• Tuberculosis and Respiratory Diseases
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• v.51 no.5
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• pp.466-473
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• 2001

Pulmonary epithelioid hemangioendothelioma (PEH), originally termed an intravacular bronchioloalveolar tumor, is a rare pulmonary neoplasm with a vascular origin and slow rate of malignancy. It affects various organs such as the liver, the central nervous system, lung, etc. Clinically, pulmonary epithelioid hemangioendothelioma has been considered to be a borderline malignancy, a generally indolent and nonaggressive tumor that displaces the pulmonary parenchyma over a number of years by slowly enlarging the tumor nodule. The clinical course of PEH is known to be usually benign. Here we report an unusual case of PEH that was highly malignant and was eventually fatal. The PEH was confirmed by microscopic analysis and immunohistochemical staining of CD31+(a membrane receptor and a sensitive and specific marker for vascular lesions) from an open lung biopsy specimen.

• The Korean Journal of Cytopathology
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• v.19 no.2
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• pp.126-135
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• 2008

Malignant mesothelioma (MM) is a highly lethal neoplasm arising in pleura and the peritoneum and a rapid and accurate diagnosis is crucial for treatment of the disease. However, the sensitivity of cytological analysis using pleural or ascitic fluid is relatively low, yielding an accurate diagnosis in only $32{\sim}79%$ of cases. We tested the diagnostic value of epigenetic alterations in body fluid cytology as a supplement to conventional methods. Paraffin-embedded tissue blocks from 21 MM patients and associated body fluid cytology slides considered no evidence of malignancy were used to test for epigenetic alteration. Using methylation-specific PCR, we detected methylation of RASSF1A and p16 in 47.6% (10/21) of both surgically resected tumor samples, respectively. Body fluid samples of MM also showed abnormal methylation of RASSF1A and p16INK4a genes in 38.1% (8/21) and 33.3% (7/21) of cases. The concordance in the rates of RASSF1A and p16INK4a gene-methylation abnormalities determined from cytology samples and tissue samples were 61.9% (13/21) and 66.7% (14/21), respectively. Combining both genes increases the sensitivity of the test to 57.1 % (12 of 21) of cases. Our results suggest that testing for methylation abnormalities in selected individual genes or gene combinations has diagnostic value as an alternative or adjunct method to conventional cytological diagnosis.

• Nutrition Research and Practice
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• v.12 no.2
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• pp.101-109
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• 2018

BACKGROUD/OBJECTIVES: The objective of this study was to investigate the effects of vitamin C on inflammation, tumor development, and dysbiosis of intestinal microbiota in an azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced inflammation-associated early colon cancer mouse model. MATERIALS/METHODS: Male BALB/c mice were injected intraperitoneally with AOM [10 mg/kg body weight (b.w)] and given two 7-d cycles of 2% DSS drinking water with a 14 d inter-cycle interval. Vitamin C (60 mg/kg b.w. and 120 mg/kg b.w.) was supplemented by gavage for 5 weeks starting 2 d after the AOM injection. RESULTS: The vitamin C treatment suppressed inflammatory morbidity, as reflected by disease activity index (DAI) in recovery phase and inhibited shortening of the colon, and reduced histological damage. In addition, vitamin C supplementation suppressed mRNA levels of pro-inflammatory mediators and cytokines, including cyclooxygenase-2, microsomal prostaglandin E synthase-2, tumor necrosis $factor-{\alpha}$, Interleukin $(IL)-1{\beta}$, and IL-6, and reduced expression of the proliferation marker, proliferating cell nuclear antigen, compared to observations of AOM/DSS animals. Although the microbial composition did not differ significantly between the groups, administration of vitamin C improved the level of inflammation-related Lactococcus and JQ084893 to control levels. CONCLUSION: Vitamin C treatment provided moderate suppression of inflammation, proliferation, and certain inflammation-related dysbiosis in a murine model of colitis associated-early colon cancer. These findings support that vitamin C supplementation can benefit colonic health. Long-term clinical studies with various doses of vitamin C are warranted.

• Journal of Chest Surgery
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• v.38 no.1 s.246
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• pp.38-43
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• 2005

Matrix metalloproteinase-2 (MMP-2) is a class of proteolytic enzymes that digest collagen type IV and other components of the basement membrane. It plays a key role in the local invasion and the formation of distant metastases by various malignant tumors. The aim of this study was to evaluate the activity of MMP-2 and its significance as a prognostic marker in resected stage I non-small cell lung cancer (NSCLC). Material and Method: In this study we obtained fresh-frozen samples of tumor and non-tumor tissues from 34 patients with stage I NSCLC who underwent resection without preoperative radiotherapy or chemotherapy. After the extraction of total protein from tissue samples, MMP-2 activities were assessed by gelatin-substrate-zymography. The activities were divided into the higher or lower groups. Result: The MMP-2 activities were higher in tumor tissues than in non-tumor tissues. The MMP-2 activity of non-tumor tissues in recurrent group was higher than in non-recurrent group (p<0.01). Also the patients with higher MMP-2 activity of non-tumor tissues showed poor 5 year survival (p<0.01). Conclusion: This result indicates that the higher level of MMP-2 activity in the non-tumor tissue is associated with the recurrence and survival after the resection of stage I NSCLC. Therefore, MMP-2 activity in the non-tumor tissue could be used as a potential prognostic marker for the resected stage I-NSCLC.

• Journal of Chest Surgery
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• v.31 no.4
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• pp.362-368
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• 1998

The aim of this study was to evaluate a usefulness of serum SCC antigen in diagnosis or evaluation of therapeutic effect of lung cancer by investigation of the differences of SCC antigen concentration in lung mass according to TNM staging, and mass size of lung cancer. And the other aim was to know whether SCC antigen plays a role in infiltrative growth of lung cancer or not, comparing with concentration of epidermal growth factor receptor(EGFr) in tissue which is related with growth and differentiation of tumor cell. The results of this study were as follows. The concentration of SCC antigen in squamous cell carcinoma of lung(69${\pm}$25ng/ml) was higher than in unaffected lung tissue(34${\pm}$7ng /ml).(p＜0.05). The concentration of SCC antigen was higher in squamous cell carcinoma (69${\pm}$25ng/ml) than in adenocarcinoma (35${\pm}$25ng/ml) (p＜0.05), but the concentration of EGFr showed no any significant difference in both histological types. In small sized mass(＜3cm in diameter) the concentration of SCC antigen in central portion of tumor was higher than that of peripheral portion, whereas in large sized mass($\geq$5cm in diameter), the concentration of SCC antigen in peripheral portion of tumor was higher than that of central portion.(p＜0.05). The concentration of EGFr according to tumor size was not significantly different in central and peripheral portion of tumor. The concentration of SCC antigen according to TNM staging of lung cancer was that from central portion was higher in stage I, II, but that from peripheral portion was higher in stage III, IV (p＜0.05). The concentration of EGFr from central portion was higher in higher TNM stage(not significant) but that from peripheral portion shows no significant changes. In conclusion, the concentration of SCC antigen in tissue was higher in squamous cell carcinoma than in unaffected lung tissue or adenocarcinoma, and the concentration of SCC antigen increased according to tumor size or TNM staging like in serum level. so, serum SCC antigen is a useful tumor marker to diagnose or evaluate therapeutic effect of squamous cell carcinoma of lung. But further studies are necessary to confirm the relation of infiltrative growth in lung cancer and concentration of SCC antigen because there was a different pattern of regional tissue concentration of SCC antigen and EGFr

• Journal of Chest Surgery
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• v.39 no.11 s.268
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• pp.828-837
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• 2006

Background: Tissue hypoxia is characteristic of many human malignant neoplasm, and hypoxia inducible factor-1(HIF-1) plays a pivotal role in essential adaptive response to hypoxia, and activates a signal pathway for the expression of the hypoxia-regulated genes, resulting in increasing $O_2$ delivery or facilitating metabolic adaptation to hypoxia. Increased level of HIF-$1{\alpha}$ has been reported in many human malignancies, but in non-small cell lung carcinoma the influence of HIF-$1{\alpha}$ on tumor biology, including neovascularization, is not still defined. In present study the relationship of HIF-$1{\alpha}$ expression on angiogenetic factors, relationship between the tumor proliferation and HIF-$1{\alpha}$ expression, interaction of HIF-$1{\alpha}$ expression and p53, and relationship between HIF-$1{\alpha}$ expression and clinico-pathological prognostic parameters were investigated. Material and Method: Archival tissue blocks recruited in this study were retrieved from fifty-nine patients with primary non-small cell lung carcinoma, who underwent pneumonectomy or lobectomy from 1997 to 1999. HIF-$1{\alpha}$, VEGF(vascular endothelial growth factor), and p53 protein expression and Ki-67 labeling index in tumor tissues were evaluated, using a standard avidin-biotin-peroxidase complex(ABC) immunohistochemistry. Relationship between the HIF-$1{\alpha}$ expression and VEGF, p53 overexpression and correlation between the HIF-$1{\alpha}$ expresseion and Ki-67 index were analyzed. Clinico-pathologic prognostic parameters were also analyzed. Result: HIF-$1{\alpha}$ expression in cancer cells was found in 24 of 59 cases of non-small cell lung carcinoma(40.7%). High HIF-$1{\alpha}$ expression was significantly associated with several pathological parameters, such as pathological TMN stage(p=0.004), pT stage(p=0.020), pN stage (p=0.029), and lymphovascular invasion(p=0.019). High HIF-$1{\alpha}$ expression was also significantly associated with VEGF immunoreactivity(p<0.001), and aberrant p53 expression(p=0.040). but was marginally associated with Ki-67 labeling index(p=0.092). The overall 5-year survival rate was 42.3%. The survival curve of patients with a high HIF-$1{\alpha}$ expression was worse than that of patients with low-expression(p=0.002). High HIF-$1{\alpha}$ expression was independent unfavorable factors with a marginal significance in multivariate analysis performed by Cox regression. Conclusion: It is suggested that high HIF-$1{\alpha}$ expression may be associated with intratumoral neovascularization possibly through HIF-VEGF pathway, and high HIF-$1{\alpha}$ expression could be associated with lymph node metastasis and post operative poor prognosis in patients with non-small cell lung carcinoma.

• Journal of Chest Surgery
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• v.36 no.10
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• pp.711-720
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• 2003

Bakground : Complete resection by the surgery has been selected as the treatment of choice in lung cancer patients, but in cases of recurrence after excision or inoperable cases, the importance of anticancer chemotherapy has been emphasized. If one can select a set of the sensitive chemotherapeutic agents before anticancer chemotherapy, it will give more favourable results. Subrenal capsular assay has been recognized as a useful in-vivo chemosensitivity test of thoracic and abdominal tumors and it can be done in a short time for a rapid interpretation of tumor responsiveness to anticancer chemotherapeutic drugs. It has been reported that various kinds of cancer cells can be implantable to the kidney, but so far there is no comparative study of xenogeneic cell implantation on liver, spleen and kidney. The author implanted the human lung cancer cells under the capsule of S.D rat's liver, spleen and kidney respectively and compared the pattern of growth and histology. Material and Method: After incubation of human lung cancer cell line (SW-900 G IV) in RPMI 1640 (Leibovitz L-15 medium) culture media, 3${\times}$3${\times}$3 mm size fibrin clots which contain 108 cancer cells were made. Thereafter the fibrin clots were implanted at subcapsule area of liver, spleen and kidney of S.D. female rat. For immune suppression, cyclosporin-A (80 mg/Kg) was injected subcutaneously daily from post-implantation first day to sixth day. The body weight was measured at pre and post implantation periods. The growth pattern and the size of tumor mass were observed and the pathologic examination and serum tumor marker tests were performed. Result: Body weight increased in both of control and experimental groups. Serum Cyfra 21-1 was not detected. Serum levels of CEA and NSE revealed no significant change. The SCC-Ag increased significantly in implanted group. The growth rate of human lung cancer cells which was implanted on spleen was higher than on liver or kidney. The surface area, thickness, and volume of tumor mass were predominant at spleen. The success rates of implantation were 80% on kidney, 76.7% on spleen and 43.3% on liver. Pathologic examination of implanted tumors showed characteristic findings according to different organs. Tumors that were implanted on kidney grew in a round shape, small and regular pattern. In the spleen, tumors grew well and microscopic neovascularization and tumor thrombi were also found, but the growth pattern was irregular representing frequent daughter mass. Human lung cancer cells that were implanted in the liver, invaded to the liver parenchyme, and had low success rate of implantation. Microscopically, coagulation necrosis and myxoid fibrous lesion were observed. Conclusion: The success rate of implantation was highest in the kidney. And the mass revealed regular growth that could be measured easily. The SCC-Ag was presented earlier than CEA or Cyfra21-1. The Cyfra21-1 was not detected at early time after implantation. The best model for tumor implantation experiment for chemosensitivity test was subrenal capsular analysis than liver and spleen and the useful serum tumor marker in early period of implantation was the SCC-Ag.

• Journal of Chest Surgery
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• v.32 no.8
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• pp.726-731
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• 1999

Background: The distinction between non-invasive and invasive or thymic carcinoma has been severely compromised by lack of objective morphological criteria. A reliable biological marker of tumor aggressiveness is, therefore, mandatory for predicting tumor behavior. Material and Method: Thirty thymic epithelial tumors, including 7 non-invasive thymoma, 10 invasive thymoma, and 13 thymic carcinoma of the Rosai's classification; and 5 stage I, 7 stage II, 2 stage III, and 3 stage IVa of the Masaoka stage of thymoma were investigated for expression of bcl-2 and p53 proteins by immunohistochemistry. Result: The thymic epithelial cells showed positive immunostain for bcl-2 in 0 (0%), 3 (30%), 8 (61.5%) of categories in the Rosai's classification respectively and in 0 (0%), 1 (14.3%), 2 (100%), 0 (0%) of stage I, II, III, IVa of the Masaoka stage respectively. Thymic carcinoma, and high stage thymoma had significantly higher proportion of bcl-2 expression than thymoma (p=0.021) and low stage thymoma (p=0.011). However, p53 showed no correlation with the histological subtypes nor with clinical aggressiveness. Bcl-2 expression appeared to be positively correlated with p53 immunoactivity (p=0.007, kappa=0.525). Conclusion: These date indicate that bcl-2 expression correlates with aggressiveness in thymic epithelial tumors, but further studies on mutation of p53 protein is necessary because bcl-2 expression appeared to be positively correlated with p53 immunoactivity.

• Journal of Chest Surgery
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• v.37 no.8
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• pp.691-701
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• 2004

Background: Tissue hypoxia is a characteristic of many human malignant neoplasms, and hypoxia inducible factor-1 (HIF-1) plays a pivotal role in essential adaptive response to hypoxia, and activates a signal pathway for the expression of the hypoxia-regulated genes, resulting in increased oxygen delivery or facilitating metabolic adaptation to hypoxia. Increased level of HIF-1 a has been reported in many human malignancies, but in esophageal squamous cell carcinoma, the influence of HIF-1 a on tumor biology, including neovascularization, is not still defined. Material and Method: The influence of HIF-1 a expression on angiogenic factors, correlation between the tumor proliferation and HIF-1 a expression, interaction of HIF-1 a expression and p53, and correlation between HIF-1 a expression and clinicopathological prognostic parameters were investigated, using immunohistochemical stains for HIF-1 a, VEGF, CD34, p53, and Ki-67 on 77 cases of resected esophageal squamous cell carcinoma. Result: HIF-1 a expression in cancer cells was found in 33 of 77 esophageal squamous cell carcinoma cases. The 33 cases (42.9%) showed positive stain for HIF-1 a. High HIF-1 a expression was significantly associated with several pathological parameters, such as histologic grade (p=0.032), pathological TMN stage (p=0.002), the depth of tumor invasion (p=0.022), regional lymph node metastasis (p=0.002), distant metastasis (p=0.049), and lymphatic invasion (p=0.004). High HIF-1 a expression had significant VEGF immunoreactivity (p=0.008) and Ki-67 labeling index (p<0.001), but was not correlated with microvascular density within tumors (p=0.088). The high HIF-1 a expression was correlated with aberrant p53 accumulation with a marginal significance (p=0.056). The overall 5-year survival rate was 34.9%. The survival rate of patients with a high HIF-1 a expression was worse than that of patients with low-expression tumors (log-rank test, p=0.0001). High HIF-1 a expression was independent unfavorable factors although statistical significance is marginal in multivariate analysis. Conclusion: It is suggested that (1) high HIF-1 a expression in esophageal squamous cell carcinoma is associated with tumor hypoxia, or with genetic alteration in early carcinogenesis and progressive stages, (2) high HIF-1 a expression may be associated with intratumoral neovascularization through HIF-VEGF pathway, and (3) high HIF-1 a expression is associated with poor prognosis in patients with esophageal squamous cell carcinoma and may playa role as biomarker for regional lymph node metastasis.

• Journal of Chest Surgery
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• v.41 no.1
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• pp.74-81
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• 2008

Background: Fascin is an actin-bundling protein that induces membrane protrusions and it increases cell motility in various transformed cells. Esophageal cancer is one of the most lethal malignancies, and it exhibits extensive local invasion or frequent regional lymph node metastasis even after curative surgery. We investigate the expression of fascin by performing immunohistochemistry to evaluate the clinical characteristics and prognostic significance of its expression in esophageal cancer patients. Material and Method: Immunochemistry for fascin was performed on 76 tumor samples from 76 patients who underwent esophageal cancer operations. The expression levels of fascin in the 76 esophageal cancer tissues were compared with those in the corresponding normal esophageal epithelium. The fascin-positive samples were defined as those showing more than 75% of fascin-positive cells. Result: Overall, a fascin positive expression was detected in 39 (51.3%) out of the total 76 cases. The tumors with positive fascin expression tended to more frequently show a higher stage (p=0.030), and a higher T-factor (p=0.031). The prognosis of the fascin negative group was significantly better than that of the fascin positive group (p=0.004). Multivariate analysis revealed that lymphovascular invasion and the fascin expression were independent prognostic factors. Conclusion: Fascin was expressed in 513% of the esophageal cancer tissues and a positive expression of fascin was associated with more advanced tumor progression and recurrence. Our study suggests that the fascin expression may be an independent prognostic factor for an unfavorable clinical course few those patients suffering with esophageal cancer.