To date vast evidence has been accumulated showing the role of protein MTS1 in the metastasis development and cell motility regulation, both in norm and upon pathological change of various tissues. The structure of the protein and its gene, as well as the regulation of the gene expression, are studied in detail. Significant advances have been achieved in understanding molecular mechanisms involving MTS1. This paper reviews the current knowledge of the issue.

It is known that presence of xenobiotic-metabolizing gene polymorphisms in some cases correlates with hereditary predisposition to the oncological diseases. In the present work the frequencies of xenobiotic-metabolizing gene polymorphisms in 332 children with the diagnosis acute lymphoblastic leukemia (ALL), 71 children with the diagnosis acute myeloblastic leukemia (AML) and 490 healthy donors have been determined using allele-specific hybridization on the biochip. Statistically significant increase in the frequency of GSTT1 "null" genotype (OR = 1.9, p = 4.7E-5) and GSTT1/GSTM1 double "null" genotype (OR = 3.1, p = 2.5E-8) in children with acute leukemia relative to healthy donors group has been revealed. Also 1.8-fold increase in the frequency of NAT2 genotype 341T/T, 481C/C, 590G/G in children with acute leukemia relative to healthy donors group (p = 0.026) has been recognized. Analysis of gene-gene interactions has showed that in patients with acute leukemia genotype NAT2 341T/T, 481C/C, 590G/G in combination with GSTT1 "null" and/or GSTM1 "null" genotype is significantly more frequent than in population control. Besides the reduction of MTRR genotype 66G/G frequency in girls with acute leukemia relative to female healthy donors has been found (OR = 0.50, p = 0.0015). Analysis of gene-gene interactions has shown that the presence of GSTT1 "null" and/or GSTM1 "null" genotype in combination with MTRR genotype 66A/- may consider as risk factor of acute leukemia in girls. Thus, the studied polymorphic variants of genes GSTT1, GSTM1, NAT2 and MTRR can modulate the risk of childhood acute leukemia, residents of European part of Russia.

A majority of the data on the prognostic significance of distinct chromosome changes and combinations of them in pediatric acute myeloid leukemia (AML) has been derived from adult studies, with not numerous published data in pediatric patients. One of points needed to be clarified is prognostic significance of complex karyotype (at least 3 unrelated abnormalities). We investigated characteristic features of complex karyotype in newly diagnosed pediatric AML de novo. Cell clones with complex karyotype were found in 35 of 254 (13.8%) patients at the age from 0 to 15 years studied prior to therapy. The group was divided into 2 subgroups depending on presence of favorable chromosome abnormalities, i.e. (see symbols)(8;21), t(15;17) and inv(16). The abnormalities were absent in 20 cases (1st subgroup), in 15 remaining patients they were identified (2nd subgroup). In 2nd subgroup karyotypes were not so considerably changed and no adverse risk markers were detected as distinct from 1st subgroup. New data were obtained for complex karyotype differences of adult and pediatric AML. In the great majority (76%) of complex karyotypes in our adult patients chromosome abnormalities associated with adverse risk were found but in pediatric patients their frequency was significantly less (30%). The highest rate of complex karyotype we observed in children at the age from 0 to 3 years. Similar data were not published earlier. Complex karyotype is considered to be characteristic of older AML patients and in the majority of the patients the karyotype contains markers of adverse risk. Possibly, worse outcome in older AML patients is connected with the markers but not with multiple chromosome changes. New data of frequency and the peculiarities of complex karyotype in pediatric AML are important for understanding of AML pathogenesis and for development a more effective AML treatment.

The study of polymorphic variants of GSTT1, GSTM1 and GSTP1 genes from 61 patients with prostatic cancer (PC) has shown that incidence of 0/0 genotype GSTT1 and GSTM1 in PC patients was significantly higher of that in healthy men (n = 100) (34.4 and 15% in p = 0.007 and 60.7 and 43% in p = 0.04, respectively). PC risk in carriers of a GSTT1 deletion form was 2.97, CI95%--1.3-6.84, GSTM1--2.04 in CI95% 1.02-4.1. The analysis of combinations of pathological genotypes of xenobiotic biotransformation enzymes has demonstrated that 89.8% PC patients have a mutation in one of the genes GSTT1, GSTM1 or GSTP1.

Alveolar rhabgomyosarcoma is a highly malignant, small blue cell pediatric soft tissue tumor. Identification of micrometastases in alveolar rhabdomyosarcoma is important because the poor prognosis associated with this subgroup necessitates a modified therapeutic regimen. Since the obtained lymph node specimen can be very small; rhabdomyosarcoma cells are not easily detected using conventional histological methods. To assess the value of myogenin staining in the diagnosis of micrometastases in alveolar rhabdomyosarcoma, the authors examined 36 lymph nodes from children bearing this tumor. Occult tumor cells were detected in 8 cases. The PAX3/7-FKHR gene fusion that resulted from chromosomal translocation in alveolar rhabdomyosarcoma provided potential molecular diagnostic markers. Reverse-transcriptase polymerase chain reaction (RT-PCR) was used to develop an assay capable of identifying RAX3/7-FKHR positive cells in the fresh lymph nodes. Thirty-six lymph nodes were examined and of them 17 lymph nodes had PAX3/7-FKHR fusion transcripts of alveolar rhadomyosarcoma cells. The study demonstrates that molecular RT-PCR detection of micrometastases is the most sensitive method for diagnosing alveolar rhabdomyosarcoma.

Administration of DNA plasmid pPS-3-neo (brd) with synthetic bradykinin " gene " to 2-days old male spontaneously hypertensive rats (SHR) leads to 2 weeks delay in development of arterial hypertension. Lowering of SBP and positive results of PCR DNA of various organs observed in synthetic bradykinin " gene " transgenic SHR but not in control SHR confirm therapeutic effect of synthetic bradykinin " gene " . This data indicate one of possible ways of gene therapy of arterial hypertension as well as other pathological states by introduction of transgene directly into genome of the organism.

Five-ten percent of early-onset (up to age of 50) colorectal cancers are regarded as being inherited. Positive results of a medical genetic examination call for microsatellite instability test. However, that method is not absolutely reliable because although all microsatellite instability tests for hereditary nonpolyposis colorectal cancer are positive, microsatellite instability of tumor DNA occurs in 15% of sporadic colorectal carcinoma. Moreover, Russian diagnostic practices are peculiar in that "familial history" is often missed due to premature demise of relatives and lack of data. Under the circumstances, research should be focused on issues of still earlier onset of cancer as well as multifocal nature of tumor growth although similar manifestations may occur in sporadic cancer.

Extracellular DNA and RNA were extracted from blood plasma and cell surface-bound fractions of patients with breast tumors and healthy controls. Frequency of RASSF1A, Cyclin D2 and RARbeta2 methylation was detected using methylation-specific PCR in the extracellular DNA, extracted from plasma and cell-surface bound fractions of patient blood. Methylation of at least one of these genes was found in plasma of 13% patients with benign breast fibroadenoma and in 60% of breast cancer patients. Using cell-surface bound DNA as a substrate for PCR have lead to increase of gene methylation detection frequency up to 87% in fibroadenoma and 95% in breast cancer patients without false positive controls. GAPDH, RASSF8, Ki-67 RNA and 18S RNA were quantified using RT-qPCR of the extracellular RNA circulating in blood of patients with breast tumors and healthy controls. The main part of the extracellular RNA was shown to be cell-surface bound. Results show a higher amount of RASSF8, Ki-67 RNA and 18S RNA in plasma and cell-bound fraction of patients with breast cancer compared with patients with benign tumors and healthy controls. The data indicate that the specific RNA quantification in blood plasma is valuable for discrimination between cancer and benign tumors, which can be detected with high sensitivity using analysis of methylated RASSF1A, Cyclin D2 and RARbeta2 genes in extracellular circulating DNA.

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal neoplasms of the digestive tract. Inherent overexpression of receptor tyrosine kinase KIT (CD117) and mutations in c-Kit or PDGFRA genes are highly significant prognosticators. A first Russian investigation of c-Kit and PDGFRA mutations in GIST was carried out in 60 patients. c-Kit mutations were identified in 83.3% (50/60), the most frequent being mutations in c-Kit exon 11 (73.4%, 44/60). Among them, different mutations were identified in the 5'-end of c-Kit exon 11 in 37 GISTs. Duplications in the 3'-end of c-Kit exon 11 were reported in 7 tumors. Mutations in c-Kit exon 9 (73.4%, 44/60) were found in 5 tumors (8.3 3%, 5/60) while mutations in c-Kit exon 13 (0%, 44/60) and 17 (1.7%, 1/60) were rare. PDGFRA mutations in exon 18 were identified in (8.3 3%, 5/60). Substitution D842V occurred only in one gastric epithelioid-cell GIST. The remaining PDGFRA mutations contained deletions with aminoacids 842-846. There were no c-Kit and PDGFRA mutations in five tumors. Our findings point to a significant correlation between c-Kit and PDGFRA mutations, on the one hand, and tumor site and histological pattern, on the other. Hence, c-Kit and PDGFRA mutation detection should be used as an additional prognosticator for efficacy of target therapy.

A first attempt at investigating polymorphism of microsatellite TNFa and SNP-308 (G/A) in promoter of TNFalpha was made in patients with sporadic and hereditary breast cancer. 308 (A) TNFalpha and TNFa 12 alleles frequencies were significantly higher while that of TNFa10--significantly lower in the hereditary cancer group as compared with donors as well as sporadic cancer patients. That was contributed by cases of infiltrative-lobular tumors. Conversely, because of infiltrative-ductal tumors fraction, TNFa 7 allele frequency in sporadic cancer group was significantly higher than in donors and hereditary breast cancer patients. It was suggested that polymorphism of 308 (G/A) TNFalpha and TNFa depended, first of all, on patterns of breast and, secondly, on the elevated TNFalpha expression as a factor of pathogenesis of hereditary breast cancer.

Polymorphism of GSTT1 and GSTM1 variant genes of phase II biotransformation of xenobiotics was studied in 181 patients with lung cancer. Null genotype frequency in cancer patients was higher than in healthy subjects. It was still higher in metastatic cancer disseminated to the regional lymph nodes as compared with localized tumor.

Tissue precursors and genesis of female reproductive tract carcinoma vis-a-vis its carcinomatous and sarcomatous patterns remain unknown. To determine the clonal origin of 17 female reproductive tract carcinomas, such molecular, genetic and immunohistochemical techniques as PCR-SSCP and/or denaturing gel electrophoresis for K-ras, p53 and PTEN genes; D17S786, CHRNB1, TP53, BAT26 and BAT40 microsatellites and immunostaining for p53 protein were used. Carcinomatous and sarcomatous components were studied separately. Eight tumors were assumed to be monoclonal (combination or conversion tumors), while one--of an obscure origin. Our results suggest that carcinosarcomas were characterized by chromosomal instability. Moreover, it was shown that it is necessary to combine immunohistochemical techniques with a battery of methods including genetic ones to determine clonal origin of immunologically--stained carcinosarcomas.

The paper assesses c5266dupC (5382insC) mutation incidence among breast cancer patients, residents of the Republic of Bashkorstan and Tyumen Region. It appeared as high as 4%.

The authors present first results of investigations of the connexin-26 gene in DNA obtained from peripheral blood of 55 patients operated on for gastric cancer. Gastric cancer patients were found to have carriage of the Cx 26 gene that was reliably associated with the invasive ability of the tumor. Change of the connexin-26 gene in gastric cancer is evidence of an important role of intercellular gap junctions in the arising and development of gastric cancer.

Ribosomal protein L11 plays important role in ribosome, being involved in several steps in protein synthesis and also activates p53-dependent cell cycle arrest. Changes in the rpL11 levels might be implicated in cell cycle control and carcinogenesis. Therefore, the mechanism of regulation of rpL11 expression has increasing importance. Article presents research results of interaction of promotor elements of gene HRPL11 with proteins of nuclear extracts of cells of a various cell origin. Use oligonucleotide competitors containing known transcription factor-binding sites, and also polyclonal antibodies has shown, that transcription factor YY1 participates in regulation of a transcription of gene HRPL11 in all investigated cellular lines. Our data obtained from comparison of protein binding profiles using nuclear extracts from rapidly growth cells, normal cell lines and serum deprivation repressed cell allows us to consider of transcription factor YY1 as activator of HRPL11 gene transcription.

The overexpression of a new cytokine-induced apoptosis inhibitor 1 (CIAPIN1) gene has been shown previously to promote a multidrug resistant phenotype in gastric cancer cells through the upregulation of MDR1 and MRP1. In the present study, we constructed the siRNA eukaryotic expression vectors of CIAPIN1 and transfected them into SGC7901/VCR cells to examine whether the down regulation of CIAPIN1 increased cell sensitivity towards chemotherapeutic drugs. After transfection, the expression of CIAPIN1 was dramatically decreased in CIAPIN1 siRNA transfectants compared with that in parental cells and empty vector control cells. The down-regulation of CIAPIN1 significantly enhanced the sensitivity of SGC7901/VCR cells to vincristine (VCR), adriamycin (ADR) and etoposide (VP-16), but not to 5-fluorouracil (5-FU) and cisplatin (CDDP). Cell capacity to efflux adriamycin decreased markedly in CIAPIN1 siRNA transfectants, and correlation between CIAPIN1 down regulation and decreased MDR1 transcriptional activity were observed. CIAPIN1 siRNA could significantly down regulate the expression of Bcl-2, and up-regulate the expression of Bax, but not alter the expression of PTEN in gastric cancer cells. These observations suggested that the siRNA constructs of CIAPIN1 we obtained could effectively down-regulate the expression of CIAPIN1 and reverse the resistant phenotype of gastric cancer cells. The further study of the biological functions of CIAPIN1 may be helpful for understanding the mechanisms of multidrug resistance of gastric cancer and developing possible strategies to treat gastric cancer.