melphalan and Adenoma

In previous research, we focused on the discovery of K-ras biomarkers, and effects of genotoxic carcinogens on their expression were investigated in this study. It is well-known that mutated K-ras gene is involved in approximately 30% of human cancers such as lung cancer. To search for K-ras oncogene-induced modulators in lung tissues of K-ras transgenic mice, we analyzed K-ras-specific genes and proteins related to cancer development, signal transduction, inflammation as well as tumor suppression in a previous study. In this study, we investigated the modulating effects of genotoxic carcinogen treatment on expression of K-ras-dependent modulated genes and proteins in lung tissues of K-ras Tg mice. In order to evaluate candidate K-ras markers modulated by genotoxic stress and to investigate whether a genotoxic carcinogen would enhance or inhibit carcinogenesis in lung tissues of the K-ras Tg mice, the anti-cancer drug melphalan was intraperitoneally injected into K-ras Tg mice every two days for four weeks. RT-qPCR and proteomics analyses were performed in order to confirm whether K-ras-specific biomarkers would be modulated by melphalan treatment in K-ras Tg mice. The decreased adenomas were histopathologically observed and K-ras expression was suppressed in melphalan-treated K-ras Tg mice. Melphalan also recovered the expression of K-ras-dependent modulated biomarkers. These results suggest that melphalan inhibits carcinogenesis via modulating K-ras-specific genes and proteins expressed in the lung tissues of K-ras Tg mice.

Topics: Adenoma; Animals; Antineoplastic Agents, Alkylating; Biomarkers, Tumor; Cell Proliferation; Cluster Analysis; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genes, ras; Humans; Lung Neoplasms; Male; Melphalan; Mice; Mice, Transgenic; Models, Biological

Topics: Adenoma; Adolescent; Adult; Aged; Anemia, Hypochromic; Anemia, Macrocytic; Anemia, Sideroblastic; Blood Protein Disorders; Chlorambucil; Female; Hemoglobinometry; Humans; Immunosuppressive Agents; Kidney Neoplasms; Leukemia; Lupus Erythematosus, Systemic; Male; Melphalan; Multiple Myeloma; Polycythemia; Pyridoxine; Waldenstrom Macroglobulinemia