Epigenetic Modifiers and Their Potential Application in Colorectal Cancer Diagnosis and Therapy.

Colorectal cancer (CRC) is the second leading cause of mortality in western countries. Delayed diagnosis of CRC is among the major reasons for its high mortality rate and progression to advanced stages. Early diagnosis of CRC is considered very important for timely treatment. Therefore, identification of accurate biomarkers holds the potential of laying a structural foundation for successful clinical management. A multistep process including genetic and epigenetic alterations, drives the development of early premalignant lesions to advanced metastatic CRC. These genetic and epi-genetic alterations accumulated over the course of malignant transformation favor the growth of neoplastic cells and an aggressive phenotype of malignant cells. Several epigenetic modifications have been shown to play a critical role in regulating gene expression, not only causing belligerent malignant cells but also impelling the initial stages of oncogenesis. The present review discusses the diagnostic, prognostic, and predictive applications of epigenetic biomarkers along with therapeutic strategies targeting such epigenetic alterations.

Augmented macrophage differentiation and polarization of tumor-associated macrophages towards M1 subtype in listeria-administered tumor-bearing host.

This study investigates the effect of Listeria administration on differentiation of macrophages from precursor bone marrow cells and functional status of tumor-associated macrophages (TAM). Listeria administration not only resulted in an augmented infiltration of tumor by F4/80 macrophages but also repolarized the functional status of TAM displaying features of some M1 macrophage subtype with upregulated phagocytosis and tumoricidal activity accompanied by altered expression of monocarboxylate transporter-1, toll-like receptor-2, surface markers: CD11c, interleukin-2 receptor, CD62L, and secreted molecules: nitric oxide, interleukin (IL)-1, IL-6, tumor necrosis factor-α, and vascular endothelial growth factor. Declined tumor cell survival and modulated repertoire of cytokines: interferon-γ, IL-6, IL-10, and transforming growth factor-ß in tumor microenvironment indicated their role in polarization of TAM towards proinflammatory state. Bone marrow cell of Listeria-administered tumor-bearing mice showed augmented survival, declined expression of p53 upregulated modulator of apoptosis with an upregulated differentiation into activation responsive bone marrow-derived macrophages along with altered expression of macrophage-colony stimulating factor, macrophage-colony stimulating factor receptor, and granulocyte macrophage-colony stimulating factor receptor. These findings indicate that Listeria infection is associated with an augmented differentiation of macrophages accompanied by tumoricidal activation of TAM.