Friedman E J, Orth C R, Brewton K A, Ponniah S, Alexander R B
Division of Urology, University of Maryland School of Medicine, the Marlene and Stewart Greenebaum Cancer Center, VA Maryland Health Care System, Baltimore, Maryland 21201, USA.
J Urol. 1997 Oct;158(4):1585-8.
We wished to determine if cryosurgical ablation of the normal ventral prostate of Copenhagen rats confers protective immunity against a subsequent challenge with Dunning R3327 MatLyLu prostatic adenocarcinoma. In human melanoma, tumor antigens have been characterized as normal cellular proteins. We reasoned that cryosurgical ablation of the normal prostate along with immunostimulatory adjuvants might release prostatic antigens to the immune system engendering an immune response and rendering rats immune to prostatic cancer cells.
On day 0, Copenhagen rats underwent cryosurgical ablation of the normal ventral prostate, cryosurgery and intraprostatic injection of Complete Freund's Adjuvant (CFA), CFA injection alone, or laparotomy alone. On day 21, animals received a subcutaneous challenge of MatLyLu tumor cells. Tumor dimensions were recorded at regular intervals by a single blinded investigator.
Animals receiving cryosurgical ablation of the normal ventral prostate or intraprostatic CFA developed tumors more frequently than animals receiving laparotomy alone and the effect was statistically significant if animals received both cryosurgical ablation of the prostate and intraprostatic CFA (3 experiments, 1 x 10(4) MatLyLu cells), total number with tumors/total number challenged: laparotomy alone 3/17, cryosurgical ablation 7/17, cryosurgery plus CFA 10/16 (p = 0.013 versus laparotomy, Fisher's exact test), CFA alone 9/17.
Cryosurgical ablation of the normal rat ventral prostate and intraprostatic CFA does not protect against and can enhance the tumorigenicity of MatLyLu prostatic cancer cells at distant sites. This could be occurring through specific immunologic effects or non-specific mechanisms induced by cryosurgery and CFA.
我们希望确定对哥本哈根大鼠正常腹侧前列腺进行冷冻消融是否能赋予其针对随后邓宁R3327 MatLyLu前列腺腺癌攻击的保护性免疫。在人类黑色素瘤中,肿瘤抗原已被鉴定为正常细胞蛋白。我们推断,对正常前列腺进行冷冻消融并联合免疫刺激佐剂可能会将前列腺抗原释放到免疫系统中,引发免疫反应,使大鼠对前列腺癌细胞产生免疫。
在第0天,对哥本哈根大鼠进行正常腹侧前列腺的冷冻消融、冷冻手术并前列腺内注射完全弗氏佐剂(CFA)、仅注射CFA或仅进行剖腹手术。在第21天,动物接受皮下注射MatLyLu肿瘤细胞的攻击。由一名单盲研究者定期记录肿瘤大小。
接受正常腹侧前列腺冷冻消融或前列腺内注射CFA的动物比仅接受剖腹手术的动物更频繁地发生肿瘤,并且如果动物同时接受前列腺冷冻消融和前列腺内注射CFA(3个实验;1×10⁴个MatLyLu细胞),这种影响具有统计学意义,发生肿瘤的动物总数/接受攻击的动物总数:仅剖腹手术组为3/17,冷冻消融组为7/17,冷冻手术加CFA组为10/16(与剖腹手术相比,p = 0.013,Fisher精确检验),仅CFA组为9/17。
对正常大鼠腹侧前列腺进行冷冻消融和前列腺内注射CFA不能预防并可能增强远处部位MatLyLu前列腺癌细胞的致瘤性。这可能是通过冷冻手术和CFA诱导的特异性免疫效应或非特异性机制发生的。