Yonsei Cancer Research Institute

Seoul, South Korea

Yonsei Cancer Research Institute

Seoul, South Korea
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Noh S.,Cancer Metastasis Research Center | Jung J.-J.,Cancer Metastasis Research Center | Jung J.-J.,National Biochip Research Center | Jung M.,Cancer Metastasis Research Center | And 18 more authors.
Hepato-Gastroenterology | Year: 2011

Background/Aims: We evaluated matrix metalloproteinase (MMP)-2 and -9 as novel biomarkers in the body fluid of advanced gastric cancer with peritoneal and pleural metastasis. Methodology: MMPs activity from zymography was quantified with ELISA to determine the cut-off expression levels of MMPs. The expression of MMPs in patient samples were evaluated with ELISA and compared with clinical parameters. Ascitic CEA (aCEA) and pleural CEA (pCEA) were measured by chemiluminescent enzyme immunoassay. Results: MMP-2 and -9 cut-off levels were 8.6ng/mL and 0.14ng/mL, respectively. Ascitic fluid cytology of 93 patients revealed a positivity of 55.9% while for MMP-2 it was 93.3%, for MMP-9 35.2% and for aCEA 86.7%. Combining biomarkers, the positivity increased to 99.1% in patients with MMP-2 and aCEA expression. We found a negative correlation between MMP-2 expression and survival when a new prognostic cut-off of 22.6ng/mL was used. Patients with high MMP-2 expression (≥22.6ng/mL) had a median survival of 45 days and those with low MMP-2 expression (<22.6ng/mL) had a median survival of 69 days (p<0.01). Conclusions: These results suggest that MMPs could be used as diagnostic markers in body fluid and MMP-2 might be a prognostic marker in ascites of advanced gastric patients with disseminated metastasis. © H.G.E. Update Medical Publishing S.A.

Kim J.H.,Yonsei Cancer Research Institute | Kim J.H.,Cancer Metastasis Research Center | Kim J.H.,Yonsei University | Kim H.S.,Yonsei Cancer Research Institute | And 17 more authors.
Annals of Oncology | Year: 2012

Background: Nomograms are statistics-based tools that provide the overall probability of a specific outcome. In our previous study, we developed a nomogram that predicts recurrence of early gastric cancer (EGC) after curative resection. We carried out this study to externally validate our EGC nomogram. Patients and methods: The EGC nomogram was established from a retrospective EGC database that included 2923 consecutive patients. This nomogram was independently externally validated for a cohort of 1058 consecutive patients. For the EGC nomogram validation, we assessed both discrimination and calibration. Results: Within the follow-up period (median 37 months), a total of 11 patients (1.1%) experienced recurrence. The concordance index (c-index) was 0.7 (P = 0.02) and the result of the overall C index was 0.82 [P = 0.006, 95% confidence interval (CI) 0.59-1.00]. The goodness of fit test showed that the EGC nomogram had significantly good fit for 1- and 2-year survival intervals (P = 0.998 and 0.879, respectively). The actual and predicted survival outcomes showed good agreement, suggesting that the survival predictions from the nomogram are well calibrated externally. Conclusions: A preexisting nomogram for predicting disease-free survival (DFS) of EGC after surgery was externally validated. The nomogram is useful for accurate and individual prediction of DFS, patient prognostication, counseling, and follow-up planning. © The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Lee W.S.,Cancer Metastasis Research Center | Lee W.S.,Yonsei University | Jung J.J.,Cancer Metastasis Research Center | Jung J.J.,Yonsei University | And 15 more authors.
Hepato-Gastroenterology | Year: 2012

Background/Aims: Epigenetic regulations play a role in the development and progression of cancer. Therefore, discovering novel epigenetically regulated genes could provide useful information in understanding cancer. Lamin A/C is an intermediate filament protein whose expression is reported to be suppressed in tissues of gastro-intestinal malignancies. We examined expression of lamin A/C in gastric and colorectal cancer cell lines and its association with DNA methylation. Methodology: The methylation status of CpG island in 19 gastric, 5 colorectal cancer cells and 1 normal colon cell line were examined with methylation-specific PCR using paired methylated and unmethylated primers. The level of mRNA expression of lamin A/C was detected using RT-PCR. Results: Eighteen gastric cancer cell lines showed 95% unmethylation of lamin A/C and 1 cell line showed partial methylation. In colorectal cancer, only 1 out of 5 cancer cell lines (20%) was partially methylated and the remaining cell lines, including 1 normal colon cell line was unmethylated. With RT-PCR, all cell lines demonstrated mRNA expression of lamin A/C regardless of methylation status. Conclusions: We observed that the expression of lamin A/C was not suppressed in gastrointestinal cancer cell lines different from hematologic malignant cells and it is not regulated through DNA methylation. © H.G.E. Update Medical Publishing S.A.

Kim C.,Yonsei University | Chon H.J.,Yonsei University | Kang B.,Yonsei University | Kim K.,Yonsei University | And 7 more authors.
BMC Cancer | Year: 2013

Background: Due to improved survival rate, gastric cancer (GC) patients have an increased risk of developing multiple primary cancer (MPC). The purpose of this study is to evaluate the clinicopathological features of MPC and to generate useful tools for the prediction of metachronous MPC following gastrectomy.Methods: 3066 patients who underwent curative resection of GC were reviewed retrospectively, based on the clinical information and the medical record.Results: The 5-year incidence of MPC was 2.5%. Of these, 54.3% had a metachronous MPC, while 45.7% had a synchronous MPC. The most prevalent site of metachronous MPC was the colorectum (26.3%), followed by lung (23.7%) and liver (18.4%). Multivariate logistic regression analysis revealed that old age at the time of GC diagnosis (≥60 years), early stage of GC (stage I and II), and multiplicity of GC at the time of gastrectomy were independent predictive factors for metachronous MPC. GC patients with either metachronous or synchronous MPC showed poorer survival than patients without MPC. In addition, patients with a metachronous MPC showed late survival disadvantage, while patients with a synchronous MPC showed early survival disadvantage. Furthermore, we were able to develop and internally validate a nomogram to predict the metachronous MPC after curative gastrectomy (C-index = 0.72).Conclusion: Patients at high risk of developing metachronous MPC after curative resection of GC were identified. Individual risk of developing metachronous MPC could be predicted by a novel nomogram. Further external validation with independent patient cohorts is required to improve the accuracy of prediction. © 2013 Kim et al.; licensee BioMed Central Ltd.

Kim H.R.,Yonsei University | Kim H.R.,Yonsei Cancer Research Institute | Min B.S.,Yonsei University | Kim J.S.,Yonsei University | And 9 more authors.
Oncology | Year: 2011

Objectives: Although surgical resection alone has been validated as a standard treatment for patients with liver metastases from colorectal cancer, a high rate of recurrence is still an issue to be overcome. We aimed to assess the efficacy of adjuvant chemotherapy using an oxaliplatin-based regimen in patients who underwent hepatic and primary colorectal cancer resection. Methods: Sixty patients who received oxaliplatin-based postoperative chemotherapy combined with curative resection of primary colorectal cancer and synchronous liver metastases between January 2000 and February 2008 were retrospectively reviewed. The Kaplan-Meier method was used to estimate survival, and prognostic factors were evaluated with the log-rank test. Results: Median overall survival (OS) was 62.8 months [95% confidence interval (CI) 44.1-81.3], and median relapse-free survival (RFS) was 32.8 months (95% CI 5.8-59.6). The 1-, 3- and 5-year survival rates were 95.0, 68.8 and 55.5%, respectively. The relapse-free interval and modality of liver resection were independently associated with OS. Conclusions: Oxaliplatin-based adjuvant chemotherapy after radical resection resulted in increased OS and RFS with acceptable tolerability compared to surgery alone. However, it is not yet clear whether postoperative oxaliplatin-based chemotherapy improves outcome compared to patients treated with 5-fluorouracil plus leucovorin. Copyright © 2011 S. Karger AG, Basel.

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