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Fan N.-J.,Institute of Anal Colorectal Surgery | Fan N.-J.,Shanghai University | Gao C.-F.,Institute of Anal Colorectal Surgery | Zhao G.,Institute of Anal Colorectal Surgery | And 2 more authors.
Biotechnology and Applied Biochemistry | Year: 2012

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers in the world. Early diagnosis is critical for guiding the therapeutic management of ESCC. The present study aims to determine serum peptidome patterns for diagnosing ESCC. To identify novel peptidome patterns for diagnosing ESCC, sera from 31 healthy volunteers and 32 ESCC patients were subjected to a comparative proteomic analysis using a ClinProt™ Kit combined with mass spectrometry (MS). This approach enables the determination of peptidome patterns that can differentiate between ESCC sera and sera from healthy volunteers. For further validation, the diagnostic and differential diagnostic capabilities of the peptidome patterns were verified blindly by using an independent group of sera, consisting of sera from 31 ESCC patients, 33 healthy volunteers, 38 colorectal patients, and 36 gastric cancer patients. A Quick Classifier Algorithm was used to construct the peptidome patterns for the identification of ESCC from the control samples. Five of the identified peaks at mass to charge ratios 759, 786, 1,866, 3,316, and 6,634 were used to construct the peptidome patterns with almost 100% accuracy. Furthermore, the peptidome patterns could also differentiate the validation group with high accuracy. These results suggest that the ClinProt™ Kit combined with MS achieves significantly high accuracy for ESCC diagnosis and differential diagnosis. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc. Source

Lu Y.,Shanghai University | Liu Z.,Anal Colorectal Surgery Institute | Yao Z.,No. 150 Central Hospital of PLA | Li C.,Sichuan Cancer Hospital | Gao C.,Anal Colorectal Surgery Institute
Comparative and Functional Genomics | Year: 2011

Diffuse astrocytoma of (WHO grade II) has a tendency to progress spontaneously to anaplastic astrocytoma (WHO grade III) and/or glioblastoma (WHO grade IV). However, the molecular basis of astrocytoma progression is still poorly understood. In current study, an essential initial step toward this goal is the establishment of the taxonomy of tumors on the basis of their gene expression profiles. We have used gene expression profiling, unsupervised (hierarchal cluster (HCL) and principal component analysis (PCA)) and supervised (prediction analysis for microarrays (PAM)) learning methods, to demonstrate the presence of three distinct gene expression signatures of astrocytomas (ACMs), which correspond to diffuse or low-grade astrocytoma (WHO grade II), Anaplastic astrocytoma (WHO grade III) and Glioblastoma multiforme (WHO grade IV). We also demonstrate a 171 gene-based classifier that characterize the distinction between these pathologic/molecular subsets of astrocytomas. These results further define molecular subtypes of astrocytomas and may potentially be used to define potential targets and further refine stratification approaches for therapy. In addition, this study demonstrates that combining gene expression analysis with detailed annotated pathway and gene ontology (GO) category resources was applied to highly enriched normal and tumor population; it can yield an understanding of the critical biological mechanism of astrocytomas. © 2011 Zhongyu Liu et al. Source

Fan N.-J.,Institute of Anal Colorectal Surgery | Gao J.-L.,Institute of Anal Colorectal Surgery | Liu Y.,No. 150 Central Hospital of PLA | Song W.,Institute of Anal Colorectal Surgery | And 2 more authors.
BioMed Research International | Year: 2015

To identify potential biomarkers involved in CRC, a shotgun proteomic method was applied to identify soluble proteins in three CRCs and matched normal mucosal tissues using high-performance liquid chromatography and mass spectrometry. Label-free protein profiling of three CRCs and matched normal mucosal tissues were then conducted to quantify and compare proteins. Results showed that 67 of the 784 identified proteins were linked to CRC (28 upregulated and 39 downregulated). Gene Ontology and DAVID databases were searched to identify the location and function of differential proteins that were related to the biological processes of binding, cell structure, signal transduction, cell adhesion, and so on. Among the differentially expressed proteins, tropomyosin-3 (TPM3), endoplasmic reticulum resident protein 29 (ERp29), 18 kDa cationic antimicrobial protein (CAMP), and heat shock 70 kDa protein 8 (HSPA8) were verified to be upregulated in CRC tissue and seven cell lines through western blot analysis. Furthermore, the upregulation of TPM3, ERp29, CAMP, and HSPA8 was validated in 69 CRCs byimmunohistochemistry (IHC) analysis. Combination of TPM3, ERp29, CAMP, and HSPA8 can identify CRC from matched normal mucosal achieving an accuracy of 73.2% using IHC score. These results suggest that TPM3, ERp29, CAMP, and HSPA8 are great potential IHC diagnostic biomarkers for CRC. Copyright © 2015 Nai-Jun Fan et al. Source

Liu Z.,Anal Colorectal Surgery Institute | Yao Z.,No. 150 Central Hospital of PLA | Xie M.,Chongqing Medical University | Zheng L.,No. 150 Central Hospital of PLA | And 7 more authors.
African Journal of Biotechnology | Year: 2012

Grade II gliomas are morphologically and clinically heterogeneous tumors for which histopathological typing remains the major tool for clinical classification. To what extent the major histological subtypes (astrocytic, oligodendroglial, oligoastrocytic and ependymal tumors) constitute is largely unresolved. Morphological classification can often be ambiguous and would be facilitated by specific subtype markers. Gene expression profiling is becoming an established method to characterize different types of cancers, and it has been used extensively for glioblastoma analysis and for low-grade glioma to glioblastoma comparison. However, few studies of low-grade oligodendrogliomas and ependymomas have been reported. Using oligonucleotide-based microarray analysis, we compared the transcriptional profiles of grade II oligodendrogliomas and grade II ependymomas (two types of grade II gliomas). An essential initial step toward more objective tumor classification is the establishment of taxonomy for tumors based on their gene expression profiles. We aimed to identify expression profiles that differentiate these two types of grade II gliomas. After comparing the expression signature of a tumor to that of normal tissue, differentially expressed genes were used to perform hierarchal clustering, principal component analysis and prediction analysis. Hierarchal clustering and principal component analysis divided nine different tumor tissue samples and four normal brain tissue samples into categories that corresponded well with clinical pathology analysis, grade II oligodendrogliomas, grade II ependymomas and normal tissues. By using expression data from the most informative gene clusters, we constructed a tumor-clustering model. Class prediction using nearest shrunken centroid analysis with cross-validation identified 53 differentially expressed genes between the two types of grade II gliomas. © 2012 Academic Journals. Source

Wang X.,PLA Fourth Military Medical University | Wang B.,PLA Fourth Military Medical University | Li Z.,PLA Fourth Military Medical University | Zhu G.,PLA Fourth Military Medical University | And 5 more authors.
RSC Advances | Year: 2016

Oxidative stress-mediated neuron damage is believed to contribute greatly to the pathogenesis and outcome of ischemia. Y-27632, a Rho-associated kinase (ROCK) inhibitor, has been reported to protect various cells from oxidative injury. However, whether a Rho-kinase inhibitor can directly protect neurons against oxidative damage and the molecular mechanisms underlying it is poorly understood. In the present study, we investigated the potential protective effect of Y-27632 against H2O2-induced apoptosis in cultured rat cortical neurons and potential mechanisms underlying it. Both the cell viability tests and cell apoptosis assays showed that Y-27632 effectively protected the cultured rat cortical neurons from H2O2-induced injury. Furthermore, the mechanisms underlying the protective effect were determined next. Our results revealed that Y-27632 pretreatment regulated the apoptosis-related proteins by inhibiting the H2O2-induced decrease in anti-apoptotic protein Bcl-2 and an increase in the level of pro-apoptotic protein Bax. Meanwhile, Y-27632 also significantly reduced oxidative stress and the activation of JNK1/2/3 and p38 MAPKs induced by H2O2, without affecting the phosphorylation of ERK1/2. Moreover, inhibiting the JNK and p38 pathways by SP600125 and SB203580 respectively alleviated the cell viability loss induced by H2O2 and markedly disputed the neuroprotective effect of Y-27632 against H2O2-induced apoptosis. Taken together, these results demonstrate that Y-27632 can directly protect cultured cortical neurons from H2O2-induced apoptosis by inhibiting oxidative stress and the activation of JNK and p38 MAPKs pathways. Our study provides useful insights into the therapeutic mechanisms of Y-27632 and further supports that ROCK is a promising drug target for neurological diseases. © 2016 The Royal Society of Chemistry. Source

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