The review of modern achievements in morphology and genetic characteristics of pancreatic tumors with ductal phenotype is presented. Problems of intraductal pancreatic neoplasia (PanIN) as precancerous process for ductal adenocarcinoma are considered in detail.

Qualitative differentiated study and calculation of 44404 main morphofunctional types of nucleoli has been perfomed on Ag-positive punction specimens from 50 patients with glandular breast cancer. Accordance of different for their activity morhofunctional types of nucleoli and extranucleolar argentofil granules to proliferative activity rates, malignant transformation and dystrophic changes of tumor cells has been demonstrated.

To try a combined approach to the study of clinicomorphological and immunophenotypical characteristics of primary cutaneous T-cell lymphomas.

Clinico-morphological examination of adult granulosa cell tumors of the ovary was carried out in 17 patients (mean follow-up duration--146.2 +/- 22.16 months). Overall and relapse-free survival appeared significantly higher in low expression of Ki-67 (8.63 +/- 1.4%), mutant suppressor gene p53 (3.55 +/- 1.9%) and low mitotic levels in tumor (2.33 +/- 0.9 per 10 fields of microscope) (p < 0.05).

Was compared frequency of lymphocytes mutant at loci of T-cell receptor (TCR) from samples of peripheral blood taken from 186 healthy donors and 46 untreated thyroid cancer patients, including the persons exposed to ionizing radiation as a result of inhabitation in radioactive polluted region of Russian Federation. Was shown that the cell mutation rate within thyroid cancer group was significantly higher than the same parameter for the healthy person with similar age distribution (p < 0.01). It could be a result of such factors as genotoxic influence, different sensitivity or possible genome instability (including radiation-induced). It was found that 37% of patients have the increased frequency of somatic mutation cells, i.e. it exceeded 95% confidence interval for the screening group. The presented results cause to anticipate that TCR-test could be used as one of criteria for formation groups of high cancer risk development.

The structure and dynamics of actin cytoskeleton are factors important for regulation of cell adhesion, spreading, and migration. TRIP6 is a LIM domain-containing protein interacting with many actin cytoskeleton- associated proteins and modulating the activity of certain transcription factors. To study the functions of TRIP6, we inhibited its expression in A549 and A431 cells with short interfering RNAs (siRNAs). TRIP6 knockdown led to an increase in the number and length of stress fibers and acquisition of the locomotor phenotype. Staining for paxillin demonstrated a decrease in the number of focal adhesion zones and their reorganization, while staining for E-cadherin revealed a loss of cell-to-cell contacts. These morphological changes were accompanied by a twofold increase in cell motility rate, as determined by the wound-healing assay. Thus, downregulation of TRIP6 in the above cell lines led to development of more malignant phenotype of epithelial cells. Possible mechanisms underlying the effects observed are discussed.

The GIPC1 gene product promotes clustering of some transmembrane receptors, including those involved in carcinogenesis, and protects them against ubiquitin-dependent degradation. The 5' untranslated region of GIPC1 contains a polymorphic trinucleotide CGG repeat, which has not been characterized earlier. In the present study, we have carried out comparative analysis of the allele and genotype frequencies of this repeat in 129 samples of breast cancer (BC), 58 samples of non-small cell lung cancer (NSCLC), and 215 samples of healthy donors. The CGG repeat in the 5' untranslated GIPC1 gene region was shown to be highly polymorphic and represented by at least eight alleles. Alleles CGG10-13 were major, occurring at frequencies of 22, 41, 27, and 9%, respectively; the total frequency of the remaining alleles was approximately 1%. Heterozygosity of the CGG repeat was 0.70. Allele CGG12 was shown to be associated with high risk of developing NSCLC (alpha = 0.05).

Laser DNA-flow cytofluorometry (DNA-FC) was used to examine 102 primary patients with morphologically verified pathology of the epithelium of the cervix uteri. There was a significant reduction in the count of cells in the cellular cycle phase (CCP) G0/1 and its increase in the CCP S and G2 + M, as well as a rose in the cell proliferation index (PI) in actually invasive (n=45) and microinvasive cancer of the cervix uteri (CCU) (n=21) as compared with the baseline values (n=8), CIN I-II (n=7), and CIN III (21 patients with severe dysplasia and cancer in situ; their DNA-FC parameters were close and significantly indistinguishable). With unfavorable clinical and morphological factors of CCU prognosis (age over 50 years, postmenopause, stages II-III, high-grade tumor, more than 3 mm stromal invasion, more than 4 cm in size, lymphovascular invasion in the regional lymph nodes, the endophytic form of growth, and a primary focus in the endocervix), aneuploid tumors were more significantly frequently found. The poor CCU prognostic factors significantly decreasing total and relapse-free 4-year survival included tumors of aneuploid type, those containing greater than 40% of aneuploid cells, those containing less than 70% of tumor cells in CCP G0/1, those having 10% of tumor cells or more in CCP S or more than 30% cell PI. While predicting CCU, the DNA index (DNAI) and PI with 0.09 and 0.05 informative value coefficients, respectively are the most significant DNA-FC parameters (after Shenon). By using them, the risk of progressive disease may be predicted with 67.9% probability. When DNAI and PI are used in combination with the most significant clinical and morphological factors of CCU, the likelihood of the latter increases up to 89.3%.

Craniopharyngiomas (CP) were studied morphologically (52 cases), immunohistochemically (6 cases) and molecular-genetically (5 cases) in patients aged 18-65 years. Main causes of death early after surgery are disturbances in the hypothalamic region connected with surgical intervention. The highest lethality is observed after removal of extra-intraventricular neoplasms (44.4%). Lethality increases in patients with repeated surgery. Early postoperative lethality is much lower in the group of papillomatous CP. These tumors well expressed pancytokeratins, cytokeratin 14 and MUC-1, particularly in foci of pronounced keratinization. Oncoproteins c-kit and c-erbB-2 as well as estrogen and progesteron receptors were not observed. Proliferative activity (Ki-67) in CP is 11% in adamantinomatous CP and 2% in capillary CP and pronounced proliferation is observed around keratohyalin deposits. Accumulation of micromutations produced by the inactivation of genes "mismatch DNA reparation" is not typical for CP.

Polymorphism of two tumor-suppressor genes, BRCA1 and P53, was examined. DNA was extracted from blood leukocytes of the women affected with breast cancer (N = 151) and of the women with no clinical symptoms of tumor diseases (N = 191). Typing of the polymorphic variants was performed using PCR-RFLP method. It was demonstrated that the genetic structure of the patient group (taking into consideration BRCA1 and P53 polymorphic variants) differed from that of the control group. The group of genotypes, found exclusively among the patients, as well as the group of "resistant" genotypes revealed predominantly among the controls, was described. Detection of the genotype A1A1 B1B1 S1S1 C1C1 F1F1 J2J2, whose frequency in control group was eight times higher than in the patient group, was an additional confirmation of the existence of "resistant" genotypes. These findings point to the association between the combinations of the BRCA1 and P53 allelic variants and the risk of breast cancer.

We studied the role of integrins, primarily, the role of allele distribution of GP3a gene in development of prostatic cancer (PC) and assessment of its prognostic significance. From November 2003 to May 2004 we examined 32 patients with PC: 11 patients with local PC T1-2N0M0; 14 patients with locally advanced cancer T3N0M0 and 7 patients with invasive and/or metastatic cancer T3-4N10-1 or T3-4N0-1M1. The blood from all the patients we studied with PCR for alleles of GP3a gene, PSA. Seventeen patients were found to have alleles PLA1A1, 14(44%)--alleles PLA1A2, 1(3%)--alleles PLA2A2. Alleles PLA1A2 occurred significantly more often than in the population (p < 0.005). The group analysis has found that 8 patients with local PC had alleles PLA1A1, 3 patients--alleles PLA1A2 (27%). We discovered alleles PLA2A2, PLA1A1 and PLA1A2 in 1(7%), 5(36%) and 8(57%) patients with locally advanced PC, respectively. Among patients with metastatic and/or invasive prostatic cancer, there were 4 (57%) and 3 (43%) cases of alleles PLA1A1 and PLA1A2, respectively. Our study demonstrated influence of carriage of PLA2 allele on occurrence of PC risk (5-fold higher) and its invasive forms (10-fold higher and more). Probability to develop local invasion among patients with prostatic cancer--carriers allele PLA1A2 is 6 times higher than among carriers of alleles PLA1A1. A PC course in carriers of alleles PLA1A2 may be characterized by faster development of local invasion and metastasizing vs carriers of alleles PLA1A1. These findings can be used in design of nomograms for prognostication of invasion of clinically small tumors in verification of significance on greater number of the patients.

Clinical practice with the drug glivek (imatinibe mesilate, ST1571) blocking activity of oncoprotein p210 shows that a cytogenetic response can be reached in 50-60% of patients with chronic myeloid leukemia (CML), in a late chronic phase (CP) in resistance to or intolerance of interferon alpha (IF-alpha) and in 24-43% of patients in the acceleration phase (AP). This study aimed at assessment of the rate and stability of a cytogenetic response (CR) and long-term results of survival in CML patients on glivek.

To examine prognostic potential of the number of bone marrow (BM) blasts and cell karyotype as risk factors of transformation of myelodysplastic syndrome (MDS) in acute myeloblastic leukemia AML.

To develop an original therapeutic strategy in Ph-positive acute lymphoblastic leukemia (ALL).

A hypothesis about the cause of similarities of changes developing in an organism due to senescence and cancer is presented. The similarity is explained by the common origin of mechanisms of these pathological processes in the evolution. The evolutionary predecessors of destructive processes observed in an organism due to senescence and cancer were the destructions accompanying asexual reproduction in the distant ancestry.

The spectrum of mutations in the APC gene in familial adenomatous polyposis was detected in a sampling from the Russian population. Fifteen new mutations were found. Deletions associated with the loss of only 1 or 2 nucleotides (89% cases) prevailed among new (unique) mutations, while all known deletions were caused by the loss of 4 or 5 nucleotides. The detected differences in the deletion characteristics between unique and repeated mutations in the APC gene were typical of samples of patients from a number of populations. Samplings from different populations were heterogeneous by this sign. The incidence of 1-2-nucleotide deletions among unique and repeated deletions in the APC gene in patient samplings from different countries were in negative correlation.