Why not treat human cancer with interleukin-1 blockade?
Why not treat human cancer with interleukin-1 blockade?
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DOI：
10.1007/s10555-010-9229-0
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发表时间：
2010-06
影响因子：
9.2
通讯作者：
Dinarello, Charles A.
中科院分区：
文献类型：
--
作者：
Dinarello, Charles A.
靶向血管生成的临床成功为白细胞介素-1（IL-1）阻断试验提供了基础，特别是抗IL-1β作为人类转移性疾病的辅助治疗。在超过20年的动物研究中，已经证明IL-1在体外增加肿瘤细胞对内皮的粘附，并且向小鼠施用IL-1增加了转移性集落的数量和肿瘤生长。重要的是，用天然存在的IL-1受体拮抗剂（IL-1 Ra）降低内源性IL-1活性，特别是IL-1β，可降低转移和肿瘤负荷。抑制IL-1活性可防止由缺氧巨噬细胞释放的产物或血管内皮细胞生长因子本身诱导的体内血管形成。缺乏IL-1β的小鼠在包埋有血管内皮细胞生长因子或含有巨噬细胞产物的基质胶中不形成血管。重组IL-1 Ra（阿那白滞素）已被用于1,000多名感染性休克患者，导致全因28天死亡率持续下降。阿那白滞素被批准用于治疗类风湿性关节炎，有着显著的安全记录。阿那白滞素导致类风湿性关节炎患者受影响关节血管翳血管减少。针对IL-1β的中和性单克隆抗体和针对IL-1的可溶性受体被批准用于治疗慢性炎性疾病。考虑到三种治疗剂限制IL-1活性的可用性，阻断IL-1的安全性，以及阻断转移和血管生成动物模型中IL-1活性的明显益处，应启动IL-1阻断的临床试验，特别是作为接受基于抗血管生成治疗的患者的附加治疗。
The clinical successes of targeting angiogenesis provide a basis for trials of interleukin-1 (IL-1) blockade and particularly anti-IL-1β as an add-on therapy in human metastatic disease. In animal studies for over 20 years, IL-1 has been demonstrated to increase adherence of tumor cells to the endothelium in vitro, and administration of IL-1 to mice increases the number of metastatic colonies and tumor growth. Importantly, reducing endogenous IL-1 activity, particularly IL-1β, with the naturally occurring IL-1 receptor antagonist (IL-1Ra) reduces both metastasis as well as tumor burden. Inhibition of IL-1 activity prevents in vivo blood vessel formation induced by products released from hypoxic macrophages or vascular endothelial cell growth factor itself. Mice deficient in IL-1β do not form blood vessels in matrigels embedded with vascular endothelial cell growth factor or containing products of macrophages. Recombinant IL-1Ra (anakinra) has been administered to over 1,000 patients with septic shock resulting in a consistent reduction in all-cause 28-day mortality. Approved for treatment of rheumatoid arthritis, anakinra has a remarkable safety record. Anakinra resulted in decreased blood vessels in the pannus of affected joints in patients with rheumatoid arthritis. Neutralizing monoclonal antibodies to IL-1β and a soluble receptor to IL-1 are approved for treating chronic inflammatory diseases. Given the availability of three therapeutic agents for limiting IL-1 activity, the safety of blocking IL-1, and the clear benefit of blocking IL-1 activity in animal models of metastasis and angiogenesis, clinical trials of IL-1 blockade should be initiated, particularly as an add-on therapy of patients receiving antiangiogenesis-based therapies.
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影响因子：
6.4
作者：
Chang, YW;Jang, JY;Chang, R
通讯作者：
Chang, R
影响因子：
4.8
作者：
Bar, D;Apte, RN;Cohen, S
通讯作者：
Cohen, S
DOI：
10.1056/nejmoa0807865
发表时间：
2009-06-04
期刊：
The New England journal of medicine
影响因子：
--
作者：
Aksentijevich I;Masters SL;Ferguson PJ;Dancey P;Frenkel J;van Royen-Kerkhoff A;Laxer R;Tedgård U;Cowen EW;Pham TH;Booty M;Estes JD;Sandler NG;Plass N;Stone DL;Turner ML;Hill S;Butman JA;Schneider R;Babyn P;El-Shanti HI;Pope E;Barron K;Bing X;Laurence A;Lee CC;Chapelle D;Clarke GI;Ohson K;Nicholson M;Gadina M;Yang B;Korman BD;Gregersen PK;van Hagen PM;Hak AE;Huizing M;Rahman P;Douek DC;Remmers EF;Kastner DL;Goldbach-Mansky R
通讯作者：
Goldbach-Mansky R
影响因子：
2.7
作者：
Chauffier, Karine;London, Jonathan;Fautrel, Bruno
通讯作者：
Fautrel, Bruno
Anakinra在青少年中具有抗秋水仙碱的家族地中海热的功效。
影响因子：
3.6
作者：
Calligaris, Lorenzo;Marchetti, Federico;Tommasini, Alberto;Ventura, Alessandro
通讯作者：
Ventura, Alessandro