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作为正常小鼠第一代移植异种移植物的人类肿瘤的化疗反应性:六天肾包膜下测定法

Chemotherapy responsiveness of human tumors as first transplant generation xenografts in the normal mouse: six-day subrenal capsule assay.

作者信息

Bogden A E, Cobb W R, Lepage D J, Haskell P M, Gulkin T A, Ward A, Kelton D E, Esber H J

出版信息

Cancer. 1981 Jul 1;48(1):10-20. doi: 10.1002/1097-0142(19810701)48:1<10::aid-cncr2820480105>3.0.co;2-i.

Abstract

Feasibility of utilizing human tumors as first transplant generation xenografts in the normal immunocompetent mouse for determining tumor sensitivity to chemotherapeutic agents was demonstrated by applying subrenal capsule (SRC) assay methodology to fresh surgical explants in a six-day time frame. A total of 37 human breast tumors were tested in assays in which 254 xenografts were implanted into control animals. Fifty (20%) of the controls showed some degree of partial regression in the six-day assay period. Using a mean control growth having a positive change in tumor size as the criterion for evaluability, first transplant generation human breast tumors provided an evaluable assay rate of 86%. A tumor response profile was obtained as a result of testing seven clinically active drugs against 32 previously untreated breast cancers. The pattern of responses obtained indicated that no single agent was active against all tumors, nor were tumors which were responsive to one agent necessarily responsive to another, suggesting the feasibility of predicting individual tumor response to specific chemotherapeutic agents. Had these seven drugs been developmental agents of unknown activity which were being tested for the first time against such a panel of human tumors the result would have not only predicted their clinical activity, but the tumor response rates would have also provided an indication of the relative potential of each drug for the specific treatment of breast cancer.

摘要

通过在六天时间内将肾下囊(SRC)检测方法应用于新鲜手术切除组织,证明了利用人类肿瘤作为正常免疫活性小鼠第一代移植异种移植物来确定肿瘤对化疗药物敏感性的可行性。在检测中总共对37个人类乳腺肿瘤进行了测试,其中254个异种移植物被植入对照动物体内。在为期六天的检测期内,50个(20%)对照显示出一定程度的部分消退。以肿瘤大小有正向变化的平均对照生长情况作为可评估标准,第一代移植人类乳腺肿瘤的可评估检测率为86%。通过针对32例未经治疗的乳腺癌测试七种临床活性药物,获得了肿瘤反应图谱。所获得的反应模式表明,没有一种药物对所有肿瘤都有活性,对一种药物有反应的肿瘤不一定对另一种药物也有反应,这表明预测个体肿瘤对特定化疗药物反应的可行性。如果这七种药物是首次针对这样一组人类肿瘤进行测试的未知活性的研发药物,结果不仅能预测它们的临床活性,而且肿瘤反应率还能表明每种药物对乳腺癌特定治疗的相对潜力。

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