Inhibition of Tumor Progression and Paraneoplastic Syndrome Development in a Murine Lung Adenocarcinoma by Medroxyprogesterone Acetate and Indomethacin

Autor:	Alfredo Navigante, Isabel Stillitani, Slobodanka M. Klein, Stella M. Ranuncolo, Guillermo Peluffo, Miriam J. Diament, Leandro Cerchietti
Rok vydání:	2006
Předmět:	Cancer Research medicine.medical_specialty Cachexia Lung Neoplasms Antineoplastic Agents Hormonal Paraneoplastic Syndromes Indomethacin Appetite Stimulants Enzyme-Linked Immunosorbent Assay Inflammation Medroxyprogesterone Acetate Adenocarcinoma Mice Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Animals Leukocytosis Interleukin 6 Mice Inbred BALB C Lung biology Interleukin-6 business.industry Anti-Inflammatory Agents Non-Steroidal digestive oral and skin physiology Interleukin General Medicine medicine.disease medicine.anatomical_structure Endocrinology Matrix Metalloproteinase 9 Oncology Tumor progression Hypercalcemia Cancer research biology.protein Matrix Metalloproteinase 2 Female medicine.symptom business Interleukin-1
Zdroj:	Cancer Investigation. 24:126-131
ISSN:	1532-4192 0735-7907
DOI:	10.1080/07357900500524322
Popis:	Mice bearing LP07 lung adenocarcinoma present some characteristics similar to those shown in patients with several malignant diseases. LP07 tumor bearers develop paraneoplastic syndromes such as cachexia, leukocytosis, and hypercalcemia, partly due to a systemic inflammatory response. We analyzed some of the mechanisms involved in the effectiveness of the association of the appetite-stimulant medroxiprogesterone acetate (MPA) and the nonselective cyclooxigenase (COX) inhibitor indomethacin (INDO) in LP07 tumor bearing mice. INDO and INDO plus MPA treatments significantly inhibited tumor growth, which was not inhibited by MPA. The number of lung metastatic nodules was decreased with all treatments, being most effective INDO alone and INDO plus MPA. A significant decrease of plasmatic levels of the matrix metalloproteinases MMP-9 and MMP-2 correlated with these results. Paraneoplastic syndromes, leukocytosis, and cachexia were abolished by all treatments. We determined effects of the treatments on circulating cytokines shown to regulate cachexia and inflammation. Both treatments alone, and INDO plus MPA, reduced circulating IL-6 throughout tumor evolution. A pronounced increase in serum IL-1ss levels was detected in untreated tumor bearers. These levels decreased and were closer to normal serum values when LP07 mice were treated with INDO plus MPA. The combination of a nonsteroidal antiinflammatory drug as INDO and MPA showed to be effective in inhibiting tumor and metastatic growth and diminishing paraneoplastic symptoms and SIR. A variety of specific molecules are implicated as playing a role in cancer-induced cachexia and hematological alterations.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::749baf96535d1b6d14da88ef60c0576c https://doi.org/10.1080/07357900500524322 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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