In recent years, phthalocyanines (Pcs) have been widely used as photosensitizer in photodynamic therapy applications. Because of their strong absorptions in the near-infrared region (640-700 nm). The integration of phthalocyanine derivatives to a nanoparticle is expected to be efficient way to improve the activity of the photosensitizer on the targeted tissue. It is known that the integrated molecules not only show better accumulation on tumor tissue but also reduce toxicity in healthy tissues. In this study, the ZnPc molecule was synthesized and integrated to the TiO nanoparticle, to investigate the potential of PDT and its cytotoxicity. Additionally, ZnPc and ZnPc-TiO molecules were labeled with I and it was aimed to put forth the nuclear imaging/therapy potentials of I labeled ZnPc/ZnPc-TiO by determining in vitro uptakes in mouse mammary carcinoma (EMT6), human cervical adenocarcinoma (HeLa). In result of our study, it was observed that the radiolabeling yields of the synthesized ZnPc and ZnPc-TiO with I were quite high. In vitro uptake studies shown that I-ZnPc-TiO could be a potential agent for nuclear imaging/treatment of breast and cervical cancers. According to PDT results, ZnPc-TiO might have as to be a potential PDT agent in the treatment of cervical tumor. ZnPc and ZnPc-TiO might be used as theranostic agents.
Ruxolitinib is the first agent used in myelofibrosis treatment with its potent JAK2 inhibitory effect. In this novel study, we aimed to discover the anti-leukemic effect of ruxolitinib in K-562 human chronic myeloid leukemia cell line compared to NCI-BL 2171 human healthy B lymphocyte cell line. Cytotoxic effect of ruxolitinib was determined by using WST-1 assay. IC50 values for K-562 and NCI-BL 2171 cell lines were defined as 20 and 23.6 μM at the 48th hour, respectively. Autophagic effects of ruxolitinib were detected by measuring LC3B-II protein formation. Ruxolitinib induced autophagic cell death in K-562 and NCI-BL 2171 cell lines 2.11- and 1.79-fold compared to control groups, respectively. To determine the autophagy-related gene expression changes, total RNA was isolated from K-562 and NCI-BL 2171 cells treated with ruxolitinib and untreated cells as control group. Reverse transcription procedure was performed for cDNA synthesis, and gene expressions were shown by RT-qPCR. Ruxolitinib treatment caused a notable decrease in expression of AKT, mTOR, and STAT autophagy inhibitor genes in K-562 cells, contrariwise control cell line. Ruxolitinib is a promising agent in chronic myeloid leukemia treatment by blocking JAK/STAT pathway known as downstream of BCR-ABL and triggering autophagy. This is the first study that reveals the relationship between ruxolitinib and autophagy induction.
Aims: Acute myocarditis is an inflammatory disease of the myocardium and is characterized by a large heterogeneity of clinical presentation. Myocarditis is becoming to be recognized as a contributor to unexplained mortality, and is thought to be a major cause of sudden cardiac death in the first two decades of life. Myocardial inflammation, ion channel dysfunction, electrophysiological and structural remodelling may play important roles in life-threatening arrhythmias. We aimed to investigate the ventricular arrhythmia predictors in myocarditis patients by using electrocardiographic markers. Methods: A total of 56 patients (mean age 22.5 ± 3.7 years; 89% males) with acute myocarditis were enrolled in the study. Tpeak-Tend intervals, Tpeak-Tend/QT and Tpeak-Tend/corrected QT (QTc), cardio-electrophysiological balance (QT/QRS) and heart rate-corrected QT(QTc)/QRS ratios were calculated from 12-lead electrocardiogram. Results: Heart rate, QT and QTc values were similar between groups. QRS complexes were lower in arrhythmia positive group than arrhythmia negative group (p=0.004). Tpeak-Tend intervals, Tpeak-Tend/QT, Tpeak-Tend/ QTc, cardio-electrophysiological balance and heart rate-corrected QT(QTc)/QRS values were significantly higher in arrhythmia positive group (< 0.001, < 0.001, p=0.03, p=0.04 and < 0.001, respectively). Conclusion: In this study, we observed that higher Tpeak-Tend, Tpeak-Tend/QT, Tpeak-Tend/QTc , cardio-electrophysiological balance (ICEB) and heart rate-corrected QT(QTc)/QRS ratio are associated with ventricular arrhythmic episodes in acute myocarditis patients. These electrocardiographic markers may be beneficial to identify high risk patients for arrhytmias complicating myocarditis.
Anaplastic cancer constitutes 1% of thyroid cancers, and it is one of the most aggressive cancers. Treatment options are external radiation therapy and/or chemotherapy. The success rate with these treatment modalities is not satisfactory. We aimed to evaluate the effects of metformin (MET) and pioglitazone (PIO) combination on apoptosis and AMP-activated protein kinase/mammalian target of rapamycin (mTOR) signaling pathway in human anaplastic thyroid cancer cells. In this study, we evaluated the effects of MET and PIO individually and the combination of the two drugs on the cellular lines SW1736 and C643 ATC. Genes contained in the mTOR signaling pathway were examined using human mTOR Signalization RT 2 Profiler PCR Array. In C643 and SW1736 cell lines, IC 50 doses of MET and PIO were found out as 17.69 mM, 11.64 mM, 27.12 µM, and 23.17 µM. Also, the combination of MET and PIO was determined as an additive according to isobologram analyses. We have found the downregulation of the expression levels of oncogenic genes:
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