Interaction of Serum Antibodies from Breast Cancer Patients with Synthetic Peptides.

The blood serum of tumor patients contains antibodies recognizing tumor-associated antigens and other molecular products of tumor growth. We studied the interaction of blood antibodies from breast cancer patients with synthetic peptides that were applied on the microchip surface. The serum from healthy volunteers and breast cancer patients was shown to contain antibodies that interact with various peptides. Statistically significant between-group differences were observed in the level of binding with 122 informative peptides (0.01% of the total number of peptides on a microchip). Analysis of antibodies that interact with the peptide panel holds much promise for the diagnostics of breast cancer.

[Study of arginase activity of mixed saliva in cancer].

The aim of the study was to investigate the activity of arginase of mixed saliva with the subsequent application of the results obtained in clinical laboratory diagnostics. Arginine metabolic parameters were studied in particular arginase activ- ity, concentration of nitric oxide, urea and uric acid. There was found a three-fold increase of arginase activity and a four- fold reduction of nitric oxide in mixed saliva of patients on the background of cancer. There was established inverse rela- tionship between arginase activity and nitric oxide as well as between the concentration of urea and nitrogen oxides. Basic possibility of differential diagnosis of benign and malignant neoplastic disease was showed .using chemometric methods. Imbalance of arginase activity and nitric oxide in the saliva of cancer patients could be an important diagnostic and prog- nostic criterion.

Expression of B23/Nucleophosphamine Nonribosomal Nucleolar Protein in Smooth Muscle Tumors of the Corpus Uteri.

Immunohistochemical study of B23/nucleophosmine (NPM), the key argyrophilic nonribosomal protein associated with the nucleolus-producing regions, in smooth muscle formations of the body of the uterus and myometrium was carried out. The uterus index, number of positively stained nucleoli in the nucleus, integral optical density, and area of positively stained nucleoli were studied by computer-aided image analysis. The results indicated significant differences in the integral optical density and less so in the areas of NPM+ nucleoli in leiomyosarcomas, but not in intact myometrium and leiomyomas. Coefficients of variations in the integral optical density and NPM area proved to be significant parameters for differentiating leiomyosarcomas by size (≤7 cm or larger), evaluating the malignancy grade and stage of the process. NPM parameters in leiomyomas and leiomyosarcomas differed significantly, depending on the levels of Ki-67 and p53 expression and the receptor status of leiomyosarcoma. The index of area and the integral optical density of NPM could serve a accessory objective differential diagnostic criteria in cellular and mitotically active liomyomas and well-differentiated leiomyosarcoma of the corpus uteri.

[Non-small cell lung cancer: HER2 oncogene status].

OBJECTIVE: to study HER2 protein and HER2 gene, their heterogeneity in non-small cell lung cancer. MATERIAL AND METHODS: 218 intraoperative non-small cell lung samples were examined using tissue matrix methods. HER2 protein was determined by immunohistochemistry (clone 4B5, <> and HER2 gene and CEP1 7 were evaluated by in situ hybridization (SISH, <>). RESULTS: Positive and indefinite statuses were found in 59 (27%) and 47 (22%) cases, respectively; intratumor heterogeneity was detected in 32 (30%) cases. Amplification of the HER-2 gene was found in 12 (6%) cases; that of the HER2 gene along with an increase in CEPI 7 was observed in 7 (3%) cases; elevated CEP1 7 levels were seen in 19 (9%) cases. Intratumor heterogeneity of HER2 gene amplification was not found; however, one case of adenocarcinoma showed high-level HER2 gene amplification in the gland-like areas and low-level HER2 gene amplification in the solid areas. HER2-positive status and amplification were more common in adenocarcinoma than in squamous cell carcinoma (p<0.001). There was a moderate correlation between HER2 immunohistochemical status and amplification (r=0.38; p<0.001). CONCLUSION: Thus, in non-small cell lung cancer, there is an elevated HER2 protein level and, well less frequently, altered activity in the HER2 gene (amplification) as a cause of enhanced protein synthesis.

[THE PROCESSES OF CELL PROLIFERATION, APOPTOSIS AND ANGIOGENESIS IN PATHOLOGICALLY UNCHANGED LUNG AND IN NON-SMALL CELL LUNG CANCER].

The objective of this study was to examine cell proliferation, apoptosis and angiogenesis in pathologically unchanged lung and in non-small cell lung cancer with the use of appropriate markers. The material studied included samples of pathologically unchanged lung (n=80) and those obtained at operations in 237 cases of non-small cell lung cancer. Immunohistochemical methods were used to demonstrate Ki-67, topoisomerase IIalpha (TopoIIalpha), p53, bcl-2, bax, CD34 and podoplanin. Argyrophilic proteins associated with nucleolar organizer regions (Ag-NOR proteins), were detected by impregnation with silver nitrate. The quantitative data were obtained and the peculiarities of the expression of markers associated with proliferation, apoptosis and angiogenesis in pathologically unchanged lung were determined. In the alveoli, the labeling index of Ki-67 and Topolla was less than 1%, AgNOR area index was equal to 1.31 +/- 0.20; p53, bcl-2, bax expression was absent, density of blood vessels was equal to 86 (73-102), while lymphatic vessels were absent. In the bronchus, the labeling index of Ki-67 and TopoIIalpha were respectively 4 (1-8) and less than 1%, AgNOR area index--1.85 +/- 0.24, bax expression--100%, density of blood and lymph vessels--22 (17-31) and 4 (2-7) respectively; p53 and bcl-2 expression were absent. The results were compared with the expression of markers in non-small cell lung cancer. This comparison has fundamental and differential diagnostic value in the study of histopathological lung material. The expression of markers associated with proliferation, apoptosis and angiogenesis changes from pathologically unchanged lung to non-small cell lung cancer.

Relationship of argyrophilic proteins of nucleolal organizer regions in Ki-67+ cells with clinical and morphological parameters in lung adenocarcinoma.

Ninety-four lung adenocarcinoma samples obtained during surgeries were examined using a combination of immunohistochemical staining for Ki-67 antigen and silver nitrate staining for argyrophilic nucleolar organizer (Ag-NOR) proteins. In lung adenocarcinoma, we studied the correlation between the area of Ag-NOR proteins in Ki-67(+) cells and clinical and morphological TNM parameters: maximum tumor diameter (T) and stage of the disease and tumor differentiation degree (N). Survival of patients with small area of Ag-NOR proteins in Ki-67(+) cells was higher that in patients with great area of these proteins. The area of Ag-NOR proteins in Ki-67(+) cells is an independent prognostic factor in lung adenocarcinoma. The area of Ag-NOR proteins in Ki-67(+) cells correlates with clinical and morphological TNM parameters and survival of patients with lung adenocarcinoma.

[Effect of immunotherapy on the cellular immunity in patients with cervical cancer].

UNLABELLED: For the last thirty years immunotherapy has become an integral part of treatment of some cancers. The most effective approach in this context would be the use of complex immunostimulatory factors including tumor antigen in different forms, interleukins that stimulate differentiation. BACKGROUND: The aim of the study was to compare cellular immune response on specific and combined immunotherapy in patients with cervical cancer. PATIENTS AND METHODS: 76 cervical cancer patients undergoing combined radiotherapy were included into the study. Plus to basic radiation treatment two types of immunotherapy was performed: first--autolymphocytes reinfusion after in vitro incubation with tumor antigen (tumor tissue homogenate) and interleukin-2, second--combination of above mentioned immunotherapy, interleukin-2 and systemic enzyme. RESULTS: This has resulted in increase of cellular immunity parameters in the main group with combined immunotherapy an excess of cells with killer activity to ensure an effective antitumor immune response and, accordingly, the clinical efficacy of specific methods and adoptive immunotherapy in patients with cervical cancer. CONCLUSION: Immunotherapy usage in the form of a preparation of interleukin-2 and a system enzymotherapy in a combination with a specific immunotherapy is possible. This way of treatment is recommended in cases of decreasing of cellular immunity indicators.

Correlation of HER-2/Neu protein expression and HER2 gene amplification with clinical morphological parameters of nonsmall cell lung cancer.

A total of 218 operation specimens from patients with nonsmall cell lung cancer were examined. The expression of HER-2 protein was studied by the immunohistochemical method, amplification of HER2 gene and centromere part of chromosome 17 (CEP17) - by the in situ chromogenic hybridization method. Moderate correlation (r=0.38, p<0.001) between the immunohistochemical status and HER2 gene amplification was detected. A relationship between TNM clinical morphological parameters and HER-2 protein content and chromosome 17 polysomia (for N parameter), HER-2 protein content, and HER2 gene amplification (for tumor histogenesis) was detected. The content of HER-2 protein and amplification of HER2 and CEP17 correlated with the clinical morphological parameters of patients with nonsmall cell lung cancer.

Argyrophilic proteins of nucleolar organizer regions and proliferative activity of cells in squamous cell carcinoma of the lung.

Argyrophilic proteins associated with nucleolar organizer regions (Ag-NOR proteins) and Ki-67 antigen were analyzed in 118 samples of squamous cell carcinoma of the lungs. Tumors with low and high content of Ag-NOR proteins and Ki-67 index were selected. It was found that the content of Ag-NOR proteins correlated with some clinical and morphological parameters (indexes T and N, tumor size less and more that 3 cm, stage of the disease, and tumor differentiation degree) and survival rate. High survival was associated with low content of Ag-NOR proteins and Ki-67 index and low survival correlated with high content of Ag-NOR proteins and Ki-67 index, while intermediate survival was associated with opposite values of Ag-NOR protein content and Ki-67 index. The tumor size, parameter N, and the content of Ag-NOR proteins had independent effects on patient's survival. In patients with squamous cell carcinoma of the lung without metastases in lymph nodes, survival correlated with the content of Ag-NOR proteins; in patients without metastases, survival correlated with tumor size.

[The polymorphism of genes of synthesis and metabolism of estrogens and the risk of breast cancer].

The genetic polymorphism of enzymes of synthesis and metabolism of estrogens can input into predisposition to breast cancer. The purpose of actual study was to analyze the associations of polymorphic loci CYP17/B1rs10556836, CYP1A 1rs1048943, CYP1A2rs762551, CYP19A1rs2470152 and CYP17A1rs743572 with risk of development of breast cancer in Russian residents of the Western-Siberian region of Russia. The rates of alleles and genotypes of the given loci were determined in sampling of women suffering with breast cancer (n = 670 females) and in control group (480 females without oncological diseases). The sub-groups of patients with breast cancer in pre-menopause--and post-menopause were analyzed separately. The border-line association of locus CYP17A1rs743572 is demonstrated with increasing of risk of breast cancer during pre-menopause (allele C: p = 0.04). Among the rest of polymorphic loci no association was detected.

[Topoisomerase IIa expression in correlation with clinical and morphological parameters and proliferation (based on argyrophilic proteins of nucleolar organizer regions and Ki-67 antigen) in lung adenocarcinoma].

Investigated topoisomerase IIalpha (TopoII alpha), argyrophilic proteins associated with nucleolar organizer regions (Ag-NOR) and antigen Ki-67 in lung adenocarcinoma. Defined tumor with low and high TopoII alpha, Ag-NOR and Ki-67. TopoII alpha had a relationship with clinical and morphological parameters (greatest dimension, tumor differentiation) and proliferation markers (Ag-NOR, Ki-67) . Survival of patients with lung adenocarcinoma with low content of TopoII alpha is better as compared with high content of TopoII alpha. Survival of patients with lung adenocarcinoma depends on the mutual content of TopoII alpha and clinical and morphological parameters (value T, greatest dimension, value N, stage, tumor differentiation), proliferation markers (Ag-NOR). TopoII alpha content in lung adenocarcinoma is an independent prognostic factor. Mutual research of TopoII alpha with clinical and morphological parameters and Ag-NOR has prognostic value in lung adenocarcinoma.

Associations between SNPs within antioxidant genes and the risk of prostate cancer in the Siberian region of Russia.

In the present study we investigated the association of a number of polymorphic changes in antioxidant system genes (SNPs rs1050450 in the GPX1 gene, rs1695 and rs1138272 in the GSTP1 gene and rs4880 in the MnSOD gene) with the risk of prostate cancer. The association of disease stage and PSA levels with specific genotypes was also analyzed. A study was conducted with the participation of 736 Russian men. We compared the frequency of occurrence of the studied alleles in patients with prostate cancer (392) to a control group (344) of men without a history of cancer. Genotyping was performed by real-time PCR. Comparison of frequencies of alleles and genotypes were performed using logistic regression analysis. No statistically significant association with the risk of prostate cancer was found for any of the SNPs studied (p > 0.05). For SNP rs1695 in the GSTP1 gene, a correlation with cancer disease stage was observed: a GG genotype is significantly more common in patients with PCa in the 3rd and 4th stage than 1st and 2nd (OR[95%CI] = 2.66[1.15-6.18], p = 0.02). Both studied SNPs of GSTP1 gene are associated with the level of PSA: the GG rs1695 and the TT rs1138272 genotypes are associated with higher PSA levels (p = 1.5*10(-3)).

Relationship between the argyrophilic proteins of the nucleolar organizer region and stage of squamous-cell carcinoma of the lung.

Argyrophilic proteins associated with chromosome nucleolar organizer regions (Ag-NOR proteins) were studied in lung squamous-cell carcinoma cells. After routine staining with silver nitrate, the area index and coefficient of variations of Ag-NOR protein were estimated by computer-aided image analysis. The Ag-NOR protein area indexes of tumor cells differed in clinical morphological variants of squamous-cell cancer (differing by T and N parameters, size of the primary node <3 cm or larger, by disease stage, and differentiation degree). Ag-NOR protein variation coefficient can be used for discriminating the tumors by size (<3 cm and larger), presence/absence of metastases, and evaluation of squamous-cell cancer differentiation degree. Ag-NOR protein area index and variation coefficient can be used as additional objective differential diagnostic criteria of clinical and morphological forms of squamous-cell carcinoma of the lung.

[Association of chromosome 8q24 variants with prostate cancer risk in the Siberian region of Russia and meta-analysis].

Compelling evidence demonstrates chromosome 8q24 as a prostate cancer susceptibility locus. In present work we studied whether the common variants of 8q24 region, rs6983267 and rs1447295, were associated with the sporadic prostate cancer risk in the Russian population. Polymorphisms were genotyped in 393 case and 384 control Russian Caucasian men from Siberia region. The A allele of rs1447295 was significantly associated with the risk of prostate cancer (OR[CI 95%] = 1.74 [1.26-2.4], p = 7.8 x 10(-4)). A common G-A haplotype for rs6983267 - rs1447295 also showed an association with prostate cancer risk in Russian population (OR[CI 95%] = 2.03 [1.1 - 3.75], p = 0.02). We performed a meta-analysis combining our results with previous studies to evaluate the association between studied SNPs and prostate cancer risk. Meta-analysis has strongly supported the association for these SNPs (p < 10(-6)). Accordingly our study confirms the association between chromosome 8q24 and prostate cancer risk.

[Use of recombinant factor VIIa to reduce transfusional load in hemorrhaging patients after surgery for malignant tumors].

Often expanded surgical interventions in patients with malignant tumors are accompanied by huge bleeding and require transfusion of big mass of medications prepared from donor blood that may develop different complications. It is showed that with the aim of treatment of hemorrhagic complications the use of recombination factor VIIa allows reducing the surgical blood loss, as well as diminishing hemotransfusional load after surgery especially in patients with malignancies of urogenital system and malignant tumors of the colon and lung.

[Dielectric parameters of ascitic and pleural fluids in the microwave range in different nosologies].

The dielectric parameters of ascitic and pleural fluids formed in the human body in oncological and nononcological diseases of different nosology have been estimated in the range between 400 MHz and 1.2 GHZ. The dependence of refractive and absorption indices of ascitic and pleural liquids on the signal frequency and mass concentration of dissolved substances was found. Common regularities and distinctions in the behavior of their dielectric properties were revealed.

[Topoisomerase IIalpha activity and tumor cell proliferation level from the degree of bromodeoxyuridine label in uterine body leiomyosarcoma].

The investigation was undertaken to estimate the expression of the enzyme gyrase Topoisomerase IIalpha (TOPOIIalpha) and proliferative activity from the level of bromodeoxyuridine (Brdu) in uterine body leiomyosarcoma (UBL) (n=66) versus the unchanged myometrium (UM), a tumor of uncertain malignancy potential (STUMP) (n=12), and leiomyoma (LM) (n=46). An immunohistochemical technique was used to reveal TopOIIalpha and Brdu. The findings indicated that Brdu was undetectable in UM and simple LM and that TOPOIIalpha activity was low. At the same time there was an exponential rise in the activity of the enzyme and cells during the S phase of the cell cycle from cellular LM to UBL. An increase was also noted in the study markers as sarcoma malignancy progressed. Thus, it can be said that the estimation of the number of cell S fractions and the activity of TOPOIIalpha in UM, LM, STUMP, and UBL may serve as a relatively simple and reliable method for the differential diagnosis of benign and malignant smooth muscle tumors of the uterine body and the determination of the activity of the enzyme may be used to define the degree of tumor chemoresistance in the complex treatment of patients with UBL.

[Expression of sex hormones receptors in leiomyoma with uncertain potential of malignancy and endometrial leiomyosarcoma: differentiatial diagnosis and prognostic significance].

A retrospective evaluation of progesterone (PR) and alpha-estrogen (ER) expression was carried out in 16 patients with smooth muscle tumors with uncertain potential of malignancy (STUMP) and 76 patients with uterine leiomyosarcoma (ULMS). PR expression was observed in 100% of intact myometrium and leiomyoma samples, while ER was expressed only in 37.1 +/- 4.2% and 23.5 +/- 4.1% of samples. In STUMP samples PR expression was observed in 66.7 +/- 11.7% of cases, in ULMS samples in 50.5 +/- 5.7% of cases. However, there was an inverse correlation between malignancy grade and sex hormones expression, although the number of positive cells and staining intensity didn't prove to be independent risk factors. The patients with ULMS G1 and STUMP expressing sex hormones have favorable prognosis, while negative receptor status of STUMP tumors is the marker of the worse prognosis.

[Polymorphic variants of folate metabolizing genes (C677T and A1298C MTHFR, C1420T SHMT1 and G1958A MTHFD) are not associated with the risk of breast cancer in West Siberian Region of Russia].

Breast cancer is the most incident cancer among women. We investigated the role of polymorphisms of folate metabolizing genes MTHFR (C677T and A1298C), SHMT1 (C1420T) and MTHFD (G1258A) in genetic susceptibility to this type of cancer. We determined allele and genotype frequencies in case (850 women with sporadic form of breast cancer) and control (810 women) groups. None of these polymorphisms was significantly associated with breast cancer risk. To increase statistical power of our study, we conducted a meta-analysis which included published genotype data and the results of our work. Meta-analysis also revealed no significant association of studied SNPs with breast cancer.

[Argyrophilic nucleolar organizer region associated proteins in adenomas with varying colonic dysplasia and adenocarcinoma].

Argyrophilic nucleolar organizer region associated (Ag-NOR) proteins were studied in rectosigmoid epithelial tumors for diagnostic purposes. Silver nitrate staining was carried out in accordance with the standardized protocol. The quantity, area, area index of Ag-NOR proteins were automatically determined by computer image analysis. There were statistically significant differences in the quantity, area, area index of Ag-NOR proteins between the groups: the mucosa (lower 2/3 crypts), mild, moderate, and severe dysplasia of adenoma. Only the estimation of the area index of Ag-NOR proteins indicated statistically significant differences between severe dysplasia and highly differentiated adenocarcinoma. Colonic adenomas showed a correlation of the activity of Ag-NOR proteins with epithelial dysplasia, but no correlation with the size and histological type of their structure.