SCI 발표논문

2011년 177편

572011

제1저자 박경우 · 교신저자 김효수

, , , , , , , , , ,
Renal dysfunction and high levels of hsCRP are additively associated with hard endpoints after percutaneous coronary intervention with drug eluting stents.
Int J Cardiol. 2011;149(2):174-181.

Abstract
BACKGROUND Chronic kidney disease (CKD) and high C-reactive protein (CRP) are known risk factors of cardiovascular disease. In the drug eluting stent (DES) era, the relationship among CKD, CRP, and long-term outcomes after percutaneous coronary intervention (PCI) has not yet been demonstrated. We investigated the combined effects of renal dysfunction and CRP on outcomes in patients who underwent PCI using DES.
METHODS A total of 1859 patients (mean age 64 ± 10 years) who underwent PCI with DES between February 2003 and June 2006, were divided into 4 groups (quartile) according to estimated glomerular filtration rate (eGFR) and hsCRP at admission.
RESULTS The composite of cumulative death and non-fatal myocardial infarction (mortality+MI) during median follow-up of 27 months, was significantly higher in the lowest eGFR quartile than in the other three groups (hazard ratio (HR) for mortality+MI: 3.32, 95% CI: 2.21-5.00, P<0.001). Mortality+MI was also significantly higher in the highest hsCRP quartile (HR: 3.29, 95% CI: 2.02-5.37, P<0.001). A combined analysis of mortality+MI on the basis of hsCRP and renal function showed the exaggerated hazard in the combined worst quartile of hsCRP and GFR (HR of the combined worst quartile, 10.876, 95% CI: 3.74-31.63, P<0.001). Furthermore, both the lowest eGFR quartile and the highest hsCRP quartile were significantly associated with increased risk of stent thrombosis. In a multivariate analysis, low GFR and high hsCRP were independent predictors of mortality+MI after PCI with DES along with left ventricular dysfunction, diabetes, and left main disease.
CONCLUSIONS In an unselected cohort of patients receiving PCI with DES, poor renal function and high hsCRP were additively associated with a higher risk of hard endpoints and were independent predictors of mortality+MI even after correction for other factors. Our data suggest the importance of systemic factors on mortality even in the DES era.
PubMed IF 3.3 순환기내과
562011

제1저자 허진, 박종한, 이상언 · 교신저자 김효수

, , , , , , , , , , , , , ,
Human peripheral blood-born hematosphere as a niche for hematopoietic stem cell expansion.
Cell Res. 2011;21(6):987-90.

PubMed IF 31.1 순환기내과
552011

제1저자 정고은 · 교신저자 윤정환

, , , , , , , , ,
Ursodeoxycholic acid-induced inhibition of DLC1 protein degradation leads to suppression of hepatocellular carcinoma cell growth.
Oncol Rep. 2011;25(6):1739-46.

Abstract
Ursodeoxycholic acid (UDCA), a hydrophilic bile acid, has been shown to inhibit mitogenic signaling and suppressing cell proliferation in colonic tumorigenesis. The transcription of DLC1 (deleted in liver cancer), a tumor suppressor gene, is frequently silenced in various types of human cancer. In this study, we postulated that UDCA may inhibit DLC1 protein degradation in hepatocellular carcinoma (HCC) cells, and increased DLC1 expression may suppress HCC cell growth. Human HCC cell lines were used in this study. The methylation status was measured by methylation-specific PCR following sodium bisulfite treatment. Cell proliferation was assessed using an MTS assay. Kinase signaling cascades were evaluated by immunoblot analysis. For assessing ubiquitination, immunoprecipitation analysis was used. To inhibit cellular protein, specific small interfering RNAs (siRNAs) were transfected into cells. DLC1 protein levels increased over time following UDCA treatment. Specifically, UDCA increased the half-life of the DLC1 protein by inhibiting proteasomal degradation of DLC1 without affecting ubiquitination of the DLC1 protein. In addition, HCC cell growth was suppressed following UDCA treatment and this growth suppression was significantly reversed following transfection with DLC1-siRNA. Inhibition of DLC1 increased cellular proliferation; this was reduced after Rho-inhibitor treatment. Finally, RhoA activity was reduced following UDCA treatment; this result was reversed and thus increased following DLC1-siRNA transfection. In conclusion, these results demonstrate that UDCA induces DLC1 protein expression by inhibiting proteasomal DLC1 degradation in a ubiquitin-independent manner, and that DLC1 induction participates in UDCA-induced suppression of HCC cell growth. These observations implicate UDCA as an anti-proliferative agent in HCC.
PubMed IF 4.7 소화기내과
542011

제1저자 박영식 · 교신저자 권혁태

, , , , , ,
Impact of visceral adiposity measured by abdominal computed tomography on pulmonary function.
J Korean Med Sci. 2011;26(6):771-7.

Abstract
Although an inverse relationship between abdominal adiposity and pulmonary function has been suggested, direct measurement of abdominal adipose tissue has rarely been attempted. Our object is to determine the impact of abdominal adiposity on pulmonary function by directly measuring abdominal adipose tissue with abdominal computed tomography (CT). In this cross-sectional study, we included never-smokers between the ages of 18 and 85 yr, who had undergone spirometry and abdominal adipose tissue analysis with CT scans during November 1, 2005 to October 31, 2009 as part of the comprehensive health examination. Among a total of 3,469 participants, 890 (25.7%) were male. The mean body mass index and waist circumference among males and females were 24.6 kg/m(2) and 87.8 cm and 23.0 kg/m(2) and 83.0 cm, respectively. Although total adipose tissue (TAT) of the abdomen in males (269.1 cm(2)) was similar to that in females (273.6 cm(2)), the ratio of visceral adipose tissue (VAT)/subcutaneous adipose tissue (SAT) was different; 0.99 in males and 0.50 in females. In males, TAT, SAT, and VAT were inversely associated with the absolute value of forced vital capacity (FVC), and TAT and VAT were inversely associated with forced expiratory volume in one second (FEV(1)). However, in females, TAT and VAT, but not SAT, were inversely associated with absolute FVC and FEV(1) values. In conclusion, the amount of abdominal adipose tissue directly measured using CT is inversely associated with lung function.
PubMed IF 3.2 호흡기내과
532011

제1저자 정지용 · 교신저자 주권욱

, , , , , , , , ,
Effects of potassium on expression of renal sodium transporters in salt-sensitive hypertensive rats induced by uninephrectomy.
Am J Physiol Renal Physiol. 2011;300(6):F1422-30.

Abstract
Dietary potassium is an important modulator of systemic blood pressure (BP). The purpose of this study was to determine whether dietary potassium is associated with an altered abundance of major renal sodium transporters that may contribute to the modulation of systemic BP. A unilateral nephrectomy (uNx) was performed in male Sprague-Dawley rats, and the rats were fed a normal-salt diet (0.3% NaCl) for 4 wk. Thereafter, the rats were fed a high-salt (HS) diet (3% NaCl) for the entire experimental period. The potassium-repleted (HS+KCl) group was given a mixed solution of 1% KCl as a substitute for drinking water. We examined the changes in the abundance of major renal sodium transporters and the expression of mRNA of With-No-Lysine (WNK) kinases sequentially at 1 and 3 wk. The systolic BP of the HS+KCl group was decreased compared with the HS group (140.3 ± 2.97 vs. 150.9 ± 4.04 mmHg at 1 wk; 180.3 ± 1.76 vs. 207.7 ± 6.21 mmHg at 3 wk). The protein abundances of type 3 Na(+)/H(+) exchanger (NHE3) and Na(+)-Cl(-) cotransporter (NCC) in the HS+KCl group were significantly decreased (53 and 45% of the HS group at 1 wk, respectively; 19 and 8% of HS group at 3 wk). WNK4 mRNA expression was significantly increased in the HS+KCl group (1.4-fold of control at 1 wk and 1.9-fold of control at 3 wk). The downregulation of NHE3 and NCC may contribute to the BP-attenuating effect of dietary potassium associated with increased urinary sodium excretion.
PubMed IF 3.6 신장내과
522011

제1저자 김기원 · 교신저자 오국환

, , , , , , , , , ,
Pharmacokinetic profiles of ceftazidime after intravenous administration in patients undergoing automated peritoneal dialysis.
Antimicrob Agents Chemother. 2011;55(6):2523-7.

Abstract
The pharmacokinetics (PK) of ceftazidime after intravenous (i.v.) administration during automated peritoneal dialysis (APD) and their dependence on peritoneal membrane transport are the targets of the present study. Eleven patients receiving a single i.v. dose of ceftazidime (15 mg/kg of body weight) (seven males, median [interquatile] age, 59 [36 to 62]) were recruited. Serum and dialysate samples were collected at the beginning, middle, and end of each of the five dwells during a 24-h period, with dwells 1, 2, and 3 using an automated cycler (designated on-cycler) and dwells 4 and 5 being manual exchanges (designated off-cycler), together with urine collection during the same period. Population PK analysis was employed to estimate the PK parameters. Peritoneal equilibration tests were performed for all patients, and correlations between peritoneal clearance (CL(PD)) for ceftazidime and dialysate-to-plasma ratios for creatinine (D/P(cr)) were obtained using the Spearman's product correlation coefficient (ρ). Ceftazidime renal clearance (CL(renal)) was 0.052 ml/min/kg, and CL(PD) was 0.063 ± 0.050 ml/min/kg. CL(PD) for on- and off-cycler were 0.071 and 0.058 ml/min/kg (P = 0.164), respectively. A significant correlation between CL(PD) and D/P(cr) was observed, with one outlier excluded, suggesting that CL(PD) for ceftazidime during APD is dependent upon the peritoneal small-solute transport rate. A model prediction yielded adequate serum and dialysate concentrations of ceftazidime throughout a 24-h period for sensitive organisms (MIC, 8 μg/ml) by either i.v. (at 15 mg/kg) or intraperitoneal (i.p.; at 20 mg/kg) administration during off-cycler dwells. The present study suggests that the i.v. administration of ceftazidime at 15 mg/kg or i.p. administration of ceftazidime at 20 mg/kg during a long dwell every 24 h can be recommended for treating systemic or intraperitoneal infections of APD patients.
PubMed IF 4.2 신장내과
512011

제1저자 홍준식 · 교신저자 김태유

, , , , , , , , , ,
Phase II study of biweekly S-1 and oxaliplatin combination chemotherapy in metastatic colorectal cancer and pharmacogenetic analysis.
Cancer Chemother Pharmacol. 2011;67(6):1323-31.

Abstract
PURPOSE To evaluate the efficacy and safety of S-1 in combination with oxaliplatin in a biweekly schedule as first-line treatment in metastatic colorectal cancer and the association between genetic polymorphisms and treatment outcomes.
METHODS Eligibility included age 18-75 years, at least one measurable lesion, no prior chemotherapy except adjuvant chemotherapy, and Eastern Cooperative Oncology Group Performance Status (PS) 0-2. S-1 40 mg/m(2) b.i.d. on days 1-7 with 85 mg/m(2) of oxaliplatin on day 1 was repeated every 2 weeks. Genomic DNA from whole blood was analyzed for 15 single-nucleotide polymorphisms (SNPs) among 8 genes.
RESULTS Fifty-two patients (median age 63 years, range 37-74) were enrolled: 37 men and 15 women; 44 with a PS of 0 and 8 with a PS of 1; and 41 with initially metastatic cancer and 11 with relapsed disease. Among 51 evaluable patients, objective response rate was 47.1% [95% confidence interval (CI) 32.9-61.2]. Median follow-up duration was 17.1 months (range 3.9-28.2 months). Median progression-free survival (PFS) was 6.4 months (95% CI 4.8-8.1), and median overall survival had not been reached yet. Reported grade 3 toxicities were neutropenia (7.7%), thrombocytopenia (5.8%), sensory neuropathy (7.7%) and diarrhea (1.9%). There was no grade 4 toxicity or neutropenic fever. Patients with A/G or G/G genotype in GSTP1 Ile105Val SNP had longer PFS than patients with A/A (median 8.3 vs. 6.1 months, P = 0.04).
CONCLUSIONS Biweekly S-1 with oxaliplatin is effective and has improved tolerability and convenience compared to other fluoropyrimidine with oxaliplatin combinations. GSTP1 Ile105Val SNP is associated with treatment outcomes.
PubMed IF 2.5 혈액종양내과
502011

제1저자 이윤규 · 교신저자 오도연

, , , , , , , , ,
Diagnostic performance of contrast enhanced CT and 18F-FDG PET/CT in suspicious recurrence of biliary tract cancer after curative resection.
BMC Cancer. 2011;11:188.

Abstract
BACKGROUND Because of the late clinical presentation of biliary tract cancer (BTC), only 10% of patients are eligible for curative surgery. Even among those patients who have undergone curative surgery, most patients develop recurrent cancer. This study is to determine the clinical role of 18F-FDG PET/CT during post-operative surveillance of suspected recurrent BTC based on symptoms, laboratory findings and contrast-enhanced CT (ceCT) findings.
METHODS We consecutively enrolled 50 patients with BTC who underwent curative surgery. An 18F-FDG PET/CT was obtained for assessment of recurrence based on clinical suspicion during post-operative surveillance. The final confirmation of recurrence was determined pathologically or clinically. When a pathologic confirmation was impossible or inconclusive, a clinical confirmation was used by radiologic correlation with subsequent follow-up ceCT at a minimum of 3-month intervals. Diagnostic efficacy was evaluated by comparing the results of ceCT and 18F-FDG PET/CT with the final diagnosis.
RESULTS Among the 50 patients, 34(68%) were confirmed to have a recurrence. PET/CT showed higher sensitivity (88% vs. 76%, p=0.16) and accuracy (82% vs. 66%, p=0.11) for recurrence compared to ceCT, even though the difference was not significant. The positive (86% vs. 74%, p=0.72) and negative predictive values for recurrence (73% vs. 47%, p=0.55) were not significantly different between PET/CT and ceCT. However, an additional PET/CT on ceCT significantly improved the sensitivity than did a ceCT alone (94% [32/34] for PET/CT on ceCT vs. 76% [26/34] for ceCT alone, p=0.03) without increasing the specificity, positive predictive value, and negative predictive value.
CONCLUSIONS 18F-FDG PET/CT alone is not more sensitive or specific than ceCT in the detection of recurrent BTC after curative surgery. These results do not reach statistical significance, probably due to the low number of patients. However, an additional 18F-FDG PET/CT on ceCT significantly improves the sensitivity of detecting recurrences.
PubMed IF 4.1 혈액종양내과
492011

제1저자 백선경 · 교신저자 오도연

, , , , ,
Clinicopathologic characteristics and treatment outcomes of hepatoid adenocarcinoma of the stomach, a rare but unique subtype of gastric cancer.
BMC Gastroenterol. 2011;11:56.

Abstract
BACKGROUND Gastric hepatoid adenocarcinoma (HAC) is a special type of gastric cancer that morphologically mimics hepatocellular carcinoma. In this study, we performed an evaluation of clinicopathologic characteristics, treatment outcome, and prognosis in patients with gastric HAC.
METHODS We consecutively enrolled patients with pathologically proven gastric HAC at Seoul National University Hospital between January 1996 and December 2008 and conducted a retrospective review. Among 15,253 patients with gastric cancer, 26 patients (0.17%) were diagnosed as gastric HAC.
RESULTS Among 26 patients, 22 were male and the median age was 63. Stage at diagnosis was stage IB in 3 patients, stage II in 6 patients, stage III in 7 patients, and stage IV in 10 patients. Eight patients out of 18 patients with stage IB, II, III, and IV relapsed after curative surgery. Relapse-free survival for these patients was 16.67 months. The most common metastatic site was intraabdominal lymph nodes (n = 9), followed by the liver (n = 8). Thirteen patients received palliative chemotherapy. The most commonly used regimen was a combination of fluoropyrimidine and platinum. Partial response was observed in one patient and stable disease in 5 patients. Median overall survival and progression free survival of these patients were 8.03 (95% CI: 6.59-9.47) and 3.47 months (95% CI: 0.65-6.29), respectively.
CONCLUSIONS Gastric HAC is a very rare but unique type of stomach cancer. Early detection of this type of cancer is of critical importance to patient prognosis. Additional studies to reveal the biology of this tumor are warranted.
PubMed IF 3.2 혈액종양내과
482011

제1저자 차병효 · 교신저자 이상협

, , , , , ,
Pre-operative factors that can predict neoplastic polypoid lesions of the gallbladder.
World J Gastroenterol. 2011;17(17):2216-22.

Abstract
AIM To investigate the preoperative factors that can predict neoplastic polypoid lesions of the gallbladder (PLGs) as well as malignant PLGs.
METHODS A retrospective analysis was conducted on the 210 consecutively enrolled patients who underwent cholecystectomy due to a PLG larger than 10 mm, as was determined by preoperative trans-abdominal ultrasonography or endoscopic ultrasonography. We analyzed the medical, laboratory, radiologic data and the pathologic results.
RESULTS In 210 cases, 146 had non-neoplastic polyps (69.5%) and 64 cases were neoplastic polyps (30.5%). An older age (≥ 65 years), the presence of diabetes mellitus (DM) and the size of polyp (≥ 15 mm) were revealed to be independent predictive variables for neoplastic polyps with odd ratios (OR) of 2.27 (P = 0.044), 2.64 (P = 0.021) and 4.94 (P < 0.01), respectively. Among the neoplastic PLGs, an older age (≥ 65 years), the presence of DM and polyp size (≥ 15 mm) were associated with malignancy with ORs of 4.97 (P = 0.005), 6.13 (P = 0.001) and 20.55 (P < 0.001), respectively.
CONCLUSION Among patients with PLGs larger than 10 mm in size, higher risk groups such as elderly patients more than 65 years old, those with DM or a large polyp size (≥ 15 mm) should be managed by cholecystectomy.
PubMed IF 7.7 소화기내과
472011

제1저자 김유정 · 교신저자 김지현,김철호

, , , , , , ,
Comprehensive geriatric assessment in Korean elderly cancer patients receiving chemotherapy.
J Cancer Res Clin Oncol. 2011;137(5):839-47.

Abstract
BACKGROUND Growing evidence suggests that a comprehensive geriatric assessment (CGA) in older patients with cancer can detect unsuspected health problems, predict survival, and predict tolerance to chemotherapy. However, studies regarding CGA in cancer patients are scarce in Asia.
METHODS We prospectively enrolled 65 elderly cancer patients who were candidates of systemic chemotherapy between July 2006 and March 2008. Baseline CGA data including demographic information, comorbidity, functional status by means of Activities of Daily Living (ADL), and Instrumental Activities of Daily Living (IADL), cognition, psychological state, nutritional status, and medication were collected and analyzed. Quality of life (QoL) was assessed by the EORTC questionnaire QLQ-C30.
RESULTS Of the 65 patients, the median age was 71 years (range, 65-80), 49 (75%) were males, and 58 (89%) had Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1. All patients had solid tumor, 74% received palliative chemotherapy, and 18% received adjuvant chemotherapy. Twenty-five percent of patients had Charlson's comorbidity index score of 2 or more, 23% were ADL dependent, and 14% were IADL dependent. Using Mini-Mental Status Exam (MMSE), it was found that 51% of patients had mild cognitive impairment (MMSE score 17-24), and 5% had cognitive impairment (≤ 16). Forty percent of patients had depression by Short form Geriatric Depression Scale (SGDS), 19% had malnutrition by Mini-Nutritional Assessment (MNA), and 23% had body mass index (BMI) less than 19.4 kg/m(2) (lowest 10%). Global health status/quality of life (QoL) was less than 50% in 39% of patients. Frail patients according to the Balducci classification had significantly poor ECOG PS and worse global health status/QoL.
CONCLUSION CGA was feasible and could detect multiple unsuspected health problems including functional impairment and malnutrition in Korean elderly cancer patients receiving chemotherapy.
PubMed IF 3.3 혈액종양내과
462011

제1저자 신철민 · 교신저자 김나영

, , , , , ,
Intrafamilial aggregation of gastric cancer: a comprehensive approach including environmental factors, Helicobacter pylori virulence, and genetic susceptibility.
Eur J Gastroenterol Hepatol. 2011;23(5):411-7.

Abstract
BACKGROUND Familial clustering has been reported in gastric cancer (GC). However, the mechanism of the intrafamilial aggregation of GC remains unclear.
METHODS This study enrolled 123 GC relatives and their age-matched and sex-matched controls without a family history of GC, and 639 patients with GC (intestinal or diffuse type). Residence during childhood, socioeconomic status, and smoking habits were investigated as environmental factors, Helicobacter pylori (H. pylori) virulence factors (cagA, vagA s1 and m1 regions, and oipA) were evaluated, and seven biallelic polymorphisms (IL-1B-511, TNF-A-308, IL-6-572, IL-8-251, IL-10-592, IL-10-1082, and TGFB1-509) and IL-1RN variable number of tandem repeats were genotyped.
RESULTS For the group without GC, intestinal metaplasia (IM) at corpus was more prevalent in GC relatives than in controls in the age of less than 50 years [grade of IM (mean±standard deviation), 0.02±0.15 in controls vs. 0.22±0.56 in GC relatives, P=0.018]. cagA, vagA s1 and m1, and oipA positives showed an increase in GC relatives among current H. pylori-infected patients, which did not reach a statistical significance. Among intestinal-type GC patients, multivariate analyses showed that residence in a rural area during childhood (odds ratio: 2.03; 95% confidence interval: 1.05-3.95) and TGFB1-509 T (odds ratio: 0.47; 95% confidence interval: 0.26-0.88) were associated with a positive family history of GC; however, it showed only insignificant results in diffuse-type GC.
CONCLUSION The intrafamilial aggregation of GC might be associated with environmental factors during childhood or TGFB1-509 genetic polymorphism, or possibly H. pylori virulence. These factors may promote IM and development of intestinal-type GC.
PubMed IF 2.1 소화기내과
452011

제1저자 강정묵 · 교신저자 김나영

, , , , , , , ,
CDX1 and CDX2 expression in intestinal metaplasia, dysplasia and gastric cancer.
J Korean Med Sci. 2011;26(5):647-53.

Abstract
Intestinal metaplasia (IM) has been regarded as a premalignant condition. However, the pathogenesis of IM is not fully understood. The aim of this study was to evaluate the role of CDX1 and CDX2 in the formation of IM and the progression to dysplasia and gastric cancer (GC). A total of 270 subjects included 90 with GC, dysplasia and age- and sex-matched controls. Real-time PCR (RT-PCR) was performed with body specimens for CDX1 and CDX2. The expression of CDX2 was significantly higher in H. pylori positive group than H. pylori negative group (P = 0.045). CDX1 and CDX2 expression increased proportional to the IM grade of the body (P < 0.001). CDX2 expression was significantly higher in incomplete type of IM than in complete type (P = 0.045). The expression of CDX1 in dysplasia group was significantly higher than in the control group (P = 0.001); in addition, CDX1 and CDX2 in cancer group was significantly higher than control group (P < 0.001, and P < 0.001, respectively). Aberrant expression of CDX1 and CDX2 correlated with H. pylori infection and grade of IM in the body. Furthermore, the results suggest that CDX1 and CDX2 play a role in the progression to GC and dysplasia.
PubMed IF 3.2 소화기내과
442011

제1저자 김광일 · 교신저자 김철호, 오병희

, , , , , ,
Is reduced bone mineral density independently associated with coronary artery calcification in subjects older than 50 years?
J Bone Miner Metab. 2011;29(3):369-76.

Abstract
It has not been clearly defined whether reduced bone mineral density (BMD) is a direct risk factor of vascular calcification. A total of 2,160 subjects who were older than 50 years and underwent routine health examination at the Seoul National University Hospital Healthcare System Gangnam Center were included in this study. Coronary artery calcium scores (CACS) were calculated to quantify the extent of coronary artery calcification (CAC) using computed tomography. Bone dual-energy X-ray absorptiometry was also performed in all the subjects. BMD was classified as normal, osteopenia, or osteoporosis according to the lowest T score in the lumbar spine, femoral neck, or total hip. The mean value of CACS was 66.1 ± 234.0, and 1,372 subjects (63.5%) showed no coronary artery calcium deposits. A gender difference in the association between BMD and CACS was observed; a significant relationship was identified only in women. Unadjusted odds ratio for the presence of CAC in female subjects with reduced BMD was 1.925 (95% CI 1.383-2.679, p < 0.001). However, after adjusting for age and other risk factors, the association was no longer significant. Age, hypertension, glucose, and male gender were independent factors determining CAC in multiple regression analysis. Although reduced BMD and CAC were common findings among the elderly, the close association between them diminished after considering other factors affecting CAC.
PubMed IF 2.9 순환기내과
432011

제1저자 김경원 · 교신저자 박영주

, , , , , , , ,
Elevated risk of papillary thyroid cancer in Korean patients with Hashimoto's thyroiditis.
Head Neck. 2011;33(5):691-5.

Abstract
BACKGROUND Hashimoto's thyroiditis (HT) and higher levels of thyroid-stimulating hormone (TSH) have been proposed as risk factors for papillary thyroid cancer (PTC), but this issue is still being debated. The purpose of this study was whether HT was related to the risk of PTC over TSH.
METHODS We enrolled 1329 patients (1028 with PTC, 52 with follicular thyroid cancer, and 249 with benign disease) of 1490 patients who underwent thyroidectomy.
RESULTS The TSH concentration was not different among patients with PTC or benign disease. Our study showed that men (odds ratio [OR] = 1.54; p = .049) and the presence of HT (OR = 2.96; p <.001) increased the risk of PTC. Moreover, HT was associated with multifocal cancer (p = .005) and smaller tumor size (p = .031), but it did not influence the extrathyroidal invasion or nodal metastasis.
CONCLUSION Clinicians who deal with thyroid nodules should pay particular attention to HT because it is a stronger predictor for PTC than other risk factors.
PubMed IF 2.2 내분비대사내과
422011

제1저자 장혜정 · 교신저자 김태유

, , , , , , , , ,
Discordant human epidermal growth factor receptor 2 and hormone receptor status in primary and metastatic breast cancer and response to trastuzumab.
Jpn J Clin Oncol. 2011;41(5):593-9.

Abstract
BACKGROUND Recent studies have shown that the human epidermal growth factor receptor 2 status of a metastatic site may differ from that of the primary site. This difference may influence patient prognosis and response to therapy.
METHODS We conducted a retrospective study using immunohistochemistry and/or fluorescent in situ hybridization to compare human epidermal growth factor receptor 2 and hormone receptor status in primary and metastatic breast cancers.
RESULTS Fifty-six patients were included in this study. Conversion from hormone receptor positive in the primary tumor to hormone receptor negative in the metastasis occurred in 12 patients (21.4%), and hormone receptor negative to hormone receptor positive conversion occurred in two patients (3.6%). Human epidermal growth factor receptor 2 status was discordant between primary and metastatic lesions in seven patients (12.5%). All of the five patients who converted from human epidermal growth factor receptor 2 negative status to human epidermal growth factor receptor positive received trastuzumab-based chemotherapy. Overall response rate and median progression-free survival for concordant human epidermal growth factor receptor 2 positive patients were 69.2% and 16.9 months, whereas that of patients with positive conversion of human epidermal growth factor receptor 2 were 40.0% and 7.6 months, respectively (overall response rate; P = 0.169 and progression-free survival; P = 0.004).
CONCLUSION Discordance in human epidermal growth factor receptor 2 and hormone receptor status between primary and metastatic tumors was observed, which led to altered treatment decisions. Evaluation of human epidermal growth factor receptor 2 and hormone receptor in metastatic tumors should be considered in patients with breast cancer.
PubMed IF 2.5 혈액종양내과
412011

제1저자 최민호, 장윤석 · 교신저자 조상헌

, , , , , , , , , , , , ,
Clonorchis sinensis infection is positively associated with atopy in endemic area.
Clin Exp Allergy. 2011;41(5):697-705.

Abstract
BACKGROUND Epidemiologic studies have suggested that helminth infections play a protective role against allergy; this inverse association, however, has not been consistent. Clonorchis sinensis, the liver fluke of human, is prevalent in the Far East. The association between C. sinensis infection and allergy has not yet been reported.
OBJECTIVE We evaluated the association between clonorchiasis and atopy or allergic diseases in adults in endemic areas of clonorchiasis.
METHODS A total of 1116 subjects (males 419, females 697; age range, 30-86; mean age=61 years) were recruited from two endemic areas of C. sinensis in Korea. Clonorchiasis was confirmed by stool examination. Allergic symptoms were evaluated with a modified ISAAC questionnaire, and atopy was defined by skin prick test for common inhalant allergens. Total serum IgE and C. sinensis-specific IgE level was measured by ELISA and methacholine bronchial provocation test was performed to evaluate airway hyperresponsiveness (AHR).
RESULTS Clonorchiasis was positively associated with atopy [odds ratio (OR), 1.856; 95% confidence interval (CI), 1.199-2.873] and high levels of total serum IgE (OR, 1.455; 95% CI, 1.050-2.016). Higher association with clonorchiasis was shown in subjects who showed both atopy and high total serum IgE levels (OR, 2.540; 95% CI, 1.448-4.455). Clonorchiasis had no association with wheezing, AHR, asthma or allergic rhinitis.
CONCLUSION AND CLINICAL RELEVANCE Clonorchiasis was positively associated with atopy in adults in endemic area.
PubMed IF 5 알레르기내과
402011

제1저자 고영일 · 교신저자 김동완

, , , , , , , , ,
Clinicopathologic characteristics and outcomes of patients with anaplastic lymphoma kinase-positive advanced pulmonary adenocarcinoma: suggestion for an effective screening strategy for these tumors.
J Thorac Oncol. 2011;6(5):905-12.

Abstract
INTRODUCTION The purpose of this study was to analyze the clinicopathologic characteristics and outcomes of patients with anaplastic lymphoma kinase (ALK)-positive advanced pulmonary adenocarcinoma and to devise an effective screening strategy to identify such patients.
METHODS We screened advanced pulmonary adenocarcinoma patients to identify ALK-positive cases. The presence of ALK rearrangements was confirmed by fluorescence in situ hybridization.
RESULTS Of the 221 screened patients, 45 demonstrated ALK rearrangements, and these individuals were younger than the ALK-negative patients (p < 0.001). The proportion of never smokers and light smokers was found not to differ according to the ALK status (p = 0.537). Epidermal growth factor receptor (EGFR) mutations and ALK rearrangements were found to be mutually exclusive. Thyroid-transcription factor-1 (TTF-1) expression was observed in all ALK-positive tumors for which immunohistochemistry data were available. The objective response rate and progression-free survival to first-line platinum-based chemotherapy showed no significant differences between ALK-positive and ALK-negative patients. On the other hand, no patient with ALK-positive tumors achieved objective tumor responses to EGFR tyrosine kinase inhibitors (TKIs). ALK rearrangements were not found among individuals who had EGFR mutations, an objective response to a previous EGFR TKI treatment or TTF-1-negative tumors.
CONCLUSION The clinical outcomes of platinum-based chemotherapy were found not to differ according to the ALK status. Both smokers and never/light smokers should be candidates for ALK screening. We suggest that the exclusion of patients with activating EGFR mutations, an objective response to previous EGFR TKIs, or TTF-1-negative tumors from ALK screening could be an effective enrichment strategy for ALK-positive cases.
PubMed IF 23.3 혈액종양내과
392011

제1저자 최성희, 이용호 · 교신저자 김대중

, , ,
Apolipoprotein B/A1 ratio is associated with free androgen index and visceral adiposity and may be an indicator of metabolic syndrome in male children and adolescents.
Clin Endocrinol (Oxf). 2011;74(5):579-86.

Abstract
OBJECTIVE A high apolipoprotein B/apolipoprotein A1 (apoB/A1) ratio is strongly associated with cardiometabolic diseases. However, few studies have examined this ratio in children and adolescents. The aim of our study was to determine significant factors related to the apoB/A1 ratio and examine its association with paediatric metabolic syndrome.
PATIENTS AND METHODS Sixty-seven male children and adolescents were recruited. We measured anthropometric parameters, fat areas by abdominal computed tomography, fasting glucose, insulin, lipid profiles, apoB, apoA1, adiponectin, free androgen index (FAI) and oestradiol.
RESULTS Thirty per cent of participants (n = 20) were identified as having paediatric metabolic syndrome. The apoB/A1 ratio was significantly correlated with BMI z-score, waist circumference, waist-to-hip ratio (WHR), waist-to-height ratio, abdominal fat areas, total cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol, adiponectin and leptin. In addition to lipid profiles, WHR was identified as a significant independent variable correlated with the apoB/A1 ratio. Obese boys with a high FAI (>75th percentile) had significantly lower adiponectin and higher apoB/A1 ratios than those with a low FAI. The apoB/A1 ratio was higher in subjects with high visceral fat (>50th percentile) and a high FAI when compared with subjects with low visceral fat and a low FAI. The prevalence of paediatric metabolic syndrome was significantly associated with increasing tertiles of the apoB/A1 ratio (highest tertile; odds ratio = 18·8 [95% confidence interval = 1·8-198·8], P < 0·05).
CONCLUSION ApoB/A1 ratio was significantly higher in viscerally obese male children and adolescents with high levels of FAI and was associated with increased frequency of paediatric metabolic syndrome.
PubMed IF 2.8 내분비대사내과
382011

제1저자 김선문 · 교신저자 임춘수

, , , , , ,
The effects of oral iron supplementation on the progression of anemia and renal dysfunction in patients with chronic kidney disease.
Clin Nephrol. 2011;75(5):472-9.

Abstract
AIMS Oral iron traditionally has been administered to patients with chronic kidney disease (CKD). However, there are limited data on the effect of oral iron in CKD patients. Here, we evaluate the effects of oral iron therapy on renal anemia and progression of renal disease in CKD patients.
METHODS Anemic patients with nondialytic CKD who were naive to erythropoiesis-stimulating agents (ESAs) were recruited for the prospective observational study. The participants were classified into oral iron or control group, and they were asked to keep their treatment status for 1 year. The primary outcomes were change in Hb and estimated glomerular filtration rate (eGFR).
RESULTS A total of 182 participants were enrolled and 138 completed a 12-month follow-up. No change in Hb level was observed during the follow-up period in the iron group, whereas a significant decrease in Hb was observed in the control group. Oral iron supplementation was effective, especially in patients with eGFR < 30 ml/min/1.73 m2. The changes in eGFR did not differ between the two groups. The incidences of drug-related adverse events were equivalent in two groups.
CONCLUSIONS Oral iron supplementation might attenuate the progression of anemia in nondialytic CKD patients without ESAs and not impact kidney function.
PubMed IF 0.8 신장내과
372011

제1저자 임수, 문민경 · 교신저자 박경수

, , , , , , , , , , , , ,
Effect of S-adenosylmethionine on neointimal formation after balloon injury in obese diabetic rats.
Cardiovasc Res. 2011;90(2):383-93.

Abstract
AIMS The association between hyperhomocysteinaemia and cardiovascular disease has been attributed to low levels of S-adenosylmethionine (SAM), a metabolic intermediate of homocysteine. However, the role of SAM in the development of restenosis has not been explored. Therefore, we investigated the effects of SAM on neointimal formation after balloon injury in obese diabetic rats and cultured cells.
METHODS AND RESULTS Otsuka Long-Evans Tokushima fatty rats were divided into the following three groups: control (normal saline); SAM15; and SAM30 (15 and 30 mg/kg per day, respectively; n = 10 per group). SAM was administered orally from 1 week before carotid injury to 2 weeks thereafter. SAM treatment for 3 weeks caused a significant dose-dependent reduction in the intima-to-media ratio. SAM treatment significantly reduced the proliferation of vascular smooth muscle cells (VSMCs) and induced more apoptosis than was observed in the control group. This effect was accompanied by reduced circulating levels of high-sensitivity C-reactive protein and monocyte chemoattractant protein-1, reduced urine 8-hydroxy-2'-deoxyguanosine (8-OHdG), and increased adiponectin. Intima-to-media ratio correlated significantly with the levels of inflammatory markers, adiponectin, and 8-OHdG. In vitro experiments demonstrated that VSMC proliferation and migration and the adhesion of monocytes decreased in response to SAM. SAM treatment also reduced tumour necrosis factor-α-induced reactive oxygen species and tunicamycin-induced GRP78 expression in VSMCs.
CONCLUSION These findings suggest that SAM exerts protective effects against restenosis after balloon injury in a rat model of type 2 diabetes by reducing the proliferation and inducing the apoptosis of VSMCs, modifying the inflammatory processes and reducing oxidative and endoplasmic reticulum stresses.
PubMed IF 12.5 내분비대사내과
362011

제1저자 이윤규 · 교신저자 김인호

, , , , , , , , , , , , , , , ,
Impact of cytokine gene polymorphisms on risk and treatment outcomes of aplastic anemia.
Ann Hematol. 2011;90(5):515-21.

Abstract
Autoreactive cytotoxic T cells play a key role in the pathogenesis of aplastic anemia (AA) by myelosuppressive cytokines including interferon-gamma, tumor necrosis factor alpha, and transforming growth factor beta. The purpose of this study is to determine which single nucleotide polymorphisms (SNPs) in cytokine genes were relevant to AA risk and whether the relevant SNPs were associated with response to immunosuppressive therapy (IST). Among 84 screened patients, 80 patients confirmed as having acquired AA, and 84 age- and sex-matched healthy controls were analyzed consecutively. We genotyped ten polymorphisms in three cytokine genes (IFNG, TNF, and TGFB1) and FAS gene. We assessed the association between polymorphisms and AA risk, and the association between polymorphisms and response to IST in three genetic models (dominant, recessive, and additive). The IFNG -2,353 T allele (dominant model, OR = 0.43, p = .012) and TCA haplotype (dominant model, OR = 0.50, p = .038) were significantly associated with the development of AA. In addition, this relevant IFNG -2,353 T allele and TCA haplotype were related to the response of IST (dominant model, OR = 0.076, p = .034). Concerning TGFB1, although its polymorphisms are not related to AA susceptibility, P10L T allele (recessive model, OR = 0.18, p = .038) and CT haplotype (dominant model, OR = 5.68, p = .038) were associated with response to IST. This exploratory study concurred with prior studies indicating that polymorphisms in IFNG are related to AA susceptibility. In addition, it was found that polymorphisms in IFNG and TGFB1 are associated with response to IST.
PubMed IF 2.3 혈액종양내과
352011

제1저자 박경우 · 교신저자 김효수

, , , , , , , , , , , , , , ,
High plasma interleukin-6 is associated with drug-eluting stent thrombosis: possible role of inflammatory cytokines in the development of stent thrombosis from the Korea Stent Thrombosis Registry.
Circ J. 2011;75(6):1350-7.

Abstract
BACKGROUND Inflammation might contribute to the development of stent thrombosis (ST). The association between inflammatory cytokine concentrations and drug-eluting ST were evaluated.
METHODS AND RESULTS Among the 123 ST patients enrolled in the multicenter Korea Stent Thrombosis registry, plasma samples were available in 41 patients. The patients' clinical characteristics and plasma concentrations of monocyte chemoattractant protein-1, tumor necrosis factor-alpha, and interleukin (IL)-6 were compared with 81 matched controls. Although the concentrations of 3 cytokines were higher in the ST group, they did not have significant differences. When divided into quartiles, the proportion of patients with the highest quartile of IL-6 was higher in the ST group than in the control group (44% vs. 16%, P = 0.001), and the highest IL-6 quartile was an independent predictor of ST for both early (adjusted hazard ratio [HR] 6.96; 95% confidence interval [CI] 1.75-27.66) and late ST (adjusted HR 4.71; 95%CI 1.06-20.92). In addition, the highest IL-6 quartile was an independent predictor of ST in those on clopidogrel (adjusted HR 7.70; 95%CI 1.97-30.13) but not in those who were off clopidogrel.
CONCLUSIONS Highest IL-6 quartile was associated with ST, especially in clopidogrel users regardless of the time of ST, suggesting the involvement of inflammatory cytokines in ST.
PubMed IF 5.8 순환기내과
342011

제1저자 김혜정 · 교신저자 이재호

, , , ,
The impact of previous tuberculosis history on T-SPOT.TB® interferon-gamma release assay results.
Int J Tuberc Lung Dis. 2011;15(4):510-6.

Abstract
SETTING Seoul National University Bundang Hospital, a tertiary referral hospital in Korea.
OBJECTIVE To evaluate whether previous tuberculosis (TB) history has a long-term effect on T-SPOT.TB® results after anti-tuberculosis treatment.
DESIGN We retrospectively reviewed 489 adults (age ≥18 years) who underwent T-SPOT.TB as part of their evaluation between January 2008 and July 2009.
RESULTS Among 489 subjects analysed, 369 were finally included. Active TB was diagnosed in 121/369 (32.8%). T-SPOT.TB was positive in 110 (90.9%) active TB patients. Of the 248 subjects without active TB, T-SPOT.TB positivity was significantly different between the 51 patients with a previous TB history and the 197 without (84.3% vs. 26.9%, P < 0.001). The difference in T-SPOT.TB positivity between the 51 non-active TB patients with a TB history and the 121 active TB patients was not statistically significant (84.3% vs. 90.9%, P = 0.208). Among the 51 non-active TB individuals with a TB history, the mean time since anti-tuberculosis treatment was 22.7 years (range 1-59); this had no correlation with total region of difference 1 (RD1) spot-forming cells (r = -0.076, P = 0.597).
CONCLUSION T-SPOT.TB has a limited role in the diagnosis of TB infection in individuals with a previous history of TB.
PubMed IF 3.6 호흡기내과
332011

제1저자 박종선 · 교신저자 김덕겸

, , , , , , , , ,
Impact of antibiotic prophylaxis on postbronchoscopy fever: a randomised controlled study.
Int J Tuberc Lung Dis. 2011;15(4):528-35.

Abstract
BACKGROUND Postbronchoscopy fever can develop in 5-16% of adult patients. The microbiological contribution to postbronchoscopy fever is unclear.
OBJECTIVE To elucidate the effect of prophylactic antibiotics on the development of postbronchoscopy fever and pneumonia.
DESIGN Study patients were randomised to receive no treatment or oral amoxicillin/clavulanate 30 min before flexible bronchoscopy. The primary outcome variable was the frequency of postbronchoscopy fever and pneumonia. White blood cell counts, C-reactive protein and the serum pyrogenic cytokines interleukin (IL) 1β, IL-6 and tumour necrosis factor-alpha were measured before and after bronchoscopy.
RESULTS Of 143 subjects enrolled in the study, the final analysis was performed among 67 subjects in the prophylaxis group and 64 in the control group. The frequency of postbronchoscopy fever did not differ between the groups (25.4% for the prophylaxis group vs. 26.6% for controls, P > 0.05). Pneumonia developed in 1.5% of the prophylaxis group and 4.7% of the controls. There was no bacteraemia in either group. Serum pyrogenic cytokines did not differ between the groups.
CONCLUSIONS Prophylactic antibiotics before bronchoscopy did not reduce the frequency of postbronchoscopy fever and did not affect serum levels of pyrogenic cytokines. These findings suggest that microbiological factors may not be responsible for the development of postbronchoscopy fever.
PubMed IF 3.6 호흡기내과
322011

제1저자 김지원 · 교신저자 오도연

, , , , , ,
Clinical outcomes of sorafenib treatment in patients with metastatic hepatocellular carcinoma who had been previously treated with fluoropyrimidine plus platinum-based chemotherapy.
Am J Clin Oncol. 2011;34(2):125-9.

Abstract
OBJECTIVES There has been no report on sorafenib therapy in patients with metastatic hepatocellular carcinoma (HCC) who had been treated with systemic chemotherapy. The objectives of this analysis were to investigate efficacy and safety of sorafenib in these patients and to elucidate risk factors associated with clinical outcomes.
METHODS We analyzed patients with metastatic HCC who were treated with sorafenib after failure of fluoropyrimidine plus platinum-based chemotherapy between April 2007 and December 2008.
RESULTS Twenty-four patients (male, 79.2%) were included. Median age was 53 years. Chronic hepatitis B was the predominant cause of HCC (79.2%), followed by chronic hepatitis C (4.2%) and alcohol (4.2%). Twenty patients (83.3%) were Child-Pugh A and 4 patients (16.7%) were Child-Pugh B. Median follow-up duration was 11.1 months. No objective response was observed. Fourteen patients (58.3%) had stable disease. The disease control rate was 58.3%. Median progression-free survival was 2.3 months (95% confidence interval, 0.5-4.1) and overall survival was 7.1 months (95% confidence interval, 3.5-10.7). Grade 3 neutropenia was observed in 1.4% and grade 3 anemia in 1.4%. Grade 3 or 4 nonhematologic toxicities were hand-foot syndrome (16.7%), skin rash (8.3%), diarrhea (4.2%), headache (4.2%), and fatigue (4.2%). Four patients (16.7%) discontinued the therapy because of toxicities.
CONCLUSIONS Sorafenib had modest efficacy and tolerable toxicity in patients with metastatic HCC who had received fluoropyrimidine plus platinum-based chemotherapy.
PubMed IF 1.8 혈액종양내과
312011

제1저자 임수 · 교신저자 고광곤

, ,
Prevention of atherosclerosis in overweight/obese patients. - In need of novel multi-targeted approaches-.
Circ J. 2011;75(5):1019-27.

Abstract
Obesity has reached epidemic proportions and complications related to obesity contribute substantially to both healthcare costs and mortality. Obesity, particularly when accompanied by an excess of visceral/ectopic fat, is a major risk factor for diseases ranging from insulin resistance, type 2 diabetes, nonalcoholic fatty liver disease, and cardiovascular disease. The epidemic proportions reached by obesity has made these conditions a global problem in human health. Accordingly, preventive and/or therapeutic interventions should be considered in obese patients. Regular physical activity/exercise has numerous beneficial effects on the cardiometabolic risk profile and on the cardiovascular system. However, our current clinical environment is not designed to provide the regular support needed by patients to help them maintain over the long term their improved physical activity/nutritional habits. Because hypertension, dyslipidemia, hyperinsulinemia, and excess visceral adipose tissue are linked by complex reciprocal molecular interactions, it is logical to expect that targeting an interconnected pathway may provide multiple benefits. At this stage, combined therapy of statins or PPAR agonists and renin-angiotensin-aldosterone system blockers to target multiple therapeutic pathways may optimally improve the cardiometabolic risk profile through both distinct and interrelated mechanisms. In the present article, we will discuss updated novel approaches, including potential multi-targeted intervention strategies, based on underlying pathophysiological processes.
PubMed IF 5.8 내분비대사내과
302011

제1저자 강은하 · 교신저자 송영욱

, , , , , , , , ,
Associations between the HLA-A polymorphism and the clinical manifestations of Behcet's disease.
Arthritis Res Ther. 2011;13(2):R49.

Abstract
INTRODUCTION The objective was to investigate associations between the HLA-A gene and Behcet's disease (BD) and its clinical manifestations.
METHODS Genotyping for the HLA-A locus was performed using the polymerase chain reaction-Luminex typing method in 223 BD patients and 1,398 healthy controls.
RESULTS The phenotypic frequencies of HLA-A*02:07 (odds ratio (OR) = 2.03, P = 0.002), A*26:01 (OR = 1.85, P = 0.008), and A*30:04 (OR = 2.51, P = 0.006) tended to be higher in BD patients than in normal controls, but the frequency of A*33:03 (OR = 0.59, P = 0.003) tended to be lower in BD patients. A meta-analysis adopting our and the Japanese data confirmed the associations of HLA-A*02:07, A*26:01, and A*33:03 with BD. Furthermore, the frequencies of the HLA-A*02:07, A*26:01, and A*30:04 were significantly higher in patients with skin lesions (OR = 2.37, P < 0.0005, Pc < 0.012) and arthritis (OR = 2.32, P = 0.002, Pc = 0.048), with uveitis (OR = 3.01, P < 0.0005, Pc < 0.012), and with vascular lesions (OR = 9.80, P < 0.0005, Pc < 0.012) and a positive pathergy test (OR = 4.10, P = 0.002, Pc = 0.048), respectively, than in controls. In HLA-B*51 non-carriers, these associations were also significant, being much stronger between HLA-A*26:01 and uveitis (OR = 4.19, P < 0.0005, Pc < 0.012) and between HLA-A*30:04 and vascular lesions (OR = 13.97, P < 0.00005, Pc < 0.0012). In addition, HLA-A*30:04 was associated with genital ulcers in HLA-B*51 non-carriers (OR = 3.89, P = 0.002, Pc = 0.048).
CONCLUSIONS HLA-A*02:07, A*26:01, and A*30:04 were associated with increased risk for BD, while HLA-A*33:03 with decreased risk. HLA-A*02:07, A*26:01, and A*30:04 were associated with skin lesions and arthritis, with uveitis, and with vascular lesions, genital ulcers, and a positive pathergy test, respectively.
PubMed IF 5.4 류마티스내과
292011

제1저자 김소연 · 교신저자 허대석

, ,
PPARγ ligands induce growth inhibition and apoptosis through p63 and p73 in human ovarian cancer cells.
Biochem Biophys Res Commun. 2011;406(3):389-95.

Abstract
Peroxisome proliferator-activated receptor gamma (PPARγ) agonists, including thiazolidinediones (TZDs), can induce anti-proliferation, differentiation, and apoptosis in various cancer cell types. This study investigated the mechanism of the anticancer effect of TZDs on human ovarian cancer. Six human ovarian cancer cell lines (NIH:OVCAR3, SKOV3, SNU-251, SNU-8, SNU-840, and 2774) were treated with the TZD, which induced dose-dependent inhibition of cell growth. Additionally, these cell lines exhibited various expression levels of PPARγ protein as revealed by Western blotting. Flow cytometry showed that the cell cycle was arrested at the G1 phase, as demonstrated by the appearance of a sub-G1 peak. This observation was corroborated by the finding of increased levels of Bax, p21, PARP, and cleaved caspase 3 in TGZ-treated cells. Interestingly, when we determined the effect of p53-induced growth inhibition in these three human ovarian cancer cells, we found that they either lacked p53 or contained a mutant form of p53. Furthermore, TGZ induced the expression of endogenous or exogenous p63 and p73 proteins and p63- or p73-directed short hairpin (si) RNAs inhibited the ability of TGZ to regulate expression of p21 in these cells. Thus, our results suggest that PPARγ ligands can induce growth suppression of ovarian cancer cells and mediate p63 and p73 expression, leading to enhanced growth inhibition and apoptosis. The tumor suppressive effects of PPARγ ligands may have applications for the treatment of ovarian cancer.
PubMed IF 2.5 혈액종양내과
282011

제1저자 윤원재 · 교신저자 류지곤

, , , , ,
Clinical features of metastatic tumors of the pancreas in Korea: a single-center study.
Gut Liver. 2011;5(1):61-4.

Abstract
BACKGROUND/AIMS The purpose of this study was to examine the clinical features of metastatic tumors of the pancreas (MTPs) in Korea.
METHODS A total of 53 cases (31 males) of pathologically proven MTPs were collected. Clinicopathological characteristics and patient outcomes were evaluated.
RESULTS The median age at the diagnosis of the MTP was 60 years. The median interval between the diagnoses of primary malignancy and MTP was 2.2 years. Primary malignancies were renal cell carcinoma (RCC) (n=14), gastric cancer (n=11), colorectal cancer (n=5), lymphoma (n=4), non-small cell lung cancer (n=3), gastrointestinal stromal tumor (n=2), melanoma (n=2), small cell lung cancer (n=2), gallbladder cancer (n=2), hepatocellular carcinoma (n=1), thymic carcinoid (n=1), liposarcoma (n=1), cholangiocarcinoma (n=1), osteosarcoma (n=1), breast cancer (n=1), duodenal cancer (n=1), and ovarian cancer (n=1). The median survival after the diagnosis of MTP was 23.1 months. Multivariate analysis showed that prolonged survival was associated with RCC as the primary malignancy, the patient being asymptomatic upon the diagnosis of MTP, the absence of extrapancreatic involvement, and surgery included in the treatment.
CONCLUSIONS MTPs can occur after a prolonged period from the primary diagnosis. RCC as the primary malignancy, the patient being asymptomatic upon the diagnosis of MTP, the absence of extrapancreatic involvement, and surgery included in the treatment are associated with better prognosis.
PubMed IF 4.1 소화기내과

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