. Drop in breast cancer incidence linked to hormone use, not mammograms
10. Breast cancer prevention practices vary across Canada
11. First biomarker discovered that predicts prostate cancer outcome
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Cancer requires support from immune system to develop, UT Southwestern researchers report
(Date:6/26/2016)... ... June 26, 2016 , ... PawPaws brand pet supplements owned by ... to enhance the health of felines. The formula is all-natural and is made from ... the PawPaws Cat Kidney Support Supplement Soft Chews are Astragalus Root Extract ...
(Date:6/25/2016)... ... June 25, 2016 , ... The temporary closing of Bruton Memorial Library on June ... , brings up a new, often overlooked aspect of head lice: the parasite’s ability to ... is not a common occurrence, but a necessary one in the event that lice have ...
(Date:6/25/2016)... ... June 25, 2016 , ... On Friday, June 10, Van Mitchell, Secretary ... Work award to iHire in recognition of their exemplary accomplishments in worksite health promotion. ... Maryland Workplace Health & Wellness Symposium at the BWI Marriott in Linthicum Heights. iHire ...
(Date:6/24/2016)... CA (PRWEB) , ... June 24, 2016 , ... Marcy was in a crisis. Her ... would lash out at his family verbally and physically. , “When something upset him, he ... he would use it. He would throw rocks at my other children and say he ...
(Date:6/24/2016)... , ... June 24, 2016 , ... Topical BioMedics, Inc, makers of Topricin and MyPainAway ... call for a minimum wage raise to $12 an hour by 2020 and then adjusting ... restore the lost value of the minimum wage, assure the wage floor does not erode ...
Breaking Medicine News(10 mins):
(Date:6/26/2016)... -- Story Highlights: , ... health care industry is causing providers to review operating ... offers a suite of solutions for health care providers ... optimization: labor resource analysis, revenue cycle optimization and physician ... and better economics ...
(Date:6/24/2016)... CAMBRIDGE, Mass. , June 24, 2016 /PRNewswire/ ... the Spaulding Rehabilitation Network,s Dean Center for ... of Physical Medicine and Rehabilitation, MIT Hacking Medicine, ... Center for Innovation, today announced the five finalists ... Hackathon for Lyme disease.  More than 100 scientists, ...
(Date:6/24/2016)... , June 24, 2016 Dehaier Medical Systems ... "Company"), which develops, markets and sells medical devices and ... , signed a strategic cooperation agreement with Hongyuan Supply ... Supply Chain") on June 20, 2016, to develop Dehaier,s ... strategic cooperation agreement, Dehaier will leverage Hongyuan Supply Chain,s ...
Breaking Medicine Technology: