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PNAS:美開發新療法 有望戰勝7種癌癥

2012-4-10 作者:新華網   來源:新華網 我要評論0
Tags:   腫瘤  癌癥    

日前,美國科學家研制出了一種能幫助人體免疫系統摧毀癌細胞的新型藥物,對乳腺癌、腸癌、前列腺癌、子宮癌、腦癌、膀胱癌、肝癌等多種癌癥都有療效。此外前期研究表明,該藥物還可用于治療血癌(白血病)。研究人員表示,若能及早使用,該藥物甚至可以完全治愈惡性腫瘤疾病,且副作用極小。

目前這種藥物僅在小白鼠身上進行了試驗,研究人員希望能在兩年內開始臨床試驗。

據悉,新型藥物的效力集中于一種大量存在于癌細胞表面的蛋白質,這種名叫“CD47”的蛋白質能使癌細胞免于被叫作“巨噬細胞”的免疫細胞所吞噬。新藥物能去掉癌細胞這一“不要吞噬我信號”,讓免疫系統直接對惡性腫瘤細胞展開攻擊。

該藥物研究員,美國斯坦福大學醫學院博士歐文·韋斯曼表示:“沒了‘不要吞噬我信號’,小白鼠體內的幾乎所有種類的人類癌細胞都不再增長,且(新藥物)副作用極小。我們的研究表明,‘CD47’確為人類戰勝癌癥的關鍵。”

韋斯曼博士補充稱,當新藥物作用于小型腫瘤時“有治愈的可能”,但在某些小白鼠身上,卻沒有絲毫療效。即便如此韋斯曼博士還是認為,新藥物現已具備臨床試驗的條件,需“快速而慎重地推進”。

對于新藥物安全性的嚴格要求意味著該藥物的廣泛應用可能還需十幾年的時間,英國癌癥研究會免疫學專家菲利普·阿什頓·利卡特教授認為,上述研究可能會創造全新的癌癥療法。“對傳統化療或放射性治療已產生抵抗力的惡性腫瘤細胞將有可能通過這種新藥物得到控制,但新藥物還需在臨床試驗中證明其在人體內的效果。”(生物谷Bioon.com)

doi:10.1073/pnas.1121623109
PMC:

PMID:

The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors

Stephen B. Willingham, Jens-Peter Volkmer, Andrew J. Gentles, Irving L. Weissman et al.

CD47, a “don't eat me” signal for phagocytic cells, is expressed on the surface of all human solid tumor cells. Analysis of patient tumor and matched adjacent normal (nontumor) tissue revealed that CD47 is overexpressed on cancer cells. CD47 mRNA expression levels correlated with a decreased probability of survival for multiple types of cancer. CD47 is a ligand for SIRPα, a protein expressed on macrophages and dendritic cells. In vitro, blockade of CD47 signaling using targeted monoclonal antibodies enabled macrophage phagocytosis of tumor cells that were otherwise protected. Administration of anti-CD47 antibodies inhibited tumor growth in orthotopic immunodeficient mouse xenotransplantation models established with patient tumor cells and increased the survival of the mice over time. Anti-CD47 antibody therapy initiated on larger tumors inhibited tumor growth and prevented or treated metastasis, but initiation of the therapy on smaller tumors was potentially curative. The safety and efficacy of targeting CD47 was further tested and validated in immune competent hosts using an orthotopic mouse breast cancer model. These results suggest all human solid tumor cells require CD47 expression to suppress phagocytic innate immune surveillance and elimination. These data, taken together with similar findings with other human neoplasms, show that CD47 is a commonly expressed molecule on all cancers, its function to block phagocytosis is known, and blockade of its function leads to tumor cell phagocytosis and elimination. CD47 is therefore a validated target for cancer therapies.



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