• Title/Summary/Keyword: pathological parameters

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Saponins from Panax japonicus ameliorate age-related renal fibrosis by inhibition of inflammation mediated by NF-κB and TGF-β1/Smad signaling and suppression of oxidative stress via activation of Nrf2-ARE signaling

  • Gao, Yan;Yuan, Ding;Gai, Liyue;Wu, Xuelian;Shi, Yue;He, Yumin;Liu, Chaoqi;Zhang, Changcheng;Zhou, Gang;Yuan, Chengfu
    • Journal of Ginseng Research
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    • v.45 no.3
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    • pp.408-419
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    • 2021
  • Background: The decreased renal function is known to be associated with biological aging, of which the main pathological features are chronic inflammation and renal interstitial fibrosis. In previous studies, we reported that total saponins from Panax japonicus (SPJs) can availably protect acute myocardial ischemia. We proposed that SPJs might have similar protective effects for aging-associated renal interstitial fibrosis. Thus, in the present study, we evaluated the overall effect of SPJs on renal fibrosis. Methods: Sprague-Dawley (SD) aging rats were given SPJs by gavage beginning from 18 months old, at 10 mg/kg/d and 60 mg/kg/d, up to 24 months old. After the experiment, changes in morphology, function and fibrosis of their kidneys were detected. The levels of serum uric acid (UA), β2-microglobulin (β2-MG) and cystatin C (Cys C) were assayed with ELISA kits. The levels of extracellular matrix (ECM), matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), inflammatory factors and changes of oxidative stress parameters were examined. Results: After SPJs treatment, SD rats showed significantly histopathological changes in kidneys accompanied by decreased renal fibrosis and increased renal function; As compared with those in 3-month group, the levels of serum UA, Cys C and β2-MG in 24-month group were significantly increased (p < 0.05). Compared with those in the 24-month group, the levels of serum UA, Cys C and β2-MG in the SPJ-H group were significantly decreased. While ECM was reduced and the levels of MMP-2 and MMP-9 were increased, the levels of TIMP-1, TIMP-2 and transforming growth factor-β1 (TGF-β1)/Smad signaling were decreased; the expression level of phosphorylated nuclear factor kappa-B (NF-κB) was down-regulated with reduced inflammatory factors; meanwhile, the expression of nuclear factor erythroid 2-related factor 2-antioxidant response element (Nrf2-ARE) signaling was aggrandized. Conclusion: These results suggest that SPJs treatment can improve age-associated renal fibrosis by inhibiting TGF-β1/Smad, NFκB signaling pathways and activating Nrf2-ARE signaling pathways and that SPJs can be a potentially valuable anti-renal fibrosis drug.

Imaging and Clinical Findings of Primary Malignant Fibrous Histiocytoma of the Urinary Bladder: A Case Report (방광의 일차 악성 섬유성 조직구종의 영상 및 임상 소견: 증례 보고)

  • Yoon Jung Lee;Eun Ji Lee;Jae Heon Kim;So Young Jin;Seong Sook Hong;Jiyoung Hwang;Yun-Woo Chang
    • Journal of the Korean Society of Radiology
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    • v.85 no.3
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    • pp.654-660
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    • 2024
  • Primary malignant fibrous histiocytoma (MFH) is a malignant tumor of mesenchymal origin that rarely occurs in the urinary tract, particularly in the urinary bladder. Unlike urothelial carcinoma, which accounts for most bladder cancers, it occurs in the submucosal portion of the bladder wall and consists of the lamina propria, muscularis propria, and adventitia. It is presumed to originate from poorly differentiated pluripotent mesenchymal cells in which fibroblasts and histiocytes are partially differentiated. Radiologically, it is known as the "non-papillary tumor" and is commonly diagnosed as a large mass without necrosis, which shows invasion beyond the muscularis propia. Although the prognosis of this rare malignancy depends on pathological parameters, it generally has a poor prognosis with high local tumor recurrence. Here, we present a case of primary MFH in the urinary bladder with clinical symptoms of lower abdominal pain without gross hematuria that recurred rapidly and showed an aggressive disease course.

Association between RASSF1A Methylation and Clinicopathological Factors in Patients with Squamous Cell Carcinoma of Lung (편평상피폐암에서 암억제유전자 RASSF1A의 메틸화와 임상 및 병리소견과의 연관성)

  • Choi, Naeyun;Lee, Hye-Sook;Song, In Seung;Lim, Yu Sung;Son, Dae-Soon;Lim, Dae-Sik;Choi, Yong Soo;Kim, Jhingook;Kim, Hojoong
    • Tuberculosis and Respiratory Diseases
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    • v.57 no.3
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    • pp.265-272
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    • 2004
  • Background : RASSF1A, which is one of tumor suppressor genes, is frequently inactivated by hypermethylation of the promoter region in a variety of human cancers, including lung cancer. This study was performed to investigate the association between RASSF1A methylation and the clinicopathological factors in patients with squamous cell carcinoma of the lung. Methods : Eighty-one samples from the patients with squamous cell carcinoma of lung were examined. The promoter methyation of RASSF1A was analyzed by methylation specific PCR and sequencing. Statistical analysis was made to examine the association between RASSF1A methylation and the clinicopathological parameters. Results : RASSF1A methylation was observed in 37.0 % (30 of 81) of the patients with squamous cell carcinoma of the lung. RASSF1A methylation was found to be associated with cellular differentiation(p=0.0097) and the overall survival(p=0.0635). However, there was no association between RASSF1A methylation and the other clinicopathological parameters, such as the pathological TNM stage, the recurrence rate, lymph node invasion and the amount of cigarettes smoked. Conclusion : RASSF1A methylation might be associated with a poor prognosis in patients with squamous carcinoma of the lung. A larger scale study is needed.

Development of the Multi-Parametric Mapping Software Based on Functional Maps to Determine the Clinical Target Volumes (임상표적체적 결정을 위한 기능 영상 기반 생물학적 인자 맵핑 소프트웨어 개발)

  • Park, Ji-Yeon;Jung, Won-Gyun;Lee, Jeong-Woo;Lee, Kyoung-Nam;Ahn, Kook-Jin;Hong, Se-Mie;Juh, Ra-Hyeong;Choe, Bo-Young;Suh, Tae-Suk
    • Progress in Medical Physics
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    • v.21 no.2
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    • pp.153-164
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    • 2010
  • To determine the clinical target volumes considering vascularity and cellularity of tumors, the software was developed for mapping of the analyzed biological clinical target volumes on anatomical images using regional cerebral blood volume (rCBV) maps and apparent diffusion coefficient (ADC) maps. The program provides the functions for integrated registrations using mutual information, affine transform and non-rigid registration. The registration accuracy is evaluated by the calculation of the overlapped ratio of segmented bone regions and average distance difference of contours between reference and registered images. The performance of the developed software was tested using multimodal images of a patient who has the residual tumor of high grade gliomas. Registration accuracy of about 74% and average 2.3 mm distance difference were calculated by the evaluation method of bone segmentation and contour extraction. The registration accuracy can be improved as higher as 4% by the manual adjustment functions. Advanced MR images are analyzed using color maps for rCBV maps and quantitative calculation based on region of interest (ROI) for ADC maps. Then, multi-parameters on the same voxels are plotted on plane and constitute the multi-functional parametric maps of which x and y axis representing rCBV and ADC values. According to the distributions of functional parameters, tumor regions showing the higher vascularity and cellularity are categorized according to the criteria corresponding malignant gliomas. Determined volumes reflecting pathological and physiological characteristics of tumors are marked on anatomical images. By applying the multi-functional images, errors arising from using one type of image would be reduced and local regions representing higher probability as tumor cells would be determined for radiation treatment plan. Biological tumor characteristics can be expressed using image registration and multi-functional parametric maps in the developed software. The software can be considered to delineate clinical target volumes using advanced MR images with anatomical images.

Comparison of the Nutritional Status and the Acute Inflammatory Reaction between Laparoscopy-assisted Distal Gastrectomy and Conventional Open Distal Gastrectomy for Early Gastric Cancer (조기위암에서 복강경 및 개복 위아전절제술에 따른 영양학적 및 면역염증반응의 비교)

  • Chae, Hyun-Dong
    • Journal of Gastric Cancer
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    • v.10 no.1
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    • pp.19-25
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    • 2010
  • Purpose: Laparoscopy-assisted gastrectomy (LAG) is gaining wider acceptance as a minimally invasive treatment for early gastric cancer, but the safety, efficacy and clinical benefits of this type of surgery are still unclear. The purpose of this study is to compare laparoscopy-assisted gastrectomy (LADG) and conventional open distal gastrectomy (CODG) for early gastric cancer (EGC) according to the changes of the postoperative nutritional status and acute inflammatory reaction. Materials and Methods: Eighty seven patients with EGC and who underwent a LADG between March 2006 and May 2009 at Daegu Catholic University Hospital, was enrolled. Over the same period, we enrolled 30 patients who underwent CODG and they were confirmed to have EGC from their pathology. The clinico-pathological features and serologic parameters were evaluated from the medical records and then retrospectively analyzed. Results: There were no differences in the preoperative white blood cell (WBC), C-reactive protein (CRP) level, albumin level, the T4/T8 ratio and the other clinical data between the two groups. The total WBC counts gradually increased and they were significant lower at the $1^{st}$ and $3^{rd}$ postoperative days in the LADG group than that in the CODG group (P=0.001 and 0.008, respectively). The postoperative CRP levels were significantly lower at postoperative $5^{th}$ day in the LADG group (P<0.001). The postoperative albumin and T4/T8 ratio gradually decreased, and the T4/T8 ratio was significantly higher at the $3^{rd}$ postoperative day in the LADG group compared to that in the CODG group (P=0.003). Conclusion: This study demonstrates that the LADG has less of an influence on an acute inflammatory reaction than does CODG. Therefore, it is one of the safe and feasible procedures for the treatment of early gastric cancer.

Prognostic Factors in Childhood IgA Nephropathy (소아 IgA 신병증의 예후에 관한 고찰)

  • Park Jae-Hyun;Kim Pyung-Kil;Jeong Hyeon-Joo;Choi In-Joon
    • Childhood Kidney Diseases
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    • v.1 no.1
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    • pp.17-23
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    • 1997
  • After the first description of IgA nephropathy by Berger in 1968, the prognosis of this disease was considered favourable. However recent studies have revealed that IgA nephropathy result in end stage renal desease in 25-30% by 20 years. Heavy proteinuria, hypertension, histological high class are regarded as poor prognostic factors. In 1996, Yagame et al reported the new histopathologic grading with a strong correlation between the grading, heavy proteinuria, high s-Cr level and renal survival. The aims of this study are to determine whether the pathological grading and other clinical parameters could contribute to predicting the outcome of this disease eventhough pediatric patients. Seventy nine patients (59 males, 20 females) with IgA nephropathy were examined. Patients were 2.08-15.17 years of age ($9.85{\pm}2.83$). The mean follow-up duration were $27{\pm}28$ months. Six of seventy nine patients progressed to chronic renal failure during the follow-up periods. High 24h urinary protein excretion at diagnosis were significantly higher in chronic renal failure patients (p<0.05). Hypertension at diagnosis were the significant associated factors in progression of chronic renal failure (p<0.05). Histological changes of IgA nephropathy in light microscopy were classified into five classes by WHO classification, four grades in Yagame's gradings. Among the seventy nine patients, 24 were as class 1, 30 as class 2, 23 as class 3; 4 as class 4, 0 as class 5 by WHO classification. 23 were classified grade 1, 31 as grade 2, 24 as grade 3, 1 as grade 4 by Yagame's grading. Among six patients who progressed to chronic renal failure, 1 clssified as class 1, 1 as class 2, 3 as class 3, 1 as class 4, 0 as class 5 by WHO Classification. 1 patients were classified as grade 1, 1 as grade 2, 3 as grade 3, 1 as grade 4 by Yagame's grading. (p>0.05) In conclusion, hypertension and heavy proteinuria at initial presentation were significantly associated with progression of chronic renal failure. The classification of WHO & Yagame's grading has no significant association with the progression of chronic renal failure in pediatric patients.

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Comparison between FDG Uptake and Pathologic or Immunohistochemical Parametersin Pre-operative PET/CT Scan of Patient with Primary Colorectal Cancer (원발성 대장-결장암 환자의 치료 전 PET/CT 스캔에서 FDG 섭취 정도와 병리학적 및 면역조직화학적 지표들과의 비교)

  • Na, Sae-Jung;Chung, Yong-An;Maeng, Lee-So;Kim, Ki-Jun;Sohn, Kyung-Myung;Kim, Sung-Hoon;Sohn, Hyung-Sun;Chung, Soo-Kyo
    • Nuclear Medicine and Molecular Imaging
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    • v.43 no.6
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    • pp.557-564
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    • 2009
  • Purpose: To evaluate the relationship between F-18 FDG uptake of tumor in PET/CT scan and pathological or immunohistochemial parameters of colorectal cancer. Materials and Methods: 147 colorectal cancer patients who underwent both pre-operative F-18 FDG PET/CT scan and surgery were included. In cases with perceptible FDG uptake in primary tumor, the maximum standardized uptake value (SUVmax) was calculated. The pathologic results such as site, size, depth of invasion (T stage), growth pattern, differentiation of primary tumor, lymph node metastasis and Dukes-Astler & Coller stage and immunohistochemical markers such as expression of EGFR, MLH1, MSH2 and Ki-67 index were reviewed. Results: 146 out of 147 PET/CT scans with colorectal cancer showed perceptible focal FDG uptake. SUVmax showed mild positive linear correlation with size of primary tumor (r=0.277, p=0.001) and Ki-67 index (r=0.226, p=0.019). No significant difference in F-18 FDG uptake was found according to site, depth of invasion (T stage), growth pattern, differentiation of primary tumor, presence of lymph node metastasis, Dukes-Astler & Coller stage and expression of EGFR. Conclusion: The degree of F-18 FDG uptake in colorectal cancer was associated with the size and the degree of Ki-67 index of primary tumor. It could be thought that FDG uptake of primary tumor has a correlation with macroscopic and microscopic tumor growth.

Single Dose Oral Toxicity Test of Ethanol Extracts of Schisandrae fructus and Mori folium, and their Mixture in ICR Mice (ICR 마우스를 이용한 오미자, 상엽 에탄올 단독추출물 및 복합추출물의 단회경구투여 독성시험)

  • Choi, Eun Ok;Kwon, Da Hye;Kim, Min Young;Hwang-Bo, Hyun;Kim, Hong Jae;Ahn, Kyu Im;Jeong, Jin-Woo;Lee, Ki Won;Kim, Ki Young;Kim, Sung Goo;Choi, Young Whan;Hong, Su Hyun;Park, Cheol;Choi, Yung Hyun
    • Journal of Life Science
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    • v.26 no.10
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    • pp.1207-1213
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    • 2016
  • Schisandrae fructus (SF) and Mori folium (MF) have been used as traditional medicines for thousands of years in parts of Asia, including Korea, China, and Japan. Recent researches on SF and MF have documented a wide spectrum of therapeutic properties, including anti-microbial, anti-inflammatory, anti-oxidative, immunomodulatory and anti-angiogenesis effects. However, the toxicity and safety of SF and MF, and their mixture (medicinal herber mixture, MHMIX) were not confirmed. Therefore, this study was performed to evaluate the acute toxicity and safety of SF, MF and MHMIX. SF, MF and MHMIX were orally administered at a dose of 5,000 mg/kg in ICR mice. Animals were monitored for the mortality and changes in the body weight, clinical signs and gross observation during the 14 days after dosing, upon necropsy. We also measured parameters of organ weight, clinical chemistry, and hematology. No dead and no clinical signs were found during the experiment period after administration of a single oral dose of SF, MF and MHMIX. There were no adverse effects on clinical signs, body weight, or organ weight and no gross pathological findings in any treatment group. Therefore, LD50 value of SF, MF and MHMIX may be over 5,000 mg/kg and it may have no side toxic effect to ICR mice. The results on the single-dose toxicity of SF, MF and MHMIX indicate that it is not possible to reach oral dose levels related to death or dose levels with any harmful side effects.

Quantitative Differences between X-Ray CT-Based and $^{137}Cs$-Based Attenuation Correction in Philips Gemini PET/CT (GEMINI PET/CT의 X-ray CT, $^{137}Cs$ 기반 511 keV 광자 감쇠계수의 정량적 차이)

  • Kim, Jin-Su;Lee, Jae-Sung;Lee, Dong-Soo;Park, Eun-Kyung;Kim, Jong-Hyo;Kim, Jae-Il;Lee, Hong-Jae;Chung, June-Key;Lee, Myung-Chul
    • The Korean Journal of Nuclear Medicine
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    • v.39 no.3
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    • pp.182-190
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    • 2005
  • Purpose: There are differences between Standard Uptake Value (SUV) of CT attenuation corrected PET and that of $^{137}Cs$. Since various causes lead to difference of SUV, it is important to know what is the cause of these difference. Since only the X-ray CT and $^{137}Cs$ transmission data are used for the attenuation correction, in Philips GEMINI PET/CT scanner, proper transformation of these data into usable attenuation coefficients for 511 keV photon has to be ascertained. The aim of this study was to evaluate the accuracy in the CT measurement and compare the CT and $^{137}Cs$-based attenuation correction in this scanner. Methods: For all the experiments, CT was set to 40 keV (120 kVp) and 50 mAs. To evaluate the accuracy of the CT measurement, CT performance phantom was scanned and Hounsfield units (HU) for those regions were compared to the true values. For the comparison of CT and $^{137}Cs$-based attenuation corrections, transmission scans of the elliptical lung-spine-body phantom and electron density CT phantom composed of various components, such as water, bone, brain and adipose, were performed using CT and $^{137}Cs$. Transformed attenuation coefficients from these data were compared to each other and true 511 keV attenuation coefficient acquired using $^{68}Ge$ and ECAT EXACT 47 scanner. In addition, CT and $^{137}Cs$-derived attenuation coefficients and SUV values for $^{18}F$-FDG measured from the regions with normal and pathological uptake in patients' data were also compared. Results: HU of all the regions in CT performance phantom measured using GEMINI PET/CT were equivalent to the known true values. CT based attenuation coefficients were lower than those of $^{68}Ge$ about 10% in bony region of NEMA ECT phantom. Attenuation coefficients derived from $^{137}Cs$ data was slightly higher than those from CT data also in the images of electron density CT phantom and patients' body with electron density. However, the SUV values in attenuation corrected images using $^{137}Cs$ were lower than images corrected using CT. Percent difference between SUV values was about 15%. Conclusion: Although the HU measured using this scanner was accurate, accuracy in the conversion from CT data into the 511 keV attenuation coefficients was limited in the bony region. Discrepancy in the transformed attenuation coefficients and SUV values between CT and $^{137}Cs$-based data shown in this study suggests that further optimization of various parameters in data acquisition and processing would be necessary for this scanner.

The Significance of Plasma Urokinase-type Plasminogen Activator and Type 1 Plasminogen Activator Inhibitor in Lung Cancer (폐암에서 혈장 Urokinase-Type Plasminogen Activator 및 Type 1 Plasminogen Activator Inhibitor의 의의)

  • Park, Kwang-Joo;Kim, Hyung-Jung;Ahn, Chul-Min;Lee, Doo-Yun;Chang, Joon;Kim, Sung-Kyu;Lee, Won-Young
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.3
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    • pp.516-524
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    • 1997
  • Background : Cancer invasion and metastasis require the dissolution of the extracellular matrix in which several proteolytic enzymes are involved. One of these enzymes is the urokinase-type plasminogen activator(u-PA), and plasminogen activator inhibitors(PAI-1, PAI-2) also have a possible role in cancer invasion and metastasis by protection of cancer itself from proteolysis by u-PA. It has been reported that the levels of u-PA and plasminogen activator inhibitors in various cancer tissues are significantly higher than those in normal tissues and have significant correlations with tumor size and lymph node involvement. Here, we measured the concentration of plasma u-PA and PAI-1 antigens in the patients with lung cancer and compared the concentration of them with histologic types and staging parameters. Methods : We measured the concentration of plasma u-PA and PAI-1 antigens using commercial ELISA kit in 37 lung cancer patients, 21 benign lung disease patients and 24 age-matched healthy controls, and we compared the concentration of them with histologic types and staging parameters in lung cancer patients. Results : The concentration of u-PA was $1.0{\pm}0.3ng/mL$ in controls, $1.0{\pm}0.3ng/mL$ in benign lung disease patients and $0.9{\pm}0.3ng/mL$ in lung cancer patients. The concentration of PAI-1 was $14.2{\pm}6.7ng/mL$ in controls, $14.9{\pm}6.3ng/mL$ in benign lung disease patients, and $22.1{\pm}9.8ng/mL$ in lung cancer patients. The concentration of PAI-1 in lung cancer patients was higher than those of benign lung disease patients and controls. The concentration of u-PA was $0.7{\pm}0.4ng/mL$ in squamous cell carcinoma, $0.8{\pm}0.3ng/mL$ in adenocarcinoma, 0.9ng/mL in large cell carcinoma, and $1.1{\pm}0.7ng/mL$ in small cell carcinoma. The concentration of PAI-1 was $22.3{\pm}7.2ng/mL$ in squamous cell carcinoma, $22.6{\pm}9.9ng/mL$ in adenocarcinoma, 42 ng/mL in large cell carcinoma, and $16.0{\pm}14.2ng/mL$ in small cell carcinoma. The concentration of u-PA was 0.74ng/mL in stage I, $1.2{\pm}0.6ng/mL$ in stage II, $0.7{\pm}0.4ng/mL$ in stage IIIA, $0.7{\pm}0.4ng/mL$ in stage IIIB, and $0.7{\pm}0.3ng/mL$ in stage IV. The concentration of PAI-1 was 21.8ng/mL in stage I, $22.7{\pm}8.7ng/mL$ in stage II, $18.4{\pm}4.9ng/mL$ in stage IIIA, $25.3{\pm}9.0ng/mL$ in stage IIIB, and $21.5{\pm}10.8ng/mL$ in stage IV. When we divided T stage into T1-3 and T4, the concentration of u-PA was $0.8{\pm}0.4ng/mL$ in T1-3 and $0.7{\pm}0.4ng/mL$ in T4, and the concentration of PAI-1 was $17.9{\pm}5.6ng/mL$ in T1-3 and $26.1{\pm}9.1ng/mL$ in T4. The concentration of PAI-1 in T4 was significantly higher than that in T1-3. The concentration of u-PA was $0.8{\pm}0.4ng/mL$ in M0 and $0.7{\pm}0.3ng/mL$ in M1, and the concentration of PAI-1 was $23.6{\pm}8.3ng/mL$ in M0 and $21.5{\pm}10.8ng/mL$ in M1. Conclusions : The plasma levels of PAI-1 in lung cancer were higher than benign lung disease and controls, and the plasma levels of PAI-1 in T4 were significantly higher than T1-3. These findings suggest involvement of PAI-1 with local invasion of lung cancer, but it should be confirmed by the data on comparison with pathological staging and tissue level in lung cancer.

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