Youngsook Yoon

Pattern of antioxidant and DNA repair gene expression in normal airway epithelium associated with lung cancer diagnosis

In previous studies, we reported that key antioxidant and DNA repair genes are regulated differently in normal bronchial epithelial cells of lung cancer cases compared with non-lung cancer controls. In an effort to develop a biomarker for lung cancer risk, we evaluated the transcript expressions of 14 antioxidant, DNA repair, and transcription factor genes in normal bronchial epithelial cells (HUGO names CAT, CEBPG, E2F1, ERCC4, ERCC5, GPX1, GPX3, GSTM3, GSTP1, GSTT1, GSTZ1, MGST1, SOD1, and XRCC1). A test comprising these 14 genes accurately identified the lung cancer cases in two case-control studies. The receiver operating characteristic-area under the curve was 0.82 (95% confidence intervals, 0.68-0.91) for the first case-control set (25 lung cancer cases and 24 controls), and 0.87 (95% confidence intervals, 0.73-0.96) for the second set (18 cases and 22 controls). For each gene included in the test, the key difference between cases and controls was altered distribution of transcript expression among cancer cases compared with controls, with more lung cancer cases expressing at both extremes among all genes (Kolmorogov-Smirnov test, D = 0.0795; P = 0.041). A novel statistical approach was used to identify the lower and upper boundaries of transcript expression that optimally classifies cases and controls for each gene. Based on the data presented here, there is an increased prevalence of lung cancer diagnosis among individuals that express a threshold number of key antioxidant, DNA repair, and transcription factor genes at either very high or very low levels in the normal airway epithelium.

CEBPG transcription factor correlates with antioxidant and DNA repair genes in normal bronchial epithelial cells but not in individuals with bronchogenic carcinoma

BackgroundCigarette smoking is the primary cause of bronchogenic carcinoma (BC), yet only 10–15% of heavy smokers develop BC and it is likely that this variation in risk is, in part, genetically determined. We previously reported a set of antioxidant genes for which transcript abundance was lower in normal bronchial epithelial cells (NBEC) of BC individuals compared to non-BC individuals. In unpublished studies of the same NBEC samples, transcript abundance values for several DNA repair genes were correlated with these antioxidant genes. From these data, we hypothesized that antioxidant and DNA repair genes are co-regulated by one or more transcription factors and that inter-individual variation in expression and/or function of one or more of these transcription factors is responsible for inter-individual variation in risk for BC.MethodsThe putative transcription factor recognition sites common to six of the antioxidant genes were identified through in silico DNA sequence analysis. The transcript abundance values of these transcription factors (n = 6) and an expanded group of antioxidant and DNA repair genes (n = 16) were measured simultaneously by quantitative PCR in NBEC of 24 non-BC and 25 BC individuals.ResultsCEBPG transcription factor was significantly (p < 0.01) correlated with eight of the antioxidant or DNA repair genes in non-BC individuals but not in BC individuals. In BC individuals the correlation with CEBPG was significantly (p < 0.01) lower than that of non-BC individuals for four of the genes (XRCC1, ERCC5, GSTP1, and SOD1) and the difference was nearly significant for GPX1. The only other transcription factor correlated with any of these five target genes in non-BC individuals was E2F1. E2F1 was correlated with GSTP1 among non-BC individuals, but in contrast to CEBPG, there was no significant difference in this correlation in non-BC individuals compared to BC individuals.ConclusionWe conclude that CEBPG is the transcription factor primarily responsible for regulating transcription of key antioxidant and DNA repair genes in non-BC individuals. Further, we conclude that the heavy smokers selected for development of BC are those who have sub-optimal regulation of antioxidant and DNA repair genes by CEBPG.

CEBPG Exhibits Allele-Specific Expression in Human Bronchial Epithelial Cells.

Inter-individual variation in CCAAT/enhancer binding protein gamma (CEBPG) transcript expression in normal human bronchial epithelial cells (NBEC) is associated with predisposition to lung cancer. We hypothesize that this inter-individual variation is in part explained by cis-acting genetic variation in CEBPG. To test this hypothesis we measured transcript expression derived from each parental copy of CEBPG (ie, allele-specific expression; ASE). There was a significant 2.9-fold higher cell cycle-specific variation in ASE of CEBPG rs2772 A compared to C allele (P < 0.001). In 20% of NBEC samples, CEBPG rs2772 A allele was expressed on average 2.10 fold greater than rs2772 C allele. These data support the hypothesis that genetic variation in linkage disequilibrium with rs2772 influences regulation of CEBPG transcript expression through a trans-effect downstream of RNA polymerase II transcription and confirm that cis-acting genetic variation contributes to inter-individual variation in CEBPG transcript expression in NBEC, which is associated with variation in lung cancer risk.

A Literature Review Revisiting Phenytoin-Induced Sinus Arrest.

Classically, phenytoin (PTN) infusion for the treatment of status epilepticus has been proven to be associated with cardiovascular toxicity, including dysrhythmias, hypotension, and cardiovascular collapse. Subsequently, fosphenytoin (FOS) was introduced on the market in 1997 with claims of having less cardiac toxicity. However, since then, many accounts of cardiac events have been reported undermining these claims. FOS gained popularity due to its water solubility, which allows 3 times faster infusion in comparison with PTN with less venous irritation and local toxicity. FOS is the phosphate ester prodrug of PTN and is rapidly converted to PTN independent of the dose and rate of administration. Intravenous FOS and PTN are bioequivalent. Adverse cardiac effects of both intravenous FOS and PTN have been correlated to the rate of infusion, concentration of the agent, known risk factors, or pre-existing hypersensitivity, and most cases have been identified after infusing a loading dose of these medications. This case report is unique, in that, the patient developed sinus arrest while concurrently receiving oral PTN and intravenous FOS. Clinicians should be more cognizant of the association of FOS and PTN with adverse cardiac events. Baseline electrocardiogram should be obtained on all patients prescribed FOS or PTN to identify underlying cardiac problems that may place the patient in a higher risk category. Telemetry should be performed on all patients receiving PTN in an inpatient setting.

Long Esophageal Stricture in a Brittle Diabetic

Aim: We report a case of atypical esophageal stricture in a young diabetic woman. Background: Diabetes mellitus and gastroesophageal reflux disease (GERD) are two common disorders in modern society. Case report: A young diabetic woman developed a 6-cm-long esophageal stricture. This stricture was refractory to multiple esophageal dilation procedures. She underwent subtotal esophagectomy and had excellent treatment outcome. Conclusion: Gastroesophageal reflux disease can cause severe long esophageal stricture in a brittle diabetic. Clinical significance: Improving the awareness of their association between diabetes and GERD would greatly benefit the day-to-day practice of medicine. How to cite this article: Pak SC, Darr U, Alastal Y, Yoon Y. Long Esophageal Stricture in a Brittle Diabetic. Euroasian J Hepato-Gastroenterol 2017;7(2):191-192.