FDI-6 inhibits VEGF-B expression in metastatic breast cancer: a combined in vitro and in silico study.

Angiogenesis is the process by which new blood vessels are formed to meet the oxygen and nutrient needs of tissues. This process is vitally important in many physiological and pathological conditions such as tumor growth, metastasis, and chronic inflammation. Although the relationship of FDI-6 compound with FOXM1 protein is well known in the literature, its relationship with angiogenesis is not adequately elucidated. This study investigates the relationship of FDI-6 with angiogenesis and vascular endothelial growth factor B (VEGF-B) protein expression alterations. Furthermore, the study aims to elucidate the in silico interaction of FDI-6 with the VEGFR1 protein, a key player in initiating the angiogenic process, which is activated through its binding with VEGF-B. Our results demonstrate a significant effect of FDI-6 on cell viability. Specifically, we determined that the IC50 value of FDI-6 in HUVEC cells after 24 h of treatment is 24.2 µM, and in MDA-MB-231 cells after 24 h of application, it is 10.8 µM. These findings suggest that the cytotoxic effect of FDI-6 varies depending on the cell type. In wound healing experiments, FDI-6 significantly suppressed wound closure in MDA-MB-231 cells but did not show a similar effect in HUVEC cells. This finding suggests FDI-6 may have potential cell-type-specific effects. Molecular docking studies reveal that FDI-6 exhibits a stronger interaction with the VEGFR1 protein compared to its inhibitor, a novel interaction not previously reported in the literature. Molecular dynamic simulation results demonstrate a stable interaction between FDI-6 and VEGFR1. This interaction suggests that FDI-6 might modulate mechanisms associated with angiogenesis. Our Western blot analysis results show regulatory effects of FDI-6 on the expression of the VEGF-B protein. We encourage exploration of FDI-6 as a potential therapeutic agent in pathological processes related to angiogenesis. In conclusion, this study provides a detailed examination of the relationship between FDI-6 and both the molecular interactions and protein expressions of VEGF-B. Our findings support FDI-6 as a potential therapeutic agent in pathological processes associated with angiogenesis.

An analysis of the relationship between ABCC8 and KCNJ11 gene polymorphisms and diabetic retinopathy in Turkish population.

BACKGROUND: Diabetic retinopathy (DR) occurs due to high blood glucose damage to the retina and leads to blindness if left untreated. KATP and related genes (KCNJ11 and ABCC8) play an important role in insulin secretion by glucose-stimulated pancreatic beta cells and the regulation of insulin secretion. KCNJ11 E23K (rs5219), ABCC8-3 C/T (rs1799854), Thr759Thr (rs1801261) and Arg1273Arg (rs1799859) are among the possible related single nucleotide polymorphisms (SNPs). The aim of this study is to find out how DR and these SNPs are associated with one another in the Turkish population. MATERIALS AND METHODS: This study included 176 patients with type 2 diabetes mellitus without retinopathy (T2DM-rp), 177 DR patients, and 204 controls. Genomic DNA was extracted from whole blood, and genotypes were determined by the PCR-RFLP method. RESULTS: In the present study, a significant difference was not found between all the groups in terms of Arg1273Arg polymorphism located in the ABCC8 gene. The T allele and the TT genotype in the -3 C/T polymorphism in this gene may have a protective effect in the development of DR (p = 0.036 for the TT genotype; p = 0.034 for T allele) and PDR (p = 0.042 and 0.025 for the TT genotype). The AA genotype showed a significant increase in the DR group compared to T2DM-rp in the KCNJ11 E23K polymorphism (p = 0.046). CONCLUSIONS: Consequently, the T allele and TT genotype in the -3 C/T polymorphism of the ABCC8 gene may have a protective marker on the development of DR and PDR, while the AA genotype in the E23K polymorphism of the KCNJ11 gene may be effective in the development of DR in the Turkish population.

Upregulation and the clinical significance of KCNQ1OT1 and HAGLROS lncRNAs in papillary thyroid cancer: An observational study.

Long noncoding RNAs (lncRNAs) play an important role in regulating gene expression. Changes in their expression have been associated with many types of cancer, including thyroid cancer. This study aimed to investigate how changes in the expression of potassium voltage-gated channel subfamily Q member 1 opposite strand/antisense transcript 1 (KCNQ1OT1) and HAGLR opposite strand lncRNA (HAGLROS) lncRNAs correlate with the development and clinicopathological characteristics of papillary thyroid cancer (PTC). Reverse transcription-quantitative polymerase chain reaction was used to investigate the expression of lncRNAs in both tumor and adjacent normal thyroid tissue samples of the patients. Expressions of KCNQ1OT1 and HAGLROS were upregulated in the patients tumor samples compared to the adjacent normal thyroid samples. KCNQ1OT1 expression was linked to microcarcinoma and gender, while HAGLROS expression was linked to microcarcinoma and tumor size. When only microcarcinoma samples were evaluated, KCNQ1OT1 expression was higher in tumor tissues compared to normal tissues; however, no significant difference was observed in HAGLROS expression. Our data suggests that high expressions of KCNQ1OT1 and HAGLROS might contribute to the development of PTC and disease progression, and both lncRNAs may be potential therapeutic targets in PTC patients.

Expression of SOX2OT, DANCR and TINCR long non­coding RNAs in papillary thyroid cancer and its effects on clinicopathological features.

Long non­coding RNAs (lncRNAs) are molecules that are >200 base pairs long and do not encode a protein. However, they perform important roles in regulating gene expression. Recent studies have revealed that the changes in the expressions of lncRNAs serve a role in the development and metastases of a number of types of cancer. A number of studies have been published on the association of SOX2 overlapping transcript (SOX2OT), differentiation antagonizing non­protein coding RNA (DANCR) and tissue differentiation­induced non­coding RNA (TINCR) expression with various types of cancer. However, researchers have not yet studied their roles in papillary thyroid cancer or at least, those roles are not clarified. The aim of the present study was to investigate the expression and clinical significance of SOX2OT, DANCR and TINCR in papillary thyroid cancer (PTC). A total of 102 patients with PTC were included in the present study. Reverse transcription­quantitative PCR method was used to determine the relative gene expression levels of lncRNAs and then the relationship between expressions of lncRNAs and clinical characteristics of the subjects was analyzed in detail. Expression levels of SOX2OT (P=0.016) and DANCR (P=0.017) increased in the tumor samples in contrast to the normal tissues. No significant difference was observed in the expression level of TINCR (P=0.298). In addition, SOX2OT expression was associated with micro carcinoma (P<0.001), tumor size (P=0.010) and primary tumor (P=0.006), while DANCR expression was associated with age (P=0.030) and micro carcinoma (P=0.004). The findings of the present study indicated that DANCR may contribute to the development of PTC while SOX2OT may contribute to both the development and progression of PTC.

Possibility of paclitaxel to induce the stemness-related characteristics of prostate cancer cells.

BACKGROUND: Drug resistance poses a crucial problem in the treatment of prostate cancer. Recent studies have shown that chemotherapy agents may cause cancer cells to acquire stem cell-like properties, resulting in drug resistance and, eventually, treatment failure. OBJECTIVES: To evaluate whether long-term paclitaxel exposure causes an increase in the stem cell-like properties of prostate cancer cells. MATERIAL AND METHODS: Paclitaxel-resistant PC-3 cells were generated from parental PC-3 cells by treating them with increasing concentrations of paclitaxel. The expression levels of the stem cell markers NANOG, C-MYC, CD44, and ABCG2 were evaluated using quantitative real-time polymerase chain reaction (RT-qPCR). A sphere formation assay was performed to test the potential of the cells to behave as stem cells, and a wound healing assay was carried out to evaluate migration ability of the cells. RESULTS: The expression levels of C-MYC and NANOG were significantly higher in paclitaxel-resistant PC-3 cells compared to the parental PC-3 cells. However, there was no significant increase in the expression of CD44 or ABCG2. In addition, the sphere-forming capacity and migration ability of resistant PC-3 cells were increased. CONCLUSIONS: The results of the current study indicate that paclitaxel exposure may increase the stem cell-like properties of PC-3 prostate cancer cells.

Effects of menstrual cycle on divided attention in dual-task performance.

PURPOSE: Monthly hormonal fluctuation in women causes changes in peripheral systems and central nervous system structure and functions. In this study, we investigated the effects of menstrual cycle periods in women on attention during multitasking. Single and dual task conditions were tested in different menstrual cycle periods. MATERIALS AND METHODS: A total of forty women with regular menstrual cycles participated in this study. They were not any type of medication or hormonal treatment. Fine motor skills and Go/No-go tasks were performed on the 10th day of the late follicular phase, and then the tests were repeated on the 20th day of the late luteal phase. Fine motor tasks were performed by Annett's peg-moving test. Auditory stimuli were used in Go/No-go task. In dual tasks, both tasks were performed simultaneously. RESULTS: There was no difference between follicular and luteal phases in single fine motor and Go/No-go task. In dual task condition Go/No-go task % error rate decreased in the luteal phase. Similarly, Go/No-go task reaction time decreased in the luteal phase. Non-dominant hand performance was increased in the luteal phase during the dual-task condition compared to the follicular phase. CONCLUSIONS: When these results are evaluated together, declining error rates and reaction times indicates women successfully multitask in the luteal phase in dual tasks condition. This suggests that divided attention in women leads to better performance in the luteal phase than in the follicular phase.

Cytotoxic and genotoxic effects of an endemic plant of Turkey Salvia kronenburgii on breast cancer cell lines.

CONTEXT: The natural products derived from plants are the important sources that can be used for breast cancer treatment. Salvia species and their derived products were recommended as potential antitumor substances. AIM: The potential cytotoxic and genotoxic effects of Salvia kronenburgii have been investigated on breast cancer cell lines, MCF-7 and MDA-MB-231. MATERIALS AND METHODS: Determination of chemical compounds of S. kronenburgii was done using a gas chromatography coupled to time-of-flight mass spectrometry system and a dual-stage commercial thermal desorption injector. Growth inhibition of the S. kronenburgii was measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and ATP viability assays. The cell death mode was detected by fluorescent dyes. Genotoxic effect of S. kronenburgii was measured by comet assay. RESULTS: S. kronenburgii showed antiproliferative effect in a dose-dependent manner on MCF-7 and MDA-MB-231 cell lines by inducing apoptosis-like cell death. The pyknotic cell nuclei were observed at the cell lines in response to S. kronenburgii. Furthermore, significant increase was shown in genetic damage index and frequencies in the damaged cells. CONCLUSION: S. kronenburgii might be a promising natural source for cancer therapy. Further experiments need to be done in vivo to understand of the anticancer effects of this plant.

Cancer Statistics in Giresun Province, Turkey: A 12-Years Retrospective Review.

AIM: The aim of this retrospective study was to analyze 6,613 diagnosed cancer cases in the Black Sea Turkish province of Giresun over a period of 12 years. MATERIAL AND METHOD: Data of this retrospective crosssectional study was collected from 6,613 cancer patients at Prof. Dr. A. Ilhan Özdemir Education and Research Hospital between 2005- 2016. MINITAB 15 package software was used for statistical analysis. Chi-Square test and differences between two ratios significance test were used to calculate the relationship between two nominal (categorical) variables. RESULTS: Total 6,613 cancer patient's (3,759 men, 56.8% and 2,854 women, 43.2%) average age is 66.27±17.17. The most frequent types of cancer found among men included prostate (24.4%), bronchus-lung (12.5%) and colorectal (11.15%) cancer; whilst among for women it was breast (26%), thyroid (14.9%) and skin (10.6%) cancer, respectively. Kidney, bronchus-lung, skin, larynx, breast, bladder and thyroid cancer types were determined to be statistically significant according to gender (p<0.05). CONCLUSION: We reviewed the diagnosed cancer cases in Giresun province from 2005 to 2016. For men, the order of the most frequent cancer types mentioned is consistent with the statistics of both the European Union (EU) as well as the United States of America (USA); whereas for women it was consistent with Turkey's own national statistics. However, our findings state that thyroid cancer is the second most common cancer type among Turkish women, this is in contrast to most other parts of the world, the EU and USA.

Association of microsomal epoxide hydrolase gene polymorphism and pre-eclampsia in Turkish women.

AIM: To assess the association between human epoxide hydrolase exon 3 and 4 polymorphisms and pre-eclampsia by carrying out a case-control study in Turkish women. METHODS: DNA was extracted from peripheral blood leukocytes, and genotype distribution of exon 3 and exon 4 of epoxide hydrolase gene (EPHX) was carried out in 271 patients and 155 controls. RESULTS: There was no statistically significant difference in the distribution of genotypes between pre-eclampsia without HELLP and pre-eclampsia plus HELLP cases and controls for the exon 3 and 4 polymorphism of EPHX. However, we found a significant association between the predicted enzyme activity level and pre-eclampsia (P = 0.018). The distribution of subjects with predicted high, intermediate and low microsomal epoxide hydrolase enzyme (EPHX) activity were 23.2, 38.8 and 38% in cases and 12, 47.3 and 40.7% in controls, respectively. CONCLUSION: Although we could not find any association between genetic variability in exon 3 and 4 of EPHX and pre-eclampsia, genetic variability in these two exons jointly modifies the predicted enzyme activity and may be a risk factor for pre-eclampsia.

Lack of association between the CYP11B2 gene polymorphism and preeclampsia, eclampsia, and the HELLP syndrome in Turkish women.

OBJECTIVES: It is possible that altered control of aldosterone synthase gene (CYP11B2) expression or translation may be responsible for hypertension. Hypertension is one of the major components of preeclampsia. We present here a study investigating the association between the CYP11B2 gene polymorphism in the promoter region at the position of -344 and preeclampsia. STUDY DESIGN: We analyzed a group of Turkish women for preeclampsia (n=143), eclampsia (n=36), and the HELLP syndrome (n=55) and compared them with controls (n=147). Genotypes for CYP11B2 were determined by polymerase chain reaction followed by digestion with BsuRI restriction enzyme. RESULTS: The -344T/T, -344C/T, and -344C/C genotypes were found at comparable frequencies among the study groups, between the study and control groups, and between the study groups combined and the control group (p>0.05). We combined the genotypes of TC and CC (polymorphic) and compared them with the TT (wild-type) genotype. There was no significant difference in the frequency of the TC plus CC genotypes among the study groups, between the study and control groups, and between the study groups combined and the control group (p>0.05). There was no association of the CYP11B2 polymorphism among the preeclampsia, eclampsia, and HELLP groups and controls. CONCLUSIONS: The CYP11B2 gene polymorphism is not directly associated with preeclampsia, eclampsia, and the HELLP syndrome in women with these conditions. Therefore, this polymorphism may not be a risk factor for these disorders, at least not in the Turkish population.

No association of polymorphisms in the glutathione S-transferase genes with pre-eclampsia, eclampsia and HELLP syndrome in a Turkish population.

AIM: There is substantial evidence that genetic factors play a role in pre-eclampsia. The aim of this study was to determine whether genetic variability in the encoding of genes for glutathione S-transferase M1 (GSTM1) and glutathione S-transferase T1 (GSTT1) contributes to individual differences in susceptibility to pre-eclampsia, eclampsia, or hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome). METHODS: A total of 221 women with pre-eclampsia, eclampsia and HELLP syndrome and 147 healthy female controls were genotyped for GSTM1 and GSTT1 polymorphisms by polymerase chain reaction (PCR). Statistical evaluation of differences in polymorphic rates was carried out using chi(2) analysis. RESULTS: This study included 140 pre-eclamptic, 33 eclamptic and 48 HELLP syndrome cases and 147 healthy controls. The frequencies for the GSTM1 null genotype were 58%, 45%, and 60% for pre-eclampsia, eclampsia, and HELLP syndrome, respectively, and in controls it was 55%. The distribution of the GSTT1 null genotype was 22%, 21%, and 27% for pre-eclampsia, eclampsia, and HELLP syndrome, respectively, and in controls it was 22%. There was no significant association between GSTM1 and GSTT1 polymorphisms and pre-eclampsia, eclampsia, and HELLP syndrome. CONCLUSION: Our data do not support a role for polymorphisms of the GSTM1 and GSTT1 genes in the pathogenesis of pre-eclampsia, eclampsia and HELLP syndrome.