• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.1925-1931
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• 2016

Background: The XRCC1 protein facilitates various DNA repair pathways; single-nucleotide polymorphisms (SNPs) in this gene are associated with a risk of gastrointestinal cancer (GIC) with inconsistent results, but no data have been previously reported for the Sabah, North Borneo, population. We accordingly investigated the XRCC1 Arg194Trp and Arg399Gln SNPs in terms of GIC risk in Sabah. Materials and Methods: We performed genotyping for both SNPs for 250 GIC patients and 572 healthy volunteers using a polymerase chain reaction-restriction fragment length polymorphism approach. We validated heterozygosity and homozygosity for both SNPs using direct sequencing. Results: The presence of a variant 194Trp allele in the Arg194Trp SNP was significantly associated with a higher risk of GIC, especially with gastric and colorectal cancers. We additionally found that the variant 399Gln allele in Arg399Gln SNP was associated with a greater risk of developing gastric cancer. Our combined analysis revealed that inheritance of variant alleles in both SNPs increased the GIC risk in Sabah population. Based on our etiological analysis, we found that subjects ${\geq}50years$ and males who carrying the variant 194Trp allele, and Bajau subjects carrying the 399Gln allele had a significantly increased risk of GIC. Conclusions: Our findings suggest that inheritance of variant alleles in XRCC1 Arg194Trp and Arg399Gln SNPs may act as biomarkers for the early detection of GIC, especially for gastric and colorectal cancers in the Sabah population.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.1823-1828
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• 2016

Background: Biological and pharmacological activities of dryocrassin ABBA, a phloroglucinol derivative extracted from Dryopteris crassirhizoma, have attracted attention. In this study, the apoptotic effect of dryocrassin ABBA on human hepatocellular carcinoma HepG2 cells was investigated. Materials and Methods: We tested the effects of dryocrassin ABBA on HepG2 in vitro by MTT, flow cytometry, real-time PCR, and Western blotting. KM male mice were used to detect the effect of dryocrassin ABBA on H22 cells in vivo. Results: Dryocrassin ABBA inhibited the growth of HepG2 cells in a concentration-dependent manner. After treatment with 25, 50, and $75{\mu}g/mL$ dryocrassin ABBA, the cell viability was 68%, 60% and 49%, respectively. Dryocrassin ABBA was able to induce apoptosis, measured by propidium iodide (PI)/annexin V-FITC double staining. The results of real-time PCR and Western ting showed that dryocrassin ABBA up-regulated p53 and Bax expression and inhibited Bcl-2 expression which led to an activation of caspase-3 and caspase-7 in the cytosol, and then induction of cell apoptosis. In vivo experiments also showed that dryocrassin ABBA treatment significantly suppressed tumor growth, without major side effects. Conclusions: Overall, these findings provide evidence that dryocrassin ABBA may induce apoptosis in human hepatocellular carcinoma cells through a caspase-mediated mitochondrial pathway.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3111-3116
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• 2015

Background: This study was designed to investigate the value of CEA and CA199 in predicting the treatment response to palliative chemotherapy for advanced gastric cancer. Materials and Methods: We studied 189 patients with advanced gastric cancer who received first-line chemotherapy, measured the serum CEA and CA199 levels, used RECIST1.1 as the gold standard and analyzed the value of CEA and CA199 levels changes in predicting the treatment efficacy of chemotherapy. Results: Among the 189 patients, 80 and 94 cases had increases of baseline CEA (${\geq}5ng/ml$) and CA199 levels (${\geq}27U/ml$), respectively. After two cycles of chemotherapy, 42.9% patients showed partial remission, 33.3% stable disease, and 23.8% progressive disease. The area under the ROC curve (AUC) for CEA and CA199 reduction in predicting effective chemotherapy were 0.828 (95%CI 0.740-0.916) and 0.897 (95%CI 0.832-0.961). The AUCs for CEA and CA199 increase in predicting progression after chemotherapy were 0.923 (95%CI 0.865-0.980) and 0.896 (95%CI 0.834-0.959), respectively. Patients who exhibited a CEA decline ${\geq}24%$ and a CA199 decline ${\geq}29%$ had significantly longer PFS (log rank p=0.001, p<0.001). With the exception of patients who presented with abnormal levels after chemotherapy, changes of CEA and CA199 levels had limited value for evaluating the chemotherapy efficacy in patients with normal baseline tumor markers. Conclusions: Changes in serum CEA and CA199 levels can accurately predict the efficacy of first-line chemotherapy in advanced gastric cancer. Patients with levels decreasing beyond the optimal critical values after chemotherapy have longer PFS.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3389-3393
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• 2015

Background: Chronic inflammation could affect the occurrence and development of malignant tumors. To explore the levels of tumor necrosis factor ${\alpha}$ (TNF-${\alpha}$) and C-reactive protein (CRP) in patients accompanied by impaired glucose tolerance (IGT) and their clinical significance. Materials and Methods: A total of 210 patients hospitalized in Affiliated Hospital of Taishan Medical University from Jun., 2013 to Dec., 2014 were selected, in which 92 cases were accompanied by IGT. Meanwhile, 80 randomly-selected healthy people by physical examination were as the control. The levels of routine biochemical indexes, plasma TNF-${\alpha}$ and CRP in all subjects were measured. Results: Both systolic and diastolic pressures in hypertension group and hypertension plus IGT group were significantly higher than in control group (p<0.01), but there was no statistical significance between these two groups (p>0.05). The levels of fasting plasma glucose (FPG) and blood glucose 2 h after taking glucose in hypertension plus IGT group were markedly higher than other groups (p<0.01). Homeostasis model assessment-insulin resistance (HOMA-IR), TNF-${\alpha}$ and CRP contents were on the progressive increase in control, hypertension and hypertension plus IGT groups, but significant differences were presented among each group (P<0.01). Hypertension accompanied by IGT had a significantly-positive association with CRP, TNF-${\alpha}$, FPG and blood glucose 2h after taking glucose. Conclusions: The levels of plasma TNF-${\alpha}$ and CPR in patients with hypertension accompanied by IGT increase significantly, indicating that inflammatory reaction in these patient increases, thus suggesting that these patients should be focused regarding cancer prevention.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.4
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• pp.1507-1513
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• 2015

Pemetrexed is an antifolate agent which has been used for treating malignant pleural mesothelioma and non small lung cancer in the clinic as a chemotherapeutic agent. In this study, pemetrexed inhibited cell growth and induced G1 phase arrest in the A549 cell line. To explore the molecular mechanisms of pemetrexed involved in cell growth, we used a two-dimensional polyacrylamide gel electrophoresis (2-DE) proteomics approach to analyze proteins changed in A549 cells treated with pemetrexed. As a result, twenty differentially expressed proteins were identified by ESI-Q-TOF MS/MS analysis in A549 cells incubated with pemetrexed compared with non-treated A549 cells. Three key proteins (GAPDH, HSPB1 and EIF4E) changed in pemetrexed treated A549 cells were validated by Western blotting. Accumulation of GAPDH and decrease of HSPB1 and EIF4E which induce apoptosis through inhibiting phosphorylation of Akt were noted. Expression of p-Akt in A549 cells treated with pemetrexed was reduced. Thus, pemetrexed induced apoptosis in A549 cells through inhibiting the Akt pathway.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.3
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• pp.909-913
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• 2015

Background: A systematic review and meta-analysis of observational studies evaluated the association of intake of vitamin B2 with the incidence of colorectal cancer. Materials and Methods: Relevant studies were identified in MEDLINE via PubMed (published up to April 2014). We extracted data from articles on vitamin B2 and used multivariable-adjusted odds ratio (OR) and a random-effects model for analysis. Results: We found 8 articles meeting the inclusion criteria (4 of cohort studies and 4 of case-control studies) and a total of 7,750 colorectal cancer cases were included in this meta-analysis. The multivariable-adjusted OR for pooled studies for the association of the highest versus lowest vitamin B2 intake and the risk of colorectal cancer was 0.83 (95% confidence interval [95%CI]:0.75,0.91). We performed a sensitivity analysis for vitamin B2. If we omitted the study by Vecchia et al., the pooled OR was 0.86 (95%CI, 0.77,0.96). Conclusions: This is the first meta-analysis to study links between vitamin B2 and colorectal cancer. We found vitamin B2 intake was inversely associated with risk of colorectal cancer. However, further research and large sample studies need to be conducted to better validate the result.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2229-2234
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• 2012

Purpose: To assess efficacy of Ki67 combined with VEGF as a molecular grading model to predict outcomes with non-muscle invasive bladder cancer (NMIBC). Materials: 72 NMIBC patients who underwent transurethral resection (TUR) followed by routine intravesical instillations were retrospectively analyzed in this study. Univariate and multivariate analyses were performed to confirm the prognostic values of the Ki67 labeling index (LI) and VEGF scoring for tumor recurrence and progression. Results: The novel molecular grading model for NMIBC contained three molecular grades including mG1 (Ki67 $LI{\leq}25%$, VEGF $scoring{\leq}8$), mG2 (Ki67 LI>25%, VEGF $scoring{\leq}8$; or Ki67 $LI{\leq}25%$, VEGF scoring > 8), and mG3 (Ki67 LI > 25%, VEGF scoring > 8), which can indicate favorable, intermediate and poor prognosis, respectively. Conclusions: The described novel molecular grading model utilizing Ki67 LI and VEGF scoring is helpful to effectively and accurately predict outcomes and optimize personal therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.3
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• pp.767-773
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• 2012

The esophageal squamous cell carcinoma (ESCC) is an aggressive tumor with a poor prognosis. Understanding molecular changes in ESCC should improve identification of risk factors with different molecular subtypes and provide potential targets for early detection and therapy. Our study aimed to obtain a molecular signature of ESCC through the regulation network based on differentially expressed genes (DEGs). We used the GSE23400 series to identify potential genes related to ESCC. Based on bioinformatics we constructed a regulation network. From the results, we could establish that many transcription factors and pathways closely related with ESCC were linked by our method. STAT1 also arose as a hub node in our transcriptome network, along with some transcription factors like CCNB1, TAP1, RARG and IFITM1 proven to be related with ESCC by previous studies. In conclusion, our regulation network provided information on important genes which might be useful in investigating the complex interacting mechanisms underlying the disease.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.5241-5243
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• 2012

Background: Prostate cancer (Pca) is one of the most common complex and polygenic diseases in men. The X-ray repair complementing group 1 gene (XRCC1) is an important candidate in the pathogenesis of Pca. The purpose of this study was to evaluate the association between single nucleotide polymorphisms in the XRCC1 gene and susceptibility to Pca. Materials and Methods: XRCC1 gene polymorphisms and associations with susceptibility to Pca were investigated in 193 prostate patients and 188 cancer-free Chinese men. Results: The c.910A>G variant in the exon9 of XRCC1 gene could be detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing methods. Significantly increased susceptibility to prostate cancer was noted in the homozygote comparison (GG versus AA: OR=2.95, 95% CI 1.46-5.42, ${\chi}^2$=12.36, P=0.001), heterozygote comparison (AG versus AA: OR=1.76, 95% CI 1.12-2.51, ${\chi}^2$=4.04, P=0.045), dominant model (GG/AG versus AA: OR=1.93, 95% CI 1.19-2.97, ${\chi}^2$=9.12, P=0.003), recessive model (GG versus AG+AA: OR=2.17, 95% CI 1.33-4.06, ${\chi}^2$=8.86, P=0.003) and with allele contrast (G versus A: OR=1.89, 95% CI 1.56-2.42, ${\chi}^2$=14.67, P<0.000). Conclusions: These findings suggest that the c.910A>G polymorphism of the XRCC1 gene is associated with susceptibility to Pca in Chinese men, the G-allele conferring higher risk.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.3
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• pp.891-896
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• 2012

This study focused on infection rates and subtypes of human papillomavirus (HPV) in patients with oropharyngeal squamous cell carcinoma (OSCC), and the relationship between HPV status and prognosis of the disease. We evaluated sixty-six OSCC patients who met the enrollment criteria during the period from January 1999 to December 2009. The presence or absence of oncogenic HPV types in tumors was determined using the SPF10 LiPA25 assay. Overall survival (OS) and disease specific survival (DSS) for HPV positive and HPV negative patients were estimated using Kaplan-Meier analysis. The Cox regression model was applied for multivariate analysis. HPV-DNA was detected in 11(16.7%) of all specimens. Among them, 7 were type HPV-16, while other types were HPV-16/11, HPV-35, HPV-58/52, and HPV-33/52/54. Patients with HPV positive tumors were more likely to be female, non-smokers and non-drinkers (p=0.002, 0.001 and 0.001, respectively). After a median follow-up of 24.5 months, patients with HPV positive tumors had significantly better overall survival (HR=0.106[95%CI=0.014-0.787], p=0.016,) and disease specific survival (HR=0.121[95%CI=0.016-0.906], p=0.030). Patients with HPV positive OSCC have significantly better prognosis than patients with HPV negative tumors. HPV infection is an independent prognostic factor.