• Asian Pacific Journal of Cancer Prevention
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• v.15 no.4
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• pp.1667-1670
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• 2014

Background: Calprotectin in feces seems to be a more sensitive marker for gastrointestinal (GI) cancers than fecal occult blood, but its specificity may be too low for screening average risk populations. This study aims at evaluating the diagnostic value of fecal calprotectin as a screening biomarker for GI malignancies. Materials and Methods: In a case-control study, 100 patients with GI malignancies (50 patients with colorectal cancer and 50 patients with gastric cancer) and 50 controls were recruited in Tabriz Imam Reza and Sina hospitals during a 24-month period. One to two weeks after the last endoscopy/colonoscopy, fecal specimens were collected by the patients and examined by ELISA method for quantitative measurement of calprotectin content. The results were compared between the three groups. Results: The mean fecal calprotectin level was $109.1{\pm}105.3$ (2.3-454.3, median:74), $241.1{\pm}205.2$ (3.4-610.0, median:19.3) and $45.9{\pm}55.1{\mu}g/g$ (1.3-257.1, median:19.3) in gastric cancer, colorectal cancer and control group, respectively, the differences being significant (p<0.001) and remaining after adjustment for age. The optimal cut-off point for fecal calprotectin was ${\geq}75.8{\mu}g/g$ for distinguishing colorectal cancer from normal cases (sensitivity and specificity of 80% and 84%, respectively). This value was ${\geq}41.9{\mu}g/g$ for distinguishing gastric cancer from normal cases (sensitivity and specificity of 62%). Conclusions: Our results revealed that fecal calprotectin might be a useful and non-invasive biomarker for distinguishing colorectal cancer from non-malignant GI conditions. However, due to low sensitivity and specificity, this biomarker may not help physicians distinguishing gastric cancer cases from healthy subjects.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7713-7718
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• 2014

Background: Despite evidence suggesting roles for caspase-8 (CASP8) -652 6N del and D302H polymorphisms in prostate cancer (PCa), the association of these polymorphisms with PCa risk remains inconclusive. Therefore, a meta-analysis was performed to more precisely estimate the association of CASP8 -652 6N del and D302H polymorphisms with PCa susceptibility. Materials and Methods: A comprehensive literature search was conducted to identify all case-control studies of CASP8 D302H and -652 6N del polymorphisms and PCa risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association and the precision of the estimate, respectively. Results: Nine -625 6N del studies and 4 D302H studies were included. CASP8 -652 6N del and D302H polymorphisms were not significantly associated with PCa risk in the overall analyses. However, in the subgroup analysis stratified by ethnicity, -625 6N del was significantly associated with PCa risk in the East Asian and Indian populations under the recessive model. Furthermore, the subgroup analysis strongly suggested that D302H was associated with lower PCa risk in the Non-Indian population under the dominant model. Conclusions: In our meta-analysis, ethnic-specific differences were evident in the association of CASP8-625 6N del and D302H polymorphisms with PCa risk.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7563-7567
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• 2014

Background: Hepatocellular carcinoma (HCC) is the first cause of death in cirrhotic patients, mostly due to viral hepatitis with HCV or HBV infection. This study was performed to estimate the true prevalence of viral hepatitis-related HCC and the demographic and clinical-pathological associations with the two virus types. Materials and Methods: This cross sectional observational study enrolled clinical data base of 188 HCC patients and variables included from baseline were age, sex, area of residence, clinical-pathological features such as underlying co-morbidity, presence or absence of liver cirrhosis, macrovascular involvement, tumor extension and metastasis, liver lobes involved, serum alpha-fetoprotein level, and hepatitis serologies. Results: Overall prevalence of HCV- and HBV-related HCC was 66.0% and 34.0%, respectively. Patients with HCV were more likely to develop HCC at advanced age ($52.4{\pm}11.9$ vs. $40.7{\pm}12.09$ years), with highly raised serum AFP levels (${\geq}400ng/ml$) 78.2% (HBV 67.1%), large tumor size (HCV-66% >5 cm, HBV-59.3%), and presence of portal vein thrombosis (8.06%, HBV 1.56%). A binominal multivariate analysis showed that HCV-HCC group were more likely to be cirrhotic (OR=0.245, 95%CI: 0.117, 0.516) and had more than two times higher rate of solitary macrovascular involvement (OR=2.533, 95%CI: 1.162, 5.521) as compared with HBV associated HCC. Conclusions: Statistically significant variations were observed from baseline to clinical-pathological characteristics in HCV vs HBV associated HCC. Our study suggests prompt and early screening for high risk patients so that the rate of progression of these chronic viral diseases to cirrhosis and cancer can be decreased.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6481-6486
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• 2013

Background: Our previous study demonstrated cytotoxicity of a crude extract from Patrinia heterophylla Bunge (PHEB). In the present study, we aimed to investigate the effects of isovaltrate acetoxyhydrin (IA) isolated from PHEB on the gastric cancer cell SGC-7901, in order to explore a potential treatment for gastric cancer. Methods: MTT assays were employed to determine the effects of IA on cell vitality and proliferation, with monitoring of cell morphology changes and examination of apoptosis with Annexin V-PI staining. Flow cytometry was used to assess cell cycle progression and mitochondrial membrane potential. The activity of caspase 3, 9 was evaluated by spectrophotometry, and the protein levels of Bax, Bcl2 and Cyclin B1 were analyzed with Western blotting of total proteins extracted from cultured cells. Results: The results demonstrated direct toxicity of IA towards SGC-7901 cells. Evidence of apoptosis included blebbing and chromatin condensation. Annexin V-PI assays revealed early apoptosis, involving rapid depolarization of mitochondrial membranes and activity of caspase 3, 9 signaling pathways. Western blotting showed that Bcl2 and Bax proteins was down- and up-regulated, respectively, and cyclin B1 was up-regulated. Cell cycle analysis further indicated that IA could induce G2/M phase arrest in SGC-7901 cells. Conclusions: In conclusion, we believe that IA induces apoptosis of SGC-7901 cells, therefore providing a potential therapeutic agent for treatment of gastric cancer.

• Korean Journal of Clinical Pharmacy
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• v.27 no.2
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• pp.77-82
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• 2017

Background: Clostridium difficile associated diarrhea (CDAD) is a leading cause of hospital-associated gastrointestinal illness. Risk factors for CDAD include advanced age, long-term admission, antibiotics, proton-pump inhibitor or $H_2$ blocker use and immunosuppression. The practice guideline of American Journal of Gastroenterology (2013) suggests metronidazole for the first-line therapy of mild-moderate CDAD as well as vancomycin for severe CDAD. MICU inpatients receiving stress ulcer prophylaxis and antibiotics are susceptible to nosocomial CDAD. Therefore, this study aimed to evaluate occurrence and treatment of CDAD in MICU. Methods: Patients who were admitted to the MICU and had CDAD from August 2012 to August 2015 were analyzed retrospectively. Results: Of the 90 patients with CDAD, 20 patients (2.22%) had mild-moderate CDAD (16 received metronidazole and 4 received vancomycin therapy) and 70 patients (77.8%) had severe CDAD(54 received metronidazole and 16 received vancomycin therapy). Among the patients with mild- moderate CDAD, treatment with metronidazole or vancomycin resulted in same clinical cure in 50% of the patients (p=1.00). Among the patients with severe CDAD, treatment with metronidazole or vancomycin resulted in clinical cure in 40.7% and 50.0% of the patients, respectively (p=0.511). Clinical symptoms recurred in 7.4% of the severe CDAD patients treated with metronidazole and 6.3% of those treated with vancomycin(p=0.875). Conclusion: Our findings suggest that metronidazole and vancomycin are equally effective for the treatment of mild-moderate CDAD; however, vancomycin demonstrated higher clinical cure rate and lower recurrence rate for severe CDAD, although the difference was not statistically significant. For better clinical outcomes, appropriate medication use by disease severity is needed.

• Journal of Gastric Cancer
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• v.20 no.1
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• pp.29-40
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• 2020

Purpose: Gastrointestinal stromal tumors (GISTs) frequently harbor activating gene mutations in either KIT or platelet-derived growth factor receptor A (PDGFRA) and are highly responsive to several selective tyrosine kinase inhibitors. In this study, a targeted next-generation sequencing (NGS) assay with an Oncomine Focus Assay (OFA) panel was used for the genetic characterization of molecular targets in 30 Korean patients with GIST. Materials and Methods: Using the OFA that enables rapid and simultaneous detection of hotspots, single nucleotide variants (SNVs), insertion and deletions (Indels), copy number variants (CNVs), and gene fusions across 52 genes relevant to solid tumors, targeted NGS was performed using genomic DNA extracted from formalin-fixed and paraffin-embedded samples of 30 GISTs. Results: Forty-three hotspot/other likely pathogenic variants (33 SNVs, 8 Indels, and 2 amplifications) in 16 genes were identified in 26 of the 30 GISTs. KIT variants were most frequent (44%, 19/43), followed by 6 variants in PIK3CA, 3 in PDGFRA, 2 each in JAK1 and EGFR, and 1 each in AKT1, ALK, CCND1, CTNNB1, FGFR3, FGFR4, GNA11, GNAQ, JAK3, MET, and SMO. Based on the mutation types, majority of the variants carried missense mutations (60%, 26/43), followed by 8 frameshifts, 6 nonsense, 1 stop-loss, and 2 amplifications. Conclusions: Our study confirmed the advantage of using targeted NGS with a cancer gene panel to efficiently identify mutations associated with GISTs. These findings may provide a molecular genetic basis for developing new drugs targeting these gene mutations for GIST therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.13
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• pp.5163-5167
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• 2015

Background: Colon polyps need to be excised upon detection during colonoscopy due to the risk of malignancy irrespective of their size. In our study, we retrospectively evaluated the clinicopathological characteristics of polyps detected during colonoscopy. Materials and Methods: We assessed 379 patients with polyps detected during colonoscopy between January 2010 and May 2012. The demographics, complaints, colonoscopy findings (shape, place and size of the polyp) and histopathological findings were recorded. We carried out statistical analysis using PASW 18.0 for Windows. Results: There were 227 males (59.9%) and 152 females (40.1%) in the trial. The mean age was 53.8 years (32-90). The most common complaint was rectal bleeding (36.1%), followed by abdominal pain (35.4%). Polyps were detected most commonly in the rectosigmoid region (43.8%), followed by the descending colon (17.4%). Some 239 patients had a single polyp (63.1%) while 140 were found to have multiple polyps (36.9%). While tubular adenoma was the most common pathological type, occurring in 181 patients (47.8%), tubulovillous adenoma (14.2%) and hyperplastic polyp (12.7%) followed, occurring in 54 and 48 patients respectively. While 313 patients (82.6%) did not feature dysplasia, 37 patients (9.7%) exhibited low-grade dysplasia, 28 (7.7%) had high-grade dysplasia and 4 had cancer (1.1%). The rates of villous components and dysplasia were detected to be high among pedunculated polyps and polyps larger than 1 cm (p<0.001). Conclusions: Due to the fact that large-diameter polyps with malignant potential are commonly located in the left colon and have a high prevalence among the middle-aged individuals, it would be appropriate to screen this population at regular intervals via rectosigmoidoscopy.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3379-3383
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• 2012

Objective: To investigate uPA and VEGF expression in esophageal cancer and relations with tumorous invasion and metastasis. Methods: Immunohistochemistry was used to detect uPA and VEGF expression in the normal epithelial tissue of esophageal mucosa and cancer tissue and detect CD34 labeled micrangium and analyze the relationships with clinical pathological features and tumor angiogenesis. Results: Positive rates for uPA and VEGF protein expression were significantly greater in esophageal cancer than normal epithelial tissue (P < 0.05), the two being linked (P <0.05). In addition, uPA and VEGF protein expression of the high microvessel density (MVD) group was significantly lower than in the low MVD group (P < 0.05), with relation to clinical pathological staging, differentiation and lymph node metastasis (P < 0.05). Conclusion: In esophageal cancer tissue, uPA and VEGF proteins are overexpressed and promote tumor angiogenesis, indicative of a poor prognosis.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8883-8886
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• 2014

Background: Tetracycline is an antibiotic widely used for the treatment of Helicobacter pylori infection, but its effectiveness is decreasing due to increasing bacterial resistance. The aim of this study was to investigate the occurrence of 16S rRNA mutations associated with resistance or reduced susceptibility to tetracycline ofHelicobacter pylori by real-time PCR (RT-PCR) assays from culture. Materials and Methods: Tetracycline susceptibility and minimal inhibition concentration (MIC) was determined by the Epsilometer test (Etest) method. A LightCycler assay developed to detect these mutations was applied to DNA extracted from culture. The 16S rRNA of these isolates was sequenced and resistance-associated mutations were identified. From 104 isolates of H. pylori examined, 11 showed resistance to tetracycline. Results: LightCycler assay was applied to DNA extracted from 11 tetracycline-susceptible and 11 tetracycline resistance H. pylori isolates. In our study the sequencing of the H. pylori wild types in 16 s rRNA gene were AGA 926-928 with MIC (0.016 to $0.5{\mu}g/ml$), while the sequencing and MIC for resistant were GGA and AGC, (0.75 to $1.5{\mu}g/ml$), respectively. Also we found a novel mutation in 2 strains with $84^{\circ}C$ as their melting temperatures and exhibition of an A939C mutation. Conclusions: We conclude that real-time PCR is an excellent method for determination of H. pylori tetracycline resistance related mutations that could be used directly on biopsy specimens.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.2363-2367
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• 2014

The association between the NAD(P)H:quinone oxidoreductase 1 (NQO1) gene C609T polymorphism (rs1800566) and gastric cancer has been widely evaluated, but a definitive answer is so far lacking. We first conducted a case-control study to assess this association in a large Han Chinese population, and then performed a meta-analysis to further address this issue. Although our case-control association study indicated no significant difference in the genotype and allele distributions of C609T polymorphism between gastric cancer patients and controls, in the meta analysis involving 4,000 subjects, comparison of alleles 609T and 609C indicated a significantly increased risk (46%) for gastric cancer (95% confidence interval (95%CI) for odds ratio (OR)=1.20-1.79) in individuals with the T allele. The tendency was similar to the homozygote (OR=1.81, 95%CI: 1.16-2.84), dominant models (OR=1.41, 95%CI: 1.12-1.79), as well as recessive model (OR=1.58, 95%CI: 1.06-2.35). Stratified analysis by study design demonstrated stronger associations in population-based than in hospital-based studies. And ethnicity-based analysis demonstrated a significant association in Asians. We conclude that the NQO1 gene C609T polymorphism increases the risk for gastric cancer, especially in Asian populations.