[Immunological studies at the N.N. Petrov Research Institute of Oncology (100th anniversary of birth of Prof. T.A. Korosteleva)].

Historical essay devoted to the life and work of Professor Tamara Alexandrovna Korosteleva (1913-1991), the former Head of the Laboratory of Oncoimmunology at the N.N. Petrov Research Institute of Oncology, St. Petersburg.

[Experimental evaluation of immunotoxicity of olipifat]. / Eksperimental'noe issledovanie immunotoksicheskikh svoistv olipifata.

The paper presents our data on the influence of Olipifat on the mass and cell patterns of the immune system organs, phagocytic activity of macrophages, number of antibody-producing B-lymphocytes and immune rosette-forming T-lymphocytes. Olipifat showed no immunotoxic characteristics; it stimulated T-system immunity as evidenced by a significant increase in the number of immune rosette-forming T-lymphocytes in mice after injection of 100 or 50 mg/kg.

Chemoprevention of mammary, cervix and nervous system carcinogenesis in animals using cultured Panax ginseng drugs and preliminary clinical trials in patients with precancerous lesions of the esophagus and endometrium.

The anticarcinogenic effects and mechanisms of the biotechnological drugs of Panax ginseng C.A. Meyer cultivated in Russia, bioginseng, panaxel and panaxel- 5, were studied. Bioginseng was produced from a tissue culture of ginseng root cultured on standard medium, whereas panaxel and panaxel-5 were produced from ginseng tissue root cultures using standard mediums enriched with 2-carboxyethylgermanium sesquioxide and 1-hydroxygermatran-monohydrate respectively. All three ginseng drugs inhibited the development of mammary tumors induced by intramammary injections of N-methyl-N-nitrosourea (MNU) in rats, the development of the brain and spinal cord tumors induced by transplacental administration of N-ethyl-N-nitrosourea (ENU) in rats, and the development of uterine, cervical and vaginal tumors induced by intravaginal applications of 7,12-dimethylbenz(a)anthracene (DMBA) in mice. The ginseng drugs induced the cytotoxic activity of macrophages in mice, enhanced T-lymphocyte rosette formation in guinea pigs exposed to cyclophosphamide, and stimulated the production of thyroid hormones in rats. These mechanisms may contribute to the anticarcinogenic action of the ginseng drugs. The organic germanium compounds present in panaxel and panaxel-5 did not potentiate the anticarcinogenic or immuno- stimulatory effects as much as biogeinseng. Preliminary clinical trials with panaxel and bioginseng were carried out in patients with precancerous lesions of the esophagus and endometrium. Panaxel was found to have a strong therapeutic effect in patients suffering from chronic erosive esophagitis. Bioginseng induced the regression of adenomatous-cystic hyperplasia of the endometrium in some patients. Thus, we conclude that the drugs of ginseng appear to hold considerable promise for future cancer chemoprevention.

The synthetic peptide related to the central part of human interleukin-2 molecule accelerates growth and vascularization of sarcoma 180 in mice.

The synthetic peptide C-1-6 related to the central part of human interleukin 2 molecule (sequence 59-72; N- and C-modified) had been shown previously to inhibit cytotoxic activity of macrophages converting them to synthesis of growth factors. In this paper the effect of C-1-6 on growth of sarcoma 180 in mice was studied. C-1-6 significantly accelerated tumor growth having been injected into mice in dose 5 or 50 microg per animal since the 4th day after tumor cells transplantation. Supernatants of Mphi in vitro activated by C-1-6 (10 microg/ml) and injected into mice also accelerated significantly sarcoma mass diurnal increasing as compared to mice treated with supernatants of non-activated Mphi or activated with bacterial lipopolysaccharide. A single injection of C-1-6 into mice either at the day or at the next day of tumor cells inoculation increased significantly the number of vessels growing up to transplant, thus the forming of the vascular bed had preceded tumor volume enlargement.

[The MDR gene and cellular sensitivity to various effects]. / Gen mdr i chuvstvitel'nost' kletok k razlichnym vozdeistviiam.

mdr-Transfected K-562 cells revealed a relatively high resistance to cytotoxic monokines and ionizing radiation as compared to parental cells. Taken together with what is known about the resistance of mdr-expressing cells to multiple cytotoxic drugs, our results point to malignant cells having universal mechanisms of chemo-, bio- and radioresistance.

[Effect of ionizing radiation on functional activity of macrophagesi]. / Vliianie ioniziruiushchei radiatsii na funktsional'nuiu aktivnost' makrofagov.

It was shown that in vitro irradiation (8 Gy) of murine peritoneal macrophages suppressed their spontaneous cytotoxity and induced growth-stimulating activity. Exposure to 4 Gy induced mRNA proximal factors--TGF-beta and TNF-alpha and boosted growth-stimulating activity. These effects should be considered when evaluating efficacy of radiotherapy for tumors.

[The effect of brain peptides on nerve tissue cells in vitro]. / Vliianie peptidov golovnogo mozga na kletki nervnoi tkani in vitro.

The effect of cortexin and epithalamin on the cell growth rate was investigated in the organotypic tissue culture of dorsal root ganglia (DRG), and of cortex and subcortical structures of 10-11-day old chick embryos. Cortexin in concentrations of 20 and 100 ng/ml is active, inducing a more intensive neurite outgrowth in DRG, compared to the control. Epithalamin was active in concentrations 20 and 200 ng/ml. Cortexin (100 ng/ml) was active in the cortex tissue culture, but inhibited the neurite growth in the subcortical structures culture. The stimulation of this culture to development was evident after using 200 ng/ml epithalamin. The neurite stimulating effect of cortexin and epithalamin is presumably associated with neurotrophic factors.

[Changes of Willebrand factor level in blood plasma of cancer patients and its role in hemostatic disturbances]. / Izmeneniia urovnia faktora Villebranda v plazme krovi onkologicheskikh bol'nykh i rol' ego v narushenii sistemy gemostaza.

Plasma concentrations of von Willebrand (WF) factor were measured in patients with different tumors and healthy donors. The study has shown the level of WF in cancer patients to be significantly higher than in healthy donors. Hypercoaggulation was identified by laboratory analysis in breast cancer patients only while patients with other malignant tumors revealed the signs of chronic DIC syndrome. Chemotherapy provoked further increase in WF level in the plasma of patients with acute myeloleukemia and breast cancer. The importance of plasma WF assay for diagnosis and prediction of thromboembolic complications in cancer patients is discussed.

[Synthesis and expression of transforming growth factor-beta in activated macrophages]. / Sintez i èkspressiia transformiruiushchego faktora rosta-beta aktivirovannymi makrofagami.

It has been established that once macrophages become activated, they pass through different stages of functional activity. Mouse macrophages activated by BCG "exerted" pronounced cytotoxic effects for 2-5 days to be followed later by growth-stimulating ones. However, in other experiments, the cytotoxic effect was either absent or occurred at later stages which was probably due to a certain functional state of macrophages before activation. The synthesis of TGF-beta increased 1-2 days after activation with BCG vaccine, lipopolysacharide and gamma radiation. An increase in mRNA TGF-beta i expression was observed only 5 days after activation of macrophages.