• Journal of Gastric Cancer
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• v.21 no.1
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• pp.103-109
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• 2021

Gastric adenocarcinoma of the fundic gland mucosa type (GA-FGM) was proposed as a new variant of gastric adenocarcinoma of the fundic gland type (GA-FG). However, at present, the influence of Helicobacter pylori and the speed of progression and degree of malignancy in GA-FGM remain unclear. Herein, we report the first case of intramucosal GA-FGM that was endoscopically observed before and after H. pylori eradication over 15 years. The lesion showed the same tumor size with no submucosal invasion and a low MIB-1 labeling index 15 years after its detection using endoscopy. The endoscopic morphology changed from 0-IIa before H. pylori eradication to 0-IIa+IIc and then 0-I after H. pylori eradication. These findings suggest that the unaltered tumor size reflects low-grade malignancy and slow growth, and that the endoscopic morphology is influenced by H. pylori eradication.

• Radiation Oncology Journal
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• v.19 no.2
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• pp.171-180
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• 2001

Purpose : Expression of TIMP, intrinsic inhibitor of MMP, is regulated by signal transduction in response to genotoxins and is likely to be an important step in metastasis, angiogenesis and wound healing after ionizing radiation. Therefore, we studied radiation mediated TIMP expression and its mechanism in head and neck cancer cell lines. Materials and Methods : Human head and neck cancer cell lines established at Asan Medical Center were used and radiosensitivity $(D_0)$, radiation cytotoxicity and metastatic potential were measured by clonogenic assay, n assay and invasion assay, respectively. The conditioned medium was prepared at 24 hours and 48 hours after 2 Gy and 10 Gy irradiation and expression of TIMP protein was measured by Elisa assay with specific antibodies against human TIMP. hTIMP1 promoter region was cloned and TIMP1 luciferase reporter vector was constructed. The reporter vector was transfected to AMC-HN-1 and -HN-9 cells with or without expression vector Ras, then the cells were exposed to radiation or PMA, PKC activator. EMSA was peformed with oligonucleotide (-59/-53 element and SP1) of TIMP1 promoter. Results : $D_0$ of HN-1, -2, -3, -5 and -9 cell lines were 1.55 Gy, 1.8 Gy, 1.5 Gt, 1.55 Gy and 2.45 Gy respectively. n assay confirmed cell viability, over $94\%$ at 24hrs, 48hrs after 2 Gy irradiation and over 73% after 10 Gy irradiation. Elisa assay confirmed that cells secreted TIMP1, 2 proteins continuously. After 2 Gy irradiation, TIMP2 secretion was decreased at 24hrs in HN-1 and HN-9 cell lines but after 10 Gy irradiation, it was increased in all cell lines. At 48hrs after irradiation, it was increased in HN-1 but decreased in HN-9 cells. But the change in TIMP secretion by RT was mild. The transcription of TIMP1 gene in HN-1 was induced by PMA but in HN-9 cell lines, it was suppressed. Wild type Ras induced the TIMP-1 transcription by 20 fold and 4 fold in HN-1 and HN-9 respectively. The binding activity to -59/-53, AP1 motif was increased by RT, but not to SP1 motif in both cell lines. Conclusions : We observed the difference of expression and activity of TIMPs between radiosensitive and radioresistant cell line and the different signal transduction pathway between in these cell lines may contribute the different radiosensitivity. Further research to investigate the radiation response and its signal pathway of TIMPs is needed.

• Radiation Oncology Journal
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• v.18 no.1
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• pp.11-16
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• 2000

Purpose :We peformed the retrospective analysis to find the outcome of external beam radiotherapy alone in advanced esophageal cancer patients. Methods and Materials : One hundred and six Patients treated with external beam radiotherapy alone between July 1990 and December 1996 were analyzed retrospectively. We limited the site of the lesions to the thoracic esophagus and cell type to the squamous cell carcinoma. Follow-up was completed in 100 patients (94$\%$) and ranged from 1 month to 92 months (median; 6 months). Results :The median age was 62 years old and male to female ratio was 104 2. Fifty-three percent was the middle thorax lesion and curative radiotherapy was peformed in 83$\%$. Mean tumor dose delivered with curative aim was 58.6 Gy (55$\~$70.8 Gy) and median duration of the radiation therapy was 53 days. The median survival of all patients was 6 months and )-year and 2-year overall survival rate was 27$\%$ and 12$\%$, respectively, Improvement of dysphagia was obtained in most patients except for 7 patients who underwent feeding gastrostomy. The complete response rate immediately after radiation therapy was 32$\%$ (34/106). The median survival and 2-year survival rate of the complete responder was 14 months and 30$\%$ respectively, while those of the nonresponder was 4 months and 0$\%$ respectively (p=0.000). The median survival and 2-year survival rate of the patients who could tolerate regular diet was 9 months and 16$\%$ while those of the patients who could not tolerate regular diet was 3 months and 0$\%$, respectively (p=0.004). The survival difference between the patients with S cm or less tumor length and those with more than 5 cm tumor length was marginally statistically significant (u=0,06). However, the survival difference according to the periesophageal invasion or mediastinal tyrnphadenopathy in the chest CT imaging study was not statistically significant in this study. In a multivariate analysis, the statistically significant covariates to the survival were complete response to radiotherapy, tumor length, and initial degree of dysphagia in a decreasing order. The complication was observed in 10 patients (9$\%$). Conclusion :The survival outcome for advanced esophageal cancer patients treated by external beam radiotherapy alone was very poor. In the treatment of these patients, the brachytherapy and chemotherapy should be added to improve the treatment outcome.

• Radiation Oncology Journal
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• v.19 no.4
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• pp.335-344
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• 2001

Purpose : The aim of this study was to clarify the role of VEGF expression as an independent prognostic factor and to identify the patients at high risk for poor prognosis in stage IB cervical cancer. Materials and methods : A total of 118 patients with stage IB cervical cancer who had radical hysterectomy and pelvic lymph node dissection were included in the study. All known high risk factors of the patients were pathologically confirmed from the surgical specimen. Of the 118 patients, n patients were treated with postoperative radiotherapy and/or chemotherapy. VEGF expression was examined using immunohistochemistry in formalin-fixed, paraffin-embedded specimens of post-hysterectomy surgical materials. A semiquantitative analysis was made using a scoring system of 0, +, ++, and +++ for increasing intensity of stain. We classified the patients with scores from 0 to ++ as low VEGF expression and the patients with a score of +++ as high VEGF expression. Results : Of the 118 patients, 35 patients $(29.7\%)$ showed high VEGF expression. Strong correlations were found between the high VEGF expression and both deep stromal invasion (p=0.01) and the positive pelvic node (p=0.03). The 5-year overall and disease-free survival rates for all 118 patients were $95.5\%\;and\;93.8\%$. The 5-year overall (p=0.03) and disease-free survival (p<0.001) rates were $98.5\%\;and\;100%$ for low VEGF expression (0, +, and ++) and $85.5\%\;and\;79.7\%$ for high VEGF expression, respectively. Pelvic and distant failures for low versus high VEGF expression were $1.2\%$ versus $17.1\%$, (p=0.001) and $0\%$ versus $14.3\%$ (p<0.001), respectively. In a Cox multivariate analysis of survival, the high VEGF expression (p=0.02) and the bulky mass (p=0.02) were significant prognostic factors for overall survival. The high VEGF expression (p=0.002), and bulky mass (p=0.01) demonstrated as significant prognostic indicators for disease free survival. Conclusion : These results showed that VEGF expression was a highly significant predictor for pelvic and distant failure and the most significant prognostic factor of overall and disease free survival for the patients with stage IB cervix cancer treated with radical surgery. We strongly suggest that the immune-histochemistry for VEGF expression be performed in a routine clinical setting in order to identify the patients at high risk for poor prognosis in early stage cervical cancer. Furthermore, postoperative and/or chemotherapy did not reduce the pelvic failure and distant metastasis. To improve the cure rate for the patients with high VEGF expression in stage IB cervical cancer, antiangiogenic therapy including anti-VEGF Ab may be new treatment option.

• Journal of Gastric Cancer
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• v.5 no.2
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• pp.89-94
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• 2005

Purpose: Early gastric cancer (EGC) has an excellent prognosis compared to advanced gastric cancer. The 5-year survival rate for EGC now exceeds $90\%$, and EGC is recognized as a curable malignancy. The important prognostic factor in EGC is the status of lymph-node metastasis. Despite conserving surgery being suggested for EGC at present, it is of vital importance to select a surgical method appropriate to each individual case. This retrospective study was undertaken to clarify clinicopathologic features and factors related to lymph-node metastasis in submucosal gastric cancer in order to determine an appropriate therapy. Materials and Methods: This study analyzed the clinicopathologic features for 279 patients with a submucosal gastric carcinoma (Group I) and compared with those of patients with mucosal (Group II) or muscularis proprial gastric carcinoma (Group III). All patients were operated on from 1981 to 1999 at Chonnam University Hospital. There were no statistically significant differences among the groups with respect to age, gender, tumor location, hepatic metastasis, or peritoneal dissemination. Results: Positive lymph node metastasis was found in 47 ($16.8\%$) of the 279 patients with a submucosal gastric carcinoma. The incidence of lymph-node metastasis was significantly higher in patients with a submucosal gastric carcinoma than in patients with a mucosal gastric carcinoma ($16.8\%\;vs.\;3.9\%\;$; P<0.01). Therefore, depth of invasion was a significant factor affecting in lymph-node metastasis. The 5-year survival rates were $88.6\%$ for patients in Group I, $95.2\%$ for patients in Group II, and $72.7\%$ for patients in Group III (P<0.01 for Group I vs. Group II; Group I vs. Group III). In patients with a submucosal gastric carcinoma, the survival rate with positive lymph nodes was significantly poorer than that of patients without lymph-node metastasis ($87.3\%\;vs.\;94.2\%$; P<0.01). Conclusion: Gastrectomy with D2 lymph node dissection is an appropriate operative procedure for patients with a submucosal gastric carcinoma.

• Journal of Chest Surgery
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• v.32 no.6
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• pp.536-542
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• 1999

Background: The purpose of this study is to improve the quality of the diagnostic procedures in the preoperative evaluation so as to reduce the unnecessary thoracotomy and to ensure resectability in non-small cell lung cancer. Material and Method: Of 616 patients who underwent thoracotomy for primary lung cancer from January 1990 to December 1996, 59 patients(9.6%) turned out to have inoperable lesions after the thoracotomy. We reprospectively reviewed the bronchoscopic findings, methods of tissue diagnosis, CT scans, pulmonary function test and lung perfusion scan, reasons for nonresectability, and adjuvant therapy, and then followed up on the survival rate after exploratory thoracotomy. Result: The cell types were squamous cell carcinoma in 38, adenocarcinoma in 15, large cell carcinoma in 3 and others in 3. Primary loci were RUL in 20, RML in 6, RLL in 8, LUL in 13, LLL in 4 and others in 8. The reasons for non-resectability were various; direct tumor invaison to mediastinal structures(n=41), seeding on pleural cavity(n=8), poor pulmonary function(n=2), invasions to extranodal mediastinal lymph node(n=2), technical non- resectability due to extensive chest wall invasion (n=3), small cell carcinoma (n=1), malignant lymphoma(n=1), and multiple rib metastases(n=1). In the follow-up of 58 patients, 1-year survival rate was 55.2% and 2-year survival rate was 17.2% and the mean survival time was 14 months. When compared according to cell types or postoperative adjuvant therapeutic modalities, no significant difference in the survival rates were found. The squamous cell carcinoma was frequently accompanied by local extension to contiguous structures and was the main cause of non-resectability. In adenocarcinoma, pleural seeding with malignant effusion was frequently encountered, and was the major reason for non-resectability. Conclusion: These data revealed that if appropriate preoperative diagnostic tools had been available, many unnecessary thoracotomies could have been avoided. Both the use of thoracoscopy in selected cases of adenocarcinoma and the more aggressive surgical approach to the locally advanced tumor could reduce the incidence of unnecessary thoracotomies for non-small cell lung cancers.

• Nuclear Medicine and Molecular Imaging
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• v.43 no.1
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• pp.26-34
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• 2009

Purpose: The purpose of this study was to find out what clinicopathologic or immunohistochemical parameter that may affect FDG uptake of primary tumor in PET/CT scan of the gastric carcinoma patient. Materials and Methods: Eighty-nine patients with stomach cancer who underwent pre-operative FDG PET/CT scans were included. In cases with perceptible FDG uptake in primary tumor, the maximum standardized uptake value (SUVmax) was calculated. The clinicopathologic results such as depth of invasion (T stage), tumor size, lymph node metastasis, tumor differentiation and Lauren's classification and immunohistochemical markers such as Ki-67 index, expression of p53, EGFR, Cathepsin D, c-erb-B2 and COX-2 were reviewed. Results: Nineteen out of 89 gastric carcinomas showed imperceptible FDG uptake on PET/CT images. In cases with perceptible FDG uptake in primary tumor, SUVmax was significantly higher in T2, T3 and T4 tumors than T1 tumors ($5.8{\pm}3.1$ vs. $3.7{\pm}2.1$, p=0.002). SUVmax of large tumors (above or equal to 3 cm) was also significantly higher than SUVmax of small ones (less than 3 cm) ($5.7{\pm}3.2$ vs. $3.7{\pm}2.0$, p=0.002). The intestinal types of gastric carcinomas according to Lauren showed higher FDG uptake compared to the non-intestinal types ($5.4{\pm}2.8$ vs. $3.7{\pm}1.3$, p=0.003). SUVmax between p53 positive group and negative group was significantly different ($6.0{\pm}2.8$ vs. $4.4{\pm}3.0$, p=0.035). No significant difference was found in presence of LN metastasis, tumor differentiation, Ki-67 index, and expression of EGFR, Cathepsin D, c-erb-B2 and COX-2. Conclusion: T stage of gastric carcinoma influenced the detectability of gastric cancer on FDG PET PET/CT scan. When gastric carcinoma was perceptible on PET/CT scan, T stage, size of primary tumor, Lauren's classification and p53 expression were related to degree of FDG uptake in primary tumor.

• Nuclear Medicine and Molecular Imaging
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• v.43 no.5
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• pp.429-435
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• 2009

Purpose: The purpose of this study was to assess the prognostic value of preoperative FDG-PET in colorectal cancer (CRC) patients with hepatic metastasis (HM). Materials and Methods: 24 CRC patients (M:F=14:10; age, $63{\pm}10$ yrs) with HM who had undergone preoperative FDG PET were included. Cure-intent surgery was performed in all the patients and HMs were controlled using resection (n=13), radio-frequency ablation (RFA) (n=7), and resection plus RFA (n=4). Potential prognostic markers tested were maxSUV of primary tumor, maxSUV of HM, maxSUV ratio of HM over primary tumor (M/P ratio), histologic grade, CEA level, venous/lymphatic/nerve invasion, T stage, N stage, no. of HM, no. of lymph node metastasis, and treatment modality of HM. Results: 14 CRC patients developed a recurrence with a median follow-up duration of 244 days, whereas 10 patients did not develop recurrence with a median follow-up duration of 504 days. M/P ratios but other potential prognostic markers were significantly higher in the recurrent patients ($0.72{\pm}0.14$) than recurrence-free patients ($0.54{\pm}0.23$) (p=0.038). M/P ratio only was found to predict recurrence by Cox multivariate analysis (hazard ratio 37.7, 95% confidence interval 2.01-706.1, p=0.016). The 11 patients with lower M/P ratio of <0.61 had significantly better disease-free survival rate than the 13 patients with higher M/P ratio (${\geq}0.61$) (p=0.026). Conclusion: maxSUV ratio of HM over primary tumor (M/P ratio) may be useful for prognosis prediction of CRC patients with HM. Higher FDG uptake of HM than that of primary tumor may indicate a more advanced status in stage IV CRC.

• Tuberculosis and Respiratory Diseases
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• v.52 no.2
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• pp.117-127
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• 2002

Backgroud : MUC1 mucin is a heavily glycosylated large glycoprotein and is expressed aberrantly in carcinoma. CD44 is polymorphic family of cell surface glycoproteins participating in cell-cell adhesion and modulation of the cell-matrix interaction. MUC1 mucin and CD44 expression have been implicated in a tumor invasion and metastasis in certain malignancies. In this study, the expression of MUC1 and the standard form of CD44 (CD44s) was examined in non-small cell lung cancer (NSCLC). Methods : Immunohistochemical staining using monoclonal antibodies including MUC1 glycoprotein and CD44s was performed on 80 NSCLC surgical specimens. The association between MUC1 and CD44s expression and the histological type and tumor stage was investigated. Results : Depolarized MUC1 expression in more than 10% of cancer cells was found in 12 (27.9%) out of 43 squamous cell carcinomas (SCCs) and 12 (32.4%) out of 37 adenocarcinomas (ACs). It was not associated with the tumor histological type and the TNM-stage in SCCs. Depolarized MUC1 expression correlated with the N-stage in ACs (p=0.036). CD44s was expressed in 36 (83.7%) out of 43 SCCs and 14 (37.8%) out of 37 ACs. Reduced CD44s expression correlated with the N-stage (p=0.031) and the TNM-stage (p=0.006) in SCCs. Conclusions : Depolarized MUC1 expression was related to the nodal stage in NSCLC adenocarcinoma. Reduced CD44s expression was related to nodal involvement and the TNM-stage in squamous cell carcinoma. This suggests that MUC1 and CD44s expression in NSCLC might play important roles in tumor progression and cap be used as prognostic variables.

• Journal of Life Science
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• v.29 no.1
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• pp.9-17
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• 2019

As tumors develop, they encounter microenvironmental stress, such as hypoxia and glucose depletion, due to poor vascular function, thereby leading to necrosis, which is observed in solid tumors. Necrotic cells are known to release cellular cytoplasmic contents, such as high mobility group box 1 (HMGB1), into the extracellular space. The release of HMGB1, a proinflammatory and tumor-promoting cytokine, plays an important role in promoting inflammation and metabolism during tumor development. Recently, HMGB1 was shown to induce the epithelial-mesenchymal transition (EMT) and metastasis. However, the underlying mechanism of the HMGB1-induced EMT, invasion, and metastasis is unclear. In this study, we showed that noninvasive breast cancer cells MCF-7 formed tightly packed, rounded spheroids and that the cells in the inner regions of a multicellular tumor spheroid (MTS), an in vitro model of a solid tumor, led to necrosis due to an insufficient supply of O2 and glucose. In addition, after 7 d of MTS culture, the EMT was induced via the transcription factor Snail. We also showed that HMGB1 receptors, including RAGE, TLR2, and TLR4, were induced by MTS culture. RAGE, TLR2, and TLR4 shRNA inhibited MTS growth, supporting the idea that RAGE/TLR2/TLR4 play critical roles in MTS growth. They also prevented MTS culture-induced Snail expression, pointing to RAGE/TLR2/TLR4-dependent Snail expression. RAGE, TLR2, and TLR4 shRNA suppressed the MTS-induced EMT. In human cancer tissues, high levels of RAGE, TLR2, and TLR4 were detected. These findings demonstrated that the HMGB-RAGE/TLR2/TLR4-Snail axis played a crucial role in the growth of the MTS and MTS culture-induced EMT.