Modulation of the immune response by interferon gamma administration in a rat cardiac allograft model.
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Biomedical subjects
Publications and source records attributed to J Jeekel.
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The effect of pretransplant specific blood transfusions and irradiation of the donor were studied in total orthotopic small bowel transplantation in rats, with the aim of ameliorating the graft-versus-host reaction. Syngeneic transplantation with or without irradiation of the donor with 10 Gy showed that small bowel transplantation is compatible with a normal nutritional status, when no rejection is involved. Transplantation in the histoincompatible WAG-to-BN combination without pretreatment resulted in rejection of the small bowel grafts in 16.6 +/- 2.7 days. Pretreatment with 3 BN blood transfusions to the WAG donor did not prolong the survival time; surprisingly, the transfusions induced a more-severe GVH reaction. Irradiation of the donor with 10 Gy was very effective in ameliorating the GVH disease, but the absence of the immunosuppressive effect of the GVH disease did lead to an accelerated graft rejection (7.5 +/- 0.9 days).
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Clinical studies report reduced recurrence-free survival and increased cancer-related death after surgical treatment for cancer, when peri-operative blood transfusions were given. In this study we collected transfusion data of 212 patients who participated in a prospective study of two different resection techniques for colorectal cancer. One hundred and fifty-eight patients were transfused and 54 were not. The follow-up period for almost all patients was 5 years. The 5-year survival rate was 52% both for the transfused patients and the nontransfused patients. For subgroups of patients with Dukes' B and Dukes' C tumours no statistically significant differences were found. In the group of patients that were transfused the number of transfusions did not affect survival. In this study we could not confirm the deleterious effect of peri-operative blood transfusions on survival.
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Previous studies have shown that lung metastases from a nonimmunogenic sarcoma (LS175) in BN (homozygous for RTln) rats were stimulated by blood transfusions. Enhanced growth was also observed after abdominal surgery combined with allogeneic blood transfusions while syngeneic blood transfusions had no effect. These experimental findings have been confirmed in retrospective clinical studies. The allogeneic blood transfusion effect may be avoided in cancer patients by autologous blood transfusions although this implies blood donation before surgery. The aim of the present study was to investigate the effect of blood loss before surgery on formation ('take') of lung colonies, and on the outgrowth of established metastases in the BN rat model. These aspects of tumour behaviour were also investigated in rats undergoing surgery, or receiving blood transfusion, or both, after blood loss. The results indicate that blood loss has a profound stimulating effect on the growth of established metastases, but not on the 'take' of tumour cells. This stimulating effect was also present when blood loss was combined with surgery, while previously surgery alone was found to have no effect. Allogeneic and syngeneic transfusions in combination with blood loss both had a strong stimulating effect on growth of established lung metastases. The results indicate that blood loss may be an important factor in determining the outcome of metastatic growth.
Median cervical cysts are congenital anomalies arising from remaining thyroglossal duct epithelium. A major problem in the surgical treatment of these cysts is the high frequency of recurrence. Embryonic considerations indicate an important causal role for the hyoid bone in these recurrences. We studied the relationship between operative techniques and the number of recurrences in 36 patients treated in our hospital. Fourteen patients sent from other hospitals had a recurrent fistula; in thirteen cases the hyoid bone was still in place. All patients who had the central part of the hyoid bone excised were cured. In 14 patients without adequate excisions of the hyoid bone we found four recurrences. To prevent recurrence a total excision of thyroglossal duct epithelium is necessary.
In order to assess the effect of the no-touch isolation technique, in the treatment of large bowel cancers, on the site of first recurrence and disease-free and overall survival, 236 patients were prospectively and randomly assigned to either the no-touch isolation technique (117 patients) or to a conventional resection technique (119 patients). No patient with distant metastases or unresectable disease entered the study. The two treatment groups were comparable with regard to patient characteristics. Pre- and postoperative complications (including mortality within 30 days) were similar in both groups. After a complete follow-up of 5 years, a tendency for reduction in the number of, and time to, occurrences of liver metastases was seen in the no-touch isolation group (P = 0.14). This effect was most obvious in the sigmoid colon with angio-invasive growth. Overall (P = 0.42) and corrected (P = 0.25) survival did not differ significantly among the treatment groups although in every analysis the survival data of the no-touch isolation group were superior. The data do suggest a limited benefit of the no-touch isolation technique. This observation is important since the morbidity and mortality of surgery were equal in both groups.
The capacity of the interferon inducer ABPP and recombinant interleukin-2 (IL-2) to generate lymphokine activated killer (LAK) cell activity in vivo was examined and compared to the cytolysis of fresh tumor cells by in vitro generated LAK cells. Various tumors differing in histology and immunogenicity were used in vitro and in vivo experiments. The i.p. administration of ABPP or IL-2 generated much higher levels of LAK cell activity in the peritoneal exudate than in the spleen. Administration of 2 injections of ABPP was as effective as a 3-day course of moderate doses of IL-2. Generation of LAK cell activity by IL-2 was dose dependent. ABPP had significant antitumor activity in vivo in both the i.p. tumor model and the pulmonary metastasis model when administered early (24-48 h after tumor inoculation), but was ineffective against established (day 3) tumor or advanced grossly visible i.p. (day 8) tumor. Treatment of established tumor with IL-2 and LAK cells was not more effective when ABPP was given concurrently. In contrast when ABPP preceded IL-2 and LAK treatment an additional antitumor effect was seen. Immunogenic tumors were more sensitive to treatment with ABPP than nonimmunogenic tumors. Only a marginal difference in lysability in vitro existed. The antitumor effects of ABPP in vivo may therefore be mediated by mechanisms other than cytolysis by activated killer cells alone. These data taken together suggest that ABPP and IL-2 induce discernable levels of LAK cell activity, but do not synergize when combined.