Cancer immunotherapy using local interleukin 2 administration

Peri-tumoural administration of human recombinant interleukin-2 (RIL-2) into C57BL/10ScSnPh (B10) mice carrying subcutaneous transplants of syngeneic methylcholanthrene (MC)-induced sarcomas substantially inhibited tumour growth. Experiments were designed to compare the tumour-inhibitory effect of highly purified RIL-2 with that of unpurified human and rat lymphoid interleukin-2 (IL-2) preparations. It was found that the effect of RIL-2 was significantly lower than that of the lymphoid IL-2 preparations. These findings indicate that other lymphokines may participate in the positive results of local IL-2 immunotherapy using unpurified lymphoid IL-2 preparations. However, the admixture of human recombinant interleukin-1 (RIL-1) did not potentiate the immunotherapeutic effects of RIL-2. Sensitivity of MC-induced sarcomas to local RIL-2 immunotherapy was a general phenomenon. The growth of approximately eighty percent (5/6) of the MC-induced sarcomas could be inhibited with local RIL-2 administration. Moreover, direct correlation between the sensitivity of tumours to the tumour-inhibitory effect of RIL-2 in vivo and their susceptibility to the cytolytic effect of RIL-2-activated syngeneic killer spleen (LAK) cells in vitro was observed. This correlation indicates that LAK cells represent the effector cell mechanism responsible for the anti-tumour efficacy of local RIL-2 immunotherapy and that in vitro testing of sensitivity to the LAK cell-mediated cytolysis may be used to detect tumours responding to the local RIL-2 immunotherapy in vivo.     

Abdominal zygomycotic thromboangiitis in a patient with AML and t(1;13;14)

 The case report of a 61 year-old man with AML M2 FAB, t(1; 13; 14) and zygomycotic mesenterial thromboangiitis is presented. Two induction cycles of chemotherapy were administered due to primary drug resistance. They were complicated by pneumonia, colonic pseudo-obstruction and perforation with peritonitis. The patient died on the 40th day of therapy, 4 days after undergoing palliative surgery. Zygomycotic thromboangiitis, which very probably contributed to the intestinal perforation, was confirmed morphologically at necropsy. The novel complex chromosomal translocation t(1; 13; 14) (q31; q32; q24) and the problems connected with the diagnosis of invasive fungal infections are discussed. Received: 26 January 1996 / Accepted: 12 June 1996     

Follow-up of outpatients with essential hypertension. A comparison of three methods of blood pressure measurement.

Compared with conventional, routine blood pressure measurement in the outpatient department of a hospital, 24-hour blood pressure monitoring provides more comprehensive information about blood pressure values in day-to-day life of the hypertensive patient. The hospital setting with all its stimuli affects the hypertensive patients so that their values will be statistically significantly higher compared with normal ones. Recent years have seen the introduction into clinical practice of self-monitoring by the patients themselves. Comparison of these three methods for blood pressure measurements revealed that self-monitoring may provide fairly accurate values comparable with those obtained by the "standard method", i.e., 24-hour monitoring. In view of the low variability of the mean value of blood pressure over a period of several days, self-monitoring can be employed in groups of selected outpatients on long-term follow-up.     

Fusion-induced malignancy? A preliminary study. (a challenge to today's common wisdom).

Five fusions between mouse embryonic cells and syngeneic adult peritoneal macrophages were performed. The resulting hybrids as well as both parental cells (6 cultures of embryonal cells and 6 cultures of adult macrophages) were grown in vitro under the same culture conditions. All populations of explanted macrophages died during the second month in primary culture and five populations of cultured embryonic cells were lost within six months under in vitro conditions as well. One embryonic cell line survived and acquired transformed and/or malignant phenotype: When inoculated into either newborn or adult syngeneic mice, progressive growth of tumors with 100% take (6/6), histologically classified as poorly differentiated fibrosarcoma with areas of metaplastic bone and osteoid, was observed. Two out of five wild hybrid strains died within six months of cell culture. The resulting three hybrid cultures adapted themselves to in vitro conditions and finally permanent lines were established with all features of transformed phenotype in vitro and with the capacity to grow as undifferentiated fibrosarcomas with 100% take (6/6) when inoculated into syngeneic mice either s.c. or i.p. Cytogenetic studies were performed and phenotypic characteristics of these lines were explored as well. Biological assays performed for the presence of oncogenic viruses were negative and none of the malignant cell lines showed positive staining with the monoclonal antibody specific for large T-antigen. It is suggested that cell fusion of two normal partners may switch on the cascade of abnormal processes which may culminate in neoplastic conversion. Cell fusion might play also a significant role in the so called "spontaneous" transformation.     

Neurotoxicity and dermatotoxicity of cyanomorpholinyl adriamycin

Summary The highly lipophilic cyanomorpholinyl adriamycin (CMA) is the most potent antineoplastic anthracycline yet described. CNS distribution and toxicity were examined after i.v. administration of CMA to mice. At doses 0.1 mg/kg, a neurotoxic syndrome including ataxia, hypokinesia, and tremors appeared. At doses of 0.05 mg/kg, which have been reported to be antineoplastic, no neurotoxicity was observed. On histopathologic examination, no changes were observed in the brain, spinal cord, or dorsal root ganglia. Unlike adriamycin (ADR), which rapidly appears in the nuclei of several tissues, CMA showed no fluorescence, suggesting a different cellular microcompartmentalization. The i.d. injection of CMA disclosed a 200-fold increase in toxicity compared with that of adriamycin. In comparisons of CMA and ADR, neurotoxicity and cardiotoxicity occurred equally only at higher doses; however, the dermatotoxicity and antineoplastic activity of CMA were increased several hundred-fold.     

DNA synthesis of human XYY cells

The autoradiographic YY labelling pattern of the DNA replication in 47, XYY cells of two patients has been studied. Both Y chromosomes began DNA replication simultaneously but later than the rest of the chromosomes. During later stages the YY labelling pattern in both patients was correlated to the position of the cells in S, as indicated by the cell grain count: in cells with more than approximately 500 grains the synchronous labelling of the Y chromosomes was the rule; whereas during later stages in cells with approximately 100–400 grains, synchronous as well as asynchronous labelling in the same patient was found. In cells with less than about 100 grains, both Y chromosomes usually had completed replication. No obvious difference between the labelling pattern of the two Y chromosomes was found when cells from the 2 patients were compared at the same stage of S. Our results demonstrate the importance of analysing cells of comparable developmental stages of S when comparing DNA labelling patterns of different XYY individuals in search of a possible correlation between labelling pattern and phenotypic expression of the syndrome.
In one of the patients the QM fluorescence pattern as well as the autoradiographic pattern of the same cells was studied. The characteristic intense fluorescence pattern of both Y chromosomes was found even in cells where the autoradiographic labelling pattern indicated distinct asynchrony between the two Y chromosomes. The significance of these findings is discussed.     

Effect of IFN-γ receptor gene deletion on vaccinia virus virulence

Summary.  Two vaccinia virus (VV) strains, WR and Praha, were selected for a study undertaken to determine whether the virus-encoded interferon-γ receptor (IFN-γR) plays any role in virus virulence. Both of the viruses expressed the B8R gene coding for IFN-γR in infected cell cultures. The nucleotide sequence of the Praha virus B8R gene was determined, and, when compared with the published sequence of the WR virus, it only displayed one silent nucleotide substitution. Mutants of the WR and Praha viruses with deleted B8R gene were constructed. In rabbits, skin lesions produced by the WR B8R-deleted mutants were smaller and tended to disappear earlier than those caused by wild-type WR virus. Similar results were obtained with both independently prepared WR B8R-deleted mutants. These data strongly suggested that the product of B8R gene did play a role in virus virulence. A similar comparison of the wild-type Praha virus and its mutant could not be done because of the very low virulence of the parental virus for rabbits. Received March 13, 2000 Accepted August 16, 2000