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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.

A Study on the Expression of CD44s and CD44v6 in Non-Small Cell Lung Carcinomas (비소세포성 폐암종의 CD44s 및 CD44v6의 발현에 대한 연구 -CD44의 발현에 대한 연구-)

  • Chang, Woon-Ha;Oh, Tae-Yun;Kim, Jung-Tae
    • Journal of Chest Surgery
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    • v.39 no.1 s.258
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    • pp.1-11
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    • 2006
  • Background: CD44 is a glycoprotein on the cell surface which is involved in the cell-to-cell and cell-to-matrix interaction. The standard form, CD44s and multiple isoforms are determined by alternative splicing of 10 exons. Recent studies have suggested that CD44 may help invasion and metastasis of various epithelial tumors as well as activation of Iymphocytes and monocytes. The expression pattern of CD44 can be different according to tumor types. The author studied the expression pattern of CD44s and one of its variants, CD44v6 in non-small cell lung carcinomas (NSCLC) to find their implications on clinicopathologic aspects, including the survival of the patients. Material and Method: A total of 89 primary NSCLSs (48 squamous cell carcinomas, 33 adenocarcinomas, and 8 undifferentiated large cell carcinomas) were retrieved during the years between 1985 to 1994. The immunohisto chemistry was done by using monoclonal antibodies and the CD44 expression for angiogenesis was evaluated by counting the number of tumor microvessels. Result: Seventy-one (79.8$\%$) and 64 (71 .9$\%$) among 89 NSCLSs revealed the expression of CD44s and CD44v6, respectively. The expression of CD44s was well correlated with that of CD44v6 (r=0.710, p < 0.0001). The expression of CD44s and CD44v6 was associated with the histopathologic type of the NSCLCs, and squamous cell carcinoma was the type that showed the highest expression of CD44s and CD44v6 (p < 0.0001). Microvessel count was the highest in adenocarcinomas (113.6$\pm$69.7 on 200-fold magnification and 54.8$\pm$41.1 on 400-fold magnification) and correlated with the tumor size of TNM system (r=0.217, p=0.043) and CD44s expression (r=0.218, p=0.040). In adenocarcinoma, the patients with higher CD44s expression survived shorter than those with lower CD44s expression (p=0.0194) but there was no statistical significance on multivariate analysis(p=0.3298). Conclusion: The expression of both CD44s and CD44v6 may be associated with the squamous differentiation in non-small cell lung carcinomas. The relationship of CD44s expression with micro-vessel density of the tumor suggests an involvement of CD44s in tumor angiogenesis, which in turn would help tumor growth.

The Expression of Adhesion Molecules on Alveolar Macrophages and Lymphocytes and Soluble ICAM-1 Level in Serum and Bronchoalveolar Lavge(BAL) Fluid of Patients with Diffuse Interstitial Lung Diseases(DILD) (간질성 폐질환환자들의 기관지 폐포세척액내 폐포 대식세포와 임파구의 접착분자 발현 및 Soluble ICAM-1 농도에 관한 연구)

  • Kim, Dong-Soon;Choi, Kang-Hyun;Yeom, Ho-Kee;Park, Myung-Jae;Lim, Chai-Man;Koh, Yoon-Suck;Kim, Woo-Sung;Kim, Won-Dong
    • Tuberculosis and Respiratory Diseases
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    • v.42 no.4
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    • pp.569-583
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    • 1995
  • Background: The expression of the adhesion molecules on the cell surface is important in the movement of cells and the modulation of immune response. DILD starts as an alveolitis and progresses to pulmonary fibrosis. So adhesion molecules in these patients is expected to be increased. There are several reports about adhesion molecules in DILD in terms of the percentage of positive cells in immuno-stain, in which the interpretation is subjective and the data were variable. Methods: So we measured the relative median fluorescence intensity(RMFI) which is the ratio of the FI emitted by bound primary monoclonal antibody to FI emitted by isotypic control antibody of the cells in BALF of 28 patients with DILD(IPF:10, collagen disease:7, sarcoidosis:9, hypersensitivity pneumonitis:2) and 9 healthy control. Results: RMFI of the ICAM-1 on AM($3.30{\pm}1.16$) and lymphocyte($5.39{\pm}.70$) of DILD were increased significantly than normal control($0.93{\pm}0.18$, $1.06{\pm}0.21$, respectively, p=0.001, P=0.003). RMFI of the CD18 on lymphocyte was also higher($24.9{\pm}14.9$) than normal($4.59{\pm}3.77$, p=0.0023). And there was a correlation between RMFI of ICAM on AM and the % of AM(r=-0.66, p=0.0001) and lymphocyte(r=0.447, p=0.0116) in BALF. Also RMFI of ICAM on lymphocyte had a significant (r=0.593, p=0.075) correlation with the % of IL-2R(+) lymphocyte in BALF. The soluble ICAM(sICAM) in serum was also significantly elevated in DILD($499.7{\pm}222.2\;ng/ml$) compred to normal($199.0{\pm}38.9$) (p=0.00097) and sICAM in BAL fluid was also significantly higher than normal control group($41.8{\pm}23.0\;ng/ml$ vs $20.1{\pm}13.6\;ng/ml$). There was a Significant correlation between sICAM level in serum and the expression of ICAM-l on AM(r=0.554, p=0.0259).Conclusion: These data suggest that in DILD the expression of adhesion molecules is increased in the AM and BAL lymphocytes with elevated serum sICAM, and these parameter may be useful in determining disease activity.

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Effects of Taeumin, Soeumin and Soyangin Prescriptions on the Adipocyte Induced by Gold Thioglucose in the Rat (태(太)·소음인(少陰人), 소양인(少陽人)의 처방(處方)이 Gold thioglucose로 유발(誘發)된 백서(白鼠)의 비만병(肥滿病)에 미치는 효과(效果))

  • Kim, Kyung-Yo
    • Journal of Sasang Constitutional Medicine
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    • v.8 no.1
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    • pp.295-317
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    • 1996
  • It is researched to elucidate the effects of Taeumjowuitang(TE,太陰調胃湯), Sibimikwanjungtang(SE, 十二味寬中湯) and Yangkeogsanwhatang(SY,凉膈散火湯) on the obesity induced by gold thioglucose and the differentiation and growth of preadipocyte 3T3-L1 in the mouse. The result were as follows: 1. TE,SE and SY extracts improved the blood level of transaminase in the obese mouse induced by gold thioglucose. 2. TE,SE and SY extracts inhibited the increase of liver fat and body fat in the obese mouse induced by gold thioglucose. 3. TE,SE and SY extracts inhibited the increase of body weight in the obese mouse induced by gold thioglucose. 4. TE,SE and SY extracts inhibited the growth of undifferentiate preadipocyte 3T3-L1. 5. TE,SE and SY extracts showed inhibitory effect on the differentiation of preadipocyte 3T3-L1. The above results suggest that the TE,SE and SY extracts may be used on the obesity induced by the overgrowth and differentiation of adipocyte, and the accumulation of fat in liver and body.

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National Survey of Sarcoidosis in Korea (유육종증 전국실태조사)

  • 대한결핵 및 호흡기학회 학술위원회
    • Tuberculosis and Respiratory Diseases
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    • v.39 no.6
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    • pp.453-473
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    • 1992
  • Background: National survey was performed to estimate the incidence of sarcoidosis in Korea. The clinical data of confirmed cases were analysed for the practice of primary care physicians and pulmonary specialists. Methods: The period of study was from January 1991 to December 1992. Data were retrospectively collected by correspondence with physicians in departments of internal medicine, dermatology, ophthalmology and neurology of the hospitals having more than 100 beds using returning postcards. In confirmed and suspicious cases of sardoidosis, case record chart for clinical and laboratory findings were obtained in detail. Results: 1) Postcards were sent to 523 departments in 213 hospitals. Internal medicine composed 41%, dermatology 20%, ophthalmology 20% and neurology 19%. 2) Postcards were returned from 241 departments (replying rates was 48%). 3) There were 113 confirmed cases from 50 departments and 10 cases. The cases were composed from internal medicine (81%), dermatology (13%), ophthalmology (3%) and neurology (3%). 78 confirmed cases were analysed, which were composed from department of internal medicine (92%), dermatology (5%), and neurology (3%). 4) The time span for analysed cases was 1980 to 1992. one case was analysed in 1980 and the number gradually increased to 18 cases in 1991. 5) The majority of patients (84.4%) were in the age group of 20 to 49 years. 6) The ratio of male to female was 1 : 1.5. 7) The most common chief complains were respiratory symptoms, dermatologic symptoms, generalized discomforts, visual changes, arthralgia, abdominal pains, and swallowing difficulties in order. 16% of the patients were asymptomatic. 8) Mean duration between symptom onset and diagnosis was 2 months. 9) The most common symptoms were respiratory, general, dermatologic, ophthalmologic, neurologic and cardiac origin in order. 10) Hemoglobin, hematocrits and platelet were in normal range. 58% of the patients had lymphopenia measuring less than 30% of white cell count. The ratio of CD4 to CD8 lymphocytes was $1.73{\pm}1.16$ with range of 0.43 to 4.62. ESR was elevated in 43% of the cases. 11) Blood chemistry was normal in most cases. Serum angiotensin converting enzyme (S-ACE) was $66.8{\pm}58.6\;U/L$ with the range of 8.79 to 265 U /L. Proteinuria of more than 150 mg was found in 42. 9% of the patients. 12) Serum IgG was elevated in 43.5%, IgA in 45.5%, IgM in 59.1% and IgE in 46.7%. The levels of complement C3 and C4 were in the normal range. Anti-nuclear antibody was detected in 11% of the cases. Kweim test was performed in 3 cases, and in all cases the result was positive. 13) FVC was decreased in 17.3%, FEV1 in 11.5%, FEV1/FVC in 10%, TLC in 15.2%, and DLco in 64.7%. 14) PaO2 was decreased below 90 mmHg in 48.6% and PaCO2 was increased above 45 mmHg in 5.7%. 15) The percentage of macrophages in BAL fluid was $51.4{\pm}19.2%$, lymphocytes $44.4{\pm}21.1%$, and the ratio of CD4 to CD8 lymphocytes was $3.41{\pm}2.07$. 16) There was no difference in laboratory findings between male and female. 17) Hilar enlargement on chest PA was present in 87.9% (bilaterally in 78.8% and unilaterally in 9.1%). 18) According to Siltzbach's classification, stage 0 was 5%, stage 158.3%, stage 228.3%, and stage 38.3%. 19) Hilart enlargement on chest CT was present in 92.6% (bilaterally 76.4% and unilaterally in 16.2%). 20) HRCT was done in 16 cases. The most common findings were nodules, interlobular thickening, focal patchy infiltrations in order. Two cases was normal finding. 21) Other radiologic examinations showed bone change in one case and splenomegaly in two cases. 22) Gallium scan was done in 12 cases. Radioactivity was increased in hilar and mediastinal lymph nodes in 8 cases and in parenchyme in 2 cases. 23) The pathologic diagnosis was commonly performed by transbrochial lung biopsy (TBLB, 47.3%), skin and mediastinal lymph nodes biopsy (34.5%), peripheral lymph nodes biopsy (23.6%), open lung biopsy (18.2%) and bronchial biopsy in order. 24) The most common findings in pathology were non·caseating granuloma (100%), multi-nucleated giant cell (47.3%), hyalinized acellular scar (34.5%), reticulin fibrin network (20%), inclusion body (10.9%), necrosis (9.1%), and lymphangitic distribution of granuloma (1.8%) in order. Conclusion: Clinical, laboratory, radiologic and pathologic findings were summarized. This collected data will assist in finding a test for detection and staging of sarcoidosis in Korea in near future.

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