Honda N
Hinyokika Kiyo. 1986 Oct;32(10):1423-41.
Using two xenografts of human renal cell carcinomas serially transplanted in nude mice (AM-RC-1 and AM-RC-6), both of which maintained the basic histologic features of the original tumor and showed a constant growth rate, the effects of various anticancer agents against 2 target tumors were evaluated. MitomycinC (MMC), adriamycin (ADM), cisplatinum diaminodichloride (CDDP), 5-fluorouracil (5FU), 5-fluro-2'-deoxy-beta-uridine (FUDR) and human lymphoblastoid interferon (HLBI) against AM-RC-1, and MMC, ADM, CDDP, vinblastin (VBL) and etoposide (VP-16) against AM-RC-6. Drugs other than HLBI were administered 3 times in total every three to five days by intraperitoneal injection according to Battelle Columbus Laboratories Protocol and HLBI was injected daily for 10 days intraperitoneally. Anti-cancer effects were evaluated based on tumor growth curve and changes of histologic findings. In terms of tumor growth only MMC (in a dose of 3 mg/kg) revealed a statistically significant inhibitory effect against both AM-RC-1 and AM-RC-6 (respectively P less than 0.001 and P less than 0.05). Concerning AM-RC-1, a significant difference (P less than 0.01) was recognized in the ADM group (5 mg/kg) at the time of the second administration, but evaluation could not ultimately be done owing to appearance of acute toxity after the last dose. The most remarkable histologic changes by light microscopy were recognized in the MMC group (in a dose of 3 mg/kg) against AM-RC-1. They were degenerative findings such as intracellular and nuclear vacuolation, karyorrhexis, karyolysis, karyopyknosis and marginal hyperchromatosis, which corresponded to grade IIa of the classification of the National Cancer Center. The other drugs administered to AM-RC-1 exhibited only grade O to grade I changes. On the other hand, in AM-RC-6, histologic changes were mild (less than grade II) for all the drugs. Electron microscopic features were as follows. AM-RC-1: Marked increase of vacuole of organella was observed and lumens were filled with a large quantity of debris in MMC group (3 mg/kg). In the ADM group (5 mg/kg) there was debris in lumens, although almost no changes of organella were seen. CDDP groups (both 5.6 mg/kg and 2.8 mg/kg) showed autophagic vacuole in the cytoplasm and increased collagen fibers in the stroma but little changes of organella. AM-RC-6: Mild intracellular vacuolation was recognized in the MMC group (3 mg/kg). Watery degeneration and microfibrils were found in the cytoplasm in both ADM (5 mg/kg) and CDDP (5.6 mg/kg, 2.8 mg/kg) groups.
使用在裸鼠中连续移植的两株人肾细胞癌异种移植瘤（AM-RC-1和AM-RC-6），这两株移植瘤均保持了原发肿瘤的基本组织学特征且显示出恒定的生长速率，评估了各种抗癌药物对这两种靶肿瘤的作用。丝裂霉素C（MMC）、阿霉素（ADM）、顺铂二氯二氨（CDDP）、5-氟尿嘧啶（5FU）、5-氟-2'-脱氧-β-尿苷（FUDR）和人淋巴母细胞样干扰素（HLBI）作用于AM-RC-1，MMC、ADM、CDDP、长春碱（VBL）和依托泊苷（VP-16）作用于AM-RC-6。除HLBI外的药物按照巴特尔哥伦布实验室方案每三至五天通过腹腔注射共给药3次，HLBI则每天腹腔注射10天。基于肿瘤生长曲线和组织学结果的变化评估抗癌效果。就肿瘤生长而言，仅MMC（剂量为3mg/kg）对AM-RC-1和AM-RC-6均显示出统计学上显著的抑制作用（分别为P<0.001和P<0.05）。关于AM-RC-1，ADM组（5mg/kg）在第二次给药时出现显著差异（P<0.01），但由于最后一剂后出现急性毒性，最终无法完成评估。光镜下最显著的组织学变化见于MMC组（剂量为3mg/kg）作用于AM-RC-1时。这些变化为退行性改变，如细胞内和核空泡形成、核碎裂、核溶解、核固缩和边缘性核染色质增多，这与国立癌症中心分类中的IIa级相对应。给予AM-RC-1的其他药物仅表现出0级至I级变化。另一方面，在AM-RC-6中，所有药物的组织学变化均较轻（小于II级）。电镜特征如下。AM-RC-1：MMC组（3mg/kg）可见细胞器空泡明显增多，管腔内充满大量碎片。ADM组（5mg/kg）管腔内有碎片，尽管细胞器几乎未见变化。CDDP组（5.6mg/kg和2.8mg/kg）均显示细胞质中有自噬空泡，间质中胶原纤维增多，但细胞器变化不大。AM-RC-6：MMC组（3mg/kg）可见轻度细胞内空泡形成。ADM组（5mg/kg）和CDDP组（5.6mg/kg、2.8mg/kg）的细胞质中均发现水样变性和微原纤维。
