The results of the whole-exome DNA sequencing of eight prostate adenocarcinoma patients are presented. DNA was isolated from the peripheral blood as well as healthy and tumor prostate tissue from each patient. Bioinformatics analysis was conducted and the most significant mutations in prostate cancer patients were revealed. The obtained data could be important for understanding of the molecular mechanisms of prostate cancer pathogenesis and facilitate development of new approaches for treatment of the disease.

Discovery of activating EGFR mutations led to dramatic modification of treatment schemes for nonsquamous lung cancer. 70 patients with activating EGFR mutations were treated by gefitinib being either a part of prospective phase II trial (n = 25) or, subsequently, subjected to routine clinical management (n = 45). Objective response rate approached to 32.7%. Median time to disease progression was 14 months, and median overall survival was 26.1 months. Subgroup analysis revealed statistically longer time to disease progression (p < 0,0001) and overall survival (p = 0,001) in latter vs. former group, despite the lower rate of objective response (22% vs 48%). Possible explanations include more relaxed standards for routine gefitinib use, i.e. inclusion of the patients with non-measurable tumor lumps, continuation of gefitinib uptake upon slow disease progression, and increasing availability and quality of radiosurgery for brain metastases.

To make a randomized comparison of 2 consolidation treatment options (two patient groups): 2 cycles of cytarabine in average (Ig/m2 in Group 2) and standard (100 mg/mi2 in Group 1) doses in combination with idarubicin (8-12 mg/m2) and mitoxantrone (10 mg/m2), after two 7+3 induction cycles of daunorubicin (60 mg/mi2) and subsequent 6 cycles of maintenance therapy.

A 5-year survival of patients with Stage III colon cancer with prophylactic panhysterectomy in anamnesis was 83.3%, significantly higher than that of patients with Stage III colon cancer without panhysterectomy (69.3%) and than in colon cancer patients with metachronous ovarian metastases (42%). In families of patients with primary multiple malignant tumors (PMMT) of colon, endometrium and/or ovaries as well as in cases of accumulation in the same family of solitary tumors of the above locations it is necessary to carry out genetic testing to identify mutations in genes MSH2, MLH1, MSH6. Carriers of mutations in genes of mismatch repair MSH2, MLH1, MSH6 should be assumed to the high-risk group for the development of malignancies both PMMT of colon and organs of the female reproductive system and solitary tumors of the above locations. All women suffering from colon cancer, especially in the presence of mutations in genes of mismatch repair, in pre- and menopause should be undergone simultaneous prophylactic surgery: panhysterectomy. The question about the greater omentum should be decided situationally.

State Research Center "GosNIIgenetika", Moscow, 117545 Russia). Association of polymorphic markers Arg72Pro of TP53 gene and T309G of MDM2 gene with risk of non small cell lung cancer has been studied in Russians of Moscow region. We found an association of minor Pro/Pro genotype of polymorphic marker Arg72Pro (OR = 5.46, p = 8 x 10(-6)) and TG genotype of polymorphic marker T309G (OR = 5.57, p = 0.007) with non small cell lung cancer development. We have also showed a strong association of both Pro/Pro and TG genotypes with development of adenocarcinoma (OR = 8.71, p = 3 x 10(-6) and OR = 8.13, p = 0.003) and squamous-cell lung cancer (OR = 4.2, p = 0.001 and OR = 7.02, p = 0.002). We have finally found highly reliable association of combined susceptible genotypes of polymorphic markers Arg72Pro and T309G of TP53 and MDM2 genes with non small cell lung cancer and both its subtypes (OR = 7.9, p = 0.01; OR = 9.12,p = 0.02; OR = 7.31, p = 0.03, respectively).

Several studies have shown, that mutation in CHEK2 gene can increase the risk of different cancers, including breast cancer (BC). Clearly, that character of mutations distribution in the defined regions is depended on genetic structure of the population. We conducted the screening of mutations c.1100delC, c.444 + 1G>A, de15395, p.I157T andIp.R145Win CHEK2 gene in patients with breast cancer (n = 977) and in control group (n = 1069) originating from the Republic of Bashkortostan. The mutation de15395 in CHEK2 gene was detected with frequency of 1,23% (12/977)in woman with BC and 0.09% (1/1069) in controls (OR:13.28, CI 95%: 1.72-102.33, p = 0.003). Mutations c.1100delC and c.444 + 1G>A were found in BC patients and controls with frequencies of 0.4%, 0.4% (4/977) and 0.09% (1/1069), 0.2% (2/1069), respectively. The missense mutation p.I157T in CHEK2 was found as the most common variant in two studied cohorts (approximately 5%), but differences did not achieved statistical significance. We found the ethnic specificity in distribution of truncating mutations, which occurs mainly among the women of Slavic origin. All three mutations were identified in women of Russian and Ukrainian ethnic origin. Mutations c.1100delC and c.444 + 1G>A in CHEK2 gene were not detected in Bashkirs and Tatars, but CHEK2 de15395 mutation was observed in Tatars.

To evaluate the efficiency of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with acute myeloblastic leukemia in first remission depending on the regimens of conditioning, the source of a graft, and the characteristics of a donor and a recipient.

Tumor regression was reported in 20-30% of patients with inoperable non-small-cell lung cancer (NSLC) following standard first-line chemotherapy. Clinical trials with second-line gefitinib (Iressa) showed a strikingly high response in patients with mutated EGFR. However, clinical experience with gefitinib as first-line therapy had been limited to small-scale trials mostly among subjects of Asian origin. Our study was not associated with the drug manufacturer and included 25 chemotherapy-naive patients with mutated EGFR inoperable lung adenocarcinoma. Standard dose was 250 mg/day. Complete response was observed in 1 patient (4%), partial--11 (44%), sustained stabilization--13 (52%); median time until tumor progression--186 days. Median overall survival failed to be registered within the duration of the study. Among most frequent side-effects were skin rash (19; 76%) and diarrhea (14; 56%): marked side-effect -toxicity grade III (4; 16%). Gefitinib appeared highly efficient and tolerable and may be recommended as first-line treatment of mutated EGFR inoperable NSLC.

To study efficacy of maintenance therapy of patients with acute promyelocytic leukemia (APL) in the APL treatment Russian multicenter trial.

Present-day evidence on uterine leiomyomata has pointed to progesterone and its receptors as a key factor in the mechanisms of auto- and paracrine influences on tumor development and growth. Treatment was determined by a correlation between tumor size and stage of molecular-genetical disorders. A clinico-genealogical study of familial predisposition to uterine leiomyoma, particularly in patients from accumulated disease families contributed to the potential of early detection of tumor and timely effective correction for preservation of reproductive function.

Evaluation of clinical effectiveness of two regimens of induction therapy of an early chronic stage of Ph'-positive chronic myeloid leukemia including interferon-alpha 2b (intron-A, "Schering Plough") in a cooperative randomised trial on the protocol CML MIG-97.

Clinicomorphological analysis of 15 lung carcinomas of patients who had been exposed for a long time to the radiation after the Chernobyl accident was performed. The material consisted of 10 surgical and 5 autopsy cases and was studied at the light, electron microscopic and immunohistochemical level. There were 6 peripheral, 8 central carcinomas and one massive tumor. Fibrous areas with many dust particles were found in peripheral carcinomas. In central tumors chronic obstructive bronchitis with epithelial dysplasia and metaplasia was observed. Carcinoma was represented by various histologic types: small cell (4 cases), combined small cell with squamous differentiation (5 cases), adenocarcinoma (5 cases), adenosquamous type (1 case). Peculiar calcium deposits in both stroma and parenchyma were found in tumors with glandular differentiation. Morphogenesis of calcium microdeposits may be connected with dust radioactive particles elimination. Central carcinoma had, in the majority of cases, a neuroendocrine differentiation and can be related to some types of small cell carcinoma. Peripheral cancer was mostly of a glandular differentiation and was, as a rule, carcinoma in the scar. Lung carcinomas studied had peculiar molecular-genetic features: lack or low bcl-2 expression, low Ki-67 expression and a high degree of c-myc expression. Tumors were characterized by a low apoptosis index independently of a histologic type. Apoptosis was not complete: lack of apoptotic bodies phagocytosis this resulting in postapoptotic detritus formation.

The majority of thyroid tumors are not homogeneous histologically, this creating difficulties in interpretation of different carcinoma variants. The aim of the study was a complex comparative study of morphogenetic changes in carcinoma, adenoma and surrounding thyroid tissue. Surgical material from 48 patients operated because of nodular (multinodular) euthyroid goiter in Moscow Medical Academy in 1990-1997 was used. It was established that all the observations of early thyroid carcinoma diagnosed clinically as a nodular (multinodular) euthyroid goiter were represented by differentiated forms of thyroid carcinoma. Thyroid carcinoma was characterized by higher values of biomolecular markers as compared to adenomas and surrounding tissue. High values of c-myc expression in adenomas and surrounding tissue may indicate possible genetic rearrangements. A peculiar feature of carcinomas was the fact that deletions and replication errors in malignant tumors in this study were found simultaneously in the three genes investigated. As to different histological types of carcinoma, the most frequent deletions of the genes studied were observed in medullary and papillary-follicular carcinoma. High values of heterozygosity loss were found already in adenomas and surrounding tissues, this indicating the presence of the genetic changes already in the benign tumors and surrounding tissue.

104 surgery cases of non-small cell (NSLC) and small cell lung carcinoma (SLC) are studied. Oncoprotein bcl-2 is found in 49 out of 104 (47%) cases, more frequently in SLC (71%) than in NSLC (44%) and this correlated with carcinoma morphological malignancy. L-myc oncoprotein and EGFR were expressed practically in all cases, oncoprotein of the p53 mutated gene in 57% cases. The highest content of p53 was in SLC, large cell and poorly differentiated squamous cell carcinoma. Percentage of cells with mutated p53 statistically correlated with morphological malignancy of lung carcinoma. Oncoprotein of Rb gene was revealed in 51%, most frequently in squamous cell carcinoma (71%) and particularly in its well differentiated types. IGFII was found in 74% NSLC and in 100% SLC with cytoplasmic location in tumor cells; the level of expression was higher in SLC. IGFII 2 and 5 were more frequently observed in the foci of keratinization of squamous cell carcinoma. For the first time IGFP B3 was found not only in the cytoplasm but in the nuclei of tumor cells as well. There was a significant positive correlation between the content of IGFIBP3 in the nuclei of tumor cells and morphological malignancy (poor tumor cell differentiation, larger size and metastases). The mean number of proliferating Ki-67 positive cells was 24% but this figure was much higher (47%) in SLC. Squamous cell carcinoma is characterized by a more frequent and stronger expression of CD44 types 5 and 6 in the cytolemma and this may be considered as a marker of squamous cell differentiation of lung carcinoma.

Phenotypic characteristics of cells and extracellular matrix (ECM) of 14 salivary gland pleomorphic adenomas were studied by indirect immunofluorescence. All cells in the epithelial structures expressed cytokeratin 8, the majority of cells produced vimentin, laminin and IV type collagen. Cells of myxoid areas expressed vimentin: type IV collagen was observed in the form of fibrillar structures. Fibrous areas were characterized by vimentin and cytokeratin 8 expression; types I, III, IV collagens and fibronectin with ED-A sequence were present in ECM. Terms "epithelial structures", "epithelial" and "myoepithelial" cells in relation to pleomorphic adenoma may be used only relatively as it is mainly represented by cells with features of both epithelial and mesenchymal phenotype. Characteristics of ECM synthesized in various structures of pleomorphic adenoma may serve an additional criterion of cell transformation.

55 breast carcinomas and 9 its benign conditions were studied immunohistochemically. Oncoprotein c-erbB-2 was found in 22% carcinomas and in 33-37% comedo-carcinomas. Coincidence of predominant expression of oncoprotein c-erbB-2 and tenascin was observed. Maximal damage of the basal membrane in the intraductal carcinoma detected by the disturbance of type IV collagen staining was observed in cases of the highest expression of oncoprotein c-erbB-2 and tenascin.

The previously established fact of low activity of Ca, Mg-dependent endonucleolysis of cell nucleus DNA in lymphoproliferative diseases (CME-activity) brought the authors to study intranuclear characteristics of lymphoid cells in childhood acute lymphoblastic leukemia (ALL). The intensity of DNA-endonucleolysis was measured in 0.7% agarose gel using electrophoresis. Peripheral blood and bone marrow samples from 13 untreated ALL patients and 23 children in remission were examined. The age of the patients ranged from 4 to 14 years. CME-activity before treatment appeared to be 2-10 times less than normal in 8 out of 13 patients. In bone marrow cell nuclei CME-activity was universally reduced 3-20-fold. In ALL remission endonuclease activity in blood and bone marrow cells returned to normal.

Specific features of metastatic spreading of lung cancer have been compared in 258 surgical patients from families with a history of lung cancer incidence (group I) and in 861 controls (group II). Lesions in lymph nodes at various stages were more frequent in group I, metastatic spreading incidence increasing in step with stage. In is noteworthy that more frequent lesions in mediastinal lymph nodes (stage IV) were observed in group I (54.2%), as compared with 11.8% in controls (P < 0.001). Multiple lesions of lymph nodes at all stages of metastatic spreading featured prominently in 48.5% of group I, as compared with 17.0% in group II (P < 0.001). Metastatic spreading was studied versus such characteristics of primary tumor as size, histologic pattern and pattern of tumor growth.

Natural leucocyte interferon (IF) upon injection to two patients affected with Xeroderma pigmentosum for three weeks stimulated the inhibited DNA replication and Host reactivation at the level of healthy donors. Tigasol--the drug used traditionally for the treatment of diseases caused by Xeroderma pigmentosum proved less effective than IF.