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NSAIDs reduce lung cancer growth, cachexia in mice


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NSAIDs reduce lung cancer growth, cachexia in mice

Mat■as A. Loewy

Reuters Health

Posting Date: June 9, 2004

Last Updated: 2004-06-09 14:26:02 -0400 (Reuters Health)

BUENOS AIRES (Reuters Health)- Non-steroidal inflammatory drugs (NSAIDs) appear to reduce tumor growth, metastasis and related cachexia in a mouse model of non-small cell lung cancer (NSCLC), a new study shows.

Argentine researchers administered the nonselective COX inhibitor indomethacin and the selective COX-2 inhibitor celecoxib in mice inoculated with LP07 lung adenocarcinoma. These animals "show some characteristics that are similar to those present in patients with NSCLC," they write in the July 20th online edition of the International Journal of Cancer.

As expected, both drugs were effective in delaying cancer progression, authors reported. Treatment reduced the growth of LP07 tumors, as well as the number and size of lung metastases, by about two thirds.

Furthermore, indomethacin and celecoxib were able to relieve some symptoms of paraneoplastic syndrome, including cachexia, leukocytosis and hypercalcemia.

Total leukocyte counts and cachexia, evaluated by weight loss, were reduced in treated groups. "Control mice lost about 10% of their body weight, while treated mice maintained or slightly gained weight," authors report.

NSAIDs appeared to prevent tumor growth and metastasis by interfering with angiogenesis, and cell migration and invasion. Researchers suggest that angiogenesis and cell invasiveness may be partly mediated by inhibition of metalloproteinase MMP-9.

Prevention of cachexia may be related to reduction of interleukin 6 (IL-6) and IL-1-beta, which were modulated by NSAIDs treatment.

"As far as I know, this is the first time that NSAIDs have been shown to prevent cachexia in an animal model of lung cancer," said lead author Guillermo Peluffo, of the University of Buenos Aires Oncology Institute Angel Roffo.

According to authors, additional NSAID therapy might help overcome cachexia and improve quality of life of patients with lung cancer and those with other types of tumors.

Recently, Dr. Peluffo took part in a pilot study exploring the effects of selective NSAIDs on cachexia in 15 patients with advanced lung adenocarcinoma. Thirteen of the 15 patients maintained or gained weight after 6-week treatment with the combination of celecoxib, medroxyprogesterone and fish oil supplementation.

Additional large clinical trials are needed to prove the benefits of NSAIDs for the treatment of lung cancer progression and cachexia, researchers added.

In J Cancer 2004;11:825-830.

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