This study was designed to evaluate the interaction of photodynamic therapy (PDT) and chemotherapy in an animal model. PDT is based on the interaction of hematoporphyrin derivative and red light of the appropriate wavelength (630 nm) and intensity. Two tumor models were utilized: C3H/Km mice bearing the RIF-1 tumor and BALB/c mice bearing the EMT-6 tumor. Tumor-bearing mice were treated with either cisplatin (DDP), doxorubicin (ADM), PDT, or a combination of drug and PDT. It was demonstrated that the RIF-1 tumor was sensitive to DDP and insensitive to both PDT and ADM. There was no additional antitumor effect when either drug was combined with PDT. The EMT-6 tumor was moderately sensitive to PDT and mildly sensitive to both DDP and ADM. Although the addition of DDP did not potentiate tumor destruction, the addition of ADM significantly enhanced the effect of PDT (P = .01). The enhanced activity of the combination of PDT and ADM appeared to be the result of increased activity of ADM alone, when illuminated with red (630 nm) light. This potentiation may be due to a photochemical process or may be secondary to the mild hyperthermia generated by illumination with the laser. This study demonstrates that PDT combined with cytotoxic chemotherapy is well tolerated in these animals and that certain combinations of PDT and chemotherapy may result in an enhanced tumoricidal effect.

No abstract

Serum-mediated impairment of lymphocyte function was studied in an animal model. Sprague-Dawley rats inoculated intraperitoneally or subcutaneously with the Walker 256 carcinoma underwent sequential sampling of blood. The effect of these serum samples upon phytohemagglutinin-induced blastogenesis of normal rat splenocytes was monitored in an assay utilizing incorporation of (3H)-thymidine. The effect of serum samples from both the subcutaneously and the intraperitoneally inoculated tumor-bearing animals was biphasic. Early on, serum enhanced blastogenesis and later suppressed blastogenesis. Separation of sera into high and low molecular weight components by ultrafiltration demonstrated the enhancing activity to reside in the high molecular weight fraction. The enhancing activity of sera decreased over time from tumor inoculation. Conversely, suppressor activity increased over time from tumor inoculation. This study demonstrated that suppressor activity of sera obtained from animals with advanced tumors is the result of the lack of enhancing activity coupled with the elaboration of suppressor activity.

A study was undertaken to enumerate and partially characterize soluble factors generated by tumor-bearing animals capable of suppressing PHA-induced splenocyte proliferation. Sprague-Dawley rats were induced to form malignant ascites by the intraperitoneal injection of the Walker 256 carcinoma. Intact ascites suppressed splenocyte proliferation by 96%. Molecular sieving of the ascites by means of ultrafiltration (10-kilodalton particle cutoff) revealed suppressor activity to reside in both the ultrafiltrate and retentate. Further enumeration of suppressor factors was achieved by preparative polyacrylamide gel electrophoresis of the ascites ultrafiltrate and retentate. Five discrete bands of suppressor activity were resolved in the ultrafiltrate, three of which were heat-labile. Three discrete bands of suppressor activity were resolved in the retentate, none of which were heat-labile. This study underscores the complexity and heterogeneity of soluble factors elaborated in a cancer-bearing animal.