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兔VX-2癌瘤周围白细胞介素-2的初步研究

Perilesional interleukin-2 in the VX-2 carcinoma in rabbits: a preliminary investigation.

作者信息

Carroll W R, Bunge F R, Wolf G T, Carey T E, McClatchey K D, Poore J

机构信息

Department of Otolaryngology-Head and Neck Surgery, University of Michigan Medical Center, Ann Arbor.

出版信息

Otolaryngol Head Neck Surg. 1995 Mar;112(3):430-6. doi: 10.1016/S0194-59989570279-2.

Abstract

Immune system amplification by perilesional injection of interleukin-2 is a promising adjuvant approach for treating squamous cell carcinoma of the head and neck. A pilot study was designed to develop an animal model bearing squamous cell carcinoma in which to test the efficacy of perilesional interleukin-2. Rabbits were inoculated intramuscularly with the papilloma virus-induced squamous carcinoma VX-2 cell line. Tumor regression and host lymphatic response after perilesional interleukin-2 were measured. Variable responses were found. Growth of tumor cells implanted from cell culture was rapid in most animals. Tumor growth was prevented in animals receiving 10,000 units of interleukin-2 per injection initiated 9 days after tumor inoculation. This inhibition approached statistical significance when compared with growth of saline controls. Histologic responses consisted primarily of plasma cell and eosinophil infiltration. The intensity of the inflammatory response did not correlate with interleukin-2 dose. A trend toward enhanced tumor growth was seen with lower doses of interleukin-2 and when interleukin-2 therapy was initiated simultaneously with tumor inoculation. These findings suggest that high-dose recombinant interleukin-2 can prevent tumor growth if initiated after tumor inoculation. Whether this effect was caused by direct tumor cytotoxicity or mediated by the immune system is unclear. These preliminary results underscore the importance of understanding the effects of dose and schedule in the design of immunotherapy models before clinical use.

摘要

通过在肿瘤周围注射白细胞介素-2来增强免疫系统是一种很有前景的辅助治疗头颈部鳞状细胞癌的方法。一项初步研究旨在建立一种携带鳞状细胞癌的动物模型,以测试肿瘤周围注射白细胞介素-2的疗效。给兔子肌肉注射乳头瘤病毒诱导的鳞状癌VX-2细胞系。测量肿瘤周围注射白细胞介素-2后的肿瘤消退和宿主淋巴反应。发现了不同的反应。在大多数动物中,从细胞培养物植入的肿瘤细胞生长迅速。在肿瘤接种后9天开始,每次注射10000单位白细胞介素-2的动物中,肿瘤生长得到了抑制。与生理盐水对照组的生长相比,这种抑制接近统计学意义。组织学反应主要包括浆细胞和嗜酸性粒细胞浸润。炎症反应的强度与白细胞介素-2剂量无关。当白细胞介素-2剂量较低以及在肿瘤接种同时开始白细胞介素-2治疗时,观察到肿瘤生长有增强的趋势。这些发现表明,如果在肿瘤接种后开始使用,高剂量重组白细胞介素-2可以预防肿瘤生长。这种效应是由直接的肿瘤细胞毒性引起还是由免疫系统介导尚不清楚。这些初步结果强调了在临床应用前,在免疫治疗模型设计中了解剂量和给药方案影响的重要性。

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