• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.9 no.2
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• pp.226-232
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• 2006

Purpose: The aim of this study was to evaluate the influence of leptin on biochemical markers of bone metabolism in childhood obesity. Methods: A total of 50 male children (25 obese and 25 controls) were recruited from the pediatric outpatient clinic at the Chosun University Hospital from November 1st 2005 to May 30th 2006. BMI, body fat percentage, serum leptin, bone-specific alkaline phosphatase (B-ALP), C-terminal propeptide of type 1 collagen (CICP), total deoxypyridinoline crosslinks (total DPD) were measured. The correlations of leptin with BMI, body fat percentage, B-ALP, CICP, total DPD were analyzed by Pearson's correlation. In a multiple stepwise regression analysis, leptin after correction for body weight was evaluated if there was a correlation with biochemical markers of bone formation and resorption respectively. Results: The leptin levels of the obese group were significantly higher than those of the control group (p=0.012). In the obese group, the leptin level was significantly positively correlated with the BMI (r=0.551, p=0.01) and the percentage of body fat (r=0.584, p=0.018). In the obese group, of bone markers, B-ALP (r=-0.613, p=0.026) and CICP (r=-0.583, p=0.037) were negatively correlated with leptin. B-ALP (r=-0.728, p=0.007) and CICP (r=-0.684, p=0.014) were negatively correlated with leptin when corrected for body weight. In the control group, bone markers were not correlated with leptin. In the multiple stepwise regression analyses, there was a negative correlation between the leptin and B-ALP (Y=-39.653X+356.341, p=0.026), CICP (Y=-13.437X+ 116.013, p=0.037) respectively in the obese group. Conclusion: Leptin was a significant factor in the bone formation but not in bone resorption in childhood obesity.

• Journal of Life Science
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• v.29 no.2
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• pp.265-271
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• 2019

In general, specific gravity (SG) and urinary creatinine (CR) have been used to adjust urinary cadmium (Cd) concentrations. However, the validity of correction methods has been controversial. We compared the two adjustments to evaluate associations between urinary Cd and various renal damage markers and to evaluate the relationship between urinary Cd concentration and renal disease markers, such as estimated glomerular filtration rate (eGFR), in a relatively large general population sample. Among the 1,086 volunteers who were enrolled in this study, 862 healthy volunteers who did not have kidney disease were included in the final analysis. Urinary Cd, malondialdehyde (MDA), and N-acetyl-${\beta}$-D-glucosaminidase (NAG) concentrations were measured, the creatinine-based eGFR was calculated, and the relationships between these markers were subsequently analyzed. This study showed the use of urinary Cd concentration adjusted with SG rather than with urinary creatinine may be appropriate in studies evaluating renal function based on Cd exposure. Urinary Cd concentration adjusted with SG had a positive correlation with urinary MDA levels and a negative correlation with eGFR. This relationship was relatively stronger in women than in men. This study showed that urinary Cd level was associated with decreased eGFR in the general population, and oxidative stress was likely to act as an intermediator in this process. These results suggest that eGFR can be a very good indicator of kidney damage caused by Cd exposure in the general population.

• Journal of Chest Surgery
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• v.33 no.5
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• pp.407-418
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• 2000

Background: With open heart surgery(OHS), it has been recognized that many postoperative complications and postperfusion syndrome are associated with the activations of complements and leulocytes. Recently, some investigators also demonstrated that interlukin-6(IL-6) linked highly with postperfusion syndrome. The puropose of this study was to investigate the sequential changes of the IL-6 and to clarify each IL-6 relationship to the complements(C3, C4) and inflammatory response following cardiopulmonary bypass(CPB). Material and Method: To determine serum levels of IL-6, complements, leukocytes, and biochemistric markers of liver and renal function, blood samples were taken from th radial artery in 30 adult patients undergoing OHS with CPB. Result: Serum IL-6 levels incrased significantly at 10 minutes after CPB-on(CPB-10) in comparison with the control levels and reached the peak at CPB-off(p<0.05). Serum complement levels declined rapidly at CPB-10 and remained at the lower levels during CPB(p<0.01). Sequential changes of IL-6 levels had positive correlations with the changes of total leukocytes and neutrophil fractions(p<0.05), but had negative correlations with lymphocyte fractions(p<0.05). Changes of C3 related postively to monocyte fractions(p<0.05). Postoperative levels of total protein and albumin, decreased significantly in comparison with the control levels(p<0.01), while the postoperative levels of AST(aspartate transaminase) and bilirubin increased (p<0.01). At CPB-off, IL-6 levels had negative correlations with total protein and albumin levels(r=-0.60, -0.47 respectively, p<0.05), whereas C3 levels had positive correlations with albumin levels(r=0.40, p<0.05). IL-6 levels, as well as neutrophil fractions, had positive correlations with aortic clamp time(ACT) and total bypass time(TBT) (IL-6; r=0.82, 0.79 respectively, neutrophil fractions; r=0.50, 0.56 respectively, p<0.05), wheres lymphocyte frations and albumin levels had negative correlations whith ACT and TBT(lymphocyte fractions; r=-0.52, -0.58 respectively, albumin; r=-0.58, -0.55 respectively, p<0.05). Conclusion: These data showed that elevated production of serum IL-6 during CPB may play a pivotal role in systemic inflammatory responses and prologed CPB period may be assosiated with more sever postperfusion syndromes.

• Journal of Breast Cancer
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• v.21 no.4
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• pp.406-414
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• 2018

Purpose: T-cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3) is an emerging immune response molecule related to T-cell anergy. There has been tremendous interest in breast cancer targeting immune checkpoint molecules, especially in the triple-negative breast cancer (TNBC). This study was designed to investigate TIM-3 expression on tumor infiltrating lymphocytes (TILs), its relationships with clinicopathological parameters and expression of programmed death receptor 1 (PD-1)/programmed death receptor ligand 1 (PD-L1), and its prognostic role. Methods: Immunohistochemistry on tissue microarray blocks produced from 109 samples of invasive ductal carcinoma type TNBC was performed with antibodies toward TIM-3, PD-1, PD-L1 and breast cancer-related molecular markers. Associations between their expression and clinicopathological parameters as well as survival analyses were performed. Results: TIM-3 was expressed in TILs from all 109 TNBCs, consisting of 17 cases (<5%), 31 cases (6%-25%), 48 cases (26%-50%), and 13 cases (>51%). High TIM-3 was significantly correlated with younger patients (p=0.0101), high TILs (p=0.0029), high tumor stage (p=0.0018), high PD-1 (p=0.0001) and high PD-L1 (p=0.0019), and tended to be associated with higher histologic grade, absence of extensive in situ components and microcalcification. High TIM-3 expression was significantly associated with a combinational immunophenotype group of high PD-L1 and high PD-1 (p<0.0001). High TIM-3 demonstrated a significantly better disease-free survival (DFS) (p<0.0001) and longer overall survival (OS) (p=0.0001), together with high TILs and high PD-1. In univariate survival analysis, high TIM-3 showed reduced relapse risk (p<0.0001) and longer OS (p=0.0003), together with high PD-1 expression. In multivariate analysis, high TIM-3 was statistically significant in predicting prognosis, showing better DFS (hazard ratio [HR], 0.0994; 95% confidence interval [CI], 0.0296-0.3337; p=0.0002) and longer OS (HR, 0.1109; 95% CI, 0.0314-0.3912; p=0.0006). Conclusion: In this study, we demonstrate that TIM-3 expression is an independent positive prognostic factor in TNBC, despite its association with poor clinical and pathologic features.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5427-5432
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• 2012

Background and Purpose: Ovarian cancer is the leading cause of death among gynecologic cancers because of the lack of effective early detection methods. Accuracies of the human epididymis protein 4 (HE4) and mesothelin in detecting ovarian cancer have never been systematically assessed. The current systematic review aimed to tackle this issue. Methods: MEDLINE, EMBASE, and Cochrane databases were searched (September 1995-November 2011) for studies on the diagnostic performances of HE4 and mesothelin in differentiating ovarian cancer from other benign gynecologic diseases. QUADAS items were used to evaluate the qualities of the studies. Meta-DiSc software was used to handle data from the included studies and to examine heterogeneity. All included studies for diagnostic performance were combined with sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratios (DORs) with 95% confidence intervals (CIs), summary receiver operating characteristic (SROC) curves, and areas under the SROC curves (AUC). Results: A total of 18 studies and 3,865 patients were eligible for the final analysis. The pooled sensitivity estimates for HE4 (74.4%) were significantly higher than those for mesothelin (49.3%). The pooled specificity estimates for mesothelin (94.5%) were higher than those for HE4 (85.8%). The pooled DOR estimates for HE4 (26.22) were higher than those for mesothelin (24.01). The SROC curve for HE4 showed better diagnostic accuracy than that for mesothelin. The PLR and NLR of HE4 were 6.33 (95% CI: 3.58 to 11.18) and 0.27 (95% CI: 0.21 to 0.34), respectively. The PLR and NLR for mesothelin were 11.0 (95% CI: 6.21 to 19.59) and 0.51 (95% CI: 0.42 to 0.62), respectively. The combination of the two tumor markers or their combination with CA-125 increased sensitivity and specificity to different extents. Conclusion: The diagnostic accuracy of HE4 in differentiating ovarian cancer from other benign gynecologic diseases is better than that of soluble mesothelin-related protein. Combinations of two or more tumor markers show more sensitivity and specificity.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3521-3526
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• 2013

Objective: The current study explored the expression of KAI1/CD82 and MRP1/CD9 and its significance in laryngeal squamous cell carcinoma (LSCC). Methods: The expression levels of KAI1/CD82 and MRP1/CD9 in 100 LSCC tissue specimens, as well as in 30 para-LSCC non-carcinomatous tissue specimens randomly taken from the patients, were assessed using the quantitative polymerase chain reaction (Q-PCR) and immunohistochemistry and correlations with pathological parameters of LSCC and their influence on survival function were analyzed. Results: KAI1/CD82 and MRP1/CD9 showed basically consistent changes in both mRNA and protein expression. Their expression in the 30 LSCC specimens was significantly lower compared with that in the corresponding non-carcinous tissues (P < 0.01 or 0.05), notably correlating with TNM stage, differentiation degree, clinical stage, and lymphatic metastasis (P < 0.01 or 0.05), but not gender, age, and LSCC growth sites (P > 0.05). The median survival of patients with positive KAI1/CD82 and MRP1/CD9 protein expression was longer than that of patients with negative protein expression (P < 0.01 or 0.05). KAI1/CD82 protein expression negatively correlated with MRP1/CD9 protein expression in LSCC (${\chi}^2$= 31.25, P < 0.01). Conclusion: KAI1/CD82 and MRP1/CD9 may jointly participate in the development of LSCC. They may serve as the markers for judging the infiltration, metastasis, and prognosis of LSCC.

• Korean Journal of Community Nutrition
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• v.10 no.5
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• pp.693-699
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• 2005

Protein-calorie malnutrition is common in maintenance dialysis patients. Indeed, diabetic patients with chronic renal failure are considered to be at increased risk of malnutrition. The aim of this study was to compare the nutritional status and markers of inflammation of hemodialysis patients with and without type 2 diabetes. We compared nutritional parameters and C-reactive protein (CRP) as a marker of inflammation in 30 type 2 diabetic patients and age-matched 30 non-diabetic patients with hemodialysis. Serum albumin was significantly lower in patients with type 2 diabetes $(3.45\pm0.43g/dL)$ than in non-diabetic patients $(3.64\pm0.36 g/dL)$ (p<0.05). In contrast, the concentration of serum CRP was significantly higher in type 2 diabetes $(1.42\pm1.8mg/dL)$ (p<0.05). There were significant negative-relationships between serum albumin and CRP level in both diabetic (r=-0.553, p<0.01) and non-diabetic (r=-0.579, p<0.01) patients. In diabetic patients, serum albumin level was significantly correlated with hemoglobin (r = 0.488, p < 0.01) and hematocrit (r=0.386, p < 0.01). Diabetic patients as compared to non-diabetic patients showed a significant (p < 0.01) increased serum triglyceride (TG) $(153.1\pm80.1mg/dL\;vs\;101.6\pm62.4mg/dL)$ and decreased serum HDL cholesterol $(36.89\pm13.48mg/dL\;vs\;47.00\pm14.02mg/dL,\;P<0.05)$. There were significant correlations in the intake of calorie and serum albumin levels in both diabetic (r=0.438, p< 0.05) and non-diabetic (r=0.527, p<0.05) patients. Serum CRP level was negatively correlated with calorie (r= -0.468, p < 0.05), protein (r=-0.520, p < 0.01) and fat intakes (r=-0.403, p < 0.05) in diabetic patients and calorie (r=-0.534, p<0.05) and protein intakes (r=-0.559, p<0.05) in non-diabetic patients. The prevalence of protein malnutrition and the risk factors of cardiovascular disease were significantly higher in type 2 diabetic patients than in non-diabetic hemodialysis patients. Thus, we can suggest that the higher comorbidity and mortality rate in diabetic hemodialysis patients are partially explained by malnutrition and inflammation.

• Journal of Korean Neurosurgical Society
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• v.53 no.4
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• pp.207-212
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• 2013

Objective : Recent studies have shown encouraging progress toward the use of autogenic and allogenic mesenchymal stem cells (MSCs) to arrest, or even lead to partial regeneration in, intervertebral disc (IVD) degeneration. However, this technology is still in its infancy, and further development is required. The aim of this study was to analyze whether rat adipose-derived mesenchymal stem cells (ADMSC) can differentiate towards IVD-like cells after treatment with transforming growth factor ${\beta}3$ (TGF-${\beta}3$) in vitro. We also performed quantitative analysis of gene expression for ADMSC only, ADMSCs treated with TGF-${\beta}3$, and co-cultured ADMSCs treated with TGF-${\beta}3$. Methods : ADMSCs were sub-cultured to homogeneity and used in fluorocytometry assays for CD11, CD45, and CD90/Thy1. ADMSCs were differentiated in spheroid culture towards the chondrogenic lineage by the presence of TGF-${\beta}3$, dexamethasone, and ascorbate. We also co-cultured pure ADMSCs and nucleus pulposus cells in 24-well plates, and performed immunohistochemical staining, western blotting, and RT-PCR for quantitative analysis of gene expression. Results : Results of fluorocytometry were positive for CD90/Thy1 and negative for CD11 and CD45. TGF-${\beta}3$-mediated induction of ADMSCs led to the expression of the differentiation markers of intervertebral disc-like cells, such as aggrecan, collagen II, and sox-9. Co-cultured ADMSCs treated with TGF-${\beta}3$ showed higher expression of differentiation markers and greater extracellular matrix production compared with ADMSCs treated with TGF-${\beta}3$ alone. Conclusion : ADMSC treated with TGF-${\beta}3$ may be an attractive source for regeneration therapy in degenerative IVD. These findings may also help elucidate the pathologic mechanism of MSC therapy in the degeneration of IVD in vivo.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.823-829
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• 2015

The aim of the present study was to investigate the expression of the transcription factor Ki-67, ER, PR, Her2/neu, p21, EGFR, and TOP II-${\alpha}$ in the tumor tissue of patients with invasive ductal carcinoma(IDC); in addition, we examined correlations between these markers. Two hundred and sixteen IDC patients, who were not previously been treated with chemo- or radiotherapy, were included in the study. All tumors were grade I-III. Expression of molecular markers was determined by immunohistochemical analysis on paraffin-embedded tissue sections. Follow-up data were collected for 3 months to 10 years and analyzed for tumor recurrence, survival time, and prognostic risk factors. We determined Ki-67 expression correlates with the expression of ER, PR, HER-2, EGFR, and TOP-${\alpha}$, as well as lymph node involvement, high tumor grade, lymphovascular invasion, high tumor stage, and high TNM stage in IDC. Positive Ki-67 expression was a risk factor for rapid tumor recurrence and may help tumor progression, leading to poor prognosis in IDC. Ki-67 was directly correlated with EGFR, TOP II-${\alpha}$, lymph node involvement, high tumor grade, lymphovascular invasion, high tumor stage, and high TNM stage in the hormone receptor subtypes of breast cancer. In triple negative breast cancer, Ki-67 correlated with TOP II-${\alpha}$. Expression of Ki-67 correlated with that of ER, PR, HER-2, EGFR, TOP II-${\alpha}$, and p21. In addition, the biomarker Ki-67 has a role as a prognostic factor and indicates a poor prognosis in IDC.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.3
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• pp.2037-2042
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• 2013

Background: Different methods of diagnosis have been found to be inefficient in terms of screening and early diagnosis of lung cancer. Cancer cells produce proteins whose serum levels may be elevated during the early stages of cancer development. Therefore, those proteins may be recognized as potential cancer markers. The aim of this study was to differentiate healthy individuals and lung cancer cases by analyzing their serum protein profiles and evaluate the efficacy of this method in the early diagnosis of lung cancer. Materials and Methods: 170 patients with lung cancer, 53 under high risk of lung cancer, and 47 healthy people were included in our study. Proteomic analysis of the samples was performed with the SELDI-TOF-MS approach. Results: The most discriminatory peak of the high risk group was 8141. When tree classification analysis was performed between lung cancer and the healthy control group, 11547 was determined as the most discriminatory peak, with a sensitivity of 85.5%, a specificity of 89.4%, a positive predictive value (PPV) of 96.7% and a negative predictive value (NPV) of 62.7%. Conclusions: We determined three different protein peaks 11480, 11547 and 11679 were only present in the lung cancer group. The 8141 peak was found in the high-risk group, but not in the lung cancer and control groups. These peaks may prove to be markers of lung cancer which suggests that they may be used in the early diagnosis of lung cancer.