• Title/Summary/Keyword: 암치료

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Tumorigenesis after Injection of Lung Cancer Cell Line (SW-900 G IV) into the Pleural Cavity of Nude Mice (누드마우스의 흉강에 폐암세포주의 주입에 의한 종양형성과 HER2/neu와 TGF-${\beta}_1$의 발현)

  • Park, Eok-Sung;Kim, Song-Myung;Kim, Jong-In
    • Journal of Chest Surgery
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    • v.43 no.6
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    • pp.588-595
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    • 2010
  • Background: Base on types of tumor, the types of expressed tumor is diverse and the difference in its expression rate is even more various. Due to such reasons an animal model is absolutely needed for a clinical research of lung cancer. The author attempted oncogenesis by cultivating a cell line of non-small cell carcinoma and then injecting it inside thoracic cavities of nude mice. The author conducted quantitative analyses of HER2/neu tumor gene - an epidermal growth factor receptor (EGFR) related to lung cancer, and TGF-${\beta}_1$, which acts as a resistance to cell growth inhibition and malignant degeneration. In order to investigate achievability of the oncogenesis, histological changes and the expression of cancer gene in case of orthotopic lung cancer is necessary. Material and Method: Among 20 immunity-free male BALB/c, five nude mice were selected as the control group and rest as the experimental group. Their weights ranged from 20 to 25 gm (Orient, Japan). After injection of lung cancer line (SW900 G IV) into the pleural cavity of nude mice, They were raised at aseptic room for 8 weeks. HER2/neu was quantitatively analyzed by separating serum from gathered blood via chemiluminiscent immunoassay (CLIA), and immunosandwitch method was applied to quantitatively analyze TGF-${\beta}_1$. SPSS statistical program (SPSS Version 10.0, USA) was implemented for statistical analysis. Student T test was done, and cases in which p-value is less than 0.05 were considered significant. Result: Even after lung cancer was formed in the normal control group or after intentionally injected lung cancer cell line, no amplification of HER2/neu gene showed reaction. However, the exact quantity of TGF-${\beta}_1$ was $28,490{\pm}8,549pg/mL$, and the quantity in the group injected with lung cancer cell was $42,362{\pm}14,449pg/mL$, meaning 1.48 times highly Significant (p<0.483). It proved that HER2/neu gene TGF-${\beta}_1$ had no meaningful interconnection. Conclusion: TGF-${\beta}_1$ gene expressed approximately 1.48 times amplification in comparison to the control group. The amplification of TGF-${\beta}_1$ meant somatic recuperation inhibition mechanism due to carcinogenesis in nude mice was definitely working. It may be implemented as a quantitative analysis that allows early detection of lung cancer in human body.

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.

Evaluation of Standardized Uptake Value and Metabolic Tumor Volume between Reconstructed data and Re-sliced data in PET Study (PET 검사 시 Reconstructed data와 Re-sliced data의 표준섭취계수와 Metabolic Tumor Volume의 비교 평가)

  • Do, Yong Ho;Lee, Hong Jae;Kim, Jin Eui
    • The Korean Journal of Nuclear Medicine Technology
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    • v.20 no.2
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    • pp.3-8
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    • 2016
  • Purpose SUV is one of the parameters that assist diagnosis in origin, metastasis and staging of cancer. Specially, it is important to compare SUV before and after chemo or radiation therapy to find out effectiveness of treatment. Storing PET data which has no quantitative change is needed for SUV comparison. However, there is a possibility to loss the data in external hard drive or MINIpacs that are managed by department of nuclear medicine. The aim of this study is to evaluate SUV and metabolic tumor volume (MTV) among reconstructed data (R-D) in workstation, R-D and re-sliced data (S-D) in PACS. Materials and Methods Data of 20 patients (aged $60.5{\pm}8.3y$) underwent $^{18}F-FDG$ PET (Biograph truepoint 40, mCT 40, mCT 64, mMR, Siemens) study were analysed. $SUV_{max}$, $SUV_{peak}$ and MTV were measured in liver, aorta and tumor after sending R-D in workstation, R-D and S-D in PACS to syngo.via software. Results R-D of workstation and PACS showed the same value as mean $SUV_{max}$ in liver, aorta and tumor were $2.95{\pm}0.59$, $2.35{\pm}0.61$, $10.36{\pm}6.15$ and $SUV_{peak}$ were $2.70{\pm}0.51$, $2.07{\pm}0.43$, $7.67{\pm}3.73$(p>0.05) respectively. Mean $SUV_{max}$ of S-D in PACS were decreased by 5.18%, 7.22%, 12.11% and $SUV_{peak}$ 2.61%, 3.63%, 10.07%(p<0.05). Correlation between R-D and S-D were $SUV_{max}$ 0.99, 0.96, 0.99 and $SUV_{peak}$ 0.99, 0.99, 0.99. And 2SD in balnd-altman analysis were $SUV_{max}$ 0.125, 0.290, 1.864 and $SUV_{peak}$ 0.053, 0.103, 0.826. MTV of R-D in workstation and PACS show the same value as $14.21{\pm}12.72cm^3$(p>0.05). MTV in PACS was decreased by 0.12% compared to R-D(p>0.05). Correlation and 2SD between R-D and S-D were 0.99 and 2.243. Conclusion $SUV_{max}$, $SUV_{peak}$, MTV showed the same value in both of R-D in workstation and PACS. However, there was statistically difference in $SUV_{max}$, $SUV_{peak}$ of S-D compare to R-D despite of high correlation. It is possible to analyse reliable pre and post SUV if storing R-D in main hospital PACS system.

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Facters Affecting Recurrence after Video-assisted Thoracic Surgery for the Treatment of Spontaneous Pneumothotax (자연기흉에 대한 비디오흉강경수술후 재발에 영향을 미치는 요인들)

  • 이송암;김광택;이일현;백만종;최영호;이인성;김형묵;김학제
    • Journal of Chest Surgery
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    • v.32 no.5
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    • pp.448-455
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    • 1999
  • Background: Recent developments in techniques of video-assisted thoracic surgery(VATS) and endoscopic equipment has expanded the application of video-assisted surgical procedures in the field of thoracic surgery. Especially, it will probably become the treatment of choice of spontaneous pneumothorax(SP). There is, however, a high recurrence rate, high cost, and paucity of long-term results. We report the results of postoperative follow-up and analyze perioperative parameters affected to recurrence, retrospectively. Material and Method: From march 1992 to march 1997, 276 patients with spontaneous pneumothorax underwent 292 VATS procedures. Conversion to open thoracotomy was necessitated in eight patients, and this patients excluded from the study. Result: The sex distribution was 249 males and 31 females. The mean age was 28.1 12.2 years(range, 15 to 69 years). Primary SP was 237cases(83.5%) and secondary SP was 47cases(16.5%). The major underlying lung diseases associated with secondary SP were tuberculosis 27cases(57.4%) and emphysema 8cases (38.3%). Operative indications included Ipsilateral recurrence 123(43.9%), persistent air-leak 53(18.9%), x-ray visible bleb 40(14.3%), tension 30(10.7%), contralateral recurrence 21(7.5%), uncomplicated first episode 8(2.9%), bilateral 3(1.1%), complicated episode 2(0.7%). Blebs were visualized in 247cases(87%) and 244cases(85.9%) performed stapled blebectomy. Early postoperative complications occurred in 33 cases(11.6%): 16 prolonged air-leak more than 5 days(four of them were required a second operation and found missed blebs); 5 bleeding; 5 empyema; 2 atelectasis; 1 wound infection. No deaths occured. The mean operative time was 52.8 23.1 minutes(range, 20 to 165 minutes). The mean d ration of chest tube drainage was 5.0 4.5 days(range, 2 to 37 days). The mean duration ofhospital stay was 8.2 5.5 days (range, 3 to 43days). At a mean follow-up 22.3 18.4 months(range, 1 to 65 months), 12 patients(4.2%) were lost to follow-up. There were 24 recurrences and seven patients underwent second operation and 6 patients(85.7%) were found the missed blebs. 12 perioperative parameters(age, sex, site, underlying disease, extent of collapse, operative indication, size of bleb, number of bleb, location of bleb, bleb management, pleural procedure, prolonged postoperative air-leak) were analyzed statistically to identify significant predictors of recurrence. The significant predictors of recurrence was the underlying disease[17.0%(8/47): 6.8%(16/237), p=0.038], prolonged postoperative air-leakage[37.5%(6/16): 6.7%(18/268), p=0.001], and pleural procedure [11.4%(19/167): 4.3%(5/117), p=0.034]. Blebectomy has less recurrence rate then non-blebectomy [8.2%(20/244) : 10.0%(4/40), p>0. 5]. However, this difference was not statistically significant(p=0.758). Conclusion: We conclude that it is important that we shoud careful finding of bleb during VATS due to reducing of recurrnece, and cases of no bleb identified and secondary spontaneous pneumothorax were indicated of pleurodectomy. VATS is a valid alternative to open procedure for the treatment of spontaneous pneumothorax with less pain, shorter hospital stay, more rapid return to work, high patient acceptance, less scar and exellent cosmetics. But, there is high recurrence rate and high cost, and than it is necessary to evaluate of long-term results for recurrence and to observate carefully during VATS.

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Metabolic risk and nutritional state according to breakfast energy level of Korean adults: Using the 2007~2009 Korea National Health and Nutrition Examination Survey (한국 성인의 아침식사 에너지 수준에 따른 대사적 위험과 영양상태: 2007~2009년 국민건강영양조사 자료 이용)

  • Jang, So-Hyoun;Suh, Yoon Suk;Chung, Young-Jin
    • Journal of Nutrition and Health
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    • v.48 no.1
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    • pp.46-57
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    • 2015
  • Purpose: The aim of this study was to determine an appropriate energy level of breakfast with less risk of chronic disease for Korean adults. Methods: Using data from the 2007~2009 Korean National Health & Nutrition Examination Survey, from a total of 12,238 adults aged 19~64, the final 7,769 subjects were analyzed except subjects who were undergoing treatment for cancer or metabolic disorder. According to the percent of breakfast energy intake versus their estimated energy requirement (EER), the subjects were divided into four groups: < 10% (very low, VL), 10~20% (low, L), 20~30% (moderate, M), ${\geq}30%$ (sufficient, S). All data were analyzed on the metabolic risk and nutritional state after application of weighted value and adjustment of sex, age, residential area, income, education, job or jobless, and energy intake using a general linear model or logistic regression. Results: The subjects of group S were 16.9% of total subjects, group M 39.2%, group L 37.6%, and group VL 6.3%. The VL group included more male subjects, younger-aged (19 to 40 years), urban residents, higher income, higher education, and fewer breakfasts eaters together with family members. Among the 4 groups, the VL group showed the highest waist circumference, while the S group showed the lowest waist circumference, body mass index, and serum total cholesterol. The groups of VL and L with lower intake of breakfast energy showed high percent of energy from protein and fat, and low percent of energy from carbohydrate. With the increase of breakfast energy level, intake of energy, most nutrients and food groups increased, and the percentage of subjects consuming nutrients below EAR decreased. The VL group showed relatively higher intake of snacks, sugar, meat and eggs, oil, and seasonings, and the lowest intake of vegetable. Risk of obesity by waist circumference was highest in the VL group by 1.90 times of the S group and the same trend was shown in obesity by BMI. Risk of dyslipidemia by serum total cholesterol was 1.84 times higher in the VL group compared to the S group. Risk of diabetes by Glu-FBS (fasting blood sugar) was 1.57 times higher in the VL group compared to the S group. Conclusion: The results indicate that higher breakfast energy level is positively related to lower metabolic risk and more desirable nutritional state in Korean adults. Therefore, breakfast energy intake more than 30% of their own EER would be highly recommended for Korean adults.

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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Antitumor and Antimetastatic Effects of Toxoplasma Gondii in Mice with Lewis Lung Carcinoma (Lewis 폐암 마우스 모델에서 톡소포자충에 의한 항암 및 항전이 효과)

  • Kim, Ju-Ock;Jung, Sung-Soo;Park, Hee-Sun;Kim, Myoung-Hoon;Kim, Sun-Young;Lee, Young-Ha
    • Tuberculosis and Respiratory Diseases
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    • v.52 no.4
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    • pp.317-329
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    • 2002
  • Background : Immunotherapy is another treatment modality for various cancers. There is little information on the antitumor effects of immunotherapy on implanted lung cancer mouse models. Toxoplasma gondii is able to potently induce a nonspecific stimulation of the host immune system. Therefore, this study evaluated the antitumor and antimetastatic effect of nonspecific immune stimulation by T. gondii in a Lewis lung cancer mouse model. Methods : Female C57BL/6 mice were injected with either Lewis lung cancer cells ($1{\times}10^6$ per mouse) or 5 cysts from the T. gondii Me49 strain with various schedules. The number of survival days, the tumor size of the implanted muscle and the histopathological findings of each group were noted. In addition to these mice, the Toxoplasma antigen($50{\mu}g$ per mouse) or a lymphokine (0.5 ml per mouse) was added to boost the immunotherapy. Results : No mouse in the Toxoplasma-infected group had died, whereas the mice receiving only the cancer cells (cancer control) survived for $29.1{\pm}4.4$ days. Cancer cells were revealed from 1 week after cancer cell inceulation in the muscle and from 3 weeks in the lung of the cancer control, whereas cancer cells were found in both the preinfection control and coinfection control groups from 2 weeks and 4 weeks in the lung respectively. The in the number of survival days were $32.4{\pm}3.3$ in the mice receiving T. gondii 2 weeks prior to the cancer cells inoculation (preinfection control), $30.9{\pm}5.1$ in mice received both simultaneously (coinfection control), and $34.9{\pm}2.9$ in mice received T. gondii 2 weeks after cancer cells implantation (postinfection control). These 3 infection groups had significantly longer survival days and suppressed tumor growth than those of the cancer control. In addition to these mice, and injection with the Toxoplasma antigen alone or in combination with lymphokine resulted in a significant increase in the number of survival days. Conclusion : These findings suggest that an injection with T. gondii can induce the antitumor and antimetastatic effects in Lewis lung cancer mouse models. Moreover, these effects were increased with an injection of the Toxoplasma antigen alone or in combination with lymphokine. However, this therapy can not prevent the development of cancer.

The Relationship between Expression of EGFR, MMP-9, and C-erbB-2 and Survival Time in Resected Non-Small Cell Lung Cancer (수술을 시행한 비소세포 폐암 환자에서 EGFR, MMP-9 및 C-erbB-2의 발현과 환자 생존율과의 관계)

  • Lee, Seung Heon;Jung, Jin Yong;Lee, Kyoung Ju;Lee, Seung Hyeun;Kim, Se Joong;Ha, Eun Sil;Kim, Jeong-Ha;Lee, Eun Joo;Hur, Gyu Young;Jung, Ki Hwan;Jung, Hye Cheol;Lee, Sung Yong;Lee, Sang Yeub;Kim, Je Hyeong;Shin, Chol;Shim, Jae Jeong;In, Kwang Ho;Kang, Kyung Ho;Yoo, Se Hwa;Kim, Chul Hwan
    • Tuberculosis and Respiratory Diseases
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    • v.59 no.3
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    • pp.286-297
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    • 2005
  • Background : Non-small cell lung cancer (NSCLC) is a common cause of cancer-related death in North America and Korea, with an overall 5-year survival rate of between 4 and 14%. The TNM staging system is the best prognostic index for operable NSCLC . However, epidermal growth factor receptor (EGFR), matrix metalloproteinase-9(MMP-9), and C-erbB-2 have all been implicated in the pathogenesis of NSCLC and might provide prognostic information. Methods : Immunohistochemical staining of 81 specimens from a resected primary non-small cell lung cancer was evaluated in order to determine the role of the biological markers on NSCLC . Immunohistochemical staining for EGFR, MMP-9, and C-erbB-2 was performed on paraffin-embedded tissue sections to observe the expression pattern according to the pathologic type and surgical staging. The correlations between the expression of each biological marker and the survival time was determined. Results : When positive immunohistochemical staining was defined as the extent area>20%(more than Grade 2), the positive rates for EGFR, MMP-9, and C-erbB-2 staining were 71.6%, 44.3%, and 24.1% of the 81 patients, respectively. The positive rates of EGFR and MMP-9 stain for NSCLC according to the surgical stages I, II, and IIIa were 75.0% and 41.7%, 66.7% and 47.6%, and 76.9% and 46.2%, respectively. The median survival time of the EGFR(-) group, 71.8 months, was significantly longer than that of the EGFR(+) group, 33.5 months.(p=0.018, Kaplan-Meier Method, log-rank test).. The MMP-9(+) group had a shorter median survival time than the MMP-9(-) group, 35.0 and 65.3 months, respectively (p=0.2). The co-expression of EGFR and MMP-9 was associated with a worse prognosis with a median survival time of 26.9 months, when compared with the 77 months for both negative-expression groups (p=0.0023). There were no significant differences between the C-erbB-2(+) and C-erbB-2 (-) groups. Conclusion : In NSCLC, the expression of EGFR might be a prognostic factor, and the co-expression of EGFR and MMP-9 was found to be associated with a poor prognosis. However, C-erbB-2 expression had no prognostic significance.

Muc5ac Gene Expression Induced by Cigarette Smoke is Mediated Via a Pathway Involving ERK1/2 and p38 MAPK (담배 연기에 의한 Muc5ac 유전자 발현에 관여하는 세포 내 신호 전달 경로로서의 ERK1/2와 p38 MAPK)

  • Kim, Yong Hyun;Yoon, Hyoung Kyu;Kim, Chi Hong;Ahn, Joong Hyun;Kwon, Soon Seog;Kim, Young Kyoon;Kim, Kwan Hyoung;Moon, Hwa Sik;Park, Sung Hak;Song, Jeong Sup;Cho, Kyung Sook
    • Tuberculosis and Respiratory Diseases
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    • v.58 no.6
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    • pp.590-599
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    • 2005
  • Object : Cigarette smoking is a major cause of mucus hypersecretion, which is a pathophysiological feature of many inflammatory airway diseases. Mucins, which are an important part of the airway mucus, are synthesized from the Muc gene in airway epithelial cells. However, the signaling pathways for cigarette smoke-induced mucin synthesis are unknown. The aim of this study was to determine the signal pathway for smoking induced Muc5ac gene expression. Methods : A549 cells were cultured and transiently transfected with the Muc5ac promoter fragment. These cells were stimulated with 5% cigarette smoke extract (CSE) alone or with CSE after a pretreatment with various signal transduction pathway inhibitors (AG1478, PD98059 and SB203580). The Muc5ac promoter activity was examined using the luciferase reporter system, and the level of phosphorylated EGFR, ERK1/2, p38 MAPK and JNK were all examined using Western blot analysis. Muc5ac mRNA expression was also examined using reverse transcriptase polymerase chain reactions (RT-PCR). Results : 1. The peak level of luciferase activity of the Muc5ac promoter was observed at 5% concentration and after 3 hours of incubation with the CSE. The level of EGFR phosphorylation and the luciferase activity of the transfected cells caused by the CSE were significantly suppressed by AG1478 or PD98059 (P<0.01). 2. CSE phosphorylated ERK1/2 or p38 MAPK but not JNK. The Muc5ac mRNA expression level was increased by the CSE but that was suppressed by PD98059 or AG1478. 3. The CSE-induced phosphorylation of ERK1/2 was blocked by PD98059 and that of p38 MAPK was blocked by either PD98059 or SB203580. Either PD98059 or SB203580 suppressed the luciferase activity of the transfected cells (P<0.0001). Conclusion : The Muc5ac mRNA expression level was increased by the CSE. The increased CSE-induced transcriptional activity was mediated via EGF receptor activation, which led to ERK1/2 and p38 MAPK phosphorylation.

Clinical Analysis According to $p21^{Waf1/Cip1}\;and\;p27^{kip1}$ Expression in Gastric Cancer (위암에서의 $p21^{Waf1/Cip1}\;and\;p27^{kip1}$ 단백 발현)

  • Kim, Sin-Sun;Park, Yong-Geun;Jun, Kyong-Hwa;Jung, Hun;Song, Gyo-Young;Kim, Jin-Joo;Chin, Hyung-Min;Kim, Wook;Park, Cho-Hyun;Park, Seung-Man;Lim, Keun-Woo;Kim, Seung-Nam;Jeon, Hae-Myung
    • Journal of Gastric Cancer
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    • v.6 no.1
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    • pp.36-42
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    • 2006
  • Purpose: The $p21^{Waf1/Cip1}$ protein Inhibits the cell cycle by Inhibiting the phosphorylation at the $G1{\rightarrow}S$ check point, and the $p27^{kip1}$ protein similarly performs the suppressor function by controlling the p27-mediated G1 arrest. In this study, we analysed the clinical status and survival rates in correlations with p21 and p27 expression patterns in gastric cancer. Materials and Methods: Between 1993 and 1997, 192 patients who underwent surgeries in Catholic Medical Center were analysed retrospectively in this study. Immunohistochemical staining was performed and if the nuclei of the tumor cells were stained, we assumed those as positive results. Statistical analysis was based on clinicopathological findings and differences in survival rates. Results: The expression rate of p27 was 28.1% and 15.6% in p21 each. The ratio of T1-2(80.0%) was significantly high in p21 (+), but the ratio of T3-4 (50.6%) was slightly high in p21 (-). There was no statistical significance regarding other factors. The results in p27 was not much different from expression rate of p21 in T-stage. In addition, p27 expression in diffuse type (91.3%) was higher than in intestinal type (62.7%) by Lauren's classification (P<0.05). Also, there was no statistical significance in other factors. In the correlation of p21 and p27, p27 was positive when p21 was positive (53.5%). Conversely, p27 was negative when p21 was negative (76.5%, p<0.05). In the p21 and p27 combination test, there was higher rate of T1-2 (87.5%) in p21 (+)/p27 (+), and higher rate of T3-4 (58.1%) in p21 (-)/p27 (-) (P<0.05). Results showed higher rate of intestinal type (100%) in p21 (+)/p27 (+), and diffuse type (87.0%) was dominant in p21 (-)/p27 (-) (P<0.05) by Lauren's classification. Moreover, there was no statistical significance in the 5-year survival rate in the expression of p21 and p27, and the 5-year survival rate was highest in the case of p21 (+)/p27 (+) without statistical significance. Conclusion: In our study, $p21^{Waf1/Cip1}\;and\;p27^{kip1}$ expressed similar patterns. The expression of $p21^{Waf1/Cip1}\;and\;p27^{kip1}$ affected the degree of invasiveness of the tumor, and. Combined examination result revealed the correlation of $p21^{Waf1/Cip1}\;and\;p27^{kip1}$ with Lauren's classification and depth of invasion of the tumor. However, we assumed that little difference between the survival rates depending on expression of $p21^{Waf1/Cip1}\;and\;p27^{kip1}$ has limited their value as predictable prognostic indicators.

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