Levi F A, Blum J P, Lemaigre G, Bourut C, Reinberg A, Mathé G
Cancer Res. 1984 Jun;44(6):2660-7.
The subrenal capsule assay may predict to which anticancer drug a given patient's tumor is sensitive and may also be used to screen new anticancer drugs. The present study documents that the use of this model requires a histological assessment of both the exploitability of a subrenal capsule assay and the extent of drug-induced antitumor lesions. Thirty-five tumors from 34 patients with solid tumor were submitted to a subrenal capsule assay in a total of 1130 male B6D2F1 mice. After being biopsied, each tumor was dissected by a pathologist and cut into 50 pieces (1.5 X 1.5 X 1.5 cu mm), and one piece was implanted under the renal capsule of 35 mice; the mean tumor diameter was measured on Day 0. Mice were randomized into groups of 6 to 10 animals each. On Days 1, 2, and 3, mice were treated either with placebo (control group) or with various anticancer agents. On Days 4 or 6, mice were sacrificed, the mean tumor diameter measured, and the tumor-bearing kidney fixed in Bouin's picroformol solution and processed for histological analysis after staining with hematein -eosin. Seven histological parameters were blindly rated in a semiquantitative fashion yielding a compound score ( PAPAN ) which estimated the overall quality of each xenograft between -3 and +11. On Day 4, as opposed to Day 6, mean lymphocytic infiltration was 3-fold lower (p less than 0.01), and the rate of xenografts containing well-preserved cancer cells was 2-fold larger (p less than 0.01) in three different tumor specimens. Twenty-two of 31 (71%) assays were evaluable, as defined by a histological quality control test. In those, drug effects were demonstrable by statistically significant differences among groups in 2 assays (9%) by using the relative variation in tumor size as an index of drug effectiveness and in 12 assays (54%) by PAPAN histological score. This suggests the higher sensitivity of histological scoring over tumor size measurements. Moreover, no correlation between relative variation in tumor size and PAPAN was demonstrable with statistical significance indicating the poor reliability of tumor size measurements as an index of the antitumor effectiveness of cytostatic drugs.
肾包膜下移植试验可以预测特定患者的肿瘤对哪种抗癌药物敏感，也可用于筛选新的抗癌药物。本研究证明，使用该模型需要对肾包膜下移植试验的可利用性以及药物诱导的抗肿瘤损伤程度进行组织学评估。对34例实体瘤患者的35个肿瘤在总共1130只雄性B6D2F1小鼠中进行了肾包膜下移植试验。活检后，病理学家对每个肿瘤进行解剖并切成50片（1.5×1.5×1.5立方毫米），将其中一片植入35只小鼠的肾包膜下；在第0天测量平均肿瘤直径。将小鼠随机分成每组6至10只动物的组。在第1、2和3天，小鼠分别接受安慰剂治疗（对照组）或各种抗癌药物治疗。在第4天或第6天，处死小鼠，测量平均肿瘤直径，将荷瘤肾脏固定在布因氏苦味酸福尔马林溶液中，苏木精-伊红染色后进行组织学分析。以半定量方式对七个组织学参数进行盲法评分，得出一个综合评分（PAPAN），该评分估计每个异种移植瘤的总体质量在-3至+11之间。在第4天，与第6天相反，在三种不同的肿瘤标本中，平均淋巴细胞浸润低3倍（p<0.01），含有保存良好癌细胞的异种移植瘤发生率高2倍（p<0.01）。根据组织学质量控制测试的定义，31项试验中有22项（71%）可评估。在这些试验中，通过将肿瘤大小的相对变化作为药物有效性指标，2项试验（9%）中各治疗组间有统计学显著差异，通过PAPAN组织学评分，12项试验（54%）中各治疗组间有统计学显著差异，证明了药物效果。这表明组织学评分比肿瘤大小测量更具敏感性。此外，肿瘤大小的相对变化与PAPAN之间无统计学显著相关性，表明肿瘤大小测量作为细胞毒性药物抗肿瘤有效性指标的可靠性较差。
