Jeeyun Lee

Samsung Medical Center, Sŏul, Seoul, South Korea

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Publications (199)707.17 Total impact

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    ABSTRACT: Background The granisetron transdermal system (GTS) showed non-inferior efficacy to oral granisetron to control chemotherapy-induced nausea and vomiting (CINV) during multiday chemotherapy. We compared the efficacy and safety of GTS with that of intravenous and oral granisetron in Korean patients receiving moderately emetogenic chemotherapy (MEC). Patients and methods A total of 276 patients were randomized into GTS (n = 139, one patch on days 1–4) or control group (n = 137, intravenous on day 1 and oral on days 2–4). The primary endpoint was the percentage of patients achieving complete response (CR) from chemotherapy initiation until 24 h after the final administration. Results Out of 234 patients (112 in GTS and 122 in control group) included in the per protocol analysis, 97.9 % had gastrointestinal cancer and 76.9 % received 3-day chemotherapy. The GTS showed non-inferior efficacy achieving CR in 75.0 % of the patients; 74.6 % of the patients in the control group achieved CR (95 % confidence interval −10.73 to 11.55 %). The CR rate did not change after subgroup analyses by sex, age, and chemotherapy naivety and analysis per day and overall days of treatment. The GTS group showed sustained CR from day 1 to day 4. Patients’ satisfaction, assessed using Functional Living Index—Emesis (FLI-E), showed no difference. Both treatments were well tolerated and safe. Conclusion The GTS showed non-inferior efficacy to intravenous and oral granisetron. The safety, tolerability, and FLI-E scores of the GTS were comparable to those of control group. The GTS offers a convenient alternative option for relieving CINV in patients receiving MEC.
    Supportive Care Cancer 12/2014; · 2.65 Impact Factor
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    ABSTRACT: The aims of this study were to demonstrate the tumorigenicity of CD133+ colon cancer cells in vitro, analyze the correlations between spheroid formation and clinicopathologic variables, and screen for overexpressed genes in CD133+ colon cancer stem cells. Moreover, the aim of this study was to establish a living tumor tissue bank using surgically resected specimens. Using LoVo cell line, we isolated CD133+ cells and performed clonogenic assay and animal experiment to test tumorigenicity of CD133+ cells. Twenty-nine surgical samples were freshly collected from 27 patients who received curative or palliative surgery, and the samples were mechanically and enzymatically dissociated into single cells. We confirmed the enhanced tumorigenicity of CD133+ cells isolated from LoVo cell line both in vitro and in vivo. Of these 29 samples, 8 (28%) contained >3% CD133+ cells. Sphere formation was significantly higher in samples from patients with lymphatic invasion than in those without lymphatic invasion [54.5% (6/11) vs. 12.5% (2/16); P=0.033] and in samples containing >3% of CD133+ cells than in those containing ≤3% of CD133+ cells [36.4% (4/11) vs. 0% (0/16); P=0.019]. These findings indicate that CD133 is a valid marker for identifying cancer stem cells from fresh surgically resected colorectal cancer tissues. Furthermore, we successfully established a living tumor tissue bank using surgically resected colorectal tissues with a viability of >70%.
    Journal of gastrointestinal oncology 12/2014; 5(6):447-456.
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    ABSTRACT: We report updated progression-free survival (PFS) and overall survival (OS) data from a trial that compared capecitabine plus oxaliplatin (CapeOX) versus S-1 plus oxaliplatin (SOX) for the first-line treatment of metastatic colorectal cancer. This trial was a randomized, two-armed, non-inferiority phase 3 comparison of CapeOX (capecitabine 1000 mg/m2 twice daily on days 1-14 and oxaliplatin 130 mg/m2 on day 1) versus SOX (S-1 40mg/m2 twice daily on days 1-14 and oxaliplatin 130 mg/m2 on day 1). The primary end point was to show non-inferiority of SOX relative to CapeOX in terms of PFS. Thus, a follow-up exploratory analysis of PFS and OS was performed. The intention to treat (ITT) population was comprised of 340 patients (SOX arm: 168 and CapeOX arm: 172). The updated median PFS was 7.1 months (95% CI 6.4-8.0) in the SOX group and 6.3 months (95% CI 4.9-6.7) in the CapeOX group (hazard ratio [HR], 0.83 [0.66-1.04], p = .10). The median OS was 19.0 months (95% CI 15.3-23.0) in the SOX group and 18.4 months (95% CI 14.1-20.7) in the CapeOX group (HR, 0.86 [0.68-1.08], p = .19). Subgroup analyses according to principal demographic factors such as sex, age, ECOG (Eastern Cooperative Oncology Group) performance status, primary tumor location, measurability, previous adjuvant therapy, number of metastatic organs, and liver metastases showed no interaction between any of these characteristics and the treatment. Updated survival analysis shows that SOX is similar to CapeOX, confirming the initial PFS analysis. Therefore, the SOX regimen could be an alternative first-line doublet chemotherapy strategy for patients with metastatic colorectal cancer.Trial registration: NCT00677443 and May 12 2008.
    BMC Cancer 11/2014; 14(1):883. · 3.33 Impact Factor
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    ABSTRACT: Patients with gastric and esophageal (GE) adenocarcinoma tumors in which the oncogene ERBB2 has been amplified are routinely treated with a combination of cytotoxic chemotherapy and the ERBB2-directed antibody trastuzumab; however, the addition of trastuzumab, even when tested in a selected biomarker-positive patient population, provides only modest survival gains. To investigate the potential reasons for the modest impact of ERBB2-directed therapies, we explored the hypothesis that secondary molecular features of ERBB2-amplified GE adenocarcinomas attenuate the impact of ERBB2 blockade. We analyzed genomic profiles of ERBB2-amplified GE adenocarcinomas and determined that the majority of ERBB2-amplified tumors harbor secondary oncogenic alterations that have the potential to be therapeutically targeted. These secondary events spanned genes involved in cell-cycle regulation as well as phosphatidylinositol-3 kinase and receptor tyrosine kinase signaling. Using ERBB2-amplified cell lines, we demonstrated that secondary oncogenic events could confer resistance to ERBB2-directed therapies. Moreover, this resistance could be overcome by targeting the secondary oncogene in conjunction with ERBB2-directed therapy. EGFR is commonly coamplified with ERBB2, and in the setting of ERBB2 amplification, higher EGFR expression appears to mark tumors with greater sensitivity to dual EGFR/ERBB2 kinase inhibitors. These data suggest that combination inhibitor strategies, guided by secondary events in ERBB2-amplified GE adenocarcinomas, should be evaluated in clinical trials.
    The Journal of clinical investigation. 11/2014;
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    ABSTRACT: Purpose: We retrospectively analyzed the feasibility and adverse events for two regimens, postoperative chemoradiation (CRT) with 5-fluorouracil/leucovorin (5-FU/LV) compared to S-1 in D2-resected gastric cancer patients. Patients and Methods: The study included 405 gastric cancer patients who underwent curative gastrectomy with D2 lymph node dissection and received adjuvant therapy between January 2008 and July 2009. Feasibility and adverse events for the CRT and S-1 regimens were analyzed. Results: Out of the 405 patients, 244 (60.2%) had CRT and 161 (39.8%) had S-1 treatment. The regimen was selected based on the preferences of the physician and the patient. S-1 was more frequently administered to patients with older age (age ≥70) and those with early-stage disease (stage II). The stage was significantly more advanced in the CRT group compared to the S-1 group (S-1 vs. CRT: stage II, 59.6% vs. 36.1%; stage III/IV, 28.0% vs. 48.3%, respectively; p<0.001). The completion rate of the planned therapy was significantly higher in the CRT group than in the S-1 group (95.1% vs. 72.8%, respectively; p<0.001). Regarding severe adverse events (grade 3-4), neutropenia (CRT vs. S-1; 40.2% vs. 8.7%, respectively, p<0.001), nausea (CRT vs. S-1; 5.7% vs. 0%, respectively; p=0.002) and stomatitis (CRT vs. S-1; 7.4% vs. 2.5%, respectively; p=0.034) were significantly more frequent in the CRT cohort compared to the S-1 group. Conclusion: Both adjuvant CRT with 5-FU/LV and adjuvant S-1 are safe and feasible in D2-resected gastric cancer patients. Patients with old age or early stage disease tend to prefer S-1 therapy to chemoradiation.
    Anticancer research 11/2014; 34(11):6585-6591. · 1.71 Impact Factor
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    ABSTRACT: Angiomyolipomas (AMLs) are relatively rare hamartomatous or benign tumors that occasionally occur as part of tuberous sclerosis complex (TSC). Mutations in either of the two genes, TSC1 and TSC2, have been attributed to the development of TSC. Between 1994 and January 2009, 83 patients were diagnosed with AML at the Samsung Medical Center. In that group of patients, 5 (6%) had AML with TSC (AML-TSC). Mutational analysis of the TSC2 gene was performed using 7 samples from the 5 AML-TSC patients and 14 samples from 14 patients with sporadic AML without TSC (AML-non-TSC). From this analysis, mutations in TSC genes were identified in 5 samples from the AML-TSC patients (mutation detection rate = 71%) and 3 samples from AML-non-TSC patients (mutation detection rate = 21%). In the case of AML-TSC, 6 mutations were found including 3 recurrent mutations and 3 novel mutations, while in the case of AML-non-TSC, 4 mutations were identified once, including 1 novel mutation. Also MLPA analysis of the TSC2 gene showed that TSC2 exon deletion is more frequently observed in AML-TSC patients than in AML-non-TSC patients. This is the first mutation and multiplex ligation-dependent probe amplification (MLPA) analyses of TSC2 in Korean AMLs that focus on TSC. This study provides data that are representative of the distribution of mutations and exon deletions at TSC genes in clinically diagnosed AML-TSC cases of the Korean population.
    Experimental and Molecular Pathology 10/2014; · 2.13 Impact Factor
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    ABSTRACT: Pazopanib is an orally bioavailable, ATP-competitive, multi-targeted kinase inhibitor mainly targeting VEGFR2 and PDGFR tyrosine kinases, but the biological sequences of pazopanib activities beyond anti-angiogenesis are poorly defined. We used a panel of 38 GC cell lines in order to test the efficacy of pazopanib. In a growth inhibition assay, genomic changes indicated that pazopanib had differential effects on cell growth. Treatment of the KATO-III, OCUM-2M, SNU-16 and HSC-39 GC cell lines harboring FGFR2 amplification with pazopanib resulted in marked decreases of cell survival with IC50 in ranges of 0.1 - 2.0 microM, while the same treatment of those cell lines without FGFR2 amplification had no growth inhibitory effects. In the ectopic FGFR2-expressing model, treatment with the indicated concentrations of pazopanib significantly inhibited cell growth and colony formation by FGFR2-expressing NIH 3T3 cells with WT FGFR2 and mutant FGFR2 (S252W). Pazopanib also selectively suppressed constitutive FGFR2 signaling and phosphorylation of downstream effectors. In cell cycle analysis, FGFR2-amplified cells underwent cell cycle arrest at the G1-S phase after pazopanib treatment, whereas there were no significant effects on cell cycle progression in cells without FGFR2 amplification treated with pazopanib. In addition, pazopanib increased a substantial fraction of sub-G1 only in FGFR2-amplified cells. These findings show that the activation of FGFR2 signaling by amplification may be a critical mediator of cell proliferation in a small subset of GC patients and that pazopanib may provide genotype-correlated clinical benefits beyond the setting of highly vascular tumors.
    Molecular Cancer Therapeutics 09/2014; · 5.60 Impact Factor
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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 07/2014; 31(7):23. · 2.15 Impact Factor
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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. · 3.91 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: In the era of targeted therapy, mutation profiling of cancer is a crucial aspect of making therapeutic decisions. To characterize cancer at a molecular level, the use of formalin-fixed paraffin-embedded tissue is important. We tested the Ion AmpliSeq Cancer Hotspot Panel v2 and nCounter Copy Number Variation Assay in 89 formalin-fixed paraffin-embedded gastric cancer samples to determine whether they are applicable in archival clinical samples for personalized targeted therapies. We validated the results with Sanger sequencing, real-time quantitative PCR, fluorescence in situ hybridization and immunohistochemistry. Frequently detected somatic mutations included TP53 (28.17%), APC (10.1%), PIK3CA (5.6%), KRAS (4.5%), SMO (3.4%), STK11 (3.4%), CDKN2A (3.4%) and SMAD4 (3.4%). Amplifications of HER2, CCNE1, MYC, KRAS and EGFR genes were observed in 8 (8.9%), 4 (4.5%), 2 (2.2%), 1 (1.1%) and 1 (1.1%) cases, respectively. In the cases with amplification, fluorescence in situ hybridization for HER2 verified gene amplification and immunohistochemistry for HER2, EGFR and CCNE1 verified the overexpression of proteins in tumor cells. In conclusion, we successfully performed semiconductor-based sequencing and nCounter copy number variation analyses in formalin-fixed paraffin-embedded gastric cancer samples. High-throughput screening in archival clinical samples enables faster, more accurate and cost-effective detection of hotspot mutations or amplification in genes.
    PLoS ONE 01/2014; 9(11):e111693. · 3.53 Impact Factor

Publication Stats

2k Citations
707.17 Total Impact Points

Institutions

  • 2010–2014
    • Samsung Medical Center
      • Department of Hematology and Oncology
      Sŏul, Seoul, South Korea
    • University of California, Irvine
      • Division of Hematology/Oncology
      Irvine, CA, United States
  • 2004–2014
    • Sungkyunkwan University
      • • School of Medicine
      • • Department of Pathology
      • • Samsung Medical Center
      Sŏul, Seoul, South Korea
  • 2012
    • Ulsan University Hospital
      Urusan, Ulsan, South Korea
  • 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