• Title/Summary/Keyword: 치료(治療)

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Analysis of 5-aza-2'-deoxycytidine-induced Gene Expression in Lung Cancer Cell Lines (폐암 세포주에서 5-aza-2'-deoxycytidine 처치에 의해 발현되는 암항원 유전자 분석)

  • 김창수;이해영;김종인;장희경;박종욱;조성래
    • Journal of Chest Surgery
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    • v.37 no.12
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    • pp.967-977
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    • 2004
  • Background: DNA methylation is one of the important gene expression mechanisms of the cell. When cytosine of CpG dinucleotide in promotor is hypomethylated, expression of some genes that is controlled by this promoter is altered. In this study, the author investigated the effect of DNA demethylating agent, 5-aza-2'-deoxycytidine (ADC), on the expressions of cancer antigen genes, MHC and B7 in 4 lung cancer cell lines, NCIH1703, NCIH522, MRC-5, and A549. Material and Method: After treatment of cell lines, NCIH1703, NCIH522, MRC-5 and A549 with ADC (1 uM) for 48 hours, RT-PCR was performed by using the primers of MAGE, GAGE, NY-ESO-1, PSMA, CEA, and SCC antigen gene. In order to find the optimal ADC treatment condition for induction of cancer antigen, we studied the effect of ADC treatment time and dose on the cancer antigen gene expression. To know the effect of ADC on the expression of MHC or B7 and cell growth, cells were treated with 1 uM of ADC for 72 hours for FACS analysis or cells were treated with 0.2, 1 or 5 uM of ADC for 96 hours for cell counting. Result: After treatment of ADC (1 uM) for 48 hours, the expressions of MAGE, GAGE, NY-ESO-1, and PSMA genes increased in some cell lines. Among 6 MAGE isotypes tested, and gene expression of MAGE-1, -2, -3, -4 and -6 could be induced by ADC treatment. However, CEA gene expression did not change and SCC gene expression was decreased by ADC treatment. Gene expression was generally induced 24 - 28 hours after ADC treatment and expression of MAGE, GAGE, and NY-ESO-1 was maintained at least 14 days after ADC ADC teatment, and expression of MAGE, GAGE, and NY-ESO-1 was maintained at least 14 days after ADC teatment in ADC-Free medium. Most gene expression could be induced at 0.2 uM of ADC, but gene expression increased dependently on ADC treatment dose. The expression of MHC and B7 was not increased by ADC treatment in all four cell lines, and the growth rate of 4 cell lines decreased significantly with the increase of ADC concentrations. Conclusion: Treatment of lung cancer cell lines with ADC increases the gene expression MAGE, GAGE and NY-ESO-1 that are capable of induction of cytotoxic T lymphocyte response. We suggest that treatment with 1 uM of ADC for 48 hours and then culturing in ADC-free medium is optimal condition for induction of cancer antigen. However, ADC has no effect on MHC and B7 induction, additional modification for increase of expression of MHC, B7 and cytokine will be needed for production of efficient cancer cell vaccine.

The Use of Analgesics in the Last 24 hours of Life of Patients with Advanced Cancer : A Comparison of Medical Physicians and Surgeons (말기 암 환자의 마지막 24시간 동안 진통제 사용의 분석 : 내과의사와 외과의사의 비교)

  • Choi, Youn-Seon;Kim, Jong-Min;Lee, Young-Mee;Lim, Jong-Kuk;Lee, Tai-Ho;Hong, Myung-Ho
    • Journal of Hospice and Palliative Care
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    • v.1 no.1
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    • pp.47-55
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    • 1998
  • Background : It is almost important therapy modality to control pain for the terminal cancer patients for the last 24 hours because those terminally illed patient deserved to have pain free and peaceful time before death. Physician who is deal with terminal cancer patients for their last 24 hours does not need to worry about drug addiction or other untoward side reactions of pain medications. The purpose of this study was to evaluate if terminally illed cancer patient was given pain medication properly and sufficiently and if there was any different behavior to control pain of terminal cancer patients between medical physicians and surgeons in terms of type, amount and administration route and frequency. Methods : A retrospective chart audit of analgesic type, amount and administration route was performed on the medical recorders of 160 hospitalized terminal cancer patients who had died in the Korea University Medical Center Anam Hospital during the period of July 1, 1994 to June 30, 1995. Patients were classified into 103 patients were cared for by medical physicians and 57 patients were cared for by surgeons. After then, we analysed the difference of pain control pattern between them. Different types and amount of analgesics were converted to a common standard, an oral morphine equivalents(OME) relative to 1mg of oral morphine. Results : 1) The total number of patients was 160, male 102 cases(63.8%), and the female was 58 cases(36.2%) respectively. 2) The mean age was 56.4(${\pm}14.62$) years old and mean admission period was 27.8 days(${\pm}34.85$). 3) The frequent cancer site was stomach 42 cases(26.315), lung and liver 29 cases(18.1%) each, pancreas 10 cases(6.2%) in order 4) 125 out of 160 subjects (78.13%) complained pain, and 66 out of 103(64.08%) and 31 out of 57(54.39%) were treated with analgesics to relieve pain. 50 out of 97(51.55%) were able to continue on oral medication. 5) 86 cases(53.75%) were well oriented 24 hours prior to death. 6) The frequent analgesics for regular basis were long acting form of oral morphine 34 cases(Medical phsicians 24, Surgeons 10), intravenous morphine 26 cases(Medical physicians 20, Surgeons 6) in order, and the most common p.r.n.(pro re nata) analgesics used was intravenous morphine. 7) The mean amount of analgesics on regular basis was 115.41 OME by medical physicians and 52.7 OME by surseons(P<0.05). The mean amount of p.r.n. analgesics was significantly larger in patients are for by surgeons(66.64 OME) than medical physicians 23.49 OME(P<0.01). 8) The mean frequency of administrated number of p.r.n. analgesics was 0.62 times/day on medical part and 1.88 times/day on surgical part (P<0.001). Conclusion : Of the 97 patients with advanced cancer, 51.55% were able to take oral medications in the last day of life. The parenteral analgesics were more frequently used in the patients cared for by surgeons than medical physicians. Over the half of terminal cancer patients were well oriented in the last day of life. Doctor's knowledge and attitude towards pain is very important to mange the pain, effectively.

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CLINICAL AND NEUROPSYCHOLOGICAL CHARACTERISTICS OF DSM-IV SUBTYPES OF ATTENTION DEFICIT HYPERACTIVITY DISORDER (주의력결핍 과잉행동장애의 아형별 신경심리학적 특성 비교)

  • Cheung, Seung-Deuk;Lee, Jong-Bum;Kim, Jin-Sung;Seo, Wan-Seok;Bai, Dai-Seg;Chun, Eun-Jin;Suh, Hae-Sook
    • Journal of the Korean Academy of Child and Adolescent Psychiatry
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    • v.13 no.1
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    • pp.139-152
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    • 2002
  • Objectives:This study was conducted to compare the clinical and neuropsychological characteristics by DSM-IV subtypes of attention deficit hyperactivity disorder(ADHD) patients who did not have comorbid psychiatric disorders. Methods:5-15 year old children with ADHD were recruited at psychiatric outpatient clinic of Yeungnam University hospital and the patients with comorbidity or neurological abnormalities were excluded. Finally, total 404 children with ADHD were selected for this study. There were 234 subjects of ADHD-C(57.9%), 156 subjects of ADHD-I(38.6%) and 14 subjects of ADHD-HI(3.5%), who fulfilled the DSM-IV diagnostic criteria. The mean age of the total subjects was 9.63±2.49 years old. The psychopathology, IQ, behavioral problems, neuropsychological executive function were evaluated before pharmacological treatment. The measures were Korean Personality Inventory of Child(K-PIC) for psychopathology, 4 behavioral check lists(ADDES-HV, ACTeRS, CAP, SNAP) for behavioral symptoms of ADHD, K-ABC and KEDI-WISC for IQ and Conner's CPT, WCST, SST for neuropsychological executive functions. Results:1) The prevalence of subtypes was ADHD-C, ADHD-I, ADHD-HI in decreasing order. There was no sex difference of prevalence among three subtypes. The mean age of ADHD-I was older than other subtypes. 2) There was significant differences of psychopathology among subtypes, the ADHD-C and ADHD-HI had higher than the ADHD-I in the scores of delinquent, hyperactivity and psychosis;the ADHD-C had higher than the ADHD-I in the scores of family relation and autism, the scores of ego resilience were lower than the ADHD-I. However, there was no difference in anxiety, depression and somatization scores among them. 3) The results of behavioral symptom check lists, the ADHD-C had higher the score of inattention, hyperactivity and impulsivity than the ADHD-I. Meanwhile the results of ACTeRs, which rated by the teachers, were different. 4) There were significant differences of sequential processing scale and arithmetics among subtypes in IQ using K-ABC, but there was no significant difference between the ADHD-C and the ADHD-I after excluding the ADHD-HI due to small numbers. 5) There was numerical difference among subtypes but did not reach statistical significance in three neuropsychological executive function tests. Conclusion:In conclusion, our results revealed that there was significant difference in clinical features among three subtypes but, no significant difference in executive functions.

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CLINICAL CHARACTERISTICS OF CHILD AND ADOLESCENT PSYCHIATRIC INPATIENTS WITH MOOD DISORDER (입원한 기분장애 소아청소년의 임상특성 - 주요 우울증과 양극성장애의 우울삽화 비교를 중심으로 -)

  • Cho, Su-Chul;Paik, Ki-Chung;Lee, Kyung-Kyu;Kim, Hyun-Woo;Hong, Kang-E;Lim, Myung-Ho
    • Journal of the Korean Academy of Child and Adolescent Psychiatry
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    • v.11 no.2
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    • pp.209-220
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    • 2000
  • The purpose of this study is to find out the characteristics of depressive episode about major depression and bipolar disorder in child and adolescent. The subjects of this study were 34 major depression patients and 17 bipolar disorder patients hospitalized at child and adolescent psychiatry in OO university children's hospital from 1st March 1993 to 31st October 1999. The method of this study is to review socio-demographic characteristics, diagnostic classification, chief problems and symptoms at admission, frequency of symptoms, maternal pregnancy problem history, childhood developmental history, coexisting psychiatric disorders, family psychopathology and family history and therapeutic response through their chart. 1) The ratio of male was higher than that of female in major depressive disorder while they are similar in manic episode, bipolar disorder. 2) Average onset age of bipolar disorder was 14 years 1 month and it was 12 years 8 months in the case of major depression As a result, average onset age of major depression is lower than that of bipolar disorder. 3) The patients complained of vegetative symptoms than somatic symptoms in both bipolar disorder and depressive disorder. Also, the cases of major depression developed more suicide idea symptom while the case of bipolar disorder developed more aggressive symptoms. In the respect of psychotic symptoms, delusion was more frequently shown in major depression, but halucination was more often shown in bipolar disorder. 4) Anxiety disorder coexisted most frequently in two groups. And there coexisted symptoms such as somartoform disorder, mental retardation and personality disorder in both cases. 5) The influence of family loading was remarkable in both cases. Above all, the development of major depression had to do with child abuse history and inappropriate care of family. It is apparent that there are distinctive differences between major depression and bipolar disorder in child and adolescent through the study, just as in adult cases. Therefore the differences of clinical characteristics between two disorders is founded in coexisting disorders and clinical symptoms including onset age, somatic symptoms and vegetative symptoms.

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Survival Value of Myocutaneous Flaps in the Management of Epidermoid Carcioma of the Oral Cavity (구강내 상피암의 치료에서 근피부판이 생존율에 미치는 영향)

  • Seel David John;Park Chul-Young;Yoo Chung-Joon;Lee Samuel;Park Yoon-Kyu
    • Korean Journal of Head & Neck Oncology
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    • v.6 no.2
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    • pp.79-84
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    • 1990
  • This paper is a review of our experience with radical resection for cancer of the oral cavity with particular emphasis upon the value of myocutaneous(i.e., musculocutanous) flaps employed in the surgical reconstruction in patient survival. During the past 15 years, 98 patients underwent resection of cancer arising in the oral cavity and oropharynx. Of these, 14 had composite resections in which the mandible was not sectioned, and 4 underwent en bloc resections without neck dissections in the face of post-radiation recurrence. When these excluded, 84 patients who underwent COMMANDO procedures with or without myocutaneous flaps were suitable for analysis of recurrence and survival according to the various surgical technics employed. 1) According to the surgical technic, there were 24 standard COMMANDO procedures in whom no regional or myocutanous flap was used; 12 patients who underwent reconstruction employing a forehead flap; 19 patients in whom a posterior cervical 'nape' flap was employed; 27 patients who underwent myocutaneous or osteo-myocutaneous flap repair; and two patients who had double flap repair. 2) The uncorrected two-year disease free survival was 41% for standard COMMANDOs, 17% for forehead flap COMMANDOs; 35% for nape flap COMMANDOs; and 35% for myocutaneous flap COMMANDO procedures. 3) The two-year disease-free survival by Stage was 100% in Stage I, 45% in Stage II, 41% in Stage III, and 18% in Stage IV. 4) When myocutanous flaps cases were compared with Group I, comprised of matched historical controls including both Standard COMMANDOs and those who had undergone regional flap repairs(that is, forehead and nape flap COMMANDOs)there was no difference, both groups showing a 40% 2-year disease-free survival. 5) When musculocutanous flap cases were compared with Goup II, which was composed of matched historical controis limited to patients who had undergone regional flap repairs(that is, forehead and nape flap cases only)there was no difference, both groups showing a 27% 2-year desease-free survival. 6) When musculocutanous flap cases were compared with Group III, composed of patients who had undergone classic COMMANDO procedures without any sort of flap repair, there was a striking difference; the patients undergoing MC flap repair showed 50% 2-year disease-free survival, whereas the classic COMMANDO cases showed a 25% survival free of disease. 7) Locoregional recurrence was also evaluated in the four categories; for standard COMMANDO cases it was 25%, for nape flap cases 26% ; for forehead flap cases, 33%, and for the musculocutaneous flap cases, the lowest recurrence rate, 22%. These results are of particular significance in view of the fact that the proportion of advanced cases(Stage III and IV)in each category was 67% of standard cases, 79% of nape flap patients, 100% of forehead flap cases, and 96% of musculocutaneous flap cases.

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Depositional Environment and Formation Ages of Eurimji Lake Sediments in Jaechon City, Korea (제천 의림지 호저퇴적물 퇴적환경과 형성시기 고찰)

  • 김주용;양동윤;이진영;김정호;이상헌
    • The Korean Journal of Quaternary Research
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    • v.14 no.1
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    • pp.7-31
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    • 2000
  • Quaternary Geological and geophysical investigation was performed at the Eurimji reservoir of Jaechon City in order to interprete depositional environment and genesis of lake sediments. For this purpose, echo sounding, bottom sampling and columnar sampling by drilling on board and GPR survey were employed for a proper field investigation. Laboratory tests cover grain size population analysis, pollen analysis and $^{14}C$ datings for the lake sediments. The some parts of lake bottom sediments anthropogenically tubated and filled several times to date, indicating several mounds on the bottom surface which is difficult to explain by bottom current. Majority of natural sediments were accumulated both as rolling and suspended loads during seasonal flooding regime, when flash flow and current flow are relatively strong not only at bridge area of the western part of Eurimji, connected to stream valley, but at the several conduit or sewage system surrounding the lake. Most of uniform suspend sediments are accumulated at the lake center and lower bank area. Some parts of bottom sediments indicate the existence of turbid flow and mudflow probably due to piezometric overflowing from the lake bottom, the existence of which are proved by CM patterns of the lake bottom sediments. The columnar samples of the lake sediments in ER-1 and ER-3-1 boreholes indicate good condition without any human tubation. The grain size character of borehole samples shows poorly sorted population, predominantly composed of fine sand and muds, varying skewness and kurtosis, which indicate multi-processed lake deposits, very similar to lake bottom sediments. Borehole columnar section, echo sounding and GPR survey profilings, as well as processed data, indicate that organic mud layers of Eurimji lake deposits are deeper and thicker towards lower bank area, especially west of profile line-9. In addition the columnar sediments indicate plant coverage of the Eurimji area were divided into two pollen zones. Arboreal pollen ( AP) is predominant in the lower pollen zone, whreas non-aboreal pollen(NAP) is rich in the upper pollen zone. Both of the pollen zones are related to the vegetation coverage frequently found in coniferous and deciduous broad-leaved trees(mixed forest) surrounded by mountains and hilly areas and prevailing by aquatic or aquatic margin under the wet temperate climate. The $^{14}C$ age of the dark gray organic muds, ER1-12 sample, is 950$\pm$40 years B.P. As the sediments are anthropogenetically undisturbed, it is assumed that the reliability of age is high. Three $^{14}C$ ages of the dark gray organic muds, including ER3-1-8, ER3-1-10, ER3-1-11 samples, are 600$\pm$30 years B.P., 650$\pm$30 years B.P., 800$\pm$40 years B.P. in the descending order of stratigraphic columnar section. Based on the interpretation of depositional environments and formation ages, it is proved that Eurimji reservoir were constructed at least 950$\pm$40 years B.P., the calibrated ages of which ranges from 827 years, B.P. to 866 years B.P. Ancient people utilize the natural environment of the stream valley to meet the need of water irrigation for agriculture in the local valley center and old alluvium fan area.

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Factors influencing the axes of anterior teeth during SWA on masse sliding retraction with orthodontic mini-implant anchorage: a finite element study (교정용 미니 임플랜트 고정원과 SWA on masse sliding retraction 시 전치부 치축 조절 요인에 관한 유한요소해석)

  • Jeong, Hye-Sim;Moon, Yoon-Shik;Cho, Young-Soo;Lim, Seung-Min;Sung, Sang-Jin
    • The korean journal of orthodontics
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    • v.36 no.5
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    • pp.339-348
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    • 2006
  • Objective: With development of the skeletal anchorage system, orthodontic mini-implant (OMI) assisted on masse sliding retraction has become part of general orthodontic treatment. But compared to the emphasis on successful anchorage preparation, the control of anterior teeth axis has not been emphasized enough. Methods: A 3-D finite element Base model of maxillary dental arch and a Lingual tipping model with lingually inclined anterior teeth were constructed. To evaluate factors influencing the axis of anterior teeth when OMI was used as anchorage, models were simulated with 2 mm or 5 mm retraction hooks and/or by the addition of 4 mm of compensating curve (CC) on the main archwire. The stress distribution on the roots and a 25000 times enlarged axis graph were evaluated. Results: Intrusive component of retraction force directed postero-superiorly from the 2 mm height hook did not reduce the lingual tipping of anterior teeth. When hook height was increased to 5 mm, lateral incisor showed crown-labial and root-lingual torque and uncontrolled tipping of the canine was increased.4 mm of CC added to the main archwire also induced crown-labial and root-lingual torque of the lateral incisor but uncontrolled tipping of the canine was decreased. Lingual tipping model showed very similar results compared with the Base model. Conclusion: The results of this study showed that height of the hook and compensating curve on the main archwire can influence the axis of anterior teeth. These data can be used as guidelines for clinical application.

Intestinal Atresia - A Survey by the Korean Association of Pediatric Surgeons - (선천성 장폐쇄증 - 대한소아외과학회 정회원을 대상으로 한 전국조사 -)

  • Kim, I.K.;Kim, S.Y.;Kim, S.K.;Kim, W.K.;Kim, J.E.;Kim, J.C.;Kim, H.H.;Park, K.W.;Park, Y.S.;Park, W.H.;Song, Y.T;Yang, J.W.;Oh, S.M.;Yoo, S.Y.;Lee, D.S.;Lee, M.D.;Lee, S.K.;Lee, S.C.;Chang, S.I.
    • Advances in pediatric surgery
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    • v.5 no.1
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    • pp.75-81
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    • 1999
  • A survey on the intestinal atresias was made among 34 members of Korean Association of Pediatric Surgeons. The response rate was 82.4 %. Two hundred and fifteen patients from the January 1, 1994 to December 31, 1996 were analyzed. The lesions were 73 cases of duodenum(DA), 72 cases of jejunum(JA), 71 cases ileum(IA) and 2 cases cecum and sigmoid colon respectively. There were 2 cases of combined anomalies (DA + JA + IA and DA + JA). Male to female ratio was 1:1 in DA, and 1.8:1 in JA. Seventy four cases(34.3 %) were premature babies(DA 35.2 %, JA:48.6 %, IA:19.2 %), and 62 cases(28.7 %) had low birth weight (DA:39.4 %, JA 33.0 %, IA:13.7 %). Antenatal diagnosis was made in 92 cases(43.6 %). However 22 cases (23.9 %) of them were transferred to pediatric surgeon after delivery. Maternal polyhydramnios was observed in 63 cases(28.9 %). Seventy· five cases(34.4 %) were taken only simple abdominal film for diagnostic studies. The associated malformations were observed in 54 aresia and were observed more frequently in DA(35 cases, 47.9 %). Meconium peritonitis due to intrauterine bowel perforation was more frequently associated with IA compared to DA and JA. The overall mortality rate was 30 %. (Abbreuations: $P_{T}$;p-value in total, $P_{DJ,DI,JI}$;p value between two groups among duodenal, jejunal and ileal groups).

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Morphological Changes of Mouse Ovary by X-Ray Irradiation (방사선 조사선량에 따른 생쥐 난소의 형태학적 변화)

  • Yoon, Chul-Ho;Choi, Jong-Woon;Yoon, Surk-Hwan
    • Journal of Radiation Protection and Research
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    • v.32 no.4
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    • pp.140-156
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    • 2007
  • This research was performed to investigate the morphological changes of folliculus ovary according to the radiation dose. The whole body radiation of 200 cGy, 400 cGy, and 600 cGy was given to the each groups of 5 months-aged female mouse. Various staining methods used in this research are: Hematosylin-Eosin method, and immunohistochemistrical methods using BrdU, TUNEL, p53, p21, PCNA and inhibin. The minute structural changes of folliculus ovary were observed through an electron microscope with high magnification. The morphological changes of growing folliculus ovary became distinct as the dose of X-rays increased. Especially, the nuclei of granular cells showed manifest condensation and the changes of the transparent zone were distinct. As a result of histochemical reaction according to Masson's trichrome method and reticular fiber method, the changed granular cells, the deformed basilar membrane of folliculus ovary and the abnormal arrangement of the reticular fiber were observed. In the reaction of BrdU, the granular cells of normal folliculus ovary with positive reaction rapidly decreased according to the increase of the dose of X-rays. In TUNEL study, granular cells showing positive reaction in retarded folliculus ovary were expanded to growing folliculus ovary and primordial folliculus ovary according to the increase of the dose of X-rays. In case of 600 cGy of X-rays, oocyte underwent apoptosis. In p53 immunohistochemistry, p53 manifested to be stronger as the dose of X-rays increased. p53 reactivity was manifested distinctively in all cells comprising folliculus ovary following irradiation of 600 cGy. p21 was manifested in granular cells of folliculus ovary and showed very positive reaction around follicular antrum according to the increase of the dose of X-rays. In PCNA, positive reaction was manifested in growing folliculus ovary, mature folliculus ovary and primordial folliculus ovary, but the extent of the reaction decreased as the dose of the X-rays decreased. The finding that the reaction of granular cells around folliculus ovary was stronger than that near follicular membrane indicates that what was damaged first by X-ray was the cells near folliculus ovary and follicular antrum. The reactivity of $inhibin-{\alpha}$ showed difference according to the growing stage of folliculus ovary: $inhibin-{\alpha}$ showed the most strong reaction in mature folliculus ovary with follicular antrum. There was strong reaction in granular cells around follicular membrane but $inhibin-{\alpha}$ did not occur at all in theca cells comprising follicular membrane. $Inhibin-{\alpha}$ in ovary tissue exposed to 400 cGy of X-rays was manifested more strongly than in ovary tissue exposed to 600 cGy of X-rays, which was related to the phenomenon that granular cells of mature folliculus ovary underwent necrosis or apoptosis increasingly due to X-rays. In an electron microscope with high magnification, nuclei and protoplasm of granular cells in growing folliculus ovary abruptly underwent minute structural changes according to the increase of dose of X-rays. Cell residue, by-product of cell decease, neutrophil and macrophage around follicular antrum were observed. The minute structural changes in granular cells showed typical characteristics of apoptosis: the increase of electronic density due to nuclear condensation, fragmentation of nuclei and atrophy of protoplasm. Necrosis of cells was identified but it was not so remarkable. Macrophage with apoptotic bodies was scattered. Proportional to the radiation dose, we found that the generation of heterogeneous substance of normal ovary texture's follicular fluid, the emergence of dyeing characteristic in the basilar membrane of folicle, the generation of apoptosis, and the transformation of macrophages, etc. From this results, we can infer the possible radiation hazard on the ovary of cervix cancer patient with radiation therapy.

The Role of NF-${\kappa}B$ in the TNF-$\alpha$-induced Apoptosis of Lung Cancer Cell Line (폐암세포주의 TNF-$\alpha$ 유발 apoptosis에서 NF-${\kappa}B$의 역할)

  • Kim, J.Y.;Lee, S.H.;HwangBo, B.;Lee, C.T.;Kim, O.H.;Han, S.K.;Shim, O.S.;Yoo, C.G.
    • Tuberculosis and Respiratory Diseases
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    • v.48 no.2
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    • pp.166-179
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    • 2000
  • Background: The main reason for the failure of anti-cancer chemotherapy is the build up of resistance by cancer cells to apoptosis. The activation of NF-${\kappa}B$ in many cancer cell lines is reported to be underlying mechanism behind the build up of resistance of cancer cells to apoptosis. However, this relationship varied depending on the cells used in the experiments. In this study, the role of NF-${\kappa}B$ activation in the TNF-$\alpha$-induced apoptosis in lung cancer cell line was evaluated. Methods: NCI-H157 cells were used in all experiments. Cells were exposed to a high dose of TNF-$\alpha$(20 ng/ml) for 24 or 48 hours with or without blocking NF-${\kappa}B$ activation. TNF-$\alpha$-induced activation of NF-${\kappa}B$ was inhibited either by overexpression of $I{\kappa}B{\alpha}$-super repressor($I{\kappa}B{\alpha}$-SR) or by pre-treatment with proteasome inhibitor. Cell viability and apoptosis were evaluated with MTT assay and Western blot analysis for PARP fragment, respectively. Results: Cell viability of NCI-H157 cells was not affected by TNF-$\alpha$ treatment alone; however, combined treatment with TNF-$\alpha$ and cycloheximide reduced cell viability significantly, indicating that resistance to TNF-$\alpha$ is mediated by the new proteins synthesized after TNF-$\alpha$ stimulation. To evaluate the role of NF-${\kappa}B$ in the transcription of anti-apoptotic proteins. delete NF-${\kappa}B$ activation was inhibited before TNF-$\alpha$ stimulation. as described above. $AD5I{\kappa}B{\alpha}$-SR-transduction inhibited TNF-$\alpha$-induced nuclear translocation of p65. TNF-$\alpha$-induced cell death and apoptosis increased after inhibition of TNF-$\alpha$-induced activation of NF-${\kappa}$ by methods. Conclusion: These results suggest that TNF-$\alpha$-induced activation of NF-${\kappa}B$ may be closely related to the acquisition of the resistance to TNF-$\alpha$-induced apoptosis in lung cancer cells. Therefore. blocking of NF-${\kappa}B$ pathway can be a useful therapeutic modality in the treatment of lung cancer.

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