17 results on '"Wuguo Deng"'
Search Results
2. PD-1 and PD-L1 expression in 132 recurrent nasopharyngeal carcinoma: the correlation with anemia and outcomes
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Jingjing Miao, Jing Kuang, Hao Tang, Chong Zhao, Haijun Wu, Yajuan Zhou, Yi Peng, Conghua Xie, Xiaoyi Zhou, Dingbo Shi, Desheng Hu, Wuguo Deng, and Xinyue Cao
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PD-L1 ,0301 basic medicine ,Oncology ,medicine.medical_specialty ,Pathology ,Anemia ,medicine.medical_treatment ,HIF-1α ,Immunofluorescence ,03 medical and health sciences ,recurrent ,0302 clinical medicine ,Internal medicine ,PD-1 ,medicine ,biology ,medicine.diagnostic_test ,business.industry ,nasopharyngeal carcinoma ,Immunosuppression ,Hypoxia (medical) ,medicine.disease ,030104 developmental biology ,Nasopharyngeal carcinoma ,030220 oncology & carcinogenesis ,biology.protein ,Immunohistochemistry ,Tumor necrosis factor alpha ,medicine.symptom ,business ,Research Paper - Abstract
The expression of Programmed death-1 (PD-1) / programmed death-ligand 1 (PD-L1) has been reported to be reliable prognostic factors in various malignances including primary nasopharyngeal carcinoma (NPC). However, the exact role of PD-1/PD-L1 in recurrent NPC remains unclear. In this study, we aimed to investigate the relationship between the expression of PD-1 / PD-L1 and the clinical-pathology as well the outcomes of recurrent NPC patients (n = 132). The expression of PD-1 and PD-L1 was measured by immunohistochemistry staining. The relationship between PD-1 / PD-L1 and factors involved in clinic-pathology and outcomes of patients with NPC was assessed by correlation analysis. To further explore the association between PD-L1 and anemia, immunofluorescence analysis was performed to investigate the correlation of PD-L1 with hypoxia inducible factor-1α (HIF-1α). We observed that advanced rT classification and anemia status before salvage treatment was associated with high level of PD-L1 in recurrent NPC patients, and PD-L1 and was co-located with HIF-1α in recurrent tumors by immunofluorescence analysis. Moreover, our result suggested that PD-L1 might be a negative indicator for recurrent NPC patients as well as age, rT classification, anemia and tumor necrosis at diagnose of recurrence. Taken together, our results revealed that PD-L1 might be a potential prognostic biomarker for recurrent NPC patients, and advanced re-stage, anemia might represent as candidate biomarkers for evaluating patients’ response to anti-PD-1 / PD-L1-treatment. However, further studies are needed to clarify the underlying mechanism of hypoxia in immunosuppression process induced by PD-1 / PD-L1 axis.
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- 2017
3. Effect of intensity-modulated radiotherapy versus two-dimensional conventional radiotherapy alone in nasopharyngeal carcinoma
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Yuanhong Gao, Lu Ning Zhang, Rui Sun, Wuguo Deng, Ze Ying Chen, Dingbo Shi, Yu Jia Zhu, Pu Yun OuYang, Xiao Wen Lan, Jie Tang, Jun Ma, Xu Hui Zhang, Yao Xiao, and Fang Yun Xie
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Oncology ,Adult ,Male ,medicine.medical_specialty ,Time Factors ,medicine.medical_treatment ,Nasopharyngeal neoplasm ,Kaplan-Meier Estimate ,Disease-Free Survival ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Carcinoma ,medicine ,Humans ,Propensity Score ,Proportional Hazards Models ,Retrospective Studies ,Chi-Square Distribution ,Nasopharyngeal Carcinoma ,propensity score matching ,business.industry ,Proportional hazards model ,Cancer ,Retrospective cohort study ,Nasopharyngeal Neoplasms ,Pharyngeal Neoplasms ,Middle Aged ,medicine.disease ,intensity-modulated radiotherapy ,Surgery ,Radiation therapy ,Logistic Models ,Treatment Outcome ,Nasopharyngeal carcinoma ,030220 oncology & carcinogenesis ,Propensity score matching ,Multivariate Analysis ,Disease Progression ,Female ,Radiotherapy, Intensity-Modulated ,Clinical Research Paper ,Neoplasm Recurrence, Local ,business ,two-dimensional conventional radiotherapy - Abstract
// Pu-Yun OuYang 1, * , Dingbo Shi 2, * , Rui Sun 3, * , Yu-Jia Zhu 1, * , Yao Xiao 1 , Lu-Ning Zhang 1 , Xu-Hui Zhang 1 , Ze-Ying Chen 1 , Xiao-Wen Lan 1 , Jie Tang 1 , Yuan-Hong Gao 1 , Jun Ma 1 , Wuguo Deng 2, ** , Fang-Yun Xie 1, ** 1 Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China 2 Department of Experimental Research, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China 3 Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China * Co-first authors ** Co-senior authors Correspondence to: Fang-Yun Xie, e-mail: xiefy@sysucc.org.cn Keywords: intensity-modulated radiotherapy, nasopharyngeal carcinoma, propensity score matching, two-dimensional conventional radiotherapy Received: February 12, 2016 Accepted: March 27, 2016 Published: April 4, 2016 ABSTRACT Background: Albeit intensity-modulated radiotherapy (IMRT) is currently the recommended radiation technique in treating nasopharyngeal carcinoma, the effect of IMRT versus two-dimensional conventional radiotherapy (2DCRT) alone is still contradictory. Results: In the original unmatched cohort of 1198 patients, IMRT obtained comparable 5-year overall survival (OS) (91.3% vs 87.1%, P = 0.120), locoregional relapse-free survival (LRFS) (92.3% vs 90.4%, P = 0.221) and distant metastasis-free survival (DMFS) (92.9% vs 92.1%, P = 0.901) to 2DCRT. In the propensity-matched cohort of 604 patients, no significant survival differences were observed between the two arms (5-year OS 90.9% vs 90.5%, P = 0.655; LRFS 92.5% vs 92.4%, P = 0.866; DMFS 92.5% vs 92.9%, P = 0.384). In multivariate analysis, IMRT did not significantly lower the risk of death, locoregional relapse or distant metastasis, irrespective of tumor stage. Methods: Overall, 1198 patients who underwent IMRT (316 patients) or 2DCRT (882 patients) without any chemotherapy was retrospectively analyzed. Patients in both arms were matched at equal ratio using propensity-score matching method. OS, LRFS and DMFS were assessed with Kaplan-Meier method, log-rank test and Cox regression. Conclusions: In this propensity-matched study, IMRT showed no survival advantage over 2DCRT alone in nasopharyngeal carcinoma.
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- 2016
4. Tumor suppressor Spred2 interaction with LC3 promotes autophagosome maturation and induces autophagy-dependent cell death
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Quentin Liu, Peng Gong, Jozsef Gal, Wuguo Deng, Guibin Lin, Xiaolin Bi, Wei Cheng, Ke Jiang, Han Liu, Songshu Meng, Min Liu, Zengqiang Yuan, Haining Zhu, and Beibei Mao
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0301 basic medicine ,Programmed cell death ,autophagy ,tumor suppressor ,Autophagosome maturation ,p62/SQSTM1 ,ATG5 ,HeLa ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,Cell Line, Tumor ,LC3 ,Humans ,Spred2 ,A549 cell ,LAMP2 ,biology ,Autophagy ,Autophagosomes ,biology.organism_classification ,Cell biology ,Repressor Proteins ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Immunology ,Microtubule-Associated Proteins ,Research Paper - Abstract
The tumor suppressor Spred2 (Sprouty-related EVH1 domain-2) induces cell death in a variety of cancers. However, the underlying mechanism remains to be elucidated. Here we show that Spred2 induces caspase-independent but autophagy-dependent cell death in human cervical carcinoma HeLa and lung cancer A549 cells. We demonstrate that ectopic Spred2 increased both the conversion of microtubule-associated protein 1 light chain 3 (LC3), GFP-LC3 puncta formation and p62/SQSTM1 degradation in A549 and HeLa cells. Conversely, knockdown of Spred2 in tumor cells inhibited upregulation of autophagosome maturation induced by the autophagy inducer Rapamycin, which could be reversed by the rescue Spred2. These data suggest that Spred2 promotes autophagy in tumor cells. Mechanistically, Spred2 co-localized and interacted with LC3 via the LC3-interacting region (LIR) motifs in its SPR domain. Mutations in the LIR motifs or deletion of the SPR domain impaired Spred2-mediated autophagosome maturation and tumor cell death, indicating that functional LIR is required for Spred2 to trigger tumor cell death. Additionally, Spred2 interacted and co-localized with p62/SQSTM1 through its SPR domain. Furthermore, the co-localization of Spred2, p62 and LAMP2 in HeLa cells indicates that p62 may be involved in Spred2-mediated autophagosome maturation. Inhibition of autophagy using the lysosomal inhibitor chloroquine, reduced Spred2-mediated HeLa cell death. Silencing the expression of autophagy-related genes ATG5, LC3 or p62 in HeLa and A549 cells gave similar results, suggesting that autophagy is required for Spred2-induced tumor cell death. Collectively, these data indicate that Spred2 induces tumor cell death in an autophagy-dependent manner.
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- 2016
5. Melatonin inhibits AP-2β/hTERT, NF-κB/COX-2 and Akt/ERK and activates caspase/Cyto C signaling to enhance the antitumor activity of berberine in lung cancer cells
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Lijun Qin, Dingbo Shi, Lingyi Fu, Wenlin Huang, Fangyun Xie, Changlin Zhang, Wuguo Deng, Zhipeng Tang, Jian Jun Lu, Zhenlong Yu, Xiangsheng Xiao, and Jingshu Wang
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Male ,0301 basic medicine ,MAPK/ERK pathway ,Lung Neoplasms ,Berberine ,Apoptosis ,Mice ,chemistry.chemical_compound ,0302 clinical medicine ,Antineoplastic Combined Chemotherapy Protocols ,Medicine ,Extracellular Signal-Regulated MAP Kinases ,Promoter Regions, Genetic ,Telomerase ,Melatonin ,Mice, Inbred BALB C ,NF-kappa B ,Cytochromes c ,Caspase 9 ,DNA-Binding Proteins ,Proto-Oncogene Proteins c-bcl-2 ,Oncology ,030220 oncology & carcinogenesis ,Poly(ADP-ribose) Polymerases ,Signal transduction ,hTERT ,Signal Transduction ,Research Paper ,medicine.drug ,Active Transport, Cell Nucleus ,Mice, Nude ,Antineoplastic Agents ,03 medical and health sciences ,Cancer stem cell ,Cell Line, Tumor ,Animals ,Telomerase reverse transcriptase ,Protein kinase B ,Cyclooxygenase 2 Inhibitors ,business.industry ,melantonin ,COX-2 ,Xenograft Model Antitumor Assays ,lung cancer ,030104 developmental biology ,Transcription Factor AP-2 ,chemistry ,Cyclooxygenase 2 ,Immunology ,Cancer research ,business ,Proto-Oncogene Proteins c-akt - Abstract
// Jian-Jun Lu 1, * , Lingyi Fu 2, 3, * , Zhipeng Tang 4, * , Changlin Zhang 2 , Lijun Qin 5 , Jingshu Wang 2 , Zhenlong Yu 4 , Dingbo Shi 2 , Xiangsheng Xiao 2 , Fangyun Xie 2 , Wenlin Huang 2, 6 , Wuguo Deng 2, 6 1 Department of Thoracic Surgery, The First Affiliated Hospital, Yat-sen University, Guangzhou, China 2 Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China 3 Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China 4 Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China 5 Department of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China 6 State Key Laboratory of Targeted Drug for Tumors of Guangdong Province, Guangzhou Double Bioproduct Inc., Guangzhou, China * These authors have contributed equally to this article Correspondence to: Jian-Jun Lu, e-mail: ljj508@21cn.com Wuguo Deng, e-mail: dengwg@sysucc.org.cn Keywords: melantonin, berberine, lung cancer, hTERT, COX-2 Received: August 04, 2015 Accepted: November 16, 2015 Published: November 27, 2015 ABSTRACT Melatonin, a molecule produced throughout the animal and plant kingdoms, and berberine, a plant derived agent, both exhibit antitumor and multiple biological and pharmacological effects, but they have never been combined altogether for the inhibition of human lung cancers. In this study, we investigated the role and underlying mechanisms of melatonin in the regulation of antitumor activity of berberine in lung cancer cells. Treatment with melatonin effectively increased the berberine-mediated inhibitions of cell proliferation, colony formation and cell migration, thereby enhancing the sensitivities of lung cancer cells to berberine. Melatonin also markedly increased apoptosis induced by berberine. Further mechanism study showed that melatonin promoted the cleavage of caspse-9 and PARP, enhanced the inhibition of Bcl2, and triggered the releasing of cytochrome C (Cyto C), thereby increasing the berberine-induced apoptosis. Melatonin also enhanced the berberine-mediated inhibition of telomerase reverses transcriptase (hTERT) by down-regulating the expression of AP-2β and its binding on hTERT promoter. Moreover, melatonin enhanced the berberine-mediated inhibition of cyclooxygenase 2 (COX-2) by inhibiting the nuclear translocation of NF-κB and its binding on COX-2 promoter. Melatonin also increased the berberine-mediated inhibition of the phosphorylated Akt and ERK. Collectively, our results demonstrated that melatonin enhanced the antitumor activity of berberine by activating caspase/Cyto C and inhibiting AP-2β/hTERT, NF-κB/COX-2 and Akt/ERK signaling pathways. Our findings provide new insights in exploring the potential therapeutic strategies and novel targets for lung cancer treatment.
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- 2015
6. Targeting PDK1 with dichloroacetophenone to inhibit acute myeloid leukemia (AML) cell growth
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Yun Tian, Congcong Liu, Xuezhen Chen, Wenlin Huang, Yiming Chen, Lijun Qin, Wuguo Deng, Changlin Zhang, Ruoyu Peng, Dingbo Shi, Jingshu Wang, and Zhenlong Yu
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0301 basic medicine ,Time Factors ,Apoptosis ,0302 clinical medicine ,AML ,hemic and lymphatic diseases ,BCL-xl ,Medicine ,Molecular Targeted Therapy ,biology ,U937 cell ,Myeloid leukemia ,U937 Cells ,Tumor Burden ,Leukemia, Myeloid, Acute ,Oncology ,PDK1 ,030220 oncology & carcinogenesis ,Female ,Signal transduction ,Research Paper ,Signal Transduction ,autophagy ,animal structures ,Cell Survival ,Mice, Nude ,Bcl-xL ,Caspase 3 ,Antineoplastic Agents ,Protein Serine-Threonine Kinases ,03 medical and health sciences ,Animals ,Humans ,Protein Kinase Inhibitors ,PI3K/AKT/mTOR pathway ,Cell Proliferation ,Mice, Hairless ,Dose-Response Relationship, Drug ,business.industry ,Cell growth ,Akt/PKB signaling pathway ,Acetophenones ,Pyruvate Dehydrogenase Acetyl-Transferring Kinase ,Xenograft Model Antitumor Assays ,030104 developmental biology ,Immunology ,biology.protein ,Cancer research ,Phosphatidylinositol 3-Kinase ,business ,Apoptosis Regulatory Proteins ,Proto-Oncogene Proteins c-akt - Abstract
Pyruvate dehydrogenase kinase-1 (PDK1), a key metabolic enzyme involved in aerobic glycolysis, is highly expressed in many solid tumors. Small molecule compound DAP (2,2-dichloroacetophenone) is a potent inhibitor of PDK1. Whether targeting PDK1 with DAP can inhibit acute myeloid leukemia (AML) and how it works remains unknown. In this study, we evaluated the effect of inhibition of PDK1 with DAP on cell growth, apoptosis and survival in AML cells and identified the underlying mechanisms. We found that treatment with DAP significantly inhibited cell proliferation, increased apoptosis induction and suppressed autophagy in AML cells in vitro, and inhibited tumor growth in an AML mouse model in vivo. We also showed that inhibition of PDK1 with DAP increased the cleavage of pro-apoptotic proteins (PARP and Caspase 3) and decreased the expression of the anti-apoptotic proteins (BCL-xL and BCL-2) and autophagy regulators (ULK1, Beclin-1 and Atg). In addition, we found that DAP inhibited the PI3K/Akt signaling pathway. Furthermore, we demonstrated that PDK1 interacted with ULK1, BCL-xL and E3 ligase CBL-b in AML cells, and DPA treatment could inhibit the interactions. Collectively, our results indicated that targeting PDK1 with DAP inhibited AML cell growth via multiple signaling pathways and suggest that targeting PDK1 may be a promising therapeutic strategy for AMLs.
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- 2015
7. Propensity score matching analysis of cisplatin-based concurrent chemotherapy in low risk nasopharyngeal carcinoma in the intensity-modulated radiotherapy era
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Jun Ma, Yuanhong Gao, Lu Ning Zhang, Xiao Wen Lan, Jie Tang, Fang Yun Xie, Zhen Su, Wuguo Deng, and Pu Yun OuYang
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Adult ,Male ,Oncology ,medicine.medical_specialty ,medicine.medical_treatment ,Nasopharyngeal neoplasm ,Antineoplastic Agents ,Kaplan-Meier Estimate ,survival ,Disease-Free Survival ,Internal medicine ,medicine ,Humans ,Stage (cooking) ,Propensity Score ,Aged ,Retrospective Studies ,AJCC staging system ,Nasopharyngeal Carcinoma ,propensity score matching ,business.industry ,Carcinoma ,Cancer ,Nasopharyngeal Neoplasms ,Retrospective cohort study ,Chemoradiotherapy ,Middle Aged ,intensity-modulated radiotherapy ,Prognosis ,medicine.disease ,Surgery ,concurrent chemotherapy ,Radiation therapy ,Nasopharyngeal carcinoma ,Female ,Radiotherapy, Intensity-Modulated ,Clinical Research Paper ,Cisplatin ,business - Abstract
// Lu-Ning Zhang 1 , Yuan-Hong Gao 1 , Xiao-Wen Lan 1 , Jie Tang 1 , Zhen Su 1 , Jun Ma 1 , Wuguo Deng 2 , Pu-Yun OuYang 1, * , Fang-Yun Xie 1, * 1 Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China 2 Department of Experimental Research, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China * Co-senior authors Correspondence to: Fang-Yun Xie, e-mail: xiefy@sysucc.org.cn Pu-Yun OuYang, e-mail: ouyangpy@sysucc.org.cn Keywords: concurrent chemotherapy, intensity-modulated radiotherapy, nasopharyngeal carcinoma, propensity score matching, survival Received: June 19, 2015 Accepted: October 09, 2015 Published: October 19, 2015 ABSTRACT Background: Patients with stage II nasopharyngeal carcinoma were reported to benefit from adding cisplatin-based concurrent chemotherapy to two-dimensional conventional radiotherapy. But this benefit becomes uncertain in the intensity-modulated radiotherapy (IMRT) era, owing to its significant advantage. Methods: We enrolled 661 low risk (T1N1M0, T2N0-1M0 or T3N0M0, the 2010 UICC/AJCC staging system) patients who underwent IMRT with or without concurrent chemotherapy. Particularly, patients with IMRT alone or IMRT plus cisplatin-based concurrent chemotherapy were equally matched using propensity-score matching method. Overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRFS) were assessed with Kaplan-Meier method, log-rank test and Cox regression. Results: Among 661 patients, IMRT alone achieved parallel OS ( P = 0.379), DMFS ( P = 0.169) and LRFS ( P = 0.849) to IMRT plus concurrent chemotherapy. In the propensity-matched cohort of 482 patients, similar survival were observed between both arms (4-years OS 97.4% vs 96.1%, P = 0.134; DMFS 96.5% vs 95.1%, P = 0.763; LRFS 93.8% vs 91.5%, P = 0.715). In multivariate analysis, cisplatin-based concurrent chemotherapy did not lower the risk of death, distant metastasis or locoregional relapse. And this association remained unchanged in subgroups by age, sex, histology and stage. Conclusions: In this study, low risk nasopharyngeal carcinoma patients who underwent IMRT could not benefit from cisplatin-based concurrent chemotherapy.
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- 2015
8. RFPL3 and CBP synergistically upregulate hTERT activity and promote lung cancer growth
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Wangbing Chen, Meng Dai, Yu Qin, Wuguo Deng, Wendan Yu, Wei Guo, Taihua Wu, Wenlin Huang, Xin Cai, Yao Xiao, and Tingting Xu
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Male ,Transcriptional Activation ,Telomerase ,Lung Neoplasms ,Cell Survival ,Sialoglycoproteins ,RFPL3 ,Adenocarcinoma ,Biology ,CBP ,Downregulation and upregulation ,Carcinoma, Non-Small-Cell Lung ,Cell Line, Tumor ,medicine ,Humans ,Gene Regulatory Networks ,Telomerase reverse transcriptase ,RNA, Small Interfering ,Promoter Regions, Genetic ,Lung cancer ,neoplasms ,Aged ,Cell Proliferation ,Proportional Hazards Models ,Cell growth ,Promoter ,Middle Aged ,Prognosis ,medicine.disease ,Immunohistochemistry ,Peptide Fragments ,Up-Regulation ,Telomere ,Gene Expression Regulation, Neoplastic ,lung cancer ,enzymes and coenzymes (carbohydrates) ,Microscopy, Fluorescence ,Oncology ,embryonic structures ,Cancer research ,Female ,Signal transduction ,hTERT ,Carrier Proteins ,Research Paper ,Signal Transduction - Abstract
hTERT is the key component of telomerase and its overactivation contributes to maintaining telomere length and cell immortalization. Previously, we identified RFPL3 as a new transcription activator of hTERT in lung cancers. However, the exact mechanism of RFPL3 in mediating hTERT activation and its associated signal regulatory network remain unclear. In this study, we found that RFPL3 colocalized and interacted directly with CBP in the nucleus of lung cancer cells. Immunohistochemical analysis of tissue microarrays of lung cancers revealed the simultaneous overexpression of both RFPL3 and CBP predicted relatively poor prognosis. Furthermore, we confirmed their synergistic stimulation on hTERT expression and tumor cell growth. The binding of RFPL3 to hTERT promoter was reduced markedly when CBP was knocked down by its specific siRNA or suppressed by its inhibitor in lung cancer cells with stable overexpression of RFPL3. When one of the two proteins RFPL3 and CBP was upregulated or downregulated, whereas the another remains unchanged, hTERT expression and telomerase activity were activated or repressed accordingly. In the meantime, the growth of lung cancer cells was also promoted or attenuated accordingly. Furthermore, we also found that RFPL3 coordinated with CBP to upregulate hTERT through the CBP-induced acetylation of RFPL3 protein and their co-anchoring at hTERT promoter region. Collectively, our results reveal a new mechanism of hTERT regulation in lung cancer cells and suggest the RFPL3/CBP/hTERT signaling pathway may be a new targets for lung cancer treatment.
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- 2015
9. RPS3 regulates melanoma cell growth and apoptosis by targeting Cyto C/Ca2+/MICU1 dependent mitochondrial signaling
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Lijun Qin, Wenbing Li, Guowen Wang, Yun Tian, Tianze Liu, Wei Guo, Huijuan Qiu, Tiebang Kang, Wuguo Deng, Dingbo Shi, Wenlin Huang, Rui Sun, Tingting Xu, and Jingshu Wang
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Ribosomal Proteins ,Blotting, Western ,Mice, Nude ,Apoptosis ,Mitochondrion ,Mitochondrial Membrane Transport Proteins ,Mitochondrial membrane transport protein ,Cell Line, Tumor ,medicine ,melanoma ,calcium ion ,Animals ,Humans ,Inner mitochondrial membrane ,neoplasms ,Cation Transport Proteins ,Cell Proliferation ,Gene knockdown ,biology ,Cell growth ,Mitochondrial Permeability Transition Pore ,Melanoma ,Calcium-Binding Proteins ,Cytochromes c ,medicine.disease ,mitochondrial ,Molecular biology ,Xenograft Model Antitumor Assays ,Mitochondria ,Tumor Burden ,RNAi Therapeutics ,Oncology ,Mitochondrial permeability transition pore ,Microscopy, Fluorescence ,biology.protein ,Cancer research ,MICU1 ,Calcium ,RNA Interference ,Apoptosis Regulatory Proteins ,Research Paper ,RPS3 ,Signal Transduction - Abstract
Melanoma is one of the most aggressive and lethal cancers. Discovery and identification of novel therapeutic targets is urgently needed. In this study, we demonstrated that ribosomal protein S3 (RPS3) was a potential target involved in melanoma growth. Knockdown of RPS3 by siRNA suppressed cell growth and induced apoptosis in melanoma cells. Further mechanism studies showed that RPS3 knockdown in melanoma cells triggered the release of cytochrome C (Cyto C) from mitochondrial, increased the location of BID on mitochondrial membrane and the cleavage of the pro-apoptotic proteins (PARP, caspase-3 and -9), promoted the opening of mitochondrial permeability transition pore and the flooding of calcium ions (Ca(2+)) into the mitochondrial, and decreased the expression of the Ca(2+) gatekeeper MICU1 and its location on the mitochondrial. We also found that knockdown of RPS3 significantly inhibited tumor growth in a melanoma xenograft mouse model. Furthermore, we showed that RPS3 was highly expressed in melanoma cell lines and melanoma tumor tissues, and overexpression of RPS3 was associated with the poor prognosis of melanoma patients. Our results therefore demonstrate that RPS3 regulates melanoma growth through the modulation of the Cyto C/Ca(2+)/MICU1 dependent mitochondrial signaling and suggest that RPS3 is a potential therapeutic target for melanoma treatment.
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- 2015
10. Ku80 cooperates with CBP to promote COX-2 expression and tumor growth
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Wei Cheng, Wenlin Huang, Yao Xiao, Yiming Chen, Shilei Zhao, Quentin Liu, Canhui Yi, Yang Xuan, Xiangsheng Xiao, Yunlu Jia, Wendan Yu, Jingshu Wang, Wenxian Hu, Wuguo Deng, Meng Dai, Mei Li, Taihua Wu, Songshu Meng, Shusen Wang, Zhenglin Li, Wei Guo, Sha Du, Yu Qin, and Yuhui Yuan
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MAPK/ERK pathway ,Ku80 ,Lung Neoplasms ,Mice ,Random Allocation ,Cell Movement ,2.1 Biological and endogenous factors ,RNA, Small Interfering ,Promoter Regions, Genetic ,Lung ,Cancer ,Gene knockdown ,Tumor ,Lung Cancer ,Antigens, Nuclear ,Transfection ,DNA-Binding Proteins ,Oncology ,Disease Progression ,Heterografts ,Biotechnology ,Research Paper ,Oncology and Carcinogenesis ,Adenocarcinoma of Lung ,Biology ,Adenocarcinoma ,Small Interfering ,CBP ,Cell Line ,Promoter Regions ,Rare Diseases ,Genetic ,Cell Line, Tumor ,Genetics ,medicine ,Gene silencing ,Animals ,Humans ,Nuclear ,Antigens ,Lung cancer ,Ku Autoantigen ,Cell Proliferation ,Cell growth ,Promoter ,COX-2 ,medicine.disease ,lung cancer ,Cyclooxygenase 2 ,Cancer research ,RNA - Abstract
Cyclooxygenase-2 (COX-2) plays an important role in lung cancer development and progression. Using streptavidin-agarose pulldown and proteomics assay, we identified and validated Ku80, a dimer of Ku participating in the repair of broken DNA double strands, as a new binding protein of the COX-2 gene promoter. Overexpression of Ku80 up-regulated COX-2 promoter activation and COX-2 expression in lung cancer cells. Silencing of Ku80 by siRNA down-regulated COX-2 expression and inhibited tumor cell growth in vitro and in a xenograft mouse model. Ku80 knockdown suppressed phosphorylation of ERK, resulting in an inactivation of the MAPK pathway. Moreover, CBP, a transcription co-activator, interacted with and acetylated Ku80 to co-regulate the activation of COX-2 promoter. Overexpression of CBP increased Ku80 acetylation, thereby promoting COX-2 expression and cell growth. Suppression of CBP by a CBP-specific inhibitor or siRNA inhibited COX-2 expression as well as tumor cell growth. Tissue microarray immunohistochemical analysis of lung adenocarcinomas revealed a strong positive correlation between levels of Ku80 and COX-2 and clinicopathologic variables. Overexpression of Ku80 was associated with poor prognosis in patients with lung cancers. We conclude that Ku80 promotes COX-2 expression and tumor growth and is a potential therapeutic target in lung cancer.
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- 2015
11. Activating enhancer-binding protein-2α induces cyclooxygenase-2 expression and promotes nasopharyngeal carcinoma growth
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Tiebang Kang, Dingbo Shi, Wenlin Huang, Rui Sun, Tianze Liu, Yao Xiao, Wenbin Li, Huijuan Qiu, Yuqing Xiong, Fangyun Xie, Wei Guo, Jingshu Wang, Xiangsheng Xiao, Wendan Yu, Chong Zhao, Wuguo Deng, Yun Tian, and Lijun Qin
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Male ,p300 ,Mice ,AP-2α ,Cancer stem cell ,Enhancer binding ,Cell Line, Tumor ,medicine ,otorhinolaryngologic diseases ,Animals ,Humans ,Cell Proliferation ,Gene knockdown ,Nasopharyngeal Carcinoma ,biology ,Traditional medicine ,Cell growth ,business.industry ,Carcinoma ,Cancer ,Nasopharyngeal Neoplasms ,Histone acetyltransferase ,COX-2 ,Middle Aged ,medicine.disease ,stomatognathic diseases ,Oncology ,Nasopharyngeal carcinoma ,Transcription Factor AP-2 ,Cell culture ,Cyclooxygenase 2 ,Enzyme Induction ,biology.protein ,Cancer research ,Heterografts ,Female ,business ,Research Paper ,Signal Transduction - Abstract
// Dingbo Shi 1,* , Xiangsheng Xiao 1,* , Yun Tian 1,* , Lijun Qin 3 , Fangyun Xie 1 , Rui Sun 1 , Jingshu Wang 1 , Wenbin Li 1 , Tianze Liu 1 , Yao Xiao 2 , Wendan Yu 2 , Wei Guo 2 , Yuqing Xiong 1 , Huijuan Qiu 1 , Tiebang Kang 1 , Wenlin Huang 1,4 , Chong Zhao 1 and Wuguo Deng 1,4 1 Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China 2 Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China 3 Department of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China 4 State Key Laboratory of Targeted Drug for Tumors of Guangdong Province, Guangzhou Double Bioproduct Inc., Guangzhou, China * These authors contributed equally to this manuscript Correspondence: Chong Zhao, email: // Wuguo Deng, email: // Keywords : AP-2α, COX-2, p300, nasopharyngeal carcinoma Received : November 07, 2014 Accepted : December 26, 2014 Published : December 31, 2014 Abstract Activating enhancer-binding protein-2α (AP-2α) regulates the expression of many cancer-related genes. Here, we demonstrated a novel mechanism by which AP-2α up-regulated cyclooxygenase-2 (COX-2) expression to promote the growth of nasopharyngeal carcinomas (NPCs). High expression of AP-2α in NPC cell lines and tumor tissues from NPC patients was detected and significantly correlated with COX-2 expression. Overexpression of AP-2α and COX-2 in tumor tissues was associated with advanced tumor stage, clinical progression, and short survival of patients with NPCs. Knockdown of AP-2α by siRNA markedly inhibited COX-2 expression and PGE2 production in NPC cells. Exogenous expression of AP-2α up-regulated the COX-2 and PGE2. Knockdown of AP-2α also significantly suppressed cell proliferation in NPC cells in vitro and tumor growth in a NPC xenograft mouse model. Moreover, we found that p300 played an important role in the AP-2α/COX-2 pathway. AP-2α could co-localize and interact with p300 in NPC cells. Overexpression of the p300, but not its histone acetyltransferase (HAT) domain deletion mutant, promoted the acetylation of AP-2α and its binding on the COX-2 promoter, thereby up-regulated COX-2 expression. Our results indicate that AP-2α activates COX-2 expression to promote NPC growth and suggest that the AP-2α/COX-2 signaling is a potential therapeutic target for NPC treatment.
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- 2014
12. Ret finger protein-like 3 promotes tumor cell growth by activating telomerase reverse transcriptase expression in human lung cancer cells
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Xiangsheng Xiao, Taihua Wu, Guo Wei, Yun Tian, Yu Qin, Wangbing Chen, Lu Liu, Jingshu Wang, Jianjun Lu, Shusen Wang, Yao Xiao, Dingbo Shi, Bilian Jin, Wuguo Deng, Tie Bang Kang, Wenlin Huang, and Meng Dai
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Chromatin Immunoprecipitation ,Telomerase ,Lung Neoplasms ,Blotting, Western ,Mice, Nude ,Enzyme-Linked Immunosorbent Assay ,Kaplan-Meier Estimate ,Biology ,Transfection ,Polymerase Chain Reaction ,Small hairpin RNA ,Mice ,Cancer stem cell ,Carcinoma, Non-Small-Cell Lung ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Telomerase reverse transcriptase ,Lung cancer ,neoplasms ,Proportional Hazards Models ,Cancer ,medicine.disease ,Immunohistochemistry ,Gene Expression Regulation, Neoplastic ,enzymes and coenzymes (carbohydrates) ,Oncology ,Tissue Array Analysis ,embryonic structures ,Cancer research ,Heterografts ,Carrier Proteins ,Chromatin immunoprecipitation ,Research Paper - Abstract
// Wangbing Chen 1, 4, * , Jianjun Lu 3, * , Yu Qin 2, * , Jingshu Wang 1, * , Yun Tian 1 , Dingbo Shi 1 , Shusen Wang 1 , Yao Xiao 2 , Meng Dai 2 , Lu Liu 2 , Guo Wei 2 , Taihua Wu 2 , Bilian Jin 2 , Xiangsheng Xiao 1 , Tie-Bang Kang 1 , Wenlin Huang 1, 5 , Wuguo Deng 1, 5 1 Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China 2 Institute of Cancer Stem Cell & The First Affiliated Hospital, Dalian Medical University, Dalian, China 3 Department of Thoracic Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China 4 Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China 5 State Key Laboratory of Targeted Drug for Tumors of Guangdong Province, Guangzhou Double Bioproduct Inc., Guangzhou, China * These authors contributed equally to this article Correspondence to: Shusen Wang, e-mail: wangshs@sysucc.org.cn Bilian Jin, e-mail: bjinmcg@gmail.com Wuguo Deng, e-mail: dengwg@sysucc.org.cn Received: August 10, 2014 Accepted: October 01, 2014 Published: November 13, 2014 ABSTRACT In this study, we identified ret finger protein-like 3 (RFPL3) as a hTERT promoter binding protein in lung cancer cells. The high hTERT promoter-binding activity of RFPL3 was detected in lung cancer cells compared to normal cells. Chromatin immunoprecipitation confirmed RFPL3 as a tumor-specific hTERT promoter binding protein. Overexpression of RFPL3 activated hTERT promoter and up-regulated hTERT expression and telomerase activity. Inhibition of RFPL3 expression by siRNA suppressed hTERT promoter activation and telomerase activity. Inhibition of RFPL3 by siRNA or shRNA also significantly inhibited tumor cell growth in vitro and in a xenograft mouse model in vivo . Immunohistochemical analysis of 181 human lung adenocarcinomas specimens showed a significant correlation between RFPL3 and hTERT expression. The overexpression of RFPL3 was also associated significantly with lymph node metastasis. Univariate and multivariate Cox model analyses of NSCLC clinical specimens revealed a strong correlation between RFPL3 expression and overall survival. These results demonstrate that RFPL3 is an important cellular factor which promotes lung cancer growth by activating hTERT expression and may be a potential novel therapeutic target for lung cancer.
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- 2014
13. Paradoxical role of CBX8 in proliferation and metastasis of colorectal cancer
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Boqing Wang, Rongzhen Luo, Kaishun Hu, Wuguo Deng, Li-Li Wang, Jingying Cao, Xiaoshi Zhang, Gang Wang, Meifang Zhang, Jianjun Tang, Dan Xie, Ruhua Zhang, Dan Liao, Yi Sang, Xin-Xin Wang, Rui-Hua Xu, Tiebang Kang, Yuanzhong Wu, and Feng-Yan Li
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p53 ,Chromatin Immunoprecipitation ,RHOA ,Colorectal cancer ,integrin ,proliferation ,Blotting, Western ,Fluorescent Antibody Technique ,Mice, Nude ,colorectal cancer ,Apoptosis ,Biology ,Metastasis ,Immunoenzyme Techniques ,Mice ,Cell Movement ,medicine ,Tumor Cells, Cultured ,metastasis ,Animals ,Humans ,RNA, Small Interfering ,Survival rate ,neoplasms ,Cell Proliferation ,Polycomb Repressive Complex 1 ,Gene knockdown ,Mice, Inbred BALB C ,Cell growth ,Polycomb Group protein ,Integrin beta4 ,Liver Neoplasms ,Cancer ,medicine.disease ,Prognosis ,Xenograft Model Antitumor Assays ,digestive system diseases ,Up-Regulation ,Survival Rate ,Oncology ,Cancer research ,biology.protein ,CBX8 ,Female ,Tumor Suppressor Protein p53 ,Colorectal Neoplasms ,Research Paper - Abstract
// Jianjun Tang 1, * , Gang Wang 1, * , Meifang Zhang 1, * , Feng-yan Li 1 , Yi Sang 1 , Boqing Wang 1, 2 , Kaishun Hu 1 , Yuanzhong Wu 1 , Rongzhen Luo 1 , Dan Liao 1 , Jingying Cao 1 , Xin Wang 1 , Li Wang 1 , Ruhua Zhang 1 , Xiaoshi Zhang 1 , Wu-Guo Deng 1 , Dan Xie 1 , Rui-hua Xu 1 , Tiebang Kang 1 1 State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, China 2 Department of Hepatobiliarypancreatic Surgery, Affiliated Tumor Hospital, Xinjiang Medical University, Urumqi 830000, China * These authors contributed equally to this work Correspondence to: Tiebang Kang, e-mail: kangtb@mail.sysu.edu.cn Keywords: CBX8, Polycomb Group protein, colorectal cancer, metastasis, proliferation, p53, integrin Received: July 23, 2014 Accepted: September 13, 2014 Published: October 24, 2014 ABSTRACT The effect of polycomb chromobox (Cbx) proteins in cancer is context-dependent. The Chromobox homolog 8 (CBX8) was originally characterized as a transcriptional repressor, which inhibits cell proliferation in Ink4a-Arf-dependent and -independent manner. However, the role of CBX8 in colorectal cancer remains unknown. Here, we found that high CBX8 expression was associated with a low rate of distant metastasis and good prognosis in CRC patients, even though CBX8 was up-regulated in CRC cell lines and clinical samples. Knockdown of CBX8 inhibited CRC proliferation in vitro and in vivo, mostly by increasing p53 and its downstream effectors. However, knockdown of CBX8 enhanced CRC migration, invasion and metastasis in vitro and in vivo, in part through direct up-regulation of integrin β4 (ITGB4) that in turn decreased RhoA activity. Collectively, the knockdown of CBX8 inhibited CRC proliferation, while promoting its metastasis, thus exerting paradoxical effects in CRC progression.
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- 2014
14. Transcriptional coactivator CBP upregulates hTERT expression and tumor growth and predicts poor prognosis in human lung cancers
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Wei Guo, Xiangsheng Xiao, Yao Xiao, Wangbing Chen, Wuguo Deng, Wendan Yu, Taihua Wu, Yuhui Yuan, Meng Dai, Quentin Liu, Jianjun Lu, Guangwei Du, Tingting Xu, Canhui Yi, Jingshu Wang, Zhipeng Tang, Dingbo Shi, and Zhenlong Yu
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Telomerase ,Lung Neoplasms ,Transcription, Genetic ,cells ,medicine.disease_cause ,Mice ,RNA, Small Interfering ,Promoter Regions, Genetic ,biology ,Acetylation ,Prognosis ,CREB-Binding Protein ,Gene Expression Regulation, Neoplastic ,Oncology ,embryonic structures ,Adenocarcinoma ,RNA Interference ,biological phenomena, cell phenomena, and immunity ,hTERT ,Protein Binding ,Research Paper ,Transcriptional Activation ,Cell Survival ,Sp1 Transcription Factor ,Transplantation, Heterologous ,Mice, Nude ,Adenocarcinoma of Lung ,CBP ,Sp1 ,Cancer stem cell ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Telomerase reverse transcriptase ,CREB-binding protein ,Lung cancer ,neoplasms ,Cell Proliferation ,promoter ,medicine.disease ,Molecular biology ,Transplantation ,enzymes and coenzymes (carbohydrates) ,lung cancer ,biology.protein ,Cancer research ,Carcinogenesis ,Neoplasm Transplantation - Abstract
// Wei Guo 1,* , Jianjun Lu 3,* , Meng Dai 1 , Taihua Wu 1 , Zhenlong Yu 1 , Jingshu Wang 2 , Wangbing Chen 2 , Dingbo Shi 2 , Wendan Yu 1 , Yao Xiao 1 , Canhui Yi 1 , Zhipeng Tang 1 , Tingting Xu 1 , Xiangsheng Xiao 2 , Yuhui Yuan 1 , Quentin Liu 1,2 , Guangwei Du 4 and Wuguo Deng 1,2 1 Institute of Cancer Stem Cell & First Affiliated Hospital, Dalian Medical University, Dalian, China 2 Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China; Colaborative Innovation Center of Cancer Medicine, Guangzhou, China 3 Department of Thoracic Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China 4 Department of Integrative Biology and Pharmacology, The University of Texas Health Science Center, Houston, Texas, USA * These authors contributed equally to this work Correspondence: Wuguo Deng, email: // Wei Guo, email: // Keywords : CBP, hTERT, promoter, Sp1, lung cancer Received : July 17, 2014 Accepted : September 02, 2014 Published : September 03, 2014 Abstract Upregulated expression and activation of human telomerase reverse transcriptase (hTERT) is a hallmarker of lung tumorigenesis. However, the mechanism underlying the aberrant hTERT activity in lung cancer cells remains poorly understood. In this study, we found the transcriptional co-activator CBP as a new hTERT promoter-binding protein that regulated hTERT expression and tumor growth in lung adenocarcinoma cells using a biotin-streptavidin-bead pulldown technique. Chromatin immunoprecipitation assay verified the immortalized cell and tumor cell-specific binding of CBP on hTERT promoter. Overexpression of exogenous CBP upregulated the expression of the hTERT promoter-driven luciferase and endogenous hTERT protein in lung cancer cells. Conversely, inhibition of CBP by CBP-specific siRNA or its chemical inhibitor repressed the expression of hTERT promoter-driven luciferase and endogenous hTERT protein as well as telomerase activity. Moreover, inhibition of CBP expression or activity also significantly reduced the proliferation of lung cancer cells in vitro and tumor growth in an xenograft mouse model in vivo . Immunohistochemical analysis of tissue microarrays of lung cancers revealed a positive correlation between CBP and hTERT. Importantly, the patients with high CBP and hTERT expression had a significantly shorter overall survival. Furthermore, CBP was found to interact with and acetylate transactivator Sp1 in lung cancer cells. Inhibition of CBP by CBP-specific siRNA or its chemical inhibitor significantly inhibited Sp1 acetylation and its binding to the hTERT promoter. Collectively, our results indicate that CBP contributes to the upregulation of hTERT expression and tumor growth, and overexpression of CBP predicts poor prognosis in human lung cancers.
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- 2014
15. Age at diagnosis indicated poor prognosis in locoregionally advanced nasopharyngeal carcinoma
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Wuguo Deng, Lu-Ning Zhang, Fangyun Xie, Pu-Yun OuYang, Xing-Sheng Qiu, Xiao-Wen Lan, Yao Xiao, and Xi-Cheng Wang
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Poor prognosis ,medicine.medical_specialty ,Multivariate analysis ,South china ,business.industry ,Cancer ,Age at diagnosis ,medicine.disease ,Surgery ,Oncology ,Cancer Medicine ,Nasopharyngeal carcinoma ,Internal medicine ,medicine ,In patient ,business - Abstract
// Lu-Ning Zhang 1,2,* , Xing-Sheng Qiu 3,* , Pu-Yun OuYang 2,* , Yao Xiao 2 , Xiao-Wen Lan 2 , Wuguo Deng 2 , Fang-Yun Xie 2 and Xi-Cheng Wang 1 1 Department of Oncology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China 2 Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China 3 Department of Radiation Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China * Co-first authors Correspondence to: Xi-Cheng Wang, email: // Fang-Yun Xie, email: // Wuguo Deng, email: // Keywords : age; concurrent chemoradiotherapy; distant metastasis; mortality; nasopharyngeal carcinoma Received : August 10, 2016 Accepted : September 29, 2016 Published : October 09, 2016 Abstract Background: Effect of age at diagnosis on treatment failure and mortality was rarely evaluated in nasopharyngeal carcinoma. Methods: We analyzed 1252 patients staged III-IVb and underwent concurrent chemoradiotherapy. Age was categorized as 20 to 49 years ( n =804), 50 to 59 years ( n =282) and 60 years or older ( n =166). Distant metastasis-free survival (DMFS), cancer-specific survival (CSS), overall survival (OS) and locoregional relapse-free survival (LRFS) were assessed by age group. Results: The 4-years DMFS decreased with age group (86.7% [20-49 years], 86.7% [50-59 years], 77.1% [≥60 years]; P =0.014); likewise, 4-years CSS were 91.0%, 87.4% and 74.2% ( P
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- 2016
16. Butein inhibits cell proliferation and induces cell cycle arrest in acute lymphoblastic leukemia via FOXO3a/p27kip1 pathway
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Xue Qun Luo, Anchuan Li, Huan Juan Zhou, Wenlin Huang, Yan Ni Liang, Dingbo Shi, Ge Qin, Zhi Yong Ke, Yan Lai Tang, Li-Bin Huang, Li-Na Wang, Yun Tian, Jingshu Wang, Wuguo Deng, and Wen Hao Lin
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0301 basic medicine ,Male ,Cell cycle checkpoint ,Cyclin E ,acute lymphoblastic leukemia ,butein ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Chalcones ,medicine ,Humans ,Child ,Butein ,Cell Proliferation ,Traditional medicine ,biology ,Cell growth ,business.industry ,Cyclin-dependent kinase 2 ,Forkhead Box Protein O3 ,Cancer ,Cell Cycle Checkpoints ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,FOXO3α ,medicine.disease ,Leukemia ,030104 developmental biology ,Oncology ,chemistry ,Cell culture ,030220 oncology & carcinogenesis ,Child, Preschool ,biology.protein ,Cancer research ,Female ,business ,p27kip1 ,Cyclin-Dependent Kinase Inhibitor p27 ,Signal Transduction ,Research Paper - Abstract
// Yan-Lai Tang 1, * , Li-Bin Huang 1, * , Wen-Hao Lin 1, * , Li-Na Wang 1 , Yun Tian 2 , Dingbo Shi 2 , Jingshu Wang 2 , Ge Qin 2 , Anchuan Li 3 , Yan-Ni Liang 1 , Huan-Juan Zhou 1 , Zhi-Yong Ke 1 , Wenlin Huang 2, 4 , Wuguo Deng 2, 4 , Xue-Qun Luo 1 1 Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China 2 Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China 3 Department of Radiation Oncology, Fujian Medical University Union Hospital, Fuzhou, China 4 State Key Laboratory of Targeted Drug for Tumors of Guangdong Province, Guangzhou Double Bioproduct Inc., Guangzhou, China * These authors have contributed equally to this work Correspondence to: Xue-Qun Luo, e-mail: l-xuequn@126.com Wuguo Deng, e-mail: dengwg@sysucc.org.cn Keywords: butein, acute lymphoblastic leukemia, FOXO3a, p27kip1 Received: November 22, 2015 Accepted: February 14, 2016 Published: February 23, 2016 ABSTRACT Acute lymphoblastic leukemia (ALL) is a common hematological malignancy characterized by the uncontrolled proliferation of leukemia cells in children. Discovering and developing effective chemotherapeutic drugs are needed for ALL. In this study, we investigated the anti-leukemic activity of butein and its action mechanisms in ALL. Butein was found to significantly suppress the cellular proliferation of ALL cell lines and primary ALL blasts in a dose-dependent manner. It also induced cell cycle arrest by decreasing the expression of cyclin E and CDK2. We also found that butein promoted nuclear Forkhead Class box O3a (FOXO3a) localization, enhanced the binding of FOXO3a on the p27kip1 gene promoter and then increased the expression of p27kip1. Moreover, we showed that FOXO3a knockdown significantly decreased the proliferation inhibition by butein, whereas overexpression of FOXO3a enhanced the butein-mediated proliferation inhibition. However, overexpression of FOXO3a mutation (C-terminally truncated FOXO3a DNA-binding domain) decreased the proliferation inhibition by butein through decreasing the expression of p27kip1. Our results therefore demonstrate the therapeutic potential of butein for ALL via FOXO3a/p27kip1 pathway.
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- 2015
17. Proteomics-based identification of VDAC1 as a tumor promoter in cervical carcinoma
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Yuan Liu, Wuguo Deng, Hui Wang, Weican Zhang, Xiaoli Wang, Ding Ma, Kezhen Li, Ci Ren, Da Zhu, Liming Wang, Wencheng Ding, Danhui Weng, Lan Yu, Zheng Hu, Changlin Zhang, and Hui Shen
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0301 basic medicine ,Proteomics ,cervical cancer ,Genetic enhancement ,Papillomavirus E7 Proteins ,Uterine Cervical Neoplasms ,Cervical intraepithelial neoplasia ,03 medical and health sciences ,medicine ,Humans ,Carcinogen ,Cervical cancer ,Gene knockdown ,Traditional medicine ,business.industry ,Voltage-Dependent Anion Channel 1 ,Papillomavirus Infections ,virus diseases ,medicine.disease ,HPV16 E7 ,female genital diseases and pregnancy complications ,immunohistochemistry (IHC) ,VDAC1 ,030104 developmental biology ,Oncology ,Apoptosis ,Cancer research ,Carcinogens ,Carcinoma, Squamous Cell ,Female ,business ,Oxidation-Reduction ,Research Paper - Abstract
We used oxidative isotope-coded affinity tags (OxICAT) to investigate the global redox status of proteins in human papillomavirus (HPV)-related cervical cancer cells, in order to identify a potential target for gene therapy. Voltage-dependent anion channel 1 (VDAC1) was found to be highly oxidized in HPV-positive cervical cancer cells. VDAC1 expression correlated significantly with the invasion of cervical cancer, the grade of cervical intraepithelial neoplasia (CIN) and the expression of HPV16 E7 in CIN. Knockdown of VDAC1 in cell lines increased the rate of apoptosis, while overexpression of the VDAC1 (respectively) partly reversed the effect. Thus, VDAC1 may promote the malignant progression of HPV-related disease, and treatments designed to suppress VDAC1 could prevent the progression of HPV-induced cervical disease.
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- 2015
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