Jeeyun Lee

Sungkyunkwan University, Sŏul, Seoul, South Korea

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Publications (188)674.38 Total impact

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    ABSTRACT: We aimed to the addition of synthetic 3-hydroxy-3-methyglutaryl coenzyme A (HMG-CoA) reductase inhibitor, simvastatin to capecitabine-cisplatin (XP) in patients with previously untreated advanced gastric cancer (AGC).
    European journal of cancer (Oxford, England: 1990) 09/2014; · 4.12 Impact Factor
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    ABSTRACT: Capecitabine is known to increase mean corpuscular volume (MCV). To define the incidence of capecitabine-induced macrocytosis and its association with chemotherapy outcomes, we investigated data of 89 patients with advanced gastric cancer (AGC) who were enrolled in a randomized chemotherapy trial involving capecitabine.
    Cancer research and treatment : official journal of Korean Cancer Association. 08/2014;
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    ABSTRACT: Growth factor receptors, often carrying tyrosine kinase activities in their cytoplasmic domains, are overexpressed in many cancers. Coactivation of receptor tyrosine kinases (RTKs) plays a critical role in tumor response to targeted therapeutics. We examined concomitant overexpression of EGFR and MET in patients with HER2+ and HER2- gastric cancers (GCs). Tissue microarray samples obtained from 1,589 GC patients who received R0 gastrectomy with extensive node dissection and adjuvant chemoradiationtherapy were analyzed by immunohistochemistry and fluorescence in situ hybridization. HER2+ was observed in 169 patients (11%). Out of 169 HER2+ patients, 15 (9%) were EGFR+ and MET+, 29 (17%) were EGFR+, 37 (22%) were MET+, and the remaining 88 patients (52%) were HER2+ only, without concomitant EGFR or MET overexpression. Greater number of overexpressed RTKs correlated with younger age (p<0.001), larger tumor size (p=0.027), intestinal histology (p<0.001), and shorter overall survival (p=0.002). The mean overall survival was 113 months for HER2-/EGFR-/MET- and 63 months for HER2+/EGFR+/MET+ subgroups. Patients with HER2+/EGFR+/MET+ GCs had a substantial risk of death with a hazard ratio of 3.01 (95% CI, 1.54–5.90), compared to HER2-/EGFR-/MET- GC patients. Using patient-derived tumor cell models isolated from pericardial effusion of HER2+ and MET+ GC cases, we demonstrated that the combination of HER2-inhibitor (lapatinib) and MET-inhibitor offered a more profound inhibition in the ERK/AKT pathway and cell proliferation than lapatinib alone. Co-overexpression of RTKs was demonstrated in small subsets of GC associated with aggressive behavior, and in these cases, combination therapy may be considered as potential treatment options. © 2014 Wiley Periodicals, Inc.
    International Journal of Cancer 08/2014; · 6.20 Impact Factor
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    ABSTRACT: This study aimed to evaluate the prognostic significance and predictive performance of volume-based parameter of (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) in biliary tract cancer (BTC). Of the 268 patients who were enrolled onto phase III gemcitabine/oxaliplatin (GEMOX) versus GEMOX/erlotinib trial, a total of 48 patients had pretreatment (18)F-FDG PET/CT available for analysis. Maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis for the primary tumor were measured. The prognostic significance of these parameters and clinicopathological variables was assessed by Cox proportional hazards regression analysis. A cutoff of 98.8 ml for the MTVliver was the best discriminative value for predicting overall survival (>9 months). Multivariate analyses with adjustments for age, performance status, and disease status showed that only MTVliver was an independent prognostic factor associated with overall survival (HR 2.149, 95 % CI 1.124-4.109, P = 0.021). SUVmax did not show any correlation with overall survival. For patients in the high-MTVMBP group, overall survival was longer in the chemotherapy plus erlotinib group than in the chemotherapy-alone group [median 8.3 months (5.5-11.1) vs. 4.0 months (0.0-8.0); P = 0.048]. MTV may be considered as a significant independent metabolic prognostic factor for overall survival in patients with BTC and predictive marker for the selection of patients for the addition of erlotinib to first-line chemotherapy.
    Medical oncology (Northwood, London, England). 07/2014; 31(7):23.
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    ABSTRACT: Extramammary Paget disease (EMPD) is a rare disease, especially in Asian populations. Surgical resection is considered the primary treatment option. Recently, radiotherapy has been suggested as an EMPD treatment, either as an alternative to surgical resection or in combination with surgical resection. This report reviewed a patient with EMPD who was treated with wide excision of the EMPD site followed by radiotherapy for remaining gross lymph node metastases. The aim of this report was to determine the optimal treatment for advanced EMPD.
    Radiation oncology journal. 06/2014; 32(2):95-8.
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    ABSTRACT: Colorectal cancer (CRC) is one of the most common cancers worldwide, with 5%-15% of CRC patients eventually developing lung metastasis (LM). Despite doubts about the role of locoregional therapy in the management of systemic disease, many surgeons have performed pulmonary metastasectomy (PM) for CRC in properly selected patients. However, the use of pulmonary metastasectomy remains controversial due to the lack of randomized controlled studies. This article reviews the results of surgical treatment of pulmonary metastases for CRC, focusing on (1) current treatment guidelines and surgical techniques of PM in patients with LM from CRC; (2) outcomes of PM and its prognostic factors; and (3) controversial issues in PM, focusing on repeated metastasectomy, bilateral multiple metastases, and combined liver and lung metastasectomy.
    World journal of gastroenterology : WJG. 05/2014; 20(20):6133-6145.
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    ABSTRACT: Globally, gastric cancer (GC) is the second leading cancer cause of death. To date, only one targeted therapy trial generated positive survival outcomes in a selected population among many targeted therapy trial. This trial demonstrated the addition of trastuzumab to fluoropyrimidine/ platinum chemotherapy as first-line chemotherapy for human epidermal growth factor receptor 2 (HER2)-positive GC that resulted in an overall survival benefit. The increasing use of next generation sequencing approach to genomically profile GC patients allows the identification of many more GC patients who could benefit from specific targeted agents. Here we provide a comprehensive review of targeted therapy trials in GC and discuss future potential actionable driver mutations in GC.
    Clinical Genetics 04/2014; · 4.25 Impact Factor
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    ABSTRACT: Background Colorectal cancer (CRC) is the fourth leading cause of cancer-related deaths worldwide. The combination of oxaliplatin-based treatments (oxaliplatin plus infusional 5-fluorouracil and leucovorin [FOLFOX] or oxaliplatin plus capecitabine [CapeOX]) and bevacizumab is a standard chemotherapy regimen for metastatic CRC (mCRC). However, several clinical studies that tested S-1 plus oxaliplatin (SOX) indicate that SOX is also a treatment option for mCRC. TSU-68 is an oral compound that inhibits vascular endothelial growth factor receptor and platelet-derived growth factor receptor. The recommended dose of TSU-68 + SOX was previously determined in a phase I study of mCRC patients. The goal of this trial was to evaluate the efficacy of TSU-68 in combination with SOX. Methods This open-label multicenter randomized phase II trial was performed in Korea. Treatment-naive mCRC patients with a performance status of 0 or 1 were randomized in a 1:1 ratio to receive either TSU-68 + SOX or SOX alone. The primary endpoint was progression-free survival (PFS). Results A total of 105 patients (TSU-68 + SOX, 52 patients; SOX alone, 53 patients) were randomized. The median PFS was 7.0 months in the TSU-68 + SOX group (hazard ratio [HR], 1.057) and 7.2 months in the SOX group (p = 0.8401). The most frequent grade 3 and 4 adverse events were thrombocytopenia (9.6 % [TSU-68 + SOX] vs. 26.4 % [SOX]), neutropenia (13.5 % [TSU-68 + SOX] vs. 15.1 % [SOX]), and anemia (3.8 % [TSU-68 + SOX] vs. 13.2 % [SOX]). We observed a difference between the 2 groups for all grades of anemia (15.4 % [TSU-68 + SOX] vs. 32.1 % [SOX]), diarrhea (30.8 % [TSU-68 + SOX] vs. 47.2 % [SOX]), vomiting (50.0 % [TSU-68 + SOX] vs. 26.4 % [SOX]), and chromaturia (23.1 % [TSU-68 + SOX] vs. 0.0 % [SOX]). Analysis using a Cox proportional hazard model showed that baseline interleukin 6 (IL-6) levels were associated with a survival benefit of TSU-68 (p = 0.012). Conclusion TSU-68 + SOX had a favorable safety profile. However, TSU-68 did not have a synergistic effect on the efficacy of SOX. The baseline serum IL-6 level could be a prognostic factor for TSU-68 efficacy.
    Investigational New Drugs 02/2014; · 3.50 Impact Factor
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    ABSTRACT: Purpose Preclinical data has demonstrated the potential of simvastatin to overcome cetuximab resistance in KRAS mutant CRC patients. Therefore, we designed a study using simvastatin/cetuximab/irinotecan for KRAS mutant CRC patients who are refractory to irinotecan and oxaliplatin-based chemotherapy. Patients and methods In this phase II study, patients received 500 mg/m(2) cetuximab, 150-180 mg/m(2) (day 1), and 80 mg simvastatin (once daily, days 1-14, every 2 weeks). The primary endpoint was the objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), the disease control rate (DCR), and safety. We also analyzed the relationship between the RAS gene expression signature score and treatment response to simvastatin/cetuximab/irinotecan. Results Fifty-two KRAS mutant CRC patients were enrolled. The ORR (complete response [CR], 0; partial response [PR], 1) was 1.9 % (95 % confidence interval [CI], -1.8-5.6). The DCR (CR, 0; PR, 1; stable disease, 33) was 65.4 % (95 % CI, 52.5-78.3). The median PFS and OS from the time of study drug administration were 7·6 months (95 % CI, 4.4-10.8) and 12.8 months (95 % CI, 9.5-16.2), respectively. The most common grade 3/4 adverse events were anemia (28.8 %), neutropenia (13.5 %), and diarrhea (7.7 %). The RAS signature score was significantly correlated with the maximal change in target lesions from baseline (r = 0.57, P = 0.014). Conclusion The simvastatin/cetuximab/irinotecan regimen showed promising efficacy and safety in KRAS mutant CRC patients who failed irinotecan and oxaliplatin-based chemotherapy. The RAS signature may be a novel predictor of treatment response to cetuximab-combined chemotherapy in CRC patients.
    Investigational New Drugs 01/2014; · 3.50 Impact Factor
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    ABSTRACT: Several studies have reported that imatinib may induce tumor responses and prolonged disease stabilization in aggressive fibromatosis (AF). This effect may relate to the PDGFR-β pathway and KIT mutations. Sunitinib not only inhibits PDGFRs, KIT, and FLT3, it also blocks VEGFRs and thus serves as an antiangiogenic agent. The aim of this prospective multicenter uncontrolled study was to evaluate the efficacy and safety of sunitinib in patients with advanced AF. Nineteen patients with pathologically proven AF were recruited between June, 2008, and March, 2012, from three centers. One treatment cycle consisted of 37.5 mg/day sunitinib for 4 weeks without a break. The primary endpoint was tumor response rate according to RECIST 1.0. Ten (53 %) patients were female and the median age was 30 years (range, 22-67). Most of the primary sites were intra-abdominal (12, 63.2 %), and AF associated with familial adenomatous polyposis in ten patients (52.6 %). With a median of six cycles per patients (range, 1-47 cycles), five patients (26.3 %) achieved a partial response and eight (42.1 %) had stable disease. The overall response rate was 26.3 % (95 % confidence interval [CI], 6.3-45.7) in intention-to-treat analysis. With a median follow-up time of 20.3 months (range, 1.8-50.7), the 2-year rates of progression-free and overall survival were 74.7 % and 94.4 %, respectively. Grade 3 or 4 adverse events of sunitinib that occurred in >5 % of patients were neutropenia (33.3 %), diarrhea (5.3 %), and hand-foot syndrome (5.3 %). In 3 of 12 patients with mesenteric AF, mesenteric mass bleeding (n = 1), bowel perforation (n = 1), and bowel fistula (n = 1) with tumor mass necrosis were observed early during sunitinib treatment. Therefore, sunitinib showed potential antitumor activity and may be useful for the management of non-mesenteric AF.
    Investigational New Drugs 01/2014; · 3.50 Impact Factor
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    ABSTRACT: To gain biological insights into lung metastases from hepatocellular carcinoma (HCC), we compared the whole-genome sequencing profiles of primary HCC and paired lung metastases. We used whole-genome sequencing at 33X-43X coverage to profile somatic mutations in primary HCC (HBV+) and metachronous lung metastases (> 2 years interval). In total, 5,027-13,961 and 5,275-12,624 somatic single-nucleotide variants (SNVs) were detected in primary HCC and lung metastases, respectively. Generally, 38.88-78.49% of SNVs detected in metastases were present in primary tumors. We identified 65-221 structural variations (SVs) in primary tumors and 60-232 SVs in metastases. Comparison of these SVs shows very similar and largely overlapped mutated segments between primary and metastatic tumors. Copy number alterations between primary and metastatic pairs were also found to be closely related. Together, these preservations in genomic profiles from liver primary tumors to metachronous lung metastases indicate that the genomic features during tumorigenesis may be retained during metastasis. We found very similar genomic alterations between primary and metastatic tumors, with a few mutations found specifically in lung metastases, which may explain the clinical observation that both primary and metastatic tumors are usually sensitive or resistant to the same systemic treatments.
    BMC Medical Genomics 01/2014; 7(1):2. · 3.47 Impact Factor
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    ABSTRACT: Oncogenic mutational analysis provides predictive guidance for therapeutics such as anti-EGFR antibodies, but it is successful only for a subset of colorectal cancer (CRC) patients.
    PLoS ONE 01/2014; 9(8):e103551. · 3.53 Impact Factor
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    ABSTRACT: Rhabdomyosarcoma (RMS) is the most commonly occurring type of soft tissue tumor in children. However, it is rare in adults, and therefore, very little is known about the most appropriate treatment strategy for adult RMS patients. We performed genomic analysis of RMS cells derived from a 27-year-old male patient whose disease was refractory to treatment. A peritoneal seeding nodule from the primary tumor, pleural metastases, malignant pleural effusion, and ascites obtained during disease progression, were analyzed. Whole exome sequencing revealed 23 candidate variants, and 10 of 23 mutations were validated by Sanger sequencing. Three of 10 mutations were present in both primary and metastatic tumors, and 3 mutations were detected only in metastatic specimens. Comparative genomic hybridization array analysis revealed prominent amplification in the 12q13-14 region, and more specifically, the CDK4 proto-oncogene was highly amplified. ALK overexpression was observed at both protein and RNA levels. However, an ALK fusion assay using NanoString technology failed to show any ALK rearrangements. Little genetic heterogeneity was observed between primary and metastatic RMS cells. We propose that CDK4, located at 12q14, is a potential target for drug development for RMS treatment.
    Scientific Reports 01/2014; 4:3623. · 5.08 Impact Factor
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    ABSTRACT: Despite the benefits from adjuvant chemotherapy or chemoradiotherapy, approximately one-third of stage II gastric cancer (GC) patients developed recurrences. The aim of this study was to develop and validate a prognostic algorithm for gastric cancer (GCPS) that can robustly identify high-risk group for recurrence among stage II patients. A multi-step gene expression profiling study was conducted. First, a microarray gene expression profiling of archived paraffin-embedded tumor blocks was used to identify candidate prognostic genes (N = 432). Second, a focused gene expression assay including prognostic genes was used to develop a robust clinical assay (GCPS) in stage II patients from the same cohort (N = 186). Third, a predefined cut off for the GCPS was validated using an independent stage II cohort (N = 216). The GCPS was validated in another set with stage II GC who underwent surgery without adjuvant treatment (N = 300). GCPS was developed by summing the product of Cox regression coefficients and normalized expression levels of 8 genes (LAMP5, CDC25B, CDK1, CLIP4, LTB4R2, MATN3, NOX4, TFDP1). A prospectively defined cut-point for GCPS classified 22.7% of validation cohort treated with chemoradiotherapy (N = 216) as high-risk group with 5-year recurrence rate of 58.6% compared to 85.4% in the low risk group (hazard ratio for recurrence = 3.16, p = 0.00004). GCPS also identified high-risk group among stage II patients treated with surgery only (hazard ratio = 1.77, p = 0.0053).
    PLoS ONE 01/2014; 9(3):e90133. · 3.53 Impact Factor
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    ABSTRACT: This study aims to determine the risk factors for lateral pelvic recurrence (LPR) in rectal cancer patients treated with neoadjuvant chemoradiotherapy (CRT) and curative surgery. Four hundred forty-three patients treated with neoadjuvant CRT and curative surgery from October 1999 through June 2009 were analyzed. All patients underwent total mesorectal resection without lateral pelvic lymph node (LPLN) dissection. Recurrence patterns and lateral pelvic recurrence-free survival (LPFS) were evaluated relative to clinicopathologic parameters including pelvic LN status. Median follow-up was 52 months, with locoregional recurrence in 53 patients (11.9 %). Of the 53 patients, 28 (52.8 %) developed LPR, of which eight had both central and lateral PR. Multivariate analysis showed a significant relationship between LPFS and the number of lateral pelvic LN (p = 0.010) as well as the ratio of the number of positive LN/number of dissected LN (p = 0.038). The relationship between LPFS and LPLN size had a marginal trend (p = 0.085). Logistic regression analysis showed positive relationships between LPR probability and the number of LPLN (odds ratio [OR] 1.507; 95 % confidence interval [CI] 1.177-1.929; p = 0.001) as well as LPLN size (OR 1.124; CI 1.029-1.227, p = 0.009). LPLN ≥ 2 and a ratio of the number of positive LN/number of dissected LN > 0.3 were prognostic of poor LPFS. The prediction curve of LPR according to the number and size of LPLN could be useful for determining the benefit of additional lateral pelvic treatment.
    International Journal of Colorectal Disease 12/2013; · 2.24 Impact Factor
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    ABSTRACT: CD151, a transmembrane protein of the tetraspanin family, is implicated in the regulation of cell-substrate adhesion and cell migration. Overexpression of CD151 has been reported in several cancers and controls MET-dependent neoplastic growth by enhancing receptor signaling. However, association of CD151 overexpression with MET or tumor progression has not been reported in gastric cancer. We conducted immunohistochemical analysis of CD151 overexpression in 491 pT3 gastric carcinomas and analyzed the relationship with MET overexpression and prognostic significance. CD151 was highly expressed in 119 gastric carcinomas (24.2 %) and was significantly associated with higher pN stages. Patients with CD151-positive gastric cancer showed shorter overall (p = 0.003) and disease-free survival (p = 0.001) compared with patients with CD151-negative gastric carcinoma. CD151 overexpression was an independent prognostic factor for overall survival [hazard ration (HR) 1.335; 95 % CI 1.005-1.775; p = 0.046] and disease-free survival (HR 1.903; 95 % CI 1.348-2.685; p < 0.001). Co-overexpression of CD151 and MET was observed in 30 (6.1 %) gastric cancers and was more frequent in advanced pN stages than in other groups. Moreover, co-overexpression of CD151 and MET was a strong independent prognostic factor for overall survival (HR 3.163; 95 % CI 1.958-5.108; p < 0.001) and disease-free survival (HR 3.834; 95 % CI 2.145-6.852; p < 0.001). CD151 overexpression is an independent prognostic factor and could be a potential molecular therapeutic target in patients with advanced gastric cancers. Further studies are needed to establish the biological significance of CD151/MET co-overexpression and the potential of targeting both molecules as a therapeutic strategy.
    Annals of Surgical Oncology 12/2013; · 4.12 Impact Factor
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    ABSTRACT: The degree of benefit from palliative chemotherapy differs widely among patients with metastatic esophageal squamous cell carcinoma (MESCC). The purpose of this study was to develop and validate a prognostic nomogram to predict survival and aid physicians and patients in the decision-making process regarding treatment options. Clinicopathologic variables and treatment outcomes of 239 patients who were diagnosed with MESCC and received either fluorouracil/cisplatin (FP) or capecitabine/cisplatin (XP) as first-line chemotherapy were reviewed. A nomogram was developed as a prognostic scoring system incorporating significant clinical and laboratory variables based on a multivariate Cox proportional hazards regression model. An independent series of 61 MESCC patients treated with FP served as an independent data set for nomogram validation. No difference in response rate was observed between the FP group (44.8%) and the XP group (54.2%). Similarly, no significant differences in median progression-free survival and median overall survival were observed between regimen groups. Multivariate analysis showed that poor performance status (Eastern Cooperative Oncology Group [ECOG] status≥2), weight loss (10% of the weight loss for 3 months), low albumin level (≤3.5 g/dL), and absence of previous esophagectomy at the time of chemotherapy were significantly associated with low OS in both groups (p<0.05). Based on these findings, patients were classified into favorable (score, 0 to 90), intermediate (91-134), and poor (>135) prognostic groups. The median survival for those with a favorable ECOG was 13.8 months (95% confidence interval [CI], 10.8 to 18.6 months), for intermediate 11.2 months (95% CI, 8.7 to 11.9 months), and for poor, 7.0 months (95% CI, 3.6 to 10.0 months). External validation of the nomogram in a different patient cohort yielded significantly similar findings. The nomogram described here predicts survival in MESCC patients and could serve as a guide for the use of FP/XP chemotherapy in MESCC patients.
    Cancer Research and Treatment 12/2013; 45(4):285-94. · 1.96 Impact Factor
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    ABSTRACT: c-N-Methyl-N'-nitro-N-nitroso-guanidine HOS transforming gene (c-MET) is a new potential drug target for treatment of patients with hepatocellular carcinoma (HCC), and a recent study of a c-MET inhibitor in such patients has shown promising results. In the present study, we investigated the incidence of c-MET overexpression and its prognostic impact. Tumor tissue microarrays were used to detect the expression of c-MET in samples from 287 patients with HCC who underwent surgical resection at Samsung Medical Center. We explored the relationships between c-MET overexpression and clinicopathological features of HCC, and investigated recurrence-free survival (RFS) and HCC-specific survival according to the level of c-MET expression. Additionally, we explored the correlation between c-MET protein overexpression, and MET mRNA expression and copy number variation. Most patients in the present study were male (n=297, 82.6%), with Child-Pugh class A liver function (n=286, 99.7%) and hepatitis B viral infection (n=217, 75.6%). c-MET overexpression was observed in 80 patients (27.9%), and was not associated with Edmondson grade, tumor size, microvascular invasion, major portal vein invasion or stage. In addition, c-MET expression levels did not affect RFS or HCC-specific survival. c-MET expression was weakly correlated with c-MET copy number variation (r=0.255, p<0.001), but more than half of all patients with c-MET overexpression had a neutral c-MET copy number. c-MET protein expression was very weakly but significantly positively correlated with its mRNA expression (r=0.199, p=0.002). c-MET overexpression did not have any prognostic impact on recurrence or survival of patients with HCC undergoing surgical resection. However, 27.9% of patients who had c-MET overexpression could be considered candidates for treatment with c-MET inhibitor.
    Anticancer research 11/2013; 33(11):5179-86. · 1.71 Impact Factor
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    ABSTRACT: The aim of this study was to characterize primary cells from extrauterine carcinosarcoma (CS) and to establish a primary CS xenograft mouse model. Primary cells were isolated from a patient with CS and cultured in vitro. Primary CS cells were verified for their ability to consecutively generate tumorigenesis in NOD/SCID mice. The properties of xenograft tumor and explants cells were investigated by immunohistochemistry, cytogenetic, and FACS analysis. Anticancer drug susceptibility of primary CS was analyzed using CCK-8. Primary CS cells greater than 27 passages in vitro showed an ability of a series of xenograft tumorigenesis in vivo having the same marker expression and cytogenetic character as that of original tumor. In addition, explants of xenograft tumors retained their original characteristics in the in vitro culture system. Finally, the analysis of the susceptibility to anticancer drug revealed that primary CS cells were susceptible to both doxorubicin and nilotinib, which are tyrosine kinase inhibitors. The primary CS cells and the primary CS xenograft tumorigenesis introduce a new therapeutic model for targeting cancer and also explore a deeper understanding of generation of the tumor itself.
    International Journal of Gynecological Cancer 11/2013; 23(9):1552-60. · 1.94 Impact Factor
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    ABSTRACT: Statins have potential antineoplastic properties via arrest of cell-cycle progression and induction of apoptosis. A previous study demonstrated in vitro and in vivo antineoplastic synergism between statins and gemcitabine. The present randomized, double-blinded, phase II trial compared the efficacy and safety of gemcitabine plus simvastatin (GS) with those of gemcitabine plus placebo (GP) in patients with locally advanced and metastatic pancreatic cancer. Patients were randomly assigned to receive a 3-week regimen with GS (gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 plus simvastatin 40 mg once daily) or GP (gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 plus placebo). The primary end point was time to progression (TTP). Between December 2008 and April 2012, 114 patients were enrolled. The median TTP was not significantly different between the two arms, being 2.4 months (95 % CI 0.7-4.1 months) and 3.6 months (95 % CI 3.1-4.1 months) in the GS and GP arms, respectively (P = 0.903). The overall disease control rate was 39.7 % (95 % CI 12.2-33.8 %) and 57.1 % (95 % CI 19.8-44.2 %) in the GS and GP arms, respectively (P = 0.09). The 1-year expected survival rates were similar (27.7 and 31.7 % in the GS and GP arms, respectively; P = 0.654). Occurrence of grade 3 or 4 adverse events was similar in both arms, and no patients had rhabdomyolysis. Adding low-dose simvastatin to gemcitabine in advanced pancreatic cancer does not provide clinical benefit, although it also does not result in increased toxicity. Given the emerging role of statins in overcoming resistance to anti-EGFR treatment, further studies are justified to evaluate the efficacy and safety of combined simvastatin and anti-EGFR agents, such as erlotinib or cetuximab, plus gemcitabine for treating advanced pancreatic cancer.
    Cancer Chemotherapy and Pharmacology 10/2013; · 2.80 Impact Factor

Publication Stats

2k Citations
674.38 Total Impact Points

Institutions

  • 2004–2014
    • Sungkyunkwan University
      • • School of Medicine
      • • Department of Pathology
      • • Samsung Medical Center
      Sŏul, Seoul, South Korea
  • 2010–2013
    • Samsung Medical Center
      • Department of Hematology and Oncology
      Seoul, Seoul, South Korea
    • University of California, Irvine
      • Division of Hematology/Oncology
      Irvine, CA, United States
  • 2011
    • Dankook University Hospital
      Anjŏ, Gyeonggi Province, South Korea
  • 2009–2010
    • Hallym University Medical Center
      • • Department of Internal Medicine
      • • Department of Hematology-Oncology
      Seoul, Seoul, South Korea
    • Michiana Hematology Oncology
      Indiana, Pennsylvania, United States
    • Seoul Medical Center
      Sŏul, Seoul, South Korea
  • 2006
    • Korea Institute of Radiological & Medical Sciences
      Sŏul, Seoul, South Korea