• Asian Pacific Journal of Cancer Prevention
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• v.15 no.24
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• pp.10713-10718
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• 2015

Purpose: To investigate the prognostic value of serum amyloid A (SAA) in patients with hepatocellular carcinoma (HCC) undergoing surgery. Materials and Methods: Preoperative serum samples of 328 patients with HCC who underwent curative resection and of 47 patients with benign liver lesion were assayed. Serum levels of SAA were measured by enzyme-linked immunosorbent assay and its correlations with clinicopathological characteristics and survival were explored. Results: Levels of SAA were significantly higher in patients with HCC than those with benign liver lesion. There were strong correlations between preoperative serum SAA level and tumor size and more advanced BCLC stage. On univariate analysis, elevated SAA was associated with reduced disease-free survival and overall survival (p=0.001 and 0.03, respectively). Multivariate analyses showed that serum SAA level was an independent prognostic factor for overall survival (hazard ratio 2.80, p=0.01). Conclusions: High SAA serum level is a novel biomarker for the prognosis of HCC patients.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.14
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• pp.5721-5727
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• 2014

Objectives: To evaluate the performance of clustering methods used in the prognostic assessment of categorical clinical data for hepatocellular carcinoma (HCC) patients in China, and establish a predictable prognostic nomogram for clinical decisions. Materials and Methods: A total of 332 newly diagnosed HCC patients treated with hepatic resection during 2006-2009 were enrolled. Patients were regularly followed up at outpatient clinics. Clustering methods including the Average linkage, k-modes, fuzzy k-modes, PAM, CLARA, protocluster, and ROCK were compared by Monte Carlo simulation, and the optimal method was applied to investigate the clustering pattern of the indices including platelet count, platelet/lymphocyte ratio (PLR) and serum aspartate aminotransferase activity/platelet count ratio index (APRI). Then the clustering variable, age group, tumor size, number of tumor and vascular invasion were studied in a multivariable Cox regression model. A prognostic nomogram was constructed for clinical decisions. Results: The ROCK was best in both the overlapping and non-overlapping cases performed to assess the prognostic value of platelet-based indices. Patients with categorical platelet-based indices significantly split across two clusters, and those with high values, had a high risk of HCC recurrence (hazard ratio [HR] 1.42, 95% CI 1.09-1.86; p<0.01). Tumor size, number of tumor and blood vessel invasion were also associated with high risk of HCC recurrence (all p< 0.01). The nomogram well predicted HCC patient survival at 3 and 5 years. Conclusions: A cluster of platelet-based indices combined with other clinical covariates could be used for prognosis evaluation in HCC.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5145-5151
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• 2013

Background: Numerous carcinogens and reactive oxygen species (ROS) may cause DNA damage including oxidative base lesions that lead to risk of nasopharyngeal carcinoma. Genetic susceptibility has been reported to play a key role in the development of this disease. The base excision repair (BER) pathway can effectively remove oxidative lesions, maintaining genomic stability and normal expression, with X-ray repair crosscomplementing1 (XRCC1), 8-oxoguanine glycosylase-1 (OGG1) and apurinic/apyimidinic endonuclease 1 (APE1) playing important roles. Aims: To analyze polymorphisms of DNA BER genes (OOG1, XRCC1 and APE1) and explore their associations, and the combined effects of these variants, with risk of nasopharyngeal carcinoma. Materials and Methods: We detected SNPs of XRCC1 (Arg399Gln), OGG1 (Ser326Cys), APE1 (Asp148Glu and -141T/G) using the polymerase chain reaction (PCR) with peripheral blood samples from 231 patients with NPC and 300 healthy people, furtherly analyzing their relations with the risk of NPC in multivariate logistic regression models. Results: After adjustment for sex and age, individuals with the XRCC1 399Gln/Gln (OR=1.96; 95%CI:1.02-3.78; p=0.04) and Arg/Gln (OR=1.87; 95%CI:1.29-2.71; p=0.001) genotype variants demonstrated a significantly increased risk of nasopharyngeal carcinoma compared with those having the wild-type Arg/Arg genotype. APE1-141G/G was associated with a significantly reduced risk of NPC (OR=0.40;95%CI:0.18-0.89) in the smoking group. The OR calculated for the combination of XRCC1 399Gln and APE1 148Gln, two homozygous variants, was significantly additive for all cases (OR=2.09; 95% CI: 1.27-3.47; p=0.004). Conclusion: This is the first study to focus on the association between DNA base-excision repair genes (XRCC1, OGG1 and APE1) polymorphism and NPC risk. The XRCC1 Arg399Gln variant genotype is associated with an increased risk of NPC. APE1-141G/G may decrease risk of NPC in current smokers. The combined effects of polymorphisms within BER genes of XRCC1 399Gln and APE1 148Gln may contribute to a high risk of nasopharyngeal carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5231-5235
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• 2013

Objective: NF-E2-related factor 2 (Nrf2) is activated in several human malignancies. However, the role of Nrf2 in gastric cancer (GC) remains incompletely understood. In this study, we therefore analyzed associations of Nrf2 expression status with clinical features and chemotherapeutic resistance in GC. Materials and Methods: A total of 186 samples from GC patients who underwent gastrectomy were used for prognostic assessment. A further 142 samples from GC cases who received first-line combination chemotherapy were applied for investigation of chemoresistance. The Nrf2 expression was evaluated by immunohistochemistry in GC samples, and its relationship with clinicopathological parameters and chemotherapy sensitivity was analyzed. The effect of Nrf2 gene silencing on chemotherapy resistance was also examined by cell viability assay in vivo. Results: Of the 186 patients with GC, 104/186 (55.9%) showed high expression for Nrf2. The overexpression of Nrf2 was an independent predictor of overall survival [OS, hazard ratio (HR) 3.9; P=0.011] and disease-free survival (DFS, HR 4.3; P=0.002). The gene silencing of Nrf2 reduced resistance to cell death induced by 5-FU in GC cell lines. Conclusion: Our data show that Nrf2 is an independent prognostic factor in GC. Furthermore, Nrf2 confers resistance to chemotherapeutic drug 5-FU in GC cells. Taken together, Nrf2 is a potential prognostic marker and predictive for 5-FU resistance in GC.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5415-5420
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• 2013

Background: Cell cycle deregulation is a major component of carcinogenesis. The p53 tumor suppressor gene plays an important role in regulating cell cycle arrest, and mouse double minute 2 (MDM2) is a key regulator of p53 activity and degradation. Abnormal expression of p53 and MDM2 occurs in various cancers including lung cancer. Methods: We investigated the distribution of the p53 Arg72Pro (rs1042522) and MDM2 SNP309 (rs2279744) genotypes in patients and healthy control subjects to assess whether these single nucleotide polymorphisms (SNPs) are associated with an increased risk of lung adenocarcinomas in Chinese female non-smokers. Genotypes of 764 patients and 983 healthy controls were determined using the TaqMan SNP genotyping assay. Results: The p53 Pro/Pro genotype (adjusted OR = 1.55, 95% CI = 1.17-2.06) significantly correlated with an increased risk of lung adenocarcinoma, compared with the Arg/Arg genotype. An increased risk was also noted for MDM2 GG genotype (adjusted OR = 1.68, 95% CI = 1.27-2.21) compared with the TT genotype. Combined p53 Pro/Pro and MDM2 GG genotypes (adjusted OR = 2.66, 95% CI = 1.54-4.60) had a supermultiplicative interaction with respect to lung adenocarcinoma risk. We also found that cooking oil fumes, fuel smoke, and passive smoking may increase the risk of lung adenocarcinomas in Chinese female non-smokers who carry p53 or MDM2 mutant alleles. Conclusions: P53 Arg72Pro and MDM2 SNP309 polymorphisms, either alone or in combination, are associated with an increased lung adenocarcinoma risk in Chinese female non-smokers.

• Journal of East Asia Management
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• v.1 no.1
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• pp.1-27
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• 2020

Military experience has a great impact on a soldier ability to handle risks. Therefore, when those soldiers become managers, they may behave differently in making risky corporate decisions, especially in activities like the R&D investment. However, studies on how military experience affect R&D have been largely missing in the largest emerging economy, i.e. China, despite that the country hires a higher percentage of military managers than the US. In addition, it remains a question whether military managers affect the state-owned enterprises (SOEs) in China, as many of the corporate decisions are made by the government. This paper tries to address these questions. The imprinting theory and the upper echelon theory suggest that managers' personal experience can affect their behaviour, which in turn influences their corporate decisions. In this paper, we examine whether managers with military experience lead to higher R&D investment and whether such an effect exists in state-owned enterprises. Based on a sample of listed firms in China's A-share market over 2008-2017, we make two findings. First, companies with military managers have high R&D investment. By dividing managers' military positions into high and low rank, we find that companies tend to have higher (lower) R&D investment if their managers hold a high-rank (low-rank) position. Second, the effect of high-rank military managers on R&D investment is more pronounced if the manager is also the founder and the company is a non-state-owned enterprise. For low-ranking military managers, a stronger effect on R&D investment is also observed if they are also the founder, but whether their companies are state-owned or not has no impact on R&D investment. This study identifies managers' military experience as a contributing factors to corporate R&D investment in the largest emerging economy. This paper tests an implication of the imprinting theory and the upper echelon theory, i.e., managers' personal experience can affect their behaviour, which in turn influences their corporate decisions. Specifically, we focus on one aspect of personal experience - military experience - and look at whether it is beneficial to firms' technological innovation, therefore enriches the literature of managerial heterogeneity. Our findings on the influence of managers' military experience on firms' technological innovation can help us better understand the role of managers play in corporate decision making, and how managers' individual traits interact with the firm's characteristics.

• Ocean and Polar Research
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• v.25 no.3
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• pp.277-286
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• 2003

Nitrification performance of fixed film biofilters using coarse sand, loess bead, or styrofoam beads in biofilter columns 1 meter high and 30cm in diameter were studied at different hydraulic and organic matter loading rates. Synthetic wastewater was supplied to the culture tank in order to maintain desired TAN concentrations in inlet water to biofilters. All the biofilters were conditioned 5 months before start of sampling. TAN and $NO_2-N$ conversion rates increased with an increase in the hydraulic loading rate (HLR). However, the improvement in biofilter performance was not linearly correlated to HLR in styrofoam bead filters. This is mainly due to the characteristics of the styrofoam beads used. TAN conversion rates of sand filters increased with the increase of HLR up to $200m^3/m^2$. per day. No increase in the TAN conversion rate was observed at the highest HLR since flooding on the media surface took place. HLR had a significant impact on the TAN conversion rates in loess bead filter up to the highest HLR tested (P<0.05). TAN conversion rates were much less at organic matter loading rates of 9 and 18kg $O_2/m^3$ per day than those without the addition of organic matter in styrofoam bead filters. The addition of glucose resulted in a reduction of the TAN conversion rate from 540 to 284g $TAN/m^3$ per day. No significant difference of TAN conversion rates between the two organic matter loading rates was found (p<0.05). This indicates that the impact of organic matter on nitrification becomes less and less sensitive with an increase in the COD/TAN ratio. At an organic matter loading rate of 9kg $O_2/m^3$. per day, a great reduction of TAN conversion rates was observed in sand filters and loess bead filters. Clearly, organic matter can be one of the most Important Impacting factors on nitrification. $NO_2-N$ conversion rates showed a similar trend for TAN. Based on the TAN and nitrite conversion rates, styrofoam beads showed the best performance among the three filter media tested. Also, the low gravity and price of styrofoam beads make the handling easier and more cost-effective for commercial application. The results obtained at the highest organic matter loading rates can be used in the biofilter design in recirculating aquaculture system.

• Journal of Microbiology and Biotechnology
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• v.26 no.12
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• pp.2214-2223
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• 2016

Toll-like receptors (TLRs) can recognize conserved molecular patterns and initiate a wide range of innate and adaptive immune responses against invading infectious agents. The aim of this study was to assess the transcript profile of mink TLRs (mTLRs) in mink peripheral blood mononuclear cells (PBMCs) and a range of tissues, and to explore the potential role of mTLRs in the antiviral immune response process. The results indicated that the mTLR partial nucleotide sequences had a high degree of nucleotide identity with ferret sequences (95-98%). Phylogenetic analysis showed that mammalian TLRs grouped into five TLR families, with a closer relationship of the mTLRs with those of ferret than the other mammalian sequences. Moreover, all the mTLRs were ubiquitously expressed in lymphoid organs (spleen and lymph nodes) and PBMCs. Interestingly, the mTLR expression patterns in lung, uterus, and heart showed quite a lot of similarity. Another remarkable observation was the wide expression of mTLR1-3 mRNAs in all tissues. Among the analyzed tissues, skeletal muscle was revealed to being the lowest repertoire of mTLR expression. Additionally, mink PBMCs exposed to the canine distemper virus revealed significant upregulation of mTLR2, mTLR4, mTLR7, and mTLR8 mRNAs, indicating that mTLRs have a role in innate immunity in the mink. Collectively, our results are the first to establish the basic expression patterns of mTLRs and the relationship between mTLRs and a virus, which will contribute to better understanding of the evolution and the functions of mTLRs in the innate immune system in minks.

• Journal of Microbiology and Biotechnology
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• v.26 no.12
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• pp.2159-2170
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• 2016

Many plant-pathogenic bacteria are dependent on quorum sensing (QS) to evoke disease. In this study, the population of QS and quorum quenching (QQ) bacteria was analyzed in a consecutive monoculture system of Pseudostellaria heterophylla. The isolated QS strains were identified as Serratia marcescens with SwrIR-type QS system and exhibited a significant increase over the years of monoculture. Only one QQ strain was isolated from newly planted soil sample and was identified as Bacillus thuringiensis, which secreted lactonase to degrade QS signal molecules. Inoculation of S. marcescens to P. heterophylla root could rapidly cause wilt disease, which was alleviated by B. thuringiensis. Furthermore, the expression of lactonase encoded by the aiiA gene in S. marcescens resulted in reduction of its pathogenicity, implying that the toxic effect of S. marcescens on the seedlings was QS-regulated. Meanwhile, excess lactonase in S. marcescens led to reduction in antibacterial substances, exoenzymes, and swarming motility, which might contribute to pathogensis on the seedlings. Root exudates and root tuber extracts of P. heterophylla significantly promoted the growth of S. marcescens, whereas a slight increase of B. thuringiensis was observed in both samples. These results demonstrated that QS-regulated behaviors in S. marcescens mediated by root exudates played an important role in replanting diseases of P. heterophylla.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.1
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• pp.9-14
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• 2016

Adenosine 3',5'-cyclic monophosphate (cAMP) participates in the regulation of numerous cellular functions, including the $Na^+-K^+$-ATPase (sodium pump). Ouabain, used in the treatment of several heart diseases, is known to increase cAMP levels but its effects on the atrium are not understood. The aim of the present study was to examine the effect of ouabain on the regulation of atrial cAMP production and its roles in atrial endothelin-1 (ET-1) secretion in isolated perfused beating rabbit atria. Our results showed that ouabain ($3.0{\mu}mol/L$) significantly increased atrial dynamics and cAMP levels during recovery period. The ouabain-increased atrial dynamics was blocked by KB-R7943 ($3.0{\mu}mol/L$), an inhibitor for reverse mode of $Na^+-Ca^{2+}$ exchangers (NCX), but did not by L-type $Ca^{2+}$ channel blocker nifedipine ($1.0{\mu}mol/L$) or protein kinase A (PKA) selective inhibitor H-89 ($3.0{\mu}mol/L$). Ouabain also enhanced atrial intracellular cAMP production in response to forskolin and theophyline ($100.0{\mu}mol/L$), an inhibitor of phosphodiesterase, potentiated the ouabain-induced increase in cAMP. Ouabain and 8-Bromo-cAMP ($0.5{\mu}mol/L$) markedly increased atrial ET-1 secretion, which was blocked by H-89 and by PD98059 ($30{\mu}mol/L$), an inhibitor of extracellular-signal-regulated kinase (ERK) without changing ouabain-induced atrial dynamics. Our results demonstrated that ouabain increases atrial cAMP levels and promotes atrial ET-1 secretion via the mitogen-activated protein kinase (MAPK)/ERK signaling pathway. These findings may explain the development of cardiac hypertrophy in response to digitalis-like compounds.