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Stathmin is a Marker of Progression and Poor Prognosis in Esophageal Carcinoma

  • Wang, Feng;Xuan, Xiao-Yan;Yang, Xuan;Cao, Lei;Pang, Li-Na;Zhou, Ran;Fan, Qin-Xia;Wang, Liu-Xing
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.8
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    • pp.3613-3618
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    • 2014
  • Stathmin, also called oncoprotein 18, is a founding member of the family of microtubule-destabilizing proteins that play a critical role in the regulation of mitosis. At the same time stathmin has been recognized as one of responsible factors in cancer cells. The aim of this study was to assess stathmin status, its correlations with clinicopathological parameters and its role as a progosnostic marker in EC patients. The protein and mRNA levels of stathmin were examined byimmunohistochemistry (IHC) and in situ hybridization in 100EC tissues and adjacent noncancerous tissues. mRNA and protein expression of stathmin in three EC cell lines(EC9706, ECa109, EC1 commonly used in research) were also analyzed using immunocytochemistry, western blot and in situ hybridization. The prognostic value of Stathmin expression within the tumor tissues were assessed by Cox regression and Kaplan-Meier analysis. We showed that stathmin expression was significantly higher in EC tissues than in adjacent noncancerous tissues. High stathmin immunostaining score in the EC was positively correlated with tumor differentiation, Tumor invasion, Lymph node metastases, and TNM stage. In addition, we demonstrated that three EC cell lines examined, were constitutively expressing a high level of stathmin. Of those, EC-1 showed the strongest mRNA and protein expression for the stathmin analyzed. Kaplan-Meier analysis showed that significantly longer 5-year survival rate was seen in EC patients with high Stathmin expression, compared to those with low expression of Stathmin expression. Furthermore, multivariate Cox proportional hazard analyses revealed that Stathmin was an independent factors affecting the overall survival probability. In conclusion, our data provide a basis for the concept that stathmin might be associated with EC development and progression. High levels of Stathmin expression in the tumor tissues may be a good prognostic marker for patients with EC.

rs10505474 and rs7837328 at 8q24 Cumulatively Confer Risk of Prostate Cancer in Northern Han Chinese

  • Zhang, Lin-Lin;Sun, Liang;Zhu, Xiao-Quan;Xu, Yong;Yang, Kuo;Yang, Fan;Yang, Yi-Ge;Chen, Guo-Qiang;Fu, Ji-Cheng;Zheng, Chen-Guang;Li, Ying;Mu, Xiao-Qiu;Shi, Xiao-Hong;Zhao, Fan;Wang, Fei;Yang, Ze;Wang, Bin-You
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.7
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    • pp.3129-3132
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    • 2014
  • Aims: Genome-wide association studies (GWAS) have identified several risk variants for prostate cancer (pCa) mainly in Europeans, which need to be further verified in other racial groups. We selected six previously identified variants as candidates and to define the association with PCa in Northern Han Chinese. Methods: 749 subjects from Beijing and Tianjin in Northern China were included. Six variants (rs10505474, rs7837328, rs4242384, rs7813, rs486907 and rs1058205) were genotyped by high resolution melting (HRM) assays. The individual and cumulative contribution for of the risk of PCa and clinical covariates were analyzed. Results: Among the six candidate variants, onlyrs10505474, and rs7837328, both locating at 8q24 region, were associated with PCa in our population.rs10505474 (A) was associated with PCa ($OR_{recessive}=1.56$, p=0.006); and rs7837328 (A) was associated with PCa ($OR_{dominant}=1.38$, p=0.042/$OR_{recessive}=1.99$, p=0.003). Moreover, we observed a cumulative effects between them ($p_{trend}=2.58{\times}10^{-5}$). The joint population attributable risk showed the two variants might account for 71.85% of PCa risk. In addition, we found the homozygotes of rs10505474 (A) and rs7837328 (A) were associated with PCa clinical covariants (age at onset, tumor stage, respectively) ($p_{age}=0.046$, $P_{tumorstage}=0.048$). Conclusion: rs10505474 (A) and rs7387328 (A) at 8q24 are associated with PCa and cumulatively confer risk, suggesting the two variations could determine susceptibility to PCa in the Northern Chinese Han population.

Identification of Homer1 as a Potential Prognostic Marker for Intrahepatic Cholangiocarcinoma

  • Wu, San-Yun;Yu, Ming-Xia;Li, Xiao-Gai;Xu, Shu-Fang;Shen, Ji;Sun, Zhen;Zhou, Xin;Chen, Xing-Zhen;Tu, Jian-Cheng
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.7
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    • pp.3299-3304
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    • 2014
  • Background: The aim of the present study was to analyze whether Homer1 is a potential prognostic marker for intrahepatic cholangiocarcinoma (ICC). Materials and Methods: The expression of Homer1 in ICC tissue was detected with immunohistochemistry and levels of protein in ICC and paratumor tissues were evaluated by Western blotting. Survival analysis by the Kaplan-Meier method was performed to assess prognostic significance. Results: Homer1 expression was high in 67.4% (58/86) of ICC samples, and there was significant difference between ICC and adjacent noncancerous tissues (p<0.001); high expression was associated with poor histologic differentiation (p=0.019), TNM stage (p=0.014), lymph node metastasis (p=0.040), and lymphatic invasion (p=0.025). On Kaplan-Meier analysis, a comparison of survival curves of low versus high expressors of Homer1 revealed a highly significant difference in OS (p=0.001) and DFS (p=0.006), indicating that high expression of Homer1 was linked with a worse prognosis. Multivariate analyses showed that Homer1 expression was an independent risk factor predicting overall survival[Hazard ratio(HR), 7.52; 95% confidence interval (CI), 2.63-21.47; p=0.002] and disease-free survival (HR, 11.56; 95%CI, 5.17-25.96; p<0.001) in ICC. Conclusions: Homer1 promotes lymphatic invasion and associates with lymph node metastasis and poor prognosis of ICC. The current study shows that Homer1 may be an independent prognostic factor for ICC patients after curative resection, and it provides an important basis for screening/treating high-risk patients.

Susceptibility of Lung Cancer with Polymorphisms of CYP1A1, GSTM1, GSTM3, GSTT1 and GSTP1 Genotypes in the Population of Inner Mongolia Region

  • Jiang, Xue-Yan;Chang, Fu-Hou;Bai, Tu-Ya;Lv, Xiao-Li;Wang, Min-Jie;Wang, Guang
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.13
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    • pp.5207-5214
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    • 2014
  • Background: To study the relationship of susceptibility to lung cancer with the gene polymorphisms of CYP1A1, GSTM1, GSTM3, GSTT1, GSTP1 and smoking status in Han and Mongolian populations of Inner Mongolia, an autonomous region of China. Materials and Methods: PCR-RFLP, allele-specific and multiplex PCR were employed to identify the genotypes of CYP1A1, GSTM1, GSTM3, GSTT1 and GSTP1 in a case-control study of 322 lung cancer patients diagnosed by bronchoscopy and 456 controls free of malignancy. Results: There is a significant difference in genotypic frequency of GSTT1 of healthy Mongolian and Han subjects. A statistically prominent association was found between CYP1A1 Msp1 (vt/vt) (OR=4.055, 95%CI:2.107-7.578, p=0.000), GSTM1 (-) (OR=2.290, 95%CI:1.467-3.573, p=0.000) and lung cancer in Mongolians. Similarly, in the Han population, CYP1A1 Msp1 (vt/vt) (OR=3.194, 95%CI:1.893-5.390, p=0.000) and GSTM1 (-) (OR=1.884, 95%CI:1.284-2.762, p=0.001) carriers also had an elevated risk of lung cancer. The smokers were more susceptible to lung cancer 2.144 fold and 1.631 fold than non-smokers in Mongolian and Han populations, respectively. The smokers who carried with CYP1A1 Msp1 (wt/vt+vt/vt), exon7 (Val/Val+Ile /Val), GSTM1 (-), GSTM3 (AB+BB), and GSTT1 (-) respectively were found all to have a high risk of lung cancer. Conclusions: CYP1A1 Msp1 (vt/vt) and GSTM1 (-) are risk factors of lung cancer in Han and Mongolian population in the Inner Mongolia region. The smokers with CYP1A1 Msp1 (wt/vt+vt/vt), CYP1A1 exon7 (Val/Val+Ile /Val), GSTM1 (-), GSTM3 (AB+BB), and GSTT1 (-) genotypes, respectively, are at elevated risk of lung cancer.

Effect of Embelin on TRAIL Receptor 2 mAb-induced Apoptosis of TRAIL-resistant A549 Non-small Cell Lung Cancer Cells

  • Jiang, Lei;Hao, Jin-Li;Jin, Mu-Lan;Zhang, Yun-Gang;Wei, Ping
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.10
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    • pp.6115-6120
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    • 2013
  • Introduction: Some non-small cell lung cancer (NSCLC) tumor cells are insensitive to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) -based therapy. This study was conducted to examine the effect of embelin on the sensitivity of the A549 NSCLC cell line to TRAIL receptor2 (TRAILR2) monoclonal antibodies and to investigate the potential mechanisms. Materials and Methods: A549 cells were treated with embelin, TRAILR2 mAb or a combination of both. Cell viability was measured using ATPlite assay and apoptosis rates were determined by flow cytometry with AnnexinV-FITC and propidium iodide staining, with the expression levels of proteins analyzed by Western blotting. Results: The cell survival rate of separate treatments with 100 ng/ml TRAILR2 antibody or 25 uM embelin were $81.5{\pm}1.57%$ and $61.7{\pm}2.84%$, respectively. Their combined use markedly decreased cell viability in A549 cells to $28.1{\pm}1.97%$ (P<0.05). The general caspase inhibitor Z-VAD-FMK could inhibit the embelin-enhanced sensitivity of A549 cells to TRAILR2 mAb ($75.97{\pm}3.17%$)(P<0.05). Both flow cytometry and cell morphological analysis showed that embelin was able to increase TRAIL-induced apoptosis in A549 cells. Combined treatment with embelin and TRAILR2 mAb augmented the activation of initiator caspases and effector caspase. In addition, A549 cells showed increasing levels of TRAILR2 protein and decreasing levels of Bcl-2, survivin and c-FLIP following the treatment with embelin+TRAILR2 mAb. Conclusions: Embelin could enhance TRAIL-induced apoptosis in A549 cells. The synergistic effect of the combination treatment might be due to modulation of multiple components in the TRAIL receptor-mediated apoptotic signaling pathway, including TRAILR2, XIAP, survivin, Bcl-2 and c-FLIP.

Growth, Productivity, and Quality of Strawberry as Affected by Propagation Method and Cultivation System (번식방법과 재배시스템에 따른 딸기의 생장, 생산성, 품질)

  • Kang, Dong Il;Hu, Jiangtao;Li, Yali;Jeong, Byoung Ryong
    • Journal of Bio-Environment Control
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    • v.29 no.4
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    • pp.326-336
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    • 2020
  • This study was conducted to investigate productivity of strawberry plants as affected by propagation method and cultivation system. Transplants propagated by cutting propagation and pinning propagation were planted and grown for a whole production period in soil and hydroponic cultivation systems. Growth parameters, fruit productivity, and fruit quality were measured during the whole harvest period. The results showed that propagation method and cultivation system had significant effects on vegetative growth of strawberry plants. Total fruit yield per plant and average fruit weight per fruit during the whole harvest period were significantly lower in the plants grown in soil cultivation system. Total unmarketable fruit ratio was significantly greater in soil cultivation system than that in hydroponic cultivation system. Small fruits were the primary unmarketable fruits in soil cultivation system, while malformed fruits were the primary unmarketable fruits in hydroponic cultivation system. The overall high quality of fruit was found in February, and the plants cultivated in hydroponic cultivation system had higher quality of fruit as compared with that in soil cultivation system. It is concluded that cutting propagation is better than pinning propagation, and hydroponic cultivation system is better than soil cultivation system for fruit productivity of strawberry.

The Existence of a Putative Regulatory Element in 3'-Untranslated Region of Proto-oncogene HOX11's mRNA

  • Li, Yue;Jiang, Zhao-Zhao;Chen, Hai-Xu;Leung, Wai-Keung;Sung, Joseph J.Y.;Ma, Wei-Jun
    • BMB Reports
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    • v.38 no.4
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    • pp.500-506
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    • 2005
  • HOX11 encodes a homeodomain-containing transcription factor which directs the development of the spleen during embryogenesis. While HOX11 expression is normally silenced through an unknown mechanism in all tissues by adulthood, the deregulation of HOX11 expression is associated with leukemia, such as T-cell acute lymphoblastic leukemia. The elucidation of regulatory elements contributing to the molecular mechanism underlying the regulation of HOX11 gene expression is of great importance. Previous reports of HOX11 regulatory elements mainly focused on the 5'-flanking region of HOX11 on the chromosome related to transcriptional control. To expand the search of putative cis-elements involved in HOX11 regulation at the post-transcriptional level, we analyzed HOX11 mRNA 3'-untranslated region (3'UTR) and found an AU-rich region. To characterize this AU-rich region, in vitro analysis of HOX11 mRNA 3'UTR was performed with human RNA-binding protein HuR, which interacts with AU-rich element (ARE) existing in the 3'UTR of many growth factors' and cytokines' mRNAs. Our results showed that the HOX11 mRNA 3'UTR can specifically bind with human HuR protein in vitro. This specific binding could be competed effectively by typical ARE containing RNA. After the deletion of the AU-rich region present in the HOX11 mRNA 3'UTR, the interaction of HOX11 mRNA 3'UTR with HuR protein was abolished. These findings suggest that HOX11 mRNA 3'UTR contains cis-acting element which shares similarity in the action pattern with RE-HuR interactions and may involve in the post-transcriptional regulation of the HOX11 gene.

Cordycepin inhibits chondrocyte hypertrophy of mesenchymal stem cells through PI3K/Bapx1 and Notch signaling pathway

  • Cao, Zhen;Dou, Ce;Li, Jianmei;Tang, Xiangyu;Xiang, Junyu;Zhao, Chunrong;Zhu, Lingyu;Bai, Yun;Xiang, Qiang;Dong, Shiwu
    • BMB Reports
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    • v.49 no.10
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    • pp.548-553
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    • 2016
  • Mesenchymal stem cells (MSCs) are widely used in cartilage tissue engineering to repair articular cartilage defects. However, hypertrophy of chondrocytes derived from MSCs might hinder the stabilization of hyaline cartilage. Thus, it is very important to find a suitable way to maintain the chondrogenic phenotype of chondrocytes. It has been reported that cordycepin has anti-inflammatory and anti-tumor functions. However, the role of cordycepin in chondrocyte hypertrophy remains unclear. Therefore, the objective of this study was to determine the effect of cordycepin on chondrogenesis and chondrocyte hypertrophy in MSCs and ATDC5 cells. Cordycepin upregulated chondrogenic markers including Sox9 and collagen type II while down-regulated hypertrophic markers including Runx2 and collagen type X. Further exploration showed that cordycepin promoted chondrogenesis through inhibiting Nrf2 while activating BMP signaling. Besides, cordycepin suppressed chondrocyte hypertrophy through PI3K/Bapx1 pathway and Notch signaling. Our results indicated cordycepin had the potential to maintain chondrocyte phenotype and reconstruct engineered cartilage.

The Nutritional Value of Brown Rice and Maize for Growing Pigs

  • Li, X.L.;Yuan, S.L.;Piao, X.S.;Lai, C.H.;Zang, J.J.;Ding, Y.H.;Han, L.J.;Han, In K.
    • Asian-Australasian Journal of Animal Sciences
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    • v.19 no.6
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    • pp.892-897
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    • 2006
  • An experiment was designed to study the nutritional value of Chinese brown rice and maize for growing pigs. Six male grower pigs (Duroc${\times}$Landrace${\times}$Large White, $24.3{\pm}1.26$ kg average initial BW) were surgically fitted with a simple T-cannula at the terminal ileum and allotted within a $2{\times}2$ Latin square design. The pigs were fed either a maize or brown rice diet in a direct method to determine their digestibility. The brown rice used in this experiment was husked from one kind of early, long grain, and non-glutinous rice (ELGNR, indica rice: non-waxy rice, containing amylopectin and amylose) in southern China. Chromic oxide was used as a marker. The diets were supplied at about 4.0% of body weight in dry matter/d. Total faeces and urine were collected on days 4 and 5; digesta was collected on days 6-8 in each period. The average body weight was 24.3 kg at the start of the experiment and 27.6 kg at the end. The results showed that the apparent ileal digestibilities of most amino acids of brown rice were significantly higher than those in maize (p<0.01), as were the apparent ileal digestibilities of crude protein (CP), digestible energy (DE), organic matter (OM) and dry matter (DM) (p<0.05). However, the apparent ileal starch digestibilities of the two treatments were similar (p>0.05). The values of the apparent faecal digestibilities derived from the two methods, marker and total faecal-collection methods, were very similar and also correlated with each other. The difference in absolute value of the apparent faecal digestibilities between brown rice and maize was smaller compared to that of the apparent ileal digestibilities. The net protein utilization was higher (p = 0.07) and the DE metabolizable rate was significantly higher (p<0.01) for brown rice than for maize. The metabolizable energy (ME) of brown rice is similar to that of maize, while the DE of brown rice was relatively lower. It can be concluded that Chinese brown rice are better than maize not only in apparent ileal digestibilities, but also in metabolizable rate of amino acids and gross energy under the present study conditions.

Dietary Supplementation with Acanthopanax senticosus Extract Modulates Gut Microflora in Weaned Piglets

  • Yin, Fugui;Yin, Yulong;Kong, Xiangfeng;Liu, Yulan;He, Qinghua;Li, Tiejun;Huang, Ruilin;Hou, Yongqing;Shu, Xugang;Tan, Liangxi;Chen, Lixiang;Gong, Jianhua;Kim, Sung Woo;Wu, Guoyao
    • Asian-Australasian Journal of Animal Sciences
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    • v.21 no.9
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    • pp.1330-1338
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    • 2008
  • This study was conducted to investigate the effects of Acanthopanax senticosus extract (ASE) as a dietary additive on gut microflora in weaned piglets. A total of sixty pigs were weaned at 21 d of age (BW = $5.64{\pm}0.23kg$) and allocated on the basis of BW and litter to three dietary treatments in a randomized complete block design. The dietary treatments were: control group (basal diet), antibiotics group (basal diet+0.02% colistin), and ASE group (basal diet+0.1% ASE). On d 7, 14 and 28 after consuming the experimental diets, five piglets per group were sacrificed and then the contents from the jejunum, ileum and cecum were collected to determine changes in the microbial community by using a polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) technique and estimating the contents of Lactobacillus and E. coli by in vitro culturing methods. The results showed that the ASE promoted the microflora diversity in the cecum. Enumeration of bacteria in the gut contents showed that the number of Lactobacillus increased (p<0.05), while that of E. coli decreased (p<0.05) when compared with the other 2 groups as the days of age progressed post-weaning. These findings suggested that the ASE, as a substitute for dietary antimicrobial products, could improve the development of the normal gut microflora and suppress bacterial pathogens, and effectively promote a healthy intestinal environment.