2011年8月2日 星期二

Inflammation and cancer: How hot is the link?

Bharat B. Aggarwal , Shishir Shishodia , Santosh K. Sandur , Manoj K. Pandey , Gautam Sethi

Abstract

Although inflammation has long been known as a localized protective reaction of tissue to irritation, injury, or infection, characterized by pain, redness, swelling, and sometimes loss of function, there has been a new realization about its role in a wide variety of diseases, including cancer. While acute inflammation is a part of the defense response, chronic inflammation can lead to cancer, diabetes, cardiovascular, pulmonary, and neurological diseases. Several pro-inflammatory gene products have been identified that mediate a critical role in suppression of apoptosis, proliferation, angiogenesis, invasion, and metastasis. Among these gene products are TNF and members of its superfamily, IL-1a, IL-1b, IL-6, IL-8, IL-18, chemokines, MMP-9, VEGF, COX-2, and 5-LOX. The expression of all these genes are mainly regulated by the transcription factor NF-kB, which is constitutively active in most tumors and is induced by carcinogens (such as cigarette smoke), tumor promoters, carcinogenic viral proteins (HIV-tat, HIV-nef, HIV-vpr, KHSV, EBV-LMP1, HTLV1-tax, HPV, HCV, and HBV), chemotherapeutic agents, and g-irradiation. These observations imply that antiinflammatory agents that suppress NF-kB or NF-kB-regulated products should have a potential in both the prevention and treatment of cancer. The current review describes in detail the critical link between inflammation and cancer.

中文摘要:
雖然,我們很早便知道發炎是一個為保護受傷、感染、刺激而產生之局部地區之過程,跟而引起之疼痛、紅腫及一些身體之功能消失;現在我們更清楚,發炎其實在很多疾病上扮演著很多種功能,包括癌症。急性發炎是自衛免疫的一部分,但慢性發炎卻會英氣癌症、糖尿病、心血管疾病、肺病及神經性疾病。有數個發炎基因所產生之化學分子已被認出,它們會在抵抗凋零、擴散、血管增生、侵犯、轉移的過程中,扮演主要的角色。這些基因化學分子便是TNF,及一個超級家庭中之IL-1α,IL-1β,IL-6,IL-8,IL-18,化學激素如MMP-9,VEGF,COX-2及5-LOX都在其中。這些基因之表現,是由一個叫NF-Kβ錄制因子所調控,而該錄制因子在腫瘤中非常活躍,且是有致癌物質(如抽煙)、腫瘤催化劑、致癌病毒蛋白質(如HIV-tat、HIV-vpr、HIV-nef、KHSV、EBV-LMP1、HTLV1-tax、HPV、HOV與HBV),化學治療之藥物,及γ-輻射所啟動。這些事實表示抗發炎因素可以經過壓制NF-Kβ或是NF-Kβ之產生化學物來進行癌症之預防及治療。

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