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首頁> 美國(guó)衛(wèi)生研究院文獻(xiàn)>Oncolytic Virotherapy >Myxoma virus therapy for human embryonal rhabdomyosarcoma in a nude mouse model
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Myxoma virus therapy for human embryonal rhabdomyosarcoma in a nude mouse model

機(jī)譯:黏液瘤病毒在裸鼠模型中治療人胚橫紋肌肉瘤

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摘要

Rhabdomyosarcoma (RMS) is a devastating tumor of young people that is difficult to cure. To determine if oncolytic virus therapy can improve outcomes in individuals with RMS, myxoma virus expressing a red fluorescent protein (MYXV-red) was evaluated for antitumoral effects using a murine model of RMS. Fluorescent protein was expressed in four RMS cell lines inoculated with MYXV-red, indicating that these cells were semipermissive to MYXV infection. MYXV-red replication and cytopathic effects were further evaluated using human embryonal RMS (CCL-136) cells. Logarithmic growth of MYXV-red and significant cell death were observed 72 hours after inoculation with MYXV. The oncolytic effects of MYXV-red were then studied in nude mice that were injected subcutaneously with CCL-136 cells to establish RMS xenografts. Once tumors measured 5 mm in diameter, mice were treated with multiple intratumoral injections of MXYV-red or saline. The average final tumor volume and rate of tumor growth were significantly decreased, and median survival time was significantly increased in MYXV-red-treated mice (P-values =0.0416, 0.0037, and 0.0004, respectively). Histologic sections of MYXV-red-treated tumors showed increased inflammation compared to saline-treated tumors (P-value =0.0002). In conclusion, MXYV-red treatment of RMS tumors was successful in individual mice as it resulted in decreased tumor burden in eight of eleven mice with nearly complete tumor remission in five of eleven mice. These data hold promise that MYXV-red treatment may be beneficial for people suffering from RMS. To our knowledge, this is the first report of successful treatment of RMS tumors using an oncolytic poxvirus.
機(jī)譯:橫紋肌肉瘤(RMS)是一種難以治愈的破壞性年輕人腫瘤。為了確定溶瘤病毒療法是否可以改善RMS個(gè)體的預(yù)后,使用RMS鼠模型評(píng)估了表達(dá)紅色熒光蛋白(MYXV-red)的粘液瘤病毒的抗腫瘤作用。熒光蛋白在接種了MYXV-red的四個(gè)RMS細(xì)胞系中表達(dá),表明這些細(xì)胞對(duì)MYXV感染具有半寬容性。使用人類胚胎RMS(CCL-136)細(xì)胞進(jìn)一步評(píng)估MYXV紅色復(fù)制和細(xì)胞病變作用。接種MYXV 72小時(shí)后,觀察到MYXV-red的對(duì)數(shù)增長(zhǎng)和明顯的細(xì)胞死亡。然后在裸鼠中研究了MYXV-red的溶瘤作用,該裸鼠皮下注射了CCL-136細(xì)胞以建立RMS異種移植物。一旦腫瘤的直徑測(cè)量為5毫米,就通過多次瘤內(nèi)注射MXYV-red或生理鹽水治療小鼠。在MYXV-紅色治療的小鼠中,平均最終腫瘤體積和腫瘤生長(zhǎng)速率顯著降低,中位生存時(shí)間顯著增加(P值分別為0.0416、0.0037和0.0004)。與生理鹽水治療的腫瘤相比,MYXV紅色治療的腫瘤的組織學(xué)切片顯示炎癥增加(P值= 0.0002)??傊瑢?duì)個(gè)體小鼠進(jìn)行RMS腫瘤的MXYV-red治療是成功的,因?yàn)樗梢詼p少11只小鼠中的8只的腫瘤負(fù)擔(dān),而11只小鼠中的5只幾乎完全緩解腫瘤。這些數(shù)據(jù)表明,MYXV紅色療法可能對(duì)患有RMS的人有益。據(jù)我們所知,這是首次使用溶瘤性痘病毒成功治療RMS腫瘤的報(bào)道。

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