• Asian Pacific Journal of Cancer Prevention
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• v.16 no.1
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• pp.125-131
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• 2015

Currently, taxol is mainly extracted from the bark of yews; however, this method can not meet its increasing demand on the market because yews grow very slowly and are a rare and endangered species belonging to first-level conservation plants. Recently, increasing efforts have been made to develop alternative means of taxol production; microbe fermentation would be a very promising method to increase the production scale of taxol. To determine the activities of the taxol extracted from endophytic fungus N. sylviforme HDFS4-26 in inhibiting the growth and causing the apoptosis of cancer cells, on comparison with the taxol extracted from the bark of yew, we used cellular morphology, cell counting kit (CCK-8) assay, staining (HO33258/PI and Giemsa), DNA agarose gel electrophoresis and flow cytometry (FCM) analyses to determine the apoptosis status of breast cancer MCF-7 cells, cervical cancer HeLa cells and ovarian cancer HO8910 cells. Our results showed that the fungal taxol inhibited the growth of MCF-7, HeLa and HO8910 cells in a dose-and time-dependent manner. IC50 values of fungal taxol for HeLa, MCF-7 and HO8910 cells were $0.1-1.0{\mu}g/ml$, $0.001-0.01{\mu}g/ml$ and $0.01-0.1{\mu}g/ml$, respectively. The fungal taxol induced these tumor cells to undergo apoptosis with typical apoptotic characteristics, including morphological changes for chromatin condensation, chromatin crescent formation, nucleus fragmentation, apoptotic body formation and G2/M cell cycle arrest. The fungal taxol at the $0.01-1.0{\mu}g/ml$ had significant effects of inducing apoptosis between 24-48 h, which was the same as that of taxol extracted from yews. This study offers important information and a new resource for the production of an important anticancer drug by endofungus fermentation.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.15
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• pp.6295-6300
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• 2014

Our aim was to investigate the value of combined detection of serum carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, CA 242 and CA 50 in diagnosis and assessment of prognosis in consecutive gastric cancer patients. Clinical data including preoperative serum CEA, CA 19-9, CA 242, and CA 50 values and information on clinical pathological factors were collected and analyzed retrospectively. Univariate and multivariate survival analyses were used to explore the relationship between tumor markers and survival. Positive rates of tumor markers CEA, CA 19-9, CA 242 and CA 50 in the diagnosis of gastric cancer were 17.7, 17.1, 20.4 and 13.8%, respectively, and the positive rate for all four markers combined was 36.6%. Patients with elevated preoperative serum concentrations of CEA, CA 19-9, CA 242 and CA 50, had late clinical tumor stage and significantly poorer overall survival. Five-year survival rates in patients with elevated CEA, CA 19-9, CA 242 and CA 50 were 28.1, 25.8, 27.0 and 24.1%, respectively, compared with 55.0, 55.4, 56.4 and 54.5% in patients with these markers at normal levels (p<0.01). In multivariate Cox proportional hazards analyses, an elevated CA 242 level was determined to be an independent prognostic marker in gastric cancer patients. Combined detection of four tumor markers increased the positive rate for gastric cancer diagnosis. CA 242 showed higher diagnostic value and CA 50 showed lower diagnostic value. In resectable gastric carcinoma, preoperative CA 242 level was associated with disease stage, and was found to be a significant independent prognostic marker in gastric cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3629-3633
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• 2014

Background: Glioblastoma (GBM) is an immunosuppressive tumor whose median survival time is only 12-15 months, and patients with GBM have a uniformly poor prognosis. It is known that heredity contributes to formation of glioma, but there are few genetic studies concerning GBM. Materials and Methods: We genotyped six tagging SNPs (tSNP) in Han Chinese GBM and control patients. We used Microsoft Excel and SPSS 16.0 statistical package for statistical analysis and SNP Stats to test for associations between certain tSNPs and risk of GBM in five different models. ORs and 95%CIs were calculated for unconditional logistic-regression analysis with adjustment for age and gender. The SHEsis software platform was applied for analysis of linkage disequilibrium, haplotype construction, and genetic associations at polymorphism loci. Results: We found rs891835 in CCDC26 to be associated with GBM susceptibility at a level of p=0.009. The following genotypes of rs891835 were found to be associated with GBM risk in four different models of gene action: i) genotype GT (OR=2.26; 95%CI, 1.29-3.97; p=0.019) or GG (OR=1.33; 95%CI, 0.23-7.81; p=0.019) in the codominant model; ii) genotypes GT and GG (OR=2.18; 95%CI, 1.26-3.78; p=0.0061) in the dominant model; iii) GT (OR=2.24; 95%CI, 1.28-3.92; p=0.0053) in the overdominant model; iv) the allele G of rs891835 (OR=1.85; 95%CI, 1.14-3.00; p=0.015) in the additive model. In addition, "CG" and "CGGAG" were found by haplotype analysis to be associated with increased GBM risk. In contrast, genotype GG of CCDC26 rs6470745 was associated with decreased GBM risk (OR=0.34; 95%CI, 0.12-1.01; p=0.029) in the recessive model. Conclusions: Our results, combined with those from previous studies, suggest a potential genetic contribution of CCDC26 to GBM progression among Han Chinese.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.1961-1970
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• 2014

Pyruvate kinase isozyme type M2 (PKM2) was first found in hepatocellular carcinoma (HCC), and its expression has been thought to correlate with prognosis. A large number of studies have demonstrated that epithelial-mesenchymal transition (EMT) is a crucial event in hepatocellular carcinoma (HCC) and associated metastasis, resulting in enhanced malignancy of HCC. However, the roles of PKM2 in HCC EMT and metastasis remain largely unknown. The present study aimed to determine the effects of PKM2 in EGF-induced HCC EMT and elucidate the molecular mechanisms in vitro. Our results showed that EGF promoted EMT in HCC cell lines as evidenced by altered morphology, expression of EMT-associated markers, and enhanced invasion capacity. Furthermore, the present study also revealed that nuclear translocation of PKM2, which is regulated by the ERK pathway, regulated ${\beta}$-catenin-TCF/LEF-1 transcriptional activity and associated EMT in HCC cell lines. These discoveries provide evidence of novel roles of PKM2 in the progression of HCC and potential therapeutic target for advanced cases.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.10
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• pp.4469-4475
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• 2015

Transient receptor potential melastain 7 (TRPM7) is a bifunctional protein with dual structure of both ion channel and protein kinase, participating in a wide variety of diseases including cancer. Recent researches have reported the mechanism of TRPM7 in human cancers. However, the correlation between TRPM7 and prostate cancer (PCa) has not been well studied. The objective of this study was to investigate the potential the role of TRPM7 in the apoptosis of PC-3 cells, which is the key cell of advanced metastatic PCa. In this study, we demonstrated the influence and potential function of TRPM7 on the PC-3 cells apoptosis induced by TNF-related apoptosis inducing-ligand (TRAIL). The study also found a novel up-regulated expression of TRPM7 in PC-3 cells after treating with TRAIL. Suppression of TRPM7 by TRPM7 non-specific inhibitors ($Gd^{3+}$ or 2-aminoethoxy diphenylborate (2-APB) ) not only markedly eliminated TRPM7 expression level, but also increased the apoptosis of TRAIL-treated PC-3 cells, which may be regulated by the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway accompany with up-regulated expression of cleaved Caspase-3, (TRAIL-receptor 1, death receptors 4) DR4, and (TRAIL-receptor 2, death receptors 5) DR5. Taken together, our findings strongly suggested that TRPM7 was involved in the apoptosis of PC-3 cells induced by TRAIL, indicating that TRPM7 may be applied as a therapeutic target for PCa.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.3
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• pp.1015-1018
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• 2012

Objective: To improve the diagnosis of primary gallbladder carcinoma (GBC) with/without hepatic metastases by analyzing our experience of different GBC treatment in our patients. Methods: A retrospective study was carried out to analyze the clinical data of the 139 patients with GBC who underwent hepatic resection in our unit from January 2003 to December 2007. Patients were divided into two groups according to whether they demonstrated hepatic invasion. Tumor presentation, surgical modes, and prognosis of each patient were retrospectively reviewed. Kaplan-Meier curves and log-rank tests were employed to compare the survival rates of those patients undergoing different surgical procedures. Results: Of the 139 patients, 46 were men and 93 were women with the male to female ratio of 1:2.0. Their ages were ranged from 35 to 86 years with a mean age of $62.8{\pm}10.4$ years. There were 73 patients complicated with hepatic invasion (group A), and no hepatic invasion occurred in the other 66 patients (group B). Compared with the group B, the patients with hepatic invasion suffered lower differentiation of tumor (p=0.000), more advanced Nevin staging (p=0.008) and poorer prognosis (p=0.013). Radical resection were more frequently performed in group B (75.76%) than in group A (45.20%) with better outcomes (p=0.000). Conclusion: GBC patients complicated with hepatic invasion had poorer prognosis than those without invasion in long-term follow-ups. Radical resection might result in a satisfied prognosis in patients without hepatic invasion, but appears less favorable than palliative resection in those who were complicated with hepatic invasion.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.3
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• pp.827-831
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• 2012

To determine the relationship between comorbidity and outcome after radical cystectomy in Chinese patients by using the Adult Comorbidity Evaluation (ACE)-27 index. Two-hundred-and-forty-six patients treated with radical cystectomy at the Second Xiangya Hospital of Central South University, Hunan Province, China between 2000 and 2010 were retrospectively analyzed. Medical records were reviewed for age, gender, delayed time of radical cystectomy, urinary diversion type, pelvic lymphadenectomy status, TNM stage, and pathological grade. Comorbidity information was assessed by the ACE-27 index. The outcome measurement was overall survival. Univariate and multivariate Cox proportional hazards regression analyses were used to determine the association between comorbidity and outcome. The study population consisted of 215 (87.40%) males and 31 (12.60%) females with a mean age of $62{\pm}11$ years. Median duration of follow-up was $47{\pm}31$ months. A total of 151 (61.38%) patents died during follow-up. Of those, 118 (47.97%) had at least one comorbidity. According to the ACE-27 scores, 128 (52.03%) patients had no comorbidity, 79 (32.11%) had mild, 33 (13.41%) had moderate, and 6 (2.45%) had severe comorbidities. Multivariate analysis indicated that moderate (p=0.002) and severe (p<0.001) comorbidity was significantly associated with decreased overall survival. In addition, age ${\geq}70$ years (p=0.002), delayed time of radical cystectomy >12 weeks (p=0.044), pelvic lymphadenectomy status (p=0.014), and TNM stage >T3 (p<0.001) were determined to be independent risk factors of overall survival. Increasing severity of comorbidity statistically correlated with decreased overall survival after radical cystectomy.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.999-1003
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• 2014

Objective: To validate the relationship between MACC1 and 6-phosphofructo-2-kinase/fructose 2, 6 bisphosphatase (PFKFB2) expression as well as its clinicopathological features and prognostic significance in hepatocellular carcinoma. Methods: By using immunohistochemistry, we investigated the MACC1 and PFKFB2 protein expression in 60 pairs of hepatocellular carcinoma and corresponding non-tumor tissues. Using the Mann-Whitney U test, the Chi-square test, Kaplan-Meier survival analysis, Cox proportional hazard regression analysis and Spearman analysis, we studied the relationship between MACC1 and PFKFB2 protein expression and postoperative overall survival (OS) of the HCC patients. Results: MACC1 and PFKFB2 positive staining rates were significantly higher in hepatocellular carcinoma than in the corresponding nontumor tissues (P=0.012 and 0.04, respectively). The clinicopathological features evaluation revealed that positive expression of MACC1 was associated with a high Edmondson classification (P=0.007) and advanced TNM stage (P=0.027). Similar findings were evident for PFKFB2 expression (P=0.002 and P=0.027). MACC1 and PFKFB2 positive expression was associated with a lower OS rate (P=0.004 and 0.03, respectively). Kaplan-Meier survival and Cox proportional hazard regression analyses revealed MACC1 positive expression to be a prognostic factor for postoperative OS, but PFKFB was not. Conclusion: Highly expressed MACC1 and PFKFB2 protein were associated with TNM stage, Edmondson-Steier classification and overall survival. MACC1 may affect tumor metabolism partly through expression and phophorylation of PFKFB2.

• Asian-Australasian Journal of Animal Sciences
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• v.14 no.11
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• pp.1568-1579
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• 2001

This study is aimed at evaluating the effect of Aspergillus oryzae fermentation extract (AFE) on corn silage fermentation characteristics. Trial included two groups of treatments, with or without AFE inclusion in corn ensilage. Sixty corn silage containers, including two treatments with thirty replicates each, were processed in a laboratory scale mini-silo of 21 cm radius by 45 cm height. Three replicate containers were opened and sampled for analysis at 0, 0.5, 1, 2, 3, 4, 6, 10, 18 and 34 days after being ensiled. One silage container from each treatment was installed with a remote controlled electronic thermometer to record the temperature changes. Analysis included silage temperature, pH, fermentation acids, the water-soluble carbohydrates and chemical compositions and the silage protein fractions. Results showed that on the first day, the temperature of the ensiled corn was slightly higher than room temperature, but returned to room temperature on the second day. The pH and concentrations of WSC, ADF, lignin and acetic acid in the AFE treated silage were significantly lower than the control groups (p<0.05). The lactic acid and crude protein on the other hand were significantly higher in the AFE treated silage as compared to the control (p<0.05) at the end of the ensilage period. The DM content was significantly higher (p<0.05) whereas the butyric acid content of the AFE treated silage was significantly lower (p<0.05) than the control at the end of the 34 day ensilage period. Titratable acid and buffering capacity in the corn silage were not significantly different between treatment groups (p>0.05). Ammonia N concentration in the AFE treated silage showed a trend of decrease (p>0.05). NPN and the protein fraction A in both groups increased during the conservation period, but fraction A in the AFE treated corn silage was significantly higher than the control silage (p<0.05). During the conservation period, the AFE treated corn silage showed a trend toward a decrease in fractions $B_1$, $B_3$ and C (p<0.05). The protein fraction B2 showed a trend toward increase in the control group and an inconsistent trend in the AFE treated silage during the ensiling period. The AFE treated silage showed a better Flieg score over the control silage (97 vs. 75) as calculated from the concentrations of lactic acid, acetic acid and butyric acid.

• Asian-Australasian Journal of Animal Sciences
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• v.26 no.10
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• pp.1399-1405
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• 2013

The present study focused on establishing the effects of interferon-gamma (IFN-${\gamma}$) on interleukin-18 (IL-18) expression patterns and pregnancy outcomes in pregnant rats. Pregnant rats at the post-implantation stage were randomized into control, low IFN-${\gamma}$ (L-IFN-${\gamma}$) and high IFN-${\gamma}$ groups (H-IFN-${\gamma}$) that received normal saline, 100 IU/g of IFN-${\gamma}$ and 500 IU/g of IFN-${\gamma}$ vaginal muscular injection, respectively. The effects of IFN-${\gamma}$ on IL-18 expression and pregnancy outcomes were assessed systematically using several methods, including immunohistochemistry streptavidin-perosidase (SP), image pattern analysis, enzyme-linked immune-sorbent assay (ELISA), whole blood count (WBC) count, microscopy and visual observation. IL-18 was detected in the uteri of all pregnant rats, and mainly distributed in the endometrium, decidual cells, vascular endothelium and myometrium. Immunohistochemistry and image pattern analyses revealed significantly lower IL-18 expression in the H-IFN-${\gamma}$ group compared to the L-IFN-${\gamma}$ and control groups (p<0.01), indicating that high doses of IFN-${\gamma}$ induce downregulation of IL-18 in the uterus of pregnant rats. ELISA results disclosed that IL-18 expression in peripheral blood of the H-IFN-${\gamma}$ group was lower than that of the L-IFN-${\gamma}$ group (p<0.05), and significantly reduced compared to the control group (p<0.01). Moreover, the number of peripheral leukocytes in the H-IFN-${\gamma}$ group was significantly higher than those in the control and L-IFN-${\gamma}$ groups (p<0.01). Morphology analysis showed no evident differences between the L-IFN-${\gamma}$ and control groups. However, for the H-IFN-${\gamma}$ group, uterine mucosa bleeding, necrosis and excoriation were observed using microscopy. Visual observation revealed marroon, swelling, crassitude and no embryo in the uterus, which are obvious indicators of abortion. These results indicate that IFN-${\gamma}$ plays a regulatory role in IL-18 expression in the uterus and peripheral blood of pregnant rats at the post-implantation stage. Moreover, high levels (500 IU/g) of IFN-${\gamma}$ influence normal pregnancy at the early stages in rats by downregulating IL-18 expression in the uterus and peripheral blood and increasing the number of peripheral leukocytes, consequently triggering termination of pregnancy.