Navigation Links
With muscle-building treatment, mice live longer even as tumors grow
Date:8/19/2010

In the vast majority of patients with advanced cancer, their muscles will gradually waste away for reasons that have never been well understood. Now, researchers reporting in the August 20 issue of Cell, a Cell Press Publication, have found some new clues and a way to reverse that process in mice. What's more, animals with cancer that received the experimental treatment lived significantly longer, even as their tumors continued to grow.

"This is the first demonstration that muscle mass plays a key role in cancer survival," said H.Q. Han of Amgen Research.

While it has long been recognized that this muscle wasting condition, known as cachexia, affects advanced cancer patients' quality of life, Han explained, its importance for survival had primarily been a matter of speculation. Nearly 30 percent of cancer-related deaths have been attributed to cachexia, but that was based on correlative evidence only. That is, there has seemed to be a connection in cancer patients between weight loss and mortality.

Still, cachexia had typically been considered a "multi-factorial" process with many causes. "That would make it hard to target," Han said. Indeed, few therapeutic options are available and efforts to treat this aspect of the disease haven't been top of mind. Given the new results, that could change.

The researchers suspected that a pathway known as ActRIIB might be involved. ActRIIB is what's known as an activin type 2 receptor. There was evidence to suggest that tumors secrete activin, such that circulating levels of the protein rise in those with cancer. Activin is closely related to another protein, called myostatin, which is known to be important in muscle. Animals lacking myostatin or taking treatments that block it grow bigger muscles. There was some evidence to suggest that activin blockers might have a similar effect.

Based on that hunch, the researchers treated mice with cancer and associated cachexia with a recombinant and soluble version of the ActRIIB receptor (sActRIIB), a kind of molecular "decoy" that potently inhibited both activin and myostatin activity. That treatment reversed the animals' muscle loss and prolonged their survival by several weeks on average. That was despite the fact that the tumors appeared to be unaffected. The animals also kept losing fat and still had high levels of inflammatory factors.

"In tumor-bearing mice with profound cachexia, blocking this pathway not only prevents muscle wasting but completely reverses the loss of muscle, strength and anorexia," Han said. (Anorexia is another symptom of cachexia, but appetite stimulants and nutritional supplements don't help much.)

The researchers also found something that had apparently gone unnoticed before. Just as the skeletal muscles of mice with cancer withered away, so too did their heart muscle. The ActRIIB inhibiting treatment completely reversed that too.

Han said that finding may point to an unappreciated role for heart atrophy in muscle wasting conditions more broadly.

Further experimentation showed that the ActRIIB blockade prevented muscle proteins from being marked for degradation and markedly stimulated muscle stem-cell growth. Muscle stem cells were successfully activated even in muscle that had lost 50 percent of its weight prior to treatment, Han said.

"This is the first indication that there may be a major medical benefit in extending life span by combating cachexia," Han said, emphasizing however that there is a long way to go from preclinical studies in mice to clinical trials in human patients.

Still, he added, "as drug discovery scientists, we are very excited by the implications. This suggests a promising strategy for treating cachexia and underscores the need for further investigation and translational research to fully understand this pathway and explore the benefits of its antagonism."

The researchers say it will be important to explore levels of myostatin and other components of the ActRIIB pathway in various patient groups. "The dramatic, reversible changes in body mass shown here emphasize the importance of obtaining such information not only for understanding disease mechanisms but also to provide a fuller rationale for anti-activin therapies," they wrote. "However, since the inhibition of ActRIIB signaling by sActRIIB induces growth of normal muscle, this treatment is likely to be anabolic and help combat muscle loss in many catabolic conditions, even if the wasting is not triggered by excessive signaling by activin or related ligands of the ActRIIB pathway."

Han says he and his colleagues hope the findings will renew interest among cancer researchers and oncologists in cachexia. "Our results argue that blocking the catabolic actions of tumors should be a major therapeutic objective, not only to enhance quality of life but also to prolong survival," he said.


'/>"/>

Contact: Cathleen Genova
cgenova@cell.com
617-397-2802
Cell Press
Source:Eurekalert

Related medicine news :

1. Arsenic shows promise as cancer treatment, Stanford study finds
2. Immune cells predict success of head and neck cancer treatment, U-M study finds
3. BHR Pharma Statement on Brain Injury Awareness Month - Better Awareness, Treatment, Research Needed Now
4. Despite Treatment, Employees with Depression Generate Higher Absentee Costs, According to Thomson Reuters Study
5. Longer Time Frame for Clot-Busting Drug May Help Beat Stroke
6. The Longer You Sit, the Shorter Your Life Span: Study
7. Women live longer but in worse condition
8. Diabetes patients admitted for acute exacerbations of COPD have longer hospital stay
9. Longer Antiviral Therapy Reduces Lung Transplant Complications
10. iStayYoung Launches – Live Longer, and Better. Free for Seniors 65+
11. Intervention program helps breast cancer patients live longer after recurrence
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:8/24/2017)... ... August 24, 2017 , ... DrinkingTutors.com, a startup focused on ... tutorials, or ‘drinktorials,’ are mailed directly to teenagers’ homes every week. , ... their teenagers avoid the serious risks associated with binge drinking in high school, ...
(Date:8/23/2017)... ... ... Drs. Steven White and Brad Haines are pleased to announce an exclusive ... offer, valued at more than $300 per year, new patients can enjoy a lifetime ... a complimentary professional whitening procedure. , Stained or yellowed tooth enamel is common ...
(Date:8/23/2017)... , ... August 23, 2017 , ... Nightingale College continues ... Give Back Day is a time Nightingale College dedicates to serving and volunteering for ... thrive on donations and volunteers or those that need a little extra help. ...
(Date:8/23/2017)... (PRWEB) , ... August 23, 2017 , ... ... vans, announced today that has been named to the 2017 Inc. 500|5000, an ... based on a three-year growth rate of 139 percent, marking the twelfth year ...
(Date:8/23/2017)... ... August 23, 2017 , ... ... (SNAC) is holding an inaugural State of the Science Symposium in partnership ... Wednesday, Sept. 20, 2017. , This symposium provides a forum for global leaders ...
Breaking Medicine News(10 mins):
(Date:8/7/2017)... (NYSE: DPLO), the nation,s largest independent specialty pharmacy, announced financial ... unless otherwise noted, are to the quarter ended June 30, ... 2017 Highlights include: Revenue of $1,126 ... Total prescriptions dispensed of 220,000, compared to 241,000 ... Gross profit per prescription dispensed of $371, ...
(Date:8/4/2017)... , Aug. 4, 2017 The search ... shortly after a physician/patient consult has long been the ... was a notable focus of the largest meeting of ... according to healthcare market research firm Kalorama Information.  The ... testing (POCT) offerings or related supplies and software were ...
(Date:8/3/2017)... Aug. 3, 2017  Opioid addiction and other drugs ... healthcare costs and threatening outcomes, were problems taken on ... IVD industry that support them, met this week. This ... said that drugs of abuse, procalcitonin and acute kidney ... the organization,s 69th meeting in San Diego, ...
Breaking Medicine Technology: