The paper presents data on the role of some genes that provide normal positive and negative regulation of cell proliferation. It considers their structural and functional changes that lead to the occurrence and progression of tumors. The characteristics of tumor suppressive genes whose inactivation determines hereditary predisposition to some forms of malignant neoplasms.

Clinicomorphological analysis of 15 lung carcinomas of patients who had been exposed for a long time to the radiation after the Chernobyl accident was performed. The material consisted of 10 surgical and 5 autopsy cases and was studied at the light, electron microscopic and immunohistochemical level. There were 6 peripheral, 8 central carcinomas and one massive tumor. Fibrous areas with many dust particles were found in peripheral carcinomas. In central tumors chronic obstructive bronchitis with epithelial dysplasia and metaplasia was observed. Carcinoma was represented by various histologic types: small cell (4 cases), combined small cell with squamous differentiation (5 cases), adenocarcinoma (5 cases), adenosquamous type (1 case). Peculiar calcium deposits in both stroma and parenchyma were found in tumors with glandular differentiation. Morphogenesis of calcium microdeposits may be connected with dust radioactive particles elimination. Central carcinoma had, in the majority of cases, a neuroendocrine differentiation and can be related to some types of small cell carcinoma. Peripheral cancer was mostly of a glandular differentiation and was, as a rule, carcinoma in the scar. Lung carcinomas studied had peculiar molecular-genetic features: lack or low bcl-2 expression, low Ki-67 expression and a high degree of c-myc expression. Tumors were characterized by a low apoptosis index independently of a histologic type. Apoptosis was not complete: lack of apoptotic bodies phagocytosis this resulting in postapoptotic detritus formation.

The analysis is presented of clinicomorphological and laboratory characteristics of myxoma syndrome which are of prognostic value. Early diagnosis of the syndrome is essential in making decision on the intraoperative and long-term postoperative treatment policy.

Data on allelotyping of minisatellite sequence within the Hras1 protooncogene locus in 60 patients with lung adenocarcinoma (LAC) are presented. Allele distribution was analyzed with respect to the effect of tobacco smoke carcinogens (smoking factor). Results were compared with the analogous data obtained for patients with squamous-cell-carcinoma and for individuals without cancer. In contrast to the patients with squamous cell-carcinoma, the frequency of the Hras1 locus rare alleles in patients with lung-adenocarcinoma was higher than in individuals without cancer. More striking difference between the latter groups was demonstrated for nonsmoking patients (17.6% versus 2.7% of healthy individuals, P = 0.0005). In smoking LAC patients, higher frequencies of the common a4 allele (2.5 kb in size under the MspI/HpaII digestion) were found. Our findings point to the combined effect of endogenous and exogenous factors on the development of lung adenocarcinomas in humans. In this work, we discuss the possible mechanism of association between the rare minisatellite alleles and the predisposition to lung cancer.

We have demonstrated earlier that the replacement of the plasma membrane components of Erlich adenocarcinoma cells by the ones of thymocytes facilitates induced apoptosis in the tumor cells. Here we questioned whether similar effect can be achieved by transfection of thymocyte DNA. Lyposome transfer of normal DNA did not change the basal level of the programmed cell death. However, transfection activated apoptosis induced by Roentgen irragiation or glucocorticoids. Probably, this effect was due to restoration suppressor genes, which had been lost during the process malignant transformation. These experiments may be useful for the development of gene therapy approaches for tumor sensibilisation.

Tissue was sampled from 121 tumors of the breast. The activity of aromatase (estrogen synthetase) was assessed by radiobiochemical means in 61 cases; gene expression was evaluated with the aid of polymerase chain reaction in 14 and the same--by the dot-blot procedure in 46 patients. Inveterate smokers (15 years and more) made up 16.5%. The smokers revealed a distinct tendency towards aromatase activity decreasing in tumor tissue (chiefly in menopausal patients) as well as lower intensity of aromatase gene expression assessed in terms of polymerase chain reaction. Alongside with other evidence, our finding point to long-term-smoking-related sensitivity of intratissular estrogen synthesis being higher than in general circulation. It also demonstrated local aromatization inhibition in tumor tissue, the latter being a possible mechanism which causes tumor tissue hormone sensitivity to change in smokers and affects course of disease.

In order to compare the frequency of damage to the transforming growth factor TGF-beta receptor type II gene (RII gene) and microsatellite instability (MIN) in oncogenesis of sporadic and hereditary cancer of gastrointestinal tract (GIT), 4 groups of carcinomas were analyzed. They included sporadic gastric (GC), family gastric (FGC), sporadic colorectal (CC) and hereditary nonpolyposis colorectal (HNPCC) carcinomas having appropriate clinical and pathological characteristics. Each group consisted of two types of carcinomas, one of them showing MIN. The RII gene damage occurred in 89% of GC (8 cases out of 9), 86% of CC (6 out of 7), 71% of FGC (5 out of 7), 50% of HNPCC (3 out of 6) for carcinomas coupled with MIN, whereas only in 6% (1 out of 18) of GC and 5% (1 out of 22) of CC for carcinomas without MIN. No damage to RII gene was found in the cases of hereditary carcinomas which did not show MIN though the number of cases analyzed was not sufficient for final conclusions (3 cases of FGC and 3 HNPCC). The data revealed a correlation between the MIN phenotype and mutations in RII gene both for sporadic (p < 0.001) and for hereditary (p < 0.02) cases. For all 4 groups the frequency of RII gene damage was found for early and advanced carcinomas. This suggests that the deficiency of TGF-beta receptor complex in both sporadic and hereditary carcinomas of GIT is revealed at early stages of tumor development and consequently may be responsible for tumor progression. The correlation between RII gene damages and MIN in GIT carcinoma cells suggests that genetic change predetermined the neoplasia of colorectal and gastric epithelium and partially overlapped for both sporadic and hereditary cases.

The study of neoplastic growth capacity in gag-myc F3-F4 transgenic mice showed that they retain the capacity to develop hyperplasia and benign and malignant tumors same as F0-F2 transgenic mice do. However, the histological spectrum of tumors was much narrower, chiefly, due to the absence of rare patterns. The tumors in F3-F4 transgenic mice were mainly lymphomas and epithelial tumors of endocrine or exocrine glands. The incorporation of gag-myc in the genome of F3-F4 transgenic mice failed to tell on the variation of such quantitative polygenic characteristics as body mass and growth.

Microsatellite instability (MIN) of human genome, i.e. instability of very short (1-5 nt) DNA tandem repeats, points to a deficiency in the mismatch repair system (MMR). To investigate the role of MMR in sporadic and hereditary carcinogenesis in the gastrointestinal tract, four types of carcinomas were compared: sporadic (GC), familial (FGC) gastric carcinoma, sporadic colorectal (CC) and hereditary nonpolyposis colorectal (HNPCC) carcinoma. No significant difference in MIN frequency was found between GC (9 out of 27) (33%) and CC (7 out of 29) (24%). In hereditary carcinoma group, MIN occurrence appeared 2-3 times as high: FGC in 7 out of 10 (70%) and HNPCC in 6 out of 8 patients (75%). No significant differences were recorded in MIN occurrence at early and later stages of the disease in all groups. Therefore, it can be suggested that disorders in the MMR develop at earlier stages of carcinogenesis and may be responsible for tumor progression.

Retrospective estimation of the prognostic importance of parameters, that are different in biological essence, for the persons that have died from malignant melanoma of the skin with use of the adequate mathematical approaches is carried out. A spectrum of important cytogenetic, morphologic and clinical factors which have influence on the prognosis of disease is determined. For group of living patients the prognosed survival time are individually calculated.

In an immunohistochemical investigation designed to study a mutated p53 protein in transitional-cell tumours (n = 44) we succeeded in identifying the presence of two types of transitional-cell tumours of human urinary bladder, such as p53 immunopositive and p53 immunonegative transitional-cell tumours. Thus, the results of the immunohistochemical investigation into the protein p53 were found out to directly correlate with the clinical course of transitional-cell tumours, that are held to be of great differential-diagnostic and prognostic significance.

DNA transcription and replication are organized by the nuclear matrix. It has been recently shown that the osteocalcin gene promoter binds specifically two proteins, NMP-1 and NMP-2 (nuclear matrix proteins 1 and 2), from cell line ROS 17/2.8 (Bidwell et al., 1993). Osteocalcin in one of the proteins taking part in extracellular matrix mineralization during osteogenic differentiation. Osteopontin gene is also active at the late stages of osteogenesis, so we supposed that its promoter could be bound to the nuclear matrix as well. Among the nuclear matrix proteins of ROS 17/2.8 we have found a protein factor which binds the promoter region of the osteopontin gene specifically with the help of gel shift assay. Two proteins with isoelectric points of pH > 8.0 and mol. masses of 38 and 43 kDa, respectively, have been purified by affinity chromatography with the promoter region of osteopontin attached to cellulose. The mol. masses of the revealed proteins are similar to those of already characterized NMP-2 (38 kDa) and one of subunits of heterodimer NMP-1 (43 kDa). Computer analysis shows that the binding sites for these proteins exist in the osteopontin gene promoter region. So, it is very likely that we dealt with the same proteins. A further investigation could lead to characterization of a group of nuclear matrix attached osteogenic-specific transcriptional factors.

Diagnostic criteria of T-cell lymphoma and Hodgkin's disease are presented which are the basis of the European-American classification schema (REAL). Brief morphological, immunophenotypical, genetic and clinic characteristics of every tumor type (subtypes variants) are given. The comparison of this REAL section with the Kiel's classification is made with some critical notes concerning, in particular, the Hodgkin's disease classification.