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Deubiquitination and Stabilization of PD-L1 by CSN5
Lim, Seung-Oe,Li, Chia-Wei,Xia, Weiya,Cha, Jong-Ho,Chan, Li-Chuan,Wu, Yun,Chang, Shih-Shin,Lin, Wan-Chi,Hsu, Jung-Mao,Hsu, Yi-Hsin,Kim, Taewan,Chang, Wei-Chao,Hsu, Jennifer L.,Yamaguchi, Hirohito,Ding Elsevier 2016 Cancer cell Vol.30 No.6
<P><B>Summary</B></P> <P>Pro-inflammatory cytokines produced in the tumor microenvironment lead to eradication of anti-tumor immunity and enhanced tumor cell survival. In the current study, we identified tumor necrosis factor alpha (TNF-α) as a major factor triggering cancer cell immunosuppression against T cell surveillance via stabilization of programmed cell death-ligand 1 (PD-L1). We demonstrated that COP9 signalosome 5 (CSN5), induced by NF-κB p65, is required for TNF-α-mediated PD-L1 stabilization in cancer cells. CSN5 inhibits the ubiquitination and degradation of PD-L1. Inhibition of CSN5 by curcumin diminished cancer cell PD-L1 expression and sensitized cancer cells to anti-CTLA4 therapy.</P> <P><B>Highlights</B></P> <P> <UL> <LI> TNF-α stabilizes cancer cell PD-L1 in response to chronic inflammation </LI> <LI> Activation of NF-κB by TNF-α induces CSN5 expression leading to PD-L1 stabilization </LI> <LI> CSN5 enzyme activity controls T cell suppression via PD-L1 deubiquitination </LI> <LI> Destabilization of PD-L1 by CSN5 inhibitor curcumin benefits anti-CTLA4 therapy </LI> </UL> </P> <P><B>Graphical Abstract</B></P> <P>[DISPLAY OMISSION]</P>
Incidence and Mortality of Female Breast Cancer in Jiangsu, China
Wu, Li-Zhu,Han, Ren-Qiang,Zhou, Jin-Yi,Yang, Jie,Dong, Mei-Hua,Qian, Yun,Wu, Ming Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.6
Objectives: The aim of this study was to describe and analyze the incidence and mortality of female breast cancer in Jiangsu Province of China. Methods: Incidence and mortality data for female breast cancer and corresponding population statistics from eligible cancer registries in Jiangsu from 2006 to 2010 were collected and analyzed. Crude rates, age-specific rates and age-standardized rates of incidence and mortality were calculated, and annual present changes (APCs) were estimated to describe the time trends. Results: From 2006 to 2010, 11,013 new cases and 3,068 deaths of female breast cancer were identified in selected cancer registry areas of Jiangsu. The annual average crude incidence and age-standardized incidence by world population (ASW) were 25.2/ and 17.9/100,000 respectively. The annual average crude and ASW for mortality rates were 7.03/ and 4.81/100,000. The incidence was higher in urban areas than that in rural areas, and this was consistent in all age groups. No significant difference was observed in mortality between urban and rural areas. Two peaks were observed when looking at age-specific rates, one at 50-59 years and another at over 85 years. During the 5 years, incidence and mortality increased with APCs of 4.47% and 6.89%, respectively. Compared to the national level, Jiangsu is an area with relatively low risk of female breast cancer. Conclusion: Breast cancer has become a main public health problem among Chinese females. More prevention and control activities should be conducted to reduce the burden of this disease, even in relatively low risk areas like Jiangsu.
Yi-Xin Zou,Jia Qiao,Hua-Yuan Zhu,Rui-Nan Lu,Yi Xia,Lei Cao,Wei Wu,Hui Jin,Wen-Jie Liu,Jin-Hua Liang,Jia-Zhu Wu,Li Wang,Lei Fan,Wei Xu,Jian-Yong Li 대한암학회 2019 Cancer Research and Treatment Vol.51 No.2
Purpose Chronic lymphocytic leukemia (CLL) is one of the most frequent type of B-cell chronic lymphoproliferative disorders and chronic inflammation takes part in the development of CLL. However, there has been no valid immune biomarker to predict the prognosis of untreated CLL patients. Materials and Methods In this retrospective study, we analyzed the clinical correlations and prognostic value of albumin-to-fibrinogen ratio (AFR) detected at diagnosis in 191 CLL patients. Results The cut-off value of AFR was 9.7 calculated by X-tile. Patients who were more than 65 years old were often accompanied by low level of AFR (p < 0.001). Survival analysis showed that patients with low level of AFR had shorter overall survival (OS) than patients with high level of AFR (p < 0.001). Multivariate analysis illustrated that AFR had a negative impact on OS (p=0.003) and was independent of parameters involved in CLL international prognostic index and other prognostic markers such as CD38 and ZAP-70. Conclusion These data provide a comprehensive view of AFR and shows that AFR at diagnosis is an adverse prognostic factor in untreated CLL patients.
Wu, Bing-Li,Zou, Hai-Ying,Lv, Guo-Qing,Du, Ze-Peng,Wu, Jian-Yi,Zhang, Pi-Xian,Xu, Li-Yan,Li, En-Min Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.5
Lysyl oxidase-like 2 (LOXL2), a member of the lysyl oxidase (LOX) family, is a copper-dependent enzyme that catalyzes oxidative deamination of lysine residues on protein substrates. LOXL2 was found to be overexpressed in esophageal squamous cell carcinoma (ESCC) in our previous research. We later identified a LOXL2 splicing variant LOXL2-delta72 and we overexpressed LOXL2-delta72 and its wild type counterpart in ESCC cells following microarray analyses. First, the differentially expressed genes (DEGs) of LOXL2 and LOXL2-delta72 compared to empty plasmid were applied to generate protein-protein interaction (PPI) sub-networks. Comparison of these two sub-networks showed hundreds of different proteins. To reveal the potential specific roles of LOXL2- delta72 compared to its wild type, the DEGs of LOXL2-delta72 vs LOXL2 were also applied to construct a PPI sub-network which was annotated by Gene Ontology. The functional annotation map indicated the third PPI sub-network involved hundreds of GO terms, such as "cell cycle arrest", "G1/S transition of mitotic cell cycle", "interphase", "cell-matrix adhesion" and "cell-substrate adhesion", as well as significant "immunity" related terms, such as "innate immune response", "regulation of defense response" and "Toll signaling pathway". These results provide important clues for experimental identification of the specific biological roles and molecular mechanisms of LOXL2-delta72. This study also provided a work flow to test the different roles of a splicing variant with high-throughput data.
Wu Sing-Shan,Tseng Ching-Tzu,Yang Yu-Hung,Liu Yao-Chia,Chang Ju-Chun,Gyawali Purushottam,Li Yi-Hsuan,Yang Tzu-Hao,Tsai Yi-Fang,Tang Li-Cheng,Nai Yu-Shin 한국응용곤충학회 2022 Journal of Asia-Pacific Entomology Vol.25 No.4
The fall armyworm, Spodoptera frugiperda, is an emerging invasive pest in Taiwan that feeds on a wide range of crops and causes serious damage. Herein, an entomopathogenic fungal library (EFLib) was constructed to identify potential microbes to control FAW. Twenty-eight indigenous entomopathogenic fungi (EPF) were iso lated and investigated for their potential pathogenicity, with Metarhizium pinghaense (Mp-NCHU-124) and Beauveria bassiana (Bb-NCHU-157) exerting dose-dependent effects on the 4th instar FAW larvae. The non-ionic surfactant Silwet L-77 rapidly killed FAW larvae after spraying at a concentration of 300 mg/kg and the toxic effect of Silwet L-77 on FAW larvae was dose-dependent. When the EPF isolates (10 6 conidia/mL) were applied to FAW larvae in combination with the non-ionic surfactant Silwet L-77 (30–90 mg/kg), the mortality rate dramatically increased and the LT 50 reduced, with increased fungal mycosis (Mp-NCHU-124: 38% to 72% and Bb-NCHU-157: 20 to 62%), indicating the high compatibility of EPF with the non-ionic surfactant. Thus, the Silwet L-77+EPF combined formulation has potential for practical field application for FAW pest control and sustainable agriculture in the future.
Li, Yi-Min,Lin, Qin,Zhao, Long,Wang, Li-Chen,Sun, Long,Dai, Ming-Ming,Luo, Zuo-Ming,Zheng, Hua,Wu, Hua Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.3
Objectives: To study application of the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) with $^{18}F$-FDG PET/CT for predicting prognosis of esophageal squamous cell cancer (ESC) patients. Methods: Eighty-six patients with ESC staged from I to IV were prospectively enrolled. Cisplatin-based chemoradiotherapy (CCRT) or palliative chemoradiotherapy were the main treatment methods and none received surgery. $^{18}F$-FDG PET/CT scans were performed before the treatment. SUVmax, MTV, and TLG were measured for the primary esophageal lesion and regional lymph nodes. Receiver operating characteristic curves (ROCs) were generated to calculate the P value of the predictive ability and the optimal threshold. Results: MTV and TLG proved to be good indexes in the prediction of outcome for the ESC patients. An MTV value of 15.6 ml and a TLG value of 183.5 were optimal threshold to predict the overall survival (OS). The areas under the curve (AUC) for MTV and TLG were 0.74 and 0.70, respectively. Kaplan-Meier analysis showed an MTV less than 15.6 ml and a TLG less than 183.5 to indicate good media survival time (p value <0.05). In the stage III-IV patient group, MTV could better predict the OS (P < 0.001), with a sensitivity and specificity of 0.80 and 0.67, respectively. Conclusions: Pre-treatment MTV and TLG are useful prognostic factors in nonsurgical ESC.
Wu, Bing-Li,Luo, Lie-Wei,Li, Chun-Quan,Xie, Jian-Jun,Du, Ze-Peng,Wu, Jian-Yi,Zhang, Pi-Xian,Xu, Li-Yan,Li, En-Min Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.12
Background: Fascin, an actin-bundling protein forming actin bundles including filopodia and stress fibers, is overexpressed in multiple human epithelial cancers including esophageal squamous cell carcinoma (ESCC). Previously we conducted a microarray experiment to analyze fascin knockdown by RNAi in ESCC. Method: In this study, the differentially expressed genes from mRNA expression profilomg of fascin knockdown were analyzed by multiple bioinformatics methods for a comprehensive understanding of the role of fascin. Results: Gene Ontology enrichment found terms associated with cytoskeleton organization, including cell adhesion, actin filament binding and actin cytoskeleton, which might be related to fascin function. Except GO categories, the differentially expressed genes were annotated by 45 functional categories from the Functional Annotation Chart of DAVID. Subpathway analysis showed thirty-nine pathways were disturbed by the differentially expressed genes, providing more detailed information than traditional pathway enrichment analysis. Two subpathways derivated from regulation of the actin cytoskeleton were shown. Promoter analysis results indicated distinguishing sequence patterns and transcription factors in response to the co-expression of downregulated or upregulated differentially expressed genes. MNB1A, c-ETS, GATA2 and Prrx2 potentially regulate the transcription of the downregulated gene set, while Arnt-Ahr, ZNF42, Ubx and TCF11-MafG might co-regulate the upregulated genes. Conclusions: This multiple bioinformatic analysis helps provide a comprehensive understanding of the roles of fascin after its knockdown in ESCC.