• Title/Summary/Keyword: tumor response

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Results of Preoperative Concurrent Chemoradiotherapy for the Treatment of Rectal Cancer (직장암의 수술 전 동시적 항암화학방사선치료 결과)

  • Yoon, Mee-Sun;Nam, Taek-Keun;Kim, Hyeong-Rok;Nah, Byung-Sik;Chung, Woong-Ki;Kim, Young-Jin;Ahn, Sung-Ja;Song, Ju-Young;Jeong, Jae-Uk
    • Radiation Oncology Journal
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    • v.26 no.4
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    • pp.247-256
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    • 2008
  • Purpose: The purpose of this study is to evaluate anal sphincter preservation rates, survival rates, and prognostic factors in patients with rectal cancer treated with preoperative chemoradiotherapy. Materials and Methods: One hundred fifty patients with pathologic confirmed rectal cancer and treated by preoperative chemoradiotherapy between January 1999 and June 2007. Of the 150 patients, the 82 who completed the scheduled chemoradiotherapy, received definitive surgery at our hospital, and did not have distant metastasis upon initial diagnosis were enrolled in this study. The radiation dose delivered to the whole pelvis ranged from 41.4 to 46.0 Gy (median 44.0 Gy) using daily fractions of $1.8{\sim}2.0\;Gy$ at 5 days per week and a boost dose to the primary tumor and high risk area up to a total of $43.2{\sim}54\;Gy$ (median 50.4 Gy). Sixty patients (80.5%) received 5-fluorouracil, leucovorin, and cisplatin, while 16 patients (19.5%) were administered 5-fluorouracil and leucovorin every 4 weeks concurrently during radiotherapy. Surgery was performed for 3 to 45 weeks (median 7 weeks) after completion of chemoradiotherapy. Results: The sphincter preservation rates for all patients were 73.2% (60/82). Of the 48 patients whose tumor was located at less than 5 cm away from the anal verge, 31 (64.6%) underwent sphincter-saving surgery. Moreover, of the 34 patients whose tumor was located at greater than or equal to 5 cm away from the anal verge, 29 (85.3%) were able to preserve their anal sphincter. A pathologic complete response was achieved in 14.6% (12/82) of all patients. The downstaging rates were 42.7% (35/82) for the T stage, 75.5% (37/49) for the N stage, and 67.1% (55/82) for the overall stages. The median follow-up period was 38 months (range $11{\sim}107$ months). The overall 5-year survival, disease-free survival, and locoregional control rates were 67.4%, 58.9% and 84.4%, respectively. The 5-year overall survival rates based on the pathologic stage were 100% for stage 0 (n=12), 59.1% for stage I (n=16), 78.6% for stage II (n=30), 36.9% for stage III (n=23), and one patient with pathologic stage IV was alive for 43 months (p=0.02). The 5-year disease-free survival rates were 77.8% for stage 0, 63.6% for stage I, 58.9% for stage II, 51.1% for stage III, and 0% for stage IV (p<0.001). The 5-year locoregional control rates were 88.9% for stage 0, 93.8% for stage I, 91.1% for stage II, 68.2% for stage III, and one patient with pathologic stage IV was alive without local recurrence (p=0.01). The results of a multivariate analysis with age (${\leq}55$ vs. >55), clinical stage (I+II vs. III), radiotherapy to surgery interval (${\leq}6$ weeks vs. >6 weeks), operation type (sphincter preservation vs. no preservation), pathologic T stage, pathologic N stage, pathologic overall stage (0 vs. I+II vs. III+IV), and pathologic response (complete vs. non-CR), only age and pathologic N stage were significant predictors of overall survival, pathologic overall stage for disease-free survival, and pathologic N stage for locoregional control rates, respectively. Recurrence was observed in 25 patients (local recurrence in 10 patients, distant metastasis in 13 patients, and both in 2 patients). Acute hematologic toxicity ($\geq$grade 3) during chemoradiotherapy was observed in 2 patients, while skin toxicity was observed in 1 patient. Complications developing within 60 days after surgery and required admission or surgical intervention, were observed in 11 patients: anastomotic leakage in 5 patients, pelvic abscess in 2 patients, and others in 4 patients. Conclusion: Preoperative chemoradiotherapy was an effective modality to achieve downstaging and sphincter preservation in rectal cancer cases with a relatively low toxicity. Pathologic N stage was a statistically significant prognostic factor for survival and locoregional control and so, more intensified postoperative adjuvant chemotherapy should be considered in these patients.

A BIOCHEMICAL INVESTIGATION OF THE ROLE OF $IL-1{\beta}$ UPON INFlAMMATION IN MOUSE (마우스에서 $IL-1{\beta}$가 염증의 발현에 미치는 영향에 관한 연구)

  • Yoon, Duk-Sang;Lee, Ki-Soo
    • The korean journal of orthodontics
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    • v.28 no.4 s.69
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    • pp.611-626
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    • 1998
  • Cytokines are intercellular peptide mediators that regulate homeostasis and host defense reactions in living body. Of the diversity of cytokines in terms of biological accomplishment, interleukin $1-{\beta}$($IL-1{\beta}$) and tumor necrosis factor(TNF) are the most conspicuous cytokines with a wide variety of effects on cells involved in inflammatory and immune responses, and likely to be involved in the inflammatory pathogenesis of oral tissue as well. The present study was designed to explicate the role of $IL-1{\beta}$ on inflammatory revelation of oral tissues in mice biochemically. In the Induced arthritis by injection of 10${\mu}g$ LPS shown the relaese of 0.93 ${\mu}g$ $IL-1{\beta}$/joint with a peak at at 4-5 h. and diminished at 24t and the release of $TNF_{\alpha}$ of 1.25 ${\mu}g$/joint with a peak at 2-3h and diminished at 6h. After injection of th $IL-1{\beta}$ into the joint, the mumber of leucocytes proliferated with a peak at 4-5h and diminished at 36h and the loss of proteoglycan showed with maximum at 15-30h. After injection of $IL-1{\beta}$ into the oral tissue, cycloosygenase metabolites ($PGE_2$) accumulated in the oral tissue with dose dependant. These elucidated $IL-1{\beta}$ to be inflammatory mediator in the early phase of its pathogenesis. Intraoral injection of recombinant $IL-1{\beta}$ induced the proliferation of leukocytes in situ. $IL-1{\beta}$ took an pertinent part in the development of inflammation and the succession of cellular infiltration. The results exemplify that $IL-1{\beta}$ plays a significant role in mediating inflammatory response induced by LPS in oral tissue, the inflammatory response is regulated by $IL-1{\beta}$ at an acute phase of pathogenesis.

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The Results of Radiation Therapy in Stage III Non-Small Cell Lung Cancer (III기 비소세포성 폐암의 방사선치료 성적)

  • Choi, Sang-Gyu;Oh, Do-Hoon;Bae, Hoon-Sik
    • Radiation Oncology Journal
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    • v.13 no.4
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    • pp.311-319
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    • 1995
  • Purpose : To evaluate the survival and prognostic factors in patients with stage III non-small cell lung cancer treated with curative radiotherapy alone or combined with chemotherapy Materials and Methods : A retrospective analysis was undertaken of 35 patients who had locally advanced non-small-cell lung cancer and treated with curative radiotherapy in Department of Therapeutic Radiology, Kangdong Sacred Heart Hospital, from January 1991 through December 1993. According to AJCC staging, 15 patients were stage IIIA, and 20 were stage IIIB. Radiotherapy was delivered with 1 8-2 Gy per fraction/day. 5 days per week using 6 MV X-ray, to a total dose ranging from 48.8 Gy to 66.6 Gy (median, 61.2 Gy) in 4 to 9 weeks. Ten patients received neoadjuvant or concurrent chemotherapy with FIP (5-FU, ifosfamide, and cisplatin) or FP (5-FU and cisplatin) Results : For all Patients, median survival was 6 months. 1-year and 2-year survival rates were 23.3% and 6.7%, respectively The median survival was 8 months in stage IIIA and 5.5 months in stage IIIB. In patients treated with radiation therapy alone, median survival was 5 months and 1-year survival rate was 9%. In patients who received chemotherapy, median survival was 11 months and 1-year survival rate was 60%. The difference of survival between these two groups was statistically significant (p=0.03). Total radiation dose, degree of response, and Post-treatment ECOG score were also significantly associated with survival. But it was not affected by age, sex, pretreatment ECOG score, presence or absence of weight loss, tumor location. pathologic type, N stage, and degree of response to treatment. Conclusion : Conventional radiotherapy alone is unlikely to achieve long term survival in patients with stage III NSCLC. Radiotherapy with altered fractionation schedule or multimodality treatment combined with surgery and/or chemotherapy should be considered if feasible.

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Combined Transcatheter Arterial Chemoembolization and Local Radiotherapy for Unresectable Hepatocellular Carcinoma (절제불가능 원발성 간암에서 경간동맥 항암 색전술과 국소 방사선의 병용요법)

  • Seong Jinsil;Keum Ki Chang;Han Kwang Hyub;Lee Do Yun;Lee Jong Tae;Chon Chae Yoon;Moon Young Myoung;Kim Gwi Eon;Suh Chang Ok
    • Radiation Oncology Journal
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    • v.16 no.2
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    • pp.159-165
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    • 1998
  • Purpose : The best prognosis for hepatocellular carcinoma can be achieved with surgical resection. However, the number of resected cases is limited due to the advanced lesion or associated liver disease. A trial of combined transcatheter arterial chemoembolization(TACE) and local radiotherapy(RT) for unresectable hepatocellular carcinoma(HCC) was prospectively conducted and its efficacy and toxicity were investigated. Materials and Methods : From 1992 to 1994, 30 Patients with unresectable HCC due either to advanced lesion or to associated cirrhosis were entered in the study Exclusion criteria included the presence of extrahepatic metastasis, liver cirrhosis of Child's class C, tumors occupying more than two-thirds of the whole liver, and an ECOG scale of more than 3. Patient cHaracteristics were : mean tumor size $8.95\pm3.4cm$, serum AFP+ in all patients, portal vein thrombosis in all patients, liver cirrhosis in 22 patients, and UICC stage III and IVA in 10 and 20 patients, respectively. TACE was performed with the mixture of Lipiodol(5ml) and Adriamycin(50mg) and Gelfoam embolizatin. RT(mean dose $44.0\pm9.3Gy$) 10 days with conventional fractionation. Results : An objective response was observed in 19 patients($63.3\%$). Survival rates at 1 2, and 3 years were $67\%,\;33.3\%$ and $22.2\%$, respectively. Median survival was 17 months. There were 6 patients surviving more than 3 years. Distant metastasis occurred in 10 patients, with 8 in the lung only and 2 in both lung and bone, Toxicity included transient elevation of liver function test in all patients, fever in 20, thrombocytopenia in 4, and nausea and vomiting in 1. There was no treatment-related death. Conclusion : Combined TACE and RT appear to produce a favorable response and survival results with minimal toxicity.

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Effect of Black Garlic Extract on Cytokine Generation of Mouse Spleen Cells (흑마늘(Black garlic) 추출물이 마우스 비장세포의 Cytokine 생성에 미치는 영향)

  • Seo, Min Jeong;Kang, Byoung Won;Park, Jeong Uck;Kim, Min Jeong;Lee, Hye Hyeon;Ryu, En Ju;Joo, Woo Hong;Kim, Kwang Hyuk;Jeong, Yong Kee
    • Journal of Life Science
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    • v.23 no.1
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    • pp.63-68
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    • 2013
  • The effect of black garlic extract on the activation of spleen cells from a C57BL6 mouse was investigated to examine immune activities of of fermented black garlic containing a variety of bioactive substances. xtract obtained from the concentration of commercial Namhae black garlic was used for the analysis of immune activities. Treatment with the extract increased the expression of interleukin-2 (IL-2) cytokine. The simultaneous administration of the extract plus lipopolysaccharide (LPS) increased the expression of IL-2, tumor necrosis factor (TNF)-${\alpha}$, and interferon (IFN)-${\gamma}$ compared with that of a control group. This result suggests that cellular immunity can be induced by macrophages, resulting in the expression of T lymphocytes and T helper type 1 (Th1) cells. In addition, treatment with the extract increased the late response of IL-6 cytokines, and the extract plus LPS augmented the expression of IL-4 and IL-6 compared with that of an LPS-treated group. Meanwhile, the extract plus LPS decreased the late response of IL-10, suggesting that humoral immunity can be activated by stimulating B lymphocytes, suppressing cellular immunity, and effectively modulating the conversion into humoral immune responses. These findings demonstrate that the black garlic extract activates Th1 and Th2 cells by stimulating T lymphocytes in mouse spleen cells and leads to immunomodulation by activating cellular and humoral immune responses of the immune system.

Preliminary Results of Stereotactic Radiosurgery Using Stereotactic Body Frame (정위 체부 고정틀을 이용한 체부 방사선수술의 예비적 결과)

  • Ahn Seung Do;Yi Byong Yong;Choi Eun Kyung;Kim Jong Hoo;Nho Young Ju;Shin Kyung Hwan;Kim Kyoung Ju;Chung Won Kyun;Chang Hyesook
    • Radiation Oncology Journal
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    • v.18 no.4
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    • pp.251-256
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    • 2000
  • Purpose : To evaluate efficacy and complication of stereotactic radiosurgery using stereotactic body frame. Methods and Materials :From December 1997 to June 1999, 11 patients with primary and metastatic tumors were treated with stereotactic radiosurgery using stereotactic body frame(Precision TherapyTu). Three patients were treated with primary hepatoma and seven with metastatic tumor from liver, lung, breast, trachea and one with arteriovenous malformation on neck. We used vacuum pillow for immobilization and made skin marker on sternum and tibia area with chest marker and leg marker. Diaphragm control was used for reducing movement by respiration. CT-simulation and treatment planning were peformed. Set-up error was checked by CT-Simulator before each treatment. Dose were calculated on the 80$\~$90$\%$ isodose of isocenter dose and given consecutive 3 fractions for total dose of 30 Gy (10 Gy/fraction). Results :Median follow-up was 12 months. One patient (9$\%$) showed complete response and four Patients (36$\%$) showed partial response and others showed stable disease. Planning target volumes (PTV) ranged from 3 to 111 cc (mean 18.4 n). Set-up error was within 5 mm in all directions (X, Y, Z axis). There was no complication in all patients. Conclusion :In Primary and metastatic tumors, stereotactic body frame is very safe, accurate and effective treatment modality.

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Predominant T Helper 1 Immune Response in Women with Reproductive Failures (반복 유산 및 착상실패를 보이는 환자에서 Th1 면역반응에 대한 연구)

  • Han, Ae-Ra;Yang, Kwang-Moon;KwakKim, Joanne
    • Clinical and Experimental Reproductive Medicine
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    • v.37 no.3
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    • pp.231-237
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    • 2010
  • Objective: To evaluate whether T helper 1 (Th1) immune response is predominant in women with reproductive failures (recurrent spontaneous abortion and recurrent implantation failure) and the activation of T cell is related to Th1 propensity. Methods: Women with a history of recurrent implantation failure or recurrent spontaneous abortion comprise the study group (n=37). Controls are normal fertile women without a history of infertility or pregnancy losses (n=11). Th1/Th2 ratios of interferon (INF)-$\gamma$/interleukin (IL)-10 and tumor necrosis factor (TNF)-$\alpha$/IL-10 expression on $CD3^+/4^+$ cells, CD154, and CD69 expression on T cells are measured by flow cytometric analysis. Results: The ratios of TNF-$\alpha$ to IL-10 expressing on $CD3^+/4^+$ cells (Th1/Th2 cell ratios) are significantly higher in study group ($42.1{\pm}2.3$) as compared with that of controls ($28.7{\pm}2.7$) (p=0.002). The overall trend of CD154 and CD69 expression on T cells are elevated in study group than those of controls. The proportion (%) of $CD3^+/4^+/154^+$ cells ($1.7{\pm}0.5$ vs. $0.3{\pm}0.2$, p=0.038) and the % of $CD3^+/8^+/154^+$ cells ($0.6{\pm}0.2$ vs. $0.1{\pm}0.0$, p=0.024) are significantly higher in study group. The % of $CD3^+/69^+$ cells ($5.6{\pm}1.9$ vs. $1.3{\pm}5.4$, p=0.046) and % of $CD3^+/8^+/69^+$ cells ($4.8{\pm}1.3$ vs. $1.8{\pm}0.2$, p=0.035) among $CD3^+/8^+$ cells are significantly increased in study group. Conclusion: Women with reproductive failures have Th1 propensity with increased T cell activation. These finding means that activated T cell has a harmful effect on early pregnancy and implantation by induction of Th1 immunity.

Thermoradiotherapy in the Treatment of Advanced Stomach Cancer - To compare the difference between the results of Pre- and post-radiotherapy hyperthermia - (진행성 위암 환자에서 방사선 치료 전후에 실시한 국소온열치료)

  • Kay Chul Seung;Choi Ihl Bohng;Jang Ji Young;Kim In Ah
    • Radiation Oncology Journal
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    • v.16 no.1
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    • pp.27-33
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    • 1998
  • Purpose : To improve the therapeutic results of postoperative recurrent disease and inoperable disease of stomach cancer, we used the thermoradiotherapy. We conducted a retrospective analysis of the results and compared the results of hyperthermia before radiotherapy and those of hyperthermia after radiotherapy Materials and Methods : From July 1994 to November 1996, we treated twenty patients with locally advanced stomach cancer and recurrent stomach cancer with thermoradiotherapy. We divided those patients into two groups : hyperthermia before radiotherapy group (PreRT group : 13 Patients) and hyperthermia after radiotherapy group (PostRT group : 7 patients). We performed radiation therapy with the total tumor dose of 3000-5040cGy in a traction of 180-300cGy and 5 fractions per week. Hyperthermia was performed with 8 MHz radiofrequency apparatus. PreRT group patients were treated daily for 30 minutes before the radiation therapy within the interval of ten minutes. And PostRT group patients were treated with 1-2 sessions Per week for 40-60 minutes after the radiation therapy within the interval of 10 minutes. Results : Overall response rate was $33.3\%$. This response rate appeared the same in both groups. Mean survival and 1 rear survival rate were 10.3 months and $16.5\%$. In PreRT group, mean survival and 1 year survival rate were 6.8 months and $9.0\%$, and in PostRT group, mean survival and 1 year survival rate were 7.7 months and $34\%$. There were no statistically significant difference between the prognostic factors and therapeutic results. Conclusion : The thermoradiotherapy was a safe treatment method in advanced and recurrent gastric cancer when compared with other treatment. Because the number of patients we treated was small and the follow up period was short. we were not able to draw any conclusions about the therapeutic efficacy of the sequence of radiation therapy and hyperthermia. Therefore, further clinical trials of thermoradiotherauy for stomach cancer appear to be warranted.

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Circulating Cytokine Levels and Changes During the Treatment in Patients with Active Tuberculosis in Korea (결핵 환자의 치료경과 중 혈청 내 Cytokine 분비와 변화)

  • Ryu, Yon-Ju;Kim, Yun-Jung;Kwon, Jung-Mi;Na, Youn-Ju;Jung, Yu-Jin;Seoh, Ju Young;Cheon, Seon Hee
    • Tuberculosis and Respiratory Diseases
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    • v.55 no.2
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    • pp.140-153
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    • 2003
  • Background : The cell-mediated immune reaction to tuberculosis infection involves a complex network of cytokines. The extent of inflammation, tissue damage and severity of the disease suggested to be determined by the balance between extent and duration of the proinflammatory cytokine response versus those of the suppressive cytokines. The systemic cytokine response in pathogenesis of tuberculosis can be assessed by measuring serum cytokine levels. Method : Serum interleukin-1 beta(IL-$1{\beta}$), IL-2, IL-4, IL-6, IL-10, IL-12(p40), tumor necrosis factor-alpha(TNF-${\alpha}$), interferon-gamma(IFN-${\gamma}$) and transforming growth factor-beta(TGF-${\beta}$) levels were measured in 83 patients with pulmonary tuberculosis, 10 patients with endobronchial tuberculosis before treatment and 20 healthy subjects by using a sandwich ELISA. In patients with pulmonary tuberculosis, they were divided into mild, moderate and far advanced group according to the severity by ATS guidelines. To compare with those of pretreatment levels, we measured serum IL-$1{\beta}$, IL-2, IL-4, IL-6, IL-10, IL-12(p40), TNF-${\alpha}$, IFN-${\gamma}$ and TGF-${\beta}$ levels in 45 of 83 patients with pulmonary tuberculosis after 2 and 6 months of treatment. Results : 1) In sera of patients with active pulmonary tuberculosis(n=83), IL-$1{\beta}$, IL-6(p<0.05), TNF-${\alpha}$, and IFN-${\gamma}$ were elevated and TGF-${\beta}$ was decreased comparing to control. IL-2, Il-12(p40), IL-4 and IL-10 were similar between the patients with tuberculosis and control. 2) In endobronchial tuberculosis, IL-6 and TNF-${\alpha}$ were elevated and TGF-${\beta}$ was decreased comparing to control. IL-12(p40) seemed to be elevated comparing to pulmonary tuberculosis. 3) Far advanced tuberculosis showed markedly elevated IL-6 and IFN-${\gamma}$ level(p<0.05). 4) The significant correlations were noted between IL-1, IL-6 AND TNF-${\alpha}$ and between IL-12, Il-2 and IL-4(p<0.01). 5) After 2 and 6 months of standard treatment, the level of IL-6 and IFN-${\gamma}$ was significantly decreased(p<0.05). Conclusion : These results showed that an altered balance between cytokines is likely to be involved in the extent of inflammation, tissue damage and severity of the disease tuberculosis. But, it should be considered diversities of cytokine response according to type of tuberculosis and immunity in clinical application and interpreting future studies.

The Role of Poly(ADP-ribose) Polymerase-1 in Ventilator-Induced Lung Injury (기계환기로 인한 급성 폐손상에서 poly(ADP-ribose) polymerase-1의 역할)

  • Kim, Je-Hyeong;Yoon, Dae Wui;Hur, Gyu Young;Jung, Ki Hwan;Lee, Sung Yong;Lee, Sang Yeub;Shin, Chol;Shim, Jae Jeong;In, Kwang Ho;Yoo, Se Hwa;Kang, Kyung Ho
    • Tuberculosis and Respiratory Diseases
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    • v.60 no.4
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    • pp.451-463
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    • 2006
  • Background : Reactive oxygen species (ROS) take center stage as executers in ventilator-induced lung injury (VILI). The protein with DNA-damage scanning activity, poly (ADP-ribose) polymerase-1 (PARP1), signals DNA rupture and participates in base-excision repair. Paradoxically,overactivation of PARP1 in response to massive genotoxic injury such as ROS can induce cell death through ${\beta}$ -nicotinamide adenine dinucleotide ($NAD^+$) depletion, resulting in inflammation. The purpose of this study is to investigate the role of PARP1 and the effect of its inhibitor in VILI. Methods : Forty-eight male C57BL/6 mice were divided into sham, lung protective ventilation(LPV), VILI, and PARP1 inhibitor (PJ34)+VILI (PJ34+VILI) groups. Mechanical ventilator setting for the LPV group was $PIP\;15cmH_2O$ + $PEEP\;3cmH_2O$ + RR 90/min + 2 hours. The VILI and PJ34+VILI groups were ventilated on a setting of $PIP\;40cmH_2O$ + $PEEP\;0cmH_2O$ + RR 90/min + 2 hours. As a PARP1 inhibitor for the PJ34+VILI group, 20 mg/Kg of PJ34 was treated intraperitoneally 2 hours before mechanical ventilation. Wet-to-dry weight ratio and acute lung injury (ALI) score were measured to determine the degree of VILI. PARP1 activity was evaluated by using an immunohistochemical method utilizing biotinylated NAD. Myeloperoxidase (MPO) activity and the concentration of inflammatory cytokines such as tumor necrosis factor $(TNF)-{\alpha}$, interleukin $(IL)-1{\beta}$, and IL-6 were measured in bronchoalveolar lavage fluid (BALF). Results : In the PJ34+VILI group, PJ34 pretreatment significantly reduced the degree of lung injury, compared with the VILI group (p<0.05). The number of cells expressing PARP1 activity was significantly increased in the VILI group, but significantly decreased in the PJ34+VILI group (p=0.001). In BALF, MPO activity, $TNF-{\alpha}$, $IL-1{\beta}$, and IL-6 were also significantly lower in the PJ34+VILI group (all, p<0.05). Conclusion : PARP1 overactivation plays a major role in the mechanism of VILI. PARP1 inhibitor prevents VILI, and decreases MPO activity and inflammatory cytokines.