Glioblastoma growth is a genetically regulated process. Loss or inactivation of genes - tumor suppressors may give rise to tumors and their progression. Glioblastoma multiforme is followed by a number of genetic breakages. Expression of a number of genes may affect the prognosis of the disease and tumor sensitivity to chemotherapy. Comprehensive studies of glioblastomas showed that there were at least two immunologic phenotypes: 1) that with a picture of pronounced immunodeficiency and 2) that without obvious immunodeficiency. This should be considered when elaborating present-day programs of geno- and immunodiagnosis, as well as clinicoimmunological criteria for the treatment of these tumors.

The results of an investigation of the RB 1, p16 and p53 genes in sporadic breast cancer through molecular and immunohistochemical studies are presented.

The review highlights analytics capacities of immunochemical and molecular-genetic methods used in the non-invasive test for prostate cancer and monitoring of efficacy of anticancer therapy. The perspectives of their applications in clinical practice also have been evaluated.

Expression of certain neurotrophin genes and their receptors, as well as NGF-induced gene EGRI was studied in human normal lung, squamous cell lung cancer, and adenocarcinoma tissues. Differential expression pattern of NGF, BDNF, and NT-3 mRNA was established by RT-PCR in normal human lung. NGF expression level varying from minor to significant was demonstrated in double specimens (histologically diagnosed human lung cancer and appropriate adjacent tissue). Interestingly, a half of the double specimens studied demonstrated the differential expression pattern in both cancer and adjacent tissues, whereas in other cases no difference in the NGF expression between these pair of tissues was observed. In the majority of the double specimens, we detected low levels of NT3 and BDNF expression for both cancer and adjacent tissue. No expression of TrkA, TrkB, p75 was found in double specimens and normal tissues. Differential expression patterns of TrkC were observed in normal tissues as well as in certain double specimens. High levels of EGR1 expression were detected in normal tissues. No EGRI expression was observed in cancer tissue compared to its high expression level in adjacent tissue in the majority of double specimens.

Alterations in the c-Met/HGF system are frequently observed in various types of tumors and can directly influence tumor progression. In particular, the c-Met/HGF system can influence progression of lung tumors. The altered c-Met and HGF expression occurs in non-small-cell lung carcinomas. In this work we analyzed changes in c-Met and HGF expression in non-small-cell lung carcinomas by comparing expression levels with those in adjacent non-malignant tissues using semi-quantitative PCR. The c-Met transcript was detected in 50% of squamous cell carcinoma samples with an elevated level observed in 2 out of 25 cases (8%). HGF expression was detected only in two squamous cell carcinomas. At the same time, the c-Met transcript was observed in all 5 studied adenocarcinoma samples with an increased level compared to adjacent non- malignant tissue in 3 cases. HGF transcript was found in 2 adenocarcinoma samples. Therefore, c-Met rather than HGF transcript is frequently observed in non-small-cell lung carcinomas, especially in adenocarcinomas. According to the results of other studies, the c-Met transcript can serve as an indicator of the aggressive behavior and progression of non-small-cell lung carcinomas.

Changes in WIFI expression, an extracellular inhibitor of Wnt pathway, in non-small cell lung carcinomas were analyzed. Frequent (67% cases) suppression of WIFI transcript in non-small cell lung carcinomas were found. Our results, together with previously published data, suggest that inhibition of WIFI expression often occurs in squamous cell carcinomas and is less typical of adenocarcinomas. It was also found that a decrease in the WIFI transcript in tumors is parallel to concomitant suppression of the WIFI protein level. Our results provide further evidence that the WIFI suppression is a frequent event in the lung carcinogenesis, which might lead to disregulation of Wnt signaling pathway and contribute to tumor progression.

To quantitatively determine minimal residual disease (MRD) by real-time polymerase chain reaction (PCR) in patients with a chronic phase (CP) of chronic myeloid leukemia (CML).

Colorectal cancer (CC) is one of two diseases, in which the link between cancer proneness and DNA repair deficiency appears to be proved. A strict relationship between mismatch repair (MMR) gene mutations, microsatellite instability (MSI) has been found in familiar colorectal cancer (Lynch syndrome). Tumorigenesis at familiar cancer is initiated by biallelic mutations in the major MMR genes, namely MSH2 or MLH1. One of these mutations is an inherited germline alteration and the other is a somatic one. The initiating mutation in sporadic colorectal tumors was not still identified although biochemical and genetic signs of MMR deficiency are observed in tumor cells. Two currently used colorectal tumor cell lines HCT116 and COLO320HSR were derived from hereditary and sporadic tumors accordingly. HCT116 cell line exhibits MMR-deficiency due to biallelic deletion in MLHL. As a consequence this shows MSI phenotype and a near-diploid karyotype. COLO320HSR cell line is characterized by MSS phenotype with mostly imbalanced aberrations. This indicates MMR proficiency in these cells. However, both MMR-deficient HCT116 and COLO320HSR cells reveal near-diploid karyotype. Earlier we have shown that the number of secondary DNA double strand breaks, induced by methylnitrosourea (MNU), represent functional activity of cellular MMR. In the present study, using this approach we evaluated sensitivity to MNU and MMR activity in two colorectal tumor cell lines (HCT 116, COLO320HSR) and compared them to that in the HeLa cell line, which have MMR-proficient phenotype. We showed that cell line COLO320HSR exhibits low MMR activity, close to the level of MMR-activity in HCT116 cell line. We found a mutation in MSH2-G520A gene in COLO320HSR. This neutral mutation apparently is not related to polymorphism as we failed to identify the same mutation in any of MSH2 gene sequences of lymphocytes from 30 patients with sporadic colorectal cancer.

Molecular alterations leading to genetic instability play a key role in tumor development. The basic reasons of genetic instability of tumor cells, i.e. up-regulation of intracellular level of endogenous mutagens, in particular reactive oxygen spesies (ROS); decreased fidelity of DNA replication and chromosome segregation in mitosis; defects in DNA repair systems; and inactivation of cell cycle checkpoints preventing proliferation of abnormal cells are reviewed. In addition, tissue-specificity of tumorigenesis connected with genetic instability and development of new therapeutic approaches based on diminishing genetic instability or selective killing of neoplastic cells showing such defects are discussed.

The cases of chromosome 11 abnormalities in leukemic bone marrow cells have constituted 14.0% in acute lymphoblastic leukemia (ALL), 18.7% in acute myeloid leukemia (AML), and 16.7% in refractory anemia (RA). The bands of the short arms 11p13, 11p14, llp15 and the long arms 11q14, 11q21, 11q23 were involved in chromosome rearrangements. The rearrangements of the band 11q23 were detected more often. Reciprocal translocations were found with the highest frequency, while para- and pericentic invertions, terminal and intestitial deletions occured with the lower incidence. Deletions were found in RA cases only. Comparison with the clinical features showed no correlation with the age and the main haematological indexes including the amount of blast cells in the initial period. The results have showed the poor prognosis of the abnormalities not only of 11q21, 11q23 in acute leukemia (AL), but of 11p13, 11p15 in AML as well, while not enough data on this subject is availalbe in the literature.

A brief review of the cytoskeleton dynamic structure in cells of two types: fibroblasts and epitheliocytes. Differences have been described between the functions of y-actin filaments and beta-actomyosin bundles. Tubulogenesis and angiogenesis have been considered as consequences of partial epitheliomesenchymal transformation and neoplastic transformation as a consequence of gamma-actomyosin bundles disturbance.

Taking into account that instability of chromosomes represents the mutagenic influence of of environmental factors; that chromosomal aberrations can be used as the markers of gene changes (including the oncologic ones); that the absence of the well-defined answer for age dependence on frequency of aberrations of the inspected persons; for oncologic patients sum up the promoted level of this index: on the basis of determination of index "frequency of aberrations of chromosomes" it is possible to form groups of the promoted risk, including oncologic for more deep study other methods.

Stable deceleration of Walker 256 tumor growth was detected in Brattleboro rats with vasopressin synthesis defect in comparison with normal WAG rats. In contrast to continuous tumor growth typical of rats, the growth of this tumor in Brattleboro rats was negligible and was observed during the first 15-18 days after transplantation, after which the tumor regressed and disappeared. The effect was age-dependent and was more pronounced in old animals. Repeated injection of Walker 256 cells does not lead to tumor development, which attested to direct involvement of the immune system in the detected phenomenon.

In this work for the first time copy number and expression changes of the tumor suppressor gene RBSP3 (3p21.3) were investigated. The study was performed on HPV-positive squamous cervical carcinoma (SCC) using real-time PCR. Deletions were detected in 42% of cases (19 of 45 studied biopsies). Frequency of deletions was significantly higher in SCC samples with metastases (64%) than in tumors without metastases (32%, P < 0.05). In a few cases amplification of RBSP3 was also found. Altogether copy number changes of RBSP3 were detected in 51% of cases (23 of 45). Expression of RBSP3 was decreased in 64% of SCC samples (21 of 33). Again decreased expression of RBSP3 was detected significantly more frequently (83%) in tumors with metastases compared with SCC without metastases (52%, P < 0.05). In several cases however increased expression was observed. Altogether changes in expression of RBSP3 were detected in 79% (26 of 33) of SCC biopsies. Comparison of copy number and expression changes showed that in 23% of SCC cases decreased expression of RBSP3 was detected in samples with deletions and in 36% cases such decrease was not associated with copy number changes. Rarely more complicated SCC cases were found. For example in some tumors increased expression of RBSP3 was detected in samples with deletions or without changes in copy number. Results of the study suggested that RBSP3 is involved in the progression of SCC and complex mechanisms for inactivation of RBSP3. We also hypothesize that these data indicate that RBSP3 in addition to dephosphorylation of pRb has other functions important for malignant transformation because pRb is almost absent in HPV-positive SCC.

The methylation status of four genes significant in prostate carcinogenesis p16, HIC1, N33 and GSTP1, were evaluated using quantitative methylationsensitive polymerase chain reaction. Tumor epithelia, tumor-associated stroma, normal epithelia, foci of PIN and benign prostate hyperplasia, and stroma adjacent to tumor tissues were isolated from whole-mount prostatectomy specimens of patients with localized prostate cancer by using laser capture microdissection. We found high levels of gene methylation in the tumor epithelium and tumor-associated stromal cells and some methylation in both hyperplastic epithelium and stromal cells in normal-appearing tissues located adjacent to tumors. Promoter methylation in the non-neoplastic cells of the prostate tumor microenvironment may play an important role in cancer development and progression. We examined the promoter methylation status of pl6, HIC1, N33 and GSTP1 in prostate biopsy fragments and prostate tissues after radical prostatectomy from patients with adenocarcinoma without laser capture microdissection. Methylation frequencies of all genes in tumor samples were considerably lower than frequencies in microdissected tumour samples (HIC1, 71 versus 89%; p16, 22 versus 78%; GSTP1, 32 versus 100%; N33, 20 versus 33%). The laser capture microdissection is required procedure in methylation studies taking into account multifocality and heterogenity of prostate cancer tissue.

Ovarian cancer (OC) is one of the leading cause of cancer death in women. Inherited BRCA1 and BRCA2 mutations strikingly increase OC risk (with lifetime risk estimates ranging at 10-60%). Mutation 1100delC in CHEK2 gene was shown to be associated with breast cancer in women carrying this mutation. Knowledge of the nature and frequency of population-specific mutations in these genes is a critical step in the development of simple and inexpensive diagnostic approaches to DNA analysis. The frequencies of 185delAG, 300T>G, 4153delA, 4158A>G, 5382insC mutations in BRCA1 gene, 695insT and 6174delT mutations in BRCA2 gene and 1100delC mutation in CHEK2 gene were analyzed using biochips in Russian OC patients. We studied 68 women who received a diagnosis of epithelial OC and 19 women with primary multiple tumors involving the ovaries. The 185delAG, 300T>G, 4153delA and 5382insC in BRCA1 gene were identified. The most prevailing mutation was 5382insC in BRCA1 gene (87.5% of all BRCA1 mutations OC patients, 50.0% in patients with primary multiple tumors involving the ovaries). No mutations in BRCA2 and CHEK2 genes were detected.

Proliferation and the state of adhesion molecules (E-cadherin, galectin-3) and estrogen and progesterone receptors were immunohistochemically analyzed in breast cancer biopsy specimens under conditions of c-erbB2 overexpression with and without gene amplification. It was hypothesized that c-erbB2 overexpression without gene amplification led to suppression of proliferation and "conservation" of tumor cell.

The C to T substitution in position 311 n. p. of K-ras gene intron 2 in mice resistant to lung cancer (M. spretus) attenuates NF-Y transcription factor binding site in comparison with sensitive ICR mice (M. musculus). Appreciable differences between ICR and M. spretus in general pattern of binding of nuclear proteins to K-ras gene DNA within 248-332 n. p. fragment are demonstrated.