On Comparing Survival Curves with Right-Censored Data According to the Events Occur at the Beginning, in the Middle and at the End of Study Period

In clinical practice the event of interest does not always occur equally across the study time period. Depending on the disease being investigated, the event that is of interest can occur intensively in different periods of the follow-up time. In such cases, choosing the correct survival comparison test has importance. This study aims to examine and discuss the results of survival comparison tests under some certain circumstances. A simulation study was conducted. We discussed the result of different tests such as Logrank, Gehan-Wilcoxon, Tarone-Ware, Peto-Peto, Modified Peto-Peto tests and tests belonging to Fleming-Harrington test family with (p, q) values; (1, 0), (0.5, 0.5), (1, 1), (0, 1) ve (0.5, 2) by means of Type I error rate that obtained from simulation study, when the event of interest occurred intensively at the beginning of the study, in the middle of the study and at the end of the study time period. As a result of simulation study, Type I error rate of tests is generally lower or higher than the nominal value. In the light of the results, it is proposed to re-examine the tests for cases where events are observed intensively at the beginning, middle and late periods, to carry out new simulation studies and to develop new tests if necessary

EXAMINING TESTS FOR COMPARING SURVIVAL CURVES WITH RIGHT CENSORED DATA

Background and objective: In survival analysis, estimating the survival probability of a population is important, but on the other hand, investigators want to compare the survival experiences of different groups. In such cases, the differences can be illustrated by drawing survival curves, but this will only give a rough idea. Since the data obtained from survival studies contains frequently censored observations some specially designed tests are required in order to compare groups statistically in terms of survival. Methods: In this study, Logrank, Gehan-Wilcoxon, Tarone-Ware, Peto-Peto, Modified Peto-Peto tests and tests belonging to Fleming-Harrington test family with (p, q) values; (1, 0), (0.5, 0.5), (1, 1), (0, 1) ve (0.5, 2) are examined by means of Type I error rate obtained from a simulation study, which is conducted in the cases where the event takes place with equal probability along the follow-up time. Results: As a result of the simulation study, Type I error rate of Logrank test is equal or close to the nominal value. Conclusions: When survival data were generated from lognormal and inverse Gaussian distribution, Type I error rate of Gehan-Wilcoxon, Tarone-Ware, Peto-Peto, Modified Peto-Peto and Fleming-Harrington (1,0) tests were close to the nominal value

Effect of valproic acid on miRNAs affecting histone deacetylase in a model of anaplastic thyroid cancer

Background Thyroid cancer is the most common malignant tumor of the endocrine system seen in the thyroid gland. More than 90% of thyroid cancers comprise papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC). Although anaplastic thyroid carcinoma (ATC) accounts for less than 2% of thyroid cancer. But patients' lifespan after diagnosis is about 6 months. Surgical interventions, radioactive iodine use, and chemotherapy are not sufficient in the treatment of ATC, so alternative therapies are needed. Methods and results The WST-1 assay test was performed to evaluate the anti-proliferative effects of Valproic acid (VPA). Also, the effect of VPA on miRNAs affecting histone deacetylase was determined by Quantitative RT-PCR. In the SW1736 cell line, IC50 dose for VPA was found 1.6 mg/ml. In our study, the level of oncogenic genes expression in cells treated with VPA, including miR-184, miR-222-5p, miR-124-3p, and miR-328-3p, decreased. Also, the expression of tumor inhibitory genes including miR-323-5p, miR-182-5p, miR-138-5p, miR-217, miR-15a-5p, miR-29b-3p, miR-324-5p and miR-101-5p increased significantly. Conclusions VPA can ad-just countless gene expression patterns, including microRNAs (miRNAs), by targeting histone deacetylase (HDAC). However, further studies are required for more accurate results

The effects of Epigallocatechin-3-gallate and Dabrafenib combination on apoptosis and the genes involved in epigenetic events in anaplastic thyroid cancer cells

Anaplastic thyroid cancer cases with poor prognosis are associated with epigenetic modifications such as abnormal DNA methylation. Epigallocathesin-3-gallate (EGCG) is a polyphenol compound of green tea that is still under investigation on its role in cancer prevention. EGCG is known as an epigenetic diet in DNA methyltransferase inhibitor. The cytotoxic effects of Dabrafenib, EGCG, and dabrafenib in combination with EGCG were assessed by using WST-8 assay; and also, Flow cytometry was utilized to identify cells undergoing apoptosis after treatments of the SW-1736 cells. We investigated the mRNA expression of genes involved in epigenetic events in SW-1736 cells by real-time qRT-PCR following the treatments. We demonstrated for the first time that the Dabrafenib-EGCG combination reduced cell viability significantly depending on concentration and induced apoptosis by 8.49-fold through investigating the additive effect together on SW-1736 cells. The IC50 doses of Dabrafenib and EGCG for 48 h were determined as 6.7 mu M and 22.5 mu M, respectively. The results of qRT-PCR demonstrated that the Dabrafenib-EGCG combination significantly caused the down-regulation of genes involved in epigenetic regulation. We suggest that the combination of Dabrafenib and EGCG following in vivo phase studies will contribute as an alternative treatment option for the treatment of ATC.This study was supported by Ege University Research Foundation (Project no:TYL-2019-20389).Ege University Research Foundation [TYL-2019-20389

The Distinct Genetic Pattern of ALS in Turkey and Novel Mutations

The frequency of amyotrophic lateral sclerosis (ALS) mutations has been extensively investigated in several populations; however, a systematic analysis in Turkish cases has not been reported so far. In this study, we screened 477 ALS patients for mutations, including 116 familial ALS patients from 82 families and 361 sporadic ALS (sALS) cases. Patients were genotyped for C9orf72 (18.3%), SOD1 (12.2%), FUS (5%), TARDBP (3.7%), and UBQLN2 (2.4%) gene mutations, which together account for approximately 40% of familial ALS in Turkey. No SOD1 mutations were detected in sALS patients; however, C9orf72 (3.1%) and UBQLN2 (0.6%) explained 3.7% of sALS in the population. Exome sequencing revealed mutations in OPTN, SPG11, DJ1, PLEKHG5, SYNE1, TRPM7, and SQSTM1 genes, many of them novel. The spectrum of mutations reflect both the distinct genetic background and the heterogeneous nature of the Turkish ALS population. (C) 2015 Elsevier Inc. All rights reserved.Wo