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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.
PMCID: PMC2710792  PMID: 19598312
Cavernous hemangioma; Cecum; Laparoscopic surgery
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.
PMCID: PMC3763829  PMID: 22261283
Prostate cancer; Catenin; LEF-1; E-cadherin; Androgen Receptor; Wnt
4.  Expression of Livin in Colorectal Cancer and Its Relationship to Tumor Cell Behavior and Prognosis 
PLoS ONE  2013;8(9):e73262.
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.
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.
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.
These results indicate that Livin is associated with tumor progression by increasing tumor cell motility and inhibiting apoptosis in colorectal cancer.
PMCID: PMC3759411  PMID: 24023847
5.  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.
PMCID: PMC3579544  PMID: 23422563
7.  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.
PMCID: PMC3491237  PMID: 23166894
Hamartoma; Pancreas; Pancreaticoduodenectomy
8.  Preoperative predictors of malignant gastric submucosal tumor 
The preoperative prediction of malignant potential in patients with gastric submucosal tumors (SMTs) plays an important role in decisions regarding their surgical management.
We evaluated the predictors of malignant gastric SMTs in 314 patients with gastric SMTs who underwent surgery in Chonnam National University Hospital.
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.
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.
PMCID: PMC3412188  PMID: 22880181
Stomach neoplasms; Submucosal tumor; Malignant factor; Preoperative predictor
9.  Balsamic Vinegar Improves High Fat-Induced Beta Cell Dysfunction via Beta Cell ABCA1 
Diabetes & Metabolism Journal  2012;36(4):275-279.
The aim of this study was to investigate the effects of balsamic vinegar on β-cell dysfunction.
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.
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.
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.
PMCID: PMC3428415  PMID: 22950058
Balsamic vinegar; Islets; Insulin; ABCA1; Diet, high-fat
10.  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.
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).
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.
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).
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.
PMCID: PMC3380125  PMID: 22737661
Abdominal fat; Attenuation of skeletal muscle; Diabetes mellitus, type 2; Exercise intensity; Mid-thigh adipose tissue
11.  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.
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.
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.
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.
PMCID: PMC3341466  PMID: 22563293
Colon cancer; CT; Perfusion; Angiogenesis
12.  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.
PMCID: PMC3267060  PMID: 22319733
Gastrointestinal stromal tumors; Neoplasm metastasis; Spleen
13.  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.
PMCID: PMC3267071  PMID: 22319744
Leiomyosarcoma; Pancreas; Primary
14.  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.
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.
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.
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.
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.
PMCID: PMC3178697  PMID: 21977456
Aerobic exercise; Diabetes mellitus, type 2; Endothelial function; Resistance training
15.  The Correlations between Extremity Circumferences with Total and Regional Amounts of Skeletal Muscle and Muscle Strength in Obese Women with Type 2 Diabetes 
Diabetes & Metabolism Journal  2011;35(4):374-383.
Insulin resistance is related to central obesity and the amount of skeletal muscle. A simple and practical anthropometric marker for muscle mass is not known, although waist circumference (WC) is used as an indicator of abdominal obesity. The aims of this study were to investigate whether arm (AC) and thigh circumferences (TC) can be used as an indicator of muscle mass and if they are related to muscle strength.
A total of 110 obese (body mass index [BMI]≥25 kg/m2) women with type 2 diabetes were enrolled, and WC, AC, and TC were measured. Abdominal visceral fat (AVF), subcutaneous fat (ASF), and total fat (ATF) were assessed by computed tomography, regional muscle (MM), and fat mass by dual-energy X-ray absorptiometry, muscle strength by one repetition maximum (1RM) of both extremities (chest and leg press) and insulin resistance by KITT.
The mean age was 56.2±7.3 years, duration of diabetes was 4.2±4.4 years, and BMI was 27.2±2.8 kg/m2. WC was correlated with ATF, AVF, and ASF (r=0.728, P<0.001; r=0.515, P<0.001; r=0.608, P<0.001, respectively). Arm MM was correlated with AC (r=0.500, P<0.001), and leg MM with TC (r=0.291, P=0.002). Upper 1RM was related to AC/WC ratio (r=0.359, P<0.001), and lower 1RM was to TC/WC ratio (r=0.286, P=0.003). Insulin resistance had significant relations with AVF, WC, and total MM (r=-0.262, P=0.008; r=-0.217, P=0.029; r=0.160, P=0.031, respectively).
The muscle mass was related to extremity circumferences, and muscle strength was to extremity/waist circumference ratio in obese women with type 2 diabetes.
PMCID: PMC3178698  PMID: 21977457
Circumference; Diabetes mellitus, type 2; Muscle mass; Muscle strength
16.  Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells 
Undifferentiated carcinoma with osteoclast-like giant cells is a rare neoplasm of the exocrine pancreas. Some similar cases have been reported, but the histogenesis of these tumors varies and is controversial. We report here on a case of undifferentiated carcinoma of the pancreas with osteoclast-like giant cells. A 77-year old woman presented with abdominal pain and anorexia. Abdominal computed tomography and magnetic resonance imaging showed an approximately 10 × 5 cm highly attenuated mass arising from the tail of the pancreas and invading the spleen and adjacent bowel loop. The initial impression was a malignant endocrine tumor or solid-pseudopapillary tumor of the pancreas. The patient underwent a distal pancreatectomy with splenectomy and left hemicolectomy. The histopathology and immunohistochemistry helped make the diagnosis that of an undifferentiated carcinoma with osteoclast-like giant cells of the pancreas.
PMCID: PMC3204565  PMID: 22066115
Osteoclast-like giant cells; Undifferentiated carcinoma; Pancreas
17.  Direct Observation of Myoglobin Structural Dynamics from 100 picoseconds to 1 microsecond with Picosecond X-ray Solution Scattering 
Here we report structural dynamics of equine myoglobin (Mb) in response to the CO photodissociation visualized by picosecond time-resolved X-ray solution scattering. The data clearly reveals new structural dynamics that occurs in the timescale of ~360 picoseconds (ps) and ~9 nanoseconds (ns), which have not been clearly detected in previous studies.
PMCID: PMC2999690  PMID: 20733999
18.  Clinicopathologic characteristics of serosa-positive gastric carcinoma in elderly patients 
The relationship between the prognosis and the age of patients with gastric carcinoma is controversial. This study examined the clinicopathologic features of elderly gastric carcinoma patients with serosal invasion.
We reviewed the hospital records of 136 elderly gastric carcinoma patients with serosal invasion retrospectively to compare the clinicopathologic findings in the elderly (aged > 70 years) and young (aged < 36 years).
The 5-year survival rates of elderly and young patients with curative resection did not differ statistically (33.9% vs. 43.3%; P = 0.318). Multivariate analysis showed that two factors were independent, statistically significant parameters associated with survival: histologic type (risk ratio, 1.805; 95% confidence interval [CI], 1.041 to 3.132; P < 0.05) and operative curability (risk ratio, 2.506; 95% CI, 1.371 to 4.581; P < 0.01).
This study demonstrated that elderly gastric carcinoma patients with serosal invasion do not have a worse prognosis than young patients. The important prognostic factor was whether the patients underwent curative resection.
PMCID: PMC3204556  PMID: 22066096
Gastric carcinoma; Serosal invasion; Elderly; Prognosis; Age
19.  Small Rice Bowl-Based Meal Plan for Energy and Marcronutrient Intake in Korean Men with Type 2 Diabetes: A Pilot Study 
Diabetes & Metabolism Journal  2011;35(3):273-281.
Koreans eat rice, which is usually served in a rice bowl. We investigated the effect of a meal plan using small rice bowls on the total energy intake (TEI) and the marcronutrient intake in Korean men with type 2 diabetes.
A total of 62 men with type 2 diabetes were divided by body mass index (BMI) (normal weight [NW], BMI<23 kg/m2; overweight [OW], 23≤BMI<25 kg/m2; obese [OB], BMI≥25 kg/m2) and proportions of carbohydrate intake to TEI (PCI) (low carbohydrate intake [LC], <55%; recommended carbohydrate intake [RC], ≥55% and ≤60%; high carbohydrate intake [HC], >60%). The 3-day dietary records were analyzed for TEI and proportions of macronutrients, before and 2 weeks after a small-sized (300 mL) rice bowl based education was given.
There were no significant differences in the age and BMI within the sub-groups by BMI and PCI groups. In baseline, the ratio of TEI to recommended total energy intake (RTR) of OW and OB were higher than that of NW. The PCI of HC was higher than that of LC and alcohol intake of HC was lower than that of LC. After education, the reduction of RTREI in OB was higher than that in OW and NW. The reduction of PCI in HC was higher than that of LC.
A small rice bowl based meal plan was effective for the reduction of energy intake and control of marcronutrient intake in Korean obese men with type 2 diabetes consuming a high carbohydrate diet.
PMCID: PMC3138099  PMID: 21785748
Carbohydrate-restrict; Diabetes mellitus, type 2; Diabetic diet; Men
20.  Basal-like breast cancer displays distinct patterns of promoter methylation 
Cancer biology & therapy  2010;9(12):1017-1024.
Recent microarray profiling studies on breast cancer have identified distinct subtypes that are associated with different clinical outcomes. Promoter hypermethylation of several known or putative tumor suppressor genes occurs frequently during the pathogenesis of breast cancer. We proposed that immunohistopathologic subtypes of breast cancer are likely to contain distinct promoter methylation patterns. A panel of ten gene promoters was assessed by quantitative multiplex methylation-specific PCR in 114 invasive ductal carcinomas from Korea representing the three major subtypes [57 luminal, 24 human epidermal growth factor 2 (HER2), and 33 basal-like] based on immunohistochemical findings of estrogen receptor, progesterone receptor, HER2, cytokeratin 5/6 and epidermal growth factor receptor. The median methylation levels of HIN1, RASSF1A and TWIST, and the average methylation ratio were significantly lower in basal-like subtype compared to luminal or HER2 subtypes. In contrast, BRCA1 methylation level was significantly higher in basal-like subtype than in luminal subtype. The methylation status of a panel of four genes (APC1, CDH, BRCA1 and RAR-β) in luminal and HER2 subtypes were dissimilar, where HER2 tumors showed a significantly higher level of methylation compared to luminal tumors. These results suggest that gene methylation in breast cancer can potentially serve as epigenetic biomarkers and may contribute further to current breast cancer classification.
PMCID: PMC3094906  PMID: 20505321
breast cancer; basal-like; luminal; HER2; methylation; quantitation
21.  Effects of Sphingosine-1-Phosphate on Neural Differentiation and Neurite Outgrowth in Neuroblastoma Cells 
Chonnam Medical Journal  2011;47(1):27-30.
Sphingosine-1-phosphate (S1P) is emerging as a new class of second messenger involved in cellular proliferation, differentiation, and apoptosis and is implicated in diverse physiological functions. Despite many studies on the biological functions of S1P, however, little is known about its role in neuronal differentiation. By use of reverse transcription-polymerase chain reaction and immunostaining, this study aimed to explore whether S1P can differentiate neuroblastoma cells into neural cells. After incubation with 1 uM or 10 uM S1P, the number of neurite-bearing cells increased. Furthermore, the neuroblastoma cells revealed immunoreactivity for neural-specific markers such as GAP43, NFH, and SYP by immunostaining. The expression of NFH, MAP2, SYP, NeuroD1, and SYT mRNA, which is specific for neurons, was increased as shown by RT-PCR studies. The results of this study suggest that that S1P can induce neuronal differentiation and may be a good candidate for the treatment of neurodegenerative diseases.
PMCID: PMC3214862  PMID: 22111053
Cell differentiation; Neurons; Sphingosine-1-phosphate
22.  The Usefulness of an Accelerometer for Monitoring Total Energy Expenditure and Its Clinical Application for Predicting Body Weight Changes in Type 2 Diabetic Korean Women 
Korean Diabetes Journal  2010;34(6):374-383.
The purpose of this study was to evaluate the usefulness of an accelerometer in predicting body weight (BW) change during a lifestyle intervention and to find out whether exercise or overall physical activity is associated with change in insulin sensitivity and body composition.
A total of 49 overweight (body mass index [BMI] ≥ 23 kg/m2) women with diabetes were enrolled and performed lifestyle intervention while monitoring BW, total energy expenditure (TEE) and physical activity energy expenditure (PAEE) using an accelerometer, and energy intake (EI) using a three-day dietary record at baseline and every 2 weeks for 12 weeks. We assessed body composition using bioimpedance analysis and compared the actual BW change to the predicted BW change, which was calculated from the energy deficit (ED) between EI and TEE (ED = EI-TEE).
Mean age was 57.2 years, duration of diabetes was 8.0 years, and BMI was 27.8 kg/m2. There was no significant difference between EI and TEE at baseline. For 12 weeks, the ED was 474.0 kcal·day-1, which was significantly correlated with BW change (-3.1 kg) (r = 0.725, P < 0.001). However, the actual BW change was 50% lower than the predicted BW change. Both TEE and PAEE correlated with change in KITT (r = 0.334, P = 0.019; r = 0.358, P = 0.012, respectively), BMI (r = -0.395, P = 0.005; r = -0.347, P = 0.015, respectively), and fat mass (r = -0.383, P = 0.007; r = -0.395, P = 0.005, respectively), but only TEE correlated with fat free mass change (r = -0.314, P = 0.030).
The accelerometer appears to be a useful tool for measuring TEE under free-living conditions for both short- and long-term periods.
PMCID: PMC3021114  PMID: 21246011
Accelerometer; Energy balance; Energy intake; Physical activity energy expenditure; Total energy expenditure
23.  Spontaneous Rupture of a Functioning Adrenocortical Carcinoma 
Yonsei Medical Journal  2010;51(6):974-977.
Adrenocortical carcinoma (ACC) is a rare malignancy with poor prognosis, and it can be classified as either a functional or nonfunctional tumor. Affected patients usually present with abdominal pain or with symptoms related to the mass effect or hormonal activity of the tumor. Several cases of spontaneously ruptured nonfunctional adrenocortical carcinoma have been reported, but no case of a spontaneous rupture of functioning adrenocortical carcinoma has been described. We report a functioning adrenocortical carcinoma that spontaneously ruptured during a work-up.
PMCID: PMC2995965  PMID: 20879070
Adrenocortical carcinoma; hormones; spontaneous rupture
24.  Apparent Diffusion Coefficient Value of Diffusion-Weighted Imaging for Hepatocellular Carcinoma: Correlation with the Histologic Differentiation and the Expression of Vascular Endothelial Growth Factor 
Korean Journal of Radiology  2010;11(3):295-303.
To evaluate whether the histopathological differentiation and the expression of vascular endothelial growth factor (VEGF) of hepatocellular carcinoma (HCC) do show correlation with the apparent diffusion coefficient (ADC) value on diffusion-weighted imaging (DWI).
Materials and Methods
Twenty-seven HCCs from 27 patients who had undergone preoperative liver MRI (1.5T) and surgical resection were retrospectively reviewed. DWI was obtained with a single-shot, echo-planar imaging sequence in the axial plane (b values: 0 and 1,000 sec/mm2). On DWIs, the ADC value of the HCCs was measured by one radiologist, who was kept 'blinded' to the histological findings. Histopathologically, the differentiation was classified into well (n = 9), moderate (n = 9) and poor (n = 9). The expression of VEGF was semiquantitatively graded as grade 0 (n = 8), grade 1 (n = 9) and grade 2 (n = 10). We analyzed whether the histopathological differentiation and the expression of VEGF of the HCC showed correlation with the ADC value on DWI.
The mean ADC value of the poorly-differentiated HCCs (0.9 ± 0.13×10-3 mm2/s) was lower than those of the well-differentiated HCCs (1.2 ± 0.22×10-3 mm2/s) (p = 0.031) and moderately-differentiated HCCs (1.1 ± 0.01×10-3 mm2/s) (p = 0.013). There was a significant correlation between the differentiation and the ADC value of the HCCs (r = -0.51, p = 0.012). The mean ADC of the HCCs with a VEGF expression grade of 0, 1 and 2 was 1.1 ± 0.17, 1.1 ± 0.21 and 1.1 ± 0.18×10-3 mm2/s, respectively. The VEGF expression did not show correlation with the ADC value of the HCCs (r = 0.07, p = 0.74).
The histopathological differentiation of HCC shows inverse correlation with the ADC value. Therefore, DWI with ADC measurement may be a valuable tool for noninvasively predicting the differentiation of HCC.
PMCID: PMC2864856  PMID: 20461183
Liver neoplasm; Liver neoplasm, MR; Magnetic resonance (MR), diffusion study
25.  Hepatocellular carcinoma with characteristic mucin production: a case report 
Cases Journal  2009;2:6789.
We present a unique case of hepatocellular carcinoma with mucin-producing gland formation. A 53-year-old man with hepatitis B infection presented with weight loss for the past month. Computed tomography demonstrated a 10 × 9.8 cm mass in the right hepatic lobe accompanied by cirrhotic changes in the hepatic parenchyma. Right hepatectomy was performed, and the tumor cut surface showed a poorly-circumscribed, white to pink tumor with numerous nodules and extensive necrosis. Microscopically, the tumor was composed of thick trabeculae and large, irregularly-shaped islands, both of which were filled with pleomorphic eosinophilic hepatoid cells or gland-forming columnar cells with mucin production. Those cells were immunoreactive for cytokeratin 19 in both the trabeculae and the glands. In some tumor cells, limited immunoreactivity for cytokeratin 7, epithelial membrane antigen and carcinoembryonic antigen was noted. The cells forming thick trabeculae were focally positive for hepatocyte paraffin 1 and alpha-fetoprotein. We suggest that this tumor shows bidirectional differentiation into hepatocytes and cholangiocytes, supporting the concepts that human hepatocarcinogenesis can be based on transformation of progenitor cells which can imply divergent differentiation.
PMCID: PMC2769314  PMID: 19918544

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