Kyung Shik Lee

Yonsei University Hospital, Seoul, Seoul, South Korea

Are you Kyung Shik Lee?

Claim your profile

Publications (21)32.11 Total impact

  • Article: Estimate of a predictive cut-off value for serum 25-hydroxyvitamin D reflecting abdominal obesity in Korean adolescents.
    [show abstract] [hide abstract]
    ABSTRACT: Vitamin D deficiency is a serious global issue. Although the serum 25-hydroxyvitamin D [25(OH)D] test is generally the most accurate way to assess vitamin D levels, the optimal range of 25(OH)D has yet to be established. Moreover, the optimal level may vary according to race, region, and age. Suboptimal vitamin D status is associated with obesity and metabolic syndrome, which are the major risk factors for cardiovascular disorders; however, these relationships in children and adolescents have yet to be clearly determined. Therefore, we identified the best predictive cut-off value for reflecting abdominal obesity and, based on this value, we investigated the relationship between suboptimal 25(OH)D status and the risk for having abdominal obesity, being overweight or obese, and having metabolic syndrome in Korean adolescents. We performed a cross-sectional analysis of 713 Korean adolescents, between 12-19 years of age, and used data collected from the 2008 Korea National Health and Nutrition Examination Survey (KNHANES). Receiver operation characteristic curve analysis was used to identify the cut-off value that reflected abdominal obesity. The cut-off value of serum 25(OH)D that reflected abdominal obesity in Korean adolescents was 17.6 ng/mL. After making adjustments for gender, age, and regular physical exercise, the group that had lower levels of serum 25(OH)D compared to the cut-off value had a significantly higher risk for abdominal obesity, obesity, and metabolic syndrome than the group with 25(OH)D levels higher than the cut-off value. Suboptimal vitamin D status based on this value is associated with increased risk for abdominal obesity, obesity, and metabolic syndrome among Korean adolescents.
    Nutrition research (New York, N.Y.) 06/2012; 32(6):395-402. · 1.20 Impact Factor
  • Article: Vinorelbine-associated myelopathy in a patient who previously received paclitaxel
    [show abstract] [hide abstract]
    ABSTRACT: Vinorelbine seems to cause less neurotoxicity than other vinca alkaloids because of its selective activity on mitotic cells over axonal microtubules. Clinical trials report very mild peripheral neurotoxicity with distal paresthesiae and there are no reports of myelopathy in these series of patients. The authors describe a patient who developed a rare event of myelopathy while on vinorelbine for non-small-cell lung cancer.
    Medical Oncology 04/2012; 18(1):95-97. · 2.14 Impact Factor
  • Article: An increase in serum uric acid concentrations is associated with an increase in the Framingham risk score in Korean adults.
    [show abstract] [hide abstract]
    ABSTRACT: Uric acid is a novel cardiovascular disease (CVD) factor, but its use as an independent risk factor for CVD remains controversial. Here, we examined the correlation between Framingham risk score (FRS) and serum uric acid concentrations in asymptomatic Korean adults. This cross-sectional study was performed on 8035 Korean adults. Besides FRS, we measured body mass index, fasting blood glucose, homeostasis model assessment of insulin resistance, creatinine, γ-glutamyltransferase, the lipid profile, uric acid, high-sensitive C-reactive protein, and the white blood cell count. All subjects were placed into one of three risk groups according to their FRS. All CVD related factors were significantly different in the three FRS groups. The increments of uric acid increased significantly FRS from the 10-year risk 0%-9% group to the >10% group after adjusting for other CVD-related factors using ordinal logistic regression analysis. Analyses of the three age groups showed similar effects. An increased uric acid concentration is associated with an increase in coronary heart disease risk calculated from the FRS, and doctors need to pay attention to this CVD risk in apparently healthy adults with hyperuricemia.
    Clinical Chemistry and Laboratory Medicine 02/2011; 49(5):909-14. · 2.15 Impact Factor
  • Article: Treatment outcome of cisplatin-based concurrent chemoradiotherapy in the patients with locally advanced nasopharyngeal cancer.
    [show abstract] [hide abstract]
    ABSTRACT: The standard treatment of locally advanced nasopharyngeal cancer is a concurrent chemoradiotherapy (CCRT), and cisplatin has been used as the most popular chemotherapeutic agent. But many different doses and schedules for cisplatin administration such as daily, weekly and 3 week cycles have been proposed. We compared and analyzed the tumor response, the overall survival, the toxicity and the chemotherapy dose intensity in the patients with locally advanced nasopharyngeal cancer who were treated with CCRT. We performed a retrospective study on 55 patients with locally advanced nasopharyngeal cancer, and they were treated with CCRT as a front-line treatment from Jan 1996 to Jun 2007 at Kangnam Saint Mary's Hospital. The patients had a median age of 53 years (range: 19 approximately 75 years). Of the total 55 patients, a 3-week cycle of 100mg cisplatin was administered in 31 patients and 30 mg weekly cisplatin was administered in 24 patients combined with radiotherapy. Twenty one patients had a complete response and four patients had a partial response for a response rate of 71.4% (95% CI: 59.5 approximately 83.3) after CCRT and followed by adjuvant chemotherapy. The complete response rates for the 30 mg and 100 mg cisplatin groups were 72.7% (95% CI: 54.9 approximately 90.5) and 54.2% (95% CI: 36.7 approximately 71.7), respectively (p=0.23). The duration of CCRT in the 100mg cisplatin group was significantly longer than that of the 30mg cisplatin group (11.1+/-2.9 weeks vs. 9.0+/-1.2 weeks, p=0.003). The major deviation group, which was defined as prolongation of the radiotherapy duration for more than 2 weeks, had a significantly lower objective response rate than did the non-deviation group (56.3% vs 84.2%, respectively, p=0.002). The major severe toxicities were leucopenia (49.1%), pharyngoesophagitis (49.1%), anorexia (43.6%), nausea (41.8%) and vomiting (40%). Weekly 30mg cisplatin-based CCRT is a practical, feasible cisplatin schedule for the patients with locally advanced nasopharyngeal cancer in regard to decreasing the interruption of radiation treatment and decreasing the treatment-related acute toxicities.
    Cancer Research and Treatment 07/2008; 40(2):62-70.
  • Article: Prognostic factors affecting the clinical outcome of adenoid cystic carcinoma of the head and neck.
    [show abstract] [hide abstract]
    ABSTRACT: Adenoid cystic carcinoma (ACC) is an uncommon tumor, constituting approximately 10% of all head and neck tumors. Classically, ACC has been described as a tumor with indolent, but persistent and recurrent, growth and late onset of metastases, leading eventually to death. This study assessed the prognostic factors affecting the clinical outcome in patients with ACC in the head and neck region. We performed a retrospective study of 42 patients who underwent primary tumor resection or radiotherapy with curative intent and evaluated the clinical parameters, treatment and clinical outcomes. Forty-two patients (18 males and 24 females with a median age of 65 years) received curative treatment. The overall 3- and 5-year survival was 87.4% and 55.3%, respectively, whereas the 3- and 5-year disease-free survival was 64.3% and 36.1%, respectively. Of the 32 patients in whom recurrence could be evaluated, 18 (56.3%) developed distant metastases, with the lung (72.2%) being the most common site. Perivascular invasion influenced metastasis to the lung with borderline significance (P = 0.053). The recurrence rate was higher (P = 0.045) in patients with high-grade tumor. The status of lymph node metastasis was significantly associated with overall survival (P = 0.030). High tumor grade and lymph node involvement were predictive of recurrence and overall survival, respectively. Despite aggressive treatment, it seems to be impossible to prevent the development of distant metastasis. Therefore, more research is needed to identify molecular biomarkers that predict the clinical outcome and to develop effective treatment for patients with ACC.
    Japanese Journal of Clinical Oncology 12/2007; 37(11):805-11. · 1.78 Impact Factor
  • Source
    Article: Docetaxel monotherapy as second-line treatment for pretreated advanced non-small cell lung cancer patients.
    [show abstract] [hide abstract]
    ABSTRACT: Second-line chemotherapy offers advanced non-small cell lung cancer (NSCLC) patients a small, but significant increase in survival. Docetaxel is usually administered as a 3-week schedule, yet there is significant toxicity with this therapy. Therefore, a weekly schedule has been explored in several previous trials. In this retrospective study, we compared the efficacy and safety of a weekly schedule and a 3-week schedule of docetaxel monotherapy in a second-line setting. Docetaxel was administered as 75 mg/m2 on day 1 every 3 weeks or as 37.5 mg/m2 on day 1 and 8 every 3 weeks until disease progression or severe toxicity developed. From October 2003 to March 2006, a total of 37 patients received docetaxel monotherapy and 36 patients could be evaluated. A total of 135 cycles were administered and then evaluated. The median overall survival was 13.3 months (95% confidence interval: 6.3-20.3) for the weekly schedule and 10.7 months (95% confidence interval: 8.3-13.0) for the 3-week schedule (p=0.41). The median time to progression was 3.0 months (95% confidence interval: 1.9-4.0) and 2.8 months (95% confidence interval: 1.0-4.6), respectively (p=0.41). The response rate was 16.7% for the weekly schedule and 21.1% for the 3-week schedule. The major form of hematologic toxicity was grade 3-4 neutropenia (3-week: 38.9%, weekly: 9.5%). The non-hematologic toxicities were similar between the two schedules. There were no treatment-related deaths. A docetaxel weekly schedule was very tolerable and it had comparable activity to that of the 3-week docetaxel schedule. Considering the efficacy and tolerability, a docetaxel weekly schedule can be an alternative schedule for the standard treatment of NSCLC in a second-line setting.
    The Korean Journal of Internal Medicine 10/2007; 22(3):178-85.
  • Article: Clinical characteristics of primary peritoneal carcinoma.
    [show abstract] [hide abstract]
    ABSTRACT: The goal of this study was to determine the clinical and therapeutic characteristics of women with a primary peritoneal carcinoma (PPC). A retrospective clinical study was conducted to evaluate 22 women diagnosed with a PPC from 1993 to 2007 at the Hospitals of The Catholic University of Korea. Diagnoses were based on the Gynecologic Oncology Group criteria and clinical data. We collected patient clinicopathological data including age, presenting symptoms, pretreatment CA-125 values (U/ml), clinical stage (based on the FIGO stage), performance status (using the Eastern Cooperative Oncology Group scale), whether cytoreductive surgery was optimal or not, types of chemotherapy and response to treatment. We evaluated the clinical characteristics and response to treatment, time to treatment failure and overall survival. The median overall survival of all patients was 23.1 months. The estimated 3-year survival rate was 29% (SE, 13%). The response rate to first-line platinum-based chemotherapy was 79% and the median time to treatment failure was 9.9 months (95% confidence interval, 1.38~18.4 months). By univariate and multivariate analysis, performance status was the only significant factor associated with overall survival (p<0.05). We evaluated the clinical characteristics and treatment response of patients with a primary peritoneal carcinoma. Our results showed that it is possible to achieve long-term survival in patients with PPC. A further clinical study is to need to establish clinical characteristics and treatment outcomes.
    Cancer Research and Treatment 06/2007; 39(2):65-8.
  • Article: Pretreatment serum endostatin as a prognostic indicator in metastatic gastric carcinoma.
    [show abstract] [hide abstract]
    ABSTRACT: Endostatin is the C-terminal antiangiogenic fragment of the extracellular matrix protein collagen XVIII, and is generated by tumor-derived proteases. The presence of serum endostatin in patients with gastric cancer has not been reported. The authors assessed the serum levels of endostatin in patients with gastric carcinoma and evaluated their association with the levels of vascular endothelial growth factor (VEGF) and the clinical outcome. A total of 107 patients with gastric cancer were included in the study. Pretherapeutic serum levels of endostatin and VEGF were measured using an ELISA, and compared with those in 23 healthy controls. The serum levels of endostatin and VEGF were higher in gastric cancer patients than in healthy controls (endostatin, 70.1 +/- 16.6 vs. 52.2 +/- 6.2 ng/mL [p < 0.001]; VEGF, 55.1 +/- 7.6 vs. 32.1 +/- 2.4 ng/mL [p < 0.001]; mean +/- SD). Serum endostatin levels were significantly associated with the presence of distant metastases (r = 0.556, p < 0.001) and VEGF levels (r = 0.335, p < 0.001), but not with the depth of tumor invasion, differentiation, or regional lymph node status. A serum endostatin level above the 75th percentile of the distribution for the patients (79.2 ng/mL) was associated with a poor outcome (last follow-up at 42 months; median survival time, 9 vs. 20 months [log-rank, p = 0.017]; median time to progression, 5 vs. 10 months [log-rank, p = 0.022]) in the patients with metastatic gastric cancer. The results suggest for the first time that an elevated serum level of endostatin at the diagnosis of metastatic gastric cancer could be predictive of a poor outcome.
    International Journal of Cancer 12/2006; 119(12):2901-6. · 5.44 Impact Factor
  • Article: Clinical pharmacokinetics of oxaliplatin and 5-fluorouracil administered in combination with leucovorin in Korean patients with advanced colorectal cancer.
    [show abstract] [hide abstract]
    ABSTRACT: Oxaliplatin and 5-fluorouracil (5-FU) act synergistically in colorectal cancer. Here, we evaluated the pharmacokinetics of oxaliplatin and 5-FU administered in combination with leucovorin in Korean advanced colorectal cancer patients. Nine patients with advanced colorectal cancer were included in this study. The 3-week regimen consisted of oxaliplatin (2-h infusion, 130 mg/m(2)on day 1) followed by 5-FU and leucovorin (2-h infusion, 425 and 20 mg/m(2), respectively, from day 1 to day 5). Blood samples were taken and platinum concentrations in total plasma, plasma ultrafiltrate, and RBCs were determined. Plasma concentrations of 5-FU were also determined. The C (max) of oxaliplatin was observed at the end of infusion, with mean values of 4.66, 0.84, and 2.69 microg/ml for total plasma, plasma ultrafiltrate, and RBC samples, respectively. C (max) ratios of total/free were significantly higher than those reported in other ethnic groups. An accumulation of platinum was observed in RBCs, but not in total plasma and plasma ultrafiltrate samples. A significant correlation was found between the total body clearance of ultrafiltrable platinum and creatinine clearance. The C (max) of plasma 5-FU ranged from 23.9 to 533.8 ng/ml, indicating large inter-patient pharmacokinetic variations. This study shows that pharmacokinetics of oxaliplatin in Korean patients is comparable with that of other ethic groups, except for the higher C (max) ratios of total/free. The C (max) of 5-FU in plasma showed large variations among patients. Antitumor efficacy in Korean advanced colorectal cancer patients given oxaliplatin and 5-FU should be further evaluated with respect to pharmacokinetic variabilities.
    Journal of Cancer Research and Clinical Oncology 06/2006; 132(5):320-6. · 2.56 Impact Factor
  • Article: Association between cyclooxygenase-2 and matrix metalloproteinase-2 expression in non-small cell lung cancer.
    [show abstract] [hide abstract]
    ABSTRACT: Cyclooxygenase-2 (COX-2) contributes to invasiveness of cancer through activation of several matrix metalloproteinases (MMPs). Matrix metalloproteinase-2 (MMP-2) is a proteolytic enzyme that degrades the extracellular matrix, and has been linked to invasion and metastasis. This study aims to assess the correlation of the COX-2 expression and the MMP-2 expression in patients with non-small cell lung cancer (NSCLC). We analyzed the protein expressions of COX-2 and MMP-2 by immunohistochemical staining on the tissue array specimens from 204 patients with completely resected NSCLC. A <10% immunostaining of the cancer cells was considered negative, while >10% was considered positive. The COX-2 expression was positive in 68.1% and that of the MMP-2 was positive in 45.6%. The positive expression rate of MMP-2 (52.5%) in the positive COX-2 group was higher than that in the negative COX-2 group (30.8%, P = 0.004). Furthermore, the MMP-2 expression was associated with lymph node involvement, the tumor stage and the histological type. The patients with a positive MMP-2 expression showed a reduced survival (P = 0.048). The COX-2 expression is associated with the MMP-2 expression in NSCLC patients: the latter may also be associated with tumor progression and reduced survival in NSCLC patients.
    Japanese Journal of Clinical Oncology 05/2006; 36(5):263-8. · 1.78 Impact Factor
  • Source
    Article: Irinotecan, continuous 5-fluorouracil, and low dose of leucovorin (modified FOLFIRI) as first line of therapy in recurrent or metastatic colorectal cancer.
    [show abstract] [hide abstract]
    ABSTRACT: Irinotecan, in combination with 5-fluorouracil (5-FU) and a high dose of leucovorin (LV), known as FOLFIRI regimen, has shown activity in recurrent or metastatic colorectal cancer. Therefore, we evaluated the efficacy and safety of irinotecan, 5-FU and a low dose of LV (modified FOLFIRI) as a first line of therapy for patients with relapsed or metastatic colorectal cancer. Between January 2002 and October 2004, 44 patients with histologically confirmed recurrent or metastatic colorectal cancer were enrolled. The chemotherapy regimen schedule consisted of 180 mg/m2 of irinotecan being administered intravenously (i.v) on Day 1, 400 mg/m2 of 5-FU via i.v bolus with 600 mg/m2 of continuous infusion for 22 hrs on both Day 1 and 2, and 20 mg/m2 of leucovorin on both Day 1 and 2 , repeated every two weeks. The overall response rate was 47.8%. Of the 40 evaluated patients, one had CR (2.3%) and 20 had PR (46.5%). Toxicities were mild and easily manageable. Three patients experienced 23 episodes of Grade 3/4 leukopenia., Only one patient developed Grade 3/4 diarrhea. None experienced Grade 3/4 thrombocytopenia. Modified FOLFIRI with a low dose of LV is an effective and tolerable regimen for patients with recurrent or metastatic colorectal cancer.
    The Korean Journal of Internal Medicine 10/2005; 20(3):205-9.
  • Article: A phase II study of epirubicin, cisplatin and uracil-tegafur for advanced gastric carcinoma.
    [show abstract] [hide abstract]
    ABSTRACT: Due to its greater convenience, a combination of uracil and tegafur (referred to as UFT) taken orally is an attractive alternative to continuous intravenous (i.v.) 5-fluorouracil (5-FU) infusion. This phase II study assessed the response rate and toxicity profile of the combination of epirubicin, cisplatin and UFT in patients with metastatic adenocarcinoma of the stomach. Epirubicin (50 mg/m(2)) and cisplatin (60 mg/m(2)) were administered i.v. to 35 patients with metastatic gastric carcinoma on day 1, and subsequently UFT (300 mg/m(2)/day) was administered orally in divided doses for 21 days. The treatment was repeated every 3 weeks. The response rate, time to disease progression, survival and toxic effects were analyzed. Thirty-two of the 35 enrolled patients were assessed subsequently for response. The median number of cycles was four. Thirteen patients (40.6%) showed partial responses, while none showed a complete response. The median time to progression of carcinoma was 20.4 weeks, and the median survival was 37 weeks. Grade 3 and 4 neutropenia was observed in 25% of patients. Grade 3 nausea and vomiting was observed in 28% of patients. No treatment-related death was observed. All patients received doses as planned, except for one who required a 75% dose reduction due to nephrotoxicity. Six of 132 cycles were delayed >7 days after four cycles. The combination of epirubicin, cisplatin and UFT showed anticancer activity against metastatic gastric adenocarcinoma, had a tolerable toxicity profile and showed excellent patient compliance.
    Japanese Journal of Clinical Oncology 02/2005; 35(1):13-7. · 1.78 Impact Factor
  • Source
    Article: Survivin expression and its clinical significance in pancreatic cancer.
    [show abstract] [hide abstract]
    ABSTRACT: Survivin, an inhibitor of apoptosis is expressed in several human cancers. Its expression is known to be associated with poor clinical outcome, but not widely studied in pancreatic cancer. We performed this study to determine the survivin expression in pancreatic cancer and its clinical significance as a prognostic factor. We performed immunohistochemical staining for survivin, p53, and Bax in formalin-fixed, paraffin-embedded block from forty-nine pancreatic tissues. To determine the association with clinical course, we reviewed the patients' clinical record. Of the 49 cases of pancreatic cancer, 46 cases (93.9%) were positive for survivin expression. There was no significant association between survivin expression and p53 or bax. For clinicopathological parameters, perineural invasion was more common in survivin positive and venous invasion was more common in survivin negative (p = 0.041 and 0.040, respectively). Responsiveness to chemotherapy appeared to be slightly better in patients with low survivin expression. Survivin expression may be associated with venous or perineural invasion, indicating metastatic route, and seems to have a potential as a predictive marker for chemotherapy. Further study of large scale is required to determine the clinical significance of survivin expression in pancreatic cancer.
    BMC Cancer 02/2005; 5:127. · 3.01 Impact Factor
  • Article: Gemcitabine and cisplatin combination chemotherapy in intrahepatic cholangiocarcinoma as second-line treatment: report of four cases.
    [show abstract] [hide abstract]
    ABSTRACT: Intrahepatic cholangiocarcinoma is a chemoresistant cancer for which effective chemotherapy is not yet available. We investigated the efficacy and toxicity of the combination of gemcitabine and cisplatin as second-line chemotherapy in four patients with advanced, progressive intrahepatic cholangiocarcinoma. Four patients were enrolled who had previous chemotherapy with epirubicin, cisplatin and protracted infusion of 5-FU. All these patients treated with gemcitabine 1000 mg/m(2) intravenously (i.v.) on days 1 and 8 for 30 min, cisplatin 75 mg/m(2) i.v. on day 1 for 90 min, given every 21 days. Two patients had partial response (PR), and two had stable disease (SD), with one of the latter showing a decrease in tumor size of 35%. Median time to progression was 5 months (range, 3-9 months) and median survival was 9 months (range, 8-16 months). Toxicity was mild and tolerable. Gemcitabine and cisplatin combination chemotherapy may be an effective regimen for advanced intrahepatic cholangiocarcinoma. Further study is warranted to determine the efficacy of this combination regimen.
    Japanese Journal of Clinical Oncology 10/2004; 34(9):547-50. · 1.78 Impact Factor
  • Article: Epirubicin, cisplatin, and protracted infusion of 5-FU (ECF) in advanced intrahepatic cholangiocarcinoma.
    [show abstract] [hide abstract]
    ABSTRACT: Intrahepatic cholangiocarcinoma usually presents late in the clinical course and has a poor prognosis. No effective systemic therapy is currently available. This study aimed to determine the efficacy and toxicity of the ECF regimen (epirubicin, cisplatin. and 24-h continuous infusion of 5-FU) in advanced intrahepatic cholangiocarcinoma. On day 1, epirubicin 50 mg/m(2) and cisplatin 60 mg/m(2) were administered i.v., repeated every 21 days. 5-FU (200 mg/m(2)/day was given continuous i.v. via an ambulatory infusion pump throughout the treatment course. A total of 24 patients (15 men and nine women) with advanced intrahepatic cholangiocarcinoma between August 1996 and April 2002 were enrolled in this study. Of the 20 evaluable patients, two had partial response (10%) and nine had stable disease (45%), including two minor response. Grade 3/4 neutropenia was observed in six patients, while grade 3/4 thrombocytopenia was seen in five patients. There was no neutropenic infection or thrombocytopenic bleeding during any of the cycles of chemotherapy. ECF regimen is well-tolerated but is not an effective treatment for advanced intrahepatic cholangiocarcinoma. Newer clinical trials with combination drugs should be developed.
    Journal of Cancer Research and Clinical Oncology 07/2004; 130(6):346-50. · 2.56 Impact Factor
  • Article: Nail changes during docetaxel containing combination chemotherapy.
    [show abstract] [hide abstract]
    ABSTRACT: Nail toxicity following systemic chemotherapy is common. Onychopathy during the period of neutropenia following chemotherapy may cause subungual abscesses and serious infection. Despite taxoid-related toxicity being increasingly reported since 2000, there are still phase II systemic chemotherapy studies using taxoid that have never mentioned nail changes. Recently, new criteria for the evaluation of nail toxicity have been suggested. The present report is the first of its kind, in Korea, to describe a case of docetaxel-associated onychopathy, which improved following a reduction in the docetaxel dose.
    The Korean Journal of Internal Medicine 07/2004; 19(2):132-3.
  • Article: Loss of estrogen receptor-alpha expression is associated with hypermethylation near its ATG start codon in gastric cancer cell lines.
    [show abstract] [hide abstract]
    ABSTRACT: The proportion of gastric cancers positive for estrogen receptor (ER)-alpha expression is reported to be between 0-67%, depending upon the study. The role of ER-alpha in gastric carcinogenesis is unclear. The ER-alpha gene is located at chromosome 6q25.1, and the long arm of chromosome 6 has been known as a site with frequent loss of heterozygosity (LOH) in gastric cancer. ER expression is linked to suppression of cell proliferation in vitro. Epigenetic inactivation might explain the loss of ER-alpha gene expression in gastric cancer. Given there is no information available regarding the methylation status of the ER-alpha gene promoter region in gastric cancer, we investigated such methylation in 13 gastric cancer cell lines. Western blot analysis, reverse transcription-polymerase chain reaction (PCR), methylation-specific PCR (MS-PCR) and bisulfite sequencing analyses were used. ER-alpha protein was not detected in any cell line, although ER-alpha mRNA was detected in 1 of 13 gastric cancer cell lines. MS-PCR and bisulfite sequencing showed all 13 gastric cancer cell lines had methylated CpG regions in their ER-alpha gene promoters. In conclusion, inactivation of ER-alpha gene expression in gastric cancer cell lines appears associated with CpG island methylation near the TGA initiation codon of the ER-alpha gene.
    Oncology Reports 04/2004; 11(3):617-22. · 1.84 Impact Factor
  • Source
    Article: Detection of Epstein-Barr virus by PCR and expression of LMP1, p53, CD44 in gastric cancer.
    [show abstract] [hide abstract]
    ABSTRACT: Epstein-Barr virus (EBV) is associated with various lymphoproliferative disorders and nasopharyngeal carcinoma. Recently, some gastric cancer cells were observed to contain the EBV sequence. We detected EBV in gastric cancer by using PCR to determine the frequency of EBV-associated gastric cancer, and performed immunohistochemical staining for the latent membrane protein (LMP1), p53 and CD44 to investigate the possible mechanism in EBV-associated gastric cancer. Eighty-seven formalin-fixed and paraffin-embedded blocks (40 gastric adenocarcinomas, 34 adjacent normal tissues, 13 metastatic lymph nodes) from 40 surgically resected gastric specimens were studied. All patients were diagnosed with gastric cancer at the Kang-Nam St. Mary's Hospital between April 1995 and April 1997. After DNA was extracted from each paraffin block, we performed PCR and immunohistochemical staining for the LMP1, p53 and CD44. EBV was detected in 4 of 40 cases (10%). In 1 of 4 EBV-positive cases, EBV was also detected in a metastatic lymph node. The immunohistochemical staining for the LMP1, p53 and CD44 were negative in all the EBV-positive cancer patients. Of the patients having these cancers, 2 had a poorly differentiated adenocarcinoma with a lymphoepithelioma-like morphology. The frequency of EBV-associated gastric cancer is about 10% in Korea. Considering the negative result of the immunohistochemical staining for the LMP1, p53 and CD44, EBV-associated gastric cancer seems to have a different mechanism of tumorigenesis from ordinary gastric cancer or other EBV-associated cancers. This specific mechanism must be determined by further large scale studies.
    The Korean Journal of Internal Medicine 04/2004; 19(1):43-7.
  • Article: Death receptor 5 and Bcl-2 protein expression as predictors of tumor response to gemcitabine and cisplatin in patients with advanced non-small-cell lung cancer.
    [show abstract] [hide abstract]
    ABSTRACT: The cytotoxic effects of gemcitabine (G) and cisplatin (C) seem to occur through induction of apoptosis. To examine whether the efficacy of GC chemotherapy might be influenced by the expression of death receptor 5 (DR5) and Bcl-2 of the tumor, we investigated the correlation between the tumor response rate and DR5 and Bcl-2 expression in a series of patients prospectively treated with GC. Thirty-four chemotherapy naïve patients with advanced non-small-cell lung cancer (NSCLC) received intravenously 1000 mg/m2 gemcitabine on d 1 and 8 along with 80 mg/m2 cisplatin on d 2, every 21 d. Tumor specimens were analyzed for DR5 and Bcl-2 expression by immunohistochemistry. The objective response rate was 56% (19 of 34 patients). With median follow-up of 10 mo, the predicted median survival time was 12 mo (95% confidence interval [CI], 9-15 mo). Eleven (32%) and 14 (41%) NSCLC cases were found positive for DR5 and Bcl-2, respectively. The response rate was significantly higher in patients with DR5 expression than those without DR5 expression (91% vs 39%; p = 0.008). Patients with Bcl-2 expression were apparently less responsive than those without Bcl-2 expression (21% vs 80%; p = 0.001). DR5 and Bcl-2 expression was significantly associated with response to GC chemotherapy. Therefore, DR5 and Bcl-2 status are useful factors for predicting the efficacy of GC.
    Medical Oncology 02/2003; 20(4):355-62. · 2.14 Impact Factor
  • Article: Expression of placental growth factor gene in lung cancer.
    [show abstract] [hide abstract]
    ABSTRACT: Differences in the gene expression profiles in small cell lung cancers (SCLC) and non-small cell lung cancers (NSCLC) may explain their different clinical characteristics. The aims of this study were (1) to identify genes differentially expressed in SCLC and NSCLC using mRNA differential display, and (2) to determine the clinical relevance of such genes in lung cancer. RNA differential display using three SCLC and six non-SCLC cell lines was used to identify a differentially expressed gene. Differential expression of the gene was confirmed in additional lung cancer cell lines using RT-PCR. Immunohistochemical staining for the gene product was performed on paraffin-embedded tissue from lung cancer patients. We examined the relationship between the expression of the gene and clinical parameters, including disease stage, response to treatment and survival time. The placental growth factor (PGF) gene was identified as preferentially expressed in SCLC compared with NSCLC cell lines using mRNA differential display. Further analysis of 45 lung cancer cell lines using RT-PCR showed that the placental growth factor (PGF) gene was expressed in nine of 13 SCLC cell lines (69%) and five of 32 NSCLC cell lines (15.6%) (p < 0.001, Fisher's exact test). Immunohistochemistry using anti-PGF antibody on the paraffin blocks from lung cancer patients showed that PGF expression was significantly higher in SCLC than NSCLC tissue sections (32 vs. 5.6%, p = 0.041, Fisher's exact test). Expression of PGF protein did not correlate with disease stage, response to treatment or survival time in SCLC patients. The present study suggests there is higher expression of PGF in SCLC compared to NSCLC. It may be that higher expression of the angiogenic factor PGF contributes to differences between the progression of SCLC and NSCLC, especially in regard to the nature of SCLC metastasis.
    Tumor Biology 25(1-2):1-6. · 1.94 Impact Factor