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针对良性肿瘤相关抗原产生的免疫球蛋白G可预防二甲基肼对大鼠的影响。

IgG generated against benign tumor-associated antigens prevented the effects of 1,2-dimethylhydrazine in rats.

作者信息

Zusman I, Zusman R, Karol D, Gurevich P

机构信息

Laboratory of Teratology & Experimental Oncology, Koret School of Veterinary Medicine, Hebrew University of Jerusalem, Rehovot, Israel.

出版信息

Anticancer Res. 1996 May-Jun;16(3A):1183-6.

PMID:8702233
Abstract

We showed the possibility of significant decreasing of the frequency of chemically induced colon cancer in rats by vaccination with polyclonal rabbit IgG generated against purified tumor-associated antigens (TAA). TAA were isolated from benign rat colon tumors by the method developed in our laboratory (Zusman et al 1994) using affinity chromatography columns with gel fiberglass membranes (R. Zusman, 1992) containing anti-tumor IgG. The IgG was isolated from rabbits following their vaccination with TAA. Sprague Dawley rats were vaccinated with anti-TAA IgG (100 micrograms/rat) suspended in Freunds adjuvant by weekly subcutaneous injections for 5 weeks. The induction of colon cancer was caused by weekly injections with 1,2-dimethylhydrazine (DMH) (20 mg/kg) for 7 weeks and was started one week after the end of the vaccination. The results of experiments were evaluated 6 months after the start of cancer induction. IgG protected against the carcinogenic effects of DMH. The number of tumor-bearing rats decreased to 64% as compared with 90% in the control group. In vaccinated rats, the incidence of tumors was almost 3 times less than of control, i.e. 3.6 and 9.3, respectively. The number of malignant tumors was also significantly smaller in vaccinated rats than in controls, being 24% and 58%, respectively. Metastases were found only in controls, 4 of 30 rats. The results of our experiments have shown that anti-TAA IgG not only has anti-tumor effects but also prevents the malignization of benign tumors. As one of the main components of TAA which was isolated from colon cancer rats was soluble p53 antigen (Zusman et al 1994), we suggest that the vaccine which has been generated in our experiments may be regarded as acting mainly against p53 antigen, and its antitumor effects should also be considered as effects of p53 antibodies. The further studies will be performed to clarify this.

摘要

我们证明了通过用针对纯化的肿瘤相关抗原(TAA)产生的多克隆兔IgG进行疫苗接种,可显著降低化学诱导的大鼠结肠癌发生率。TAA是采用我们实验室开发的方法(祖斯曼等人,1994年),从良性大鼠结肠肿瘤中分离出来的,该方法使用含有抗肿瘤IgG的玻璃纤维膜亲和层析柱(R.祖斯曼,1992年)。IgG是在兔子接种TAA后从其体内分离得到的。将抗TAA IgG(100微克/只大鼠)悬浮于弗氏佐剂中,通过每周皮下注射5周,对斯普拉格-道利大鼠进行疫苗接种。结肠癌的诱导是通过每周注射1,2 - 二甲基肼(DMH)(20毫克/千克),持续7周,并在疫苗接种结束后1周开始。在癌症诱导开始6个月后评估实验结果。IgG可抵御DMH的致癌作用。与对照组90%的荷瘤大鼠相比,接种组荷瘤大鼠数量降至64%。在接种疫苗的大鼠中,肿瘤发生率几乎比对照组低3倍,分别为3.6%和9.3%。接种疫苗的大鼠中恶性肿瘤数量也显著少于对照组,分别为24%和58%。转移仅在对照组中发现,30只大鼠中有4只出现转移。我们的实验结果表明,抗TAA IgG不仅具有抗肿瘤作用,还能预防良性肿瘤的恶性转化。由于从结肠癌大鼠中分离出的TAA的主要成分之一是可溶性p53抗原(祖斯曼等人,1994年),我们认为我们实验中产生的疫苗可能主要针对p53抗原起作用,其抗肿瘤作用也应被视为p53抗体的作用。将进行进一步研究以阐明这一点。

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