• 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.14 no.12
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• pp.7085-7090
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• 2013

Objective: Published data have shown that microRNAs (miRNAs) could play a potential role as diagnostic and prognostic indicators in cancers. Data for the predictive value of microRNA-155 are inconclusive. The aim of the present analysis was therefore to evaluate the role of miR-155 in prognosis for patients with a variety of carcinomas. Methods: Relevant studies were identified by searching PubMed and EMBASE. Data were extracted from studies comparing overall survival (OS), recurrence-free survival (RFS) or cancer-specific survival (CSS) in patients with carcinoma with higher miR-155 expression and those with lower levels. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) of miR-155 for clinical outcome were calculated. Results: A total of 15 studies were included. The pooled hazard ratio (HR) for OS of higher miR-155 expression in cancerous tissue was 1.89 (95% CI: 1.20-2.99, P=0.006), which could markedly predict poorer survival in general cancer. For RFS/CSS, elevated miR-155 was also associated with poor prognosis of cancer (HR=1.50, 95% CI: 1.10-2.05, P=0.01). On subgroup analysis, the pooled HR for OS in non-small cell lung cancer (NSCLC) was 2.09 (95% CI: 0.68-6.41, P > 0.05), but for RFS/CSS was 1.28 (95% CI: 1.05-1.55, P=0.015), with statistical significance; the pooled HRs for OS and RFS/CSS in digestive system neoplasms were 3.04 (95% CI: 1.48-6.24, P=0.003) and 2.61 (95% CI: 1.98-3.42, P<0.05), respectively. Conclusions: The results indicated that the miR-155 expression level plays a prognostic role in patients with cancer, especially NSCLCs and digestive system carcinomas.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.541-549
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• 2015

Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC) with higher metastatic rate and both local and systemic recurrence compared to non-TNBC. The generation of reactive oxygen species (ROS) secondary to oxidative stress is associated with DNA damage, chromosomal degradation and alterations of both hypermethylation and hypomethylation of DNA. This study concerns differential methylation of promoter regions in specific groups of genes in TNBC and non-TNBC Saudi females in an effort to understand whether epigenetic events might be involved in breast carcinogenesis, and whether they might be used as markers for Saudi BCs. Methylation of glutathione S-transferase P1 (GSTP1), T-cadherin (CDH13), Paired box protein 5 (PAX5), death associated protein kinase (DAPK), twist-related protein (TWIST), DNA-binding protein inhibitor (ID4), High In Normal-1 (HIN-1), cyclin-dependent kinase inhibitor 2A (p16), cyclin D2 and retinoic acid receptor-${\beta}$ ($RAR{\beta}1$) genes was analyzed by methylation specific polymerase chain reaction (MSP) in 200 archival formalin-fixed paraffin embedded BC tissues divided into 3 groups; benign breast tissues (20), TNBC (80) and non-TNBC (100). The relationships between methylation status, and clinical and pathological characteristics of patients and tumors were assessed. Higher frequencies of GSTP1, ID4, TWIST, DAPK, PAX5 and HIN-1 hypermethylation were found in TNBC than in non-TNBC. Hypermethylation of GSTP1, CDH13, ID4, DAPK, HIN-1 and PAX5 increased with tumor grade increasing. Other statistically significant correlations were identified with studied genes. Data from this study suggest that increased hypermethylation of GSTP1, ID4, TWIST, DAPK, PAX5 and HIN-1 genes in TNBC than in non-TNBC can act as useful biomarker for BCs in the Saudi population. The higher frequency of specific hypermethylated genes paralleling tumor grade, size and lymph node involvement suggests contributions to breast cancer initiation and progression.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.10
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• pp.4203-4206
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• 2014

Purpose: The objective of this study was to assess the predictive role of the neutrophil/lymphocyte ratio (NLR) for invasion of gestational trophoblastic disease (GTD). Materials and Methods: A retrospective analysis was conducted on 127 women who were managed at our clinic for GTD. Of all patients, 8 showed invasion according to histological examination. The clinical parameters of patients with invasive GTD (Group 1; n=8) were compared with patients who showed no invasion (Group 2; n=119). All underwent a prior uterine evacuation and followed up by regular assessment of ${\beta}$-hCG titers. Results: Demographic and obstetric history and pre-evacuation hCG levels of the patients showed no statistically significantly difference between the groups (p>0.05). The mean gestational weeks (GW), size of the GTD and NLR levels were statistically significantly higher in the invasive GTD group (p<0.05). Correlations between invasion and gestational weeks, size of GTD, post-evacuation chemotherapy and NLR were evident. ROC curve analysis demonstrated that GW, size of GTD and NLR may be discriminative parameters in predicting invasion of GTD. Conclusions: To the best of our knowledge, this is the first study evaluating the predictive role of NLR in invasion of GTD. In conclusion, we think that pretreatment NLR can be used as a biomarker of invasion in GTD.

• Journal of Periodontal and Implant Science
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• v.46 no.5
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• pp.320-328
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• 2016

Purpose: Human saliva, as a vital part of the immune defense system, contains a number of distinct proteins and peptides. Recently human common salivary protein 1 (CSP1) has been identified as an abundant salivary protein and may play a role in promoting the binding of cariogenic bacteria to salivary pellicles. However, nothing else is known regarding the role of CSP1 in periodontology. The aim of this study was to quantify and compare CSP1 levels between healthy subjects and periodontal patients. Methods: This controlled clinical study was conducted in periodontally healthy individuals and patients with chronic periodontitis Chonbuk National University Hospital, with Institutional Review Board approval. Whole saliva samples were collected from 36 healthy subjects and 33 chronic periodontitis patients and analyzed. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immune blotting were conducted to ensure that anti-CSP1 monoclonal antibody (mAb) binds to CSP1 in human saliva. A sandwich enzyme-linked immunosorbent assay (ELISA) system was house-fabricated using mAb-hCSP1#14 and mAb-hCSP1#4 as a capture and a detector mAb, respectively. The CSP1 concentrations in saliva from 36 healthy subjects and 33 periodontal patients were quantified using the CSP1 sandwich ELISA system, and the results were analyzed using the Student's t-test. Results: Immunoblot analysis using mAb-hCSP1 as a probe confirmed that CSP1 in human saliva existed as a single band with a molecular weight of approximately 27-kDa. The quantification of CSP1 concentrations by CSP1 ELISA showed that the median values (25th to 75th percentiles) of periodontal patients and healthy subjects were 9,474 ng/mL (range, 8,434.10,139 ng/mL) and 8,598 ng/mL (range, 7,421.9,877 ng/mL), respectively. The Student's t-test indicated the presence of a statistically significant difference between the 2 groups (P=0.024). Conclusions: The presence of a significant difference in CSP1 levels between healthy subjects and periodontal patients suggests that CSP1 may be a potential biomarker for the detection or screening of periodontitis patients.

• Journal of Gastric Cancer
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• v.18 no.2
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• pp.142-151
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• 2018

Purpose: The modification of the cancer classification system aimed to improve the classical anatomy-based tumor, node, metastasis (TNM) staging by considering tumor biology, which is associated with patient prognosis, because such information provides additional precision and flexibility. Materials and Methods: We previously developed an mRNA expression-based single patient classifier (SPC) algorithm that could predict the prognosis of patients with stage II/III gastric cancer. We also validated its utilization in clinical settings. The prognostic single patient classifier (pSPC) differentiates based on 3 prognostic groups (low-, intermediate-, and high-risk), and these groups were considered as independent prognostic factors along with TNM stages. We evaluated whether the modified TNM staging system based on the pSPC has a better prognostic performance than the TNM 8th edition staging system. The data of 652 patients who underwent gastrectomy with curative intent for gastric cancer between 2000 and 2004 were evaluated. Furthermore, 2 other cohorts (n=307 and 625) from a previous study were assessed. Thus, 1,584 patients were included in the analysis. To modify the TNM staging system, one-grade down-staging was applied to low-risk patients according to the pSPC in the TNM 8th edition staging system; for intermediate- and high-risk groups, the modified TNM and TNM 8th edition staging systems were identical. Results: Among the 1,584 patients, 187 (11.8%), 664 (41.9%), and 733 (46.3%) were classified into the low-, intermediate-, and high-risk groups, respectively, according to the pSPC. pSPC prognoses and survival curves of the overall population were well stratified, and the TNM stage-adjusted hazard ratios of the intermediate- and high-risk groups were 1.96 (95% confidence interval [CI], 1.41-2.72; P<0.001) and 2.54 (95% CI, 1.84-3.50; P<0.001), respectively. Using Harrell's C-index, the prognostic performance of the modified TNM system was evaluated, and the results showed that its prognostic performance was better than that of the TNM 8th edition staging system in terms of overall survival (0.635 vs. 0.620, P<0.001). Conclusions: The pSPC-modified TNM staging is an alternative staging system for stage II/III gastric cancer.

• 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.

• Archives of Plastic Surgery
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• v.33 no.4
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• pp.433-439
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• 2006

Purpose: DNA in most cell is regularly damaged by endogenous and exogenous mutagens. Unrepaired damage resulted in apoptosis or may lead to unregulated cell growth and cancer. Inheritance of genetic variants at one or more loci results in an reduced DNA repair capacity. These polymorphisms are highly prevalent in the population, and therefore the attributable risks for cancer could be high. Several studies have documented that polymorphisms of XRCC1, XPD and XRCC3 are associated with skin cancer, especially, XRCC1 among of them has been reported frequently. So, this study involves the relationship between mutation of XRCC1 of squamous cell and basal cell cancer of the skin and risk of cancer development in Korean population. Methods: In case control study, study population (n=100, each cancer) is patients who were pathologically diagnosed as skin cancer(squamous cell carcinoma and basal cell carcinoma) in Yonsei Wonju Christian Hospital and Bundang CHA General Hospital between 1998 and 2004. The samples of DNA from whom no history of premalignant skin lesion and other malignant diseases were reported belonged to the control group(n=210). Blood and tissue samples were analyzed for presence of XRCC1 Arg399Glu, Arg280His, Arg194Trp using PCR/ RFLP method. Results: For Korean, there was a significant correlation between XRCC1 Arg399Gln gene mutation and risk of basal cell carcinoma development(Arg 399Gln(GA), p=0.012, OR=2.016, 95% CI; 1.230-3.305) /Arg399Gln (AA), p=0.011, OR=1.864, 95% CI; 1.149-3.026)). And, there was also significant correlation between XRCC1 Arg194Trp and risk of skin squamous cell carcinoma development (Arg194Trp (CT+TT), p=0.041, OR=0.537, 95% CI; 0.301-0.960)). In contrast, there was no significant correlation between XRCC1 Arg280His and risk of either basal cell carcinoma or squamous cell carcinoma development. Conclusions: Our result present that XRCC1 Arg399 Gln in basal cell carcinoma and XRCC1 Arg194Trp in squamous cell carcinoma have possibility of cancer risk and biomarker in Korean population. But XRCC1 Arg280 His known having cancer risk on other studies is not associated with cancer risk to squamous cell carcinoma and basal cell carcinoma in Korean population.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.2
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• pp.365-371
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• 2006

Bee Venom aqua-acupuncture (BVA) simultaneously exerts pharmacological effects of biologically active compounds, existed in the whole bee venom, and medicinal effect of the stimulation of acupuncture points. BVA has been considered as a promising therapeutic method for treating various chronic diseases, mainly accompanying severe pain and inflammation. As a painless injection device, jet injectors have been commercially marketed for various clinical applications including insulin injection and vaccination. Among them, a pressure-driven jet injector system could be used for intradermal delivery of a variety of drugs. The aim of this study was to investigate the analgesic effects of the BVA using a needle-free injector (Biojector $2000^{\circledR}$, Bioject Inc., OR, USA), compared to the conventional BV aqua-acupuncture using a typical syringe. Adult Sprague-Dawley rats were injected with bee venom $(0.08mg/kg,\;50{\mu}l)$ using Biojector $2000^{\circledR}$ (BVA-B) or a syringe (BVA-5) into the Zusanli (ST36) acupoint, 30 minutes before plantar injection of 2% formalin. It was found that BVA-B-, or BVA-5-treated rats, compared to controls, exhibited significantly less licking behavior during the late phase in the rat formalin test, when compared to controls. During early phase, however, those effects were not significant but substantial. The analgesic effect of BVA-B was also compatible with that of the conventional BVA-5. In the immunohistochemical studies, BVA-B significantly suppressed the expression of formalin-evoked c-fos, a biomarker of neuronal activity, in the lumbar dorsal horn of the spinal cord. These results indicated that BVA-B waseffective in the modulation of pain in the rat formalin test, compared to BVA-5. Taken together, the needle-free jet injector system could be substituted for the conventional aqua- acupuncture with the advantage of little pain.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.12
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• pp.5089-5094
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• 2015

FADS1 (fatty acid desaturase 1) plays a crucial role in fatty acid metabolism, and it was recently reported to be involved in tumorigenesis. However, the role of FADS1 expression in esophageal squamous cell carcinoma (ESCC) remains unknown. In the current study, we investigated the expression and clinical pathologic and prognostic significance of FADS1 in ESCC. Immunohistochemical analyses revealed that 58.2% (146/251) of the ESCC tissues had low levels of FADS1 expression, whereas 41.8% (105/251) exhibited high levels of FADS1 expression. In positive cases, FADS1 expression was detected in the cytoplasm of cells. Correlation analyses demonstrated that FADS1 expression was significantly correlated with tumor location (p=0.025) but not with age, gender, histological grade, tumor status, nodal status or TNM staging. Furthermore, patients with tumors expressing high levels of FADS1had a longer disease-free survival time (p<0.001) and overall survival time (p <0.001). Univariate and multivariate analyses revealed that, along with nodal status, FADS1 expression was an independent and significant predictive factor (p<0.001). In conclusion, our study suggested that FADS1 might be a valuable biomarker and potential therapeutic target for ESCC.