[Immunohistochemical diagnosis of metastases of small round cell carcinomas with undetected primary focus].

17 small round cell tumors of unkown primary site were studied. The main location was lymph nodes and brain. Immunohistochemical study was performed.

[Molecular markers of various stages of nonsmall cell lung cancer development].

Studies performed in the recent decade in the Laboratory of the Regulation of Cell and Virus Oncogenes associated structural and functional defects of several oncogenes and tumor suppressor genes with various stages of non-small-cell lung cancer. High risk of lung cancer was established for carriers of rare alleles of the Hras1 minisatellite, the hypermethylated p16INK4A promoter, and microsatellite defects in chromosome regions 3p12, 3p14.2, 3p22-24, 3p21, 3p25, 9p21, and 17p13.

[Development of chronic obstructive pulmonary disease correlates with mini- and microsatellite locus instability].

Allele distribution at a highly polymorphic minisatellite adjacent to the c-Hras1 gene as well as deletions of microsatellite markers, D3S966, D3S1298, D9S171, and a microsatellite within p53 gene, were examined in bronchial epithelium specimens obtained from 53 chronic obstructive pulmonary disease (COPD) patients and healthy donors. A higher frequency of rare Hras1 minisatellite alleles in COPD patients than in the individuals without pulmonary pathology (6.6% versus 2.

[Suppression of the metastatic potential of oncogene v-src-transformed cells as a result of activity of the exogenous DAP kinase].

Hamster tumor cell lines obtained with the Rous sarcoma virus and characterized by a high metastatic activity in vitro were transfected with the gene for C2+/calmodulin-dependent serine-threonine death-associated protein kinase (DAPk). Expression of DAPk in tumor cells dramatically reduced their survival in the blood of syngenic animals and their ability to produce metastases, but did not affect their tumorigenicity or the primary tumor growth. The DAPk-induced change in the metastatic phenotype was not accompanied by substantial changes in production and phosphorylation of v-Src or focal adhesion proteins (focal adhesion kinase and paxilline).

[Increased risk of occurrence of pulmonary adenocarcinoma in man is associated with the presence of rare alleles of the Hras1 minisatellite].

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.

[Restriction polymorphism of the proto-oncogene c-Ha-ras-1 in patients with multiple primary malignant neoplasms and non-small-cell lung cancer].

Restriction fragment length polymorphism in the human c-Ha-ras-1 locus, associated with a minisatellite sequence, was examined in 45 multiple primary cancer (MPC) patients, 56 patients with squamous cell lung cancer (SCLC), 21 patients with lung adenocarcinoma (LAC), and 53 individuals having no oncopathology. Southern analysis of cellular DNA revealed the presence of 4 common alleles (with collective allele frequency close to 94% in the control group) and a set of rare alleles. Allele a3, (2.

[Cloning cDNA for the ha-SDGF gene from a Syrian hamster cell line with increased metastatic potential using subtractive hybridization].

Using subtractive hybridization, a cDNA library containing over 50% of clones specific for a highly metastatic cell line was obtained from two hamster embryo fibroblast lines with different metastatic potentials. Most of the clones (83%) contained new sequences. One clone contained the ha-SDGF gene cDNA homologous to SDGF cDNA from rodents.

[Effect of specific activation of phosphatidylcholine metabolism in hamster fibroblasts transformed by Rous sarcoma virus].

Transformation of embryonic hamster fibroblasts by the Rous sarcoma virus results in sharp increase of the turnover rate of one of cellular phospholipids-phosphatidylcholine. The decrease in the rate of virus-transformed cells (HETSR strain) during the monolayer formation is attended by additional activation of phosphatidylcholine turnover. A similar effect is observed after prolonged culturing of cells with dexamethasone.

[Expression of the v-src oncogene in Escherichia coli affects the rate of cell growth and leads to phosphorylation of cellular proteins].

The possible influence of expression of v-src oncogene harboring tyrosine-specific protein kinase activity on the physiological state of E. coli cells, carrying plasmid which expresses src oncoprotein was studied. The realization of this activity in the cells brings to the phosphorylation of tyrosine in some additional cellular proteins and, as a consequence, to an increased proliferative activity of cells expressing src oncoprotein.

[A new recipient cell line for transfection of biologically active oncogenes].

The properties of the new immortalized rat cell line (REF-1) were analyzed. These cells can be used as recipient ones in transfection assays. REF-1 cells never convert spontaneously to transformed phenotype during long-term passages in vitro unlike NIH3T3 cells.

[The effect of Ha-ras oncogene on cells immortalized by the gene for polyomavirus large T-antigen].

Activated human Ha-ras oncogene cloned on the plasmid pEJras6,6 was transfected into REF (LT) cells immortalized by the gene for large T-antigen of the polyoma virus. The cells were shown to become completely transformed (in the terms of morphology and tumorogeneity) only after three cycles of transfection with the plasmid pEJras6,6. The integrated sequences of the plasmid pEJras6,6 and the ras oncogene product p21Ha-ras were detected in cells only after their selection in the nude mice (in the cell culture REF (LT) ras X 3tu obtained from the tumor and directly in the tumor cells).

[Differences in the distribution of proviruses in low- and highly- metastatic variants of hamster cells, transformed by Rous sarcoma virus].

The structure of provirus in Syrian hamster cells, transformed by Rous sarcoma virus (RSV) varying in metastatic capability in vivo has been analysed. The original cell line and its low metastatic variants contain only one copy of the integrated RSV genome. The DNA of highly metastatic cell lines cloned from the same primary culture, contain an additional copy of provirus.

[Transcription and expression in Escherichia coli of src gene cloned sequences of rous sarcoma virus].

Effective transcription of virus-specific sequences was shown in Escherichia coli cells that carry recombinant plasmids pPrC11 and psrcC with fragments of the Rous sarcoma virus (RSV) genome. Analysis of transcripts revealed several classes of RNA, one of which is probably transcribed from the structural part of the RSV src gene. Analysis of the primary structure of the region adjacent to the src RSV gene showed the existence of sequences similar to the bacterial promoters from which the src-specific RNAs can be transcribed.

[Transfection of a plasmid with a retrovirus promoter: distribution of sequences in the genome of induced tumors].

The structure of the integration site of plasmid with LTR of Rous sarcoma virus (pLTR1,5) in the genome of nude mice tumors, induced as a result of N1H3T3 cells' implantation, cotransfected by pLTR1,5 with the DNA of malignant human glioma cells, carrying amplified c-Ha-ras genome, has been studied. The restriction map of the investigated region of the cell genome was obtained. Molecular cloning of the integrated plasmid and adjacent cell sequences has been carried out.

[Induction of unstable mutations in Drosophila melanogaster by microinjection of DNA from oncogenic viruses into the embryo polar plasma. II. Analysis of the role of injected DNA].

We have demonstrated that the mutagenic effect of oncovirus DNA injected into Drosophila embryos is of two-type locus specificity: the spectrum of mutations induced by the retroviral cDNA (RSV) changed in different recipient stocks and those induced by the adenoviral DNA (Sa7) did not differ in the stocks studied. The Sa7 DNA and the cDNA of RSV induce mutations in different groups of loci. Transpositions of the copia element were found in mutant lines obtained in both cases.

[Characteristics of genome sequences in mouse spleen cells activated in virus-induced Rauscher leukemia].

The restriction analysis of BALB/c and AKR mice genome DNA was used to show the translocation and amplification of gene which is expressed with the Rauscher erythroleukemia as the 35S nuclear RNA. The homology of this RNA to 10 defined oncogenes was studied. It was found that the cDNA 35S RNA is efficiently hybridized only with v-sis oncogene.

[Transfer of active oncogenes and promoters into the mouse cell genome].

Different cell DNA's (normal NIH 3T3 DNA; human osteosarcoma cell DNA; human malignant glioma cell DNA with amplified c-Ha-ras) were cotransfected onto NIH 3T3 cells with cloned long terminal repeat (LTR) sequences of Rous sarcoma virus. LTR RSV and normal NIH 3T3 DNA c-fos oncogen expression was detected in tumors induced in nude mice. In the same system human tumour cell DNA with amplified c-Ha-ras gene was used, that to the integration and amplification of LTP sequences with simultaneous maintenance of c-Ha-ras amplification.

[Structural polymorphism of the provirus integrated in the genome of mammalian cells transformed by Rous sarcoma virus].

The structural organization of integrated Rous sarcoma virus (RSV) genome in 8 different mammalian tumour cell lines has been studied. The different types of provirus rearrangements were found, e.g.

[Analysis of the gene homology of the chicken sarcoma virus D6 and the Rous sarcoma virus Prague C strain].

The results of a comparative analysis of genes of Rous sarcoma virus (Prague C strain) and those of avian sarcoma virus D6 isolated from 9,10-dimethyl-1, 2-benzoanthracene-induced avian tumor are presented. The genes of both viruses were shown to be highly homologous.