• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7635-7638
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• 2013

Background: Sperm-associated antigen 9 (SPAG9) has been recently proposed as a novel biomarker for early diagnosis of several human tumors, including ovarian, cervical and breast cancers. Its clinical value remains to be clarified for endometrial cancer (EC). In this study, we investigated the utility of serum SPAG9 levels in diagnosis of EC and its association with important clinicopathological parameters. Materials and Methods: This cross-sectional study was performed at a tertiary women's referral center in Ankara, Turkey. Preoperative serum samples were collected from patients surgically treated for endometrial cancer between June 2012-April 2013. Similar aged women with a biopsy proven benign endometrium were used as controls. Serum SPAG9 levels were measured with an enzyme-linked immunosorbent assay (ELISA) method and assessed for links with clinicopathological factors. Receiver operating characteristic (ROC) curve analysis was performed to assess power of SPAG9 levels for EC prediction. P values less than 0.05 were considered statistically significant. Results: A total of 63 women with EC and 27 with benign endometrium were included in the study. Mean age in the EC group was $58.7{\pm}1.1$. Median SPAG9 levels in the EC and control groups were 18.3 (range, 12.7-53.8) and 14.1 (range, 4.3-65.3), respectively (p<0.001). A cut-off value of 17 ng/ml for SPAG9 predicted presence of malignant endometrium with 74% sensitivity and 83% specificity [Area under curve (AUC)=0.82, p<0.001]. SPAG9 levels did not demonstrate any significant association with histological type, FIGO stage, tumor grade, size, myometrial invasion, lymphovascular space invasion, cervical involvement, adnexal involvement, peritoneal cytology or lymph node status (all p>0.05). Conclusions: Testing for SPAG9 may be useful for early detection of EC in asymptomatic high-risk women. Its role in post-treatment follow-up and early detection of recurrence should be assessed in future trials.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.2185-2193
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• 2016

Background: The pathogenesis of sporadic colorectal cancer (CRC) is influenced by the patient genetic background and environmental factors. Based on prior understanding, these are classified in two major pathways of genetic instability. Microsatellite instability (MSI) and CPG island methylator phenotype (CIMP) are categorized as features of the hypermethylated prototype, and chromosomal instability (CIN) is known to be indicative of the non-hypermethylated category. Secreted frizzled related protein 2 (SFRP2), APC1A in WNT signaling pathway and the DNA repair gene, O6-methylguanine-DNA methyltransferase (MGMT), are frequently hypermethylated in colorectal cancer. Detection of methylated DNA as a biomarker by easy and inexpensive methods might improve the quality of life of patients with CRC via early detection of cancer or a precancerous condition. Aim: To evaluate the rate of SFRP2 and MGMT hypermethylation in both polyp tissue and serum of patients in south Iran as compared with matched control normal population corresponding samples. Materials and Methods: Methylation-specific PCR was used to detect hypermethylation in DNA extracted from 48 polypoid tissue samples and 25 healthy individuals. Results: Of total polyp samples, 89.5% had at least one promoter gene hypermethylation. The most frequent methylated locus was SFRP2 followed by MGMT-B (81.2 and 66.6 percent respectively). Serologic detection of hypermethylation was 95% sensitive as compared with polyp tissue. No hypermethylation was detected in normal tissue and serum and its detection in patients with polyps, especially of serrated type, was specific. Conclusions: Serologic investigation for detection of MGMT-B, SFRP2 hypermethylation could facilitate prioritization of high risk patients for colonoscopic polyp detection and excision.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.4
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• pp.1657-1663
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• 2015

Background: Early diagnosis of hepatocellular carcinoma (HCC) is the most important step in successful treatment. However, it is usually rare due to the lack of a highly sensitive specific biomarker so that the HCC is usually fatal within few months after diagnosis. The aim of this work was to study the role of plasma nuclear factor kappa B (NF-${\kappa}B$) and serum peroxiredoxin 3 (PRDX3) as diagnostic biomarkers for early detection of HCC in a high-risk population. Materials and Methods: Plasma nuclear factor kappa B level (NF-${\kappa}B$) and serum peroxiredoxin 3 (PRDX3) levels were measured using enzyme linked immunosorbent assay (ELISA), in addition to alpha-fetoprotein (AFP) in 72 cirrhotic patients, 64 patients with HCC and 29 healthy controls. Results: NF-${\kappa}B$ and PRDX3 were significantly elevated in the HCC group in relation to the others. Higher area under curve (AUC) of 0.854 (for PRDX3) and 0.825 (for NF-${\kappa}B$) with sensitivity of 86.3% and 84.4% and specificity of 75.8% and 75.4% respectively, were found compared to AUC of alpha-fetoprotein (AFP) (0.65) with sensitivity of 72.4% and specificity of 64.3%. Conclusions: NF-${\kappa}B$ and PRDX3 may serve as early and sensitive biomarkers for early detection of HCC facilitating improved management. The role of nuclear factor kappa B (NF-${\kappa}B$) as a target for treatment of liver fibrosis and HCC must be widely evaluated.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.10
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• pp.1415-1421
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• 2015

This study was performed to investigate the effects of puffed-red ginseng (PRG) powder and drink on blood glucose level and serum lipid profile in streptozotocin (STZ)-induced diabetic rats. For the experimental design, STZ-induced diabetic rats were fed PRG powder-supplemented diets (0.3%, 0.6%) and diluted drinks (0.14%, 0.28%) for 6 weeks. Concentrations of blood glucose during the experimental period decreased to 18.3 mg/dL in the 0.6% PRG diet group and 15.1 mg/dL in the 0.14% PRG drink group. Average reduction rate of blood glucose in the last week compared to reference blood glucose concentration decreased by 19.2% (A group), 37.4% (B group), 18.7% (C group), and 17.3% (D group) in the PRG treatment groups, respectively. These results indicate that PRG affects blood glucose via ginseng saponins administered in diet or drinking water, thereby suggesting that PRG has the ability to prevent increasing blood glucose in mild-induced diabetic rats.

• Journal of Life Science
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• v.21 no.6
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• pp.884-892
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• 2011

This study was performed to investigate the increase of S-allylcysteine content, a biomarker of black garlic, during its aging period, as well as the serum lipid-lowering effects of black garlic extract in high fat diet fed rats. The highest content of S-allylcysteine was observed on the 15th day of the aging period. Sensory evaluation was also estimated to be extremely good on the 15th day of the aging period. High fat diet rats with induced hyperlipidemia were fed diets containing black garlic extract of low, medium, and high doses for 6 weeks. No significant difference in body weight gain and food efficiency was observed between normal, placebo and black garlic fed groups. Liver weight was significantly higher in black garlic fed groups than in the normal group. Total serum cholesterol and triglyceride were significantly lower in low, medium, and high dose groups than in the normal group. Also, HDL-cholesterol was significantly higher and LDL-cholesterol was significantly lower in black garlic diet fed groups than in the normal group. Hepatic levels including total lipid and cholesterol were especially decreased in the black garlic diet fed group than in the placebo group. These results suggest that black garlic intake reduces the levels of serum and hepatic cholesterol in high fat diet fed rats. In conclusion, black garlic has a potential to be used as a functional health food ingredient with beneficial effects on lowering cholesterol and triglyceride levels.

• Tuberculosis and Respiratory Diseases
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• v.71 no.3
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• pp.195-201
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• 2011

Background: Osteopontin (Opn) is recognized as an important adhesive bone matrix protein and a key cytokine involved in immune cell recruitment and tissue repair and remolding. However, serum levels of osteopontin have not been evaluated in patients with chronic obstructive pulmonary disease (COPD). Thus, the aim of this study was to evaluate and compare the serum levels of osteopontin in patients experiencing COPD exacerbations and in patients with stable COPD. Methods: Serum samples were obtained from 22 healthy control subjects, 18 stable COPD patients, and 15 COPD with exacerbation patients. Serum concentrations of osteopontin were measured by the ELISA method. Results: Serum levels of osteopontin were higher in patients with acute exacerbation than with stable COPD and in healthy control subjects ($62.4{\pm}51.9ng/mL$, $36.9{\pm}11.1ng/mL$, $30{\pm}11ng/mL$, test for trend p=0.003). In the patients with COPD exacerbation, the osteopontin levels when the patient was discharged from the hospital tended to decrease compared to those at admission ($45{\pm}52.1ng/mL$, $62.4{\pm}51.9ng/mL$, p=0.160). Osteopontin levels significantly increased according to patient factors, including never-smoker, ex-smoker and current smoker ($23{\pm}5.7ng/mL$, $35.5{\pm}17.6ng/mL$, $58.6{\pm}47.8ng/mL$, test for trend p=0.006). Also, osteopontin levels showed a significantly negative correlation with forced expiratory volume in one second ($FEV_1$%) predicted in healthy controls and stable COPD patients (r=-0.389; p=0.013). C-reactive protein (CRP) was positively correlated with osteopontin levels in patients with COPD exacerbation (r=0.775; p=0.002). Conclusion: The serum levels of osteopontin increased in patients with COPD exacerbation and tended to decrease after clinical improvement. These results suggest the possible role of osteopontin as a biomarker of acute exacerbation of COPD.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10209-10215
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• 2015

To assess the contribution of tumor necrosis factor $(TNF){\beta}$ +252 polymorphisms to risk and prognosis of hepatocellular carcinoma (HCC), we enrolled 150 pairs of sex- and age-matched patients with HCC, patients with cirrhosis alone, and unrelated healthy controls. $TNF{\beta}$ +252 genotypes were determined by polymerase chain reaction with restriction fragment length polymorphism. Multivariate analysis indicated that $TNF{\beta}$ G/G genotype [odds ratio (OR), 3.64; 95%CI, 1.49-8.91], hepatitis B surface antigen (OR, 16.38; 95%CI, 8.30-32.33), and antibodies to hepatitis C virus (HCV) (OR, 39.11; 95%CI, 14.83-103.14) were independent risk factors for HCC. There was an additive interaction between $TNF{\beta}$ G/G genotype and chronic hepatitis B virus (HBV)/HCV infection (synergy index=1.15). Multivariate analysis indicated that factors associated with $TNF{\beta}$ G/G genotype included cirrhosis with Child-Pugh C (OR, 4.06; 95%CI, 1.34-12.29), thrombocytopenia (OR, 6.55; 95%CI, 1.46-29.43), and higher serum ${\alpha}$-fetoprotein concentration (OR, 2.53; 95%CI, 1.14-5.62). Patients with $TNF{\beta}$ G/G genotype had poor cumulative survival (p=0.005). Cox proportional hazard model indicated that $TNF{\beta}$ G/G genotype was a biomarker for poor HCC survival (hazard ratio, 1.70; 95%CI, 1.07-2.69). In conclusion, there are independent and additive effects between $TNF{\beta}$ G/G genotype and chronic HBV/HCV infection on risk for HCC. It is a biomarker for poor HCC survival. Carriage of this genotype correlates with disease severity and advanced hepatic fibrosis, which may contribute to a higher risk and poor survival of HCC. Chronic HBV/HCV infected subjects with this genotype should receive more intensive surveillance for early detection of HCC.

• Journal of Veterinary Clinics
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• v.28 no.1
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• pp.52-56
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• 2011

Acute renal injury induced by ischemia is a major cause of high morbidity and mortality in hospitalized patients and a common complication in hospitalized patients. Thus, the work with acute renal failure and renal ischemia has been studied for many years. Although serum creatinine concentration that is widely used as an index of renal function performs fairly well for estimating kidney function in patients with stable chronic kidney disease, it performs poorly in the setting of acute disease. Thus, an ideal biomarker for acute kidney injury would help clinicians and scientists diagnose the most common form of acute kidney injury in hospitalized patients, acute tubular necrosis, early and accurately, and may aid to risk-stratify patients with acute kidney injury by predicting the need for renal replacement therapy, the duration of acute kidney injury, the length of stay and mortality. In this study, renal ischemia and reperfusion were performed by clapming and un-clamping right renal artery in miniature pigs. Plasma blood urea nitrogen (BUN) and creatinine were examined at pre- clamping, after-clamping at 0, 1 and 3 hours. And we searched initial indicators in these samples. Also, renal tissue was collected and searched the initial indicator by PCR and western blotting. As a result, hypoxia inducible factor $1{\alpha}$ ($HIF1{\alpha}$), nuclear factor kappa-B ($NF{\kappa}B$), $I{\kappa}B$, erythropoietin (EPO), erythropoietin receptor (EPOR), angiopoietin-1 and vascular endothelial growth factor (VEGF) were showed significant changes among the renal protein. $HIF1{\alpha}$, EPO, and EPOR were showed significant changes among the renal gene. Thus, these markers will be used as initial diagnosis of acute renal failure.

• Journal of Pharmacopuncture
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• v.7 no.3
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• pp.5-25
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• 2004

Objectives : To observe changes in the serum proteins before and after intravenous injection of wild ginseng herbal acupuncture. Methods : Blood was collected before and after the administration of wild ginseng herbal acupuncture and only the serum was centrifuged. Then differences in the spots on the scanned image after running 2-Dimensionl electrophoresis were located and conducted mass analysis and protein identification. Results : Following results were obtained from the comparative analysis of serum proteins before and after the administration of wild ginseng herbal acupuncture. 1. 28 spots were identified before and after the administration. 2. In confirming manifestation degree, spots with more than two-times increase were 204, 803, 1505, 2205, 3105, 7104, 9001 spots, with more than one-time increase were 1101, 1302, 2013, 3009, 3010, 4002, 4009, 6706, 7103, 8006, 8101, and spots with decrease were 205, 801, 3205, 5202, 6105. 3. After conducting protein identification, proteins 205, 804, 1302, 4009, 6105, 6106 are unidentified yet, and 1101 is unnamed protein. Protein 204 is identified as complement receptor CR2-C3d, 801 as YAP1 protein, 803 as antitrypsin polymer, 1505 as PRO0684, 2013 and 3010 as proapolipoprotein, 2205 as USP48, 2403 as vitamin D binding protein, 3009 as complement component 4A preprotein, 3105 as immunoglobulin lambda chain, 3205 as transthyretin, 4002 as Ras-related protein Ral-A, 4204 as beta actin, 5202 and 7104 as apolipoprotein L1, 6704 as alpha 2 macroglobulin precursor, 7103 as complement component 3 precursor, 8006 as testis-specific protein Y, 8101 as Transferrin, 9001 as(Alpha-Oxy, Beta-(C112g)deoxy) T-State Human Hemoglobin, and 9003 as human hemoglobin. 4. Immune protein CR2-C3d, which acts against microbes and pathogenic organisms, and Antitrypsin(803), which is secreted with inflammatory response in the lungs, were increased by more than 200% after the administration of herbal acupuncture. 5. Immunoglobulin lambda chain(3105), Alpha-Oxy, Beta-(C112g)deoxy T-State Human Hemoglobin(9001), and human hemoglobin(9003) were increased by more than two-times after the administration of herbal acupuncture. 6. Proapolipoprotein(2013, 3010) and apolipoprotein(7104), key components of the HDL-cholesterol which plays an important role in preventing arteriosclerosis, were increased after the administration of herbal acupuncture. 7. Vitamin D binding protein(DBP, 2403), protecting the lung at the time of inflammatory response, was increased after the administration of herbal acupuncture. 8. Transthyretin(TTR, 3205), which is the main protein causing familial aimyloid polyneuropathy(FAP), was decreased after the administration of herbal acupuncture. 9. Ras-related protein Ral-A(4002) that controls phospholipid metabolism, cytoskeletal formation, and membrane traffic, was increased after the administration of herbal acupuncture. 10. Testis-specific protein Y(8006), which takes part in determination of the gender, was increased by more than two-times after the administration of herbal acupuncture. 11. Transferrin(8101), T-State Human Hemoblobin(9001), and Human Hemoblobin(9003) which balances the iron level in the body, were increased after the administration of herbal acupuncture. Conousion : Above results support the notion that intravenous injection of cultivated wild ginseng herbal acupuncture induce changes in serum proteins and this research can be a pioneer work in finding biomarkers.

• Food Science and Preservation
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• v.21 no.3
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• pp.412-420
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• 2014

This study was performed to investigate the effect of fermented Hovenia dulcis Thunb fruit water extract on biomarkers for acute (a) ethanol-induced hangover and chronic (c) ethanol-induced liver injury in rats. For acute ethanol-induced hangover, the rats were administered distilled water (D.W., 10 mL/kg body wt.), Hovenia dulcis Thunb fruit water extract (HWE, 400 mg/10 mL/kg body wt.) and fermented HWE (FHWE, 400 mg/10 mL/kg body wt.), respectively, before 40% ethanol (5 g/kg body wt.) was administered. For chronic ethanol-induced liver injury, the rats were randomly divided into the normal control (cNC), ethanol (cET), cET-HWE and cET-FHWE groups. The cNC and cET groups were administered D.W. (10 mL/kg body wt.) before 40% alcohol (5 g/kg body wt.) was administrered for 21 days. The cET-HWE and cET-FHWE groups were administered HWE (400 mg/10 mL/kg body wt.) and FHWE (400 mg/10 mL/kg body wt.), respectively before 40% ethanol (5 g/kg body wt.) administration for 21 days. For acute ethanol-induced hangover, the serum alcohol and acetaldehyde concentrations were more significantly reduced in the aHWE and aFHWE groups than in the aET group. Moreover, the effect of FHWE was greater than that of HWE. For chronic ethanol-induced liver injury, the serum ethanol, acetaldehyde, ${\gamma}$-glutamyl transpeptidase (${\gamma}$-GTP) levels and the hepatic lipids concentration more significantly dropped in the cET-HWE and cET-FHWE groups than in the cET group. The FHWE administration showed faster recovery of the serum glucose concentration than in the cET and cET-HWE groups. The body weight reduction tended to normalize in the cET-HWE and cET-FHWE groups, which is ideal for chronic ethanol administration. These results suggest that FHWE has a protective effect against ethanol-induced liver damage, as evidenced by its ability to lower the serum ethanol and acetaldehyde concentrations after alcohol administration, and by its ability to decrease the level of ${\gamma}$-GTP and hepatic lipids. FHWE also elevated serum glucose concentration. Therefore, FHWE is effective in reducing ethanol-induced hangover and can play a beneficial role in the treatment of ethanol-induced liver damage as well as body weight reduction.