The incidence of cancer increases with age in humans and in laboratory animals alike. There are different patterns of age-related distribution of tumors in different organs and tissues. Aging may increase of decrease the susceptibility of various tissues to initiation of carcinogenesis and usually facilitates promotion and progression of carcinogenesis. Aging may predispose to cancer by several mechanisms: 1) tissue accumulation of cells in late stages of carcinogenesis; 2) alterations in homeostasis, in particular, alterations in immune and endocrine system and 3) telomere instability linking aging and increased cancer risk. Increased susceptibility to the effects of tumor promoters is found both in aged animals and aged humans, as predicted by the multistage model of carcinogenesis. Available evidence supporting the relevance of replicative senescence of human cells and telomere biology to human cancer seems quite strong, however the evidence linking cellular senescence to human aging is controversial and required additional studies. Some common genetic processes (e.g. telomere dysfunction, changes in p53 and Rb activity and in DNA repair, accumulation of DNA lesions, genomic instability) play a critical role both in carcinogenesis and aging. Data on the acceleration of aging by carcinogenic agents as well as on increased cancer risk in patients with premature aging are critically discussed. In genetically modified mouse models (transgenic, knockout or mutant) characterized by the aging delay the incidence of tumors usually similar to those in controls, whereas the latent period of tumor development is increased. Practically all models of accelerated of aging in genetically modified animals show the increase in the incidence and the decline in the latency of tumors. Strategies for cancer prevention must include not only measures to minimize exposure to exogenous carcinogenic agents, but also measures to normalize the age-related alterations in internal milieu. Life-span prolonging drugs (geroprotectors) and genetic modifications may either postpone population aging and increase of tumor latency or decrease the mortality in long-living individuals in populations and inhibit carcinogenesis. At least some geroprotectors and modifications may increase the survival of a short-living individuals in populations but increase the incidence of malignancy.

Surgical and biopsy material was used from 57 patients with lung carcinoma (LC): 17 patients (group I) lived close to testing area from the childhood to 1993 and were exposed to radiation at the year dose 0.1 ber. For comparison surgical and biopsy material from 40 patients (group 2) was taken who lived in the territories of Kazakhstan (10 patients) and Moscow (30 patients) with normal radiation background. The following features of LC were found in the groups in question: constant observation of dust particles and interstitial and focal fibrosis in tumours of various localization and histological type; prevailing small cell carcinoma as compared to other histological types; high frequency of nonsmall cell lung carcinoma; higher expression of IGFII, IGFBP1,2 and rare expression of IGFB3; proliferative activity followed by an increased expression of c-myc, bcl-2.

53 histological slides obtained from 4 patients aged 35-68 years with diagnosis of uterine carcinoma without invasion (16 patients) and tumor invasion into uterine muscular membrane (24 patients) were retrospectively analyzed. On the basis of morphometry and ploidometry of 2989 nuclei on the image analyzer Imager-CG (Russia) with a computer program Avtan-San, a complex of diagnostic criteria characterizing the grade of malignancy of uterine tumors was obtained. Differential diagnostic ploidometric characteristics of 4 degrees of tumor progression are described. With the process intensification the amount of genetic material in tumor cell nuclei increase 1.7-fold, proliferative activity 2.2-fold, number of polyploid cells--1.5-fold. These data specify the degree of differentiation of uterine body adenocarcinoma and help to plan treatment policy for patients with uterine carcinoma.

Susceptibility to benz(a)pyrene (BP) has been compared between wild and knockout p53 homo- and heterozygous FVB/N, C57BL/6 and NMRI line mice. Each group included 34-80 animals. Each animal was injected 2 mg BP, s.c., in sunflower oil solution. The animals were followed up for 24 weeks. Fibrosarcomas arose at the site of injection in: wild FVB/N line mice--93%; FVB/N heterozygous--100%; p53 homozygous knockout--95%; C57B1/6--84%, and NMRI mice--83%. Mean latent period was 68, 66, 69, 112 and 109 days, respectively. Hence, FVB/N line mice developed tumors much earlier than C57B1/6 or NMRI did, suggesting their higher susceptibility to carcinogenic BP injection. No significant difference in susceptibility to carcinogen versus p53 expression was reported.

Initiation and/or promotion of endometrial carcinoma is considered to be associated with estrogens and androgens (androstendione) excess as well as hyperinsulinemia and resistance to insulin. It is possible that certain polymorphisms of the genes involved in steroidogenesis or steroid metabolism contribute to carcinoma susceptibility. In the current study, we compared the role of CYP17 biallelic MspA1) polymorphism in 114 endometrial carcinoma patients and 182 healthy women. According to our data, A2/A2 CYP17 genotype traditionally regarded as "unfavorable" was less frequent in cancer patients than in control which confirmed the results of two previous publications. For the first time, carriers of the genotype were shown to have relatively low levels of blood insulin and C-peptide. No significant difference was found between mean concentrations of testosterone, dehydroepiandrosterone sulfate and those of estradiol in the carriers of various CYP17 genotypes with endometrial cancer. Hence, CYP17 polymorphism which is represented by the "normal" A1/A1 genotype might be a factor of risk for endometrial carcinoma. Since this genetic variety may develop through an unconventional (nonsteroid) pathway, taking relevant preventive measures in high-risk groups should be recommended.

A medico-genetic investigation of a family, consisting of 25 members, revealed high predisposition to malignant pathology of the gastrointestinal tract: rectal cancer was diagnosed in 2, malignant polyposis of the large intestine--1, diffuse polyposis of the large intestine (DPLI)--3, and uterine fibromyoma--in 1 patient. Six members underwent a cytogenetic examination using the metaphase method for peripheral blood lymphocytes and G-banding of chromosomes. Two patients with DPLI carried 8.7 and 16.7% of hyperaneuploid cells and one--20% of cells with double minute chromosomes (DMS). It is suggested that formation and subsequent significant increase in hyperaneuploid and DMS cells could have been responsible for DPLI development in the family.

The structure was described for human CKAP2, which codes for the cytoskeleton-associated protein 2, is at the boundary of chromosome regions 13q14.3 and 13q21.1, and is rearranged in various tumors. The CKAP2 exonintron structure was established by collating the nucleotide sequences of the cDNA and genomic clone AL359513 (GenBank) and analyzing the gene sequence with the GENSCAN program. The results were verified by amplifying gene fragments. CKAP2 comprises nine exons ranging 70-1442 bp and is about 22 kb in size (regulatory regions included). The CKAP2 promoter contains CCAAT (-39...-33) rather than the canonical TATA box, and harbors nine binding sites for six transcription factors. Thus, CKAP2 possesses all structural elements characteristic of eukaryotic genes. The results may be used to study the CKAP2 expression in normal and tumor cells in order to elucidate its role in carcinogenesis.

The data on examination and treatment of 39 children with T-cell acute lymphoblastic leukemia (T-ALL) were assessed; all patients received ALL BFM-90-M treatment. The fraction of children with T-ALL among ALL patients in Belarus was 12.2% (pre-T-ALL--15, cortical T-ALL--46 and mature T-ALL--23%). Also, a subtype of T-ALL with atypical expression of markers was identified (13%). Overall 7-year survival in T-ALL patients was 47(20%). The worst prognosis was recorded in the T-ALL subgroup with atypical expression of markers (p < 0.001 as compared with the other subgroups). As for outcome--from best to worst, T-ALL subtypes ranged as follows: cortical T-ALL, mature T-ALL, pre-T-ALL and T-ALL with atypical expression of markers.

Since 1969 to 2000 twenty one patients from 16 families with syndrome of multiple endocrine neoplasia (MEN) type 2 were examined. Medullary cancer of the thyroid gland (MCTG) was diagnosed in 18 patients, pheochromocytoma--in 15 (in 13 of them--two-sided), primary hyperparathyroidism--in 2. In 9 patients from 5 families syndrome MEN 2 was confirmed genetically (mutation in codon 634 of 11th exon RET in 7 patients with MEN 2a and in codon 918 in 2 patients with MEN 2b). None of the patients had extraadrenal pheochromocytoma, in 9 (60%) patients multicentric tumors within one adrenal gland were diagnosed. All the 18 patients with MCTG underwent extrafascial thyroidectomy with removal of fat and lymph nodes of paratracheal zone, 9 patients--one-sided (6) or two-sided (3) removal of fat and lymph nodes of lateral triangle of neck. Prophylactic thyreoidectomy was performed in 11-year old patient with genetically verified MEN 2a and without topical data of MCTG, 2 patients of 3 and 19 years of age with genetically verified MEN 2 are to undergo prophylactic thyroidectomy. Prophylactic thyroidectomy is necessary in the presence of genetic disorders in members of families with MEN 2 despite absence of structural changes in thyroid gland. Level of basal and stimulated calcitonin may be used as marker of recurrence or metastatic growth only. In MEN 2 after organ-saving operation rate of true recurrence of tumor is high because of genetic damage of medullary layer of adrenal gland.

Despite the use of new drugs in therapy of ovarian cancer, remote results remain unsatisfactory. Traditional prognostic factors, which are often subjective, do not reflect the individual features of a tumor in a certain patient. The authors compare classical prognostic factors, the data of laser DNA flow cytometry, and the receptor status of the tumor. Tumor ploidy is the most informative independent prognostic factor: the period without relapses in patients with aneuploid tumors is significantly shorter in comparison with patients with diploid tumors. Study of tumor cell distribution by the cell cycle phases can also provide additional information for predicting the disease course in ovarian cancer.

We considered the biological effects of some chemical compounds, that stimulate cell differentiation, on the cells of tumor lines. Induced changes were analyzed in the expression of several transcriptional factors involved in the regulation of cell proliferation and apoptosis. Based on the generalized information about differentiating, apoptogenic, and antiproliferative effects of chemical inducers of differentiation, a conclusion was drawn that they affect the sensitivity of differentiated cells to the lytic action of natural killer cells.

Rat embryo fibroblasts (REF) transformed with the complementing E1A and cHa-ras oncogenes show a down-regulation of the c-fos early response gene, which is transcribed with the participation of Elk-1. The role of Elk-1 was studied with constructs coding for the full-length factor or its N- or C-terminal fragment fused with Gal. The trans-activating effect of each construct on the Gal4-Luc reporter plasmid was estimated in contransfected REF52 and E1A + cHa-ras cells stimulated with serum or treated with sodium butyrate, a histone deacetylase inhibitor. In E1A + cHa-ras cells, serum activated the expression of C-terminal Gal-Elk(206-428) but not that of full-length Gal-Elk(1-428). The serum-induced activation of Gal-Elk(206-428) was suppressed by PD98059, a MEK/ERK inhibitor, and enhanced by SB203580, an inhibitor of the p38-kinase cascade. It was assumed that p38 negatively affects the MEK/ERK cascade, which plays the major role in the Elk-1 activation in response to serum. Sodium butyrate enhanced the Gal-Elk(1-428) activity both in serum-stimulated and in starving E1A - cHa-ras cells, suggesting a high activity of Elk-1-phosphorylating kinases in the latter. The butyrate-mediated activation of Gal-Elk(206-428) and Gal-Elk(1-428) was suppressed by PD98059 and, therefore, depended on the MEK/ERK cascade. Thus, Elk-1 acted not only as a positive, but also as a negative transcription regulator. Possibly, to suppress transcription, Elk-1 binds with histone deacetylases and thereby contributes to the inactive chromatin state in E1A + cHa-ras cells.