High-flow isolation perfusion of the rat hind limb in vivo.

An in vivo model for perfusion chemotherapy of the rat hind limb is described in which perfusion at a predetermined flow rate of up to 4 ml.min-1 can be rapidly established in a tourniquet-isolated limb. Standard additions to the semisynthetic perfusion medium included glucose, insulin, and lactate from fresh human erythrocytes.

Dosimetry in isolation perfusion of the limbs by assessment of perfused tissue volume and grading of toxic tissue reactions.

The optimal single dosage of melphalan in isolation perfusion of the limbs for malignant melanoma was assessed. For this purpose a method to determine the volume of the isolated region in the individual patient and a grading system for the reaction of the normal tissues were introduced. A strictly standardized pharmacosurgical routine was developed that permitted an analysis of the correlation between dosage and the grade of toxic reaction in 90 perfusions.

Effects of alkylating agents on the DNA replication of cultured Yoshida sarcoma cells.

Logarithmically growing Yoshida sarcoma cells were treated for 1 h with low (2 decades cell kill) or high (more than 6 decades cell kill) doses of alkylating agents. Pulse and chase labelled DNA from treated cells were studied by alkaline sucrose gradient centrifugation. Nitrogen mustard (HN-2), 4-hydroperoxycyclophosphamide (CY-OOH), melphalan (L-PAM) and chlorambucil (CA) had no effect on the elongation rate of newly replicated DNA, both at low and high doses, although per cell the rate of DNA synthesis declined as inferred from the rates of [3H]thymidine incorporation compared to the increase in numbers of S phase cells in the treated populations.

Enhanced cytostatic effectiveness of aniline mustard against 7,12-dimethylbenz[a]anthracene-induced rat mammary tumors during regression in response to ovariectomy.

Sprague-Dawley rats bearing 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors were treated with either of two aromatic alkylating agents, aniline mustard or melphalan, alone or combined with ovariectomy. Both drugs were applied once a week for 8 weeks. Eight-four percent of the tumors responded to ovariectomy, 38% regressing completely and 46% regressing partially.

Effects of treatment with cyclophosphamide on hormone-dependent and hormone-independent tumor cells in transplanted GR mouse mammary tumors.

Previous studies have indicated that hormone-responsive mammary tumors of GR mice are mixed populations of hormone-dependent and autonomous cells. We have now investigated whether these two cell types differ in susceptibility to cytostatic treatment. Experiments in which cyclophosphamide was injected in tumor-bearing mice did not reveal significant differences in percentage of inhibition between hormone-dependent, hormone-responsive, and hormone-independent tumors.