Study highlights the molecular cause of cachexia, referring to a potential treatment -
New research raises the prospect of more effective treatments for cachexia, a wasting deep fat and muscles occurring in about half of cancer patients, increasing their risk of death, according to scientists at the Dana-Farber cancer Institute.
many strategies have been tried to reverse the condition, which can cause such fragility that patients can not withstand potentially life-saving treatments, but none have had great success.
scientists reporting in the July 13 advance online edition of Nature , led by Bruce Spiegelman, PhD, found that mice with lung tumors symptoms of cachexia or improved were prevented when administered an antibody that blocks the effects of PTHrP protein secreted by tumor cells. PTHrP means related protein parathyroid hormone, and is known to be released from many types of cancer cells.
The scientists said their findings are the first to explain in detail how PTHrP tumors switches on a thermogenic (heat producing) process in adipose tissue, resulting in a loss of unhealthy weight.
This protein derived from a tumor, they found, stimulated "beige" or brown fat cells mixed with white fat stored in the body, causing white fat to 'brown' - which is , generating heat and even cause weight loss when the animals were at rest
researchers conducted two experiments using mice that developed lung tumors and cachexia .. in one case, is administered a polyclonal antibody that specifically neutralizes PTHrP and found that prevents the waste almost completely, while untreated animals became slightly cachexic.
In a second experiment, treatment with the antibody prevented loss of muscle mass and improve muscle function, while the control animals developed severe muscle atrophy.
"You would have expected on the basis of our first experiments in cell culture, the blocking of PTHrP in mice reduce browning fat," said Spiegelman. "But we were surprised that it also affected the muscle loss and better health."
Research has suggested that PTHrP alone does not directly cause muscle atrophy, but blocking the activity of the protein prevents.
Thus, the role of PTHrP "is certainly not the whole answer" to the riddle of cachexia, Spiegelman noted, but perhaps a necessary part, while other factors are also involved .
a contributor to the study, Vickie E. Baracos, PhD, of the University of Alberta in Edmonton, Canada, provided that the blood of 47 lung cancer patients or colon were cachexic. Serkan Kir, PhD, Spiegelman lab - and first author on the paper -found increased levels of PTHrP in 17 patients. These patients had body mass significantly lower lean and produce more heat energy at rest than are other patients in the group.
It may be that the mechanism of PTHrP is responsible for cachexia in a subset, but not all, cancer patients, Spiegelman suggested. Before trying the anti-PTHrP antibody in human patients, he said, "clinicians probably would not know first if the protein is elevated in certain cancers, and determine which patients are good candidates for a clinical trial. "
Barrett Rollins, MD, PhD, Scientific Director of Dana-Farber, noted that the report of Spiegelman and colleagues "provides a new roadmap for development, a rational mechanistic treatment for this condition incredibly debilitating happens in so many of our patients. so far we have had no truly effective way to reverse this horrible complication. "
patients with upper gastrointestinal and pancreatic cancers are more likely to develop cachexia, and the condition affects about 80 percent of the cancer patients in the terminal phase. The current strategy is to provide appetite stimulants and nutritional supplements and drugs to counter some of the molecular pathways underlying deemed wasting process, but with limited success.
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