PurposeThe present study is to discover a new genes associated with drug resistance development in ovarian cancer.MethodsWe used microarray analysis to determine alterations in the level of expression of genes in cisplatin- (CisPt), doxorubicin- (Dox), topotecan- (Top), and paclitaxel- (Pac) resistant variants of W1 and A2780 ovarian cancer cell lines. Immunohistochemistry assay was used to determine protein expression in ovarian cancer patients.ResultsWe observed alterations in the expression of 22 genes that were common to all three cell lines that were resistant to the same cytostatic drug. The level of expression of 13 genes was upregulated and that of nine genes was downregulated. In the CisPt-resistant cell line, we observed downregulated expression of ABCC6, BST2, ERAP2 and MCTP1; in the Pac-resistant cell line, we observe upregulated expression of ABCB1, EPHA7 and RUNDC3B and downregulated expression of LIPG, MCTP1, NSBP1, PCDH9, PTPRK and SEMA3A. The expression levels of three genes, ABCB1, ABCB4 and IFI16, were upregulated in the Dox-resistant cell lines. In the Top-resistant cell lines, we observed increased expression levels of ABCG2, HERC5, IFIH1, MYOT, S100A3, SAMD4A, SPP1 and TGFBI and decreased expression levels of MCTP1 and PTPRK. The expression of EPHA7, IFI16, SPP1 and TGFBI was confirmed at protein level in analyzed ovarian cancer patients..ConclusionsThe expression profiles of the investigated cell lines indicated that new candidate genes are related to the development of resistance to the cytostatic drugs that are used in first- and second-line chemotherapy of ovarian cancer.

High-performance ion chromatography and inductively coupled plasma–mass spectrometry methods have been applied to estimate the content of Cd, Co, Cu, Fe, Mn, Zn, and Ni in whole blood, plasma, and urine of obese and nonobese children. The study was conducted on a group of 81 Polish children of age 6–17 years (37 males, 44 females). Obese children were defined as those with body mass index (BMI) >95th percentile in each age–gender-specific group. Statistical testing was done by the use of nonparametric tests (Kruskal–Wallis's and Mann–Whitney's U) and Spearman's correlation coefficient. Significant correlations appeared for control group in plasma (Mn–Cd, Ni–Co), urine (Cu–Co), and blood (Fe–Cu), while for obese patients in plasma (Cd–Mn, Ni–Cu, Ni–Zn) and urine (Fe–Cd, Co–Mn). Sex criteria did not influence correlations between metals' content in plasma and urine of obese patients. Metals' abundance was correlated in non-corresponding combinations of body fluids. Rare significant differences between content of metals according to sex and the type of body fluids were discovered: Zn in plasma from obese patients of both sexes, and Zn, Co, and Mn in blood, Mn in plasma from healthy subjects. Negative correlations between BMI and Zn in blood, Cu in plasma, and Fe in urine were discovered for girls (control group). Positive correlation between Co content in plasma and BMI was discovered for obese boys. The changes in metals' content in body fluids may be indicators of obesity. Content of zinc, copper, and cobalt should be monitored in children with elevated BMI to avoid deficiency problems.

The role of T helper 17 (Th17) and T regulatory cells (Treg) in the pathogenesis of Graves' disease (GD) remains uncertain. The influence of methimazole (MMI) on the human immune system is still poorly understood. The aim of the present research was to assess changes in the frequencies of peripheral blood Th17 and Treg cells during GD treatment in the group of teenagers. The frequencies of Th17 and Treg were measured by flow cytometry in 60 adolescents at the time of GD diagnosis and after achieving MMI-induced euthyreosis. The control group consisted of 20 healthy volunteers. Lower percentages and absolute counts of Treg cells were found in the study group before the treatment in comparison with healthy controls (p = 0.032 and p = 0.006, respectively). Treatment with MMI caused an increase in the percentages and absolute counts of Treg lymphocytes (p = 0.037 and p = 0.007). After the treatment, no clinically significant differences in Treg cells between GD patients and controls were found. Higher absolute counts of Th17 lymphocytes were found in hyperthyroid adolescents before the treatment initiation and after achieving euthyreosis than in healthy individuals (p = 0.0001 and p = 0.047). Treatment with MMI caused a significant decrease in the percentages and absolute counts of Th17 lymphocytes (p = 0.047 and p = 0.043). The present study demonstrates that both Th17 and Treg cells might play a role in the pathogenesis of GD. Increased percentage of Treg after MMI therapy seems a predictor of response to anti-hypertensive treatment as it is associated with the normalization of thyroid hormone levels.

PurposeThe aim of the present study is to determine the expression of LUM in drug-resistant ovarian cancer cell lines.MethodsDoxorubicin- (DOX), topotecan- (TOP) and vincristine- (VIN) resistant variants of the W1 ovarian cancer cell line were used in this study. We used quantitative real-time polymerase chain reactions to determine LUM mRNA levels. Protein expression was detected using Western blot and immunocytochemistry assays. Protein glycosylation was investigated using PGNase F digestion. Immunohistochemistry assays were used to determine protein expression in ovarian cancer patients.ResultsWe observed increased expression of LUM in drug-resistant cell lines at both the mRNA and the protein level. The most abundant LUM expression was observed in TOP-resistant cell line. We observed LUM bands that corresponded to different molecular masses, and the most abundant LUM form was the secreted form, which had a mass of 50 kDa. Double immunofluorescence analysis showed co-expression of LUM and COL3A1 as well as the presence of extracellular COL3A1 in the TOP-resistant cell line. Finally, we detected the LUM protein in ovarian cancer tissue.ConclusionThe expression of LUM in cytostatic-resistant cell lines suggests its role in drug resistance. The co-expression of LUM and COL3A1 indicates the significance of LUM in collagen fibre assembly. Expression in ovarian cancer tissue suggests that LUM can play a role in ovarian cancer pathogenesis in ways similar to other cancers.

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