SCI 발표논문

1. 1692012

   제1저자 김보현, 이연재 · 교신저자 김원

   Kim BH, Lee YJ, Kim W, Yoon JH, Jung EU, Park SJ, Kim YJ, Lee HS

   Efficacy of thymosin α-1 plus peginterferon α-2a combination therapy compared with peginterferon α-2a monotherapy in HBeAg-positive chronic hepatitis B: a prospective, multicenter, randomized, open-label study.

   Scand J Gastroenterol. 2012;47(8-9):1048-55.

   Abstract

   OBJECTIVE Thymosin α-1 plus interferon α-2a offers superior efficacy over interferon α-2a alone in patients with chronic hepatitis B. The aim was to compare the antiviral efficacy of thymosin α-1 plus peginterferon α-2a and peginterferon α-2a alone in HBeAg-positive chronic hepatitis B patients.

   MATERIALS AND METHODS HBeAg-positive CHB patients were enrolled in this prospective, randomized, open-label study. Fifty-one patients were assigned to either combination (26 patients; 180 μg of peginterferon α-2a weekly for 48 weeks and 1.6 mg of thymosin α-1 twice a week for the first 12 weeks) or monotherapy (25 patients; 180 μg of peginterferon α-2a weekly for 48 weeks) groups.

   RESULTS The rates of the combined response, defined as HBeAg seroconversion, HBV DNA suppression, and normalization of serum ALT, were 4/26 (15.4%) and 3/25 (12.0%) for the combination group and the monotherapy group at the end of treatment (p = 0.725), and 6/26 (23.1%) and 5/25 (20.0%) at the end of follow-up (p = 0.789), respectively. Based on multiple logistic regression analysis, a >2 log₁₀ IU/mL reduction of HBV DNA at week 12 was identified as an independent predictor for combined response (OR, 9.72; 95% CI, 1.33-71.06; p = 0.025) at the end of follow-up. A lower pretreatment HBV DNA level (≤ 7 log(10) IU/mL) was another predictor for combined response (OR, 9.64; 95% CI, 1.23-75.32; p = 0.031). No significant differences in adverse events were observed.

   CONCLUSIONS The short-term addition of thymosin α-1 was not superior to peginterferon α-2a alone in HBeAg-positive CHB patients on the basis of antiviral efficacy.

   PubMed IF 1.8 소화기내과
2. 1682012

   제1저자 박경우 · 교신저자 김효수

   Park KW, Kang J, Park JJ, Yang HM, Lee HY, Kang HJ, Koo BK, Oh BH, Park YB, Kim HS

   Amlodipine, clopidogrel and CYP3A5 genetic variability: effects on platelet reactivity and clinical outcomes after percutaneous coronary intervention.

   Heart. 2012;98(18):1366-72.

   Abstract

   OBJECTIVE To test the effect of a loss-of-function variation of the cytochrome P450 (CYP) 3A5 on drug-drug interaction between amlodipine and clopidogrel. Amlodipine is a well-known inhibitor of CYP 3A4, an isoenzyme of CYP3A that activates clopidogrel. However, controversy exists regarding whether amlodipine adversely affects clopidogrel response and clinical outcome after percutaneous coronary intervention (PCI). In the presence of CYP3A4 inhibitors such as amlodipine, the genetic variation of CYP3A5, the isoenzyme responsible for the backup CYP3A activity, may play an important role in clopidogrel activation.

   DESIGN Post hoc analysis of a prospectively enrolled cohort.

   PATIENTS Patients enrolled in the CROSS-VERIFY cohort from June 2006 to June 2010, with successful genotyping of CYP3A5.

   MAIN OUTCOME MEASURES The pharmacodynamic analysis end point was clopidogrel on-treatment platelet reactivity (OPR) and the clinical analysis end point was the composite of cardiac death, non-fatal myocardial infarction, ischaemic stroke and stent thrombosis at 12 months post-PCI.

   RESULTS 1258 patients had successful genotyping and were categorised as CYP3A5 non-expressers (749 patients) and expressers (509 patients) according to the CYP3A5 genotype. Amlodipine users showed higher OPR versus non-users only in CYP3A5 non-expressers (249 ± 83 vs 228 ± 84 P2Y12 reaction units, p=0.013). These findings was corroborated by clinical outcomes, in which amlodipine users had a higher incidence of events compared with non-users only in CYP3A5 non-expressers (4.6% vs 0.6%, HR 7.731, CI 2.042 to 29.264, p=0.004).

   CONCLUSIONS Treatment with amlodipine is associated with increased clopidogrel OPR and increased risk of thrombotic events after PCI, which is dependent on the CYP3A5 genetic status.

   PubMed IF 4.4 순환기내과
3. 1672012

   제1저자 박영주, 이은경 · 교신저자 David D. Moore

   Park YJ, Lee EK, Lee YK, Park DJ, Jang HC, Moore DD

   Opposing regulation of cytochrome P450 expression by CAR and PXR in hypothyroid mice.

   Toxicol Appl Pharmacol. 2012;263(2):131-7.

   Abstract

   Clinical hypothyroidism affects various metabolic processes including drug metabolism. CYP2B and CYP3A are important cytochrome P450 drug metabolizing enzymes that are regulated by the xenobiotic receptors constitutive androstane receptor (CAR, NR1I3) and pregnane X receptor (PXR, NR1I2). We evaluated the regulation of the hepatic expression of CYPs by CAR and PXR in the hypothyroid state induced by a low-iodine diet containing 0.15% propylthiouracil. Expression of Cyp3a11 was suppressed in hypothyroid C57BL/6 wild type (WT) mice and a further decrement was observed in hypothyroid CAR-/- mice, but not in hypothyroid PXR-/- mice. In contrast, expression of Cyp2b10 was induced in both WT and PXR-/- hypothyroid mice, and this induction was abolished in CAR-/- mice and in and CAR-/- PXR-/- double knockouts. CAR mRNA expression was increased by hypothyroidism, while PXR expression remained unchanged. Carbamazepine (CBZ) is a commonly used antiepileptic that is metabolized by CYP3A isoforms. After CBZ treatment of normal chow fed mice, serum CBZ levels were highest in CAR-/- mice and lowest in WT and PXR-/- mice. Hypothyroid WT or PXR-/- mice survived chronic CBZ treatment, but all hypothyroid CAR-/- and CAR-/- PXR-/- mice died, with CAR-/-PXR-/- mice surviving longer than CAR-/- mice (12.3±3.3 days vs. 6.3±2.1 days, p=0.04). All these findings suggest that hypothyroid status affects xenobiotic metabolism, with opposing responses of CAR and PXR and their CYP targets that can cancel each other out, decreasing serious metabolic derangement in response to a xenobiotic challenge.

   PubMed IF 3.6 내분비대사내과
4. 1662012

   제1저자 이세원 · 교신저자 김효수

   Lee SW, Jeong HK, Lee JY, Yang J, Lee EJ, Kim SY, Youn SW, Lee J, Kim WJ, Kim KW, Lim JM, Park JW, Park YB, Kim HS

   Hypoxic priming of mESCs accelerates vascular-lineage differentiation through HIF1-mediated inverse regulation of Oct4 and VEGF.

   EMBO Mol Med. 2012;4(9):924-38.

   Abstract

   Hypoxic microenvironment plays an important role in determining stem cell fates. However, it is controversial to which direction between self-renewal and differentiation the hypoxia drives the stem cells. Here, we investigated whether a short exposure to hypoxia (termed 'hypoxic-priming') efficiently directed and promoted mouse embryonic stem cells (mESCs) to differentiate into vascular-lineage. During spontaneous differentiation of embryoid bodies (EBs), hypoxic region was observed inside EB spheroids even under normoxic conditions. Indeed, hypoxia-primed EBs more efficiently differentiated into cells of vascular-lineage, than normoxic EBs did. We found that hypoxia suppressed Oct4 expression via direct binding of HIF-1 to reverse hypoxia-responsive elements (rHREs) in the Oct4 promoter. Furthermore, vascular endothelial growth factor (VEGF) was highly upregulated in hypoxia-primed EBs, which differentiated towards endothelial cells in the absence of exogenous VEGF. Interestingly, this differentiation was abolished by the HIF-1 or VEGF blocking. In vivo transplantation of hypoxia-primed EBs into mice ischemic limb elicited enhanced vessel differentiation. Collectively, our findings identify that hypoxia enhanced ESC differentiation by HIF-1-mediated inverse regulation of Oct4 and VEGF, which is a novel pathway to promote vascular-lineage differentiation.

   PubMed IF 7.9 순환기내과
5. 1652012

   제1저자 방영주 · 교신저자 방영주

   Bang YJ

   Advances in the management of HER2-positive advanced gastric and gastroesophageal junction cancer.

   J Clin Gastroenterol. 2012;46(8):637-48.

   Abstract

   In the past, patients with advanced or metastatic gastric or gastroesophageal junction cancer have had few treatment options and generally poor survival rates. The human epidermal growth factor receptor 2 (HER2) has been identified as a potential therapeutic target because of its overexpression or gene amplification in 6% to 35% of gastric or gastroesophageal junction cancers, although the methods of assessment and prognostic value of HER2 have been subject to debate. The phase III Trastuzumab for Gastric Cancer (ToGA) trial showed that adding the HER2-targeted humanized monoclonal antibody trastuzumab to chemotherapy significantly improves survival without negatively impacting quality of life in patients with advanced gastric or gastroesophageal junction cancer. As a result, trastuzumab is now the sole HER2-targeted therapy approved in several countries for this indication. The ToGA trial also demonstrated that patients who expressed higher levels of HER2 (determined by immunohistochemical screening) received the greatest benefit from trastuzumab therapy. This finding underlines the importance of accurate HER2 testing. Because of the unique characteristics of gastric cancer, a new gastric cancer-specific scoring system for HER2 expression was proposed during the ToGA trial. The aim of this review is to inform the gastroenterologist of the potential role of HER2-targeted therapy, to discuss the importance of accurate and reliable HER2 testing, and to discuss ongoing studies with HER2-targeted therapies that may have an impact on the future treatment of HER2-positive gastric cancer.

   PubMed IF 2.7 혈액종양내과
6. 1642012

   제1저자 배현미 · 교신저자 이세훈

   Bae HM, Lee SH, Kim TM, Kim DW, Yang SC, Wu HG, Kim YW, Heo DS

   Prognostic factors for non-small cell lung cancer with bone metastasis at the time of diagnosis.

   Lung Cancer. 2012;77(3):572-7.

   Abstract

   INTRODUCTION The skeletal system is one of the most common distant sites of metastatic non-small cell lung cancer (NSCLC) which may lead to skeletal-related event (SRE). The purpose of this study was to assess the frequency of SRE and the prognostic factors of overall survival (OS) in patients presenting bone metastasis in NSCLC.

   METHODS Two hundred and twenty NSCLC patients with skeletal metastases at the time of diagnosis between January 2000 and August 2007 were investigated retrospectively.

   RESULTS Forty-seven of 110 patients (43%) without a SRE at the time of diagnosis experienced their first SRE during the follow-up. Patients with squamous cell carcinoma had a 1.8-times higher risk of short OS [95% confidence interval (CI) 1.11-2.84, p=0.016], compared with patients with non-squamous cell carcinoma, and patients treated with EGFR TKIs achieved a 50% protective effect in OS compared with patients not treated with them (95% CI 0.32-0.80, p=0.004). Patients with ECOG performance status 0-1 and single bone metastasis had a 1.8-times (95% CI 1.13-2.60, p=0.003) and 2.4-times (95% CI 1.26-4.46, p=0.008) longer OS than patients with performance status≥2 and two or more bone metastases, respectively.

   CONCLUSION Our study demonstrated that the frequency of SRE was common and single bone metastasis, good performance status (ECOG 0, 1), EGFR TKI treatment had good prognosis and histology of squamous cell carcinoma had bad prognosis.

   PubMed IF 5.3 혈액종양내과
7. 1632012

   제1저자 김재성 · 교신저자 방영주

   Kim JS, Lim JH, Kim JH, Im SA, Chie EK, Hwang JH, Kim TY, Bang YJ, Ha SW, Yoon YB

   Phase II clinical trial of induction chemotherapy with fixed dose rate gemcitabine and cisplatin followed by concurrent chemoradiotherapy with capecitabine for locally advanced pancreatic cancer.

   Cancer Chemother Pharmacol. 2012;70(3):381-9.

   Abstract

   PURPOSE 5-FU-based concurrent chemoradiotherapy (CRT) has been the mainstay of treatment for locally advanced pancreatic cancer (LAPC) for the past decades, but the prognosis remains dismal.

   METHODS Patients with pathologically confirmed LAPC of the pancreas, an ECOG PS of 0-2 and no prior chemo- or radiotherapy were eligible. The treatment consisted of induction (IND) chemotherapy with a fixed dose rate gemcitabine 1,000 mg/m(2) on days 1 and 8 and CDDP 60 mg/m(2) on day 1 every 3 weeks for 3 cycles. Subsequently, the patients without progression received CRT of 55.8 Gy/31 fractions with capecitabine 650 mg/m(2) twice daily. Gemcitabine was given for 3 cycles after CRT. The primary endpoint was time to progression.

   RESULTS Thirty-seven patients with LAPC were enrolled. Median age was 55 years, there were 20 males and 17 females, and ECOG PS was 0 in 6 and 1 in 31. Three patients (9.7 %) achieved partial responses after IND chemotherapy. Twenty-five patients received CRT with a mean radiation dose of 54.0 Gy, with one additional patient achieving a partial response. The median time to progression was 7.2 months (95 % CI, 4.4-10), and the median overall survival was 16.8 months (95 % CI, 12.9-20.7). The grade 3/4 toxicities included neutropenia (29 %/6.5 %), thrombocytopenia (3.2 %/0 %) and anemia (9.7 %/0 %) during the IND phase and grade 3 neutropenia and diarrhea occurring in one and two patients during CRT phase.

   CONCLUSIONS IND chemotherapy with gemcitabine and cisplatin followed by CRT with capecitabine and maintenance gemcitabine was well tolerated and exhibited promising efficacy for the treatment of LAPC.

   PubMed IF 2.5 혈액종양내과
8. 1622012

   제1저자 오세원 · 교신저자 진호준

   Oh SW, Kim S, Na KY, Chae DW, Kim S, Jin DC, Chin HJ

   Clinical implications of pathologic diagnosis and classification for diabetic nephropathy.

   Diabetes Res Clin Pract. 2012;97(3):418-24.

   Abstract

   AIM The usefulness of renal pathologic diagnosis in type II DM (diabetes mellitus) remains debate.

   METHODS We grouped the pathologic diagnoses as pure DN (diabetic nephropathy), NDRD (non-diabetic renal disease), and NDRD mixed with DN (Mixed). We classified pure DN as the criteria suggested by Tervaert. We compared the accuracy of clinical parameters to predict DN and usefulness of pathology to predict renal prognosis.

   RESULTS Among 126 enrolled patients, there were 50 pure DN, 65 NDRN, and 11 Mixed. The sensitivity and specificity for predicting DN with the presence of retinopathy were 77.8-73.6% and, with a cut-off value of 7.5 years of diabetic duration, the sensitivity and specificity were 64.5-67.2%. ESRD (end stage renal disease) occurred in 44.0% of DN, 18.2% of Mixed, and 12.3% of NDRD (p<0.001). Among pure DN, Class IV showed the lowest estimated glomerular filtration rate (eGFR). We estimated the 5-year renal survival rate as 100.0% in Classes I and IIa, 75.0% in Class IIb, 66.7% in Class III, and 38.1% in Class IV (p=0.002).

   CONCLUSIONS Nephropathy of type II DM was diverse and could not be completely predicted by clinical parameters. The renal pathologic diagnosis was a good predictor for renal prognosis in type II DM.

   PubMed IF 4.6 신장내과
9. 1612012

   제1저자 윤영광 · 교신저자 임석아/방영주

   Yoon YK, Im SA, Min A, Kim HP, Hur HS, Lee KH, Han SW, Song SH, Youn Oh D, Kim TY, Kim WH, Bang YJ

   Sunitinib synergizes the antitumor effect of cisplatin via modulation of ERCC1 expression in models of gastric cancer.

   Cancer Lett. 2012;321(2):128-36.

   Abstract

   We evaluated the effects of sunitinib monotherapy and in combination with cisplatin in human gastric cancer cell lines. Sunitinib showed antiproliferative effect in gastric cancer cells line with high PDGFRA expression. Knockdown of PDGFRA showed that sunitinib sensitivity was correlated with the basal expression of PDGFRA. Synergistic growth inhibitory activity in combination with cisplatin was identified. We further explored how sunitinib potentiated the activity of cisplatin. We found that sunitinib treatment resulted in the down-regulation of ERCC1 expression via the modulation of PDGFRA expression in gastric cancer cells. The effect was verified via SNU484 xenograft model. Our data support the rationale of clinical trial using sunitinib in combination of cisplatin in gastric cancer.

   PubMed IF 11.8 혈액종양내과
10. 1602012

    제1저자 김정연, 이은영 · 교신저자 송영욱

    Kim JY, Lee EY, Lee EB, Lee YJ, Yoo HJ, Choi J, Song YW

    Atorvastatin inhibits osteoclastogenesis by decreasing the expression of RANKL in the synoviocytes of rheumatoid arthritis.

    Arthritis Res Ther. 2012;14(4):R187.

    Abstract

    INTRODUCTION Statins, hydroxymethylglutaryl-coenzyme A reductase inhibitors, have been reported to have antiinflammatory and/or immunomodulatory effects and prophylactic and therapeutic effects in collagen-induced arthritis, an experimental model of rheumatoid arthritis (RA). The authors undertook to determine the effect of atorvastatin on the expressions of osteoprotegerin (OPG) and receptor activator of nuclear factor κB ligand (RANKL) in RA fibroblast-like synoviocytes (FLSs), to identify the mechanisms responsible for these effects, and to determine whether the statin inhibits osteoclastogenesis.

    METHODS FLSs isolated from five RA patients were cultured in the presence of 20 ng/ml of tumor necrosis factor-α (TNF-α) with or without atorvastatin. RANKL expressions were assayed with Western blotting and enzyme-linked immunosorbent assay. RANKL, RANK, and OPG expression were assayed with reverse transcription-polymerase chain reaction (RT-PCR). Osteoclast formation was assayed by counting cells after staining for tartrate-resistant acid phosphatase in cocultures of peripheral blood mononuclear cells (PBMCs) and RA FLSs.

    RESULTS Atorvastatin inhibited the expression of RANKL in RA FLSs in a dose-dependent manner, and the suppression of RANKL was prevented by mevalonate. However, OPG expression was not affected by atorvastatin in RA FLSs, and atorvastatin did not affect RANK expression in CD14⁺ cells. Conversely, atorvastatin suppressed TNF-α-induced p38 phosphorylation in RA FLSs and significantly reduced TRAP-positive multinucleated osteoclast formation in the coculture of PBMCs and RA FLSs.

    CONCLUSION These results suggest that atorvastatin inhibits osteoclastogenesis and bone destruction in RA patients.

    PubMed IF 5.4 류마티스내과
11. 1592012

    제1저자 김지원 · 교신저자 임석아

    Kim JW, Kim JH, Im SA, Kim YJ, Han HS, Kim JS, Han SW, Jeon YK, Oh DY, Han W, Kim TY, Park IA, Noh DY, Bang YJ

    ABCB1, FCGR2A, and FCGR3A polymorphisms in patients with HER2-positive metastatic breast cancer who were treated with first-line taxane plus trastuzumab chemotherapy.

    Oncology. 2012;83(4):218-27.

    Abstract

    OBJECTIVE The aim of this study was to elucidate clinical implications of ABCB1, FCGR2A, and FCGR3A polymorphisms in patients with HER2-positive metastatic breast cancer (MBC) after taxane plus trastuzumab (TH) chemotherapy.

    METHODS Using genomic DNA samples extracted from mononuclear cells of consecutive patients with HER2-positive MBC who received first-line TH, we analyzed five polymorphisms (ABCB1 1236C>T, ABCB1 2677G>T/A, ABCB1 3435C>T, FCGR2A 131H/R, and FCGR3A 158V/F) and then correlated them with the response rate, progression-free survival (PFS), overall survival (OS), and adverse events of patients.

    RESULTS A total of 57 women were analyzed. The median age was 46 years (range 27-72). ABCB1 2677T carriers had a longer PFS (p = 0.037) along with a tendency toward a longer OS (p = 0.057). ABCB1 3435CC genotype carriers had a shorter PFS (p = 0.039) along with a tendency toward a shorter OS (p = 0.093). In combined analysis, PFS was significantly longer in ABCB1 1236CC and/or 2677TT carriers compared to the others (p = 0.006). FCGR2A 131H/R and FCGR3A 158V/F polymorphisms were not significantly associated with response rate, PFS, and OS.

    CONCLUSIONS Our data support that ABCB1 polymorphisms may predict PFS after first-line TH chemotherapy in patients with HER2-positive MBC. In contrast, FCGR2A 131H/R and FCGR3A 158V/F polymorphisms could not predict treatment outcomes.

    PubMed IF 1.9 혈액종양내과
12. 1582012

    제1저자 김미정 · 교신저자 이근욱

    Kim MJ, Lee HS, Kim JH, Kim YJ, Kwon JH, Lee JO, Bang SM, Park KU, Kim DW, Kang SB, Kim JS, Lee JS, Lee KW

    Different metastatic pattern according to the KRAS mutational status and site-specific discordance of KRAS status in patients with colorectal cancer.

    BMC Cancer. 2012;12:347.

    Abstract

    BACKGROUND We evaluated the association between a KRAS mutational status and various clinicopathologic features including the metastatic pattern in patients with metastatic or recurrent colorectal cancer (MRCRC). The concordance rates of the KRAS status between primary tumor sites and paired metastatic organs were also analyzed.

    METHODS The KRAS mutational status in codons 12, 13, and 61 from formalin-fixed sections of both primary tumors and related metastases was determined by sequencing analysis. One hundred forty-three Korean patients with MRCRC with available tissues (resection or biopsy) from both primary tumors and related metastatic sites were consecutively enrolled.

    RESULTS The KRAS mutation rate was 52.4% (75/143) when considering both the primary and metastatic sites. When the relationship between the KRAS status and initial metastatic sites at the time of diagnosis of MRCRC was analyzed, lung metastasis was more frequent as the initial metastatic site in patients with the KRAS mutation than in patients without the KRAS mutation (45.3% vs. 22.1%; P = 0.003). However, liver (37.3% vs. 70.6%; P < 0.001) or distant lymph node metastases (6.7% vs. 19.1%; P = 0.025) were less frequent as the initial metastatic organ in patients with the KRAS mutation than in patients without the KRAS mutation. The discordance rate of KRAS mutational status between primary and paired metastatic sites other than the lung was 12.3% (13/106). Compared with primary tumor sites, the KRAS discordance rate was significantly higher in matched lung metastases [32.4% (12/37)] than in other matched metastatic organs (P = 0.005).

    CONCLUSIONS Organs initially involved by distant metastasis were different according to the KRAS mutational status in MRCRC patients. The concordance rate (87.7%) of the KRAS mutation status at metastatic sites other than the lung was generally high compared with primary tumor sites; however, lung metastasis had a high rate of KRAS discordance (32.4%).

    PubMed IF 4.1 혈액종양내과
13. 1572012

    제1저자 이준구 · 교신저자 김태민

    Lee JK, Kim TM, Koh Y, Lee SH, Kim DW, Jeon YK, Chung DH, Yang SC, Kim YT, Kim YW, Heo DS, Bang YJ

    Differential sensitivities to tyrosine kinase inhibitors in NSCLC harboring EGFR mutation and ALK translocation.

    Lung Cancer. 2012;77(2):460-3.

    Abstract

    Epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) translocations in non-small cell lung cancer (NSCLC) are mutually exclusive. However, several exceptional cases harboring both genetic alterations have been reported. In this study, a total of 444 patients with lung adenocarcinoma were examined for their EGFR and ALK status at Seoul National University Hospital between July 2008 and September 2011. EGFR mutations and ALK translocations were detected in 228 (51.4%) and 34 (7.7%) patients, respectively. Four patients (0.9%) had both genetic alterations and three underwent curative surgery. One patient who received both EGFR tyrosine kinase and ALK inhibitors, separately showed an objective response to the ALK inhibitor alone. Considering our and previous studies, patients harboring both EGFR mutation and ALK translocation showed differential sensitivities to both targeted therapies, suggesting a variable dependence on EGFR and ALK oncogenes.

    PubMed IF 5.3 혈액종양내과
14. 1562012

    제1저자 윤순호 · 교신저자 임재준

    Yoon SH, Lee NK, Yim JJ

    Impact of sputum gross appearance and volume on smear positivity of pulmonary tuberculosis: a prospective cohort study.

    BMC Infect Dis. 2012;12:172.

    Abstract

    BACKGROUND Although checking specimen quality upon sputum collection for acid-fast smear of suspected tuberculosis (TB) cases is recommended, this procedure is based on expert opinion. The purpose of this study was to elucidate the impact of sputum gross appearance and volume on smear positivity among patients with suspected pulmonary TB, according to sex.

    METHODS From November 2010 through June 2011, we enrolled consecutive patients suspected to have active pulmonary TB. The association of sputum gross appearance and volume with smear positivity, along with other variables possibly affecting smear positivity such as symptoms, disease extent, and cavity on chest radiograph, were investigated.

    RESULTS Among 2,439 patients undergoing TB examination, 170 (113 men, 57 women) with active pulmonary TB were enrolled. They submitted 492 sputa. There were 73 smear-positive patients (42.9%) and 164 smear-positive sputa (33.3%). While gross appearance was associated with smear positivity in both sexes (purulent or blood-tinged sputum (rather than mucoid sputum or saliva); odds ratio (OR), 2.05, 95% confidence interval (CI), 1.21-3.47 in men; OR, 2.78, 95% CI, 1.23-6.26 in women), the amount of sputum specimens was associated with smear positivity in only female patients (≥4 ml versus <4 ml; OR, 4.96, 95% CI, 1.98-12.37).

    CONCLUSIONS Sputum gross appearance and volume were associated with smear positivity. A volume of 4 ml seems to be the the minimum sputum volume acceptable for smear microscopy in females suspected of TB. Those suspected of TB should be encouraged to expectorate grossly qualified sputum specimens.

    PubMed IF 3.2 호흡기내과
15. 1552012

    제1저자 김광일 · 교신저자 진호준

    Kim KI, Oh SW, Ahn S, Heo NJ, Kim S, Chin HJ, Na KY, Chae DW, Kim CH, Kim S

    CRP level and HDL cholesterol concentration jointly predict mortality in a Korean population.

    Am J Med. 2012;125(8):787-95.e4.

    Abstract

    BACKGROUND C-reactive protein (CRP) and high-density lipoprotein (HDL) cholesterol are well-known cardiovascular predictors. However, the joint effect of these parameters on long-term mortality has not been established.

    METHODS We studied a total of 92,500 subjects older than 20 years who underwent routine health examination at the three health care centers affiliated with Seoul National University. High-sensitivity CRP and the lipid profile were obtained at baseline. Subjects were followed for a median of 45.5 months. Mortality data were obtained from the National Statistics Office of Korea.

    RESULTS There were 649 deaths (0.7%) during the follow-up. The leading cause of death was cancer. The subjects who died were significantly older, had a male predominance, and had increased levels of inflammatory markers. A significant mortality difference was identified according to the CRP and HDL cholesterol levels. Considering both parameters jointly, subjects with a CRP ≥1.4 mg/L (highest quartile) and HDL cholesterol <45 mg/dL (lowest quartile) were at the highest risk for all-cause mortality, even after adjusting for covariates (hazard ratio 2.29, 95% confidence interval, 1.83~2.87). After matching on the propensity score, 6304 subjects with a high CRP and low HDL cholesterol were at high risk of death (hazard ratio 2.52, 95% confidence interval, 1.59~4.01). Interestingly, the joint effect of CRP and HDL cholesterol was observed for cardiovascular as well as cancer-related mortality prediction.

    CONCLUSIONS Elevated CRP and low HDL cholesterol jointly contribute to the prediction of all-cause, cancer, and cardiovascular mortality in Koreans. The interactive relationship between them in mediating inflammatory processes might explain these results.

    PubMed IF 6 순환기내과
16. 1542012

    제1저자 임석아/문형곤 · 교신저자 노동영

    Moon HG, Im SA, Han W, Oh DY, Han SW, Keam B, Park IA, Chang JM, Moon WK, Cho N, Noh DY

    Estrogen receptor status confers a distinct pattern of response to neoadjuvant chemotherapy: implications for optimal durations of therapy: distinct patterns of response according to ER expression.

    Breast Cancer Res Treat. 2012;134(3):1133-40.

    Abstract

    Estrogen receptor (ER) expression status is an independent factor predicting response to neoadjuvant systemic treatment (NST). In the current study, we aimed to investigate the characteristics of NST response and benefits of extended NST cycles according to ER expression status. We investigated the outcomes of different durations of anthracycline-taxane-based NST in 377 operable breast cancer patients treated between Aug 2008 and June 2011. In 89 patients, the serial radiologic tumor response was assessed with either ultrasonography or computed tomography. Ninety-six patients (25.5 %) received extended cycles of anthracycline-taxane-based NST (6-8 cycles) and 281 patients (74.5 %) received 3-4 cycles of NST. Treatment with extended cycles of NST led to a significant increase in the pCR rate in ER-positive tumors only (2.1-11.7 %, p = 0.008 for ER-positive tumors and 20.0-19.4 %, p = 0.941 for ER-negative tumors). Serial assessment of radiologic tumor size during extended NST therapy revealed continuous shrinkage of ER-positive tumors during the chemotherapy cycles, while ER-negative tumors mainly achieved size reduction during the first 3-4 cycles with no significant additional tumor shrinkage during the extended cycles of NST. In this study, we report a distinct pattern of response to NST according to ER expression status in breast cancer. Our observation generates the hypothesis that the optimal duration of NST can be tailored to the molecular phenotypes of tumors.

    PubMed IF 3.3 혈액종양내과
17. 1532012

    제1저자 조영진, 이활 · 교신저자 오세일

    Cho Y, Lee W, Park EA, Oh IY, Choi EK, Seo JW, Oh S

    The anatomical characteristics of three different endocardial lines in the left atrium: evaluation by computed tomography prior to mitral isthmus block attempt.

    Europace. 2012;14(8):1104-11.

    Abstract

    AIMS Additional linear ablation lesions are created to improve the outcomes of pulmonary vein (PV) isolation during atrial fibrillation (AF) ablation. We aimed to evaluate the safety and feasibility of additional ablation sites in terms of anatomical characteristics.

    METHODS AND RESULTS Multi-detector computed tomography (MDCT) data from 140 consecutive patients (40 with AF, 84 males, 59 ± 11 years old) and additional 10 heart specimens were analysed for their anatomical characteristics at three types of mitral isthmus lines: anteromedial (AM), anterolateral (AL), and posterolateral (PL) lines (from right superior, left superior, and left inferior PV to 10, 12, and 4 o'clock position of the mitral annulus, respectively). The data demonstrated that the length was shortest at the PL lines (MDCT, 36.4 ± 8.6 mm; specimens, 31 ± 6 mm) and the maximal myocardial thickness was greatest at the AL lines (MDCT, 3.2 ± 1.0 mm; specimens, 5.0 ± 0.9 mm). Ridge, cord-like structure, or diverticulum was found most frequently at the AM lines (MDCT, 20%; specimens, 20%). Sinus nodal artery (SNA) was found near the AM (MDCT, 100%; specimens, 90%) and AL lines (MDCT, 46.3%; specimens, 30%), while left coronary artery (LCA) and cardiac vein were closest to the PL lines. The trend of these findings was not significantly altered with the presence of AF.

    CONCLUSIONS The PL lines were shortest among the three mitral isthmus lines, but closest to LCA. Myocardium was thickest at the AL line, and SNAs were frequently found on the anterior lines. Multi-detector computed tomography provided detailed information, and further studies are required to clarify the clinical impact of these findings.

    PubMed IF 10.2 순환기내과
18. 1522012

    제1저자 박주경 · 교신저자 황진혁, 김용태

    Park JK, Kim MA, Ryu JK, Yoon YB, Kim SW, Han HS, Kang GH, Kim H, Hwang JH, Kim YT

    Postoperative prognostic predictors of pancreatic ductal adenocarcinoma: clinical analysis and immunoprofile on tissue microarrays.

    Ann Surg Oncol. 2012;19(8):2664-72.

    Abstract

    BACKGROUND Most pancreatic ductal adenocarcinomas (PDACs) metastasize even after curative resection. Our goal was to investigate the important factors affecting metastasis and overall survival (OS).

    METHODS We studied 88 PDACs with R0 resection and evaluated immunohistochemical markers on tissue microarrays to assess the expression levels of the following: EGFR, amphiregulin, VEGF, p-c-met, MMP2, MMP7, MMP9, CXCR3, and CXCR4.

    RESULTS The median OS in patients who had positive versus negative expression of AREG and MMP9 were 25 versus 16 months and 24 versus 13 months, respectively (P = 0.03, P = 0.006). However, the median OS in patients with positive versus negative expression of MMP2 was 22 versus 37 months (P = 0.04). Immunoprofiles also revealed that patients with positive expression of p-c-met or VEGF had significantly shorter distant metastasis-free survival. Adjuvant treatment, postoperative decrease of CA 19-9, angiolymphatic invasion, AREG, and MMP2 were independent prognostic factors affecting OS in multivariate analysis.

    CONCLUSIONS Immunoprofiles revealed the groups with unfavorable tumor biology: negative expression of AREG and positive expression of MMP2. Also, high immunoreactivity of p-c-met or VEGF seemed to be associated with early distant organ metastasis in R0 resected PDACs; however, they still need to be further investigated. These results may give us useful insights in understanding the tumor biology and the patterns of PDAC dissemination.

    PubMed IF 3.8 소화기내과
19. 1512012

    제1저자 김남주 · 교신저자 이근욱

    Kim N, Park C, Park DJ, Kim HH, Kim S, Kim YJ, Kim JH, Lee JS, Bang YJ, Khwarg SI, Choung H, Lee MJ, Lee KW

    Lacrimal drainage obstruction in gastric cancer patients receiving S-1 chemotherapy.

    Ann Oncol. 2012;23(8):2065-2071.

    Abstract

    BACKGROUND This study was conducted to determine the incidence and clinical characteristics of lacrimal drainage obstruction (LDO) in patients receiving S-1 chemotherapy.

    PATIENTS AND METHODS Consecutive 170 patients with gastric cancer who underwent curative surgery and received adjuvant S-1 chemotherapy were enrolled. S-1 was administered orally (40 mg/m2 b.i.d. on days 1-28 every 6 weeks) for 1 year. Ophthalmologic examinations were carried out on patients complaining of epiphora.

    RESULTS Thirty-one patients (18%) developed epiphora. Among 31 patients, 25 underwent ophthalmologic examinations and 22 (88%) were diagnosed with LDO. The median time to the onset of LDO was 2.9 months. The most common site of obstruction was the nasolacrimal duct [86% (19/22)]; punctal [23% (5/22)] and canalicular obstruction [14% (3/22)] were also noted. In multivariate analysis, total gastrectomy [versus partial gastrectomy: hazard ratio (HR), 2.9; P=0.014] and creatinine clearance<50 ml/min (versus ≥50 ml/min: HR, 2.9; P=0.038) were independent risk factors for the development of LDO.

    CONCLUSION Considering the high incidence of LDO in patients receiving S-1 chemotherapy, oncologists should be alert to epiphora and cooperate with ophthalmologists in the early stages to improve the quality of life of patients and avoid more complicated ophthalmologic procedures.

    PubMed IF 80.4 혈액종양내과
20. 1502012

    제1저자 박진아 · 교신저자 오도연

    Park J, Park E, Han SW, Im SA, Kim TY, Kim WH, Oh DY, Bang YJ

    Down-regulation of P-cadherin with PF-03732010 inhibits cell migration and tumor growth in gastric cancer.

    Invest New Drugs. 2012;30(4):1404-12.

    Abstract

    P-cadherin is frequently up-regulated in solid tumors such as gastric, colon, lung, pancreatic and breast cancers. Although P-cadherin promotes cadherin-mediated cell adhesion, the gastric cancer-linked regulation of P-cadherin has not been extensively investigated. In this study, we found epigenetic regulation of P-cadherin in human gastric cancer cells that was induced by treatment with DNA demethylating drug and histone deacetylase inhibitor. Silencing P-cadherin by using siRNA induces apoptosis in gastric cells and blocks expression of Tie-2, an angiogenic receptor tyrosine kinase. In contrast, ectopically expressed P-cadherin by generating P-cadherin stable cell line enhances Tie-2 expression and cell mobility. We also demonstrated that inhibition of P-cadherin by PF-03732010, a fully humanized anti-P-cadherin IgG1 monoclonal antibody, suppressed cell migration in vitro and tumor growth in BALB/c nude mice bearing SNU620 gastric cancer xenograft. The data reported here are the first to reveal that the inhibition of P-cadherin decreases tumor cell migration and blocks a tumorigenesis by down-regulation of Tie-2 in gastric cancer. This demonstrates the potential for P-cadherin to be used as a target for treatment of gastric cancer.

    PubMed IF 3.4 혈액종양내과
21. 1492012

    제1저자 문기원 · 교신저자 송영욱

    Moon KW, Song R, Kim JH, Lee EY, Lee EB, Song YW

    The correlation between durometer score and modified Rodnan skin score in systemic sclerosis.

    Rheumatol Int. 2012;32(8):2465-70.

    Abstract

    The aims of the present study were to determine the correlation between durometer scores with modified Rodnan skin scores (MRSS), scleroderma symptoms, and physical functions. A total of 31 patients with systemic sclerosis (SSc, 16 diffuse and 15 limited type) were enrolled in this study. Skin involvement was measured using a durometer and MRSS. Health assessment questionnaire (HAQ) disability indices, Keitel function test (KTF) scores, grip strengths, and scleroderma-visual analog scale (scleroderma-VAS) scores were measured. The correlations between durometer scores with MRSS, HAQ disability indices, and scleroderma-VAS scores were assessed. Durometer scores correlated well with MRSS at fingers, hands, forearms, upper arms, thighs, and feet, but poorly correlated with MRSS at the chest, abdomen, and lower legs. Total durometer scores correlated well with MRSS (r = 0.537, P = 0.002) and KTF scores (r = 0.608, P < 0.001), but poorly correlated with HAQ disability indices (r = 0.202, P = 0.276), and individual scleroderma-VAS scores. Durometer-measured skin hardnesses were found to correlate well with the MRSS scores of fingers, hands, forearms, upper arms, thighs, and feet. The authors suggest that these skin sites should be included when durometer measurements are made in systemic sclerosis.

    PubMed IF 3.5 류마티스내과
22. 1482012

    제1저자 임철현 · 교신저자 송영욱

    Im CH, Kim J, Lee YJ, Lee EY, Lee EB, Park KS, Song YW

    Mannose-binding lectin 2 gene haplotype analysis in Korean patients with ankylosing spondylitis.

    Rheumatol Int. 2012;32(8):2251-5.

    Abstract

    Mannose-binding lectin (MBL) serum levels or genetic polymorphisms are known to be associated with autoimmune diseases. We investigated MBL2 genetic polymorphisms in 95 patients with ankylosing spondylitis (AS) and in 252 healthy controls. MBL2 promoter polymorphisms at -550 (H/L), -221 (Y/X), +4 (P/Q), and exon polymorphisms at codon 52 (Arg/Cys), 54 (Gly/Asp, or A/B), and 57 (Gly/Glu) were investigated using polymerase chain reaction and restriction fragment length polymorphism. Genetic polymorphisms were analyzed using SPSS (ver 12.0) and Haploview (ver 4.2). MBL2 single-nucleotide polymorphisms (SNPs) were not significantly different between patients with AS and controls. By haplotype analysis, LYPB frequency was significantly lower in AS (10.7% vs. 21.3%, OR 0.441, 95% CI: 0.266-0.733, P value = 0.001, Pc value = 0.008). The frequency of LYPA (15.4% vs. 9.2%, OR 1.802, 95% CI: 1.097-2.961, P value = 0.019, Pc value = 0.101) and HYPB (3.5% vs. 0.8%, OR 4.457, 95% CI: 1.289-15.409, P value = 0.011, Pc value = 0.060) tended to be higher in AS. Clinical characteristics of AS were not associated with any MBL2 SNP or haplotype. In summary, haplotypes of MBL2 genetic polymorphisms were found to be associated with AS, which suggests that MBL2 genetic polymorphisms may play a role during the development of AS.

    PubMed IF 3.5 류마티스내과
23. 1472012

    제1저자 문민경 · 교신저자 박영주, 장학철

    Moon MK, Cho BJ, Lee YJ, Choi SH, Lim S, Park KS, Park YJ, Jang HC

    The effects of chronic exercise on the inflammatory cytokines interleukin-6 and tumor necrosis factor-α are different with age.

    Appl Physiol Nutr Metab. 2012;37(4):631-6.

    Abstract

    Aging is associated with chronic low-grade inflammation, and interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) are key mediators of the inflammatory process. IL-6, especially muscle-derived IL-6, is expected to mediate the beneficial metabolic effects of exercise. There was no report that directly compares the effects of chronic endurance exercise on cytokine responses between old and young subjects in the same situation. Therefore, we compared the effects of endurance exercise on the expression of IL-6 and TNF-α in old and young rats. Young (3-month-old) and old (20-month-old) male Fisher rats were trained for 12 weeks on the treadmill. We measured serum TNF-α and IL-6 concentrations by enzyme-linked immunosorbent assay and examined mRNA expression of TNF-α and IL-6 in muscle, liver, and white adipose tissue using reverse transcription - polymerase chain reaction. We found that old rats had higher basal IL-6 levels in the liver, as well as in the serum and the muscle. After chronic endurance exercise, young rats exhibited significant decreases in serum TNF-α levels and hepatic IL-6 expression. However, old rats exhibited no significant changes in either serum or tissue cytokine levels after endurance exercise. These findings suggest that chronic endurance exercise could influence the inflammatory response of hepatic tissues, as well as muscle, and that the effects of chronic endurance exercise on inflammatory cytokine levels are different between old and young rats and an exercise program tailored for old subjects will be needed to obtain beneficial anti-inflammatory effects from exercise.

    PubMed IF 2.4 내분비대사내과
24. 1462012

    제1저자 이세원 · 교신저자 임재준

    Lee SW, Lee SH, Yim JJ

    Serial interferon-gamma release assays after chemoprophylaxis in a tuberculosis outbreak cohort.

    Infection. 2012;40(4):431-5.

    Abstract

    PURPOSE Interferon-gamma release assay (IGRA) results have been suggested as a surrogate marker of treatment response in latent tuberculosis infection (LTBI). However, data have not been consistent, and most previous studies focused on participants taking isoniazid prophylaxis. The aim of this study was to elucidate the changes in the IGRA results in patients who underwent chemoprophylaxis with isoniazid and rifampicin daily for 3 months.

    METHODS In a TB outbreak cohort, 26 asymptomatic close contacts with normal chest radiographs and positive QuantiFERON-TB Gold In-Tube assay (QFT-GIT) results were recruited. These patients were treated with isoniazid and rifampicin daily for 3 months. The QFT-GIT was repeated at 3 and 6 months following treatment initiation.

    RESULTS Compared with the initial QFT-GIT results (3.59 ± 3.39 IU/mL), the interferon-gamma (IFN-γ) levels had decreased significantly at 6 months (0.84 ± 1.14 IU/mL; P = 0.005), but not at 3 months (3.58 ± 3.64 IU/mL; P = 0.98). Reversions occurred in seven (26.9 %) patients at 3 months and in an additional two participants at 6 months; a total of nine participants (34.6 %) had reversions. Recent conversion was associated with reversion of the test results (odds ratio 26.3, 95 % confidence interval 3.04-226.6).

    CONCLUSION Chemoprophylaxis with isoniazid and rifampicin generally decreased IFN-γ levels among tuberculosis contacts. However, only a small portion of participants achieved reversion.

    PubMed IF 3.9 호흡기내과
25. 1452012

    제1저자 박진주, 채인호 · 교신저자 조영석

    Park JJ, Chae IH, Cho YS, Kim SW, Yang HM, Seo JB, Kim SY, Oh IY, Yoon CH, Suh JW, Park KW, Chung WY, Youn TJ, Choi DJ, Kim HS

    The recanalization of chronic total occlusion leads to lumen area increase in distal reference segments in selected patients: an intravascular ultrasound study.

    JACC Cardiovasc Interv. 2012;5(8):827-36.

    Abstract

    OBJECTIVES This study sought to investigate the extent of and factors related to lumen and vessel area change in coronary arteries after total occlusion (TO) recanalization.

    BACKGROUND TO of a coronary artery promotes negative remodeling in distal reference segments. Recanalization can restore blood flow, potentially leading to positive vascular remodeling.

    METHODS From March 2005 to June 2008, 58 consecutive patients with de novo TO lesions of at least 1-month duration were enrolled. We performed intravascular ultrasound after successful percutaneous coronary intervention and at the 6-month follow-up, and we quantified changes in the distal reference segments.

    RESULTS At the 6-month follow-up, there was a significant increase in the mean lumen diameter (+0.21 mm, p = 0.001), the mean external elastic membrane diameter (+0.13 mm, p = 0.010), the lumen area (+0.87 mm(2), p < 0.001), and the external elastic membrane area (+0.85 mm(2), p = 0.001) in the distal reference segments and an increase in the left ventricular ejection fraction (+2.77%, p = 0.010). Overall, 40 of 58 patients (69%) showed lumen area increase; these patients had increase in lumen diameter by 0.40 ± 0.34 mm (p < 0.001) and increase in incomplete stent apposition rate (p = 0.006). A TO duration of longer than 3 months (odds ratio [OR]: 14.8; 95% confidence interval [CI]: 1.28 to 172.8, p = 0.032), a poor collateral flow (OR: 12.0; 95% CI: 1.92 to 74.2, p = 0.008), and statin use (OR: 7.4; 95% CI: 1.03 to 53.6, p = 0.047) were independent predictors of lumen area increase.

    CONCLUSIONS Recanalization of TO led to lumen area increase in two-thirds of the patients. Independent predictors of lumen area increase were occlusion duration, a poor collateral flow, and statin use. These factors could be used as guides in choosing the optimal stent size during percutaneous coronary intervention to TO lesions and optimal medical therapy during follow-up.

    PubMed IF 12.7 순환기내과
26. 1442012

    제1저자 김동희 · 교신저자 김동희

    Kim D, Choi SY, Park EH, Lee W, Kang JH, Kim W, Kim YJ, Yoon JH, Jeong SH, Lee DH, Lee HS, Larson J, Therneau TM, Kim WR

    Nonalcoholic fatty liver disease is associated with coronary artery calcification.

    Hepatology. 2012;56(2):605-13.

    Abstract

    UNLABELLED Nonalcoholic fatty liver disease (NAFLD) is related to risk factors of coronary artery disease, such as dyslipidemia, diabetes, and metabolic syndrome, which are closely linked with visceral adiposity. The aim of this study was to investigate whether NAFLD was associated with coronary artery calcification (CAC), which is used as a surrogate marker for coronary atherosclerosis independent of computed tomography (CT)-measured visceral adiposity. Out of 5,648 subjects who visited one of our health screening centers between 2003 and 2008, we enrolled 4,023 subjects (mean age, 56.9 ± 9.4 years; 60.7% males) without known liver disease or a history of ischemic heart disease. CAC score was evaluated using the Agatston method. On univariate analysis, the presence of CAC (score >0) was significantly associated with age, sex, body mass index, aspartate aminotransferase, alanine aminotransferase, high-density lipoprotein cholesterol, triglycerides, and increased risk of diabetes, hypertension, smoking, and NAFLD. Increasing CAC scores (0, <10, 10-100, ≥ 100) were associated with higher prevalence of NAFLD (odds ratio [OR], 1.84; 95% confidence interval [CI], 1.61-2.10; P<0.001). Multivariable ordinal regression analysis was adjusted for traditional risk factors, and CT-measured visceral adipose tissue area in a subgroup of subjects showed that the increased CAC scores were significantly associated with the presence of NAFLD (OR, 1.28, 95% CI, 1.04-1.59; P = 0.023) independent of visceral adiposity.

    CONCLUSION Patients with NAFLD are at increased risk for coronary atherosclerosis independent of classical coronary risk factors, including visceral adiposity. These data suggest that NAFLD might be an independent risk factor for coronary artery disease.

    PubMed IF 18 소화기내과
27. 1432012

    제1저자 오태정 · 교신저자 조영민

    Oh TJ, Kim MY, Park KS, Cho YM

    Effects of chemosignals from sad tears and postprandial plasma on appetite and food intake in humans.

    PLoS One. 2012;7(8):e42352.

    Abstract

    Chemosignals from human body fluids may modulate biological functions in humans. The objective of this study was to examine whether chemosignals from human sad tears and postprandial plasma modulate appetite. We obtained fasting and postprandial plasma from male participants and sad tears and saline, which was trickled below the eyelids, from female volunteers. These samples were then randomly distributed to male participants to sniff with a band-aid containing 100 µl of each fluid on four consecutive days in a double-blind fashion. We checked appetite by a visual analogue scale (VAS) and food intake by measuring the consumption of a test meal. In addition, the serum levels of total testosterone and LH were measured. Twenty men (mean age 26.3±4.6 years) were enrolled in this study. They could not discriminate between the smell of fasting and postprandial plasma and the smell of sad tears and trickled saline. Appetite and the amount of food intake were not different between the groups. Although the VAS ratings of appetite correlated with the food intake upon sniffing fasting plasma, postprandial plasma, and trickled saline, there was no such correlation upon sniffing sad tears. In addition, the decrease in serum testosterone levels from the baseline was greater with sad tears than with the trickled saline (-28.6±3.3% vs. -14.0±5.2%; P = 0.019). These data suggest that chemosignals from human sad tears and postprandial plasma do not appear to reduce appetite and food intake. However, further studies are necessary to examine whether sad tears may alter the appetite-eating behavior relation.

    PubMed IF 2.8 내분비대사내과
28. 1422012

    제1저자 박혜성, 이준구 · 교신저자 김동완

    Park HS, Lee JK, Kim DW, Kulig K, Kim TM, Lee SH, Jeon YK, Chung DH, Heo DS

    Immunohistochemical screening for anaplastic lymphoma kinase (ALK) rearrangement in advanced non-small cell lung cancer patients.

    Lung Cancer. 2012;77(2):288-92.

    Abstract

    Fluorescence in situ hybridization (FISH) is currently used to detect non-small cell lung cancer (NSCLC) patients with anaplastic lymphoma kinase (ALK) gene rearrangement, who are candidates for ALK inhibitor therapy. However, FISH may not be a practical method for screening for ALK-positive patients in a large population due to its cost and difficulty in interpretation. We investigated the role of immunohistochemistry (IHC) to screen for ALK rearrangement in advanced NSCLC. We identified 1,166 stage IIIB or IV NSCLC patients with non-squamous histology from the Seoul National University Hospital NSCLC database. To enrich ALK-positive cases, we selected 262 patients who were either EGFR wild-type or non-responders to previous EGFR tyrosine kinase inhibitors (TKI). ALK IHC and ALK FISH were performed on formalin-fixed, paraffin-embedded tissue. ALK protein was expressed in 28 (10.7%) tumors in 262 patients. ALK FISH was positive in 25 (9.5%) cases. All patients with IHC score of 3 (n=9) were FISH-positive and all patients with score of 0 (n=234) were FISH-negative. Among patients with IHC scores of 1 and 2, five (83.3%, 5/6) and eleven (84.6%, 11/13) were FISH-positive, respectively. The sensitivity and specificity of ALK IHC with intensity score of 1 or more were 100% and 98.7%, respectively. IHC can be a useful test for screening ALK FISH-positive cases in advanced NSCLC. FISH testing should be considered for advanced NSCLC patients with tumors showing mild to moderate staining for ALK by IHC to confirm ALK translocation.

    PubMed IF 5.3 혈액종양내과
29. 1412012

    제1저자 임수 · 교신저자 장학철

    Lim S, An JH, Shin H, Khang AR, Lee Y, Ahn HY, Yoon JW, Kang SM, Choi SH, Cho YM, Park KS, Jang HC

    Factors predicting therapeutic efficacy of combination treatment with sitagliptin and metformin in type 2 diabetic patients: the COSMETIC study.

    Clin Endocrinol (Oxf). 2012;77(2):215-23.

    Abstract

    OBJECTIVE We assessed the predictive parameters for therapeutic efficacy of initial combination therapy with sitagliptin and metformin in drug-naïve type 2 diabetic patients. DeSIGN, PATIENTS, AND MEASUREMENTS: In this 52-week treatment study, 150 patients (mean age, 54·9 ± 12·5 years) with type 2 diabetes and HbA1c of 7·0-10% were treated with sitagliptin 100 mg once and metformin 500 mg twice daily. To assess the predictive parameters for therapeutic efficacy, a multivariate regression analysis was performed with baseline fasting glucose, insulin, C-peptide, and glucagon levels, homoeostasis model assessment-insulin resistance (HOMA-IR) and β-cell function (HOMA-B), insulinogenic index (IGI, defined as 30-0 min insulin/30-0 min glucose), and area under the curve for glucose, insulin, and C-peptide obtained after 75-g oral glucose tolerance test.

    RESULTS After 52 weeks, mean HbA1c levels and fasting and postload 2-h glucose were significantly decreased from 8·7 ± 1·4% to 7·2 ± 1·3%, 9·2 ± 3·0 to 7·2 ± 1·8 mm, and 17·5 ± 5·1 to 10·9 ± 3·6 mm, respectively (P < 0·01). HOMA-B and IGI increased significantly from 50·3 ± 33·5 to 75·1 ± 32·8 and from 11·3 ± 1·3 to 35·0 ± 6·3 at 52 weeks, respectively (P < 0·01). Multivariate regression analysis indicated that the reduction in HbA1c was significantly associated with high baseline HbA1c, low IGI, and short duration of diabetes after adjusting for age, sex, body mass index, blood pressure, triglycerides, creatinine, high-sensitivity CRP, glucagon, C-peptide, HOMA-B, and HOMA-IR. No severe adverse events were observed.

    CONCLUSION These results suggest that drug-naïve type 2 diabetic patients with low β-cell function would benefit the most from early initial combination therapy of sitagliptin and metformin.

    PubMed IF 2.8 내분비대사내과
30. 1402012

    제1저자 박진현 · 교신저자 이세훈

    Park JH, Lee SH, Keam B, Kim TM, Kim DW, Yang SC, Kim YW, Heo DS

    EGFR mutations as a predictive marker of cytotoxic chemotherapy.

    Lung Cancer. 2012;77(2):433-7.

    Abstract

    BACKGROUND Epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) are important predictive markers for the response to EGFR-tyrosine kinase inhibitors (EGFR-TKIs). Whether EGFR mutations can also predict the clinical outcomes in NSCLC patients receiving chemotherapy has not yet been established.

    METHODS We included 217 locally advanced/metastatic NSCLC cases in our study cohort. Each patient had received platinum doublet chemotherapy as a first line treatment, and had been screened for an EGFR mutation.

    RESULTS The subject cohort comprised 80 EGFR wild type and 137 EGFR-mutated lung cancer patients. Gemcitabine-based and taxane-based regimens were administered in 131 (60.4%) and 86 (39.6%) cases, respectively. Among the patients with a wild type EGFR, there was no significant difference in the response rate (RR), disease control rate (DCR), or progression-free survival (PFS) between gemcitabine-based and taxane-based therapies. Among the patients with EGFR mutations, no difference in RR was observed between gemcitabine-based and taxane-based treatments. On the other hand, the DCR and PFS associated with taxane-based therapy were superior when compared with the gemcitabine-based treatments. When we analyzed patients with an EGFR exon 19 deletion, the PFS of the taxane treated cases was better than that of the gemcitabine treated cases (5.3 months vs 3.7 months, P=0.012).

    CONCLUSIONS Our current data indicate that lung cancer patients with EGFR-mutations had longer PFS with taxane than gemcitabine when receiving a platinum-based doublet regimen. The predictive meaning of EGFR mutations for cytotoxic chemotherapy should be further investigated.

    PubMed IF 5.3 혈액종양내과

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