Immune ribonucleic acid (I-RNA) in the treatment of metastatic renal cell carcinoma.
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Biomedical subjects
Publications and source records attributed to F Corrado.
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A monoclonal antibody (MAb) to human transitional-cell carcinoma of the bladder (TCCB) was obtained by immunization of a BALB/c mouse with formalin-fixed TCCB cells and subsequent fusion of the spleen cells with SP2-OAg14 myeloma line. GF 26.7.3 MAb was selected by indirect immunofluorescence (IIF) as reacting agent with target cells and negative with autologous lymphocytes and Epstein-Barr virus (EBV)-transformed lymphoblastoid cell-line. GF 26.7.3 reacts with a high percentage of bladder and colon carcinomas when examined by IIF and immunoperoxidase techniques and cross-reacts with a determinant expressed on neutrophilic cell lineage. The IIF analysis performed on bone marrow and peripheral blood (PB) from healthy subjects and leukemic patients and on leukemic cell lines showed that the expression of the structure detected by GF 26.7.3 is restricted to the neutrophilic cell lineage and first expressed at the promyelocytic level. Immunoprecipitation and SDS-polyacrylamide gel electrophoresis (PAGE) of 125 I-labelled membrane proteins from target cells were performed, but no bands were detected by autoradiography. In addition, pronase insensitivity and periodate sensitivity suggest the possible involvement of a carbohydrate determinant.
Six bladder cancer patients received intralesional injections by needle, under cystoscopic control, of 1969-4046 units (U) of xenogeneic IL-2 of high biological activity (324 U/ml; 397 micrograms/ml protein; 1.22 protein/U ratio). The treatment was spread over 7-54 days and 0.5 ml was injected each time. In 3/6 patients complete tumour regression was seen 43, 60 and 105 respectively days after the first IL-2 injection. In 2 a 70% regression was observed at days 45 and 75. In the last patient massive necrosis throughout the tumour mass was recorded on day 25 at radical cystectomy. In order to evaluate the minimum IL-2 U required to obtain positive clinical results and/or to assess whether the anti-tumour effect observed could be ascribed to the foreign protein of bovine origin contained in our IL-2 preparation, 4 additional bladder cancer patients were treated in 7-14 days with 156-1404 U of a second IL-2 lot with a much lower biological activity and similar protein content (52 U/ml; 289 micrograms/ml of protein; 5.55 protein/U ratio). No clinical or histological improvement was noted over a 42- to 54-day observation period. When we evaluated the 2 groups of patients by Student's t-test for both total U injected and U/kg of body weight (bw) we found a statistically significant differences (0.0025 less than p less than 0.0005 and p less than 0.0005, respectively). In contrast, no difference was seen for the injected protein amounts. The reported observations are in favour of a dose-dependent anti-tumour action mediated by IL-2 instead of foreign proteins. In none of the patients treated were any early or late adverse clinical side effects observed. Immunological monitoring (E, EAC, E-active rosettes, mitogen lymphocyte stimulations and leukocyte migration inhibition in the presence of allogeneic bladder cancer cells) performed on the peripheral blood (PB) showed significant but contrasting modifications after IL-2 injection. There was no clear correlation with the clinical course. The patients in whom we observed complete regression are still tumour free after 2, 4 and 7 months. In addition, in all the patients of the first group we observed an increase in tumour lymphoid infiltrate after IL-2 injection and in 2 patients lymphoid pseudo-follicles were also noted. In 2 of these patients we also observed scar-like areas in the place of the tumours previously seen.
A case of a female infant with karyotype 46,XX,r(21)/45,XX,-21 is reported. From comparison of the phenotypic anomalies with the other similar cases the large variability of the 21q- syndrome is evident.
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The authors studied 24 girls with distal urethral narrowing at voiding cystourethrography. Their observation seem to confirm that the distal urethral stenosis is generally functional, because often an anatomical obstruction can not be detected with the bougie a boule calibration. The urodynamic and urovideocystographic methods of study allow to differentiate three types of functional urethral stenosis that are not detectable with the radiologic examination alone. The physiopathologic mechanism of the obstruction is the condition for a successful pharmacologic treatment of these small girls.
The presence of tumour-associated antigens in bladder carcinomas has been shown in leucocyte migration inhibition and lymphocyte stimulation using formalin-treated autologous tumour cells as antigen. The treatment of patients with an in vitro produced specific transfer factor enhances their reactivity in these tests. However, when tumour cells from relapses were substituted for those of the primary tumour, the reactivity previously observed was abolished. An antigenic modulation and/or a polymorphic expression of bladder tumour-associated antigens in secondary tumours is suggested and might be responsible for some immunological escapes.
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Human dialysable Transfer Factor (TFd) extracted from lymphocytes of patients with transitional cell carcinoma of bladder (TCCB) was replicated in culture by lymphoblastoid cell lines. The effectiveness of two such TFdLs produced in vitro in transferring sensitivity to TCCB was assessed in the lymphocyte migration test (LMT) using formalin-treated TCCB cells as antigen. The results, showed that one TFdL transferred sensitivity in 5/14 cases and the other in 12/15, not only to leucocytes of healthy individuals but also to leucocytes of TCCB patients. Preliminary results showing an in vivo transfer of sensitivity are discussed.
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