• The Korean Journal of Physiology and Pharmacology
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• v.24 no.2
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• pp.185-191
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• 2020

Interstitial cells of Cajal (ICC) are known as the pacemaker cells of gastrointestinal tract, and it has been reported that acute gastroenteritis induces intestinal dysmotility through antibody to vinculin, a cytoskeletal protein in gut, resulting in small intestinal bacterial overgrowth, so that anti-vinculin antibody can be used as a biomarker for irritable bowel syndrome. This study aimed to determine correlation between serum anti-vinculin antibody and ICC density in human stomach. Gastric specimens from 45 patients with gastric cancer who received gastric surgery at Kangwon National University Hospital from 2013 to 2017 were used. ICC in inner circular muscle, and myenteric plexus were counted. Corresponding patient's blood samples were used to determine the amount of anti-vinculin antibody by enzyme-linked immunosorbent assay. Analysis was done to determine correlation between anti-vinculin antibody and ICC numbers. Patients with elevated anti-vinculin antibody titer (above median value) had significantly lower number of ICC in inner circular muscle (71.0 vs. 240.5, p = 0.047), and myenteric plexus (12.0 vs. 68.5, p < 0.01) compared to patients with lower anti-vinculin antibody titer. Level of serum anti-vinculin antibody correlated significantly with density of ICC in myenteric plexus (r = -0.379, p = 0.01; Spearman correlation). Increased level of circulating anti-vinculin antibody was significantly correlated with decreased density of ICC in myenteric plexus of human stomach.

• Tuberculosis and Respiratory Diseases
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• v.74 no.5
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• pp.207-214
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• 2013

Background: Community-acquired pneumonia (CAP) is one of the leading causes of death among the elderly. Several studies have reported the clinical usefulness of serum procalcitonin, a biomarker of bacterial infection. However, the association between the levels of procalcitonin and the severity in the elderly with CAP has not yet been reported. The aim of this study was to evaluate usefulness of procalcitonin as a predictor of severity and mortality in the elderly with CAP. Methods: This study covers 155 CAP cases admitted to Pusan National University Hospital between January 2010 and December 2010. Patients were divided into two groups (${\geq}65$ years, n=99; <65 years, n=56) and were measured for procalcitonin, C-reactive protein (CRP), white blood cell, confusion, uremia, respiratory rate, blood pressure, 65 years or older (CURB-65) and pneumonia severity of index (PSI). Results: The levels of procalcitonin were significantly correlated with the CURB-65, PSI in totals. Especially stronger correlation was observed between the levels of procalcitonin and CURB-65 in the elderly (procalcitonin and CURB-65, ${\rho}$=0.408 with p<0.001; procalcitonin and PSI, ${\rho}$=0.293 with p=0.003; procalcitonin and mortality, ${\rho}$=0.229 with p=0.023). The correlation between the levels of CRP or WBC and CAP severity was low. The existing cut-off value of procalcitonin was correlated with mortality rate, however, it was not correlated with mortality within the elderly. Conclusion: The levels of procalcitonin are more useful than the levels of CRP or WBC to predict the severity of CAP. However, there was no association between the levels of procalcitonin and mortality in the elderly.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6391-6395
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• 2012

Background: Ovarian cancer is ranked as the fifth most common cause of cancer death in women. In Malaysia, it is the fourth most common cancer in females. CA125 has been the tumor marker of choice in ovarian cancer but its diagnostic specificity in early stages is only 50%. Hence, there is a critical need to identify an alternative tumor marker that is capable of detecting detect ovarian cancer at an early stage. HE4 is a new tumor marker proposed for the early diagnosis of ovarian cancer and disease recurrence. Currently, none of the normal ranges of HE4 quoted in the literature are based on data for a multiethnic Asian population. Therefore, the aim of this study was to determine reference intervals for HE4 in an Asian population presenting in University Malaya Medical Centre, a tertiary reference hospital. Materials and Methods: 300 healthy women were recruited comprising 150 premenopausal and 150 postmenopausal women, aged from 20-76 years. All women were subjected to a pelvic ultrasonograph and were confirmed to be free from ovarian pathology on recruitment. Serum HE4 levels were determined by chemiluminescent microparticle immunoassay (CMIA, Abbott Architect). The reference intervals were determined following CLSI guidelines (C28-A2) using a non-parametric method. Results: The upper limits of the $95^{th}$ percentile reference interval (90%CI) for all the women collectively were 64.6 pmol/L, and 58.4 pmol/L for premenopausal) and 69.0 pmol/L for postmenopausal. The concentration of HE4 was noted to increase with age especially in women who were more than 50 years old. We also noted that our proposed reference limit was lower compared to the level given by manufacturer Abbott Architect HE4 kit insert (58.4 vs 70 pmol/L for premenopausal group and 69.0 vs 140 pmol/L in the postmenopausal group). The study also showed a significant difference in HE4 concentrations between ethnic groups (Malays and Indians). The levels of HE4 in Indians appeared higher than in Malays (p<0.05), while no significant differences were noted between the Malays and Chinese ethnic groups. Conclusions: More data are needed to establish a reference interval that will better represent the multiethnic Malaysian population. Probably a larger sampling size of equal representation of the Malay, Chinese, Indians as well as the other native ethnic communities will give us a greater confidence on whether genetics plays a role in reference interval determination.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5635-5641
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• 2015

Background: Cirrhosis is regarded as a possible end stage of many liver diseases, including viral infection. It occurs when healthy liver tissue becomes damaged and is replaced by scar tissue and finally may lead to hepatocellular carcinoma. Interferons (IFNs)are two general categories, type I and II. Type I includes one beta interferon and over 20 different alpha interferons. Alpha interferons are very similar in how they work, interacting with other proteins on cells like receptors. The main objective of this study was to compare Mx gene productivity post different cell line treatment with imported and Egyptian biosimilar locally produced IFNs, as well as the efficacy of those tested IFNs. Also, an assessment was made of sensitivity of different cell lines as alternatives to that recommended for evaluation of antiviral activity. Materials and Methods: Different cell lines (Vero, MDBK and Wish) were employed to evaluate cytotoxicity using the MTT assay. Antiviral activity was evaluated compared with standard IFN against VSV, Indiana strain -156, on tested rh-IFNs (imported; innovated and Egyptian biosimilar locally produced IFNs) in the pre-treated cell lines previously mentioned. The virus was propagated in the Wish cell line as recommended. Finally we estimated up-regulation of the Mx gene as a biomarker. Results: Data recorded revealed that test IFNs were safe in test cell lines. Viability was around 100%. Locally tested interferon did not realize the international potency limits, while the imported one was accepted compared with the standard IFN. These results were the same either using infectivity titer reduction assay or crystal violet staining of residual non- infected cells. Mx protein production was cell type related and confirmed by the detected Mx gene expressed in imported and locally produced IFN pre-treated cell lines. The expression of the gene was arranged in the order of Vero> wish > MDBK for the imported IFN, while for the Egyptian biosimillar locally produced one it was MDBK> Vero> wish. With regard to the antiviral activity there was a significant difference of imported IFN potency compared with the locally produced IFN (P<0.05), the IFN potential (antiviral activity) was not cell line related and showed non-significant difference for each separate product. Conclusions: Vero cells can be used as an alternative cell line for evaluation of IFN potency in case of unavailable USP recommended cell lines. Alternative potency evaluation assay could be used and proved significant difference in IFN potency in case of local and imported agents. Evaluation of antiviral activity could be used in parallel to viral infectivity reduction assay for better accuracy. Mx gene can be used as a marker for IFN potential.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.15
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• pp.6397-6403
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• 2014

Background: Aberrant promoter hypermethylation has been recognized in human breast carcinogenesis as a frequent molecular alteration associated with the loss of expression of a number of key regulatory genes and may serve as a biomarker. The E-cadherin gene (CDH1), mapping at chromosome 16q22, is an intercellular adhesion molecule in epithelial cells, which plays an important role in establishing and maintaining intercellular connections. The aim of our study was to assess the methylation pattern of CDH1 and to correlate it with the expression of E-cadherin, clinicopathological parameters and hormone receptor status in breast cancer patients of Kashmir. Materials and Methods: Methylation specific PCR (MSP) was used to determine the methylation status of CDH1 in 128 invasive ductal carcinomas (IDCs) paired with the corresponding normal tissue samples. Immunohistochemistry was used to study the expression of E-cadherin, ER and PR. Results: CDH1 hypermethylation was detected in 57.8% of cases and 14.8% of normal adjacent controls. Reduced levels of E-cadherin protein were observed in 71.9% of our samples. Loss of E-cadherin expression was significantly associated with the CDH1 promoter region methylation (p<0.05, OR=3.48, CI: 1.55-7.79). Hypermethylation of CDH1 was significantly associated with age at diagnosis (p=0.030), tumor size (p=0.008), tumor grade (p=0.024) and rate of node positivity or metastasis (p=0.043). Conclusions: Our preliminary findings suggest that abnormal CDH1 methylation occurs in high frequencies in infiltrating breast cancers associated with a decrease in E-cadherin expression. We found significant differences in tumor-related CDH1 gene methylation patterns relevant to tumor grade, tumor size, nodal involvement and age at diagnosis of breast tumors, which could be extended in future to provide diagnostic and prognostic information.

• 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.1403-1407
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• 2015

Background: New tumour biomarkers are being intensely investigated for malignant mesothelioma (MM). Fibulin-3 is produced in MM but its role remains uncertain. The aim of this study was to evaluate the validity of measuring serum fibulin-3 in the diagnosis and prognosis of MM. Materials and Methods: This prospective study was performed on 43 patients and 40 healthy controls who were admitted to our hospital between January 2012 and January 2014. Data from MM patients, including demographic and clinical features, routine laboratory data, levels of serum fibulin-3, and treatment outcomes were defined as potential prognostic factors. The receiver operating characteristic (ROC) curve for fibulin-3 was used to detect the cut-off value with highest sensitivity and specificity. Univariate survival analysis was performed using the Kaplan-Meier method in patients with MM. Afterwards, the possible factors identified with univariate analyses were entered into the cox regression analysis. Results: Our results revealed that patients with MM had significantly higher serum levels of fibulin-3 than controls. The results showed that the best cut-off point was 36.6 ng/ml with an AUC (area under the curve)=0.976, sensitivity=93.0% and specificity=90.0. In our study, the initial significant poor prognostic factors were advanced stage, high white blood cell count, high platelet count, high C-reactive protein (p<0.05 for each variable). Later, according to multivariate analysis the results showed only advanced stage as significant parameter (p=0.040). Conclusions: We determined that real use for serum fibulin-3 was not for prognosis but for diagnosis in MM. Also advanced stage was associated with poor MM prognosis.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.10
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• pp.4215-4218
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• 2015

Gastric cancer (GC) is one of the most common malignancies in the world. It is the first cause of cancer deaths in both sexes In Iranian population. Circulating insulin-like growth factor-one (IGF-1) levels have been associated for gastric cancer. IGF-1 protein has central roles involved in the regulation of epithelial cell growth, proliferation, transformation, apoptosis and metastasis. Single nucleotide polymorphism in IGF-1 regulatory elements may lead to alter in IGF-1expression level and GC susceptibility. The aim of this study was to investigate the influence of IGF-1 gene polymorphism (rs5742612) on risk of GC and clinicopathological features for the first time in Iranian population. In total, 241 subjects including 100 patients with GC and 141 healthy controls were recruited in our study. Genotypes were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay with DNA from peripheral blood. The polymorphism was statistically analyzed to investigate the relationship with the risk of GC and clinicopathological properties. Logistic regression analysis revealed that there was no significant association between rs5742612 and the risk of GC. In addition, no significant association between genotypes and clinicopathological features was observed (p value>0.05). The frequencies of the CC, CT, and TT genotypes were 97%, 3%, and 0%, respectively, among the cases, and 97.9%, 2.1%, and 0%, respectively, among the controls. CC genotype was more frequent in cases and controls. The frequencies of C and T alleles were 98.9% and 1.1% in controls and 98.5% and 1.5% in patient respectively. Our results provide the first evidence that this variant is rare in Iranian population and it may not be a powerful genetic predisposing biomarker for prediction GC clinicopathological features in an Iranian population.

• Clinical and Experimental Pediatrics
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• v.61 no.9
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• pp.285-290
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• 2018

Purpose: To study the usefulness of the procalcitonin (PCT) test in young febrile infants between 1 and 3 months of age. Methods: We evaluated the medical records of 336 febrile infants between 1 and 3 months of age who visited the Emergency Department or outpatient department of Samsung Changwon Hospital from May 2015 to February 2017, and analyzed the clinical characteristics between infants in the serious bacterial infection (SBI) group and non-SBI group. Results: Among the 336 infants, 38 (11.3%) had definitive SBI (bacteremia, n=3; meningitis, n=1; urinary tract infection, n=34). The mean PCT ($6.4{\pm}11.9ng/mL$) and C-reactive protein (CRP) level ($3.8{\pm}2.6mg/dL$), and the absolute neutrophil count (ANC) ($6,984{\pm}4,675$) for patients in the SBI group were significantly higher than those for patients in the non-SBI group (PCT, $0.3{\pm}1.2ng/mL$; CRP, $1.3{\pm}1.6mg/dL$; ANC, $4,888{\pm}3,661$). PCT had lower sensitivity (43.6%), but higher specificity (92.6%) and accuracy (86.9%) than CRP (92.3%, 25.3%, and 33.0%) for identifying SBI. The area under the receiver operating characteristic curves (AUCs) for definitive SBI were PCT 77.0%, CRP 80.8%, WBC 56.8%, ANC 67.8%, and PLT 48.1%. The AUCs for definitive SBI were PCT+CRP 85.4%, PCT+WBC 77.2%, PCT+ANC 81.3%, CRP+WBC 80.1%, and CRP+ANC 81.6%. Conclusion: Our results suggest that the PCT test or a combination of PCT and CRP tests is a more accurate and specific biomarker to detect and rule out SBIs.

• Journal of Veterinary Clinics
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• v.23 no.2
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• pp.144-148
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• 2006

Apoptotic death of articular chondrocytes has been implicated in the pathogenesis of osteoarthritis. Tartrate resistant acid phosphatase (TRAP) has been used for several years as a marker enzyme of bone-resorbing osteoclasts. This study investigated the activity of TRAP in media of apoptotic cell death-induced canine chondrocyte. We exposed canine chondrocyte to capsaicin and the results showed that capsaicin induced cell death in a dose dependent manner. And we measured TRAP activity in media of chondrocyte death induced by capsaicin treatment and the results capsaicin significantly increased the activity of TRAP in media for dose dependent. We also investigated whether the combination treatment with capsaicin and TRAIL enhance apoptotic cell death in canine chondrocyte. We exposed canine chondrocyte to capsaicin for 24 hrs at the indicated dose, and then treated with recombinant TRAIL protein for 24 hrs. TRAIL alone did not induce cell death after 24 hours, but the combined treatment of both induced more cell death compared with capsaicin alone in a dose dependent manner. Also, the combination treatment with capsaicin and TRAIL increased the activity of TRAP in culture media. These results suggest that TRAP can flow out into extracellular after chondrocyte damage, and TRAP may be a successful biomarker for detection of joint disease such as osteoarthritis.