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In this study, profiles of epidermal growth factor receptor (EGFR) and Kirsten ras sarcoma (KRAS) mutations and response to erlotinib therapy have been investigated in patients with non-small cell lung cancer (NSCLC). DNA from 300 patients with NSCLC was extracted from paraf-fin-embedded tissues. After the extracted DNA was sequenced by pyrosequencing method, a total of 97 (32.0%) patients out of 300 were detected to carry an EGFR mutation and 75 (25.0%) patients out of 300 carried a KRAS mutation; 20 (6.6%) patients were detected to carry both of EGFR and KRAS mutations. The EGFR mutations were found to be statistically significant in female patients (48.0 women vs. 28.0% men, non smokers (49.0 vs. 26.0%) and adenocarcinoma (37.8 vs. squamous 26.8%). The overall rate of survival in patients receiving erlotinib therapy than in patients who did not. In patients without the KRAS mutation, the median overall survival rate was 161 ± 30 weeks with erlotinib therapy and 90 ± 13 weeks in patients without erlotinib therapy. In patients having KRAS mutation, the median overall survival was 98 ± 16 weeks with erlotinib therapy and 34 ± 16 weeks with no erlotinib therapy. In our study, we once again demonstrated that the presence of these mutations affected response to erlotinib therapy. The KRAS mutations negatively affected survival rate with and without erlotinib therapy.

Acute myeloid leukemia (AML) was first categorized in 1976 by French, American and British researchers, and divided into eight subgroups (M0 to M7), depending on the cytochemical or histological changes in the leukemic cells. The gene mutations of FLT3-ITD, CEBPA and NPM1 are the most common that cooperate together in the prognosis of AML. The CEBPA gene that is a hematopoietic transcription factor, is located on chromosome 19q13.11, and its prevalence is between 5.0 and 14.0% in AML. The patient was referred to our clinic suffering from menorrhagia, unplanned weight loss in a month and low platelet levels, and was diagnosed with AML on clinical and laboratory examination. Here, we report a patient carrying two novel pathogenic mutations that create a frameshift mutation on the CEBPA gene, c.940_941insCCGTCG TGGAGACGA CGAAGG and c.221_222delAC by Sanger sequencing methodology.

Mouse fetuses generated by in vitro embryo culture and embryo transfer exhibit impaired lung development, altered composition of pulmonary epithelial cells associated with downregulation of several genes involved in lung development and toll-like receptor (TLR) signaling pathway. The aims of the present study were to determine the expression of all TLRs and to examine if the expression of TLRs, along with genes involved in TLR signaling pathway, is altered in the lung tissue of mouse fetuses generated through embryo culture and embryo transfer. Two experimental (EGs) and one control (CG) group were included in the study. Embryos cultured at 5% CO2-95% air for 95 h or less than 24 h were transferred to pseudo-pregnant females to obtain fetuses comprising EGin vitro (n = 18) and EGin vivo (n = 18), respectively. Fetuses obtained from naturally ovulating females on day 18 of pregnancy served as the CG (n = 18). Western blot and immunohistochemistry were used to determine the expression of TLR proteins. The expression of transcripts encoding TLRs, and the genes involved in TLR signaling pathway (Lbp, Pik3r1, Pik3cb, Nfkbia, and Fos), was determined using qRT-PCR. While all TLRs were expressed by cells lining the bronchial/bronchiolar epithelium of lung tissues in all groups, some of the TLRs were expressed in a specific pattern. When compared to CG, the expression of transcripts encoding TLR-2, -3, -4, -5, -7, -8, -9, -12, -13, Lbp, Pik3r1, Pik3cb, Nfkbia, and Fos was significantly downregulated in both EGs. It appears that stress imposed on embryos at preimplantation stages of development is associated with downregulation of TLRs, along with some of the genes involved in TLR signaling pathway, in the lung tissue during the perinatal period. It remains to be determined if downregulation of TLRs, along with the genes involved in TLR signaling pathway, has any functional consequences in the adult lung tissue., (© 2023 S. Karger AG, Basel.)

In vitro culture under atmospheric oxygen puts embryos under oxidative stress and impairs preimplantation development. However, to what extent this process alters the redox balance in the perinatal period remains largely unknown. The aim of the present study was to examine if the redox balance is altered in the lung tissue of fetuses generated through transfer of mouse embryos exposed to atmospheric oxygen at different stages of development and to determine if this has any effect on lung morphogenesis and gene expression. Two experimental groups (EGs) were generated by transferring in vitro- and in vivo-derived blastocysts to pseudo-pregnant females. In vivo-developed fetuses served as control. Enzymatic/nonenzymatic antioxidants, malondialdehyde (MDA) levels, total antioxidant capacity, stage of lung development and gene expression were evaluated on day 18 of pregnancy. Weight of fetuses was significantly less in both experimental cohorts (ANOVA, P < 0.001 versus control), associated with delayed lung development, higher amounts of MDA (ANOVA, P < 0.001 versus control) and altered expression of several genes in oxidative stress/damage pathways. Evidence gathered in the present study indicates that pre-implantation stress caused by culture under atmospheric oxygen, even for a short period of time, leads to fetal growth restriction, impaired lung development and redox balance along with dysregulation of several genes in oxidative stress response. Absence of an EG in which in vitro embryo culture was performed at 5% oxygen and the use of genetically heterogeneous F2 fetuses are the limitations of the study. In any case, the long-term impact of such dramatic changes in the developmental programming of resulting fetuses warrants further investigations., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Background: The aim of this study was to elucidate a possible source of oxidant stress in experimental sepsis., Methods: For this aim, 32 Sprague-Dawley type rats were used in the study. After all the animals underwent laparotomy, nonlethal cecum ligation and puncture (CLP) technique was used to create an experimental sepsis model in two groups (CLP-6 and CLP-48 groups). Rats in the other groups (Sham operated) were used as controls. Animals in the control-6 and CLP-6 groups were killed 6 hours after the beginning of the study whereas the other animals were killed 48 hours after the beginning. Part of the terminal ileum of each animal was removed to be used in the measurements of xanthine oxidase and superoxide dismutase enzyme activities., Results: Xanthine oxidase activity in the CLP-48 group was found to increase significantly as compared with that of the control-48 group, but superoxide dismutase activity did not change. No significant changes, however, were observed between analysis parameters in the terminal ileum tissues when obtained 6 hours after the beginning of sepsis., Conclusion: Our results suggest that increased xanthine oxidase activity is one of the leading factors for the oxidant stress in the late phase of sepsis.

Background & Objectives: The aim of this study was to investigate LDL oxidation in the ethiopathogenesis of diabetes mellitus. Diabetes mellitus a disease caused due to severe insulin dysfunction, is associated with lipid and protein metabolic disorders., Methods: A total of 90 type 2 diabetes patients were grouped according to their glycoted haemoglobin (HbA1c) values as regulated (<5.7%), poorly regulated (5.7 - 7.7%) and unregulated (>7.7%). Further, a healthy control group of 37 individuals was included for comparison in terms of sensitivity of low density lipoprotein (LDL) to oxidation and measurements of antioxidant potential (AOP). A heparin - citrate precipitation method was used to obtain LDL from the serum samples of patients and control groups. The LDL fractions were exposed to oxidation with CuSO4 and sensitivity to oxidation was evaluated. Ten patients each from regulated and unregulated groups, and 10 healthy controls were examined for antioxidant potential., Results: The sensitivity of LDL fraction to oxidation was significantly lower in all diabetic groups compared to the control group. AOP was significantly decreased in unregulated diabetic group compared to the control group., Interpretation & Conclusion: We hypothesize that oxidant stress increases in diabetes mellitus and oxidant defense systems weaken during the chronic course of the illness. Due to decreased antioxidant potential, that probably shortens the LDL oxidation lag phase, the sensitivity to oxidation appears to be lower in diabetes mellitus patients.