• Title/Summary/Keyword: Chromosomal damage

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Increased Hypermethylation of Glutathione S-Transferase P1, DNA-Binding Protein Inhibitor, Death Associated Protein Kinase and Paired Box Protein-5 Genes in Triple-Negative Breast Cancer Saudi Females

  • Hafez, Mohamed M.;Al-Shabanah, Othman A.;Al-Rejaie, Salim S.;Al-Harbi, Naif O.;Hassan, Zeinab K.;Alsheikh, Abdulmalik;Theyab, Abdurrahman I. Al;Aldelemy, Meshan L.;Sayed-Ahmed, Mohamed M.
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.2
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    • pp.541-549
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    • 2015
  • Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC) with higher metastatic rate and both local and systemic recurrence compared to non-TNBC. The generation of reactive oxygen species (ROS) secondary to oxidative stress is associated with DNA damage, chromosomal degradation and alterations of both hypermethylation and hypomethylation of DNA. This study concerns differential methylation of promoter regions in specific groups of genes in TNBC and non-TNBC Saudi females in an effort to understand whether epigenetic events might be involved in breast carcinogenesis, and whether they might be used as markers for Saudi BCs. Methylation of glutathione S-transferase P1 (GSTP1), T-cadherin (CDH13), Paired box protein 5 (PAX5), death associated protein kinase (DAPK), twist-related protein (TWIST), DNA-binding protein inhibitor (ID4), High In Normal-1 (HIN-1), cyclin-dependent kinase inhibitor 2A (p16), cyclin D2 and retinoic acid receptor-${\beta}$ ($RAR{\beta}1$) genes was analyzed by methylation specific polymerase chain reaction (MSP) in 200 archival formalin-fixed paraffin embedded BC tissues divided into 3 groups; benign breast tissues (20), TNBC (80) and non-TNBC (100). The relationships between methylation status, and clinical and pathological characteristics of patients and tumors were assessed. Higher frequencies of GSTP1, ID4, TWIST, DAPK, PAX5 and HIN-1 hypermethylation were found in TNBC than in non-TNBC. Hypermethylation of GSTP1, CDH13, ID4, DAPK, HIN-1 and PAX5 increased with tumor grade increasing. Other statistically significant correlations were identified with studied genes. Data from this study suggest that increased hypermethylation of GSTP1, ID4, TWIST, DAPK, PAX5 and HIN-1 genes in TNBC than in non-TNBC can act as useful biomarker for BCs in the Saudi population. The higher frequency of specific hypermethylated genes paralleling tumor grade, size and lymph node involvement suggests contributions to breast cancer initiation and progression.

Protodioscin protects porcine oocytes against H2O2-induced oxidative stress during in vitro maturation

  • So-Hee Kim;Seung-Eun Lee;Jae-Wook Yoon;Hyo-Jin Park;Seung-Hwan Oh;Do-Geon Lee;Da-Bin Pyeon;Eun-Young Kim;Se-Pill Park
    • Animal Bioscience
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    • v.36 no.5
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    • pp.710-719
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    • 2023
  • Objective: The present study investigated whether protodioscin (PD), a steroidal saponin mainly found in rhizome of Dioscorea species, alleviates oxidative stress-induced damage of porcine oocytes during in vitro maturation. Methods: Oocytes were treated with different concentrations of PD (0, 1, 10, 100, and 200 µM) in the presence of 200 µM H2O2 during in vitro maturation. Following maturation, spindle morphology and mitogen-activated protein kinase activity was assessed along with reactive oxygen species level, GSH activity, and mRNA expression of endogenous antioxidant genes at the MII stage. On the day 7 after parthenogenetic activation, blastocyst formation rate was calculated and the quality of embryo and mRNA expression of development-related genes was evaluated. Results: Developmental competence was significantly poorer in the 0 µM PD-treated (control) group than in the non-treated (normal) and 10 µM PD-treated (10PD) groups. Although the reactive oxygen species level did not significantly differ between these three groups, the glutathione level and mRNA expression of antioxidant genes (superoxide dismutase 1 [SOD1], SOD2, nuclear factor erythroid 2-related factor 2 [Nrf2], and hemo oxygenase-1 [HO-1]) were significantly higher in the normal and 10PD groups than in the control group. In addition, the percentage of oocytes with defective spindle and abnormal chromosomal alignment was significantly lower and the ratio of phosphorylated p44/42 to total p44/42 was significantly higher in the normal and 10PD groups than in the control group. The total cell number per blastocyst was significantly higher in the 10PD group than in the control group. The percentage of apoptotic cells in blastocysts was highest in the control group; however, the difference was not significant. mRNA expression of development-related genes (POU domain, class 5, transcription factor 1 [POU5F1], caudal type homeobox 2 [CDX2], Nanog homeobox [NANOG]) was consistently increased by addition of PD. Conclusion: The PD effectively improves the developmental competence and quality of blastocysts by protecting porcine oocytes against oxidative stress.

Clinical Features of Cricopharyngeal Incoordination in Newborns and Infants (신생아 및 영아기 윤상인두 협조불능의 임상적 고찰)

  • Han, Young-Mi;Park, Jae-Hong
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.11 no.2
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    • pp.116-121
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    • 2008
  • Purpose: Cricopharyngeal incoordination is a rare cause of swallowing difficulties in newborns and infants; it is characterized by delayed pharyngeal contractions related to cricopharyngeal relaxation. Dysphagia and repeated aspiration are common findings despite normal sucking. We conducted this study to assess the clinical features of cricopharyngeal incoordination in newborns and infants. Methods: An analysis of the clinical data from 17 patients with cricopharyngeal incoordination who were admitted to the Department of Pediatrics, Pusan National University Hospital, between 2000 and 2006 was conducted retrospectively. The diagnosis of cricopharyngeal incoordination was established by the clinical characteristics and the videofluoroscopic swallowing studies. Results: The male to female ratio was 1:1.1 (males 8, females 9) the age range 1 to 60 days. The body weight of 11 patients (64.7%) was less than the $10^{th}$ percentile at diagnosis. Six patients (35.3%) were born prematurely. The associated anomalies or diseases were chromosomal anomaly (2 cases), congenital heart disease (3 cases), and laryngomalacia, hypoxic brain damage or neonatal seizures (1 case each). The chief complaints of patients were recurrent aspiration pneumonia (10 cases), feeding difficulty (9 cases), dyspnea (4 cases), and chocking (4 cases). The severity of aspiration on the videoesophagogram or esophagogram was mild in 12 cases. The correlation between the severity of aspiration and the duration of tube feeding after the diagnosis was significant (p<0.05). Conclusion: Cricopharyngeal incoordination should be considered in the differential diagnosis of newborns and infants, without known risk factors associated with swallowing dysfunction, when they present with unexplained respiratory problems. Although the prognosis of cricopharyngeal incoordination is good, early diagnosis and tube feeding are recommended to prevent the complications associated with this disorder.

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