17 research outputs found
Synthesis, characterization and biological activity of platinum(II) and palladium(II) complexes with quinoline derivatives of thiosemicarbazones
The aim of this study was to elucidate the structure, geometry and biological activity of platinum(II) and palladium(II) complexes with different quinoline derivatives of thiosemicar-bazones. Four novel platinum(II) and palladium(II) complexes with 2-quinolinecarboxaldehyde thiosemikarbazone (H2QATSC) and 8-quinolinecarboxaldehyde thiosemikarbazone (H8QATSC) were synthesized. The complexes of platinum(II) and palladium(II) with H2QATSC ligand, [PtCl(2QATSC)] (1) and [PdCl(2QATSC)] (2), were synthesized by direct reaction and charac-terized by single crystal X-ray analysis. The complexes of platinum(II) and palladium(II) with H8QATSC ligand, [PtCl(8QATSC)] (3) and [PdCl(8QATSC)] (4), were characterized by NMR spectroscopy. In the complexes 1–4 ligands are coordinated tridentately via the quinoline and imine nitrogen atoms and thiosemicarbazone sulfur atom, forming two five-membered rings with metal ion. The geometry around metal ions is square-planar, where chloride ion occupies fourth coordination site. Antitumor activity of the complexes 1–4 was investigated and com-pared with the activity of cisplatin
Comparative toxicity evaluation of targeted anticancer therapeutics in embryonic zebrafish and sea urchin models
Cancer drug resistance and poor selectivity towards cancer cells demand the constant search for new therapeutics. PI3K-Akt-mTOR and RAS-MAPK-ERK signaling pathways are key mechanisms involved in cell survival, proliferation, differentiation, and metabolism and their deregulation in cancer can promote development of therapy resistance. We investigated the effects of targeted inhibitors (wortmannin, GSK690693, AZD2014 and tipifarnib) towards these two pathways on early zebrafish and sea urchin development to assess their toxicity in normal, fast proliferating cells. PI3K inhibitor wortmannin and RAS inhibitor tipifarnib displayed highest toxicity while GSK690693, a pan-Akt kinase inhibitor, exhibited a less significant impact on embryo survival and development. Moreover, inhibition of the upstream part of the PI3K-Akt-mTOR pathway (wortmannin/GSK690693 co-treatment) produced a synergistic effect and impacted zebrafish embryo survival and development at much lower concentrations. Dual mTORC1/mTORC2 inhibitor AZD2014 showed no considerable effects on embryonic cells of zebrafish in concentrations substantially toxic in cancer cells. AZD2014 also caused the least prominent effects on sea urchin embryo development compared to other inhibitors. Significant toxicity of AZD2014 in human cancer cells, its capacity to sensitize resistant cancers, lower antiproliferative activity against human normal cell lines and fast proliferating embryonic cells could make this agent a promising candidate for anticancer therapy
The use of autologous fascia lata graft in the laparoscopic reinforcement of large hiatal defect: initial observations of the surgical technique
Primary inflammatory myofibroblastic tumor of the stomach in an adult woman: a case report and review of the literature
Short-term outcomes of laparoscopic radical gastrectomy for advanced gastric neoplasms: A single center experience
The burden of gastroesophageal reflux disease on patients’ daily lives: A cross-sectional study conducted in a primary care setting in Serbia
Gastroesophageal reflux disease and functional dyspepsia: What is the real burden on health-related quality of life?
The lack of genotype-phenotype relationship between platelet serotonin concentration and serotonin transporter gene promoter polymorphism in healthy subjects
A polymorphism in the serotonin transporter gene (5-HTTLPR) is frequently studied for association with antidepressant treatment response, different personality traits, and psychiatric disorders. Baseline platelet serotonin (5-HT) concentration has been proposed to indicate a good or a poor treatment response to antidepressant drugs and to be associated with particular symptoms in psychiatric disorders. The aim of the study was to elucidate the genotype-phenotype relationship between platelet 5-HT concentration and 5-HTTLPR in healthy subjects. The frequency of 5-HTTLPR genotypes and alleles, as well as platelet 5-HT concentration was evaluated in 434 male and 86 female unrelated healthy medication-free Caucasian subjects of Croatian origin. A two-way ANOVA revealed no significant difference in platelet 5-HT concentration subdivided according to the particular 5-HTTLPR genotype, no significant effect of sex, no significant effect of genotype, and no significant interaction between sex and genotype on platelet 5-HT concentration. In addition, one-way ANOVA did not detect significant effects of homozygous S/S genotype, or homozygous L/L genotype on platelet 5-HT concentration. Our results showed a lack of significant association between platelet 5-HT concentration and 5-HTTLPR variants, suggesting that there is no functional relationship between 5-HTTLPR alleles and platelet 5-HT concentration in the large groups of healthy male and female medication-free Caucasian subjects, free of neuro-psychiatric disorders
Estradiol decreases blood pressure in association with redox regulation in preeclampsia
In this study, we tested a hypothesis that a short-term estradiol therapy may reduce blood pressure in preeclampsia by modulating plasma oxidative stress. The intramuscular injections of 10 mg 17-beta-estradiol were prescribed to preeclamptic pregnant women during the 3-day therapy before a labor induction. The analyses of mean arterial pressure (MAP), serum estradiol concentrations, plasma superoxide anion (O2.), hydrogen peroxide (H2O2), nitrites (NO2−), and peroxynitrite (ONOO−) were conducted before and during the therapy. We found that the plasma concentrations of oxidative stress markers, such as O2– and H2O2, are higher in preeclampsia and positively correlated with the MAP value. Moreover, it was shown that the plasma concentration of NO2– as an indicator of NO levels is higher in preeclampsia. A short-term intramuscular application of estradiol decreases the MAP value and the plasma concentration of O.–, H2O2, NO2−, and ONOO– in preeclampsia. A positive correlation between the decrease of MAP values and the decrease of plasma concentrations of O2–, H2O2, and ONOO– was found in preeclampsia during a short-term estradiol therapy. We conclude that the short-term estradiol therapy decreases the MAP value in preeclampsia by modulating the plasma oxidative stress. We speculate that the estradiol metabolism in preeclampsia is an important mechanism that contributes to vascular dysfunction