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Expression and mutational analysis of TGF-β/Smads signaling in human cervical cancers
기경도,동서연,허주엽,이선경,지성길,이종민 대한부인종양학회 2009 Journal of Gynecologic Oncology Vol.20 No.2
Objective: To define the molecular basis of TGF-β1 function in cervical carcinogenesis, we explored the expression and mutational status of TGF-β1, TGF-β1 receptors, and Smads, the regulators of the TGF-β1 signaling pathway, in human cervical cancers. Methods: Expression of TGF-β1, TGF-β1 receptors, and Smads transcripts were determined by quantitative reverse transcription-polymerase chain reaction (RT-PCR), and sequence alteration was analyzed using RT-PCR-single-strand conformation polymorphism (SSCP) analysis. Genomic levels of TGF-β1, TGF-β1 receptors and Smads was also measured by quantitative genomic PCR. Results: Abnormal overexpression of TGF-β1 and abnormal reduction of type II TGF-β1 receptor were identified in 36% (18 of 50) and 20% (10 of 50) of cervical cancer tissues, respectively. 22% (11 of 50) in Smad2 and 14% (7 of 50) in Smad4 revealed tumor specific mRNA reduction less than a half of normal means. In addition, no evidence for sequence alterations of the gene was found by RT-PCR-SSCP analysis. Conclusion: Our study demonstrates that disruption of TGF-β/Smad signaling pathway exist in human cervical cancer, suggesting that abnormal expressions of the member of TGF-β/Smad signaling pathway might contribute to the malignant progression of human cervical tumors via suppressing the tumor suppression function of TGF-β1 1's tumor suppression function. Objective: To define the molecular basis of TGF-β1 function in cervical carcinogenesis, we explored the expression and mutational status of TGF-β1, TGF-β1 receptors, and Smads, the regulators of the TGF-β1 signaling pathway, in human cervical cancers. Methods: Expression of TGF-β1, TGF-β1 receptors, and Smads transcripts were determined by quantitative reverse transcription-polymerase chain reaction (RT-PCR), and sequence alteration was analyzed using RT-PCR-single-strand conformation polymorphism (SSCP) analysis. Genomic levels of TGF-β1, TGF-β1 receptors and Smads was also measured by quantitative genomic PCR. Results: Abnormal overexpression of TGF-β1 and abnormal reduction of type II TGF-β1 receptor were identified in 36% (18 of 50) and 20% (10 of 50) of cervical cancer tissues, respectively. 22% (11 of 50) in Smad2 and 14% (7 of 50) in Smad4 revealed tumor specific mRNA reduction less than a half of normal means. In addition, no evidence for sequence alterations of the gene was found by RT-PCR-SSCP analysis. Conclusion: Our study demonstrates that disruption of TGF-β/Smad signaling pathway exist in human cervical cancer, suggesting that abnormal expressions of the member of TGF-β/Smad signaling pathway might contribute to the malignant progression of human cervical tumors via suppressing the tumor suppression function of TGF-β1 1's tumor suppression function.
기경도,이종민,이선경,동서연,허주엽,류정규,김교영 대한의학회 2010 Journal of Korean medical science Vol.25 No.2
Pulmonary toxicity is one of the most serious adverse effects associated with a quick course of vincristine, bleomycin, and cisplatin neoadjuvant chemotherapy (NACVBP). The aim of this study was to evaluate pulmonary toxicity related to a quick course NAC-VBP. A total of consecutive 61 patients, who underwent at most 3 cycles of NAC-VBP every 10 days in the International Federation of Gynecology and Obstetrics (FIGO) stage IB-IIB cervical cancer from 1995 to 2007, were retrospectively analyzed. Of the 61 study subjects, 7 (11.5%) were identified to have pulmonary toxicity and 2 (3.3%) died of pulmonary fibrosis progression despite aggressive treatment and the use of a multidisciplinary approach. No factor predisposing pulmonary toxicity was identified. Initial symptoms were non-specific, but bronchiolitis obliterans organizing pneumonia and interstitial pneumonitis were characteristic findings by high-resolution computed tomography of the chest. The benefit of steroid therapy was uncertain and was associated with steroid-induced diabetes mellitus requiring insulin therapy in two patients. Fatal pulmonary toxicity is a major concern of a quick course NAC-VBP. In conclusion, these patients require special monitoring for bleomycin-induced pulmonary toxicity.
ROLE OF 5’-CpG ISLAND HYPERMETHYLATION OF THE FHIT GENE IN CERVICAL CARCINOMA
기경도,동서연,송동화,이종민,지성길,이선경 대한부인종양학회 2008 Journal of Gynecologic Oncology Vol.19 No.2
Objective: The abnormal expression of fragile histidine triad (FHIT) gene has been frequently reported in a variety of epithelial malignancies including cervical carcinoma. Furthermore, in a recent study it was proposed that transcriptional inactivation of FHIT, as a consequence of aberrant 5'-CpG island methylation, plays an important role in the carcinogenesis of human cervical carcinoma. The authors sought to determine whether abnormal FHIT transcription occurs in human cervical carcinoma, and if so, whether this abnormal expression is associated with aberrant 5'-CpG island methylation. In addition, the clinical significance of FHIT inactivation was investigated in Korean women with cervical cancer. Methods: To examine for abnormal transcripts of the FHIT gene, quantitative RT-PCR, genomic DNA-PCR and nonisotopic RT-PCR-SSCP analysis were performed using the standard method. The methylation status was determined by methylation specific PCR and bisulfite DNA sequencing. Results: The FHIT gene was down-regulated in 15 of 58 (25.9%) cervical carcinomas. FHIT promoter hypermethylation was detected in 15 of 15 (100%) abnormally expression in cervical carcinomas. Bisulfite DNA sequencing confirmed these findings and a significant correlation was found between CpG site hypermethylation and low FHIT expression. However, no significant correlation was found between reduced FHIT expression and clinicopathological characteristics. Conclusion: In this study, FHIT inactivation in cervical cancer was found to be strongly correlated with 5'-CpG island hypermethylation rather than a genetic alteration. Furthermore, no significant relation was found between a lack of FHIT expression and the prognostic factors of cervical cancer in our Korean cohort. Objective: The abnormal expression of fragile histidine triad (FHIT) gene has been frequently reported in a variety of epithelial malignancies including cervical carcinoma. Furthermore, in a recent study it was proposed that transcriptional inactivation of FHIT, as a consequence of aberrant 5'-CpG island methylation, plays an important role in the carcinogenesis of human cervical carcinoma. The authors sought to determine whether abnormal FHIT transcription occurs in human cervical carcinoma, and if so, whether this abnormal expression is associated with aberrant 5'-CpG island methylation. In addition, the clinical significance of FHIT inactivation was investigated in Korean women with cervical cancer. Methods: To examine for abnormal transcripts of the FHIT gene, quantitative RT-PCR, genomic DNA-PCR and nonisotopic RT-PCR-SSCP analysis were performed using the standard method. The methylation status was determined by methylation specific PCR and bisulfite DNA sequencing. Results: The FHIT gene was down-regulated in 15 of 58 (25.9%) cervical carcinomas. FHIT promoter hypermethylation was detected in 15 of 15 (100%) abnormally expression in cervical carcinomas. Bisulfite DNA sequencing confirmed these findings and a significant correlation was found between CpG site hypermethylation and low FHIT expression. However, no significant correlation was found between reduced FHIT expression and clinicopathological characteristics. Conclusion: In this study, FHIT inactivation in cervical cancer was found to be strongly correlated with 5'-CpG island hypermethylation rather than a genetic alteration. Furthermore, no significant relation was found between a lack of FHIT expression and the prognostic factors of cervical cancer in our Korean cohort.
기경도,이종민,동서연,이선경 대한산부인과학회 2012 대한산부인과학회 학술대회 Vol.99 No.-
XIAP-associated factor 1 (XAF1) is a tumor suppressor which has been known to exert proapoptotic effect. The XAF1 gene is located at 17p13.2 and its mRNA is ubiquitously expressed in all normal adult and fetal tissues, but absent or present at very low level in multiple human tumors. To explore the candidacy of XAF1 as a tumor suppressor in ovarian tumorigenesis, we investigated the expression and mutation status of the gene in 6 ovarian cancer cell lines and 16 tumor tissues. XAF1 transcript was easily detectable in all noncancerous ovarian tissues we examined. In contrast, however, its expression was not found or very low in 50% (3/6) of cancer cell lines and in 37.5% (6/16) of primary tumors. Whereas somatic mutations of the XAF1 gene were not detected, its mRNA expression was re-activated in no or low expression tumor cells following 5-aza-2-deoxycytidine treatment. Furthermore, bisulfite DNA sequencing analysis revealed that aberrant methylation at 7 CpG sites located in the 5` proximal region of the promoter is tightly associated with decreased mRNA expression, indicating that CpG sites hypermethylation of this promoter region is critical for the transcriptional silencing of XAF1. Together, our study suggests that epigenetic silencing of XAF1 by aberrant promoter methylation may contribute to the development and/or malignant progression of human ovarian tumors.
기경도 ( Kyung Do Ki ),이선경 ( Seon Kyung Lee ),노동규 ( Dong Kyu Noh ),서상기 ( Sang Gi Seo ),양문호 ( Moon Ho Yang ),김윤화 ( Yoon Wha Kim ),유영천 ( Young Chun Yoo ) 대한산부인과학회 2005 Obstetrics & Gynecology Science Vol.48 No.2
A case of fibroepithelial polyp on vulvoperineal area is described. Her age is 20 year old and the tumor measured 9cm in its largest diameter and was connected to the left labium majus. This case is very unusual in that almost all reported vulvar fibroepi