Hyun Cheol Chung

Yonsei University Hospital, Sŏul, Seoul, South Korea

Are you Hyun Cheol Chung?

Claim your profile

Publications (177)632.21 Total impact

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Gastric cancer (GC) is a heterogeneous disease that is not well detected by current tumor markers. Identifying molecular markers that can predict the potential for tumor progression is important for appropriate individualized therapy. Using the Cancer Metastasis Research Center microarray database (17K cDNA microarray), we identified genes that were differentially expressed between 96 cancer and 98 normal gastric tissues using significant analysis of microarrays. From these, we selected genes that were overexpressed more than twofold in tumor tissues that encode secreted proteins. The selected genes were validated with ELISA using the sera of 96 GC patients and 48 healthy donors. Our first round of selection included 6510 genes that were differentially expressed between 96 cancer and 98 normal gastric tissues with a minimal false discovery rate of 0.005%. Out of those genes, we picked 386 that encoded secreted proteins based on the SOURCE database. Of these genes, we focused on 55 that were overexpressed more than twofold in GC compared to normal tissues. With Ingenuity Pathway Analysis, we found 34 genes related to cancer. One in particular, chemokine growth-regulated oncogene 1, CXCL1, has been linked to cancer progression in various cancer types, but not yet to GC. Levels of CXCL1 in serum samples of GC patients were significantly higher compared with healthy donors (P < 0.05). Within GC patients, CXCL1 serum levels increased according to tumor stage and lymph node metastasis. The CXCL1 gene appears to be a candidate marker for GC progression.
    Cancer Science 10/2010; 101(10):2200-6. · 3.53 Impact Factor
  • Source
    Hei Cheul Jeung, Hyun Cheol Chung
    Asia-Pacific Journal of Clinical Oncology 09/2010; 6(3):141-3. · 0.91 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We analyzed the natural history of advanced gastric cancer with sequential salvage chemotherapy following first-line treatment. We studied 532 patients with unresectable gastric adenocarcinoma who were treated at Yonsei Cancer Center (2000-2008). The patients were managed with multiple sequential salvage chemotherapy as allowed by performance status and toxicity profiles. The tumor response was assessed every two cycles. Four hundred sixty patients received palliative chemotherapy and 72 received supportive care only. The median overall survival was 12.0 months for all patients, 12.1 months for the chemotherapy group, and 2.5 months for the supportive care group (P < 0.001). In the chemotherapy group, 87% received first-line chemotherapy, 47% second-line, 23% third-line, 9% fourth-line, and 3% fifth-line. Response rates were 24.8, 12.6, 10.9, 2.6, and 0% and disease control rates were 76.3, 60.1, 54.2, 54.2, and 53.3% for first- to fifth-line treatment, respectively. The median progression-free survival was 5.5, 3.4, 2.5, 1.9, and 2.0 months and overall survival was 12.1, 7.9, 5.5, 5.0, and 6.8 months. Performance status and metastatic pattern were consistent prognostic factors throughout salvage treatment. Clinical trials may be feasible in second- or third-line salvage chemotherapy for gastric cancer. Future clinical trials in these settings should take into account the low response rate, short progression-free survival, and the prognostic factors for optimal trial design.
    Cancer Chemotherapy and Pharmacology 03/2010; 66(4):797-805. · 2.80 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We evaluated the cytotoxic effects of combining suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, with taxanes in human gastric cancer cell lines and assessed the pre-treatment difference of gene expression to identify genes that could potentially mediate the cytotoxic response. Gastric cancer cell lines were treated with SAHA and paclitaxel or docetaxel, and the synergistic interaction between the drugs was evaluated in vitro using the combination index (CI) method. We performed significance analysis of microarray (SAM) to identify chemosensitivity-related genes in gastric cancer cell lines that were concomitantly treated with SAHA and taxane. We generated a correlation matrix between gene expression and CI values to identify genes whose expression correlated with a combined effect of taxanes and SAHA. Combination treatment with taxane and SAHA had a synergistic cytotoxic effect against taxane-resistant gastric cancer cells. We identified 49 chemosensitivity-related genes via SAM analysis. Among them, nine common genes (SLIT2, REEP2, EFEMP2, CDC42SE1, FSD1, POU1F1, ZNF79, ETNK1, and DOCK5) were extracted from the subsequent correlation matrix analysis. The combination of taxane and SAHA could be efficacious for the treatment of gastric cancer. The genes that were related to the synergistic response to taxane and SAHA could serve as surrogate biomarkers to predict the therapeutic response in gastric cancer patients.
    Journal of Cancer Research and Clinical Oncology 03/2010; 136(12):1901-13. · 2.91 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Optimal treatment for liver metastases from gastric cancer remains a matter of debate. The aim of our study is to evaluate the efficacy of radiofrequency ablation (RFA) for the treatment of liver-only metastases from gastric adenocarcinoma. We retrospectively reviewed medical records of 29 patients who developed liver-only metastases from gastric adenocarcinoma and subsequently underwent gastric resection and RFA (n = 20) or gastric resection and systemic chemotherapy (n = 9) between January 1995 and February 2008. Overall survival was estimated using the Kaplan-Meier method, and was compared using the log rank test to evaluate RFA efficacy. Twenty patients who underwent RFA showed a median overall survival of 30.7 months (range: 2.9 to 90.9 months), a median progression-free survival of 6.8 months (range: 0.8 to 45.2 months), and median overall one-, three-, and five-year survival rates were 66.8%, 40.1%, and 16.1% respectively. The RFA group showed a 76% decreased death rate compared to the chemotherapy-only group (30.7 months versus 7 months, hazard ratio, 0.24; p = 0.004). Most patients tolerated RFA well, and complications were found to be minor (transient fever (20%) and/or right upper quadrant pain (25%)). One case of treatment-related death occurred due to sepsis that originated from a liver abscess at the ablation site. The data suggest that a use of RFA as a liver-directed treatment may provide greater survival benefit than chemotherapy and is an alternative option for the treatment of liver-only metastases from gastric cancer.
    International Journal of Hyperthermia 03/2010; 26(4):305-15. · 2.77 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study is to evaluate the efficacy and safety of preoperative radiation therapy combined with S-1 and irinotecan (SI) in LARC. Patients were considered LARC if they had a T3/T4 lesion or node positive. Weekly doses of 40 mg/m(2) irinotecan were intravenously administered once per week during weeks 1-5 of radiotherapy. S-1 (70 mg/m(2)) was given from Monday to Friday in all weeks of radiotherapy. 3-D conformal radiotherapy was given at daily fractions of 1.8Gy for 5days for a total dose of 50.4 (45+5.4)Gy. Surgery was performed 4-6 weeks following the completion of chemoradiation. Between June 2006 and November 2007, 43 pts were enrolled. The stage was: cT3 24 patients, cT4 6 patients; 28 patients were cN+. Forty-one patients completed the chemoradiation and 42 patients underwent operation: a low anterior resection was performed in 36 patients, a total colectomy in 1 patient, and an abdominal perineal resection in 5 patients. T downstaging was observed in 50%; 23 N+ patients became N- (55%). The complete pathological response was observed in 9 patients (21%). The 3-year locoregional failure rate, distant failure rate, disease-free survival, and overall survival were 9.5%, 18.6%, 72.1%, and 94.3%, respectively. Only three patients experienced G3 diarrhea; one had G3 sepsis and two had septic shock. Hematological toxicity (G3-G4) was observed in five patients. This study demonstrated the efficacy of preoperative CRT with S-1 and irinotecan with 21% of complete response. However, prompt recognition and management of infection is needed to use it in patients with locally advanced rectal cancer.
    Radiotherapy and Oncology 03/2010; 95(3):303-7. · 4.86 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Here we evaluated the cytotoxic effects of a combination of the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) and taxanes in human breast cancer cell lines. Combination treatment with taxane and SAHA had a synergistic cytotoxic effect against taxane-resistant breast cancer cells. Oligonucleotide microarray analysis identified 28 genes (MAPK13, ATP2C1, ANKRD57, MT1G, RGL4, C12orf49, EXOC6, RAB4A, TM9SF3, IFNGR1, DMD, HCG9, KIFC3, SYNGR3, NDRG4, NT5E, EOMES, SMC4, LANCL1, SCHIP1, and 8 ESTs) whose expression correlated with the combined effect of paclitaxel and SAHA. Twelve of these genes were down-regulated in cell lines that were paclitaxel-resistant but combination synergistic. SAHA induced NT5E mRNA expression in paclitaxel-resistant YCC-B1 cell. Our results indicate that a combination of taxane and SAHA could be efficacious for the treatment of breast cancer and that genes involved in the synergistic response to paclitaxel and SAHA could serve as biomarkers to predict therapeutic response in breast cancer patients.
    Breast Cancer Research and Treatment 03/2010; 125(1):55-63. · 4.47 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: This study was undertaken to determine the ability of protein expression in primary colorectal cancer and metastatic liver tumour tissues to predict hepatic metastasis and intrahepatic recurrence. Sixty patients with colorectal cancer were enrolled in this study. The expression of the following five proteins was assessed by immunohistochemical (IHC) staining: carcinoembryonic antigen (CEA); vascular endothelial growth factor (VEGF); matrix metalloproteinase (MMP)-1; MMP-7; and tissue inhibitor of metalloproteinases (TIMP)-1. Protein expression was measured in patients with primary colorectal cancer without liver metastasis (Group A), in patients with primary colorectal cancer with liver metastasis (primary tumour; Group B), and in patients with resected metastatic liver tumour tissues (liver metastasis; Group C). IHC staining revealed more protease activity (MMP-1 and -7) in Group B than in Group A. Angiogenic activity (positive VEGF expression) was significantly greater in Group C than in Group B. Multivariate analysis showed that positive MMP-1 expression, the presence of lymphovascular invasion, and an elevated pre-operative serum CEA level (> 5 ng/ml) were significantly related to synchronous liver metastasis. However, intrahepatic recurrence was not related to protein expression, the presence of lymphovascular invasion, or the pre-operative CEA level. Our findings suggest that protease activity is important for metastasis, and that angiogenic activity is essential for metastatic tumour growth. Furthermore, positive MMP-1 expression in primary colorectal tumour tissues was a significant predictor of liver metastasis. However, the prognostic impact of protein marker expression in terms of intrahepatic recurrence appears to be minimal.
    Scandinavian Journal of Gastroenterology 02/2010; 45(2):217-25. · 2.33 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We evaluated the frequency of ABCB1 polymorphisms (2677G/T>A and 3435C>T) and studied the association between the polymorphisms and clinical outcomes of paclitaxel-based chemotherapy in advanced gastric cancer patients. This study was performed in 43 gastric cancer patients and a control group consisting of 118 healthy volunteers. Patients were treated with paclitaxel combined with an infusional 5-fluorouracil and low-dose leucovorin. Genomic DNA from peripheral blood mononuclear cells was used to determine ABCB1 polymorphisms by direct sequencing. Genotypes were investigated for their association with survival and toxicity. The ABCB1 3435 C allele was more frequent in gastric cancer patients than healthy volunteers (p<0.001). The 2677G>T/A and 3435C>T polymorphisms were independent factors associated with shorter progression-free survival (PFS) (p=0.024, p=0.001, respectively). In combined analysis of 2677 and 3435 polymorphisms, the 3435C>T polymorphism was an independent factor for poor PFS (p=0.01). The 3435CT and TT genotypes were associated with mucositis (p=0.04), and the variant genotypes at 2677 loci were associated with diarrhea (p=0.034). Our data suggest that the ABCB1 polymorphism at 3435 is associated with clinical outcomes after paclitaxel-based combined chemotherapy in advanced gastric cancer patients.
    Oncology Reports 01/2010; 23(1):271-8. · 2.19 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We investigated the efficacy and safety of weekly paclitaxel monotherapy in previously treated patients with advanced gastric cancer (AGC) and poor performance status (PS) according to the Eastern Cooperative Oncology Group (ECOG). Patients with evaluable disease who failed at least one previous chemotherapy and had a PS of 2-3, received paclitaxel 70 mg/m(2) on days 1, 8 and 15 every 4 weeks. The median overall survival (OS) was 5.5 months (95% confidence interval, CI, 3.3-7.8) and progression-free survival was 2.1 months (95% CI, 1.2-3.0). The overall response rate was 3.8% and the disease control rate was 25.0%. Treatment-related toxicities were tolerable. OS was 7.1 (95% CI, 5.4-9.5) and 3.7 months (95% CI, 2.1-5.3) for patients with PS-ECOG 2 and 3, respectively (p < 0.001). When evaluated according to the previous treatment, OS was 5.1 (95% CI, 3.3-7.0) and 6.5 months (95% CI, 3.8-9.3) for patients receiving two and three or more lines of treatment, respectively (p = 0.815). With multivariate analysis, PS was a significant factor for OS. Survival in patients treated with weekly paclitaxel monotherapy was comparable to other second- or third-line chemotherapies for AGC, with acceptable toxicities in previously treated patients with poor PS.
    Oncology 12/2009; 77(6):349-57. · 2.17 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We evaluated the efficacy and tolerability of combined paclitaxel and ifosfamide in anthracycline- and docetaxel-pretreated metastatic breast cancer (MBC). Patients received paclitaxel (175 mg/m(2) i.v. in a 3-h infusion) on day 1 and ifosfamide (1.5 g/m(2) i.v. in a 15-min infusion) on days 1-3, every 3 weeks for a maximum of nine cycles. The tumor response was assessed every two cycles. We enrolled 34 patients with a median age of 50 years. Thirty patients had visceral metastases. Anthracycline- and docetaxel-based chemotherapy had previously been administered to 18/13 and 13/21 patients, respectively, in (neo)adjuvant/metastatic settings. Three patients had not previously received anthracycline due to abnormal cardiac functions. A total of 174 cycles of chemotherapy were delivered with a median of six cycles. The response rate under the intent-to-treat analysis was 23.5% (all partial responses) with a median response duration of 14 months. The disease control rate was 70.6%. The median progression-free and overall survival were 5.9 and 8.5 months, respectively. There was no apparent relationship between activity and prior docetaxel resistance. The incidence of grade III/IV neutropenia was 46.6% (81 of 174 cycles) with febrile neutropenia of only 1.7%. Major grade III/IV non-hematological toxicities included peripheral neuropathy (6 of 34 patients) and infection (4 of 34 patients). There were no treatment-related deaths. Paclitaxel combined with ifosfamide was effective and tolerable in anthracycline-/docetaxel-pretreated MBC. Overcoming docetaxel resistance by using paclitaxel in combination with ifosfamide needs to be addressed through further investigation.
    Cancer Chemotherapy and Pharmacology 12/2009; 66(3):425-31. · 2.80 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: This is an ad hoc analysis of two phase II studies which compared the efficacy and safety of two taxanes (paclitaxel and docetaxel) combined with 5-fluorouracil (5-FU) and leucovorin (LV) in advanced gastric cancer. Patients with advanced gastric adenocarcinoma who were untreated or had only received first-line chemotherapy, were treated with either paclitaxel (PFL; 175 mg/m(2)) or docetaxel (DFL; 75 mg/m(2)) on day 1, followed by a bolus of LV (20 mg/m(2) days 1~3) and a 24-hour infusion of 5-FU (1,000 mg/m(2) days 1~3) every 3 weeks. The primary endpoint was overall response rate (ORR) and the secondary endpoint included survival and toxicity. Sixty-six patients received DFL (first-line [n=38]; and second-line [n=28]) and 60 patients received PFL (first-line [n=37]; and second-line [n=23]). The ORRs were not significantly different between the 2 groups (DFL, 26%; PFL, 38%). With a median follow-up of 9.5 months, the progression free survival was 5.2 months (95% confidence interval [CI], 4.2~6.5 months) for DFL and 3.3 months (95% CI, 1.3~5.5 months) for PFL (p=0.17). The overall survival was also comparable between the patients who received DFL and PFL (10.0 months [95% CI, 7.2~12.5 months] and 13.9 months [95% CI, 10.9~19.2 months], respectively; p=0.37). The most frequent grade 3~4 adverse event was neutropenia (DFL, 71%; PFL, 62%). DFL and PFL had different non-hematologic toxicities; specifically, grade >or=3 mucositis (5%) and diarrhea (3%) were common in DFL, while nausea/vomiting (15%) and peripheral neuropathy (5%) were common in PFL. Thus, the two taxanes had similar efficacy in the treatment of advanced gastric cancer, but different toxicity profiles. Prospective comparative studies are required to further clarify the role of taxanes in the treatment of advanced gastric cancer.
    Cancer Research and Treatment 12/2009; 41(4):196-204. · 1.96 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Many solid cancers are known to exhibit a high degree of heterogeneity in their deregulation of different oncogenic pathways. We sought to identify major oncogenic pathways in gastric cancer (GC) with significant relationships to patient survival. Using gene expression signatures, we devised an in silico strategy to map patterns of oncogenic pathway activation in 301 primary gastric cancers, the second highest cause of global cancer mortality. We identified three oncogenic pathways (proliferation/stem cell, NF-kappaB, and Wnt/beta-catenin) deregulated in the majority (>70%) of gastric cancers. We functionally validated these pathway predictions in a panel of gastric cancer cell lines. Patient stratification by oncogenic pathway combinations showed reproducible and significant survival differences in multiple cohorts, suggesting that pathway interactions may play an important role in influencing disease behavior. Individual GCs can be successfully taxonomized by oncogenic pathway activity into biologically and clinically relevant subgroups. Predicting pathway activity by expression signatures thus permits the study of multiple cancer-related pathways interacting simultaneously in primary cancers, at a scale not currently achievable by other platforms.
    PLoS Genetics 10/2009; 5(10):e1000676. · 8.17 Impact Factor
  • Ki-Yeol Kim, Hyun Cheol Chung, Sun Young Rha
    [Show abstract] [Hide abstract]
    ABSTRACT: Microarray experiments are often performed to detect differently expressed genes among different clinical phenotypes. The method used to calculate the appropriate sample size for this purpose differs from the sample size calculation used for general clinical experiments, because microarrays include tens of thousands of genes. We proposed a sample size calculation method that considers variance among an entire gene set and used the Bonferroni correction to address the multiplicity problem. Specifically, by adjusting for the multiplicity problem, the existing equation for sample size calculation was modified based on the Bonferroni correction. By k-means cluster analysis, the variances across all genes can be divided into several groups with similar values, and the sample sizes for each group were subsequently calculated and weight-averaged. The results of this study show that the sample size was related to the number of genes on a chip. The weighted sample size, calculated by the proposed method, preserved the Type I error for selection of significant genes within a microarray data set.
    Journal of Bioscience and Bioengineering 10/2009; 108(3):252-8. · 1.74 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In this study, we compared the pharmacokinetic profiles of 5-fluorouracil (5-FU), tegafur, 5-chloro-2,4-dihydroxypyridine (CDHP) and potassium oxonate (Oxo) after administration of S-1 at 35 or 40 mg/m(2) bid for 28 consecutive days, in Cycles 1 and 3, in patients with advanced gastric cancer. Three patients were enrolled for each dosage. S-1 dosage was assigned based on body surface area (BSA), which is different from the Japanese dosing system. The median daily dose per BSA was 76 mg/m(2), ranging from 70 to 88 mg/m(2). Plasma levels of 5-FU, tegafur, CDHP and Oxo at 4 h post-dose reached steady-state on day 8. The estimated steady-state level was dependent on S-1 dosage. There were no intercyclic differences of pre-dose and 4 h post-dose levels between Cycles 1 and 3, implying no cumulative effect of S-1 was shown probably due to 2-week drug-resting period. Pharmacokinetic profiles on day 28 were similar to previous Japanese report. C(max) and AUC(0-48 h) values of each S-1 component increased depending on S-1 dosage. Pharmacokinetic parameters were not correlated with tumor response or toxicity. We suggest that these pharmacokinetic profiles of Asian population could provide a basis for schedule optimization and for additional studies on interaction with other antitumor drugs.
    Japanese Journal of Clinical Oncology 10/2009; 40(1):29-35. · 1.75 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Array comparative genomic hybridization (aCGH) provides a technique to survey the human genome for chromosomal aberrations in disease. The identification of genomic regions with aberrations may clarify the initiation and progression of cancer, improve diagnostic and prognostic accuracy, and guide therapy. The analysis of variance (ANOVA) model is widely used to detect differentially expressed genes after accounting for common sources of variation in microarray analysis. In this study, we propose a method, shifted ANOVA, to detect significantly altered regions. This method, based on the standard ANOVA, analyzes changes in copy number variation for regions. The selected regions have the group effect only, but no effect within samples and no interactive effects. The performance of the proposed method is evaluated from the homogeneity and classification accuracies of the selected regions. Shifted ANOVA may identify new candidate genes neighboring known because it detects significantly altered chromosomal regions, rather than independent probes.
    Genomics 09/2009; 94(5):317-23. · 2.79 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: This study was carried out to evaluate the clinical significance of ascitic fluid carcinoembryonic antigen (CEA) in advanced gastric cancer patients with ascites. From November 2001 to February 2008, 119 gastric cancer patients with concurrent ascites who were clinically diagnosed with carcinomatosis, were retrospectively reviewed with regard to ascitic fluid cytology and clinicopathological parameters. Serum CEA (sCEA) and ascitic fluid CEA (aCEA) were measured using a chemiluminescent enzyme immunoassay. The patients' median age was 50 years (range 23-80 years). The median value of aCEA was significantly higher than sCEA [130.5 ng/ml (range 0.2-12.211 ng/ml) vs. 2.1 ng/ml (range 0.02-8.152 ng/ml), p < 0.001]. Sixty-five patients (54.6%) had positive ascitic fluid cytology. The median overall survival of all patients was 3.0 months (95% CI 2.0-4.0 months). The patients with low aCEA (<5 ng/ml) had a significantly longer overall survival compared to patients with high aCEA (>or=5 ng/ml) (7.4 months vs. 2.3 months, p = 0.003). However, we found no difference in overall survival according to ascitic fluid cytology (median, 3.0 months vs. 2.5 months, p = 0.530). Multivariate analysis also demonstrated that aCEA levels of more than 5 ng/ml were associated with poor prognosis (HR = 2.88; 95% CI 1.45-5.74; p = 0.003), while sCEA levels were not associated with poor prognosis (HR = 1.15; 95% CI 0.67-2.03; p = 0.622). These results suggest that aCEA levels can be used as a prognostic marker for advanced gastric cancer patients with ascites.
    Journal of Cancer Research and Clinical Oncology 09/2009; 136(4):517-26. · 2.91 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: There is no universally confirmed standard chemotherapeutic regimen for advanced gastric cancer (AGC). The aim of this study was to investigate the efficacy and safety of combined biweekly irinotecan and monthly cisplatin treatments of patients with AGC. The primary end point was progression-free survival. AGC patients with or without measurable lesions received 70 mg/m2 irinotecan on days 1 and 15, and 80 mg/m2 cisplatin on day 1 every 4 weeks. Of 40 enrolled patients, 21 patients had measurable disease. With a median follow-up duration of 35 weeks, the median progression-free survival and overall survival were 2.2 months and 8.0 months, respectively. The progression-free survival rate at 6 months was 30.0%. The most common adverse event of grade 3 to 4 was neutropenia (32.5%). Grade 3 diarrhea was observed in 2 patients (5.0%). There was no treatment-related death. Current combined biweekly irinotecan and monthly cisplatin treatment did not show activity comparable with other active regimens in AGC.
    American journal of clinical oncology 09/2009; 33(1):56-60. · 2.21 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We conducted a phase I trial of the antiangiogenic agent 6-O-(4-dimethylaminoethoxy) cinnamoyl fumagillol hemioxalate (CKD-732). Our aims were to determine the maximum tolerated dose (MTD), pharmacokinetics (PK), and safety profiles as well as identify the biologically active dose (BAD) from ex vivo pharmacodynamics (PD) and biomarkers of CKD-732. Using a dose escalation schedule, 19 patients with refractory solid tumors were enrolled at dose levels of CKD-732 ranging from 1 to 15 mg/m(2) given twice weekly for 2 weeks followed by a 1-week rest. No treatment-related deaths occurred in this study. Confusion and insomnia were dose-limiting toxicities (DLTs), and MTD was 15 mg/m(2). The area under the concentration-time curve (AUC) and maximum concentration (Cmax) increased dose dependently with increasing doses. The BAD was 5 mg/m(2) according to ex vivo PD. A decrement in soluble vascular endothelial growth factor receptor-3 (sVEGF-3) level was correlated with a reduction in tumor size (r = 0.54, P = 0.045). The results from this study showed an MTD of 15 mg/m(2) and a BAD of 5 mg/m(2).
    Investigational New Drugs 08/2009; 28(5):650-8. · 3.50 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Dystroglycan (DG) is a recently focused adhesion molecule with possible roles in cancer development and progression. We investigated correlations between alpha-DG expression and prognosis in gastric carcinoma with liver metastasis. For 40 patients with gastric adenocarcinoma and liver-only metastasis, alpha-DG expression was determined by immunohistochemistry in paraffin-embedded surgical specimens of resected stomach tumor, resected liver metastasis, and their normal counterpart tissues. Correlations between alpha-DG expression and prognosis were retrospectively analyzed. alpha-DG expression was higher in primary gastric cancer (P = 0.006) and lower in liver metastasis (P = 0.002) than in each normal counterpart. In primary stomach cancer, patients who had lower alpha-DG expression in tumors than in normal counterparts showed poor overall survival (OS) (P = 0.028). In contrast, in the liver, patients who had higher alpha-DG expression in tumors than in normal counterparts showed poor OS (P = 0.022). Also, higher alpha-DG expression in liver metastasis than in stomach tumors led to poor recurrence-free survival (P = 0.023) and OS (P = 0.056). This approach may be used to further understanding of the pathogenesis of liver metastasis from gastric cancer. Further studies are warranted to reveal the mechanisms of alpha-DG dysregulation in liver metastasis.
    Journal of Surgical Oncology 08/2009; 100(6):459-65. · 2.84 Impact Factor

Publication Stats

2k Citations
632.21 Total Impact Points

Institutions

  • 1997–2014
    • Yonsei University Hospital
      • Department of Internal Medicine
      Sŏul, Seoul, South Korea
  • 2013
    • Konkuk University
      Sŏul, Seoul, South Korea
  • 2012
    • Seoul National University Hospital
      • Department of Internal Medicine
      Seoul, Seoul, South Korea
  • 2003–2012
    • Yonsei University
      • • Department of Surgery
      • • Department of Internal Medicine
      • • Oral Cancer Research Institute
      • • College of Medicine
      Seoul, Seoul, South Korea
  • 2011
    • National University of Singapore
      • Department of Physiology
      Singapore, Singapore
  • 2009–2011
    • Duke-NUS Graduate Medical School Singapore
      • PhD Program in Cancer and Stem Cell Biology
      Singapore, Singapore
  • 2004–2011
    • National Cancer Center Korea
      • Colorectal Cancer Branch
      Kōyō, Gyeonggi Province, South Korea
  • 2008
    • Genome Institute of Singapore
      Tumasik, Singapore
  • 2004–2007
    • Eulji University
      • Department of Internal Medicine
      Seoul, Seoul, South Korea