Likhite V V
J Natl Cancer Inst. 1976 May;56(5):985-9. doi: 10.1093/jnci/56.5.985.
F344 rats received grafts of syngeneic 13762 mammary adenocarcinoma cells previously admixed with either living BCG of killed Corynebacterium parvum administered sc or intradermally (id). Animals given id transplants of tumor cells admixed with either BCG or killed C. parvum exhibited tumor growth for an average of 10 days, then regression in size and rejection of the tumor nodules. Lesions were found in rats given sc transplants of tumor cells admixed with the killed microorganism for an average of 13 days with the same results. When live BCG was added to the sc transplants, accelerated rates of tumor growth and early death were noted, compared with the group receiving tumor cells alone sc. Suppressed rates of tumor growth and prolonged survival were observed in the groups receiving id inoculations of tumor cells followed by treatment with killed C. parvum administered weekly ip or id 1 cm away and around the growing tumor. On the other hand, weekly treatment of BCG injected either ip or id 1 cm away and around the growing tumor resulted in accelerated rates of tumor growth and early death. Animals exhibiting C. parvum of BCG-mediated tumor rejection displayed tumor-specific protection to sc challenge injections of the cell line initially used, but they died with growing tumors and metastases when challenged with tumor cells of an antigenically different line syngeneic to F344 RATS. Microscopic examination of histologic sections of tumors formed from id inoculations of tumor cells admixed with either BCG or killed C. parvum revealed a nonspecific infiltrate of macrophages and polymorphonuclear leukocytes in the tumor, whereas sections of tumors formed from sc grafts of cells admixed with killed C. parvum revealed a specific organized infiltrate of mostly macrophages around the tumor follicles.
将同基因的13762乳腺腺癌细胞与活卡介苗或灭活的短小棒状杆菌混合,通过皮下或皮内注射接种到F344大鼠体内。接受皮内移植混合了卡介苗或灭活短小棒状杆菌的肿瘤细胞的动物,肿瘤平均生长10天,随后肿瘤大小缩小,肿瘤结节被排斥。接受皮下移植混合了灭活微生物的肿瘤细胞的大鼠,肿瘤平均生长13天,结果相同。当将活卡介苗添加到皮下移植中时,与仅接受皮下肿瘤细胞移植的组相比,观察到肿瘤生长加速和早期死亡。在接受皮内接种肿瘤细胞,随后每周腹腔内或在距生长肿瘤1厘米处及周围皮内注射灭活短小棒状杆菌进行治疗的组中,观察到肿瘤生长速率受到抑制,生存期延长。另一方面,每周在距生长肿瘤1厘米处及周围腹腔内或皮内注射卡介苗进行治疗,导致肿瘤生长加速和早期死亡。表现出卡介苗介导的肿瘤排斥的短小棒状杆菌的动物,对最初使用的细胞系的皮下攻击注射显示出肿瘤特异性保护,但当用与F344大鼠同基因的抗原性不同的细胞系的肿瘤细胞进行攻击时,它们死于不断生长的肿瘤和转移。对皮内接种混合了卡介苗或灭活短小棒状杆菌的肿瘤细胞形成的肿瘤组织切片进行显微镜检查,发现肿瘤中有巨噬细胞和多形核白细胞的非特异性浸润,而对皮下移植混合了灭活短小棒状杆菌的细胞形成的肿瘤切片进行检查,发现肿瘤滤泡周围主要是巨噬细胞的特异性有组织浸润。