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PKM2 Regulates Hepatocellular Carcinoma Cell Epithelial-mesenchymal Transition and Migration upon EGFR Activation

  • Fan, Fang-Tian;Shen, Cun-Si;Tao, Li;Tian, Chao;Liu, Zhao-Guo;Zhu, Zhi-Jie;Liu, Yu-Ping;Pei, Chang-Song;Wu, Hong-Yan;Zhang, Lei;Wang, Ai-Yun;Zheng, Shi-Zhong;Huang, Shi-Le;Lu, Yin
    • 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.

Efficacy of Taxane-Based Regimens in a First-line Setting for Recurrent and/or Metastatic Chinese Patients with Esophageal Cancer

  • Jiang, Chang;Liao, Fang-Xin;Rong, Yu-Ming;Yang, Qiong;Yin, Chen-Xi;He, Wen-Zhuo;Cai, Xiu-Yu;Guo, Gui-Fang;Qiu, Hui-Juan;Chen, Xu-Xian;Zhang, Bei;Xia, Liang-Ping
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.13
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    • pp.5493-5498
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    • 2014
  • Objective: To compare the efficacy of taxane-based regimens in the first line setting retrospectively in Chinese patients with recurrent and/or metastatic esophageal cancer. Methods: We analyzed 102 recurrent and/or metastatic esophageal cancer patients who received taxanes-based regimens in a first-line setting from January 2009 to December 2013. Sixteen (15.7%) patients were administered Nab-PTX based chemotherapy and 86 patients (84.3%) received paclitaxel (PTX) or docetaxel (DTX) based chemotherapy. Patients in the PTX/DTX group could be further divided into TP (71 patients) and TPF (15 patients) groups. Results: The objective response rate (ORR) of all patients was 20.6%, and the disease control rate (DCR) was 67.6%. The median overall survival (OS) was 10.5 months (95% CI 10.1-16.4) and the median progression-free survival (PFS) was 6.04 months (95% CI 5.09-7.91). The DCR was higher in the TPF group than the TP group (93.3% vs. 59.1%; p = 0.015 ). There were no significant differences in ORR, OS, and PFS among Nab-PTX, TPF and TP groups. Conclusions: The three regimens of Nab-PTX based, TP and TPF proved active in a first line setting of Chinese patients with recurrent and/or metastatic esophageal cancer, and should thus be regarded as alternative treatments.

Prediction Models for Solitary Pulmonary Nodules Based on Curvelet Textural Features and Clinical Parameters

  • Wang, Jing-Jing;Wu, Hai-Feng;Sun, Tao;Li, Xia;Wang, Wei;Tao, Li-Xin;Huo, Da;Lv, Ping-Xin;He, Wen;Guo, Xiu-Hua
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.10
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    • pp.6019-6023
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    • 2013
  • Lung cancer, one of the leading causes of cancer-related deaths, usually appears as solitary pulmonary nodules (SPNs) which are hard to diagnose using the naked eye. In this paper, curvelet-based textural features and clinical parameters are used with three prediction models [a multilevel model, a least absolute shrinkage and selection operator (LASSO) regression method, and a support vector machine (SVM)] to improve the diagnosis of benign and malignant SPNs. Dimensionality reduction of the original curvelet-based textural features was achieved using principal component analysis. In addition, non-conditional logistical regression was used to find clinical predictors among demographic parameters and morphological features. The results showed that, combined with 11 clinical predictors, the accuracy rates using 12 principal components were higher than those using the original curvelet-based textural features. To evaluate the models, 10-fold cross validation and back substitution were applied. The results obtained, respectively, were 0.8549 and 0.9221 for the LASSO method, 0.9443 and 0.9831 for SVM, and 0.8722 and 0.9722 for the multilevel model. All in all, it was found that using curvelet-based textural features after dimensionality reduction and using clinical predictors, the highest accuracy rate was achieved with SVM. The method may be used as an auxiliary tool to differentiate between benign and malignant SPNs in CT images.

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.

CCNG2 Suppressor Biological Effects on Thyroid Cancer Cell through Promotion of CDK2 Degradation

  • Li, Wei-Juan;Liu, Ge-Ling;Yu, Fang;Xiang, Xiu-Xiu;Lu, Yi-Fang;Xiao, Hong-Zhen;Shi, Yan-Ping
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.10
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    • pp.6165-6171
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    • 2013
  • This study aimed to analyze the expression and clinical significance of cyclin G2 (CCNG2) in thyroid carcinoma and the biological effects of CCNG2 overexpression in a cell line. Immunohistochemistry and Western blotting were used to analyze CCNG2 protein expression in 63 cases of thyroid cancer and normal tissues to allow the relationship with clinical factors to be assessed. CCNG2 lentiviral and empty vectors were transfected into the thyroid cancer K1 cell line. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were applied to detect the mRNA and protein levels of CCNG2. MTT assay and cell cycle were also conducted to assess the influence of up-regulated expression of CCNG2 on K1 cell biology. The level of CCNG2 protein expression was found to be significantly lower in thyroid cancer tissue than normal tissues (P<0.05). Western blot: The relative amount of CCNG2 protein in thyroid cancer tissue was respectively found to be significantly lower than in normal tissues (P<0.05), correlating with lymph node metastasis, clinic stage and histological grade (P<0.05), but not gender, age or tumor size (P>0.05). Loss of CCNG2 expression correlated significantly with poor overall survival time on Kaplan-Meier analysis (P<0.05). The results for biological functions showed that K1 cell transfected CCNG2 had a lower survival fraction, a greater percentage in the G0/G1 phases, and lower cyclin-dependent kinase 2 (CDK2) protein expression compared with K1 cells non-transfected with CCNG2 (P<0.05). CCNG2 expression decreased in thyroid cancer and correlated significantly lymph node metastasis, clinic stage, histological grade and poor overall survival, suggesting that CCNG2 may play important roles as a negative regulator in thyroid cancer K1 cells by promoting degradation of CDK2.

The DNA Repair Gene ERCC6 rs1917799 Polymorphism is Associated with Gastric Cancer Risk in Chinese

  • Liu, Jing-Wei;He, Cai-Yun;Sun, Li-Ping;Xu, Qian;Xing, Cheng-Zhong;Yuan, Yuan
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.10
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    • pp.6103-6108
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    • 2013
  • Objective: Excision repair cross-complementing group 6 (ERCC6) is a major component of the nucleotide excision repair pathway that plays an important role in maintaining genomic stability and integrity. Several recent studies suggested a link of ERCC6 polymorphisms with susceptibility to various cancers. However, the relation of ERCC6 polymorphism with gastric cancer (GC) risk remains elusive. In this sex- and age-matched case-control study including 402 GC cases and 804 cancer-free controls, we aimed to investigate the association between a potentially functional polymorphism (rs1917799 T>G) in the ERCC6 regulatory region and GC risk. Methods: The genotypes of rs1917799 were determined by Sequenom MassARRAY platform and the status of Helicobacter pylori infection was detected by enzyme-linked immunosorbent assay. Odd ratios (ORs) and 95% confidential interval (CI) were calculated by logistic regression analysis. Results: Compared with the common TT genotype, the ERCC6 rs1917799 GG genotype was associated with increased GC risk (adjusted OR=1.46, 95%CI: 1.03-2.08, P=0.035). When compared with (GT+TT) genotypes, the GG genotype also demonstrated a statistical association with increased GC risk (adjusted OR=1.38, 95%CI: 1.01-1.89, P=0.044). This was also observed for the male subpopulation (GG vs. TT: adjusted OR=1.71, 95%CI: 1.12-2.62, P=0.013; G allele vs. T allele: adjusted OR=1.32, 95%CI: 1.07-1.62, P=0.009). Genetic effects on increased GC risk tended to be enhanced by H. pylori infection, smoking and drinking, but their interaction effects on GC risk did not reach statistical significance. Conclusions: ERCC6 rs1917799 GG genotype might be associated with increased GC risk in Chinese, especially in males.

Analysis of Geographic and Pairwise Distances among Chinese Cashmere Goat Populations

  • Liu, Jian-Bin;Wang, Fan;Lang, Xia;Zha, Xi;Sun, Xiao-Ping;Yue, Yao-Jing;Feng, Rui-Lin;Yang, Bo-Hui;Guo, Jian
    • Asian-Australasian Journal of Animal Sciences
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    • v.26 no.3
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    • pp.323-333
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    • 2013
  • This study investigated the geographic and pairwise distances of nine Chinese local Cashmere goat populations through the analysis of 20 microsatellite DNA markers. Fluorescence PCR was used to identify the markers, which were selected based on their significance as identified by the Food and Agriculture Organization of the United Nations (FAO) and the International Society for Animal Genetics (ISAG). In total, 206 alleles were detected; the average allele number was 10.30; the polymorphism information content of loci ranged from 0.5213 to 0.7582; the number of effective alleles ranged from 4.0484 to 4.6178; the observed heterozygosity was from 0.5023 to 0.5602 for the practical sample; the expected heterozygosity ranged from 0.5783 to 0.6464; and Allelic richness ranged from 4.7551 to 8.0693. These results indicated that Chinese Cashmere goat populations exhibited rich genetic diversity. Further, the Wright's F-statistics of subpopulation within total (FST) was 0.1184; the genetic differentiation coefficient (GST) was 0.0940; and the average gene flow (Nm) was 2.0415. All pairwise FST values among the populations were highly significant (p<0.01 or p<0.001), suggesting that the populations studied should all be considered to be separate breeds. Finally, the clustering analysis divided the Chinese Cashmere goat populations into at least four clusters, with the Hexi and Yashan goat populations alone in one cluster. These results have provided useful, practical, and important information for the future of Chinese Cashmere goat breeding.

Role of microRNAs in myogenesis and their effects on meat quality in pig - A review

  • Iqbal, Ambreen;Jiang, Ping;Ali, Shaokat;Gao, Zhen;Liu, Juan;Jin, Zi Kang;Pan, Ziyi;Lu, Huixian;Zhao, Zhihui
    • Asian-Australasian Journal of Animal Sciences
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    • v.33 no.12
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    • pp.1873-1884
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    • 2020
  • The demand for food is increasing day by day because of the increasing global population. Therefore, meat, the easiest and largely available source of protein, needs to be produced in large amounts with good quality. The pork industry is a significant shareholder in fulfilling the global meat demands. Notably, myogenesis- development of muscles during embryogenesis- is a complex mechanism which culminates in meat production. But the molecular mechanisms which govern the myogenesis are less known. The involvement of miRNAs in myogenesis and meat quality, which depends on factors such as myofiber composition and intramuscular fat contents which determine the meat color, flavor, juiciness, and water holding capacity, are being extrapolated to increase both the quantity and quality of pork. Various kinds of microRNAs (miRNAs), miR-1, miR-21, miR22, miR-27, miR-34, miR-127, miR-133, miR-143, miR-155, miR-199, miR-206, miR-208, miR-378, and miR-432 play important roles in pig skeletal muscle development. Further, the quality of meat also depends upon myofiber which is developed through the expression of different kinds of miRNAs at different stages. This review will focus on the mechanism of myogenesis, the role of miRNAs in myogenesis, and meat quality with a focus on the pig.

Feasibility and Efficacy of Concurrent Chemoradiotherapy in Elderly Patients with Esophageal Squamous Cell Carcinoma: a Respective Study of 116 Cases from a Single Institution

  • Li, Xue;Zhao, Lu-Jun;Liu, Ning-Bo;Zhang, Wen-Cheng;Pang, Qing-Song;Wang, Ping;Yuan, Zhi-Yong
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.4
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    • pp.1463-1469
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    • 2015
  • Background: To evaluate the safety and efficacy of combined chemoradiotherapy or radiotherapy alone in elderly patients with esophageal carcinoma to identify the best method of treatment. Materials and Methods: One hundred and sixteen patients with esophageal carcinoma aged 70 and older who received definitive radiotherapy or chemoradiotherapy entered the study. Overall survival (OS), disease-free survival (DFS) and treatment-related toxicities were assessed. Results: The median OS of the overall population was 17.9 months. For patients treated with cCRT, sCRT and radiotherapy alone, the median OS was 22.3 months, 18.0 months and 12.4 months respectively(P=0.044). Median OS for patients treated with radiotherapy dose ${\geq}60Gy$ and <60Gy was 20.2 months and 10.9 months respectively (p=0.017). By univariate analysis, Chemoradiotherapy (include cCRT and sCRT) and radiotherapy dose ${\geq}60Gy$ were found to achieve higher survival rates compared with radiotherapy alone and radiotherapy dose <60Gy (P=0.015, P=0.017). By multivariate analysis, chemoradiotherapy (HR=1.645, P=0.022) and radiotherapy dose ${\geq}60Gy$ (HR=1.642, P=0.025) were identified as independent prognostic factors of OS. Conclusions: Definitive concurrent chemoradiotherapy could be considered as a feasible and effective treatment in esophageal carcinoma patients aged 70 and older. Radiotherapy dose 60Gy is an effective treatment option compared with standard dose radiotherapy, while higher doses are not beneficial to improve survival.

Adjuvant Radiotherapy after Breast Conserving Treatment for Breast Cancer:A Dosimetric Comparison between Volumetric Modulated Arc Therapy and Intensity Modulated Radiotherapy

  • Liu, Zhe-Ming;Ge, Xiao-Lin;Chen, Jia-Yan;Wang, Pei-Pei;Zhang, Chi;Yang, Xi;Zhu, Hong-Cheng;Liu, Jia;Qin, Qin;Xu, Li-Ping;Lu, Jing;Zhan, Liang-Liang;Cheng, Hong-Yan;Sun, Xin-Chen
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.8
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    • pp.3257-3265
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    • 2015
  • Background: Radiotherapy is an important treatment of choice for breast cancer patients after breast-conserving surgery, and we compare the feasibility of using dual arc volumetric modulated arc therapy (VMAT2), single arc volumetric modulated arc therapy (VMAT1) and Multi-beam Intensity Modulated Radiotherapy (M-IMRT) on patients after breast-conserving surgery. Materials and Methods: Thirty patients with breast cancer (half right-sided and half left-sided) treated by conservative lumpectomy and requiring whole breast radiotherapy with tumor bed boost were planned with three different radiotherapy techniques: 1) VMAT1; 2) VMAT2; 3) M-IMRT. The distributions for the planning target volume (PTV) and organs at risk (OARs) were compared. Dosimetries for all the techniques were compared. Results: All three techniques satisfied the dose constraint well. VMAT2 showed no obvious difference in the homogeneity index (HI) and conformity index (CI) of the PTV with respect to M-IMRT and VMAT1. VMAT2 clearly improved the treatment efficiency and can also decrease the mean dose and V5Gy of the contralateral lung. The mean dose and maximum dose of the spinal cord and contralateral breast were lower for VMAT2 than the other two techniques. The very low dose distribution (V1Gy) of the contralateral breast also showed great reduction in VMAT2 compared with the other two techniques. For the ipsilateral lung of right-sided breast cancer, the mean dose was decreased significantly in VMAT2 compared with VMAT1 and M-IMRT. The V20Gy and V30Gy of the ipsilateral lung of the left-sided breast cancer for VMAT2 showed obvious reduction compared with the other two techniques. The heart statistics of VMAT2 also decreased considerably compared to VMAT1 and M-IMRT. Conclusions: Compared to the other two techniques, the dual arc volumetric modulated arc therapy technique reduced radiation dose exposure to the organs at risk and maintained a reasonable target dose distribution.