Carcinogenesistumorigenesis

The process of tumorigenesis is a process that requires cellular transformation, hyperproliferation, invasion, angiogen-esis, and metastasis. This process is activated by various carcinogens (such as cigarette smoke), inflammatory agents (such as TNF and H2O2), and tumor promoters (such as phor-bol ester and okadaic acid) (1). Although initially identified as an anticancer agent (2), TNF has now been shown to be involved in cellular transformation (3), tumor promotion (4), and induction of metastasis (5-7). In agreement with these observations, mice deficient in TNF have been shown to be resistant to skin carcinogenesis (8). For several tumors,

TNF has been shown to be a growth factor (9,10). Like phorbol ester, TNF mediates these effects in part through activation of a protein kinase C pathway (11). Similar to TNF, other inflammatory cytokines have also been implicated in tumorigenesis (12,13). Thus, agents that can suppress the expression of TNF and other inflammatory agents have chemopreventive potential (14,15). Most carcinogens, inflammatory agents, and tumor promoters including cigarette smoke, phorbol ester, okadaic acid, H2O2, and TNF, have been shown to activate the transcription factor NF-kB.

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