Effects of immunosuppressive acidic protein on DMBA-induced pancreatic cancer in rats.

Abstract

In order to determine the effect of immunosuppressive acidic protein (TAP) on the formation of pancreatic carcinoma, rats of the Sprague-Dawley strain were embedded with 7,12-dimethylbenzanthracene (DMBA) in the pancreas with and without administration of TAP. In these animals, the growth of pancreatic cancer was studied both immunologically and histologically. Tumor was induced in 51 animals (85%) of 60 treated with embedding of 1 mg DMBA alone. Tumors began to appear from the 16th week after the embedding. Among animals in which tumor was induced, tubular adenocarcinoma and pleomorphic carcinoma accounted for 55% of the cases. When administration of TAP was combined, the period required for development of tumor was shortened. It became shorter with increases in the dosage and frequency of administration of TAP. In animals which received TAP in a mean dose of 75 mg/kg the area showing cancerous changes appeared as early as at the 8th week after the embedding of DMBA. A significant increase in the volume of tumors was seen in the group treated with TAP as compared to the group not treated with TAP. Animals which received TAP in increasing doses and frequencies showed an accelecrated increase in the volume of the tumors which underwent cancerous changes. TAP was eliminated from the serum of rats within 72 hr after the administration, and acid protein was clearly recovered from the serum when tumors proliferated. These findings indicate that the acceleration of carcinogenesis in DMBA-induced pancreatic carcinoma may be attributable to the immunosuppressive effect of TAP administered and tend to be dependent on the dosage and frequency of its administration in the early phase of tumor induction.experimental pancreatic cancer ; 7,12-dimethyl benzanthracene ; immunosuppressive acidic proteinAs an approach to the diagnosis and treatment of pancreatic carcinoma, establishment of experimental models of pancreatic carcinoma has been attemped (Druckrey et al. 1968;Pour et al. 1975). Heretofore, few papers have been published describing the preparation of experimental models of pancreatic car-

The pathobiological impact of cigarette smoke on pancreatic cancer development (Review)

“…Intriguingly, DMBA induces pancreatic carcinogenesis in rats as well (58,154,155). DMBA-induced carcinogenesis was increased through pancreatic hyper-stimulation as well as systemic immunosuppression through immunosuppressive acidic protein (156,157). Metabolization of DMBA has been investigated in rats.…”

Modulation of CD4 Antigen Expression on the Lymphocyte Surface by Immunosuppressive Acidic Protein in Cancer Patients

“…Immunosuppressive acidic protein (IAP) was isolated from ascitic fluids and serum of cancer patients as an immunosuppressive factor [I], IAP has a molecular weight of 50,000 and belongs to the cii glyco proteins [1], It has been shown that IAP impairs phyto hemagglutinin (PHA)-induced lymphocyte blastogenesis and the 2-way mixed lymphocyte reaction [1], and en hanced tumor development in rats [2], Clinical examina tions have revealed that serum levels of IAP increase with progress of the disease in patients with various types of tumor, including gastric and ovarian cancers and adult T cell leukemia [3][4][5]. The mechanism of the immunosup pressive effects of IAP, however, has not been elucidated in detail, although induction of suppressor macrophages has been demonstrated by intravenous administration of IAP in mice [6], In the present study, we attempted to explore further the immunosuppressive mechanisms of IAP, with respect to its action against the lymphocyte sur face antigens, using direct immunofluorescence flow cy tometry.…”