Serum miR-181a and miR-25 in patients with malignant and benign breast diseases.

Breast tumor diseases include a wide range of pathologies that require different approaches to their treatment. MicroRNA (miR) levels, reflecting regulation of the gene expression involved in tumorigenesis, can be diagnostic and prognostic markers of breast diseases. The levels of circulating miR-181a and miR-25 were measured in patients with benign breast diseases (BBD), patients with invasive carcinoma of a nonspecific type (ICNT) and also in conditionally healthy women. Expression of both miRs was higher in patients of both groups as compared to controls; at the same time, the content of serum miR-181a and miR-25 was higher in BBD patients than in ICNT patients. The detected changes may be of interest in the context of precancerous changes in BBD. It seems possible to use them in the future as markers of the pathological process as a part of a large diagnostic panel.

Detection of antibodies against benzo[a]pyrene in blood sera of lung cancer patients by ELISA using human recombinant idiotypic and anti-idiotypic antibodies.

Aim of this study was to develop and apply an ELISA method for assessment of the levels of endogenous antibodies against benzo[a]pyrene (Bp) in blood sera of lung cancer (LC) patients. MATERIALS AND METHODS: ELISA was developed and applied for the detection of endogenous idiotypic and anti-idiotypic antibodies against Bp in human blood sera using recombinant human idiotypic and anti-idiotypic antibodies against Bp. RESULTS: Serum samples of LC patients (n = 22) and healthy donors (n = 24) were analyzed by the new method. Statistical analysis showed that in sera of LC patients the levels of endogenous idiotypic and anti-idiotypic antibodies against Bp were significantly higher than in healthy donors. A logistic regression model for the LC detection utilizing such predictors as the serum levels of idiotypic and anti-idiotypic antibodies against Bp, smoking status, and age, identified LC patients with 83% specificity and 82% sensitivity. CONCLUSION: The proposed method could be further developed as additional lung cancer screening tool.

[Cytogenetic effects in the population in agricultural regions of the Kemerovo region].

There was performed an analysis of chromosomal aberrations in peripheral blood lymphocytes of the inhabitants of 9 settlements from 6 agricultural regions of the Kemerovo region. 267 children-adolescents and 124 adults not involved in the industry were examined. The average level of chromosomal aberrations was 2.65% in children and 3.35% in adults. It can be regarded as a background regional level. There was no revealed the modifying ability of such factors as gender age, presence of harmful habits (smoking) on the formation of the frequency of cytogenetic abnormalities in residents of rural areas of the Kemerovo region.

[Calculation of prognoses of lung cancer in males from technogenic contamination of atmosphere in the Kemerovo region].

In this paper there are described the variants of the models of the regression analysis (linear exponential, exponential and hyperbolic) for the detection of relationships between the lung cancer rate in the male population and anthropogenic emissions in the Kemerovo region. After analyzing of the each model there was chosen the one seemed to be the most adequate to describe the dependence of cancer incidence from pollutant emissions into the atmosphere. At a later stage this model has served for the calculation of the medium-term forecasting of lung cancer rate in males in the dependence on the actual number of man-made emissions in previous years.

Antibodies against benzo[a]pyrene in immunized mouse and in lung cancer patients.

AIM: To evaluate the production of antibodies against benzo[a]pyrene (BP) (Ab1) and corresponding antiidiotypic antibodies (Ab2) in mice after immunization with BP-protein conjugate and in lung cancer patients. MATERIALS AND METHODS: The Ab1 and Ab2 levels were measured by non-competitive ELISA in blood serum of 10 mice immunized with BP-protein conjugate, and in blood serum of 288 healthy persons and 165 lung cancer patients. RESULTS: The Ab1 level of was 2-fold higher than Ab2 level in blood serum of BP-immunized mice. In lung cancer patients the Ab1 level was almost 3 times higher and the Ab2 level was by 30% higher than these indexes in healthy individuals. The Ab1/Ab2 ratio was 2 in BP-immunized mice and healthy individuals and 1 in lung cancer patients. CONCLUSION: Our data have shown that the Ab1/Ab2 ratio in lung cancer patients differ from that in healthy individuals and is close to the Ab1/Ab2 ratio in BP-immunized mouse.

[The characteristics of formation of antibodies to xeno- and endobiotics in women with inherent malformation of fetus].

The study revealed high levels of antibodies class A and G to benzopyrene and antibodies class G to estradiol and progesterone in women with pathology of fetus development. The most informative indicators of high risk of development of reproductive pathology are established The recommendations concerning the application of antibodies to benzopyrene, estradiol and progesterone in diagnostics of inherent malformations of fetus are provided.

[Role of repair gene polymorphism in estimating the sensitivity of human genome to radon in concentrations exceeding maximum permissible level].

The paper gives the results of investigating chromosome aberrations in human peripheral blood lymphocytes due to DNA repair genes, such as hOGG1, ADPRT, APE1, XRCC1, XpG, XpC, XpD, and NBS1, upon long-term exposure to excess indoor radon concentrations. The frequency of chromosome aberrations was found to be significantly lower in the carriers of the genotype hOGG1 326 Ser/Ser (versus the variant Ser/Cys), APE1 148 Asp/Asp (versus Val/Ala and Ala/Ala). The study polymorphic systems were shown to be of value in giving rise to individual types of chromosome aberrations (single fragments and chromosome exchanges).

[Preparation and characterization of the recombinant protein containing immunomimetic peptide of benzo[a]pyrene].

Two recombinant plasmids were constructed. The first plasmid contained the hybrid gene composed of immunomimetic peptide of benzo[a]pyrene, of the protein pIII of bacteriophage M13 and of cellulose binding domain encoding sequences. The second plasmid contained the hybrid gene composed of the signal peptide of the protein pIII of bacteriophage M13, of immunomimetic peptide of benzo[a]pyrene, of the protein pill of bacteriophage M13 and of cellulose binding domain sequences. The obtained recombinant plasmids were used in expression of chimeric protein containing immunomimetic peptide ofbenzo[a]pyrene based on strain E. coli M15. The lack of the recombinant protein expression using first plasmid was demonstrated. In the same time, it was shown that accumulation of recombinant protein contained immunomimetic peptide with signal peptide of the protein pIIIl of bacteriophage was present. This chimeric protein was produced in "mature" (without signal peptide) and "unprocessing" (with signal peptide) forms. Using the Western-blot analysis, it was shown that the "mature" form only specifically bound to the B2 monoclonal antibody against benzo[a]pyrene. Thus, we expressed, purified, and characterized the recombinant protein containing immunomimetic peptide of benzo[a]pyrene.

[Spread of carcinogenic and mutagenic effects in the population of Gornaia Shoria].

Mutagenic and carcinogenic effects were studied in the population of Gornaya Shoria, Kemerovo Region. The carcinogenic effects were evaluated on the basis of the data given by the Kemerovo regional cancer registry over 1990-2008. The standardized cancer morbidity index in Gornaya Shoria (342 per 100,000 population) exceeded the average index in the Kemerovo Region (286 per 100,000) in the same period. The mutagenic effects were estimated on the basis of the monitoring data on the frequency and spectrum of chromosomal aberrations in the peripheral blood lymphocytes of the dwellers of Gornaya Shoria for the 1992-2009 period. The mean level of chromosomal aberrations (5.31%) in the residents of Gornaya Shoria was found to be greater than the regional background mutation rate (2.86%) (p < 0.001). The values of individual aberration types (chromatid and chromosomal breaks, as well as chromosome-type exchange aberrations) were significantly higher in the dwellers of Gornaya Shoria than those in the basic control group. The revealed high mutagenic load in the inhabitants of Tashtagol District, Kemerovo Region, allows this area to be assigned to high genetic risk ones.

[Benz(a)pyrene antibodies are a marker of carcinogenic load in coal-processing workers].

The authors studied benz(a)pyrene-specific secretory and serum antibody ratios (Ka) in 249 workers of the Kemerovo Power Station, by applying their modified enzyme immunoassay technique. There were 37 (20.5%) and 4 (5.8%) cases with Ka >2 at the preset immunoassay parameters of the 180 and 69 workers of mainline production and auxiliary units, respectively. A Ka value of >2 was found in 35 (21.6%) of the 162 males and only in 6 (6.9%) of the 87 females of the whole sample, in 29 (26.1%) of the 111 smokers and in 12 (8.7%) of the 138 non-smokers. The technique is proposed to study specific immune reactions and exposure to carcinogens primarily in workers of the enterprises processing coal and other types of fuel.

A novel approach to the development of anticarcinogenic vaccines.

Human exposure to chemical carcinogens is an important etiological factor in cancer diseases. In this article, we will discuss a new approach to the development of anticarcinogenic vaccines. The main task in our research was to select a benzo[a]pyrene immunomimetic peptide considered as a hapten-specific component. For this purpose, we synthesized carcinogen-protein conjugates and prepared mono- and polyclonal antibodies to benzo[a]pyrene. Phage display technology was used to select the benzo[a]pyrene immunomimetic peptide, followed by an evaluation of the immunological properties of the obtained peptide. The obtained benzo[a]pyrene immunomimetic peptide could only simulate chemical carcinogens in the frame of the pIII protein. As a result, we prepared a recombinant protein composed of the benzo[a]pyrene immunomimetic peptide and pIII-encoding sequences. Using ELISA, we demonstrated that the recombinant protein specifically interacts with the anti-benzo[a]pyrene monoclonal antibody (mAB B2). Using molecular modeling, we predicted the 3-D structure of the mAB B2 active center and analyzed the characteristics of its interaction with different polycyclic aromatic hydrocarbons, as well as with the benzo[a]pyrene immunomimetic peptide. Thus, a comprehensive analysis of the results of the obtainment of hapten-specific components of anticarcinogenic vaccines allowed us to outline a strategy for future development in this direction.

[Quantitative characteristics of chromosomal aberration frequency in the residents of the regions with different levels of cancer incidences].

We present the results of cytogenetic monitoring of the districts in Kemerovo region, which differ in standardized indices of cancer incidence. It has been shown that residents of the districts with high incidence of malignancies had higher average frequency of metaphases with chromosomal aberrations than the control group (4.06 +/- 0.12% and 2.76 +/- 0.13%, respectively). This difference is caused primarily by single or paired fragments. The increase in the frequency of aberrant metaphase incidence in the districts with elevated cancer frequency was observed both in the male and female groups as well as both in adults and children.

[New approach to synthesis of peptide immunomimetic of benzo[a]pyrene].

A novel approach to discovery of the peptide with an internal immunological image of carcinogen is suggested in this work. The hybridomas producing monoclonal antibodies (mAb) B2 against benzo[a]pyrene and benz[a]antracene were prepared. Polyclonal Ab against benzo[a]pyrene (Bp) and benz[a]antracene (Ba), antracene, chrysene, and pyrene were also prepared. We identified the related peptide-presenting phage specificity binding to mAT B2 and polyclonal Ab against Bp from 12 large random peptide libraries using phage display method. ICR mice were immunized with specific binding of positive phage clone for studying its immunogenicity. The Bp antibodies were found in the blood serum. All positive phage clones carried the sequence. Thus, the unique peptide with an internal immunological image of Bp may be the new candidate for anticarcinogenic vaccine.

[The morbidity of stomach cancer among the workers of key industries of the Kuznetsk Basin (Kuzbas)].

The data research of the retrospective analysis of the morbidity of stomach cancer in the Kirov oblast (1990-2005) is presented. The dependence of morbidity rate from the volume production and processing of coal is established. The forecasting of morbidity rate of stomach cancer is estimated up to 2013 considering the factual indicators of volume of output in the key industries of Kuzbas.

[Cytogenetic analysis of genotoxic effects in subjects employed in heat power industry].

Chromosomal aberration rate has been estimated in peripheral blood lymphocytes of subjects occupationally exposed to a set of hazardous factors (employees of the Kemerovo Heat Power Plant). The frequency of metaphases with aberrations in the workers (3.23 +/- 0.26%, N = 104) is significantly higher than in control subjects (2.11 +/- 0.28%, N = 70). The cytogenetic aberrations did not depend on the sex, age, duration of employment, or smoking.

[Polymorphisms in glutathione S-transferase M1 and T1 (GSTM1 and GSTT1) in the indigenous and the nonresident population of the Kemerovo region].

GSTM1 and GSTT1 gene polymorphisms were studied in Shorians, Teleuts, and Caucasians of the Kemerovo region. It has been shown that distribution of homozygous deletions in the examined groups is significantly heterogeneous. The frequency of deletion genotypes and combinations of deletion in these genes was lower in Shorians and, Teleuts than in Caucasians.

[Impact of atmospheric by-product-coking emission on malignancy morbidity].

A statistically significant direct strong correlation was found and an interval was determined between the annual volumes of atmospheric emission from OAO "KOKS" and the standardized (lung, gastric, skin, thyroid, breast, and ovarian) malignancy morbidity rates in Kemerovo. There were gender differences in the incidence of malignancies. The calculated regression coefficients can predict a probable rise in malignancy morbidity in Kemerovo from 2010 due to the increased volumes of atmospheric emission by OAO "KOKS since 2001.

[A new immunoassay of human antibodies to chemical carcinogens].

The study was undertaken to optimize the well known immunoassay of antibodies to chemical carcinogens, designed by J. Chagnaud et al., and examine the specific features of the generation of antibodies (Ab) to benzo[a]pyrene (BP) in patients with lung cancer. Ninety-two serum samples from healthy males and 80 samples from patients with lung cancer were studied. Increased efficiency was achieved by the use of bovine serum albumin instead of thyreoglobulin in the synthesis of carrier protein conjugates with BP. Better reproducibility was accomplished, by using the control serum sample with the known content of IgM, IgG, and IgA Ab to BP. Analysis of the study serum samples has established that in healthy male smokers, the count of IgA Ab was twice greater than that in non-smokers. The patients with lung cancer were found to higher levels of IgG and IgA Ab to BP (in both smokers and non-smokers) than healthy individuals. It is proposed to use the stated method to study a role of A to chemical carcinogens in the pathogenesis of malignancies.

[Retrospective analysis and prognosis of lung cancer morbidity in Kouzbass].

The authors present results of retrospective analysis of lung cancer morbidity in Kouzbass from 1990 to 2005. The morbidity parameters appeared to depend on volumes of coal mining and treatment. Prognosis of lung cancer incidence was calculated up to 2014 with consideration of actual volumes of coal mining and treatment.