MiRNA Synergistic Network Construction and Enrichment Analysis for Common Target Genes in Small-cell Lung Cancer

Zhang, Tie-Feng,Cheng, Ke-Wen,Shi, Wei-Yin,Zhang, Jin-Tao,Liu, Ke-Di,Xu, Shu-Guang,Chen, Ji-Quan Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.12

Background: Small-cell lung cancer (also known as SCLC) is an aggressive form and untreated patients generally die within about 3 months. To obtain further insight into mechanism underlying malignancy with this cancer, an miRNA synergistic regulatory network was constructed and analyzed in the present study. Method: A miRNA microarray dataset was downloaded from the NCBI GEO database (GSE27435). A total of 546 miRNAs were identified to be expressed in SCLC cells. Then a miRNA synergistic network was constructed, and the included miRNAs mapped to the network. Topology analysis was also performed to analyze the properties of the synergistic network. Consequently, we could identified constitutive modules. Further, common target genes of each module were identified with CFinder. Finally, enrichment analysis was performed for target genes. Results: In this study, a miRNA synergistic network with 464 miRNAs and 2981 edges was constructed. According to the topology analysis, the topological properties between the networks constructed by LC related miRNAs and LC unrelated miRNAs were significantly different. Moreover, a module cilque0 could be identified in our network using CFinder. The module included three miRNAs (hsa-let-7c, hsa-let-7b and hsa-let-7d). In addition, several genes were found which were predicted to be common targets of cilque0. The enrichment analysis demonstrated that these target genes were enriched in MAPK signaling pathways. Conclusions: Although limitations exist in the current data, the results uncovered here are important for understanding the key roles of miRNAs in SCLC. However, further validation is required since our results were based on microarray data derived from a small sample size.

Coexistence of Amyotrophic Lateral Sclerosis in the Proband of an X-Linked Charcot-Marie-Tooth Disease Type 1 Pedigree in China

Shu-Yan Feng,Shu-Man Feng,Liu-Yi Li,Zhang-Yu Zou 대한신경과학회 2018 Journal of Clinical Neurology Vol.14 No.2

Human Recombinant Endostatin Combined with Cisplatin Based Doublets in Treating Patients with Advanced NSCLC and Evaluation by CT Perfusion Imaging

Zhang, Feng-Lin,Gao, Er-Yun,Shu, Rong-Bao,Wang, Hui,Zhang, Yan,Sun, Peng,Li, Min,Tang, Wei,Jiang, Bang-Qin,Chen, Shuang-Qi,Cui, Fang-Bo Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.15

Aims: To study the effectiveness of human recombinant endostatin injection (Endostar(R)) combined with cisplatin doublets in treating advanced non-small cell lung cancer (NSCLC), and to evaluate outcome by CT perfusion imaging. Methods: From April 2011 to September 2014, 76 patients with advanced NSCLC who were treated with platinum-based doublets were divided into group A (36 patients) and group B (40 patients). Endostar(R) 15mg/day was administered 4 days before chemotherapy and combined with chemotherapy from day 5 in group A, and combined with chemotherapy from the first day in Group B. Endostar(R) in the two groups was injected intravenously for 14 days. Results: Treatment effectiveness in the two groups differed with statistical significance (p<0.05). Effectiveness evaluated by CT perfusion imaging, BF, BV, MTT and PS also demonstrated significant differences (all p<0.05). Adverse reactions in the two groups did not significantly vary (p> 0.05). Conclusions: The response rate with Endostar(R) administered 4 days before chemotherapy and combined with chemotherapy from day 5 in group A was better than Endostar(R) combined with chemotherapy from the first day, and CT perfusion imaging could be a reasonable method for evaluation of patient outcomes.

Pd Nanoparticles Self-Assembled on Fluorine-Modified MWCNTs as Electro-Catalysts for Methanol Electro-Oxidation

Xiao-Feng Zhang,Peng Dong,Ying-Jie Zhang,Xi-Kun Yang,Shu-Biao Xia,Zhen-Hua Jin,Ming-Li Xu 성균관대학교(자연과학캠퍼스) 성균나노과학기술원 2017 NANO Vol.12 No.3

Multi-walled carbon nanotubes (MWCNTs) were modified by hydrogen fluoride (HF) in a simple method. With the help of fluorine, Pd nanoparticles (3.9 nm) synthesized by a one-step photochemical reduction were uniformly self-assembled on the active sites of functionalized MWCNTs and a new catalyst (Pd/HF-MWCNT) was obtained. UV–Vis absorption spectra, transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) were used. The results demonstrated that –F groups were introduced onto the surface of MWCNTs and C–F chemical bonds were formed. In addition, the electronic structure of Pd was changed. Pd–F coordination bond maybe formed between F atom and Pd atom. Cyclic voltammetry and chronoamperometry tests indicated that electrocatalytic activity of Pd/HF-MWCNTs catalyst for methanol in alkaline medium was about 1.6 times higher than that of the commercial Pd/C (JM) catalyst at the same condition. This new functionalized method has the advantages of simple step and safe operation. It is very significant to improve the wide application of MWCNTs and the commercial development of direct methanol fuel cells (DMFCs).

Increased Serotonin Signaling Contributes to the Warburg Effect in Pancreatic Tumor Cells Under Metabolic Stress and Promotes Growth of Pancreatic Tumors in Mice

Jiang, Shu-Heng,Li, Jun,Dong, Fang-Yuan,Yang, Jian-Yu,Liu, De-Jun,Yang, Xiao-Mei,Wang, Ya-Hui,Yang, Min-Wei,Fu, Xue-Liang,Zhang, Xiao-Xin,Li, Qing,Pang, Xiu-Feng,Huo, Yan-Miao,Li, Jiao,Zhang, Jun-Feng Elsevier 2017 Gastroenterology Vol.153 No.1

<P><B>Background & Aims</B></P> <P>Desmoplasia and poor vascularity cause severe metabolic stress in pancreatic ductal adenocarcinomas (PDACs). Serotonin (5-HT) is a neuromodulator with neurotransmitter and neuroendocrine functions that contributes to tumorigenesis. We investigated the role of 5-HT signaling in the growth of pancreatic tumors.</P> <P><B>Methods</B></P> <P>We measured the levels of proteins that regulate 5-HT synthesis, packaging, and degradation in pancreata from Kras<SUP>G12D/+</SUP>/Trp53<SUP>R172H/+</SUP>/Pdx1-Cre (KPC) mice, which develop pancreatic tumors, as well as in PDAC cell lines and a tissue microarray containing 81 human PDAC samples. We also analyzed expression levels of proteins involved in 5-HT synthesis and degradation by immunohistochemical analysis of a tissue microarray containing 311 PDAC specimens, and associated expression levels with patient survival times. 5-HT level in 14 matched PDAC tumor and non-tumor tissues were analyzed by ELISA. PDAC cell lines were incubated with 5-HT and cell survival and apoptosis were measured. We analyzed expression of the 5-HT receptor HTR2B in PDAC cells and effects of receptor agonists and antagonists, as well as HTR2B knockdown with small hairpin RNAs. We determined the effects of 5-HT stimulation on gene expression profiles of BxPC-3 cells. Regulation of glycolysis by 5-HT signaling via HTR2B was assessed by immunofluorescence and immunoprecipitation analyses, as well as by determination of the extracellular acid ratio, glucose consumption, and lactate production. Primary PDACs, with or without exposure to SB204741 (a selective antagonist of HTR2B), were grown as xenograft tumors in mice, and SB204741 was administered to tumor-bearing KPC mice; tumor growth and metabolism were measured by imaging analyses.</P> <P><B>Results</B></P> <P>In immunohistochemical analysis of a tissue microarray of PDAC specimens, increased levels of TPH1 and decreased level of MAOA, which regulate 5-HT synthesis and degradation, correlated with stage and size of PDACs and shorter patient survival time. We found levels of 5-HT to be increased in human PDAC tissues compared with non-tumor pancreatic tissues, and PDAC cell lines compared with non-transformed pancreatic cells. Incubation of PDAC cell lines with 5-HT increased proliferation and prevented apoptosis. Agonists of HTR2B, but not other 5-HT receptors, promoted proliferation and prevented apoptosis of PDAC cells. Knockdown of HTR2B in PDAC cells, or incubation of cells with HTR2B inhibitors, reduced their growth as xenograft tumors in mice. We observed a correlation between 5-HT and glycolytic flux in PDAC cells; levels of metabolic enzymes involved in glycolysis, the phosphate pentose pathway, and hexosamine biosynthesis pathway increased significantly in PDAC cells following 5-HT stimulation. 5-HT stimulation led to formation of the HTR2B–LYN–p85 complex, which increased PI3K–Akt–mTOR signaling and the Warburg effect by increasing protein levels of MYC and HIF1A. Administration of SB204741 to KPC mice slowed growth and metabolism of established pancreatic tumors and prolonged survival of the mice.</P> <P><B>Conclusions</B></P> <P>Human PDACs have increased levels of 5-HT, and PDAC cells increase expression of its receptor, HTR2B. These increases allow for tumor glycolysis under metabolic stress and promote growth of pancreatic tumors and PDAC xenograft tumors in mice.</P>

SPON2 Promotes M1-like Macrophage Recruitment and Inhibits Hepatocellular Carcinoma Metastasis by Distinct Integrin–Rho GTPase–Hippo Pathways

Zhang, Yan-Li,Li, Qing,Yang, Xiao-Mei,Fang, Fang,Li, Jun,Wang, Ya-Hui,Yang, Qin,Zhu, Lei,Nie, Hui-Zhen,Zhang, Xue-Li,Feng, Ming-Xuan,Jiang, Shu-Heng,Tian, Guang-Ang,Hu, Li-Peng,Lee, Ho-Young,Lee, Su-J American Association for Cancer Research 2018 Cancer research Vol.78 No.9

<P>Matricellular protein SPON2 acts as an HCC suppressor and utilizes distinct signaling events to perform dual functions in HCC microenvironment.</P><P>Tumor-associated macrophages (TAM) represent key regulators of the complex interplay between cancer and the immune microenvironment. Matricellular protein SPON2 is essential for recruiting lymphocytes and initiating immune responses. Recent studies have shown that SPON2 has complicated roles in cell migration and tumor progression. Here we report that, in the tumor microenvironment of hepatocellular carcinoma (HCC), SPON2 not only promotes infiltration of M1-like macrophages but also inhibits tumor metastasis. SPON2-α4β1 integrin signaling activated RhoA and Rac1, increased F-actin reorganization, and promoted M1-like macrophage recruitment. F-Actin accumulation also activated the Hippo pathway by suppressing LATS1 phosphorylation, promoting YAP nuclear translocation, and initiating downstream gene expression. However, SPON2-α5β1 integrin signaling inactivated RhoA and prevented F-actin assembly, thereby inhibiting HCC cell migration; the Hippo pathway was not noticeably involved in SPON2-mediated HCC cell migration. In HCC patients, SPON2 levels correlated positively with prognosis. Overall, our findings provide evidence that SPON2 is a critical factor in mediating the immune response against tumor cell growth and migration in HCC.</P><P><B>Significance:</B> Matricellular protein SPON2 acts as an HCC suppressor and utilizes distinct signaling events to perform dual functions in HCC microenvironment.</P><P><B>Graphical Abstract:</B> http://cancerres.aacrjournals.org/content/canres/78/9/2305/F1.large.jpg. <I>Cancer Res; 78(9); 2305–17. ©2018 AACR</I>.</P><P><B>Graphical Abstract</B></P><P> [Figure]</P>

Correlation of CT Perfusion Images with VEGF Expression in Solitary Brain Metastases

Zhang, Jian-Hua,Wang, Ming-Sheng,Pan, Hai-Hong,Li, Shu-Feng,Wang, Zhong-Qiu,Chen, Wang-Sheng Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.4

Objectives: To obtain permeability surface (PS) values using multi-slice helical CT perfusion imaging and to evaluate the spatial distribution correlation between PS values and vascular endothelial growth factor (VEGF) expression in solitary brain metastases. Methods: Imaging was performed on 21 patients, PS values being calculated from the central, border and peripheral parts of tumours. VEGF expression was determined by immunohistochemical staining. Results: Rim enhancement was found in 16 cases, the border of the tumour featuring PS elevation with high VEGF expression in 13 cases. In the 5 cases with nodular enhancement, the border and the central part had high permeability and VEGF expression was high in all cases, the correlation being significant (P<0.01). Conclusion: VEGF expression in brain metastases positively correlates with PS values from CT perfusion imaging, so that the latter can be used in the surveillance of angiogenic activity in brain metastases.

Association of Measures of Glucose Metabolism with Colorectal Cancer Risk in Older Chinese: A 13-Year Follow-up of the Guangzhou Biobank Cohort Study-Cardiovascular Disease Substudy and Meta-Analysis

Shu Yi Wang,Wei Sen Zhang,Chao Qiang Jiang,Ya Li Jin,Tong Zhu,Feng Zhu,Lin Xu 대한당뇨병학회 2024 Diabetes and Metabolism Journal Vol.48 No.1

Background: Abnormal glucose metabolism is a risk factor for colorectal cancer (CRC). However, association of glycosylated hemoglobin (HbA1c) with CRC risk remains under-reported. We examined the association between glycemic indicators (HbA1c, fasting plasma glucose, fasting insulin, 2-hour glucose, 2-hour insulin, and homeostasis model of risk assessment-insulin resistance index) and CRC risk using prospective analysis and meta-analysis.Methods: Participants (<i>n</i>=1,915) from the Guangzhou Biobank Cohort Study-Cardiovascular Disease Substudy were included. CRC events were identified through record linkage. Cox regression was used to assess the associations of glycemic indicators with CRC risk. A meta-analysis was performed to investigate the association between HbA1c and CRC risk.Results: During an average of 12.9 years follow-up (standard deviation, 2.8), 42 incident CRC cases occurred. After adjusting for potential confounders, the hazard ratio (95% confidence interval [CI]) of CRC for per % increment in HbA1c was 1.28 (95% CI, 1.01 to 1.63) in overall population, 1.51 (95% CI, 1.13 to 2.02) in women and 1.06 (95% CI, 0.68 to 1.68) in men. No significant association of other measures of glycemic indicators and baseline diabetes with CRC risk was found. Meta-analyses of 523,857 participants including our results showed that per % increment of HbA1c was associated with 13% higher risk of CRC, with the pooled risk ratio being 1.13 (95% CI, 1.01 to 1.27). Subgroupanalyses found stronger associations in women, colon cancer, Asians, and case-control studies.Conclusion: Higher HbA1c was a significant predictor of CRC in the general population. Our findings shed light on the pathology of glucose metabolism and CRC, which warrants more in-depth investigation.

Influence of Expression Plasmid of Connective Tissue Growth Factor and Tissue Inhibitor of Metalloproteinase-1 shRNA on Hepatic Precancerous Fibrosis in Rats

Zhang, Qun,Shu, Fu-li,Jiang, Yu-Feng,Huang, Xin-En Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.16

Background: In this study, influence caused by expression plasmids of connective tissue growth factor (CTGF) and tissue inhibitor of metalloproteinase-1 (TIMP-1) short hairpin RNA (shRNA) on mRNA expression of CTGF,TIMP-1,procol-${\alpha}1$ and PCIII in hepatic tissue with hepatic fibrosis, a precancerous condition, in rats is analyzed. Materials and Methods: To screen and construct shRNA expression plasimid which effectively interferes RNA targets of CTGF and TIMP-1 in rats. 50 cleaning Wistar male rats are allocated randomly at 5 different groups after precancerous fibrosis models and then injection of shRNA expression plasimids. Plasmid psiRNA-GFP-Com (CTGF and TIMP-1 included), psiRNA-GFP-CTGF, psiRNA-GFP-TIMP-1 and psiRNA-DUO-GFPzeo of blank plasmid are injected at group A, B, C and D, respectively, and as model control group that none plasimid is injected at group E. In 2 weeks after last injection, to hepatic tissue at different groups, protein expression of CTGF, TIMP-1, procol-${\alpha}1$ and PC III is tested by immunohistochemical method and,mRNA expression of CTGF,TIMP-1,procol-${\alpha}1$ and PCIII is measured by real-time PCR. One-way ANOVA is used to comparison between-groups. Results: Compared with model group, there is no obvious difference of mRNA expression among CTGF,TIMP-1,procol-${\alpha}1$, PC III and of protein expression among CTGF, TIMP-1, procol-${\alpha}1$, PC III in hepatic tissue at group injected with blank plasmid. Expression quantity of mRNA of CTGF, TIMP-1, procol-${\alpha}1$ and PCIII at group A, B and C decreases, protein expression of CTGF, TIMP-1, procol-${\alpha}1$, PC III in hepatic tissue is lower, where the inhibition of combination RNA interference group (group A) on procol-${\alpha}1$ mRNA transcription and procol-${\alpha}1$ protein expression is superior to that of single interference group (group B and C) (P<0.01 or P<0.05). Conclusions: RNA interference on CTGF and/or TIMP-1 is obviously a inhibiting factor for mRNA and protein expression of CTGF, TIMP-1, procol-${\alpha}1$ and PCIII. Combination RNA interference on genes of CTGF and TIMP-1 is superior to that of single RNA interference, and this could be a contribution for prevention of precancerous condition.

INTERGALACTIC MEDIUM IN THE ACDM UNIVERSE FROM COSMOLOGICAL SIMULATIONS

FENG LONG-LONG,HE PING,FANG LIZHI,SHU CHI-WANG,ZHANG MENG-PING The Korean Astronomical Society 2005 Journal of The Korean Astronomical Society Vol.38 No.2

The temperature (T) and entropy (S) fields of baryonic gas, or intergalactic medium (IGM), in the ACDM cosmology are analyzed using simulation samples produced by a hybrid cosmological hydrodynamic/N-body code based on the weighted essentially non-oscillatory scheme. We demonstrate that, in the nonlinear regime, the dynamical similarity between the IGM and dark matter will be broken in the presence of strong shocks in the IGM. The heating and entropy production by the shocks breaks the IGM into multiple phases. The multiphase and non-Gaussianity of the IGM field would be helpful to account for the high-temperature and high-entropy gas observed in groups and clusters with low-temperature IGM observed by Ly$\alpha$ forest lines and the intermittency observed by the spikes of quasi-stellar object's absorption spectrum.