N-Substituted 2-(Benzenosulfonyl)-1-Carbotioamide Derivatives Exert Antimicrobial and Cytotoxic Effects via Aldehyde Dehydrogenase Pathway: Synthesis, In Silico and In Vitro Studies.

A series of N-Substituted 2-(benzenosulfonyl)-1-carbotioamide derivatives (WZ1-WZ4) were synthesized and characterized using spectral methods. A comprehensive activity study was performed for each compound. All compounds were tested for antibacterial activity. Moreover, in silico studies were carried out to determine the anticancer potential of the designed WZ1-WZ4 ligands. Based on molecular docking, aldehyde dehydrogenase was selected as a molecular target. The obtained data were compared with experimental data in vitro tests. Novel hybrids of the thiosemicarbazide scaffold and sulfonyl groups may have promising anticancer activity via the aldehyde dehydrogenase pathway. The best candidate for further studies appears to be WZ2, due to its superior selectivity in comparison to the other tested compounds.

Serum Concentration of Fluoride in Patients with Alcoholic Liver Cirrhosis from the Lublin Region in Eastern Poland.

In view of previous reports, it is important to determine the relationship between liver function and the level of fluoride in the serum. The aim of this study was to investigate serum concentrations of fluoride in 72 patients with alcoholic liver cirrhosis, living in the region of Lublin (Eastern Poland) divided based on the severity of disease according to the Child-Turcotte-Pugh criteria. Higher plasma fluoride concentrations were associated with changes in liver related parameters. In all groups of analyzed patients with different stages of alcoholic liver cirrhosis, elevated levels of plasma fluoride and increased activities of both alanine aminotransferase (ALT) and total bilirubin concentration were shown.

Epidermal Growth Factor Receptor and its Oncogenic EGFRvIII Variant in Benign and Malignant Brain Tumors.

BACKGROUND/AIM: Tumorigenesis and cancer progression might be driven by abnormal activation of growth factor receptors. Importantly, molecular changes in EGFR-dependent signaling is one of the most common characteristics of brain tumors. PATIENTS AND METHODS: HER1 and EGFRvIII variants in meningiomas and glioblastomas were evaluated at the RNA level. RESULTS: EGFRvIII was found in 18.6% of glioblastomas (GBM), whereas 25% of EGFRvIII positive tumors express wild-type EGFR as well. HER1 was over-expressed in benign meningiomas compared to glioblastomas, whereas HER1 expression in meningiomas differed significantly between sub-types of meningiomas. EGFRvIII and HER1 where positively correlated in glioblastomas. Yet, the patient overall survival did not differ between high- and low-HER1 expressing glioblastomas or between EGFRvIII positive and negative GBMs. CONCLUSION: HER1 may be considered as an independent factor for classification of benign meningiomas. The mRNA levels of HER1 or EGFRvIII should not be used as independent prognostic factors for patients with gliomas.

Assessment of Changes over Time of Lipid Profile, C-Reactive Protein Level and Body Mass Index in Teenagers and Young Adults on Different Diets Belonging to Autism Spectrum Disorder.

BACKGROUND: Numerous scientific studies on patients with autism spectrum disorder (ASD) suggest a significant role of inflammation processes or lipid disorders in this spectrum of neurodevelopmental disorders. Unfortunately, there is a lack of assessments of changes over time regarding level of lipids and inflammatory markers in people diagnosed with ASD using different diets. The aim of this study was to evaluate changes in lipid profile, high sensitivity C-reactive protein (hs-CRP) and body mass index (BMI) in individuals diagnosed with ASD and healthy controls. Variables were assessed at two time points (2015/17 and 2017/20) for each subject. METHODS: After applying the selection criteria, for the first assessment period, 96 participants were qualified (the group consisted of 59 males with ASD and 37 healthy volunteers, i.e., age-matched control group-CG). The final assessment included 93 participants (57 from ASD group and 36 from CG). Subjects were on low-fat diet (LFD), gluten-casein-free diet (GF-CF) and regular diet (RD), respectively. All members of CG were on regular diet. A fasting lipid profile and hs-CRP level were analyzed. BMI and percentiles were calculated. Eating habits were checked by analyzing data from questionnaires. Principal component analysis (PCA) was used separately for every assessment. The Mann-Whitney U test was used to compare the medians of variables in the scheme of pairwise comparisons between control and ASD groups on different diets for separate assessment, while differences over time between variables were tested by Wilcoxon signed-rank test. RESULTS: Statistically significant differences between BMI, CRP, triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL), non-HDL-C and TC/HDL ratio were found in ASD group in comparison to healthy volunteers (increased BMI, CRP and TC/HDL and decreased HDL-C for all types of diets, increased TG in the group of LFD and RD individual and increased non-HDL-C in the group of GF-CF and RD individuals) during the first assessment period. The second assessment over time also showed increased levels of TC, non HDL-C and TC/HDL and decreased level of HDL-C for all ASD individuals regardless of diets used, while BMI and CRP increased only for individuals on LFD and RD. No statistically significant correlations between age of participants and other variables comparing with CG were found. CONCLUSIONS: Our studies suggest that targeted, individualized nutritional pattern and periodic screening for lipid and immune disorders would be beneficial for teenagers and adults diagnosed with ASD.

MMP-2 mRNA Expression in Ovarian Cancer Tissues Predicts Patients' Response to Platinum-Taxane Chemotherapy.

BACKGROUND/AIM: Ovarian cancer is the most frequent cause of death in women among gynecological cancers in Poland. MMP-2 and MMP-9 are frequently dysregulated in cancers and they are considered as potential biomarkers. Our goal was to assess the associations between MMP-2 and MMP-9 mRNA expression, clinicopathological parameters and patients' response to chemotherapy. MATERIALS AND METHODS: We evaluated MMP-2 and MMP-9 mRNA expression in epithelial ovarian cancer (EOC) tissues from 44 untreated patients, four ovarian cancer cell lines, and human skin fibroblasts (HSF). The expression of both MMPs was estimated using qPCR. RESULTS: MMP-2 expression was significantly higher (p=0.020) in EOCs sensitive to chemotherapy compared to resistant and refractory tumors. The highest MMP-2 expression was found in HSF and MMP-9 expression was the highest in EOCs (p<0.001). The expression of neither MMP was significantly associated with patients' overall survival (OS). CONCLUSION: MMP-2 may be engaged in early stages of ovarian carcinogenesis. MMP-2 expression in EOCs may discriminate patients with a favorable response to first line chemotherapy.

Heat Shock Proteins as a Potential Therapeutic Target in the Treatment of Gestational Diabetes Mellitus: What We Know so Far.

Gestational diabetes mellitus (GDM) is a complex condition that involves a variety of pathological mechanisms, including pancreatic ß-cell failure, insulin resistance, and inflammation. There is an increasing body of literature suggesting that these interrelated phenomena may arise from the common mechanism of endoplasmic reticulum (ER) stress. Both obesity-associated nutrient excess and hyperglycemia disturb ER function in protein folding and transport. This results in the accumulation of polypeptides in the ER lumen and impairs insulin secretion and signaling. Exercise elicits metabolic adaptive responses, which may help to restore normal chaperone expression in insulin-resistant tissues. Pharmacological induction of chaperones, mimicking the metabolic effect of exercise, is a promising therapeutic tool for preventing GDM by maintaining the body's natural stress response. Metformin, a commonly used diabetes medication, has recently been identified as a modulator of ER-stress-associated inflammation. The results of recent studies suggest the potential use of chemical ER chaperones and antioxidant vitamins as therapeutic interventions that can prevent glucose-induced ER stress in GDM placentas. In this review, we discuss whether chaperones may significantly contribute to the pathogenesis of GDM, as well as whether they can be a potential therapeutic target in GDM treatment.

Cyclin I mRNA expression correlates with kinase insert domain receptor expression in human epithelial ovarian cancer.

BACKGROUND/AIM: Ovarian cancer is the second most common gynecological malignancy after cancer of the uterine corpus, and the fifth leading cause of cancer-related death among women. It has been discovered that cyclin I (CCNI) protein expression correlates with the proliferation of cancer cells and expression of angiogenesis-related proteins, such as vascular endothelial growth factor (VEGF) and VEGF receptor 2/kinase insert domain receptor (VEGFR2/KDR). We examined whether any association exists between mRNA expression of CCNI and KDR genes in epithelial ovarian cancer (EOC) tissues, clinicopathological parameters and patients' response to chemotherapy. MATERIALS AND METHODS: Expression of CCNI and KDR genes was analyzed by quantitative real-time reverse transcription PCR in 40 human primary EOC tissues and four human ovarian cancer cell lines (TOV-112D, OV-90, OVCAR-3 and Caov-3). RESULTS: CCNI and KDR mRNA expression was detected in all EOC tissues and ovarian cancer cell lines. The mRNA levels of both genes were significantly higher in EOC than in ovarian cancer cell lines (p<0.001). Neither CCNI nor KDR mRNA expression in EOC tissues was significantly associated with variables such as age, menopausal status, International Federation of Gynecology and Obstetrics (FIGO) stage, residual disease, patients' response to chemotherapy, tumor histology, grade or sensitivity to chemotherapy. However, we demonstrated a significant positive correlation between the mRNA expression of KDR and CCNI in EOC tissues (R=0.530, p<0.001). CONCLUSION: Neither CCNI nor KDR mRNA expression predicts response of patients with EOC to platinum-based first-line chemotherapy. Cyclin I may be involved in angiogenesis in EOC, which needs further investigation.

[Single nucleotide polymorphisms in lung cancer patients and cisplatin treatment]. / Polimorfizm pojedynczych nukleotydów u pacjentów chorych na raka pluca a leczenie cisplatyna.

Lung cancer is a major cause of mortality worldwide and non-small cell lung cancer (NSCLC) accounts for over 80% of all cases of lung cancer. Despite efforts to develop and improve early screening methods, the majority of tumors are detected at advanced stages. For over 30 years, cisplatin (CDDP), or any of its analogues, has been used in the treatment of many types of tumors, including lung cancer. The use of platinum-based chemotherapeutics is limited by their toxicity and later on by the development of chemoresistance by tumor cells. The molecular mechanisms of CDDP resistance are not fully resolved. Genetic variants of DNA repair proteins, as well as proteins involved in drug accumulation or detoxification, play a crucial role in determining the cell's response to platinum-based chemotherapy. The identification of selected gene polymorphisms could improve the prognosis of a patient's response to therapy and overall survival. In this review we will focus on the gene polymorphisms involved in CDDP resistance, in particular in lung tumors, and discuss their potential as prognosis and survival markers.

MicroRNAs-role in lung cancer.

Regulation of gene expression is essential for normal physiological functions; thus deregulation of gene expression is common in disease conditions. One level of regulation of gene expression is performed by noncoding RNAs, among which microRNAs (miRNA) are the best studied. Abnormal expression of these molecular players can lead to pathogenic processes such as heart disease, immune system abnormalities, and carcinogenesis, to name but a few. Of a length of 18-25 nucleotides miRNAs are involved in binding partial complementary sequences within the 3'-UTR (3'-untranslated region) of the target mRNAs. Depending on the type of neoplastic transformation, miRNAs can act both as oncogenes (oncomirs) or as tumor suppressors. Because of the great importance of miRNAs, most researches focus on either their role as biomarkers or their potential as therapeutic targets. Herein, we present the review of microRNA biology, function, and tumorigenic potential with emphasis on their role in lung cancer.