Cytokines, inflammation and colon cancer.
Cytokines, inflammation and colon cancer.
复制标题
DOI：
10.2174/156800911795538066
复制
发表时间：
2011-05
影响因子：
3
通讯作者：
Klampfer L
中科院分区：
文献类型：
--
作者：
Klampfer L
患有炎症性肠道疾病的患者，如溃疡性结肠炎和克罗恩病，患结肠癌的风险增加，这证实了慢性炎症容易发生肿瘤。此外，似乎没有发展为炎症性肠病并发症的结肠癌也是由炎症驱动的，因为已经证明，定期使用非类固醇抗炎药(NSAIDs)可以降低散发性结肠癌的死亡率，并导致家族性腺瘤性息肉病(FAP)患者的腺瘤消退，这些患者遗传了APC基因的突变。因此，结直肠癌代表了炎症和癌症之间联系的一个范例。炎症是由可溶性因子、细胞因子和趋化因子驱动的，它们可以由肿瘤细胞本身产生，或者更常见的是，由被招募到肿瘤微环境的细胞产生。炎性细胞因子和趋化因子促进肿瘤细胞的生长，干扰肿瘤细胞的分化，支持癌细胞的存活。肿瘤细胞对炎性间质上瘾，表明肿瘤微环境是预防和治疗策略的一个有吸引力的靶点。促炎症细胞因子，如肿瘤坏死因子α、IL-6和IL-1β，或由这些细胞因子信号转导所需的转录因子，包括核因子-κB和STATS，确实正在成为抗癌治疗的潜在靶点。肿瘤坏死因子α拮抗剂正处于I/II期临床试验，已被证明在实体瘤患者中耐受性良好，随后可能会出现IL-1β拮抗剂，它可以改善以IL-1β产生过多为特征的几种炎症性疾病。因此，开发使肿瘤微环境正常化或阻断肿瘤与肿瘤微环境之间的串扰的药物是治疗癌症的重要途径。
Patients with inflammatory bowel diseases, such as ulcerative colitis and Crohn's disease, are at increased risk of developing colon cancer, confirming that chronic inflammation predisposes to development of tumors. Moreover, it appears that colon cancers that do not develop as a complication of inflammatory bowel disease are also driven by inflammation, because it has been shown that regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) lowers the mortality from sporadic colon cancer and results in regression of adenomas in familial adenomatous polyposis (FAP) patients, who inherit a mutation in the Apc gene. Colorectal cancer therefore represents a paradigm for the link between inflammation and cancer. Inflammation is driven by soluble factors, cytokines and chemokines, which can be produced by tumor cells themselves or, more often, by the cells recruited to the tumor microenvironment. Inflammatory cytokines and chemokines promote growth of tumor cells, perturb their differentiation, and support the survival of cancer cells. Tumor cells become addicted to inflammatory stroma, suggesting that the tumor microenvironment represents an attractive target for preventive and therapeutic strategies. Proinflammatory cytokines, such as TNFα, IL-6 and IL-1β, or transcription factors that are required for signaling by these cytokines, including NF-κB and STATs, are indeed emerging as potential targets for anticancer therapy. TNFα antagonists are in phase I/II clinical trials and have been shown to be well tolerated in patients with solid tumors, and IL-1β antagonists that ameliorate several inflammatory disorders characterized by excessive IL-1β production, will likely follow. Therefore, development of drugs that normalize the tumor microenvironment or interrupt the crosstalk between the tumor and the tumor microenvironment is an important approach to the management of cancer.
登录
查看更多内容
影响因子：
2.8
作者：
Brabletz, T;Jung, A;Kirchner, T
通讯作者：
Kirchner, T
DOI：
10.1073/pnas.0600666103
发表时间：
2006-05-23
影响因子：
11.1
作者：
Chen, Zhi;Laurence, Arian;O'Shea, John J.
通讯作者：
O'Shea, John J.
影响因子：
11.2
作者：
Camus, Matthieu;Tosolini, Marie;Galon, Jerome
通讯作者：
Galon, Jerome
影响因子：
10.5
作者：
Ancrile, Brooke;Lim, Kian-Huat;Counter, Christopher M.
通讯作者：
Counter, Christopher M.
影响因子：
50.3
作者：
Bollrath, Julia;Phesse, Toby J.;Greten, Florian R.
通讯作者：
Greten, Florian R.