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Peng-Fei Zhang,
Gu-Qing Zeng,
Rong Hu,
Cui Li,
Hong Yi,
Mao-Yu Li,
Xin-Hui Li,
Jia-Quan Qu,
Xun-Xun Wan,
Qiu-Yan He, Jian-Huang Li,
Yu Chen,
Xu Ye,
Jiao-Yang Li,
Yuan-Yuan Wang,
Xue-Ping Feng,
Zhi-Qiang Xiao
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ABSTRACT: To identify a novel lung adenocarcinoma (AdC) biomarker, iTRAQ-tagging combined with 2D LC-MS/MS analysis was used to identify differentially expressed plasma membrane (PM) proteins in primary lung AdCs and paraneoplastic normal lung tissues (PNLTs). As a result, 36 differentially expressed membrane proteins were identified. Two differential PM proteins flotillin-1 and caveolin-1 were selectively validated by Western blotting. As there has been no report on the association of flotillin-1 with lung AdC, immunohistochemistry was further performed to detect the expression of flotillin-1 in the archival tissue specimens including 42 cases of PNLTs, 62 cases of primary lung AdCs with lymph node metastasis (LNM AdCs), and 46 cases of primary lung AdCs without lymph node metastasis (non-LNM AdCs), and the correlation of flotillin-1 expression levels in lung AdCs with clinicopathological features and clinical outcomes were evaluated. The results showed that up-regulation of flotillin-1 expression in lung AdCs was significantly correlated with advanced clinical stage, lymph node metastasis, increased postoperative relapse and decreased overall survival. Cox regression analysis revealed that the expressional level of flotillin-1 was an independent prognostic factor. The data suggest that flotillin-1 is a potential novel biomarker for lymph node metastasis and prognosis of lung AdC, and flotillin-1 up-regulation might play an important role in the pathogenesis of lung AdC.
Journal of proteomics 09/2012; · 5.07 Impact Factor
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Bin Zhang,
Jia-Quan Qu,
Liang Xiao,
Hong Yi,
Peng-Fei Zhang,
Mao-Yu Li,
Rong Hu,
Xun-Xun Wan,
Qiu-Yan He, Jian-Huang Li,
Xu Ye,
Zhi-Qiang Xiao,
Xue-Ping Feng
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ABSTRACT: PURPOSE: To identify the proteins involved in radioresistance in nasopharyngeal cancer (NPC) cells. METHODS: Sublethal ionizing radiation was applied to establish a radioresistant NPC cell line from its parental NPC cell line CNE1. Clonogenic survival assay, cell growth assay and flow cytometry analysis were used to examine the difference of radiosensitivity in the radioresistant CNE1 cells (CNE1-IR) and control CNE1 cells. Comparative proteomics was performed to identify the differential proteins in the two cell lines. Association of HSP27, one of upregulated proteins in CNE1-IR cells, with NPC cell radioresistance was selected for further investigation using antisense oligonucleotides (ASOs), clonogenic survival assay, Hoechst 33258 staining of apoptotic cells and MTT assay of cell viability. RESULTS: Radioresistant NPC cell line CNE1-IR derived from its parental cell line CNE1 was established. Thirteen differential proteins in the CNE1-IR and CNE1 cells were identified by proteomics, and differential expression of HSP27, one of identified proteins, was selectively confirmed by western blot. Inhibition of HSP27 expression by HSP27 ASOs decreased clonogenic survival and cell viability and increased cell apoptosis of CNE1-IR cells after irradiation, that is, enhanced radiosensitivity of CNE1-IR cells. CONCLUSION: The data suggest that HSP27 is a radioresistant protein in NPC cells, and its upregulation may be involved in the NPC radioresistance.
Journal of Cancer Research and Clinical Oncology 07/2012; · 2.56 Impact Factor
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ABSTRACT: ObjectiveTo investigate the recurrent patterns and factors involved in node-negative advanced gastric cancer after curative resection.
Patients and MethodsClinicopathological characteristics and prognostic outcomes of 310 patients who had lymph node-negative advanced gastric adenocarcinoma
and received curative resection between 2002 and 2006 were retrospectively evaluated.
ResultsAmong the 300 patients, 15 (5.0%) had locoregional recurrence, 5 (1.7%) had lymph node recurrence, 27 (9.0%) had peritoneal
seeding recurrence, and 21 (7.0%) had hematogenous metastasis. Using multivariate analysis, we found that the maximum tumor
diameter (P=0.014), histological type (P=0.001) and Borrmann type (P=0.033) were independent factors predicting the locoregional recurrence. Lymph node recurrence was significantly affected
by lymph node dissection (P=0.029) and lymphovascular invasion (P=0.004). Clinicopathological factors predicting the peritoneal seeding recurrence were the depth of invasion (P=0.001) and Borrmann type (P=0.002). In addition, lymphovascular invasion (P=0.013) and histological type (P=0.001) were significantly associated with hematogenous metastasis.
ConclusionNode-negative advanced gastric cancer has a high amount of peritoneal seeding and hematogenous metastasis.
Key wordsGastric cancer-Recurrence-Lymph node-Prognosis
CLC numberR735.2
Chinese Journal of Cancer Research 04/2012; 22(4):285-290. · 0.18 Impact Factor
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Gu-Qing Zeng,
Pang-Fei Zhang,
Xingming Deng,
Feng-Lei Yu,
Cui Li,
Yan Xu,
Hong Yi,
Mao-Yu Li,
Rong Hu,
Jian-Hong Zuo,
Xin-Hui Li,
Xun-Xun Wan,
Jia-Quan Qu,
Qiu-Yan He, Jian-Huang Li,
Xu Ye,
Yu Chen,
Jiao-Yang Li,
Zhi-Qiang Xiao
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ABSTRACT: To discover novel biomarkers for early detection of human lung squamous cell cancer (LSCC) and explore possible mechanisms of LSCC carcinogenesis, iTRAQ-tagging combined with two dimensional liquid chromatography tandem MS analysis was used to identify differentially expressed proteins in human bronchial epithelial carcinogenic process using laser capture microdissection-purified normal bronchial epithelium (NBE), squamous metaplasia (SM), atypical hyperplasia (AH), carcinoma in situ (CIS) and invasive LSCC. As a result, 102 differentially expressed proteins were identified, and three differential proteins (GSTP1, HSPB1 and CKB) showing progressively expressional changes in the carcinogenic process were selectively validated by Western blotting. Immunohistochemistry was performed to detect the expression of the three proteins in an independent set of paraffin-embedded archival specimens including various stage tissues of bronchial epithelial carcinogenesis, and their ability for early detection of LSCC was evaluated by receiver operating characteristic analysis. The results showed that the combination of the three proteins could perfectly discriminate NBE from preneoplastic lesions (SM, AH and CIS) from invasive LSCC, achieving a sensitivity of 96% and a specificity of 92% in discriminating NBE from preneoplatic lesions, a sensitivity of 100% and a specificity of 98% in discriminating NBE from invasive LSCC, and a sensitivity of 92% and a specificity of 91% in discriminating preneoplastic lesions from invasive LSCC, respectively. Furthermore, we knocked down GSTP1 in immortalized human bronchial epithelial cell line 16HBE cells, and then measured their susceptibility to carcinogen benzo(a)pyrene-induced cell transformation. The results showed that GSTP1 knockdown significantly increased the efficiency of benzo(a)pyrene-induced 16HBE cell transformation. The present data first time show that GSTP1, HSPB1 and CKB are novel potential biomarkers for early detection of LSCC, and GSTP1 down-regulation is involved in human bronchial epithelial carcinogenesis.
Molecular & Cellular Proteomics 01/2012; 11(6):M111.013946. · 7.40 Impact Factor
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ABSTRACT: A case-control study of 300 gastric cancer patients and 300 controls was conducted to investigate whether the polymorphisms rs2294008 in PSCA and rs2070803 in MUC1 might be associated with risk of gastric cancer in a Chinese population.
Single nucleotide polymorphisms (SNPs) were genotyped using the Sequenom MassARRAY platform.
The data showed that the rs2294008 TT genotype increased gastric cancer risk to an adjusted odds ratio (OR) of 2.26 (95%CI 1.25-4.07), TC to 1.72 (95%CI 1.23-2.42) and TC/TT to 1.81 (95% CI 1.31-2.50), while the rs2070803 GA genotype was associated with a decrease in risk to an adjusted OR of 0.42 (95% CI 0.28-0.62) and rs2070803 GA / AA to 0.46 (95% CI 0.32-0.67). Further stratification analysis revealed that rs2294008 in PSCA consistently increased risk of both intestinal and diffuse-type gastric cancers. The effect of rs2070803 in MUC1 was noteworthily also consistent with both subtypes.
Our study suggested rs2294008 in the PSCA gene to be associated with increased risk of gastric cancer and rs2070803 in MUC1 to play a protective role in a Chinese population.
Asian Pacific journal of cancer prevention: APJCP 01/2012; 13(6):2593-6. · 0.66 Impact Factor
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Yan-Hua Xiao,
Xin-Hui Li,
Tan Tan,
Ting Liang,
Hong Yi,
Mao-Yu Li,
Gu-Qing Zeng,
Xun-Xun Wan,
Jia-Quan Qu,
Qiu-Yan He, Jian-Huang Li,
Yu Chen,
Zhi-Qiang Xiao
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ABSTRACT: To identify methylation-silenced genes in acute myeloid leukemia (AML).
Microarray analyses were performed in AML cell line HL-60 cells exposed to the demethylating agent 5-aza-2dC. The methylation status and expression of glioma pathogenesis-related protein 1 (GLIPR1), one of highly induced genes by demethylation, were further detected in six hematopoietic malignancy cell lines and 260 bone marrow samples from leukemia patients and nonmalignant diseases as control, as well as pre-treated and post-treated bone marrow samples from 24 complete remission AML patients received chemotherapy using MS-PCR, bisulfite DNA sequencing, RT-PCR, and Western blotting.
One hundred and nine genes were significantly induced by demethylation in HL-60 cells, 12 genes of which were confirmed by RT-PCR. GLIPR1, a tumor suppressor gene, was frequently methylation-silenced in AML cell lines and AML patients, but not in the other hematopoietic malignancy cell lines and patients. The frequencies of methylation-silenced GLIPR1 in the pre-treatment were significantly higher than those in the post-treatment in complete remission AML patients.
We identify 109 genes induced by demethylation in HL-60 cells, and demonstrate that GLIPR1 is a methylation-silenced gene in the AML patients, and may serve as a marker for monitoring disease activity during therapy in the AML patients. The data provide the important information for studying the pathogenesis of AML and discovering the target genes of methylating agents.
Journal of Cancer Research and Clinical Oncology 09/2011; 137(12):1831-40. · 2.56 Impact Factor
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Lin Ruan,
Xin-Hui Li,
Xun-Xun Wan,
Hong Yi,
Cui Li,
Mao-Yu Li,
Peng-Fei Zhang,
Gu-Qing Zeng,
Jia-Quan Qu,
Qiu-Yan He, Jian-Huang Li,
Yu Chen,
Zhu-Chu Chen,
Zhi-Qiang Xiao
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ABSTRACT: The epidermal growth factor receptor (EGFR) is usually overexpressed in nasopharyngeal carcinoma (NPC) and is associated with pathogenesis of NPC. However, the downstream signaling proteins of EGFR in NPC have not yet been completely understood at the system level. The aim of this study was identify novel downstream proteins of EGFR signaling pathway in NPC cells.
We analyzed EGFR-regulated phosphoproteome in NPC CNE2 cells using 2D-DIGE and mass spectrometry analysis after phosphoprotein enrichment. As a result, 33 nonredundant phosphoproteins including five known EGFR-regulated proteins and twenty-eight novel EGFR-regulated proteins in CNE2 were identified, three differential phosphoproteins were selectively validated, and two differential phosphoproteins (GSTP1 and GRB2) were showed interacted with phospho-EGFR. Bioinformatics analysis showed that 32 of 33 identified proteins contain phosphorylation modification sites, and 17 identified proteins are signaling proteins. GSTP1, one of the EGFR-regulated proteins, associated with chemoresistance was analyzed. The results showed that GSTP1 could contribute to paclitaxel resistance in EGF-stimulated CNE2 cells. Furthermore, an EGFR signaling network based on the identified EGFR-regulated phosphoproteins were constructed using Pathway Studio 5.0 software, which includes canonical and novel EGFR-regulated proteins and implicates the possible biological roles for those proteins.
The data not only can extend our knowledge of canonical EGFR signaling, but also will be useful to understand the molecular mechanisms of EGFR in NPC pathogenesis and search therapeutic targets for NPC.
Proteome Science 06/2011; 9:35. · 2.33 Impact Factor
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Jian-Hong Zuo,
Wei Zhu,
Mao-Yu Li,
Xin-Hui Li,
Hong Yi,
Gu-Qing Zeng,
Xun-Xun Wan,
Qiu-Yan He, Jian-Huang Li,
Jia-Quan Qu,
Yu Chen,
Zhi-Qiang Xiao
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ABSTRACT: EGFR is a potent stimulator of invasion and metastasis in head and neck squamous cell carcinomas (HNSCC). However, the mechanism by which EGFR may stimulate tumor cell invasion and metastasis still need to be elucidated. In this study, we showed that activation of EGFR by EGF in HNSCC cell line SCC10A enhanced cell migration and invasion, and induced loss of epitheloid phenotype in parallel with downregulation of E-cadherin and upregulation of N-cadherin and vimentin, indicating that EGFR promoted SCC10A cell migration and invasion possibly by an epithelial to mesenchymal transition (EMT)-like phenotype change. Interestingly, activation of EGFR by EGF induced production of matrix metalloproteinase-9 (MMP-9) and soluble E-cadherin (sE-cad), and knockdown of MMP-9 by siRNA inhibited sE-cad production induced by EGF in SCC10A. Moreover, both MMP-9 knockdown and E-cadherin overexpression inhibited cell migration and invasion induced by EGF in SCC10A. The results indicate that EGFR activation promoted cell migration and invasion through inducing MMP-9-mediated degradation of E-cadherin into sE-cad. Pharmacologic inhibition of EGFR, MEK, and PI3K kinase activity in SCC10A reduced phosphorylated levels of ERK-1/2 and AKT, production of MMP-9 and sE-cad, cell migration and invasion, and expressional changes of EMT markers (E-cadherin and N-cadherin) induced by EGF, indicating that EGFR activation promotes cell migration and invasion via ERK-1/2 and PI3K-regulated MMP-9/E-cadherin signaling pathways. Taken together, the data suggest that EGFR activation promotes HNSCC SCC10A cell migration and invasion by inducing EMT-like phenotype change and MMP-9-mediated degradation of E-cadherin into sE-cad related to activation of ERK-1/2 and PI3K signaling pathways.
Journal of Cellular Biochemistry 05/2011; 112(9):2508-17. · 2.87 Impact Factor
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ABSTRACT: To evaluate the efficacy and toxicity of paclitaxel with low-dose cisplatin and 5-fluorouracil continuous infusion in the treatment of advanced gastric carcinoma.
The patients were treated with paclitaxel liposome 60 mg/m(2) i.v. gtt on d1, 8, 15, DDP 15 mg×m(-2)×d(-1) by i.v. gtt on d1-5, 5-Fu 500 mg×m(-2)×d(-1) by civ for 120 h, administered every 21 days.
Out of the whole group, 3 cases achieved CR, 29 cases achieved PR with an ORR of 54.2% and median TTP of 7.1 months. Out of 40 cases in the primary treatment, 3 cases achieved CR, 22 cases achieved PR with an ORR of 62.5% and median TTP of 7.6 months. Out of 20 evaluable retreated cases, no case achieved CR, 7 cases achieved PR with an ORR of 36.8% and median TTP 6.3 months. The main toxicities were hematological toxicities, nausea and vomiting of grade I-II.
The combination regimen of paclitaxel, low-dose cisplatin and 5-fluorouracil is effective and well tolerated for patients with advanced gastric carcinoma, especially for primary treatment cases. It is worthy of further study.
Zhonghua zhong liu za zhi [Chinese journal of oncology] 03/2011; 33(3):229-31.
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ABSTRACT: To investigate the apoptosis of human breast cell line MCF-7 cells induced by gemcitabine and radiation.
The MTT method was applied to study the growth inhibition of MCF-7 treated with gemcitabine, radiation, gemcitabine and radiation. The apoptosis index (AI) was analyzed by flow cytometry. The morphology of the MCF-7 cells apoptosis was observed by transmission electron microscopy.
When MCF-7 cells were treated with gemcitabine at different concentrations for 24 h, the cell growth inhibition rate was increased in a concentration-dependent manner. The apoptotic indexes (AI) of MCF-7 of four groups by flow cytometry revealed. The AI of (R+D) group was significantly different from those of the radiation group and the gemcitabine group (P<0.05). Condensed chromation, nuclear fragmentation and apoptotic body of MCF-7 cells were found by transmission electron microscope.
The apoptosis of human breast cancer cell line, MCF-7 cells, could be induced by gemcitabine. Gemcitabine can significantly enhance the radiation-induced apoptosis of MCF-7 cells.
Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences 10/2006; 31(5):710-3.
