COX2 Effects on endometrial carcinomas progression.

Uterine corpus cancer is one of the most prevalent gynecologic malignancies, among which endometrial cancers (EC) represent about 90 %. Despite the proven predictive value of several immunohistochemical markers, there remains a need to identify new indicators of EC progression and exploit them for therapeutic purposes. Potential candidates with diagnostic and therapeutic efficacy include cyclooxygenases (COXs). We studied 50 EC cases: 30 endometrioid (EEC), 10 serous (SEC), 10 clear-cell endometrial carcinomas (CCEC) and 10 cases of normal endometrial tissues. We investigated the expression of COX2, ER, PR, Ki-67, EGFR, p53, Bcl-2, VEGF, MMP1, CD31, and CD163 immunohistochemically. COX2 levels in EC tissue are elevated compared to the normal endometrium and depend on tumour histological features and differentiation. Elevated COX2 leads to increased tumour cell proliferation, apoptosis inhibition, increased VEGF expression, microvessel density, and M2 macrophage infiltration, and inhibition of PR expression. ER, EGFR, and MMP1 levels are unaffected by COX2, whose levels are independent of patient age and FIGO stage.

Heavy metals effect on breast cancer progression.

BACKGROUND: Breast cancer is the most frequent localization of malignant process in American women and women of European countries. To date it is not possible to control the morbidity growth due to lack of effective ways of primary prevention. Comparing the incidence of breast cancer in developed countries with the countries of Asia and Africa, there is the fact of population predominance lesion in more urbanized countries. This suggests that the environment along with other factors, occupies a significant place in the initiation and progression of breast neoplasia. The impressive rates of industrial development led to the pollution of soil, surface water and, as a consequence, food by heavy metal salts.The purposes of this paper are as follows: the chemical composition determination of neoplastic breast tissue, evaluation of the DNA methylation level, study of prognostic-important receptors expression in the breast cancer cells, establishing linkages between all the derived indicators. METHODS: In our study we used the following methods: studying of the chemical composition of breast cancer tissue by atomic absorption spectrophotometry and energy-dispersion spectrometer; іmmunohistochemical study of ER, PR, HER2/neu, p53, Ki-67, E-cadherin and MGMT receptors; DNA extraction and investigation by oscillating infrared spectroscopy method. RESULTS: The total amount of heavy metals in breast cancer tissue ranged from 51.21 × 10-3 to 84.86 × 10-3 µg/kg. We have got the following results: the growth of heavy metals in neoplastic tissue is accompanied with the increase of HER2/neu, p53, Ki-67, MGMT expression and decrease of ER and PR expression. The increment of pathological DNA methylation is accompanied with the increasing amount of heavy metals in tumor tissue. CONCLUSIONS: Heavy metals through different pathogenetic links stimulate the progression of breast cancer and reduce its sensitivity to treatment. DNA of tumor tissue has a different level of methylation which changes with the amount of heavy metals in cancer cells. This is displayed on the synthesis of prognostically important receptors in neoplastic tissue.

Primary multiple tumor with affection of the thyroid gland, uterus, urinary bladder, mammary gland and other organs.

BACKGROUND: Nowadays multiple primary tumor is characterized by growth and development of two or more tumors in one patient. The total world sickness rate ranges from 1% to 37%. The presence of four or more tumors in one patient is rare case and presented as casuistry. CASE PRESENTATION: We showed a case of multiple primary tumor with metahronic lesion of the thyroid, uterus and breast, followed by synchronous benign tumors of the subcutaneous fat, urinary bladder and gallbladder were considered. The development of all malignant tumors in all cases was accompanied by the presence of benign precancerous processes. Analysis of neoplasia histology shows the predominance of poorly differentiated forms of cancers in women with increased aggressiveness of cancerous tissue in each subsequent case and the growth of metastatic ability. The influence of heredity on the tumors progress is confirmed by immunohistochemical characteristics of cancer cells. Steroid-sensitive tissue of the uterus and breast in both cases didn't express ER and PR, in all cases the tissue had overexpression of Ki-67, p53, bax and bcl-2 receptors. The results of DNA testing for determination the Lynch syndrome revealed the presence of microsatellite instability in genetic material. The results of studies revealed the absence of mutations in these genes (MLH1, MSH2 and MSH6). Despite the negative results of the study, it doesn't exclude the possibility of Lynch syndrome for 100%, and its presence may be caused by the mutations of other genes (PMS1, PMS2 and MLH3), responsible for DNA repair. Unfortunately there wasn't any opportunity to study their mutations. CONCLUSIONS: While studying the anamnesis of life and disease of women it was revealed that she had multiple primary tumor with lesions of the breast, urinary bladder, thyroid, uterus and other organs. This study shows that neoplastic tissue in all cases had high rates of cell proliferation, their antiapoptotic stability, expression of prognostically unfavorable-receptors, and absence of favorable prognostic markers. Histological study revealed high rates of malignant neoplastic tissue. It indicates to the existence of common mechanisms of malignant tumors and their genetic predisposition that can be clearly observed in many generations of patient.

[A FITZ-HUGH-CURTIS SYNDROME AS A PREMISE OF THE INFLAMMATORY DISEASES OF A HEPATOPANCREATOBILIARY ZONE ORGANS].

A content of a biliary ways microflora and its correlation with clinical form and severity of inflammatory-destructive processes in hepatopancreatobiliary zone were studied up. The investigation objective was the optimization of a treatment--diagnostic tactics for the complications and remote recurrences rate reduction in a complicated biliary calculous disease. There was established, that a standard bacteriological investigation do not give a possibility to estimate some causes of a biliary ducts affection, a chlamidial infection in particular. So on, for the individual antibacterial therapy choosing a more detailed and modern examination of patients is needed.

[Gastroduodenal mucosa sensitivity to estrogen in ulcers complicated by hemorrhage].

Expression of alpha-receptors of estrogen (RE) in accordance to immunohistochemical (IHC) labeling in gastroduodenal mucosa cells was studied up in patients, suffering the ulcer disease and without it. In 4 patients (group I) a gastroduodenal mucosa affection was revealed, they were operated on for hemorrhage from gastroduodenal ulcers; in 3 patients (group II) gastroduodenal mucosa affection was not observed; in 4 patients (group III, control), a mammary gland cancer was diagnosed, a positive reaction on alpha-RE was noted. In groups I and II the biopsies were studied, obtained from pylorus and gastric fundus, as well as from duodenal ampula, and in a group III--obtained from the tumor. In a control group a positive labeling of nuclei was revealed in biopsies. In patients of groups I and II the alpha-RE expression by cellular nuclei was not revealed, but, the lots of positive IHC labeling of cytoplasm in glandular and stromal mucosal cells of the investigated gut were noted. Positive IHC labeling of cytoplasm for alpha-RE witnesses about sensitivity to them in norma and pathological processes. But, a trustworthy difference of alpha-RE expression by cellular nuclei was not noted. For confirmation or denial of this hypothesis further clinical and IHC investigations are needed.

[HORMONAL-GENETIC SCREENING IN PATIENTS, SUFFERING GASTRODUODENAL ULCER HEMORRHAGE].

Genetic-hormonal regulation plays a key pathophysiologic role in a blood loss on background of complicated gastroduodenal ulcer disease, but a clinical significance of some genes of compensatory steroidogenesis remains unrevealed. Examination of 63 patients, using a chain reaction with polymerase (CRP); analysis of length of restriction fragments (CRP-RFLP) and immunohistochemical investigation of gastroduodenal mucosa were performed on the base of a Sumsky Rural Clinical Hospital. Trustworthy difference of distribution of polymorphic genes ESR1 and VKORC1 in patients of both gender in presence of the ulcer hemorrhage was not revealed, excluding genotype A/A VKORC1, what trustworthy more frequently was revealed in women (p < 0.05). There was established, that intact zone of gastric fundus owes immunoreactivity towards alpha-receptors of estrogen in nuclei of epitheliocytes and stromocytes. Diagnosis of polymorphic gene VKORC1 and expression of the estrogen receptors may serve the base for pathogenetic therapy in patients with hemorrhage occurrence.

STRUCTURAL CHANGES IN SUBMANDIBULAR SALIVARY GLAND, CAUSED BY HEAVY METAL SALTS, AND THEIR CORRECTION WITH DIALIPON (EXPERIMENTAL STUDY).

Setting of possibilities of structural changes correction in submandibular salivary gland with a Dialipone drug, caused by adverse effect of heavy metals salts on an organisms of different age group rats. Structural changes and their correction were studied on the histological preparations basis painted by hematoxylin-eozin, Van-Gizon, PAS reaction, investigated and photographed by means of the digital image display system "SEO Scan". In comparison to the results of submandibular salivary gland tissue histological research of animals without any correction of microelementosis, animals that took Dialipone are marked with a better glandular epithelium saving, less widespreading of dystrophic and dyscirculatory changes, sclerotization processes in stroma. When comparing of Dialipone restoration possibilities, it was set, that different age group animals show different application efficiency of the corrector. The rats of young and mature age have more complete renewal of structural changes. The rats of advanced age show worse reparative capabilities, less complete and effective renewal of structural changes.