20 results on '"Wenping Zhou"'
Search Results
2. A Genetic Predictive Model for Precision Treatment of Diffuse Large B-cell Lymphoma with Early Progression
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Jie Ma, Jiuyang Zhang, Qingxin Xia, Shujun Yang, Zhihua Yao, Zheng Yan, Wenping Zhou, Kangdong Liu, Yongjun Guo, Yuanlin Xu, Peipei Zhang, Yanyan Liu, Jialin Ma, Shuna Yao, Junfeng Chu, Shuang Zhao, Haiying Wang, and Bing Wei
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,Clinical Biochemistry ,CD79B ,PIM1 ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,International Prognostic Index ,Internal medicine ,medicine ,Bruton's tyrosine kinase ,biology ,Venetoclax ,business.industry ,Research ,lcsh:RM1-950 ,Biochemistry (medical) ,Diffuse large B-cell lymphoma ,medicine.disease ,Early progression ,Lymphoma ,lcsh:Therapeutics. Pharmacology ,030104 developmental biology ,chemistry ,030220 oncology & carcinogenesis ,Ibrutinib ,biology.protein ,Molecular Medicine ,business - Abstract
Background Early progression after the first-line R-CHOP treatment leads to a very dismal outcome and necessitates alternative treatment for patients with diffuse large B-cell lymphoma (DLBCL). This study aimed to develop a genetic predictive model for early progression and evaluate its potential in advancing alternative treatment. Methods Thirty-two hotspot driver genes were examined in 145 DLBCL patients and 5 DLBCL cell lines using next-generation sequencing. The association of clinical features, cell-of-origin, double expression, positive p53 protein, and gene alterations with early progression was analyzed, and the genetic predictive model was developed based on the related independent variables and assessed by the area under receiver operating characteristic. The potential of novel treatment based on the modeling was investigated in in-vitro DLBCL cell lines and in vivo xenograft mouse models. Results The frequency of CD79B (42.86% vs 9.38%, p = 0.000) and PIM1 mutations (38.78% vs 17.71%, p = 0.005) showed a significant increase in patients with early progression. CD79B and PIM1 mutations were associated with complex genetic events, double expression, non-GCB subtype, advance stage and unfavorable prognosis. A powerful genetic predictive model (AUROC = 0.771, 95% CI: 0.689–0.853) incorporating lactate dehydrogenase levels (OR = 2.990, p = 0.018), CD79B mutations (OR = 5.970, p = 0.001), and PIM1 mutations (OR = 3.021, p = 0.026) was created and verified in the other cohort. This modeling for early progression outperformed the prediction accuracy of conventional International Prognostic Index, and new molecular subtypes of MCD and Cluster 5. CD79B and PIM1 mutations indicated a better response to inhibitors of BTK (ibrutinib) and pan-PIM kinase (AZD 1208) through repressing activated oncogenic signaling. Since the two inhibitors failed to decrease BCL2 level, BCL2 inhibitor (venetoclax) was added and demonstrated to enhance their apoptosis-inducing activity in mutant cells with double expression. Conclusions The genetic predictive model provides a robust tool to identify early progression and determine precision treatment. These findings warrant the development of optimal alternative treatment in clinical trials.
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- 2020
3. LncRNA RHPN1-AS1 accelerates proliferation, migration, and invasion via regulating miR-485-5p/BSG axis in hepatocellular carcinoma
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Zhang Wei, Wenping Zhou, Han Lei, Zhongqi Sun, Peng Xing, Jiahong Dong, and Bailiang Liu
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0301 basic medicine ,Carcinoma, Hepatocellular ,Biology ,03 medical and health sciences ,0302 clinical medicine ,Cell Movement ,Cell Line, Tumor ,medicine ,Humans ,Neoplasm Invasiveness ,Adaptor Proteins, Signal Transducing ,Cell Proliferation ,Pharmacology ,Gene knockdown ,Oncogene ,Liver Neoplasms ,General Medicine ,medicine.disease ,digestive system diseases ,Long non-coding RNA ,MicroRNAs ,030104 developmental biology ,Cell culture ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Basigin ,Cancer research ,Function (biology) - Abstract
It is reported that long noncoding RNA RHPN1-AS1 (lncRNA RHPN1-AS1) functions as an oncogene among multiple types of cancers; however, the effect of lncRNA RHPN1-AS1 in hepatocellular carcinoma (HCC) is left to be investigated. The main purpose of this work was to study the effects of lncRNA RHPN1-AS1/miR-485-5p system on proliferation, migration, and invasion in HCC and future investigate the latent mechanisms. Our work found that lncRNA RHPN1-AS1 was observably up-regulated in HCC tissues and cell lines, especially HCCLM3 and SMMC-7721 cells. LncRNA RHPN1-AS1 knockdown decreased the capacity of proliferation, invasion, and migration in HCCLM3 and SMMC-7721 cells, which could be crippled by miR-485-5p inhibitor. Besides, the expression of basigin (BSG) was decreased after lncRNA RHPN1-AS1 silence, indicating the function of lncRNA RHPN1-AS1/miR-485-5p/BSG axis in HCC progression. Our study opens novel insights to help understand the mechanisms of lncRNA RHPN1-AS1/miR-485-5p/BSG axis in HCC progression, which may provide a new therapeutic target for HCC treatment.
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- 2020
4. Up‐regulation of long non‐coding RNA THRIL in coronary heart disease: Prediction for disease risk, correlation with inflammation, coronary artery stenosis, and major adverse cardiovascular events
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Haijun Qi, Jie Shen, and Wenping Zhou
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Male ,0301 basic medicine ,Clinical Biochemistry ,Coronary Disease ,Correlation ,0302 clinical medicine ,Immunology and Allergy ,Research Articles ,Hematology ,Middle Aged ,Prognosis ,Long non-coding RNA ,Up-Regulation ,Medical Laboratory Technology ,Cardiovascular Diseases ,030220 oncology & carcinogenesis ,Cardiology ,Cytokines ,Female ,RNA, Long Noncoding ,medicine.symptom ,Research Article ,Microbiology (medical) ,medicine.medical_specialty ,Inflammation ,Proinflammatory cytokine ,03 medical and health sciences ,Downregulation and upregulation ,Internal medicine ,Diabetes mellitus ,medicine ,Humans ,Genetic Predisposition to Disease ,cardiovascular diseases ,coronary heart disease ,long non‐coding RNA THRIL ,Aged ,Receiver operating characteristic ,business.industry ,Biochemistry (medical) ,Coronary Stenosis ,Public Health, Environmental and Occupational Health ,medicine.disease ,major adverse cardiovascular events ,disease risk ,030104 developmental biology ,Gene Expression Regulation ,Case-Control Studies ,business ,Mace - Abstract
Objective This study aimed to investigate the role of long non‐coding RNA (lncRNA) THRIL in coronary heart disease (CHD) patients. Methods A total of 420 patients who underwent coronary arteriography due to suspected symptoms of CHD were enrolled, in which 220 were diagnosed as CHD and 200 were set as control subjects. LncRNA THRIL in plasma samples of CHD patients and control subjects was detected by reverse transcription‐quantitative polymerase chain reaction. Gensini score and biochemical indexes were evaluated in CHD patients and control subjects. Plasma inflammatory cytokines were detected, and major adverse cardiovascular events (MACE) were recorded in CHD patients. Results Both before and after adjustment by age/gender, lncRNA THRIL was increased in CHD patients compared with control subjects (both P
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- 2020
5. 14-3-3ζ binds to hepatitis B virus protein X and maintains its protein stability in hepatocellular carcinoma cells
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Zhongyi Sun, Longfei Li, Yufu Tang, Wenping Zhou, Yibing Zhang, Chunhui Wang, and Jiahong Dong
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0301 basic medicine ,Cancer Research ,14‐3‐3ζ ,viruses ,medicine.disease_cause ,Mice ,0302 clinical medicine ,Cell Movement ,Viral Regulatory and Accessory Proteins ,Original Research ,Cancer Biology ,Portal Vein ,Protein Stability ,Chemistry ,Liver Neoplasms ,hepatocellular carcinoma ,Gene Expression Regulation, Neoplastic ,Molecular Docking Simulation ,HBx ,Oncology ,030220 oncology & carcinogenesis ,Phosphorylation ,Signal Transduction ,Hepatitis B virus ,Carcinoma, Hepatocellular ,03 medical and health sciences ,Cell Line, Tumor ,Hypertension, Portal ,medicine ,Animals ,Humans ,Akt signaling pathway ,Gene silencing ,Neoplasm Invasiveness ,Radiology, Nuclear Medicine and imaging ,Protein kinase B ,Binding Sites ,Akt/PKB signaling pathway ,portal vein tumor thrombosis ,hepatitis B virus protein X ,digestive system diseases ,030104 developmental biology ,14-3-3 Proteins ,Cancer cell ,Trans-Activators ,Cancer research ,Carcinogenesis ,Proto-Oncogene Proteins c-akt ,Neoplasm Transplantation - Abstract
14‐3‐3ζ, a phosphopeptide‐binding molecule, is reportedly overexpressed in the cancerous tissues of patients with hepatocellular carcinoma (HCC). Hepatitis B virus (HBV) protein X (HBx) draws intensive attention in HBV‐related HCC because it not only regulates HBV replication, but also promotes carcinogenesis by interacting with various tumor or antitumor molecules. This study is performed to investigate whether and how 14‐3‐3ζ interacts with HBx. The coimmunoprecipitation (Co‐IP) results showed that 14‐3‐3ζ bond to HBx in HBV‐infected Hep3B HCC cells and CSQT‐2 portal vein tumor thrombosis (PVTT) cells. By performing Co‐IP assay in HBV‐free Huh7 cells expressing wild‐type HBx, mutant HBx‐S31A, or HBx‐S31D (serine31 was mutated into alanine31 or aspartic acid31), we found that the phosphorylated serine31 with its near amino acid residues constituted a RPLphosphoS31 GP (R, arginine; P, proline; L, leucine; S, serine; G, glycine) motif in HBx for 14‐3‐3ζ docking. This 14‐3‐3ζ‐HBx interaction was partly impaired when Akt signaling transduction was blocked by LY294002. Furthermore, 14‐3‐3ζ silencing augmented HBx ubiquitination and decreased its expression in cancer cells and xenograft tumor. The migratory and invasive abilities of CSQT‐2 cells were inhibited upon 14‐3‐3ζ silencing, whereas partly restored by HBx overexpression. Additionally, 14‐3‐3ζ positively correlated with HBx to be overexpressed in the primary HCC tissues (r = 0.344) and metastatic PVTT (r = 0.348). In summary, findings of this study reveal a novel 14‐3‐3ζ‐HBx interaction in HCC cells and suggest 14‐3‐3ζ as a candidate target for treating HBV‐related HCC.
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- 2018
6. Overexpression of PCK1 Gene Antagonizes Hepatocellular Carcinoma Through the Activation of Gluconeogenesis and Suppression of Glycolysis Pathways
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Longfei Li, Shu-Qun Cheng, Chunhui Wang, Wenping Zhou, Yufu Tang, Yibing Zhang, and Zhongyi Sun
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0301 basic medicine ,Carcinoma, Hepatocellular ,Physiology ,Hepatocellular carcinoma ,Mice, Nude ,Apoptosis ,lcsh:Physiology ,Flow cytometry ,lcsh:Biochemistry ,03 medical and health sciences ,chemistry.chemical_compound ,PCK1 ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Glycolysis ,Phosphoenolpyruvate carboxykinase 1 ,lcsh:QD415-436 ,neoplasms ,Mice, Inbred BALB C ,medicine.diagnostic_test ,lcsh:QP1-981 ,Chemistry ,Liver Neoplasms ,Intracellular Signaling Peptides and Proteins ,Gluconeogenesis ,Genetic Therapy ,Hep G2 Cells ,digestive system diseases ,Up-Regulation ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,Liver ,Cell culture ,Cancer research ,Phosphoenolpyruvate Carboxykinase (GTP) ,Pyruvic acid ,Phosphoenolpyruvate carboxykinase - Abstract
Background/Aims: Gluconeogenesis, a reverse process of glycolysis, is suppressed in neoplastic livers. Cytoplasmic phosphoenolpyruvate carboxykinase (PEPCK-C/PCK1, encoded by PCK1) is a step limiting enzyme of gluconeogenesis. The induced expression of the factor is reported to initiate gluconeogenesis process and antagonize hepatocellular carcinoma (HCC). In the current study, the effect of the modulation of PCK1 expression on HCC was assessed. Methods: The levels of PCK1 in clinical HCC tissues and different HCC cell lines were investigated with real time quantitative PCR, immunochemistry, and western blotting. Thereafter, the expression of PCK1 gene was induced in two HCC cell lines and the effect of the overexpression on proliferation and migration potentials of HCC cells was detected with CCK-8 assay, flow cytometry, TUNEL staining, and transwell assay. The activities of glycolysis and gluconeogenesis pathways in PCK1-overexpressed HCC cell lines were detected with specific kits to underlie the mechanism by which PCK1 exerted its function. The results of the in vitro experiments were validated with HCC xenograft rat models. Results: The expression levels of PCK1 were suppressed in HCC samples and in cells derived from HCC tissues. According to the results of the in vitro assays, the overexpression of PCK1 decreased viability, induced apoptosis, and inhibited migration in both HCC cell lines. The effect was associated with the suppressed glycolysis and the induced gluconeogenesis pathways, represented by the enhanced production of glucose and the limited production of pyruvic acid, lactate, citrate, and malate. The results of the in vitro assays were confirmed in rat models in that the growth rate of solid HCC tumors was reduced in mice transplanted with PCK1-overexpressed HCC cells. Conclusion: Findings outlined in the current study demonstrated that activating gluconeogenesis process via PCK1 overexpression was a potential treating strategy against HCC.
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- 2018
7. Co-Upregulation of 14-3-3ζ and P-Akt is Associated with Oncogenesis and Recurrence of Hepatocellular Carcinoma
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Yufu Tang, Wenping Zhou, Shu-Qun Cheng, Ruoyu Wang, Na Qiao, Zhongyi Sun, Shenhui Lin, and Yibing Zhang
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0301 basic medicine ,Male ,Carcinoma, Hepatocellular ,Physiology ,Hepatocellular carcinoma ,Mice, Nude ,medicine.disease_cause ,lcsh:Physiology ,14-3-3ζ ,lcsh:Biochemistry ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Downregulation and upregulation ,Cell Line, Tumor ,Medicine ,Animals ,Humans ,Clinical significance ,lcsh:QD415-436 ,Hepatitis B e Antigens ,PI3K/AKT/mTOR pathway ,Aged ,Mice, Inbred BALB C ,Tissue microarray ,lcsh:QP1-981 ,business.industry ,Akt/PKB signaling pathway ,Liver Neoplasms ,Middle Aged ,medicine.disease ,Hypoxia-Inducible Factor 1, alpha Subunit ,Prognosis ,digestive system diseases ,P-Akt ,Up-Regulation ,030104 developmental biology ,14-3-3 Proteins ,Liver ,030220 oncology & carcinogenesis ,Concomitant ,Cancer research ,Female ,business ,Carcinogenesis ,Proto-Oncogene Proteins c-akt ,Signal Transduction - Abstract
Background/Aims: 14-3-3ζ is involved in the regulation of PI3K/Akt pathway which is closely associated with carcinogenesis. However, the clinical significance of combined detection of 14-3-3ζ and p-Akt in hepatocellular carcinoma (HCC) remains unclear. Methods: Two-hundred pairs of HCC and adjacent liver specimens were subjected to tissue microarray. The association of 14-3-3ζ and p-Akt levels with the postoperative survival and recurrence in HCC patients was analyzed with univariate and multivariate methods. Moreover, the effects of 14-3-3ζ overexpression on the growth of HCC and the expressions of p-Akt and HIF-1α were assessed in a xenograft mouse model. Results: Elevated levels of 14-3-3ζ and p-Akt were detected in HCC and a positive correlation between the levels of 14-3-3ζ and p-Akt was verified. HCC patients with satellite nodules, microvascular invasion, portal vein tumor thrombosis, poor tumor differentiation and an advanced tumor stage tended to have higher levels of 14-3-3ζ and p-Akt. In addition, the postoperative 3-, 5-, and 7-year overall survival rates in HCC patients with 14-3-3ζhigh and p-Akthigh were significantly lower compared with those with 14-3-3ζlow and p-Aktlow, and the cumulative recurrence rate in HCC patients with 14-3-3ζhigh and p-Akthigh was significantly higher than that in those with 14-3-3ζlow and p-Aktlow. The multivariate Cox proportional hazard analysis indicated that concomitant upregulation of 14-3-3ζ and p-Akt was an independent factor that predicted poor survival and high recurrence in HCC patients. Furthermore, animal experiment showed that overexpression of 14-3-3ζ accelerated the growth of HCC xenograft tumors and induced the expressions of p-Akt and HIF-1α in vivo. Conclusion: Co-upregulation of 14-3-3ζ and p-Akt predicts poor prognosis in patients with HCC, and 14-3-3ζ-induced activation of the Akt signaling pathway contributes to HCC progression.
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- 2018
8. PLCE1 Promotes Esophageal Cancer Cell Progression by Maintaining the Transcriptional Activity of Snail
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Cui Liu, Sifan Yu, Jinghang Zhang, Hui Wang, Zhijun Chen, Wang Weilong, Shicong Zhai, Wenping Zhou, Xiu-Min Li, Jian Zhu, Ting Zhuang, Yijun Qi, Lichen Zhang, Tingmin Chang, Jiqiang Guo, Siguang Xu, and Na Yu
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0301 basic medicine ,Regulation of gene expression ,Cancer Research ,PLCE1 ,Cell ,Snail ,Biology ,Esophageal cancer ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,lcsh:RC254-282 ,Transcriptome ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,biology.animal ,Carcinoma ,medicine ,Cancer research ,Gene silencing - Abstract
Esophageal cancer is among the most deadly malignant diseases. However, the genetic factors contributing to its occurrence are poorly understood. Multiple studies with large clinic-based cohorts revealed that variations of the phospholipase C epsilon (PLCE1) gene were associated with esophageal cancer susceptibility. However, the causative role of PLCE1 in esophageal cancer is not clear. We inactivated the functional alleles of PLCE1 by CRISPR/Cas9 genome editing technology. The resultant PLCE1 inactivated cells were analyzed both in vitro and in vivo. Our results showed that loss of PLCE1 dramatically decreased the invasion and proliferation capacity of esophageal carcinoma cells in vitro. Moreover, such PLCE1 inactivated tumor grafts exhibited significantly decreased tumor size in mice. We found that PLCE1 was required to maintain protein level of snail a key transcription factor responsible for invasion. Our further transcriptomic data revealed that deficient cells were significantly decreased in expression of genes enriched as targets of Snail. Strikingly, recovery of Snail protein at least partially rescued the invasion and proliferation capacity in PLCE1 inactivated cells. In ESCC clinical specimens, PLCE1 was correlated with tumor stage (P
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- 2017
9. A retrospective clinical study of comparing paclitaxel plus S-1 versus paclitaxel plus cisplatin as the first-line treatment for patients with advanced esophageal squamous cell carcinoma
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Shujun Yang, Suxia Luo, Haiying Wang, Wenping Zhou, Zhihua Yao, Hong Tang, Shuiling Jin, Yanyan Liu, Shuna Yao, and Yan Zhao
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Male ,0301 basic medicine ,Oncology ,Time Factors ,Esophageal Neoplasms ,cisplatin ,Kaplan-Meier Estimate ,advanced esophageal squamous cell carcinoma ,chemistry.chemical_compound ,0302 clinical medicine ,Antineoplastic Combined Chemotherapy Protocols ,Leukopenia ,S-1 ,Middle Aged ,Drug Combinations ,Treatment Outcome ,Paclitaxel ,030220 oncology & carcinogenesis ,Carcinoma, Squamous Cell ,Disease Progression ,Female ,Esophageal Squamous Cell Carcinoma ,medicine.symptom ,Research Paper ,medicine.drug ,Adult ,China ,medicine.medical_specialty ,Neutropenia ,Tegafur ,Disease-Free Survival ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,palliative chemotherap ,Survival analysis ,Aged ,Retrospective Studies ,Cisplatin ,Gynecology ,business.industry ,Cancer ,medicine.disease ,Oxonic Acid ,Regimen ,030104 developmental biology ,chemistry ,business - Abstract
// Hai-ying Wang 1 , Zhi-hua Yao 1 , Hong Tang 1 , Yan Zhao 1 , Shui-ling Jin 2 , Wen-ping Zhou 1 , Shu-na Yao 1 , Shu-jun Yang 1 , Yan-yan Liu 1 , Su-xia Luo 1 1 Department of Medical Oncology of Henan Cancer Hospital, Zhengzhou University Affiliated Cancer Hospital, Zhengzhou, Henan, China 2 Department of Internal Medicine, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China Correspondence to: Su-xia Luo, email: 470242877@qq.com Hai-ying Wang, email: luosxrm@163.com Keywords: advanced esophageal squamous cell carcinoma, Paclitaxel, S-1, cisplatin, palliative chemotherap Received: July 18, 2016 Accepted: November 14, 2016 Published: November 25, 2016 ABSTRACT Background: In advanced esophageal squamous cell carcinoma (ESCC), paclitaxel plus cisplatin are considered as active and tolerable. The current clinical study was conducted to retrospectively compare the efficacy and safety of first-line paclitaxel/S-1(PS) and paclitaxel/cisplatin(TP) regimens in advanced ESCC. Results: The overall response rate of PS was slightly, but not significantly, higher (25 patients, 46%) than that of TP (23 patients, 39%, P = 0.432). Median overall survival (OS) was similar for PS and TP (11.5 months vs. 10.4 months, p = 0.37). However PS had longer median progression-free survival than TP (PFS: 5.5 months vs5.0months, p = 0.04). When compared with PS, more grade 3 or 4 adverse events were recorded for TP, including leukopenia, neutropenia, anemia, anorexia and vomiting ( P < 0.05). No treatment-related deaths were recorded in either group. Patients and Methods: Between 2008 and 2014, all patients diagnosed with advanced ESCC and treated with paclitaxel/S-1 or paclitaxel/cisplatin at Cancer Hospital Affiliated to Zhengzhou University were analyzed retrospectively. One hundred and thirteen patients were included in this study. Disease control rates and progression-free survival (PFS) and overall survival (OS) were recorded. Survival analysis was calculated by using Kaplan–Meier method. Conclusions: The PS option improves PFS and its OS is similar to TP. Moreover, the PS regimen is an effective and safe first-line treatment for ESCC with less hematological and non-hematological toxicity.
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- 2016
10. Potential of circulating pro‐angiogenic microRNA expressions as biomarkers for rapid angiographic stenotic progression and restenosis risks in coronary artery disease patients underwent percutaneous coronary intervention
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Yi Zhou, Weijuan Li, Xiaoju Xiong, Wenping Zhou, Wei Zhou, Yijue Liu, Manhua Chen, and Rui Dai
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0301 basic medicine ,Microbiology (medical) ,pro‐angiogenesis microRNA ,Male ,medicine.medical_specialty ,Multivariate analysis ,rapid angiographic stenotic progression ,medicine.medical_treatment ,Clinical Biochemistry ,Neovascularization, Physiologic ,Coronary Artery Disease ,Coronary Angiography ,Coronary artery disease ,Coronary Restenosis ,03 medical and health sciences ,restenosis ,0302 clinical medicine ,Text mining ,Restenosis ,Risk Factors ,Internal medicine ,microRNA ,medicine ,Immunology and Allergy ,Humans ,Circulating MicroRNA ,Research Articles ,business.industry ,Rasp ,Biochemistry (medical) ,percutaneous coronary intervention ,Public Health, Environmental and Occupational Health ,Coronary Stenosis ,Percutaneous coronary intervention ,Hematology ,Middle Aged ,medicine.disease ,Medical Laboratory Technology ,030104 developmental biology ,Gene Expression Regulation ,ROC Curve ,030220 oncology & carcinogenesis ,Conventional PCI ,Cardiology ,Female ,business ,Biomarkers ,Research Article - Abstract
Background This study aimed to investigate the correlation of pro‐angiogenic microRNA (miRNA) expressions with rapid angiographic stenotic progression (RASP) and restenosis risks in coronary artery disease (CAD) patients underwent percutaneous coronary intervention (PCI) with drug‐eluting stents (DES). Methods A total of 286 CAD patients underwent PCI with DES were consecutively recruited in this study. Plasma samples were collected before PCI operation, and 14 pro‐angiogenic miRNAs were measured by real‐time quantitative reverse transcription‐polymerase chain reaction. Rapid angiographic stenotic progression at nontarget lesions and restenosis at stented lesions were evaluated by quantitative coronary angiography at 12 months after PCI operation. Results The occurrence rates of RASP and restenosis were 39.5% and 22.4%, respectively. Let‐7f, miR‐19a, miR‐19b‐1, miR‐92a, miR‐126, miR‐210, and miR‐296 were decreased in RASP patients than non‐RASP patients, among which let‐7f, miR‐19a, miR‐126, miR‐210, and miR‐296 independently correlated with lower RASP occurrence by multivariate analysis, followed by receiver‐operating characteristic (ROC) curve exhibited that these five miRNAs showed great value in predicting RASP risk with area under curve (AUC) 0.879 (95% CI: 0.841‐0.917). Besides, let‐7f, miR‐19a, miR‐92a, miR‐126, miR‐130a, and miR‐210 were reduced in restenosis patients than non‐restenosis patients, among them miR‐19a, miR‐126, miR‐210, and miR‐378 independently correlated with lower restenosis occurrence by multivariate analysis, followed by ROC curve disclosed that these four miRNAs had good value in predicting restenosis risk with AUC 0.776 (95% CI: 0.722‐0.831). Conclusions Circulating let‐7f, miR‐19a, miR‐126, miR‐210, and miR‐296 independently correlate with reduced RASP risk, while miR‐19a, miR‐126, miR‐210, and miR‐378 independently correlate with decreased restenosis risk in CAD patients underwent PCI with DES.
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- 2019
11. The effects of lncRNA MALAT1 on proliferation, invasion and migration in colorectal cancer through regulating SOX9
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Xihong Zhang, Wenping Zhou, Yanyan Liu, Peipei Zhang, Yuanlin Xu, Xiufeng Hu, Jiuyang Zhang, and Shujun Yang
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0301 basic medicine ,Cell ,Mice, Nude ,Biology ,Metastasis ,lcsh:Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,Cell Movement ,Cell Line, Tumor ,microRNA ,Genetics ,medicine ,Animals ,Gene silencing ,lcsh:QD415-436 ,Molecular Biology ,Genetics (clinical) ,Cell Proliferation ,Mice, Inbred BALB C ,MALAT1 ,lncRNA MALAT1 ,Cell growth ,lcsh:RM1-950 ,Cancer ,SOX9 Transcription Factor ,Cell cycle ,miR-145 ,medicine.disease ,Colorectal cancer ,MicroRNAs ,lcsh:Therapeutics. Pharmacology ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Cancer research ,Molecular Medicine ,Female ,RNA, Long Noncoding ,Colorectal Neoplasms ,SOX9 ,Research Article - Abstract
Background For the study, we determine the potential biomarkers and uncover the regulatory mechanisms of lncRNA MALAT1 / miR-145 / SOX9 axis on the abilities of cell growth and cell metastasis of colorectal cancer. Methods Previously published dataset GSE18105 from GEO database was used for microarray analysis to identify differential-expressed lncRNAs and mRNAs. The miRNA which had targeted relationships with both lncRNA and mRNA was predicted using miRCode and Targetscan. The association between lncRNA and miRNA, miRNA and mRNA was verified using dual-luciferase reporter assay. Expression levels of lncRNA MALAT1, miR-145 and SOX9 were examined by quantitative RT-PCR analysis. The cell viability of two cancer cell lines was compared by CCK-8 assay. Colony formation was hired to detected cell proliferation. The cell cycle distribution and apoptotic cell rate were conducted by flow cytometry assay. Wound healing as well as transwell assay were compare the cell migration and cell invasion respectively among groups. The effect of MALAT1 on colorectal cancer in vivo was constructed by xenograft model. Results Significantly dysregulated lncRNAs and mRNAs were identified by microarray analysis. By experimental verification, MALAT1 and SOX9 were expressed in a high percentage of colorectal cancer tumors and cells, while miR-145 was in a low expression. We also identified miR-145 as a target of MALAT1 and SOX9. MALAT1 played a role in regulating cancer process by functioning as a competing endogenous RNA. Silencing MALAT1 could effectively decrease the expression level of SOX9, thus suppress cell viability and metastasis. Down-regulated MALAT1 could induce resistance of G1 phase in cell cycle, and facilitation of colorectal cancer cell apoptosis. Nude mice injected with cells transfected with si-MALAT1 had smaller tumor on size and weight. Conclusions The regulatory function of lncRNA MALAT1 / miR-145 / SOX9 axis was revealed in colorectal cancer based on bioinformatics analysis. LncRNA MALAT1 could facilitate colorectal cancer cell proliferation, invasion and migration by down-regulating miR-145 and up-regulating SOX9. LncRNA MALAT1 could suppress cell cycle and apoptosis through MALAT1 / miR-145 / SOX9 axis.
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- 2018
12. CLOCK phosphorylation by AKT regulates its nuclear accumulation and circadian gene expression in peripheral tissues
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Amelia K. Luciano, William C. Sessa, Wenping Zhou, Cleo Kyriakides, Heino Velazquez, and Jeans M. Santana
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0301 basic medicine ,Male ,Active Transport, Cell Nucleus ,CLOCK Proteins ,Biochemistry ,Substrate Specificity ,03 medical and health sciences ,Mice ,Animals ,Humans ,Circadian rhythm ,Gene Knock-In Techniques ,Phosphorylation ,Molecular Biology ,Transcription factor ,Regulation of gene expression ,NPAS2 ,Chemistry ,Cell Biology ,Cell biology ,Circadian Rhythm ,PER2 ,Mice, Inbred C57BL ,030104 developmental biology ,HEK293 Cells ,Gene Expression Regulation ,NIH 3T3 Cells ,Editors' Picks Highlights ,Female ,Proto-Oncogene Proteins c-akt ,Cell Nucleolus ,PER1 - Abstract
Circadian locomotor output cycles kaput (CLOCK) is a transcription factor that activates transcription of clock-controlled genes by heterodimerizing with BMAL1 and binding to E-box elements on DNA. Although several phosphorylation sites on CLOCK have already been identified, this study characterizes a novel phosphorylation site at serine 845 (Ser-836 in humans). Here, we show that CLOCK is a novel AKT substrate in vitro and in cells, and this phosphorylation site is a negative regulator of CLOCK nuclear localization by acting as a binding site for 14-3-3 proteins. To examine the role of CLOCK phosphorylation in vivo, ClockS845A knockin mice were generated using CRISPR/Cas9 technology. ClockS845A mice are essentially normal with normal central circadian rhythms and hemodynamics. However, examination of core circadian gene expression from peripheral tissues demonstrated that ClockS845A mice have diminished expression of Per2, Reverba, Dbp, and Npas2 in skeletal muscle and Per2, Reverba, Dbp, Per1, Rora, and Npas2 in the liver during the circadian cycle. The reduction in Dbp levels is associated with reduced H3K9ac at E-boxes where CLOCK binds despite no change in total CLOCK levels. Thus, CLOCK phosphorylation by AKT on Ser-845 regulates its nuclear translocation and the expression levels of certain core circadian genes in insulin-sensitive tissues.
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- 2017
13. The AMPK Agonist PT1 and mTOR Inhibitor 3HOI-BA-01 Protect Cardiomyocytes After Ischemia Through Induction of Autophagy
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Xiaoling Wang, Wei Zhou, Ling Huang, Manhua Chen, Wenping Zhou, Jing Chen, and Kai Dai
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Male ,0301 basic medicine ,Agonist ,medicine.medical_specialty ,Indoles ,medicine.drug_class ,Myocardial Infarction ,Apoptosis ,Myocardial Reperfusion Injury ,AMP-Activated Protein Kinases ,Pharmacology ,Mice ,03 medical and health sciences ,Downregulation and upregulation ,Internal medicine ,Autophagy ,medicine ,Animals ,Myocytes, Cardiac ,Pharmacology (medical) ,Benzodioxoles ,Protein kinase A ,Protein Kinase Inhibitors ,Cells, Cultured ,PI3K/AKT/mTOR pathway ,business.industry ,TOR Serine-Threonine Kinases ,RPTOR ,AMPK ,Adenosine ,Cell Hypoxia ,meta-Aminobenzoates ,Mice, Inbred C57BL ,Oxygen ,Disease Models, Animal ,Thiazoles ,Glucose ,030104 developmental biology ,Endocrinology ,Animals, Newborn ,Cytoprotection ,Cardiology and Cardiovascular Medicine ,business ,Signal Transduction ,medicine.drug - Abstract
Myocardial ischemia has become one of the main causes of sudden cardiac death worldwide. Autophagy has been demonstrated to protect cardiomyocytes from ischemia/reperfusion (I/R)-induced damage. A novel small molecule compound 2-Chloro-5-[[5-[[5-(4,5-Dimethyl-2-nitrophenyl)-2-furanyl]methylene]-4,5-dihydro-4-oxo-2-thiazolyl]amino]benzoic acid (PT1) has been previously shown to specifically activate 5′-adenosine monophosphate-activated protein kinase (AMPK). Because AMPK activation effectively induces autophagy, we tested the protective efficacy of PT1 on cardiomyocytes after oxygen glucose deprivation/reoxygenation (OGD/R) in vitro. Mouse neonatal cardiomyocytes were treated with PT1 after OGD/R. 3-[4-(1,3-benzodioxol-5-yl)-2-oxo-3-buten-1-yl]-3-hydroxy-1,3-dihydro-2H-indol-2-one (3HOI-BA-01), a novel small compound showing potent inhibitory effect on mammalian target of rapamycin (mTOR) activation, was also tested for its cardioprotective effect, based on the established relationship between mTOR signaling and autophagy. Cell survival and autophagy-related signal pathways were examined after treatment with these agents. Our data indicate that both PT1 and 3HOI-BA-01 enhance cell survival after OGD/R. As expected, both PT1 and 3HOI-BA-01 induced autophagy in cardiomyocytes through activating AMPK pathway and inhibiting mTOR signaling, respectively. Induction of autophagy by PT1 and 3HOI-BA-01 was responsible for their cardioprotective effect, since inhibition of autophagy abolished the protective efficacy. Furthermore, simultaneous administration of PT1 and 3HOI-BA-01 profoundly upregulated autophagy after OGD/R and significantly promoted survival of cardiomyocytes. In vivo administration of PT1 and 3HOI-BA-01 in a murine myocardial (I/R injury model remarkably reduced infarct size and induced autophagy. Taken together, our research suggests that PT1 and 3HOI-BA-01 could be promising therapeutic agents for myocardial ischemia.
- Published
- 2015
14. MMP-2 together with MMP-9 overexpression correlated with lymph node metastasis and poor prognosis in early gastric carcinoma
- Author
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Shuna Yao, Junfeng Chu, Haiying Wang, Yuanlin Xu, Zhihua Yao, Yanyan Liu, Shuiling Jin, Ying Liu, Shujun Yang, Tian Yuan, Yan Zhao, and Wenping Zhou
- Subjects
0301 basic medicine ,Oncology ,Adult ,Male ,medicine.medical_specialty ,Poor prognosis ,Lymph node metastasis ,Matrix (biology) ,Matrix metalloproteinase ,03 medical and health sciences ,0302 clinical medicine ,Stomach Neoplasms ,Internal medicine ,medicine ,Carcinoma ,Biomarkers, Tumor ,Humans ,RC254-282 ,Aged ,Neoplasm Staging ,business.industry ,Proportional hazards model ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,General Medicine ,Middle Aged ,medicine.disease ,Prognosis ,Early Gastric Cancer ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,Matrix Metalloproteinase 9 ,030220 oncology & carcinogenesis ,Lymphatic Metastasis ,Cancer research ,Immunohistochemistry ,Matrix Metalloproteinase 2 ,Female ,business - Abstract
The aim of this study was to correlate matrix metalloproteinase-2 and matrix metalloproteinase-9 expression with the clinicopathological features and outcome of patients with early gastric cancer and to clinically elucidate more information on the role of matrix metalloproteinase-2 and matrix metalloproteinase-9 protein overexpression with regard to lymph node metastasis of early gastric cancer. The levels of matrix metalloproteinase-2 and matrix metalloproteinase-9 protein expression were assessed by immunohistochemistry. An association was observed between matrix metalloproteinase-2, matrix metalloproteinase-9, and matrix metalloproteinase-2/matrix metalloproteinase-9 overexpression and clinicopathological factors, such as ulceration and lymph node metastasis. Furthermore, matrix metalloproteinase-9 and matrix metalloproteinase-2/matrix metalloproteinase-9 overexpression both were strongly correlated with histological grade. In addition, matrix metalloproteinase-2/matrix metalloproteinase-9 overexpression correlated with deep invasion. Multivariate Cox regression analysis revealed that matrix metalloproteinase-2 and matrix metalloproteinase-9 expression were both independent factors of overall survival in patients with early gastric cancer. In novelty, we found that matrix metalloproteinase-2/matrix metalloproteinase-9 overexpression was an independent indicator of lymph node metastasis in early gastric cancer which will be helpful in clinic to select the appropriate treatment of these patients.
- Published
- 2017
15. Genome-wide RNAi screen reveals ALK1 mediates LDL uptake and transcytosis in endothelial cells
- Author
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Michael G. Sugiyama, Cristina M. Ramírez, Michael W. Nagle, Bruno Larrivée, Eon Joo Park, Jan R. Kraehling, Keyang Chen, Warren L. Lee, Noemi Rotllan, Joseph W. Fowler, John H. Chidlow, Anne Eichmann, Roxana Ola, Xinbo Zhang, Carlos Fernández-Hernando, Wenping Zhou, William C. Sessa, Joachim Herz, Kevin Jon Williams, Bo Tao, Monica Y. Lee, Chitra Rajagopal, Ewa Folta-Stogniew, and Leena Kuruvilla
- Subjects
Male ,0301 basic medicine ,Low-density lipoprotein receptor gene family ,Endothelium ,Science ,Activin Receptors, Type II ,General Physics and Astronomy ,Biology ,Genome ,Article ,General Biochemistry, Genetics and Molecular Biology ,Mice ,03 medical and health sciences ,medicine ,Animals ,Humans ,Cloning, Molecular ,Receptor ,Cells, Cultured ,Apolipoproteins B ,Multidisciplinary ,Endothelial Cells ,Biological Transport ,Cholesterol, LDL ,General Chemistry ,Cell biology ,Lipoproteins, LDL ,Rnai screen ,Cholesterol ,030104 developmental biology ,medicine.anatomical_structure ,Transcytosis ,Gene Knockdown Techniques ,LDL receptor ,cardiovascular system ,RNA Interference ,lipids (amino acids, peptides, and proteins) ,Activin Receptors, Type I ,Genome-Wide Association Study ,Lipoprotein - Abstract
In humans and animals lacking functional LDL receptor (LDLR), LDL from plasma still readily traverses the endothelium. To identify the pathways of LDL uptake, a genome-wide RNAi screen was performed in endothelial cells and cross-referenced with GWAS-data sets. Here we show that the activin-like kinase 1 (ALK1) mediates LDL uptake into endothelial cells. ALK1 binds LDL with lower affinity than LDLR and saturates only at hypercholesterolemic concentrations. ALK1 mediates uptake of LDL into endothelial cells via an unusual endocytic pathway that diverts the ligand from lysosomal degradation and promotes LDL transcytosis. The endothelium-specific genetic ablation of Alk1 in Ldlr-KO animals leads to less LDL uptake into the aortic endothelium, showing its physiological role in endothelial lipoprotein metabolism. In summary, identification of pathways mediating LDLR-independent uptake of LDL may provide unique opportunities to block the initiation of LDL accumulation in the vessel wall or augment hepatic LDLR-dependent clearance of LDL., Atherosclerosis is caused by low-density lipoprotein (LDL) buildup in the vessel wall, a process thought to be mediated by LDL receptor alone. Here, the authors show that the endothelium can uptake LDL via ALK1, a TGFβ signalling receptor, suggesting new therapies for blocking LDL accumulation in the vessel wall.
- Published
- 2016
16. Effects of fastigial nucleus electrostimulation on airway inflammation and remodeling in an experimental rat model of asthma
- Author
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Bo Yu, Wenhua Chen, Wen Zhang, Wenping Zhou, Qi Qi, Kunpeng Li, Zhouying Duan, and Ruijuan Zhou
- Subjects
0301 basic medicine ,Budesonide ,Male ,medicine.medical_treatment ,Immunology ,Electric Stimulation Therapy ,Enzyme-Linked Immunosorbent Assay ,Pharmacology ,Immunoglobulin E ,Rats, Sprague-Dawley ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Immunology and Allergy ,Medicine ,Animals ,Fastigial nucleus ,Asthma ,Lung ,biology ,business.industry ,General Medicine ,medicine.disease ,respiratory tract diseases ,Rats ,Disease Models, Animal ,030104 developmental biology ,Cytokine ,medicine.anatomical_structure ,030228 respiratory system ,Cerebellar Nuclei ,biology.protein ,Airway Remodeling ,business ,Airway ,medicine.drug - Abstract
Background: Asthma is a chronic disease involving an immune response, which is characterized by non-specific inflammation and airway remodeling. Glucocorticoids are clinically beneficial in controlling asthma, but further options are needed. In our study, fastigial nucleus electrostimulation (FNS) was applied in a rat asthma model for the first time to investigate the effects of pre-intervention. Objective: To observe the effects of FNS on airway inflammation and remodeling in asthmatic rats. Methods: Forty rats were assigned randomly to the normal control (CON), model (MDL), FNS, or budesonide (BUD) groups. Asthma was induced with chicken egg (OVA). The animals in the CON and MDL groups were treated with normal saline. The animals in the other two groups received FNS or budesonide, respectively. Results: The results indicated that IgE in the serum and airway fiber areas were higher in the MDL group than in other groups. After treatment for 3 weeks, collagen fibers in the bronchial wall in the FNS group were significantly lower compared with the MDL group. Conclusion: FNS significantly reduced IL-4, IL-13, TNF-α, OVA-IgE and TGF-β1 in serum and BALF, and increased IFN-γ. Our results suggest that FNS may ameliorate asthma symptoms and induce changes of cytokines in the serum and lung milieu. Keywords: asthma, rat model, fastigial nucleus electrostimulation, cytokine, airway remodeling DOI 10.12932/AP0705
- Published
- 2016
17. Reply to Fernandez-Marrero et al.: Role of BOK at the intersection of endoplasmic reticulum stress and apoptosis regulation
- Author
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Marcos A. Carpio, Jill K. Fisher, Michael Michaud, Loren D. Walensky, Wenping Zhou, and Samuel G. Katz
- Subjects
0301 basic medicine ,Genetics ,Programmed cell death ,Multidisciplinary ,Thapsigargin ,Endoplasmic reticulum ,ATF4 ,Apoptosis ,Biology ,Endoplasmic Reticulum ,Molecular biology ,03 medical and health sciences ,chemistry.chemical_compound ,Oxidative Stress ,030104 developmental biology ,chemistry ,Proto-Oncogene Proteins c-bcl-2 ,medicine ,Unfolded protein response ,Staurosporine ,Animals ,Letters ,Signal transduction ,medicine.drug - Abstract
The B-cell lymphoma 2 (BCL-2) ovarian killer (BOK) is an intriguing BCL-2 family protein with highest homology to the multidomain executioner proteins BAX and BAK, yet its role in apoptosis regulation has been questionable because of the reported absence of phenotypic findings in Bok−/− mice (1). In an independent Bok−/− model, we identify a selective apoptotic defect in response to endoplasmic reticulum (ER) stress (2). Differences in mouse model phenotypes can arise from alternate mouse strains, backgrounds, and targeting strategies. Our Bok−/− mice were backcrossed to C57BL/6 mice for eight generations, and although they contain a short transcript, notably lacking key functional domains, no BOK protein was detected by Western analyses. Ultimately, such differences in modeling approach may or may not impact the functional insights gleaned, but do necessitate rigorous mechanistic validation of the generated hypotheses. Fernandez-Marrero et al. (3) query if: (i) the selective apoptotic defect we attribute to Bok deletion derives instead from a reduction in BCL-2 interacting mediator of cell death (Bim) transcript, (ii) reversal of the apoptotic phenotype upon transient BOK reconstitution is sufficient evidence for its selective role, and (iii) quantitation of our in vivo findings would corroborate the conclusions drawn. First, we confirmed that our immortalized Bok−/− mouse embryonic fibroblasts (MEFs) and Bok−/− livers exhibit equivalent levels of BIM protein compared with the corresponding wild-type specimens (Fig. 1 A and B). Thus, differences in baseline BIM protein levels do not account for the observed phenotype. Importantly, any change in BIM level should similarly affect the apoptotic response to staurosporine, but instead we observed a selective defect in the ER stress response (2). Second, we previously probed the specificity of our Bok−/− phenotype by reconstituting MEFs with BOK protein, which reversed the apoptotic defect. Importantly, we conducted these studies using stable, not transient, BOK expression, thus avoiding any confounding effects of direct apoptosis induction by BOK itself. Intriguingly, transient overexpression of BOK has been shown to induce BIM (4), consistent with our mechanistic hypothesis that BOK functions upstream of ATF4, CHOP, and BIM, but we did not observe differences in BIM levels in the context of stable BOK expression. Finally, quantitation of our in vivo results confirmed that our Bok−/− mice are protected from thapsigargin-induced liver damage. CHOP, cleaved-caspase 3, and TUNEL all exhibit statistically significant decreases in thapsigargin-treated Bok−/− mice compared with wild-type controls (Fig. 1 C and D). To reinforce the physiologic impact of these findings, we further demonstrate a statistically significant survival advantage for Bok−/− mice challenged with thapsigargin (Fig. 1E). Fig. 1. (A and B) Loss of Bok does not affect BIM protein levels. Representative Western blots (A) and imageJ quantification (B) for BIM in SV40-transformed MEFs and livers isolated from wild-type and Bok−/− mice (mean ± SEM, n = 3). Tubulin ... Our finding of a role for BOK at the intersection of apoptosis and ER signaling is consistent with BOK’s ER localization and the observed decrease in the IRE1α branch of the unfolded protein response, as reported for independently derived Bok−/− cells (4). Importantly, we observed similar abnormalities in our Bok−/− combinatorial knock-outs as those previously reported for independently derived animals,* including rare craniofacial defects in Bax−/−Bak−/−Bok−/− mice (Fig. 1E), suggesting that the two models may have more similarities than differences. Additional links between BOK, its splice-forms, and ER signaling pathways are the subject of ongoing investigations that may reinforce a unique role for BOK in the ER stress response.
- Published
- 2016
18. 5-Fluorouracil induces apoptosis of colorectal cancer cells
- Author
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Tao Liu, Jiantao Zhang, Lielin Wang, Wenping Zhou, Chenyao Li, and Chuan He
- Subjects
0301 basic medicine ,Antimetabolites, Antineoplastic ,Colorectal cancer ,medicine.medical_treatment ,Apoptosis ,Mouse model of colorectal and intestinal cancer ,Receptors, G-Protein-Coupled ,Flow cytometry ,03 medical and health sciences ,0302 clinical medicine ,Genetics ,medicine ,Humans ,RNA, Small Interfering ,neoplasms ,Molecular Biology ,Cell Proliferation ,Regulation of gene expression ,Chemotherapy ,medicine.diagnostic_test ,Cell growth ,Chemistry ,General Medicine ,HCT116 Cells ,medicine.disease ,digestive system diseases ,Gene Expression Regulation, Neoplastic ,Blot ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer research ,Fluorouracil ,biological phenomena, cell phenomena, and immunity ,Colorectal Neoplasms - Abstract
5-Fluorouracil (5-FU) is widely used in chemotherapy for treatment of colorectal cancer. Leucine-rich repeat-containing G protein-coupled receptor (LGR) is known to participate in the occurrence and development of breast cancer by regulating the rebirth of tumor vessels. This study aimed to explore the proliferation and apoptosis of HCT116 colorectal cancer cells treated with 5-FU and related molecular mechanisms. 5-FU (20 μg/mL) was used to treat cultured HCT116 cells. An MTT test, flow cytometry, and colony formation assays were used to examine the proliferation and apoptosis of HCT116 cells. Western blotting was applied to detect the expression of the LGR4 protein in HCT116 cells. Small interference RNA or over-expression techniques were used to manipulate LGR4 expression in HCT116 cells and describe the proliferation and apoptosis of HCT116 treated with 5-FU. A dosage of 20 μg/mL 5-FU resulted in a significant decrease in the proliferation and apoptosis of HCT116 cells and significantly decreased expression levels of LGR4. The specific gene silence or over-expression of LGR4 in HCT116 cells increased and decreased the levels of apoptosis in HCT116, respectively. 5-FU induces apoptosis of colorectal cancer cells and inhibits proliferation by suppressing LGR4 proteins.
- Published
- 2016
19. Amelioration of atherosclerosis in apolipoprotein E-deficient mice by combined RNA interference of lipoprotein-associated phospholipase A2 and YKL-40
- Author
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Hui Zhang, Wenjing Zhang, Jin-Ying Zhang, Wenping Zhou, Chang Cao, and Gangqiong Liu
- Subjects
0301 basic medicine ,Apolipoprotein E ,Apolipoprotein B ,Physiology ,lcsh:Medicine ,030204 cardiovascular system & hematology ,Pathology and Laboratory Medicine ,Biochemistry ,Vascular Medicine ,White Blood Cells ,Mice ,Random Allocation ,RNA interference ,0302 clinical medicine ,Animal Cells ,Immune Physiology ,Gene expression ,Medicine and Health Sciences ,lcsh:Science ,Immune Response ,Innate Immune System ,Multidisciplinary ,Fibrous cap ,Lipids ,Nucleic acids ,medicine.anatomical_structure ,Genetic interference ,Cytokines ,Epigenetics ,lipids (amino acids, peptides, and proteins) ,Collagen ,Cellular Types ,medicine.symptom ,Research Article ,musculoskeletal diseases ,Immune Cells ,Immunology ,Genetic Vectors ,Inflammation ,Biology ,03 medical and health sciences ,Signs and Symptoms ,Apolipoproteins E ,Diagnostic Medicine ,Genetics ,medicine ,Animals ,Chitinase-3-Like Protein 1 ,Messenger RNA ,Blood Cells ,Biology and life sciences ,Macrophages ,Lipoprotein-associated phospholipase A2 ,lcsh:R ,Lentivirus ,fungi ,Proteins ,Cell Biology ,Genetic Therapy ,Molecular Development ,Atherosclerosis ,Molecular biology ,Disease Models, Animal ,RAW 264.7 Cells ,030104 developmental biology ,Immune System ,1-Alkyl-2-acetylglycerophosphocholine Esterase ,biology.protein ,RNA ,lcsh:Q ,Collagens ,Developmental Biology - Abstract
To test the hypothesis that combined RNA interference (RNAi) of lipoprotein-associated phospholipase A2 (Lp-PLA2) and YKL-40 is superior to RNAi of Lp-PLA2 or YKL-40 alone in ameliorating atherosclerosis. A total of 120 apolipoprotein E-deficient mice (apoE-/- mice) were randomly divided into five groups, including the vehicle alone, scrambled RNAi, Lp-PLA2 RNAi, YKL-40 RNAi, and combined Lp-PLA2 and YKL-40 RNAi groups. Constrictive collars were used to induce plaque formation. Lp-PLA2 RNAi and YKL-40 RNAi viral suspensions were transduced into carotid plaques of the mice. Carotid plaques were harvested for histological analysis four weeks after viral vector transduction. Inflammatory gene expression in the plasma and atherosclerotic plaques was determined by ELISA and real-time PCR. Four weeks after RNAi, the serum concentration and plaque mRNA expression of Lp-PLA2 and YKL-40 were remarkably attenuated, leading to reduced inflammatory gene expression. Plaques from the Lp-PLA2 or YKL-40 RNAi group showed lower lipid content, higher collagen content, increased fibrous cap thickness, and lower mRNA expressions of MCP-1 and MMP-8 than than those in the vehicle and scramble groups. When compared with the isolated Lp-PLA2 or YKL-40 RNAi group, the combined Lp-PLA2 and YKL-40 RNAi group exhibited higher collagen content and fibrous cap thickness, and lower lipid content and local inflammation. The beneficial effects of RNAi were independent of the plasma lipoprotein profile. Combined RNAi of Lp-PLA2 and YKL-40 is superior to RNAi of Lp-PLA2 or YKL-40 alone in ameliorating atherosclerosis.
- Published
- 2018
20. 14-3-3β Promotes Migration and Invasion of Human Hepatocellular Carcinoma Cells by Modulating Expression of MMP2 and MMP9 through PI3K/Akt/NF-κB Pathway
- Author
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Lei Han, Yufu Tang, Wenping Zhou, Zhongyi Sun, and Pengfei Lv
- Subjects
0301 basic medicine ,Male ,Pathology ,MMP2 ,lcsh:Medicine ,MMP9 ,Metastasis ,Phosphatidylinositol 3-Kinases ,0302 clinical medicine ,Cell Movement ,lcsh:Science ,Aged, 80 and over ,Venous Thrombosis ,Multidisciplinary ,Portal Vein ,Reverse Transcriptase Polymerase Chain Reaction ,Liver Neoplasms ,NF-kappa B ,Middle Aged ,Matrix Metalloproteinase 9 ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Matrix Metalloproteinase 2 ,Female ,RNA Interference ,Signal Transduction ,Research Article ,Adult ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Blotting, Western ,Biology ,03 medical and health sciences ,Cell Line, Tumor ,Carcinoma ,medicine ,Humans ,Neoplasm Invasiveness ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Aged ,lcsh:R ,medicine.disease ,Survival Analysis ,030104 developmental biology ,14-3-3 Proteins ,Cancer research ,Ectopic expression ,lcsh:Q ,Proto-Oncogene Proteins c-akt - Abstract
14-3-3β has been demonstrated to possess the oncogenic potential, and its increased expression has been detected in multiple types of carcinomas. However, majority of previous studies focused on the role of 14-3-3β in tumor cell proliferation and apoptosis, leaving much to be elucidated about its function in tumor cell invasion and metastasis. Hence, the present study aimed to investigate the role of 14-3-3β in the invasion of hepatocellular carcinoma (HCC) cells and the implications in the prognosis of HCC patients. We first examined the expression of 14-3-3β in the primary tumors of HCC patients with or without portal vein tumor thrombus (PVTT), and found that 14-3-3β expression was higher in the primary tumors with PVTT, and the level was even higher in the PVTTs. Kaplan-Meier curves and multivariate analysis revealed that high expression of 14-3-3β was associated with overall survival (OS) and time to recurrence (TTR) of HCC patients. In addition, ectopic expression of 14-3-3β in HCC cell lines led to enhanced migration ability and invasiveness, as well as up-regulation of matrix metalloproteinase 2 and 9, which could be suppressed by inhibiting the activation of Akt and nuclear factor-κB (NF-κB) signaling. Furthermore, we identified a correlated elevation of 14-3-3β and p-Akt in the primary tumors of HCC patients, and showed that a combinatory detection of 14-3-3β and p-Akt could better predict post-surgical outcome of HCC patients.
- Published
- 2015
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