BackgroundBreast 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.MethodsIn 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.ResultsThe 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.ConclusionsHeavy 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.
When increased amounts of HMS enter the rats` bodies, suppression of erythropoiesis and leukocytopoiesis occurs while thrombocytopoiesis increases. These changes depend on the period of intake of heavy metal salts. The adjustment of vitamin E reduces the severity of the cytotoxic effect of heavy metals and improves readaptation in the recovery period.
Glioblastoma multiforme (GBM) is one of the most aggressive glial cell tumors in adults. Although current treatment options for GBM offer some therapeutic benefit, median survival remains poor and does not generally exceed 14 months. Several genes, such as isocitrate dehydrogenase (IDH) enzyme and O6-methylguanine-DNA methyltransferase (MGMT), have been implicated in pathogenesis of the disease. Treatment is often adapted based on the presence of IDH mutations and MGMT promoter methylation status. Recent GBM cell line studies have associated Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) expression with high-grade tumors. Increased Nrf2 expression is often found in tumors with IDH-1 mutations. Nrf2 is an important transcription factor with anti-apoptotic, antioxidative, anti-inflammatory, and proliferative properties due to its complex interactions with multiple regulatory pathways. In addition, evidence suggests that Nrf2 promotes GBM cell survival in hypoxic environment,by up-regulating hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF). Downregulation of Nrf2 has been shown to improve GBM sensitivity to chemotherapy drugs such as Temozolomide. Thus, Nrf2 could be a key regulator of GBM pathways and potential therapeutic target. Further research efforts exploring an interplay between Nrf2 and major molecular signaling mechanisms could offer novel GBM drug candidates with a potential to significantly improve patients prognosis.
Background Although primary cancer of the fallopian tubes is a relatively rare type of tumor in female reproductive organs, its mortality is quite high. It is important to identify molecular and biological markers of this malignancy that determine its specific phenotype. Methods The study was carried out on samples received from 71 female patients with primary cancer of the fallopian tubes. The main molecular and biological properties, including hormone status (estrogen receptor [ER], progesterone receptor [PR]), human epidermal growth factor receptor (HER2)/neu expression, proliferative potential (Ki-67), apoptosis (p53, Bcl-2), and pro-angiogenic (vascular endothelial growth factor) quality of serous tumors were studied in comparison with clinical and morphological characteristics. Results ER and PR expression is accompanied by low grade neoplasia, early clinical disease stage, and absence of lymphogenic metastasis (p < .001). HER2/neu expression is not typical for primary cancer of the fallopian tubes. Ki-67 expression is characterized by an inverse correlation with ER and PR (p < .05) and is associated with lymphogenic metastasis (p < .01). p53+ status correlates with high grade malignancy, tumor progression, metastasis, negative ER/PR (p < .001), and negative Bcl-2 status (p < .05). Positive Bcl-2 status is positively correlated with ER and PR expression and low grade malignancy. Conclusions Complex morphologic (histological and immunohistochemical) study of postoperative material allows estimation of the degree of malignancy and tumor spread to enable appropriate treatment for each case.
a b s t r a c tBackground: 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.
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Introduction: Heavy metals (HM) are dangerous elements due to their toxicity and prevalence play an important role in the environmental pollution and hazards to health risk. Impact of HM at high concentrations may lead to the failures of urinary bladder (UB) structure and functions. The aim of our study was to determine the readaptive changes in the UB of the rats and effectiveness of vitamin E using after the long-term intake of the HMS mixtures. Materials and Methods: We used mature male laboratory rats which were divided into three series with special experimental conditions after the influence of HM. The detailed analysis of the UB state was performed by using morphometric, spectrophotometric, histological and electron microscopy methods. Results: We had determined that the long-term intake of HM caused the significant increase of their accumulation in the tissue and morphometric changes of UB. Obtained results after the cancelation of the HM effect demonstrate smooth morphological restructuring of the UB wall with the reduction of difference of accumulation and morphometric indicators with control. The adjustment of vitamin E during there adaptation period showed better result recovery and optimization of all parameters, but they haven’t completely returned to normal state. Conclusions: The influence of HMS mixture led to significant negative effect on the UB at all stages of research. However, under the conditions of readaptation the tendency towards a certain stabilization of all indicators was observed, but they didn’t completely pass to the end of the study. The vitamin E using has caused the acceleration and improved the development of readaptive change after HM exposure. Bangladesh Journal of Medical Science Vol.18(1) 2019 p.100-106
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