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

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.

Relation between cellular doxorubicin binding ability to nuclear DNA and histologic response to preoperative chemotherapy in patients with osteosarcoma

“…However, it is difficult to detect chemosensitivity before chemotherapy in osteosarcoma, because there are no reliable and clinically useful chemosensitivity tests for this disease. Various chemosen- sitivity tests have been reported in many kinds of cancers, [17][18][19][20] but most of these are technically complicated and have questionable reliability. Only the human tumor colony forming assay was confirmed to be reliable to assess drug sensitivity, and it has been used clinically for various carcinomas.…”

“…5,6 Like the human tumor colony forming assay, many chemosensitivity tests require a procedure of in vivo (xenograft) or in vitro tumor cell culture before assessment. [17][18][19][20] The cell culture process takes at least 1 or 2 weeks and may induce technical artifacts, such as transformation of tumor cell functions or acceleration of contaminating normal fibroblast growth. In contrast to these chemosensitivity tests, ABA 9,10 requires only isolated living tumor cells (ex vivo) with no cell culture.…”

Characteristics of human tumour xenografts transplanted under the renal capsule of immunocompetent mice

“…It was found here, in agreement with our previous findings (Aamdal et al, 1984a(Aamdal et al, , 1984b(Aamdal et al, , 1984c, that a variety of xenografts from different human tumour lines was capable of growing well under the renal capsule of conventional mice, supporting the view that the conditions under the renal capsule of mice are favourable for growth of human tumours (Bogden et al, 1979).…”

Subrenal capsule assay in selection of chemotherapy after operation for recurrent ovarian cancer

“…The subrenal capsule assay (SRCA) (Bogden et al, 1981) correctly predicts the response to cytostatic chemotherapy in 63-85% of patients with previously untreated ovarian cancer (Bogden, 1985; Griffin et al, 1983; Maenpaa et al, 1985a,b;Stratton et al, 1984Stratton et al, , 1986 Stratton et al, , 1988 (Maenpaa, 1985c). There are some data to suggest that the SRCA could be useful in the selection of the second-line chemotherapy (Griffin et al, 1983;Maenpaa, 1985c), but so far no data exist on improved survival rates in patients whose second-line chemotherapy has been guided by the use of the SRCA.…”

“…The subrenal capsule assay (SRCA) (Bogden et al, 1981) correctly predicts the response to cytostatic chemotherapy in 63-85% of patients with previously untreated ovarian cancer (Bogden, 1985;Griffin et al, 1983;Maenpaa et al, 1985a,b;Stratton et al, 1984Stratton et al, , 1986Stratton et al, , 1988. The situation may differ in cases with recurrent cancer, when cell populations resistant to first-line chemotherapy have become selected out to form clinically detectable tumours (Maenpaa, 1985c).…”