GIST are stromal tumors and the gastrointestinal tract (GIT) and some other organs of spindle-cell or epithelioid-cell structure expressing CD117 (C-kit, KIT), as well as those at different rates and in different combinations, CD34, smooth muscle and/or neurogenic differentiation antigens. It should be taken into account that CD117 are also expressed by melanomas, vascular, and some other tumors. The c-kit gene mutations leading to the expression and autoactivation of the tyrosine kinase receptor KIT underlie the oncogenesis of GIST, which results in enhanced proliferative activity and inhibited apoptosis. This is supported by successful chemotherapy for GIST with a KIT receptor inhibitor. The histogenesis of GIST is associated with GIT somatic stem, the Cajal cell precursors. Many GISTs behave like sarcomas and they are characterized by an infiltrating growth, hematogenic (mainly into the liver) and implantational (along the peritoneum) cancer spread. There are opinions that all such neoplasms are potentially malignany and small-sized GISTs are benign and have the minimum mitotic activity.

In the past 5-10 years, there has been a considerable progress the understanding of the biology of meningioma. The most important advances have been made by comprehensive studies of the pathogenesis of meningioma in molecular genetics. Several target genes could be identified for mutation or inactivation. Additional chromosomal regions that are usually subject to deletion or amplification and point to the presence of tumor suppressor genes or proto-oncogenes were found. The revised and updated 2000 WHO Classification is a major innovation in the histopathology of meningiomas. The new classification system more precisely and objectively determines the grade of meningioma, which allows one to more logically make a prognosis of the recurrence and aggressive behavior of the tumor. The present overview places particular emphasis on recent advances in its molecular biology. It summarizes the most important aspects of the classification of meningiomas, which makes it possible to include the results of biological observations into the respective context, and also considers the mechanisms of angiogenesis and edema development and the role of hormonal receptors in meningiomas.

This two-part review addresses the current diagnostic approaches towards primary cutaneous lymphomas. In this part, main T and NK-cell lymphomas are described with reference to clinical presentation, histological and immunohistochemical features, and genetic alterations based on the new WHO-EORTC classification of cutaneous lymphomas.

The diagnosis of Hodgkin lymphoma is based on the identification of Beresovsky-Reed-Sternberg (B-R-S) cells which are surrounded by inflammatory cells. The tumor cells are of B-cell origin and their mutations are sometimes observed. T-cell immunophenotype is recorded in 5% of the observations. Epstein-Barr virus is found in one third of the patients.

Ph+, bcr/abl+ cells arise due to t(9,22) chromosome translocation and Ph+ chromosome formation in hematopoietic stem cells. The cells show appreciable apoptosis suppression but retain their ability to differentiate and maturate. Ph chromosome, bcr/abl oncogene and Ph+, bcr/abl+ cells themselves are the hallmark of chronic myeloid leukemia. Under leukemia progression differentiating Ph+, bcr/abl+ cells transform into leukemic malignant cells with differentiation block. It is assumed to be a result of subsequent mutations or activation of proliferation of long silent Ph+ cells arisen previously in the stem cells because of the translocation. Real mechanism underlying the cell transformation remains unknown. This work was performed to develop a proper cell model allowing us to study functioning of differentiating Ph+, bcr/abl+ cells and their real transformation into malignant cells with block of differentiation. For this purpose we have investigated kinetics of Ph+, bcr/abl+ cells proliferation, differentiation, cell death and transcription of antiapoptotic genes in cultured 14-day of Ph+ mononuclear cells isolated from peripheral blood of a patient in chronic phase of chronic myeloid leukemia before treatment. The results obtained revealed that Ph+ cell differentiation proceeded in accord with characteristic scheme of chronic myeloid leukemia in vivo. Myeloid cells of hematopoietic cell lineage amounted to 3/4 of live Ph+ mononuclear cells undergoing accumulation and subsequent consumption in the course of differentiation. 95% myeloid cells were differentiating Ph+ granulocytes. The most deal of differentiating Ph+ cells was myelocytes. The rate ratio of myelocyte accumulation to its subsequent consumption showed that the rate of transformation into metamyelocytes was significantly decreased at this differentiation stage. Ph+ cells cultivation curves characterized cell death at different differentiation stages. There were observed the cell death of proliferating Ph+ cells and Ph+ myelocytes, and intensive death of mature cells as well. P/D index, that is ratio of immature Ph+ granulocytes differentiated by cell dividing (blasts, promyelocytes and myelocytes) to the cells differentiated without dividing (metamyelocytes and mature neutrofiles), revealed active of proliferation at the beginning of cultivation and unexpected new proliferative activity at the end of cultivation in the presence of growth factor. The peaks of antiapoptotic bcr/abl gene transcription activity coincided with the observed active proliferation at the beginning and at the end of cultivation. Cell proliferation, differentiation and apoptosis were noticeably accelerated by growth factor treatment. Thus, the study of the Ph+ cells cultivation kinetics is rather informative approach to investigation of continuous regulation of cellular and molecular processes in vitro in the case of chronic myeloid leukemia and allows more complete consideration of Ph+, bcr/abl+ cells hematopoiesis.

A4 clone cells, received by CD95-mediated selection from the parental line of Jurkat T-lymphoblast human leukosis, lost their ability of apoptosis as a result of programmed cell death mechanism breakdown. The complex of their acquired phenotypic properties meets tumor progression criteria: oxidative stress resistance, active immune suppression, and low requirement for growth factors. The loss of A4 cell ability of apoptosis is accompanied by acquisition of the phenotype of multiple medication resistance to a wide spectrum of antineoplastic chemotherapeutic drugs and cytotoxins.

The data on the discovery, specific features and evolution of the aftereffects of functioning in the cells of the ABC-transporters Pgp, MRP and BCRP, the markers of multiple drug resistance (MDRABC), are discussed. The results of the estimate of the MDRABC phenotype of human solid tumors were critically analyzed using different methodic approaches. It was shown that the frequency of the MDRABC phenotype detection by expression of the genes, encoding the ABC-transporter synthesis, was higher than that in detection of transport proteins in the cell. It was concluded that the only adequate clinical method for diagnosis of the MDRABC phenotype could be differential estimate of the functional activity of the ABC-transporters controlling not only the drug release to the cell, but also the drug intracellular compartmentization or division between the cytoplasm and nucleus.

Screening of patients with familial breast cancer from St. Petersburg for BRCA1 gene mutations resulted in identification of three mutations (414del3, 276delA, and A622V) and two polymorphisms (P871L and S1436S). Mutations 4146del3 and 276delA are novel, never previously described elsewhere. Deletion 2761delA produces a reading frame shift, premature protein synthesis termination and can cause predisposition for breast cancer. Deletion 414de13 does not cause a frame shift, but can result both in the disappearance of amino acid residue (D1343del) in the BRCA1 protein and in alteration of folding of the protein, entailing loss of its functional activity. Two variants of nucleotide sequence observed in the number of patients were classified as DNA polymorphisms (P871L and S1436S) rather than mutations as they were not tightly associated with the increased risk of breast cancer.

It is well known that AKR mice with spontaneous leucosis are more sensitive to ionizing irradiation as compared to normal F1 (CBA x C57BL) mice. A study on changes of the structural characteristics of spleen DNA and level of protein p53 in the blood serum under the action of low-level gamma-irradiation in a dose of 1.2 cGy and injections of 10(-14) or 10(-4) mol/kg phenozan was performed. The changes in the structural characteristics of DNA (the adsorption on nitrocellulose filters and number of double-strand breaks) and p53 content were observed for each line of mice under gamma-irradiation and each phenozan concentration. Both factors showed long-time post-effects, and structural changes in AKR DNA were consistent with the life span of these mice. Phenozan in the above doses has abolished the induction of double-strand breaks in case of irradiation of F1 mice in a dose of 1.2 cGy and showed long-time post-irradiation effect. These facts suggest a radioprotection property of phenozan.

We have developed a modification of methylation sensitive arbitrarily primed PCR, one of the methods of differentially methylated CpG islands in cancer cells genomes screening. Seven genes undergoing abnormal epigenetic regulation in breast cancer, SEMA6B, BIN1, VCPIP1, LAMC3, KCNH2, CACNG4 and PSMF1, have been identified by this method. Methylation and loss of expression frequencies were evaluated for each of the identified genes on 100 paired (cancer/morphologically intact control) breast tissue samples. Significant frequencies of abnormal methylation were detected for SEMA6B, BIN1, and LAMC3 (38%, 18%, and 8% correspondingly). Methylation of the above genes was not characteristic for morphologically intact breast tissues. Downregulation of SEMA6B, BIN1, VCPIP1, LAMC3, KCNH2, CACNG4 and PSMF1 in breast cancer was as frequent as 44-94% by real-time PCR expression assay. The most pronounced functional alterations were demonstrated for SEMA6B and LAMC3 genes, which allows recommending their inclusion into the panels of carcinogenesis diagnostic panels. Fine methylation mapping was performed for the genes most frequently methylated in breast cancer (SEMA6B, BIN1, LAMC3), providing a fundamental basis for the development of effective methylation tests for these genes.

To study feasibility of hemopoiesis clonality determination in assessment of remission completeness in patients with chronic myeloid leukemia (CML) using polymerase chain reaction (PCR HUMARA).

The purpose of the study was to investigate significance of the tumor marker pyruvate kinase Tumor M2 (Tu M2-PK), in diagnostics, monitoring of treatment, and evaluation of its effectiveness in patients with lung cancer (LC). This is an isoform of the glycosile enzyme pyruvate kinase, existing as an active dimer and less active tetramer. The expression of the less active form is typical of tumor cells; its blood level can be measured. The subjects of the study were 140 patients with LC of various histologic types. Serum levels of certain tumor markers (Cyfra 21-1, NSE, SCC, and Tu M2-PK) were measured; Tu M2-PK level was determined by ELISA test from ScheBoTech, a two-stage sandwich immunoassay using one type of antibodies. The marker concentration was also determined in 195 healthy volunteers (control group.) The maximum concentration of Tu M2-PK was 12.9 U/ml, determined with 95% specificity. 78% of the patients with small-cell carcinoma, 73% of patients with adenocarcinoma, and 81% of patients with non-small cell lung carcinoma displayed increase of Tu M2-PK serum concentration; this concentration was within normal limits in patients with nonmalignant diseases (e.g. bronchitis or tuberculosis). Thus, patients with lung carcinoma display a pathologic increase of Tu M2-P level. Measurement of Tu M2-P may be useful in patients with suspected LC; this marker may be of greater diagnostic significance than SCC or NSE.

Chondroblastom, benign cartilage tissue neoplasm, accounts for 1% of all bone tumors. It is encountered in any skeletal bones mainly in persons aged 10 and 25 years. Morphologically, it is represented as large homogenous cells--well-defined oval polygonal chondroblasts with a fine eosinophilic cytoplasm, and a round-to-oval nucleus. Cartilaginous portions of chondroblastoma form lobular structures. The tumor always comprises single-to-multiple multinucleate giant cells. The pathognomonic sign of chondroblastoma is intercellular reticular basophilically stained calcifications as a mesh. Mitotic cells, rather than abnormal ones, are present. There are cases of primary malignant chondroblastomas.

The review introduces real-time polymerase technique, a modern high-tech method, to the medical community. Physico-chemical principles of the method, its main stages, and variants of techniques applying fluorescent reporter platforms are considered. Equations used for quantitative estimation, methods of data processing are given; absolute and relative quantification of specific targets is considered. The special part of the review is dedicated to clinical application of the method by the example of infectious and oncological diseases.

The authors present a comparative analysis of preoperative cytological investigation of 65 bioptates of the thyroid gland obtained by the method of fine-needle aspiration puncture biopsy and smears-prints of the same tumors made during the operation. The analysis was made according to 10 cytological criteria. The degree of correspondence of the cytological and histological investigations was determined in nodular goiter and carcinomas of the thyroid gland. The maximal specificity and sensitivity was noted in capillary carcinoma (95.3% and 100% respectively).

The smears of isolated thyrocytes with micronuclei taken from 25 patients with nodular pathology of the thyroid gland were investigated. In all kinds of benign nodular pathology the number of micronucleated thyrocytes comes to 0.1-0.3%. These values correspond to the spontaneous level of the content of aberrant thyrocytes in the thyroid gland of highly specialized cell populations. In papillary carcinoma of the thyroid gland the average occurrence of micronucleated thyrocytes in the tumor nodule was about 0.4%. In the tissue outside the tumor taken from both the same and the opposite lobes, the content of cells with micronuclei proved to be substantially higher--0.93-1%. So, the marked increase of the concentration of genetically damaged cells in the thyroid parenchyma proved to be characteristic of the carcinoma of the thyroid gland.

The authors give an analysis of preoperative diagnostics of nodular tumors of the thyroid gland in 105 children and adolescents. It was shown that there are no special techniques allowing an absolute exclusion of malignant growth in the thyroid nodule before operation. The most accurate method of investigation in differential diagnostics of thyroid carcinoma in children and adolescents is thought to be fine-needle aspiration biopsy under USI control. The sensitivity of the method was 83.3%, the specificity - 98%.

Retrospective study of DNA ploidy was performed on cytologic slides derived from 30 patients with malignant melanoma (stage IV) before interleukin-2 (IL-2) treatment. Twelve patients were tested after two courses of treatment. Diploid tumors were detected in 4, aneuploid - 26. Significant differences in survival versus DNA ploidy (p=0.025) and response to treatment (p=0.016) were found by use of single-factor analysis (Caplan-Meyer). However, multivariate proportional-hazard regression method (Cox) identified high prognostic relevance (p=0.00007) of a combination of 5 factors: DNA ploidy (p=0.008), gender (p=0.015), blood group (p=0.015), sum total of metastasis diameter (p=0.035) and response to treatment (p=0.042). Significant drop in DNA level after treatment was reported in 9 out of 12 patients; no change - 1 and a rise in 2. The post treatment increase involved rapid progression of tumor.

G-banding analysis of LRec-1 and LRec-3, spontaneously immortalized cell lines from rat embryo fibroblast, revealed diploid karyotypes with specific clonal structural rearrangements of chromosomes 7 and 19 - del(7)(q11.2q22.1), t(7;19)(q11.1;q12) in malignant stage. Both clonal abnormalities of chromosomes 7 and 19 were also revealed in LRec-1k clone and LRec-1 sf cell line. Previous study of LRec-1 and LRec-3 cells showed the presence of karyotypes with pseudodiploid modal chromosome number, partial trisomy of chromosome 7 and same clonal structural rearrangements of chromosomes 7 and 19 in immortalized stage. In malignant stage, the trisomy 6 and new clonal structural rearrangements of chromosomes 1, 2, 11, 15, 18, 19 and of chromosomes 10, 20 were also found in LRec-1 sf and LRec-1 cells, accordingly. There were no new clonal structural chromosome rearrangements in LRec-1 k and LRec-3 cells. We compared locies of chromosomes involved in rearrangements with mapped genes on these chromosomes according to RATMAP. Supposedly these genes are involved in spontaneous immortalization of rat embryo fibroblast and malignant transformation of LRec-1 and LRec-3 cells and rearrangements of chromosomes 1, 2, 11, 15 and 18 facilitate expression of growth factors of LRec-1 sf cells.

Spontaneous carcinogenesis and survival were compared in female mice 129/Sv PARP-1+ and PARP-1++ controls. Survival of all animals, including that of the last 10% of mice PARP-1+ (p<0.0002), was relatively lower. It was matched by a significant rise in aging rate. Spontaneous tumor incidence was identical in both groups, although experimental animals revealed tumors at an earlier stage (612+19.2 and 706+17.6 days, respectively, (p<0.0002). The death rate of mice PARP-1+ was 67% as compared with controls (47%) (p<0.05). Tumors of uterus, ovary, liver, lung, mammary gland and soft tissues as well as malignant lymphoma were detected. Malignant tumors contributed 72% among experimental animals versus 49% in control (p<0.05). Those differences were mostly observed among uterine malignancies, adenocarcinomas of the lung and hepatocellular carcinomas. Hence, the switching-off of PARP-1+ involved accelerated aging, shorter survival and earlier and more aggressive tumor development which is in agreement with the existing views on the role played by DNA reparation in mechanisms of carcinogenesis and aging.