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author:("Lee, Jae yuk")
1.  Large cavernous hemangioma in the cecum treated by laparoscopic ileocecal resection 
A cavernous hemangioma of the cecum is a rare vascular malformation but is clinically important because of the possibility of massive bleeding. We report a case of a large cavernous hemangioma with pericolic infiltration in the cecum which was removed successfully using minimally invasive surgery.
doi:10.3748/wjg.15.3319
PMCID: PMC2710792  PMID: 19598312
Cavernous hemangioma; Cecum; Laparoscopic surgery
2.  Expression of matrix metalloproteinases and their inhibitors in different immunohistochemical-based molecular subtypes of breast cancer 
BMC Cancer  2014;14(1):959.
Background
Metalloproteinases (MMPs) and their tissue inhibitors of metalloproteinases (TIMPs) are involved in several key pathways of tumor growth, invasion and metastasis, but little is known about their expression according to different molecular subtypes of breast cancer. The aims of this study were to assess the prevalence and clinical significance of MMP and TIMP expression in invasive breast cancer and to determine its association with immunohistochemical-based molecular classification.
Methods
Tissue microarray sections were immunostained for estrogen receptor-α (ER-α), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), cytokeratin (CK) 5/6, epidermal growth factor receptor (EGFR) and with specific antibodies against MMP-1, 2, 7, 9, 11, 13, and 14 and TIMP-1, 2, and 3. Based on the immunostaining data from five of the markers used (ER-α, PR, HER2, EGFR and CK5/6), three major subtypes (123 luminal A, 31 basal-like, and 17 HER2-overexpressing) were selected.
Results
Statistically significant differences in the expression of MMPs and TIMPs among the three subtypes were found in tumoral MMP7 (P = 0.005), tumoral MMP-9 (P = 0.000), tumoral MMP-13 (P = 0.016) and stromal MMP-13 (P = 0.016). The incidence of tumoral MMP-9 expression in the HER2-overexpressing subtype was significantly higher than in the luminal A subtype (P = 0.021). Tumoral MMP-9 and stromal MMP-13 expression were significantly higher in the HER2-overexpressing subtype than in the basal-like subtype (P = 0.000 and P = 0.016, respectively). Tumoral MMP-7 expression was significantly higher in the basal-like subtype compared to luminal A (P = 0.007) and HER2-overexpressing subtype (P = 0.004). Tumoral MMP-13 showed a higher expression in the basal-like subtype than in the HER2-overexpressing subtype (P = 0.010). In multivariate analysis, stage and stromal MMP-1 expression were significantly related to overall survival. Stage was of independent prognostic significance for disease-free survival.
Conclusion
We found some variations in MMP and TIMP expression among the immunohistochemical-based molecular subtypes of breast carcinomas, suggesting differences in their tumor pathophysiology. Additional studies are needed to determine the mechanisms underlying the differences of MMP and TIMP expression in the molecular subtypes for the development of specific therapeutic targets for breast cancer subtypes.
doi:10.1186/1471-2407-14-959
PMCID: PMC4301952  PMID: 25510449
Breast cancer; Molecular subtype; Immunohistochemistry; Matrix metalloproteinase; Tissue inhibitor of metalloproteinase
3.  Arterial Stiffness by Aerobic Exercise Is Related with Aerobic Capacity, Physical Activity Energy Expenditure and Total Fat but not with Insulin Sensitivity in Obese Female Patients with Type 2 Diabetes 
Diabetes & Metabolism Journal  2014;38(6):439-448.
Background
Arterial stiffness is an important factor in atherosclerosis. Thus we examined whether aerobic exercise could reduce arterial stiffness in obese women with type 2 diabetes without diabetic complication.
Methods
A total of 35 women with type 2 diabetes (body mass index, 26.6±2.8 kg/m2; age, 56.4±1.9 years; duration of diabetes, 4.7±4.8 years) were assigned to aerobic exercise group (AEG) or control group (CG). AEG completed a 12-week exercise program (3.6 to 5.2 metabolic equivalents, 3 day/week, 60 min/day), with their exercise activities monitored by accelerometers. We measured abdominal total fat area (TFA), visceral fat area (VFA), and subcutaneous fat area (SFA) by computed tomography, insulin sensitivity by insulin tolerance test (KITT), and augmentation index (AIx) by SphygmoCor at baseline and at the end of the 12-week program.
Results
The AIx was improved in the AEG compared with the CG (P<0.001). The percent change of AIx had significant correlation with the improvement of physical activity energy expenditure (PAEE), aerobic capacity, TFA, and SFA (r=-0.416, P=0.013; r=0.560, P<0.001; r=0.489, P=0.003; r=0.531, P=0.001, respectively), but not with insulin sensitivity, energy intake, or VFA.
Conclusion
Improvement in aortic stiffness by aerobic exercise is related with the improvement of aerobic capacity, PAEE, and total fat but not with insulin sensitivity or energy intake in obese women with type 2 diabetes.
doi:10.4093/dmj.2014.38.6.439
PMCID: PMC4273030  PMID: 25541607
Abdominal fat; Augmentation index; Diabetes mellitus, type 2; Moderate aerobic exercise; Vascular stiffness
4.  Hybrid Granular Cell Tumor/Perineurioma 
Korean Journal of Pathology  2014;48(6):409-412.
doi:10.4132/KoreanJPathol.2014.48.6.409
PMCID: PMC4284484  PMID: 25588629
5.  Cytokeratin-Positive Gastrointestinal Stromal Tumor of Biphasic Morphology: A Case Report 
Korean Journal of Pathology  2014;48(5):375-378.
doi:10.4132/KoreanJPathol.2014.48.5.375
PMCID: PMC4215964  PMID: 25366074
6.  Comprehensive molecular characterization of gastric adenocarcinoma 
Bass, Adam J. | Thorsson, Vesteinn | Shmulevich, Ilya | Reynolds, Sheila M. | Miller, Michael | Bernard, Brady | Hinoue, Toshinori | Laird, Peter W. | Curtis, Christina | Shen, Hui | Weisenberger, Daniel J. | Schultz, Nikolaus | Shen, Ronglai | Weinhold, Nils | Kelsen, David P. | Bowlby, Reanne | Chu, Andy | Kasaian, Katayoon | Mungall, Andrew J. | Robertson, A. Gordon | Sipahimalani, Payal | Cherniack, Andrew | Getz, Gad | Liu, Yingchun | Noble, Michael S. | Pedamallu, Chandra | Sougnez, Carrie | Taylor-Weiner, Amaro | Akbani, Rehan | Lee, Ju-Seog | Liu, Wenbin | Mills, Gordon B. | Yang, Da | Zhang, Wei | Pantazi, Angeliki | Parfenov, Michael | Gulley, Margaret | Piazuelo, M. Blanca | Schneider, Barbara G. | Kim, Jihun | Boussioutas, Alex | Sheth, Margi | Demchok, John A. | Rabkin, Charles S. | Willis, Joseph E. | Ng, Sam | Garman, Katherine | Beer, David G. | Pennathur, Arjun | Raphael, Benjamin J. | Wu, Hsin-Ta | Odze, Robert | Kim, Hark K. | Bowen, Jay | Leraas, Kristen M. | Lichtenberg, Tara M. | Weaver, Stephanie | McLellan, Michael | Wiznerowicz, Maciej | Sakai, Ryo | Getz, Gad | Sougnez, Carrie | Lawrence, Michael S. | Cibulskis, Kristian | Lichtenstein, Lee | Fisher, Sheila | Gabriel, Stacey B. | Lander, Eric S. | Ding, Li | Niu, Beifang | Ally, Adrian | Balasundaram, Miruna | Birol, Inanc | Bowlby, Reanne | Brooks, Denise | Butterfield, Yaron S. N. | Carlsen, Rebecca | Chu, Andy | Chu, Justin | Chuah, Eric | Chun, Hye-Jung E. | Clarke, Amanda | Dhalla, Noreen | Guin, Ranabir | Holt, Robert A. | Jones, Steven J.M. | Kasaian, Katayoon | Lee, Darlene | Li, Haiyan A. | Lim, Emilia | Ma, Yussanne | Marra, Marco A. | Mayo, Michael | Moore, Richard A. | Mungall, Andrew J. | Mungall, Karen L. | Nip, Ka Ming | Robertson, A. Gordon | Schein, Jacqueline E. | Sipahimalani, Payal | Tam, Angela | Thiessen, Nina | Beroukhim, Rameen | Carter, Scott L. | Cherniack, Andrew D. | Cho, Juok | Cibulskis, Kristian | DiCara, Daniel | Frazer, Scott | Fisher, Sheila | Gabriel, Stacey B. | Gehlenborg, Nils | Heiman, David I. | Jung, Joonil | Kim, Jaegil | Lander, Eric S. | Lawrence, Michael S. | Lichtenstein, Lee | Lin, Pei | Meyerson, Matthew | Ojesina, Akinyemi I. | Pedamallu, Chandra Sekhar | Saksena, Gordon | Schumacher, Steven E. | Sougnez, Carrie | Stojanov, Petar | Tabak, Barbara | Taylor-Weiner, Amaro | Voet, Doug | Rosenberg, Mara | Zack, Travis I. | Zhang, Hailei | Zou, Lihua | Protopopov, Alexei | Santoso, Netty | Parfenov, Michael | Lee, Semin | Zhang, Jianhua | Mahadeshwar, Harshad S. | Tang, Jiabin | Ren, Xiaojia | Seth, Sahil | Yang, Lixing | Xu, Andrew W. | Song, Xingzhi | Pantazi, Angeliki | Xi, Ruibin | Bristow, Christopher A. | Hadjipanayis, Angela | Seidman, Jonathan | Chin, Lynda | Park, Peter J. | Kucherlapati, Raju | Akbani, Rehan | Ling, Shiyun | Liu, Wenbin | Rao, Arvind | Weinstein, John N. | Kim, Sang-Bae | Lee, Ju-Seog | Lu, Yiling | Mills, Gordon | Laird, Peter W. | Hinoue, Toshinori | Weisenberger, Daniel J. | Bootwalla, Moiz S. | Lai, Phillip H. | Shen, Hui | Triche, Timothy | Van Den Berg, David J. | Baylin, Stephen B. | Herman, James G. | Getz, Gad | Chin, Lynda | Liu, Yingchun | Murray, Bradley A. | Noble, Michael S. | Askoy, B. Arman | Ciriello, Giovanni | Dresdner, Gideon | Gao, Jianjiong | Gross, Benjamin | Jacobsen, Anders | Lee, William | Ramirez, Ricardo | Sander, Chris | Schultz, Nikolaus | Senbabaoglu, Yasin | Sinha, Rileen | Sumer, S. Onur | Sun, Yichao | Weinhold, Nils | Thorsson, Vésteinn | Bernard, Brady | Iype, Lisa | Kramer, Roger W. | Kreisberg, Richard | Miller, Michael | Reynolds, Sheila M. | Rovira, Hector | Tasman, Natalie | Shmulevich, Ilya | Ng, Santa Cruz Sam | Haussler, David | Stuart, Josh M. | Akbani, Rehan | Ling, Shiyun | Liu, Wenbin | Rao, Arvind | Weinstein, John N. | Verhaak, Roeland G.W. | Mills, Gordon B. | Leiserson, Mark D. M. | Raphael, Benjamin J. | Wu, Hsin-Ta | Taylor, Barry S. | Black, Aaron D. | Bowen, Jay | Carney, Julie Ann | Gastier-Foster, Julie M. | Helsel, Carmen | Leraas, Kristen M. | Lichtenberg, Tara M. | McAllister, Cynthia | Ramirez, Nilsa C. | Tabler, Teresa R. | Wise, Lisa | Zmuda, Erik | Penny, Robert | Crain, Daniel | Gardner, Johanna | Lau, Kevin | Curely, Erin | Mallery, David | Morris, Scott | Paulauskis, Joseph | Shelton, Troy | Shelton, Candace | Sherman, Mark | Benz, Christopher | Lee, Jae-Hyuk | Fedosenko, Konstantin | Manikhas, Georgy | Potapova, Olga | Voronina, Olga | Belyaev, Smitry | Dolzhansky, Oleg | Rathmell, W. Kimryn | Brzezinski, Jakub | Ibbs, Matthew | Korski, Konstanty | Kycler, Witold | ŁaŸniak, Radoslaw | Leporowska, Ewa | Mackiewicz, Andrzej | Murawa, Dawid | Murawa, Pawel | Spychała, Arkadiusz | Suchorska, Wiktoria M. | Tatka, Honorata | Teresiak, Marek | Wiznerowicz, Maciej | Abdel-Misih, Raafat | Bennett, Joseph | Brown, Jennifer | Iacocca, Mary | Rabeno, Brenda | Kwon, Sun-Young | Penny, Robert | Gardner, Johanna | Kemkes, Ariane | Mallery, David | Morris, Scott | Shelton, Troy | Shelton, Candace | Curley, Erin | Alexopoulou, Iakovina | Engel, Jay | Bartlett, John | Albert, Monique | Park, Do-Youn | Dhir, Rajiv | Luketich, James | Landreneau, Rodney | Janjigian, Yelena Y. | Kelsen, David P. | Cho, Eunjung | Ladanyi, Marc | Tang, Laura | McCall, Shannon J. | Park, Young S. | Cheong, Jae-Ho | Ajani, Jaffer | Camargo, M. Constanza | Alonso, Shelley | Ayala, Brenda | Jensen, Mark A. | Pihl, Todd | Raman, Rohini | Walton, Jessica | Wan, Yunhu | Demchok, John A. | Eley, Greg | Mills Shaw, Kenna R. | Sheth, Margi | Tarnuzzer, Roy | Wang, Zhining | Yang, Liming | Zenklusen, Jean Claude | Davidsen, Tanja | Hutter, Carolyn M. | Sofia, Heidi J. | Burton, Robert | Chudamani, Sudha | Liu, Jia
Nature  2014;513(7517):202-209.
Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. We propose a molecular classification dividing gastric cancer into four subtypes: tumours positive for Epstein–Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also knownasPD-L2); microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and tumours with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies.
doi:10.1038/nature13480
PMCID: PMC4170219  PMID: 25079317
7.  Prognosis of early mucinous gastric carcinoma 
Purpose
Little is known about the clinicopathological features of early mucinous gastric carcinoma (MGC). The purpose of this study was to compare the clinicopathological features and prognosis between patients with early MGC and those with early nonmucinous gastric carcinoma (NMGC).
Methods
We reviewed the records of 2,732 patients diagnosed with gastric carcinoma who were treated surgically. There were 14 patients (0.5%) with early MGC and 958 with early NMGC.
Results
Early MGC patients had a higher prevalence of elevated type (71.4%) compared with early NMGC patients (29.5%). More early MGC patients had submucosal carcinoma, compared with early NMGC patients (78.6% vs. 64.1%). The overall 5-year survival of the patients with early MGC was 97.2% as compared with 92.7% for the patients with early NMGC (P < 0.01). The statistically significant prognostic parameters influencing the 5-year survival rate according to Cox's proportional hazard regression model were: age (risk ratio, 2.22; 95% confidence interval [CI], 1.62-3.04; P < 0.01); sex (risk ratio, 1.97; 95% CI, 1.42-2.73; P < 0.01); and lymph node metastases (risk ratio, 1.88; 95% CI, 1.28-2.77; P < 0.01).
Conclusion
Patients with early MGC had a better prognosis than those with early NMGC. Mucinous histology itself appears not to be an independent prognostic factor. Therefore, early detection is important for improving the prognosis for patients with gastric carcinoma regardless of tumor histology.
doi:10.4174/astr.2014.87.1.5
PMCID: PMC4091442  PMID: 25025020
Gastric neoplasm; Mucinous; Prognosis; Tumor histology
8.  Evaluation of Protein Expression in Housekeeping Genes across Multiple Tissues in Rats 
Korean Journal of Pathology  2014;48(3):193-200.
Background
Housekeeping genes, which show constant protein expression patterns between different tissue types, are very important in molecular biological studies as an internal control for protein research.
Methods
The protein expression profiles of seven housekeeping genes (HPRT1, PPIA, GYS1, TBP, YWHAZ, GAPDH and ACTB) in various rat tissues (cerebrum, cerebellum, cardiac ventricle and atrium, psoas muscle, femoral muscle, liver, spleen, kidney, and aorta) were analyzed by Western blot and compared by coefficient of variation (CV).
Results
HPRT1 was stably expressed (CV≤10%) in six tissues (cerebrum, cerebellum, ventricle, femoral muscle, spleen, and kidney), PPIA was stably expressed in five tissues (cerebrum, cerebellum, ventricle, spleen and kidney), YWHAZ was stably expressed in three tissues (cerebrum, cerebellum, and kidney), and GAPDH was stably expressed in four tissues (cerebrum, ventricle, psoas muscle, and kidney). In comparison, GYS1, TBP, and ACTB were found to have CV values over 10% in all tissues. Of the seven genes examined, four (HPRT1, PPIA, YWHAZ, and GAPDH) were found to be stably expressed across multiple organs, with low CV values (≤10%).
Conclusions
These results will provide fundamental information regarding internal controls for protein expression studies and can be used for analysis of postmortem protein degradation patterns in forensic medicine.
doi:10.4132/KoreanJPathol.2014.48.3.193
PMCID: PMC4087132  PMID: 25013417
Genes, essential; Proteins; Tissues; Rats; Postmortem changes
10.  Class III β-tubulin is a predictive marker for taxane-based chemotherapy in recurrent and metastatic gastric cancer 
BMC Cancer  2013;13:431.
Background
Class III β-tubulin (TUBB3) is a prognostic marker in various tumors, but the role of TUBB3 in advanced gastric cancer is not clearly defined. We analyzed the significance of TUBB3 expression, along with that of excision repair cross-complementation group 1 (ERCC1) in recurrent and metastatic gastric cancer patients receiving taxane-based first-line palliative chemotherapy.
Methods
We reviewed the cases of 146 patients with advanced gastric adenocarcinoma who received taxane-based first-line palliative chemotherapy between 2004 and 2010 at Chonnam National University Hwasun Hospital (Gwangju, Korea). Immunohistochemical staining for TUBB3 and ERCC1 was performed using paraffin wax-embedded tumor tissues. We evaluated the patients’ response to chemotherapy, progression-free survival (PFS), and overall survival (OS).
Results
In total, 146 patients with advanced gastric cancer received docetaxel and cisplatin (n = 15) or paclitaxel and cisplatin (n = 131). The median PFS was significantly shorter for patients with high-level TUBB3 expression than for patients with low-level TUBB3 expression (3.63 vs. 6.67 months, P = 0.001). OS was not associated with TUBB3 expression (13.1 vs. 13.1 months, P = 0.769). By multivariate analysis, only TUBB3 was related to a shorter PFS (HR 2.74, 95% CI 1.91-3.91, P = 0.001). Patients with high-level ERCC1 expression showed a lower response rate than patients with low-level ERCC1 expression (24 vs. 63.2%, P = 0.001); however, ERCC1 had no clinical effect on PFS or OS.
Conclusions
TUBB3 was a strong predictive marker in recurrent and metastatic gastric cancer patients receiving taxane-based first-line palliative chemotherapy. No clinical impact of ERCC1 was evident in this setting.
doi:10.1186/1471-2407-13-431
PMCID: PMC4015872  PMID: 24053422
Class III β-tubulin (TUBB3); Excision repair cross-complementation group 1 (ERCC1); Taxane; Stomach neoplasm; Metastasis
11.  δ-CATENIN PROMOTES E-CADHERIN PROCESSING AND ACTIVATES β-CATENIN-MEDIATED SIGNALING: IMPLICATIONS ON HUMAN PROSTATE CANCER PROGRESSION 
Biochimica et biophysica acta  2012;1822(4):509-521.
δ-Catenin binds the juxtamembrane domain of E-cadherin and is known to be overexpressed in some human tumors. However, the functions of δ-catenin in epithelial cells and carcinomas remain elusive. We found that prostate cancer cells overexpressing δ-catenin show an increase in multi-layer growth in culture. In these cells, δ-catenin colocalizes with E-cadherin at the plasma membrane, and the E-cadherin processing is noticeably elevated. E-Cadherin processing induced by δ-catenin is serum-dependent and requires MMP- and PS-1/γ-secretase-mediated activities. A deletion mutant of δ-catenin that deprives the ability of δ-catenin to bind E-cadherin or to recruit PS-1 to E-cadherin totally abolishes the δ-catenin-induced E-cadherin processing and the multilayer growth of the cells. In addition, prostate cancer cells overexpressing δ-catenin display an elevated total β-catenin level and increase nuclear distribution, resulting in the activation of β-catenin/LEF-1-mediated transcription and their downstream target genes as well as androgen receptor-mediated transcription. Indeed, human prostate tumor xenograft in nude mice, which is derived from cells overexpressing δ-catenin, shows increased β-catenin nuclear localization and more rapid growth rates. Moreover, the metastatic xenograft tumor weights positively correlate with the level of 29 kD E-cadherin fragment, and primary human prostate tumor tissues also show elevated levels of δ-catenin expression and the E-cadherin processing. Taken together, these results suggest that δ-catenin plays an important role in prostate cancer progression through inducing E-cadherin processing and thereby activating β-catenin-mediated oncogenic signals.
doi:10.1016/j.bbadis.2011.12.015
PMCID: PMC3763829  PMID: 22261283
Prostate cancer; Catenin; LEF-1; E-cadherin; Androgen Receptor; Wnt
12.  Expression of Livin in Colorectal Cancer and Its Relationship to Tumor Cell Behavior and Prognosis 
PLoS ONE  2013;8(9):e73262.
Backgrounds
Expression of Livin, a member of the inhibitors of apoptosis protein family, is associated with tumor development and progression. The aims of this study were to evaluate whether Livin affects oncogenic biological behavior of colorectal cancer cells, and to document the relationship between its expression and various clinicopathological parameters in colorectal cancer.
Methods
We investigated the impact of Livin on tumor cell behavior by using the small interfering RNA and pcDNA3.1 vector in SW480 and DKO1 colorectal cancer cell lines. The expression of Livin was investigated by RT-PCR and immunohistochemistry in coloretcal cancer tissues. The apoptotic cells were visualized by TUNEL assay, and proliferative cells were visualized by Ki-67 antibody staining.
Results
Knockdown of Livin suppressed tumor cell migration and invasion in colorectal cancer cells. Knockdown of Livin induced the apoptosis by up-regulating of caspase-3, -7 and PARP activities and the cell cycle arrest by decreasing cyclin D1, cyclin D3, cyclin-dependent kinase 4 and 6, and by inducing p27 expression. The MAPK signaling cascades were significantly blocked by knockdown of Livin. In contrast, overexpression of Livin enhanced tumor cell migration and invasion, and inhibited the apoptosis and cell cycle arrest. The mean apoptotic index (AI) value of Livin positive tumors was significantly lower than AI of Livin negative tumors. However, there was no significant difference between Livin expression and Ki-67 labeling index (KI). Livin expression was significantly increased in colorectal cancer and metastatic lymph node tissues compared to normal colorectal mucosa and non-metastatic lymph node tissues and was associated with tumor stage, lymphovascular invasion, lymph node metastasis and poor survival.
Conclusions
These results indicate that Livin is associated with tumor progression by increasing tumor cell motility and inhibiting apoptosis in colorectal cancer.
doi:10.1371/journal.pone.0073262
PMCID: PMC3759411  PMID: 24023847
13.  Volume-conserving trans-cis isomerization pathways in photoactive yellow protein visualized by picosecond X-ray crystallography 
Nature chemistry  2013;5(3):212-220.
Trans-to-cis isomerization, the key reaction in photoactive proteins, cannot usually occur through the standard one-bond-flip mechanism. Due to spatial constraints imposed by a protein environment, isomerization is likely to proceed via a “volume-conserving” mechanism in which highly-choreographed atomic motions are expected, the details of which have not yet been directly observed. Here we employ time-resolved X-ray crystallography to structurally visualize isomerization of the p-coumaric acid chromophore in photoactive yellow protein with 100 picosecond time resolution and 1.6 Å spatial resolution. The structure of the earliest intermediate (IT) resembles a highly-strained transition state in which the torsion angle is located halfway between the trans and cis isomers. The reaction trajectory of IT bifurcates into two structurally distinct cis intermediates via hula-twist and bicycle-pedal pathways. The bifurcating reaction pathways can be controlled by weakening the hydrogen bond between the chromophore and an adjacent residue via E46Q mutation, which switches off the bicycle-pedal pathway.
doi:10.1038/nchem.1565
PMCID: PMC3579544  PMID: 23422563
14.  Early Colorectal Epithelial Neoplasm in Korea: A Multicenter Survey of Pathologic Diagnosis 
Korean Journal of Pathology  2013;47(3):245-251.
Background
The incidence of early colorectal epithelial neoplasm (ECEN) is increasing, and its pathologic diagnosis is important for patient care. We investigated the incidence of ECEN and the current status of its pathologic diagnosis.
Methods
We collected datasheets from 25 institutes in Korea for the incidence of colorectal adenoma with high grade dysplasia (HGD) and low grade dysplasia in years 2005, 2007, and 2009; and early colorectal carcinoma in the year 2009. We also surveyed the diagnostic terminology of ECEN currently used by the participating pathologists.
Results
The average percentage of diagnoses of adenoma HGD was 7.0%, 5.0%, and 3.4% in years 2005, 2007, and 2009, respectively. The range of incidence rates of adenoma HGD across the participating institutes has gradually narrowed over the years 2005 to 2009. The incidence rate of early colorectal carcinoma in the year 2009 was 21.2%. The participants did not share a single criterion or terminology for the diagnosis of adenoma HGD. The majority accepted the diagnostic terms that distinguished noninvasive, mucosal confined, and submucosal invasive carcinoma.
Conclusions
Further research requirements suggested are a diagnostic consensus for the histopathologic diagnosis of ECEN; and standardization of diagnostic terminology critical for determining the disease code.
doi:10.4132/KoreanJPathol.2013.47.3.245
PMCID: PMC3701820  PMID: 23837017
Colorectal neoplasms; Pathology, surgical; Multicenter study; Incidence; Diagnosis
16.  Overexpression of Snail is associated with lymph node metastasis and poor prognosis in patients with gastric cancer 
BMC Cancer  2012;12:521.
Background
Epithelial–mesenchymal transition (EMT) plays a significant role in tumor progression and invasion. Snail is a known regulator of EMT in various malignant tumors. This study investigated the role of Snail in gastric cancer.
Methods
We examined the effects of silenced or overexpressed Snail using lenti-viral constructs in gastric cancer cells. Immunohistochemical analysis of tissue microarrays from 314 patients with gastric adenocarcinoma (GC) was used to determine Snail’s clinicopathological and prognostic significance. Differential gene expression in 45 GC specimens with Snail overexpression was investigated using cDNA microarray analysis.
Results
Silencing of Snail by shRNA decreased invasion and migration in GC cell lines. Conversely, Snail overexpression increased invasion and migration of gastric cancer cells, in line with increased VEGF and MMP11. Snail overexpression (≥75% positive nuclear staining) was also significantly associated with tumor progression (P < 0.001), lymph node metastases (P = 0.002), lymphovascular invasion (P = 0.002), and perineural invasion (P = 0.002) in the 314 GC patients, and with shorter survival (P = 0.023). cDNA microarray analysis revealed 213 differentially expressed genes in GC tissues with Snail overexpression, including genes related to metastasis and invasion.
Conclusion
Snail significantly affects invasiveness/migratory ability of GCs, and may also be used as a predictive biomarker for prognosis or aggressiveness of GCs.
doi:10.1186/1471-2407-12-521
PMCID: PMC3552976  PMID: 23151184
Stomach; Adenocarcinoma; Snail; Lymph node metastasis; Survival
17.  Pancreatic hamartoma diagnosed after surgical resection 
A pancreatic hamartoma is a rare benign lesion that may be mistaken for malignancy. A pancreatic hamartoma can present with vague, non-specific symptoms, which can be difficult to diagnose despite modern diagnostic tools. We report here a pancreatic hamartoma diagnosed after surgical resection. A 52-year-old female presented with postprandial abdominal discomfort. Abdominal computed tomography and pancreatic magnetic resonance imaging revealed a 2.2 × 2.5-cm cystic mass in the pancreatic head. The patient underwent a pylorus-preserving pancreaticoduodenectomy. The histopathological and immunohistochemical studies helped make the diagnosis of pancreatic hamartoma. Here, we report a case of pancreatic hamartoma and review the relevant medical literature.
doi:10.4174/jkss.2012.83.5.330
PMCID: PMC3491237  PMID: 23166894
Hamartoma; Pancreas; Pancreaticoduodenectomy
18.  Current Trends of the Incidence and Pathological Diagnosis of Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs) in Korea 2000-2009: Multicenter Study 
Purpose
As a result of various independently proposed nomenclatures and classifications, there is confusion in the diagnosis and prediction of biological behavior of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). A comprehensive nationwide study is needed in order to understand the biological characteristics of GEP-NETs in Korea.
Materials and Methods
We collected 4,951 pathology reports from 29 hospitals in Korea between 2000 and 2009. Kaplan-Meier survival analysis was used to determine the prognostic significance of clinicopathological parameters.
Results
Although the GEP-NET is a relatively rare tumor in Korea, its incidence has increased during the last decade, with the most significant increase found in the rectum. The 10-year survival rate for well-differentiated endocrine tumor was 92.89%, in contrast to 85.74% in well differentiated neuroendocrine carcinoma and 34.59% in poorly differentiated neuroendocrine carcinoma. Disease related death was most common in the biliary tract (62.2%) and very rare in the rectum (5.2%). In Kaplan-Meier survival analysis, tumor location, histological classification, extent, size, mitosis, Ki-67 labeling index, synaptophysin expression, lymphovascular invasion, perineural invasion, and lymph node metastasis showed prognostic significance (p<0.05), however, chromogranin expression did not (p=0.148). The 2000 and 2010 World Health Organization (WHO) classification proposals were useful for prediction of the prognosis of GEP-NET.
Conclusion
The incidence of GEP-NET in Korea has shown a remarkable increase during the last decade, however, the distribution of tumors in the digestive system differs from that of western reports. Assessment of pathological parameters, including immunostaining, is crucial in understanding biological behavior of the tumor as well as predicting prognosis of patients with GEP-NET.
doi:10.4143/crt.2012.44.3.157
PMCID: PMC3467418  PMID: 23091441
Gastro-enteropancreatic neuroendocrine tumor; Incidence; Prognosis; Pathology
19.  Preoperative predictors of malignant gastric submucosal tumor 
Purpose
The preoperative prediction of malignant potential in patients with gastric submucosal tumors (SMTs) plays an important role in decisions regarding their surgical management.
Methods
We evaluated the predictors of malignant gastric SMTs in 314 patients with gastric SMTs who underwent surgery in Chonnam National University Hospital.
Results
The malignant SMTs were significantly associated with age (odds ratio [OR], 1.067; 95% confidence interval [CI], 1.042 to 1.091; P < 0.0001), presence of central ulceration (OR, 2.690; 95% CI, 1.224 to 5.909; P = 0.014), and tumor size (OR, 1.791; 95% CI, 1.483 to 2.164; P < 0.0001). Receiver operating characteristic curve analysis showed that tumor size was a good predictor of malignant potential. The most relevant predictor of malignant gastric SMT was tumor size with cut-offs of 4.05 and 6.40 cm.
Conclusion
Our findings indicated that age, central ulceration, and tumor size were significant preoperative predictors of malignant SMTs. We suggest that 4 cm be selected as a threshold value for malignant gastric SMTs. In patients with a gastric SMT larger than 4 cm with ulceration, wide resection of the full thickness of the gastric wall or gastrectomy with adequate margins should be performed because of its malignant potential.
doi:10.4174/jkss.2012.83.2.83
PMCID: PMC3412188  PMID: 22880181
Stomach neoplasms; Submucosal tumor; Malignant factor; Preoperative predictor
20.  Balsamic Vinegar Improves High Fat-Induced Beta Cell Dysfunction via Beta Cell ABCA1 
Diabetes & Metabolism Journal  2012;36(4):275-279.
Background
The aim of this study was to investigate the effects of balsamic vinegar on β-cell dysfunction.
Methods
In this study, 28-week-old Otsuka Long-Evans Tokushima Fatty (OLETF) rats were fed a normal chow diet or a high-fat diet (HFD) and were provided with tap water or dilute balsamic vinegar for 4 weeks. Oral glucose tolerance tests and histopathological analyses were performed thereafter.
Results
In rats fed both the both chow diet and the HFD, the rats given balsamic vinegar showed increased insulin staining in islets compared with tap water administered rats. Balsamic vinegar administration also increased β-cell ATP-binding cassette transporter subfamily A member 1 (ABCA1) expression in islets and decreased cholesterol levels.
Conclusion
These findings provide the first evidence for an anti-diabetic effect of balsamic vinegar through improvement of β-cell function via increasing β-cell ABCA1 expression.
doi:10.4093/dmj.2012.36.4.275
PMCID: PMC3428415  PMID: 22950058
Balsamic vinegar; Islets; Insulin; ABCA1; Diet, high-fat
21.  Effects of Aerobic Exercise Intensity on Abdominal and Thigh Adipose Tissue and Skeletal Muscle Attenuation in Overweight Women with Type 2 Diabetes Mellitus 
Diabetes & Metabolism Journal  2012;36(3):211-221.
Background
We investigated the effects of exercise intensity on abdominal and mid-thigh adipose tissue, attenuation of skeletal muscle, and insulin sensitivity in overweight women with type 2 diabetes mellitus (T2DM).
Methods
Twenty-eight patients were randomly assigned to control (CG, n=12), moderate intensity exercise (MEG, n=8), or vigorous intensity exercise (VEG, n=8) group. Subjects in both exercise groups completed a 12-week exercise program (MEG, 3.6 to 5.2 METs; VEG, ≥5.2 METs) that was monitored by accelerometers. We assessed body mass index (BMI), total fat area (TFA), visceral fat area (VFA), subcutaneous fat area (SFA), mid-thigh intramuscular adipose tissue (TIMAT), total skeletal muscle (TTM), low density skeletal muscle (TLDM), and normal density skeletal muscle (TNDM) using computed tomography, and measured insulin sensitivity with an insulin tolerance test (KITT), before and after the intervention.
Results
At baseline, the mean age was 53.8±7.9 years, duration of diabetes was 3.8±2.3 years, and BMI was 26.6±2.6 kg/m2. After 12 weeks, the percent change (%C) in BMI, TIMAT, and TLDM were not different among three groups. However, %C in TFA and VFA were significantly reduced in MEG compared to CG (P=0.026 and P=0.008, respectively). %C SFA was significantly reduced in VEG compared to CG (P=0.038) and %C TTM, TNDM, and KITT were significantly increased in VEG compared to the CG (P=0.044, P=0.007, and P=0.016, respectively).
Conclusion
Although there was no difference in the change in BMI among groups, TFA and VFA were more reduced in MEG, and only VEG increased TTM, TNDM, and insulin sensitivity compared to CG.
doi:10.4093/dmj.2012.36.3.211
PMCID: PMC3380125  PMID: 22737661
Abdominal fat; Attenuation of skeletal muscle; Diabetes mellitus, type 2; Exercise intensity; Mid-thigh adipose tissue
22.  Perfusion CT in Colorectal Cancer: Comparison of Perfusion Parameters with Tumor Grade and Microvessel Density 
Korean Journal of Radiology  2012;13(Suppl 1):S89-S97.
Objective
The purpose of this study was to prospectively compare pre-operative computed tomography (CT) perfusion parameters with tumor grade from colorectal adenocarcinoma (CRC) and to correlate pre-operative CT perfusion parameters with microvessel density (MVD) to evaluate angiogenesis in CRC.
Materials and Methods
Pre-operative perfusion CTs were performed with a 64-channel multidetector row CT in 27 patients (17 women and 10 men; age range 32-82 years) who were diagnosed with CRC involving the sigmoid and rectum between August 2006 and November 2007. All patients underwent surgery without pre-operative chemotherapy or radiation therapy. Dynamic perfusion CTs were performed for 65 seconds after intravenous injection of contrast medium (100 mL, 300 mg of iodine per mL, 5 mL/sec). Before surgery, blood flow (BF), blood volume, mean transit time (MTT), and permeability-surface area product were measured in the tumor. After surgery, one gastrointestinal pathologist evaluated tumor grade and performed immunohistochemical staining using CD 34 to determine MVD in each tumor. The Kruskal-Wallis test was used to compare CT perfusion parameters with tumor grade, and Pearson's correlation analysis was used to correlate CT perfusion parameters with MVD.
Results
In 27 patients with CRC, tumor grading was as follows: well differentiated (n = 8); moderately differentiated (n = 15); and poorly differentiated (n = 4). BF was higher in moderately differentiated CRC than well differentiated and poorly differentiated CRCs (p = 0.14). MTT was shorter in moderately differentiated than well differentiated and poorly differentiated CRCs (p = 0.039). The MVD was greater in poorly differentiated than well differentiated and moderately differentiated CRCs (p = 0.034). There was no significant correlation between other perfusion parameters and tumor grade. There was no significant correlation between CT perfusion parameters and MVD.
Conclusion
BF and MTT measurement by perfusion CT is effective in predicting moderately differentiated CRCs. However, perfusion CT is limited in distinguishing well differentiated and poorly differentiated CRCs. Pre-operative perfusion CT does not reflect the MVD of CRCs.
doi:10.3348/kjr.2012.13.S1.S89
PMCID: PMC3341466  PMID: 22563293
Colon cancer; CT; Perfusion; Angiogenesis
23.  Recurring gastrointestinal stromal tumor with splenic metastasis 
Journal of the Korean Surgical Society  2011;81(Suppl 1):S25-S29.
Malignant gastrointestinal stromal tumors (GISTs) are rare non-epithelial, mesenchymal neoplasms of the gastrointestinal tract that metastasize or recur in 30% of patients who undergo surgical resection with curative intent. A 59-year-old man visited our hospital for an examination of a palpable mass in the left abdomen. Fourteen months prior to his visit, the patient underwent gastric wedge resection to remove a GIST of the gastric cardia. At the time of surgery, no evidence of metastatic disease was observed and the pathological interpretation was a high-risk GIST. A follow-up computed tomography scan of the abdomen revealed a partially necrotic solid mass (9.8 × 7.6 cm) and enhancing mass in the spleen (2.3 cm). On exploration, multiple masses were found in the liver, greater omentum, and mesentery. Here, we report a case of recurring GIST of the stomach that metastasized to the spleen. To the best of our knowledge, few reports of metastasis to the spleen exist.
doi:10.4174/jkss.2011.81.Suppl1.S25
PMCID: PMC3267060  PMID: 22319733
Gastrointestinal stromal tumors; Neoplasm metastasis; Spleen
24.  Primary leiomyosarcoma of the pancreas 
Journal of the Korean Surgical Society  2011;81(Suppl 1):S69-S73.
Primary sarcomas of the pancreas are extremely rare, accounting for 0.1% of malignant pancreatic (non-islet) neoplasms. Pancreatic leiomyosarcoma is a highly aggressive malignancy that spreads in a similar manner to gastric leiomyosarcoma, i.e., by adjacent organ invasion, hematogenous spread, and lymph node metastasis. These tumors are large at the time of diagnosis and are usually found at an advanced stage. We report a case of a 70-year-old female with intermittent right upper quadrant abdominal discomfort. Radiological, histopathological, and immunohistochemical studies revealed the tumor to be a primary leiomyosarcoma of the pancreas. Herein, we describe a patient with a primary leiomyosarcoma of the pancreas who presented with clinical and radiological findings indicative of a mass in the pancreatic head.
doi:10.4174/jkss.2011.81.Suppl1.S69
PMCID: PMC3267071  PMID: 22319744
Leiomyosarcoma; Pancreas; Primary
25.  Effects of Aerobic Exercise vs. Resistance Training on Endothelial Function in Women with Type 2 Diabetes Mellitus 
Diabetes & Metabolism Journal  2011;35(4):364-373.
Background
There is controversy over whether aerobic or resistance exercise is more effective for improving endothelial function in type 2 diabetes mellitus (T2DM). This study was aimed to investigate the effects of an aerobic and resistance training program on endothelial function, and the influences of glycemic control, body weight changes, and aerobic capacity in T2DM.
Methods
Total 40 overweight women with T2DM were assigned into 3 groups: an aerobic exercise group (AEG, n=13), resistance exercise group (REG, n=12), and control group (CG, n=15), and followed either brisk walking for the AEG or resistance band training for the REG, 60 minutes per day, 5 days per week for 12 weeks with monitoring daily activity using accelerometers. We assessed endothelial function by flow-mediated dilation (FMD), and aerobic capacity by oxygen uptake at anaerobic threshold (AT_VO2) at baseline and following training program.
Results
The mean participants' age was 57.0±6.8 years, and body mass index (BMI) was 27.0±2.3 kg/m2. After intervention, FMD increased by 2.2±1.9% in AEG, which differed from REG and CG (P=0.002), despite of decreased body weight (BW) in both AG and RG (2.8±2.5%, P=0.002; 1.6±2.0%, P=0.017, respectively). A significant increased AT_VO2 and decreased HbA1c were found only in AEG. In all participants, FMD was changed with the significant relations to the AT_VO2 (r=0.348, P=0.035), but not to HbA1c levels or BW.
Conclusion
Aerobic exercise appears to be more beneficial than resistance exercise for improving endothelial function in T2DM. In addition, aerobic capacity could be a better predictor of changes in FMD than BW and glycemic control.
doi:10.4093/dmj.2011.35.4.364
PMCID: PMC3178697  PMID: 21977456
Aerobic exercise; Diabetes mellitus, type 2; Endothelial function; Resistance training

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