Anti-tumor Effects of Penfluridol through Dysregulation of Cholesterol Homeostasis

Wu, Lu,Liu, Yan-Yang,Li, Zhi-Xi,Zhao, Qian,Wang, Xia,Yu, Yang,Wang, Yu-Yi,Wang, Yi-Qin,Luo, Feng Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.1

Background: Psychiatric patients appear to be at lower risk of cancer. Some antipsychotic drugs might have inhibitory effects on tumor growth, including penfluridol, a strong agent. To test this, we conducted a study to determine whether penfluridol exerts cytotoxic effects on tumor cells and, if so, to explore its anti-tumor mechanisms. Methods: Growth inhibition of mouse cancer cell lines by penfluridol was determined using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Cytotoxic activity was determined by clonogenic cell survival and trypan blue assays. Animal tumor models of these cancer cells were established and to evaluate penfluridol for its anti-tumor efficacy in vivo. Unesterified cholesterol in cancer cells was examined by filipin staining. Serum total cholesterol and tumor total cholesterol were detected using the cholesterol oxidase/p-aminophenazone (CHOD-PAP) method. Results: Penfluridol inhibited the proliferation of B16 melanoma (B16/F10), LL/2 lung carcinoma (LL/2), CT26 colon carcinoma (CT26) and 4T1 breast cancer (4T1) cells in vitro. In vivo penfluridol was particularly effective at inhibiting LL/2 lung tumor growth, and obviously prolonged the survival time of mice bearing LL/2 lung tumors implanted subcutaneously. Accumulated unesterified cholesterol was found in all of the cancer cells treated with penfluridol, and this effect was most evident in LL/2, 4T1 and CT26 cells. No significant difference in serum cholesterol levels was found between the normal saline-treated mice and the penfluridol-treated mice. However, a dose-dependent decrease of total cholesterol in tumor tissues was observed in penfluridol-treated mice, which was most evident in B16/F10-, LL/2-, and 4T1-tumor-bearing mice. Conclusion: Our results suggested that penfluridol is not only cytotoxic to cancer cells in vitro but can also inhibit tumor growth in vivo. Dysregulation of cholesterol homeostasis by penfluridol may be involved in its anti-tumor mechanisms.

Implementation of online model updating with ANN method in substructure pseudo-dynamic hybrid simulation

Yan Hua Wang,Jing Lv,Yan Feng,Bo Wen Dai,Cheng Wang,Jing Wu,Zi Yan Chen 국제구조공학회 2021 Smart Structures and Systems, An International Jou Vol.28 No.2

Substructure pseudo-dynamic hybrid simulation (SPDHS) is an advanced structural seismic testing method which combines physical experiment and numerical simulation. Generally, the key components which display nonlinearity first are taken as experimental substructures for actual test, and the remaining parts are modeled in simulation. Model updating techniques can be effectively applied to enhance the model precision of nonlinear numerical elements. Specifically, the constitutive model of the experimental substructure is identified online by the instantaneously-measured data, and the corresponding numerical elements with similar hysteretic behaviors are updated synchronously. Artificial neural network (ANN) can recognize the system which cannot be represented by definite numerical model, and thus avoids the structural response distortion caused by the inherent numerical model defects. In this study, a framework for online model updating in SPDHS with ANN method is expanded to implement actual test validation. Moreover, the effectiveness of ANN method is demonstrated by practical tests of a two-story frame model with bending dampers. Additionally, the unscented Kalman filter technique and offline ANN identification approach are both examined in the test validation. The experimental results show that, under the identical loading history, the online ANN method can significantly reduce the model errors and improve the accuracy of SPDHS.

Transiting Exoplanet Monitoring Project (TEMP). IV. Refined System Parameters, Transit Timing Variations, and Orbital Stability of the Transiting Planetary System HAT-P-25

Wang, Xian-Yu,Wang, Songhu,Hinse, Tobias C.,Li, Kai,Wang, Yong-Hao,Laughlin, Gregory,Liu, Hui-Gen,Zhang, Hui,Wu, Zhen-Yu,Zhou, Xu,Zhou, Ji-Lin,Hu, Shao-Ming,Wu, Dong-Hong,Peng, Xi-Yan,Chen, Yuan-Yuan Astronomical Society of the Pacific 2018 Publications of the Astronomical Society of the Pa Vol.130 No.988

Relationship between EGFR Over-expression and Clinicopathologic Characteristics in Squamous Cell Carcinoma of the Esophagus: A Meta-analysis

Wang, Jun,Yu, Jin-Ming,Jing, Shao-Wu,Guo, Yin,Wu, Ya-Jing,Li, Na,Jiao, Wen-Peng,Wang, Li,Zhang, Yan-Jun Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.14

Over-expression of epidermal growth factor receptor (EGFR) has been identified as a common feature associated with clinical outcome in many types of cancer, including squamous cell carcinoma of the oesophagus (SCCO). However, the clinical importance of EGFR over-expression in SCCO remains unsettled as conflicting results exist. Therefore we carried out the present meta-analysis of published studies for clarification. A total of 13 studies including 1, 150 patients were enrolled. EGFR over-expression was positive in 722 of these cases. With EGFR over-expression, patients had higher depth of invasion, vascular invasion, and poor prognosis. However, expression had no relation with degree of differentiation, histological grade, lymph node metastasis, clinical stage or lymphatic invasion. EGFR over-expression is probably a valuable predictor for the T stage, vascular invasion and OS, and it could be used as a poor prognosis indicator for the esophageal SCC patients. Targeting therapy to EFGR should be considered to the combined treatment in SCCO.

Prognostic Value of MGMT Promoter Methylation and TP53 Mutation in Glioblastomas Depends on IDH1 Mutation

Wang, Kai,Wang, Yin-Yan,Ma, Jun,Wang, Jiang-Fei,Li, Shao-Wu,Jiang, Tao,Dai, Jian-Ping Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.24

Several molecular markers have been proposed as predictors of outcome in patients with glioblastomas. We investigated the prognostic significance of $O^6$-methylguanine-DNA methyltransferase (MGMT) promoter methylation and TP53 mutation status dependent on isocitrate dehydrogenase 1 (IDH1) mutation in glioblastoma patients. A cohort of 78 patients with histologically confirmed glioblastomas treated with radiation therapy and chemotherapy were reviewed retrospectively. We evaluated the prognostic value of MGMT promoter methylation and TP53 mutation status with regard to progression-free survival (PFS) and overall survival (OS). It was revealed that mutations in IDH1, promoter methylation of MGMT, TP53 mutation, age, Karnofsky performance status (KFS), and extension of resection were independent prognostic factors. In patients with an IDH1 mutation, those with an MGMT methylation were associated with longer PFS (p=0.016) and OS (p=0.013). Nevertheless, the presence of TP53 mutation could stratify the PFS and OS of patients with IDH1 wild type (p=0.003 and 0.029 respectively, log-rank). The MGMT promoter methylation and TP53 mutation were associated with a favorable outcome of patients with and without mutant IDH1, respectively. The results indicate that glioblastomas with MGMT methylation or TP53 mutations have improved survival that may be influenced by IDH1 mutation status.

Direct Interaction between Ras Homolog Enriched in Brain and FK506 Binding Protein 38 in Cashmere Goat Fetal Fibroblast Cells

Wang, Xiaojing,Wang, Yanfeng,Zheng, Xu,Hao, Xiyan,Liang, Yan,Wu, Manlin,Wang, Xiao,Wang, Zhigang Asian Australasian Association of Animal Productio 2014 Animal Bioscience Vol.27 No.12

Ras homolog enriched in brain (Rheb) and FK506 binding protein 38 (FKBP38) are two important regulatory proteins in the mammalian target of rapamycin (mTOR) pathway. There are contradictory data on the interaction between Rheb and FKBP38 in human cells, but this association has not been examined in cashmere goat cells. To investigate the interaction between Rheb and FKBP38, we overexpressed goat Rheb and FKBP38 in goat fetal fibroblasts, extracted whole proteins, and performed coimmunoprecipitation to detect them by western blot. We found Rheb binds directly to FKBP38. Then, we constructed bait vectors (pGBKT7-Rheb/FKBP38) and prey vectors (pGADT7-Rheb/FKBP38), and examined their interaction by yeast two-hybrid assay. Their direct interaction was observed, regardless of which plasmid served as the prey or bait vector. These results indicate that the 2 proteins interact directly in vivo. Novel evidence is presented on the mTOR signal pathway in Cashmere goat cells.

Identification of novel rheumatoid arthritis-associated MiRNA-204-5p from plasma exosomes

Wu Long-Fei,Zhang Qin,Mo Xing-Bo,Lin Jun,Wu Yang-Lin,Lu Xin,He Pei,Wu Jian,Guo Yu-Fan,Wang Ming-Jun,Ren Wen-Yan,Deng Hong-Wen,Lei Shu-Feng,Deng Fei-Yan 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

Rheumatoid arthritis (RA) is an autoimmune disease characterized by infiltration of immune cells in the synovium. However, the crosstalk of immune cells and synovial fibroblasts is still largely unknown. Here, global miRNA screening in plasma exosomes was carried out with a custom microarray (RA patients vs. healthy controls = 9:9). A total of 14 exosomal miRNAs were abnormally expressed in the RA patients. Then, downregulated expression of exosomal miR-204-5p was confirmed in both the replication (RA patients vs. healthy controls = 30:30) and validation groups (RA patients vs. healthy controls = 56:60). Similar to the findings obtained in humans, a decreased abundance of exosomal miR-204-5p was observed in mice with collagen-induced arthritis (CIA). Furthermore, Spearman correlation analysis indicated that plasma exosomal miR-204-5p expression was inversely correlated with disease parameters of RA patients, such as rheumatoid factor, erythrocyte sedimentation rate, and C-reactive protein. In vitro, our data showed that human T lymphocytes released exosomes containing large amounts of miR-204-5p, which can be transferred into synovial fibroblasts, inhibiting cell proliferation. Overexpression of miR-204-5p in synovial fibroblasts suppressed synovial fibroblast activation by targeting genes related to cell proliferation and invasion. In vivo assays found that administration of lentiviruses expressing miR-204-5p markedly alleviated the disease progression of the mice with CIA. Collectively, this study identified a novel RA-associated plasma exosomal miRNA-204-5p that mediates the communication between immune cells and synovial fibroblasts and can be used as a potential biomarker for RA diagnosis and treatment.

ANN based on forgetting factor for online model updating in substructure pseudo-dynamic hybrid simulation

Yan Hua Wang,Jing Lv,Jing Wu,Cheng Wang 국제구조공학회 2020 Smart Structures and Systems, An International Jou Vol.26 No.1

Substructure pseudo-dynamic hybrid simulation (SPDHS) combining the advantages of physical experiments and numerical simulation has become an important testing method for evaluating the dynamic responses of structures. Various parameter identification methods have been proposed for online model updating. However, if there is large model gap between the assumed numerical models and the real models, the parameter identification methods will cause large prediction errors. This study presents an ANN (artificial neural network) method based on forgetting factor. During the SPDHS of model updating, a dynamic sample window is formed in each loading step with forgetting factor to keep balance between the new samples and historical ones. The effectiveness and anti-noise ability of this method are evaluated by numerical analysis of a six-story frame structure with BRBs (Buckling Restrained Brace). One BRB is simulated in OpenFresco as the experimental substructure, while the rest is modeled in MATLAB. The results show that ANN is able to present more hysteresis behaviors that do not exist in the initial assumed numerical models. It is demonstrated that the proposed method has good adaptability and prediction accuracy of restoring force even under different loading histories.

Diterpenoids from Leonurus japonicus

Wu, Hankui,Wang, Sensheng,Liu, Haijuan,Yan, E.,Wang, Jinjin,Wang, Xiangbei,Wei, Wenchao,Xu, Zhiyong,Sun, Shanshan,Li, Yan,Liu, Ruijin,Li, Gang,Shi, Yunfeng Korean Chemical Society 2015 대한화학회지 Vol.59 No.2

CEA, AFP, CA125, CA153 and CA199 in Malignant Pleural Effusions Predict the Cause

Wang, Xin-Feng,Wu, Yan-Hua,Wang, Mao-Shui,Wang, Yun-Shan Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.1

Determination of the cause of malignant pleural effusions is important for treatment and management, especially in cases of unknown primaries. There are limited biomarkers available for prediction of the cause of malignant pleural effusion in clinical practice. Hence, we evaluated pleural levels of five tumor biomarkers (CEA, AFP, CA125, CA153 and CA199) in predicting the cause of malignant pleural effusion in a retrospective study. Kruskal-Wallis or Mann-Whitney U tests were carried out to compare levels of tumor markers in pleural effusion among different forms of neoplasia - lung squamous cell carcinoma, adenocarcinoma, or small cell carcinoma, mesothelioma, breast cancer, lymphoma/leukemia and miscellaneous. Receiver operator characteristic analysis was performed to evaluate sensitivity and specificity of biomarkers. The Kruskal-Wallis test showed significant differences in levels of pleural effusion CEA (P<0.01), AFP (P<0.01), CA153 (P<0.01) and CA199 (P<0.01), but not CA125 (P>0.05), among the seven groups. Receiver operator characteristic analysis showed that, compared with other four tumor markers, CA153 was the best biomarker in diagnosing malignant pleural effusions of lung adenocarcinoma (area under curve (AUC): 0.838 (95%confidence interval: 0.787, 0.888); cut-off value: 10.2U/ml; sensitivity: 73.2% (64.4-80.8)%, specificity: 85.2% (77.8-90.8)%), lung squamous cell carcinoma (AUC: 0.716 (0.652, 0.780); cut-off value: 14.2U/ml; sensitivity: 57.6% (50.7-64.3)%, specificity: 91.2% (76.3-98.0)%), and small-cell lung cancer (AUC: 0.812 (0.740, 0.884); cut-off value: 9.7U/ml; sensitivity: 61.5% (55.0-67.8)%, specificity: 94.1% (71.2-99.0)%); CEA was the best biomarker in diagnosing MPEs of mesothelioma (AUC: 0.726 (0.593, 0.858); cut-off value: 1.43ng/ml; sensitivity: 83.7% (78.3-88.2)%, specificity: 61.1% (35.8-82.6)%) and lymphoma/leukemia (AUC: 0.923 (0.872, 0.974); cut-off value: 1.71ng/ml; sensitivity: 82.8% (77.4-87.3)%, specificity: 92.3% (63.9-98.7)%). Thus CA153 and CEA appear to be good biomarkers in diagnosing different causes of malignant pleural effusion. Our findings implied that the two tumor markers may improve the diagnosis and treatment for effusions of unknown primaries.