Biomedical subjects
Publications and source records attributed to D Cupissol.
Isoprinosine was shown to alter certain T cell functions. In vitro, it has previously been shown to induce suppressor cell activity in both mouse and human lymphocytes. Our in vitro results suggest that Isoprinosine acts on immune balance by increasing the number of non-suppressor T cells and, at least partially blocks Con A induced suppressor activity. In vitro NK activity remained unaltered.
Explore the source record for details and available documents.
The antiemetic effect of alizapride was evaluated in 50 patients with advanced cancer undergoing chemotherapy with cis-platinum. Our results suggest that alizapride, in a dose of 800 or 900 mg, significantly alleviates nausea and emesis. In a preliminary study, we had established that, without antiemetic therapy, the same patients all suffered from emesis. On the whole, alizapride was well tolerated ; no major side-effects were recorded.
Explore the source record for details and available documents.
A randomized trial was initiated to compare the effects of peripheral i.v. nutrition (PIVN)-associated chemotherapy (adriamycin, vincristine, VP-16-213, and cyclophosphamide) versus a chemotherapy control group in patients with oat cell lung carcinoma. Thirty-nine evaluable patients were randomized. The test group included 19 patients, whereas 20 were followed in the control group. PIVN was scheduled each day the patient underwent chemotherapy. Each patient received 1,550 kcal day which included 10% glucose, 20% lipids, and amino acids which may or may not have been mixed in the same infusion bottle. The results show ten PIVN patients presently in complete remission at the end of three courses of treatment, compared to nine over the same time period in the chemotherapy control group. Thirty-three percent of patients are still alive after 15 months after the beginning of treatment. There was no significant difference in either general health or side effects, frequency or duration of complete remission, or survival time. After 1 year of treatment, 8 of 19 PIVN patients are still in complete remission, compared to 7 of 20 patients in the control groups.
The effect of iv injection in C57BL/6 mice of 3X10(7) bone marrow cells preincubated in either thymosin fraction V or thymosin alpha-1 was evaluated on the growth of a 3-methylcholanthrene-induced transplantable tumor in a syngeneic system. The effect was then compared to that elicited by theophylline or levamisole, which both demonstrated thymosin-like action in vitro. The results showed significantly retarded tumor growth (P less than 0.001) and prolonged survival time (P less than 0.001) when thymosin fraction V was used. The same results were obtained with thymosin alpha-1 with use of the same protocol but only one-twentieth of the concentration of fraction V. Theophylline and levamisole demonstrated no antitumor effect.
In vitro cloning of human tumor cells were carried out for 19 patients: 13 breast cancers (4 metastatic effusions and 9 primary tumors), 3 ovarian cancers, 2 glioblastomas and 1 meningioma. Cloning efficiency varied from 1 X 10(-5) to 2.8 X 10(-3). Tumor cells with the highest cloning rates were provided by patients with rapidly evolving tumors. 7 drug assays were performed: in vitro-in vivo correlation was observed in all cases (drug resistance in 5 cases: drug sensitivity in 2).
When a small dacron sponge disc containing live BCG was implanted subcutaneously in healthy subjects it became infiltrated with leukocytes which at 24 hours mainly involved neutrophils. this mycobacterial-induced inflammatory response was markedly impaired in patients with cancer. This inhibitory effect could be reproduced by injecting the plasma of these patients into guinea-pigs bearing identical discs. The differences in inflammatory reactions in the indirect technique were less marked than in the direct test, though a parallelism between the two was seen. The fact that the plasma from cancer patients interferes with neutrophil responses in this way does not exclude the possibility that abnormal cellular functions were also operative. Since tumour growth control depends on effective inflammation these data further underline the importance in cancer patients of a defect at this level.
Explore the source record for details and available documents.
A randomized trial was initiated to compare the effects of PIVN-associated chemotherapy (adriamycin, vincristine, VP16-213 and cyclophosphamide) versus as chemotherapy control group in patients with small-cell lung neoplasias. The results obtained are preliminary. The test group included ten patients whereas nine were followed in the control group. PIVN was scheduled each day the patient underwent chemotherapy. Each patient received 1550 kcal/day, which included 10% glucose, 20% lipids, and amino acids which may or may not be mixed in the same infusion bottle. The results show three PIVN patients presently in complete remission at the end of three courses of treatment compared to two over the same time period in the chemotherapy control group. Of all patients who can be evaluated at this time, five out of six PIVN patients are in complete remission compared to four out of five in the control group. There was no significant difference in either general health or side effects, such as nausea and vomiting. The median length of time for which a low white cell or platelet count was noted was the same for both groups.
Modulation of suppressor cell activity by thymosin was evaluated in vivo in a murine tumor system, and in vitro on human lymphocytes. We showed that splenocytes from tumor bearing mice were able to enhance tumor growth in a syngeneic system. This enhancement was T dependent and disappeared by Thymosin treatment. A decrease of Tumor size associated with injection of bone marrow cells treated by thymosin was observed. In the human system we showed that ConA stimulated lymphocytes were able to suppress the response of normal lymphocytes to PHA, PWM and ConA, and in MLC. This effect was significantly blocked in presence of thymosin fraction 5.
The nutritional state of the cancer patient is still a poorly defined parameter that most probably presents specific differences when compared with other states of denutrition. By definition, the immune response is altered in the denutritive condition. Factors such as amino acids, lipids, insulin, vitamin A, vitamin C and, zinc should be studied in more depth since existing studies have already shown that changes in plasma levels of these factors can modulate the immune response. Present information on hypernutrition is clearly inadequate and often difficult to evaluate, since it is based on nonrandomized trials in cancer patients, and for whom the relationship between nutritional state and the associated immune response was not clearly established. In addition, the effects on lymphocyte subpopulation functions within this context have not been adequately studied. These and other factors employed, is of limited interest and also expensive. We propose a more specific approach to nutritional therapy that would lead to a more specific modulation of the overall immune response.
C57BL/6 mice were injected subcutaneously with Lewis-tumor cells and syngeneic spleen lymphocytes. When these lymphocytes had been preincubated with a thymic extract, tumor development was impaired: the tumor weight and volume were significantly decreased and the number and size of lung metastases were strikingly diminished. In addition, the increase in weight of adrenals and spleen, common in tumor-bearing animals, was not observed. Lymphocytes incubated with a thymic factor preparation can therefore enhance the defense against this tumor.
Explore the source record for details and available documents.
We have demonstrated that splenic lymphocytes from normal syngeneic animals can stimulate tumor growth. This effect is T-cell dependent. Preincubation of these lymphocytes with thymosin not only blocks facilitated tumor growth but can induce a significant reduction of local tumor growth and number of pulmonary metastases. Furthermore, thymosin can also block the expression of suppressor activity of lymphocytes either stimulated by Con A or originating from various advanced solid tumor bearing patients. These results therefore suggest that thymosin is able to modulate, directly or indirectly, functional expression of suppressor cells.
The immune status of the tumor-bearing patient remains poorly defined. In various solid-tumor-bearing patients, we demonstrated the absence of ADCC modifications in the patient in relapse or in evolution. These same patients presented a significant increase in immune complexes when compared with patients in remission. Furthermore, we noted a decreased NK activity, a decreased number of ARFC, corresponding to a helper T cell subpopulation, and a corollary increase in T-dependent suppressor activity. These results, on the whole, suggest an immune imbalance and that the helper cell-suppressor cell ratio should be investigated in greater depth within the context of the immune response in the cancer patient.
The infiltration by inflammatory cells of dacron mesh tissue containing live BCG, implanted under the skin of male and female guinea-pigs treated with normal control and cancer patients' plasmas, was investigated. These cells migrated from the blood vessels to the peri-implant region under the influence of local chemotactic mechanisms generated by the bacilli. Animals given normal or cancer patients' plasmas were unable to produce normal levels of cellular infiltration. This was more markedly reduced with plasma from patients with malignant disease. Cell counts in treated animals have shown significant reduction in while-cell counts but the more marked effect was seen on the polymorphonuclear neutrophil level. Ketoprofen restored normal infiltration responses to animals simultaneously given plasma from cancer patients. These observations further underline the importance of prostaglandins in both inflammation and malignant disease.
The effect of thymosin on suppressor-cell function was evaluated in vivo in a murine tumor system and in vitro on human lymphocytes. In mice, the Lewis tumor system was used. We showed that splenocytes from tumor-bearing animals were able to enhance tumor growth in a syngeneic system. This enhancement was similar when thymocytes from tumor-bearing animals were used and disappeared after anti-Thy 1-2 antiserum treatment, suggesting a T-dependence. Treatment of the tumor-growth-enhancing lymphocytes with corticosteroids or irradiation caused this effect to disappear completely suggesting that the tumor-growth-enhancing T-lymphocytes were suppressor T-cells. Furthermore thymosin (fraction 5)-treated, tumor-growth-enhancing T-lymphocytes were not able to enhance tumor growth and even significantly decreased it. In the human system we showed that Con A-stimulated lymphocytes were able to suppress the response of normal lymphocytes to PHA, PWM, and Con A, and in MLC. This effect was significantly blocked in presence of thymosin fraction 5.