• Title/Summary/Keyword: 암 예방

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Regulatory Mechanism of Insulin-Like Growth Factor Binding Protein-3 in Non-Small Cell Lung Cancer (비소세포성 폐암에서 인슐린 양 성장 인자 결합 단백질-3의 발현 조절 기전)

  • Chang, Yoon Soo;Lee, Ho-Young;Kim, Young Sam;Kim, Hyung Jung;Chang, Joon;Ahn, Chul Min;Kim, Sung Kyu;Kim, Se Kyu
    • Tuberculosis and Respiratory Diseases
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    • v.56 no.5
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    • pp.465-484
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    • 2004
  • Background : Insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) inhibits the proliferation of non-small cell lung cancer (NSCLC) cells by inducing apoptosis. Methods : In this study, we investigated whether hypermethylation of IGFBP-3 promoter play an important role in the loss of IGFBP-3 expression in NSCLC. We also studied the mechanisms that mediate the silencing of IGFBP-3 expression in the cell lines which have hypermethylated IGFBP-3 promoter. Results : The IGFBP-3 promoter has hypermethylation in 7 of 15 (46.7%) NSCLC cell lines and 16 (69.7%) of 23, 7 (77.8%) of 9, 4 (80%) of 5, 4 (66.7 %) of 6, and 6 (100%) of 6 tumor specimens from patients with stage I, II, IIIA, IIIB, and IV NSCLC, respectively. The methylation status correlated with the level of protein and mRNA in NSCLC cell lines. Expression of IGFBP-3 was restored by the demethylating agent 5'-aza-2'-deoxycytidine (5'-aza-dC) in a subset of NSCLC cell lines. The Sp-1/ Sp-3 binding element in the IGFBP-3 promoter, important for promoter activity, was methylated in the NSCLC cell lines which have reduced IGFBP-3 expression and the methylation of this element suppressed the binding of the Sp-1 transcription factor. A ChIP assay showed that the methylation status of the IGFBP-3 promoter influenced the binding of Sp-1, methyl-CpG binding protein-2 (MeCP2), and histone deacetylase (HDAC) to Sp-1/Sp-3 binding element, which were reversed by by 5'-aza-dC. In vitro methylation of the IGFBP-3 promoter containing the Sp-1/Sp-3 binding element significantly reduced promoter activity, which was further suppressed by the overexpression of MeCP2. This reduction in activity was rescued by 5'-aza-dC. Conclusion : These findings indicate that hypermethylation of the IGFBP-3 promoter is one mechanism by which IGFBP-3 expression is silenced and MeCP2, with recruitment of HDAC, may play a role in silencing of IGFBP-3 expression. The frequency of this abnormality is also associated with advanced stages among the patients with NSCLC, suggesting that IGFBP-3 plays an important role in lung carcinogenesis/progression and that the promoter methylation status of IGFBP-3 may be a marker for early molecular detection and/or for monitoring chemoprevention efforts.

A Case-Control Study on Effects of Genetic Polymorphisms of GSTM1, GSTT1, CYP1A1 and CYP2E1 on Risk of Lung Cancer (GSTM1과 GSTT1, 그리고 CYP1A1, CYP2E1 다형성이 폐암발생에 미치는 영향에 대한 환자-대조군연구)

  • Nan, Hong-Mei;Kang, Jong-Won;Bae, Jang-Whan;Choe, Kang-Hyeon;Lee, Ki-Hyeong;Kim, Seung-Taik;Won, Choong-Hee;Kim, Yong-Min;Kim, Heon
    • Journal of Preventive Medicine and Public Health
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    • v.32 no.2
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    • pp.123-129
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    • 1999
  • Objectives: This study was performed to investigate sweets of genetic polymorphisms of glutathione S-transferase M1 (GSTM1), glutathione S-transferase M1 (GSTT1), cytochrome P450 1A1 (CYP1A1) and cytoehrome P450 2E1 (CYP2E1) on lung cancer development. Methods: Ninety-eight lung cancer patients and 98 age-sex matched non-cancer patients hospitalized in Chungbuk National University Hospital form March 1997 to August 1998, were the subjects of this case-control study. Direct interview was done and genotypes of GSTM1, GSTT1, CYP1A1 and CYP2E1 were investigated using multiplex PCR or PCR-RFLP methods with DNA extracted from venous blood. Effects of the polymorphisms of GSTM1, GSTT1, CYP1A1 and CYP2E1, lifestyle factors including smoking, and their interactions on lung rancor were statistically analyzed. Results: GSTM1 was deleted in 67.01% of the cases and 58.16% of the controls, and the odds ratio(95% CI) was 1.46(0.82-2.62). GSTT1 deletion was 58.76% for the lung cancer patients and 50.00% for the controls[OR:1.43(0.81-2.51)]. The frequencies of lle/lle, lle/Val and Val/Val of the CYP1A1 polymorphisms were 59.18-18%, 35.71%, and 5.10% for the cases, and 52.04%, 45.92%, 2.04% for the controls, respectively. Risk of lung cancer was not associated with polymorphism of CYP1A1 ($x^2trend=0.253$, p-value>0.05). The respective frequency of c1/c1 c1/c2, c2/c2 genotypes for CYP2E1 were 50.00%, 42.86%, 7.14% for the lung cancer patients, and 66.33%, 30.61%, 3.06% for the controls $(x^2trend=5.783,\;p<0.05)$. c2 allele was a significant risk factor for lung cancer. We also observed a significant association of cigarette smoking history with lung cancer risk. The odds ratio(95% Cl) of cigarette smoking was 3.03(1.58-5.81). In multiple logistic analysis including genotypes of GSTM1, GSTT1, CYP1A1 and CYP2E1, and smoking habit, only snaking habit came out to be a significant risk factor for lung cancer. Conclusion: Genetic polymorphisms of GSTM1, GSTT1, CYP1A1 and CYP2E1 are not so strongly associated with lung cancer as lifestyle factors including cigarette smoking.

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Statistical Analysis of Operating Efficiency and Failures of a Medical Linear Accelerator for Ten Years (선형가속기의 10년간 가동률과 고장률에 관한 통계분석)

  • Ju Sang Gyu;Huh Seung Jae;Han Youngyih;Seo Jeong Min;Kim Won Kyou;Kim Tae Jong;Shin Eun Hyuk;Park Ju Young;Yeo Inhwan J.;Choi David R.;Ahn Yong Chan;Park Won;Lim Do Hoon
    • Radiation Oncology Journal
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    • v.23 no.3
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    • pp.186-193
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    • 2005
  • Purpose: To improve the management of a medical linear accelerator, the records of operational failures of a Varian CL2l00C over a ten year period were retrospectively analyzed. Materials and Methods: The failures were classified according to the involved functional subunits, with each class rated Into one of three levels depending on the operational conditions. The relationships between the failure rate and working ratio and between the failure rate and outside temperature were investigated. In addition, the average life time of the main part and the operating efficiency over the last 4 years were analyzed. Results: Among the recorded failures (total 587 failures), the most frequent failure was observed in the parts related with the collimation system, including the monitor chamber, which accounted for $20\%$ of all failures. With regard to the operational conditions, 2nd level of failures, which temporally interrupted treatments, were the most frequent. Third level of failures, which interrupted treatment for more than several hours, were mostly caused by the accelerating subunit. The number of failures was increased with number of treatments and operating time. The average life-times of the Klystron and Thyratron became shorter as the working ratio increased, and were 42 and $83\%$ of the expected values, respectively. The operating efficiency was maintained at $95\%$ or higher, but this value slightly decreased. There was no significant correlation between the number of failures and the outside temperature. Conclusion: The maintenance of detailed equipment problems and failures records over a long period of time can provide good knowledge of equipment function as well as the capability of predicting future failure. Wore rigorous equipment maintenance Is required for old medical linear accelerators for the advanced avoidance of serious failure and to improve the qualify of patient treatment.

Trend of Medical Care Utilization and Medical Expenditure of the Elderly Cohort (노인 코호트의 의료이용 및 입원진료비 변화 추이 -공.교 의료보험 대상자를 대상으로-)

  • Lee, Kyeong-Soo;Kang, Pock-Soo
    • Journal of Preventive Medicine and Public Health
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    • v.30 no.2 s.57
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    • pp.437-461
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    • 1997
  • Because of a significant improvement in the economic situation and development of scientific techniques in Korea during the last 30 years, the life expectancy of the Korean people has lengthened considerably and as a result, the number of the elderly has markedly increased. Such an increase of the number of aged population brought about many social, economic, and medical problems which were never seriously considered before. This study was conducted to assess the trend of medical care utilization and medical expenditure of the elderly. The data of each patient in the study were taken from computer database maintained for administrative purpose by the Korea Medical Insurance Corporation. The study population was 132,670 who were 60 years old or more and registered in Korean Medical Insurance Corporation from 1989 to 1993. The study subjects were predominantly female(56.3%) and 10,000-20,000 Won premium group(50.6%). The following are summaries of findings : The total increase of the number of inpatient cases was 40.5% from 1989 through 1993. The average annual increase was 3.7% in inpatient medical expenditures per case, 4.4% in inpatient medical expenditures per day and 0.08% in length of stay per case from 1989 through 1993. Cataract was the most prevalent disease of 10 leading frequent diseases in all ages from 1989 through 1993. The case mix in 1993 compared to 1989 revealed that cataract and ischemic cerebral disease were increased whereas essential hypertension and pulmonary tuberculosis were decreased . The average annual increase of medical expenditures was 3.8% in general hospitals, 6.3% in hospitals and 2.4% in clinics. From 1989 through 1993, medical expenditures used by high-cost patients accounted for about 14% to 20% of all expenditures for inpatient care, while they represented less than 2.5% of the elderly population. Time series analysis revealed that total medical expenditures and doctor's fee for inpatient will be progressively increased whereas drug expenditures for inpatient will be decreased. And there will be no change in length of stay. Based on the above results, the factors increasing medical cost and utilization should be identified and the method of cost containment for the elderly health care should be developed systematically.

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Comparative Analysis of Community Health Practitioner's Activities and Primary Health Post Management Before and After Officialization of Community Health practitioner (보건진료원의 정규직화 전과 후의 보건진료원 활동 및 보건진료소 관리운영체계의 비교 분석)

  • Yun, Suk-Ok;Jung, Moon-Sook
    • Journal of agricultural medicine and community health
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    • v.19 no.2
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    • pp.141-158
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    • 1994
  • To provide better health care services to the rural population, the government has made the Community Health Practitioner(CHP) a regular government official from April 1, 1992. This study was carried out to study the impact of officialization of CHP on the activities and management system of Primary Health Post(PHP). Fifty PHPs were selected by two stage sampling, cluster and simple random, from 595 PHPs in Kyungnam and Kyungpook provinces. Data were collected by a personal interview with CHPs and review of records and reports kept in the PHPs. The study was done for the periods of January 1-March 31, 1992 (before officialization) and January 1-March 31, 1993 (after officialization). Ninety-six percent of the CHPs wanted to become a regular government official in the hope of better job security and higher salary. The proportion of CHPs who were proud of their iob was increased from 24% to 46% after officialization. Those CHPs who felt insecure for their job decreased from 30% to 10%. Monthly salary was increased by 34% from 802,600 Won to 1,076,000 Won and 90% of the CHPs were satisfied with their salary, also more CHPs responded that they have autonomy in their work planning, implementation of plan, management of the post, and evaluation of their activity. There were no appreciable changes in such CHPs' activities as assessment of local health resources, drawing map for the catchment area, utilization of community organization, grasping the current population structure in the catchment area, keeping the family health records, individual and group health education, and school health service. However, the number of home visits was increased from 13.6 times on the average per month per CHP to 27.5 times. More mothers and children were referred to other medical facilities for the immunization and family planning services. Average number of patients of hypertension, cancer, and diabetes in three months period was decreased from 12.7 to 11.6, from 1.5 to 1.2, and 4.3 to 3.4, respectively. Records for the patient care, drug management, and equipment were well kept but not for other records. The level of record keeping was not changed after officialization. The proportion of PHPs which had support from the health center was increased for drug supply from 14.0% to 30.0%, for consumable commodities from 22.0% to 52.0%, for maintenance of PHP from 54.0% to 68.0%, for supply of health education materials from 34.0% to 44.0%, and supply of equipment from 54.0% to 58.0%. Total monthly revenue of a PHP was increased by about 50,000 Won; increased by 22,000 Won in patient care and 34,700 Won in the government subsidy but decreased in the membership due and donation. However, there was no remarkable changes in the expenditure. The proportion of PHPs which had received official notes from the health center for the purpose of guidance and supervision of the CHPs was increased from 20% to 38% during three months period and the average number of telephone call for supervision from the health center per PHP was increased from 1.8 to 2.1 times(p<0.01). However, the proportion of PHPs that had supervisory visit and conference was reduced from 79% to 62%, and from 88% to 74%, respectively. The proportion of CHPs who maintained a cooperative relationship with Myun Health Workers was reduced from 42% to 36%, that with the director of health center from 46% to 24%, that with the chief of public health administration section from 56% to 36%, and that with the chairman of PHP management council from 62% to 38%. Most of the CHPs (92% before and 82% after officialization) stated that the PHP management council is not helpful for the PHP. CHPs who considered the PHP management council unnecessary increased from 4% to 16%(p<0.05). Suggestions made by the CHPs for the improvement of CHP program included emphasis on health education, assurance of autonomy for PHP management, increase of the kind of drugs that can be dispensed by CHPs, and appointment of an experienced CHP in the health center as the supervisor of CHPs. The results of this study revealed that the role and function of CHPs as reflected in their activities have not been changed after officialization. However, satisfaction in job security and salary was improved as well as the autonomy. Support of health center to the PHP was improved but more official notes were sent to the PHPs which required the CHPs more paper works. Number of telephone calls for supervision was increased but there was little administrative and technical guidance for the CHP activities.

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