Targeting Epstein-Barr virus oncoprotein LMP1-mediated high oxidative stress suppresses EBV lytic reactivation and sensitizes tumors to radiation therapy.


:Generating oxidative stress is a critical mechanism by which host cells defend against infection by pathogenic microorganisms. Radiation resistance is a critical problem in radiotherapy against cancer. Epstein-Barr virus (EBV) is a cancer-causing virus and its reactivation plays an important role in the development of EBV-related tumors. This study aimed to explore the inner relationship and regulatory mechanism among oxidative stress, EBV reactivation, and radioresistance and to identify new molecular subtyping models and treatment strategies to improve the therapeutic effects of radiotherapy. Methods: ROS, NADP+/NADPH, and GSSG/GSH were detected to evaluate the oxidative stress of cells. 8-OHdG is a reliable oxidative stress marker to evaluate the oxidative stress in patients. Its concentration in serum was detected using an ELISA method and in biopsies was detected using IHC. qPCR array was performed to evaluate the expression of essential oxidative stress genes. qPCR, Western blot, and IHC were used to measure the level of EBV reactivation in vitro and in vivo. A Rta-IgG ELISA kit and EBV DNA detection kit were used to analyze the reactivation of EBV in serum from NPC patients. NPC tumor tissue microarrays was used to investigate the prognostic role of oxidative stress and EBV reactivation. Radiation resistance was evaluated by a colony formation assay. Xenografts were treated with NAC, radiation, or a combination of NAC and radiation. EBV DNA load of tumor tissue was evaluated using an EBV DNA detection kit. Oxidative stress, EBV reactivation, and the apoptosis rate in tumor tissues were detected by using 8-OHdG, EAD, and TUNEL assays, respectively. Results: We found that EBV can induce high oxidative stress, which promotes its reactivation and thus leads to radioresistance. Basically, EBV caused NPC cells to undergo a process of 'Redox Resetting' to acquire a new redox status with higher levels of ROS accumulation and stronger antioxidant systems by increasing the expression of the ROS-producing enzyme, NOX2, and the cellular master antioxidant regulator, Nrf2. Also, EBV encoded driving protein LMP1 promotes EBV reactivation through production of ROS. Furthermore, high oxidative stress and EBV reactivation were positively associated with poor overall survival of patients following radiation therapy and were significant related to NPC patients' recurrence and clinical stage. By decreasing oxidative stress using an FDA approved antioxidant drug, NAC, sensitivity of tumors to radiation was increased. Additionally, 8-OHdG and EBV DNA could be dual prognostic markers for NPC patients. Conclusions: Oxidative stress mediates EBV reactivation and leads to radioresistance. Targeting oxidative stress can provide therapeutic benefits to cancer patients with radiation resistance. Clinically, we, for the first time, generated a molecular subtyping model for NPC relying on 8-OHdG and EBV DNA level. These dual markers could identify patients who are at a high risk of poor outcomes but who might benefit from the sequential therapy of reactive oxygen blockade followed by radiation therapy, which provides novel perspectives for the precise treatment of NPC.






Hu J,Li Y,Li H,Shi F,Xie L,Zhao L,Tang M,Luo X,Jia W,Fan J,Zhou J,Gao Q,Qiu S,Wu W,Zhang X,Liao W,Bode AM,Cao Y




Has Abstract


2020-10-25 00:00:00












  • Supramolecular PEGylated Dendritic Systems as pH/Redox Dual-Responsive Theranostic Nanoplatforms for Platinum Drug Delivery and NIR Imaging.

    abstract::Recently, self-assembling small dendrimers into supramolecular dendritic systems offers an alternative strategy to develop multifunctional nanoplatforms for biomedical applications. We herein report a dual-responsive supramolecular PEGylated dendritic system for efficient platinum-based drug delivery and near-infrared...


    pub_type: 杂志文章


    authors: Li Y,Li Y,Zhang X,Xu X,Zhang Z,Hu C,He Y,Gu Z

    更新日期:2016-06-05 00:00:00

  • Extracellular vesicles derived from hypoxic glioma stem-like cells confer temozolomide resistance on glioblastoma by delivering miR-30b-3p.

    abstract::Rationale: Glioma stem-like cells (GSCs) contribute to temozolomide (TMZ) resistance in gliomas, although the mechanisms have not been delineated. Methods:In vitro functional experiments (colony formation assay, flow cytometric analysis, TUNEL assay) were used to assess the ability of extracellular vesicles (EVs) from...


    pub_type: 杂志文章


    authors: Yin J,Ge X,Shi Z,Yu C,Lu C,Wei Y,Zeng A,Wang X,Yan W,Zhang J,You Y

    更新日期:2021-01-01 00:00:00

  • Breaking the Barrier - Potent Anti-Inflammatory Activity following Efficient Topical Delivery of Etanercept using Thermoresponsive Nanogels.

    abstract::Topical administration permits targeted, sustained delivery of therapeutics to human skin. Delivery to the skin, however, is typically limited to lipophilic molecules with molecular weight of < 500 Da, capable of crossing the stratum corneum. Nevertheless, there are indications protein delivery may be possible in barr...


    pub_type: 杂志文章


    authors: Giulbudagian M,Yealland G,Hönzke S,Edlich A,Geisendörfer B,Kleuser B,Hedtrich S,Calderón M

    更新日期:2018-01-01 00:00:00

  • A Microfluidic Platform for Single Cell Fluorometric Granzyme B Profiling.

    abstract::Granzyme B (GrB) is an essential cytotoxic effector in cancer immunotherapy as it can be a potential biomarker to predict the efficacy of immunotherapies including checkpoint inhibitors. Monitoring the Granzyme B activity in cells would help determine a patient's clinical response to treatment and lead to better treat...


    pub_type: 杂志文章


    authors: Briones JC,Espulgar WV,Koyama S,Yoshikawa H,Park J,Naito Y,Kumanogoh A,Tamiya E,Takamatsu H,Saito M

    更新日期:2020-01-01 00:00:00

  • GPR124 facilitates pericyte polarization and migration by regulating the formation of filopodia during ischemic injury.

    abstract::Prolonged occlusion of multiple microvessels causes microvascular injury. G protein-coupled receptor 124 (GPR124) has been reported to be required for maintaining central nervous system (CNS) angiogenesis and blood-brain barrier integrity. However, the molecular mechanisms by which GPR124 regulates pericytes during is...


    pub_type: 杂志文章


    authors: Chen DY,Sun NH,Lu YP,Hong LJ,Cui TT,Wang CK,Chen XH,Wang SS,Feng LL,Shi WX,Fukunaga K,Chen Z,Lu YM,Han F

    更新日期:2019-08-14 00:00:00

  • Sensitive detection of protein biomarkers using silver nanoparticles enhanced immunofluorescence assay.

    abstract::Detection of biomarkers is extremely important for the early diagnosis of diseases. Here, we developed an easy and highly sensitive fluorescence detection system for the determination of biomarkers by combining the rapid separation of magnetic beads and silver nanoparticles labeled antibodies. An ultrasensitive silver...


    pub_type: 杂志文章


    authors: Zhao LJ,Yu RJ,Ma W,Han HX,Tian H,Qian RC,Long YT

    更新日期:2017-02-08 00:00:00

  • LPA3-mediated lysophosphatidic acid signaling promotes postnatal heart regeneration in mice.

    abstract::Background: Lysophosphatidic acid (LPA) is a small glycerophospholipid that acts as a potent extracellular signal in various biological processes and diseases. Our previous work demonstrated that the expression of the LPA receptors LPA1 and LPA3 is elevated in the early postnatal heart. However, the role of this stage...


    pub_type: 杂志文章


    authors: Wang F,Liu S,Pei J,Cai L,Liu N,Liang T,Dong X,Cong X,Chun J,Chen J,Hu S,Chen X

    更新日期:2020-08-29 00:00:00

  • Tumor-targeted Dual-modality Imaging to Improve Intraoperative Visualization of Clear Cell Renal Cell Carcinoma: A First in Man Study.

    abstract::Intraoperative imaging with antibodies labeled with both a radionuclide for initial guidance and a near-infrared dye for adequate tumor delineation may overcome the main limitation of fluorescence imaging: the limited penetration depth of light in biological tissue. In this study, we demonstrate the feasibility and sa...


    pub_type: 杂志文章


    authors: Hekman MC,Rijpkema M,Muselaers CH,Oosterwijk E,Hulsbergen-Van de Kaa CA,Boerman OC,Oyen WJ,Langenhuijsen JF,Mulders PF

    更新日期:2018-03-08 00:00:00

  • RNA Nanotechnology-Mediated Cancer Immunotherapy.

    abstract::RNA molecules (e.g., siRNA, microRNA, and mRNA) have shown tremendous potential for immunomodulation and cancer immunotherapy. They can activate both innate and adaptive immune system responses by silencing or upregulating immune-relevant genes. In addition, mRNA-based vaccines have recently been actively pursued and ...


    pub_type: 杂志文章,评审


    authors: Lin YX,Wang Y,Blake S,Yu M,Mei L,Wang H,Shi J

    更新日期:2020-01-01 00:00:00

  • Diagnostic Accuracy of Ga-68-HBED-CC-PSMA-Ligand-PET/CT before Salvage Lymph Node Dissection for Recurrent Prostate Cancer.

    abstract::Background: By targeting the prostate-specific membrane antigen (PSMA) on prostate cancer (PCa) cells PSMA-PET/CT shows great potential in locating the site of biochemical recurrence even at low PSA (Prostate-specific antigen)-levels. Accurate imaging of PCa recurrent lymph node metastases (LNM) is crucial for metasta...


    pub_type: 杂志文章


    authors: Jilg CA,Drendel V,Rischke HC,Beck T,Vach W,Schaal K,Wetterauer U,Schultze-Seemann W,Meyer PT

    更新日期:2017-04-10 00:00:00

  • Anti-tumor Efficiency of Lipid-coated Cisplatin Nanoparticles Co-loaded with MicroRNA-375.

    abstract::One of the major challenges in the hepatocellular carcinoma (HCC) treatment is its insensitivity to chemotherapeutic drugs. Here, we report the development of novel lipid-coated cisplatin nanoparticles co-loaded with microRNA-375 (NPC/miR-375) as a potential treatment for chemotherapy insensitive HCC. The NPC/miR-375 ...


    pub_type: 杂志文章


    authors: Yang T,Zhao P,Rong Z,Li B,Xue H,You J,He C,Li W,He X,Lee RJ,Ma X,Xiang G

    更新日期:2016-01-01 00:00:00

  • RGD Peptide Cell-Surface Display Enhances the Targeting and Therapeutic Efficacy of Attenuated Salmonella-mediated Cancer Therapy.

    abstract::Bacteria-based anticancer therapies aim to overcome the limitations of current cancer therapy by actively targeting and efficiently removing cancer. To achieve this goal, new approaches that target and maintain bacterial drugs at sufficient concentrations during the therapeutic window are essential. Here, we examined ...


    pub_type: 杂志文章


    authors: Park SH,Zheng JH,Nguyen VH,Jiang SN,Kim DY,Szardenings M,Min JH,Hong Y,Choy HE,Min JJ

    更新日期:2016-06-20 00:00:00

  • Novel Bioluminescent Activatable Reporter for Src Tyrosine Kinase Activity in Living Mice.

    abstract::Aberrant activation of the Src kinase is implicated in the development of a variety of human malignancies. However, it is almost impossible to monitor Src activity in an in vivo setting with current biochemical techniques. To facilitate the noninvasive investigation of the activity of Src kinase both in vitro and in v...


    pub_type: 杂志文章,收录出版


    authors: Leng W,Li D,Chen L,Xia H,Tang Q,Chen B,Gong Q,Gao F,Bi F

    更新日期:2016-02-24 00:00:00

  • Shape-, size- and structure-controlled synthesis and biocompatibility of iron oxide nanoparticles for magnetic theranostics.

    abstract::In the past decade, iron oxide nanoparticles (IONPs) have attracted more and more attention for their excellent physicochemical properties and promising biomedical applications. In this review, we summarize and highlight recent progress in the design, synthesis, biocompatibility evaluation and magnetic theranostic app...


    pub_type: 杂志文章,评审


    authors: Xie W,Guo Z,Gao F,Gao Q,Wang D,Liaw BS,Cai Q,Sun X,Wang X,Zhao L

    更新日期:2018-05-11 00:00:00

  • Low-intensity Pulsed Ultrasound regulates alveolar bone homeostasis in experimental Periodontitis by diminishing Oxidative Stress.

    abstract::Periodontitis is a widespread oral disease that results in the loss of alveolar bone. Low-intensity pulsed ultrasound (LIPUS), which is a new therapeutic option, promotes alveolar bone regeneration in periodontal bone injury models. This study investigated the protective effect of LIPUS on oxidative stress in periodon...


    pub_type: 杂志文章


    authors: Ying S,Tan M,Feng G,Kuang Y,Chen D,Li J,Song J

    更新日期:2020-08-01 00:00:00

  • RUNX2 overexpression and PTEN haploinsufficiency cooperate to promote CXCR7 expression and cellular trafficking, AKT hyperactivation and prostate tumorigenesis.

    abstract::Rationale: The overall success rate of prostate cancer (PCa) diagnosis and therapy has been improved over the years. However, genomic and phenotypic heterogeneity remains a major challenge for effective detection and treatment of PCa. Efforts to better classify PCa into functional subtypes and elucidate the molecular ...


    pub_type: 杂志文章


    authors: Bai Y,Yang Y,Yan Y,Zhong J,Blee AM,Pan Y,Ma T,Karnes RJ,Jimenez R,Xu W,Huang H

    更新日期:2019-05-24 00:00:00

  • Transcriptional Downregulation of miR-4306 serves as a New Therapeutic Target for Triple Negative Breast Cancer.

    abstract::Rationale: Triple-negative breast cancer (TNBC) is characterized by the absence of estrogen receptor alpha (ER-α), human epidermal growth factor receptor 2 (HER2) and progesterone receptor (PR) expression, but the effect of lacking the three factors on TNBC is unclear. Whether loss of the three factors contributes to ...


    pub_type: 杂志文章


    authors: Zhao Z,Li L,Du P,Ma L,Zhang W,Zheng L,Lan B,Zhang B,Ma F,Xu B,Zhan Q,Song Y

    更新日期:2019-02-20 00:00:00

  • IL20RA signaling enhances stemness and promotes the formation of an immunosuppressive microenvironment in breast cancer.

    abstract::Rationale: Tumor microenvironment interacts with tumor cells to regulate their stemness properties through various cytokines and cytokine receptors. Previous studies revealed the possible role of interleukin 20 receptor subunit alpha (IL20RA) signaling in the progression of several types of tumors. However, its regula...


    pub_type: 杂志文章


    authors: Gao W,Wen H,Liang L,Dong X,Du R,Zhou W,Zhang X,Zhang C,Xiang R,Li N

    更新日期:2021-01-01 00:00:00

  • Forkhead box K2 promotes human colorectal cancer metastasis by upregulating ZEB1 and EGFR.

    abstract::Background: Metastasis is the major reason for high recurrence rates and poor survival among patients with colorectal cancer (CRC). However, the underlying molecular mechanism of CRC metastasis is unclear. This study aimed to investigate the role of forkhead box K2 (FOXK2), one of the most markedly increased FOX genes...


    pub_type: 杂志文章


    authors: Du F,Qiao C,Li X,Chen Z,Liu H,Wu S,Hu S,Qiu Z,Qian M,Tian D,Wu K,Fan D,Nie Y,Xia L

    更新日期:2019-05-31 00:00:00

  • A paclitaxel prodrug with bifunctional folate and albumin binding moieties for both passive and active targeted cancer therapy.

    abstract::Folate receptor (FR) has proven to be a valuable target for chemotherapy using folic acid (FA) conjugates. However, FA-conjugated chemotherapeutics still have low therapeutic efficacy accompanied with side effects, resulting from complications such as short circulation half-life, limited tumor delivery, as well as hig...


    pub_type: 杂志文章


    authors: Shan L,Zhuo X,Zhang F,Dai Y,Zhu G,Yung BC,Fan W,Zhai K,Jacobson O,Kiesewetter DO,Ma Y,Gao G,Chen X

    更新日期:2018-02-16 00:00:00

  • Pretargeted molecular imaging and radioimmunotherapy.

    abstract::Pretargeting is a multi-step process that first has an unlabeled bispecific antibody (bsMAb) localize within a tumor by virtue of its anti-tumor binding site(s) before administering a small, fast-clearing radiolabeled compound that then attaches to the other portion of the bsMAb. The compound's rapid clearance signifi...


    pub_type: 杂志文章


    authors: Goldenberg DM,Chang CH,Rossi EA,J W,McBride,Sharkey RM

    更新日期:2012-01-01 00:00:00

  • PI3K/AKT inhibition reverses R-CHOP resistance by destabilizing SOX2 in diffuse large B cell lymphoma.

    abstract::Up to one-third of diffuse large B cell lymphoma (DLBCL) patients eventually develop resistance to R-CHOP regimen, while the remaining therapeutic options are limited. Thus, understanding the underlying mechanisms and developing therapeutic approaches are urgently needed. Methods: We generated two germinal center B ce...


    pub_type: 杂志文章


    authors: Chen J,Ge X,Zhang W,Ding P,Du Y,Wang Q,Li L,Fang L,Sun Y,Zhang P,Zhou Y,Zhang L,Lv X,Li L,Zhang X,Zhang Q,Xue K,Gu H,Lei Q,Wong J,Hu W

    更新日期:2020-02-10 00:00:00

  • Preparation of quantum dot/drug nanoparticle formulations for traceable targeted delivery and therapy.

    abstract::Quantum dots (QDs) are luminescent nanocrystals with rich surface chemistry and unique optical properties that make them useful as probes or carriers for traceable targeted delivery and therapy applications. QDs can be functionalized to target specific cells or tissues by conjugating them with targeting ligands. Recen...


    pub_type: 杂志文章


    authors: Yong KT,Wang Y,Roy I,Rui H,Swihart MT,Law WC,Kwak SK,Ye L,Liu J,Mahajan SD,Reynolds JL

    更新日期:2012-01-01 00:00:00

  • Development of Paper-Based Analytical Devices for Minimizing the Viscosity Effect in Human Saliva.

    abstract::Rationale: Saliva as a sample matrix is rapidly gaining interest for disease diagnosis and point-of-care assays because it is easy to collect (non-invasive) and contains many health-related biomarkers. However, saliva poses particular problems relative to more common urine and blood matrices, which includes low analyt...


    pub_type: 杂志文章


    authors: Noiphung J,Nguyen MP,Punyadeera C,Wan Y,Laiwattanapaisal W,Henry CS

    更新日期:2018-06-13 00:00:00

  • Theranostics in immuno-oncology using nanobody derivatives.

    abstract::Targeted therapy and immunotherapy have become mainstream in cancer treatment. However, only patient subsets benefit from these expensive therapies, and often responses are short-lived or coincide with side effects. A growing modality in precision oncology is the development of theranostics, as this enables patient se...


    pub_type: 杂志文章,评审


    authors: Lecocq Q,De Vlaeminck Y,Hanssens H,D'Huyvetter M,Raes G,Goyvaerts C,Keyaerts M,Devoogdt N,Breckpot K

    更新日期:2019-10-15 00:00:00

  • Water-Mediated Nanostructures for Enhanced MRI: Impact of Water Dynamics on Relaxometric Properties of Gd-DTPA.

    abstract::Recently, rational design of a new class of contrast agents (CAs), based on biopolymers (hydrogels), have received considerable attention in Magnetic Resonance Imaging (MRI) diagnostic field. Several strategies have been adopted to improve relaxivity without chemical modification of the commercial CAs, however, unders...


    pub_type: 杂志文章


    authors: De Sarno F,Ponsiglione AM,Russo M,Grimaldi AM,Forte E,Netti PA,Torino E

    更新日期:2019-02-28 00:00:00

  • An Activatable Near-Infrared Chromophore for Multispectral Optoacoustic Imaging of Tumor Hypoxia and for Tumor Inhibition.

    abstract::Hypoxia is a key hallmark of solid tumors and tumor hypoxia usually contributes to cancer progression, therapeutic resistance and poor outcome. Accurately detecting and imaging tumor hypoxia with high spatial resolution would be conducive to formulating optimized treatment plan and thus achieving better patient outcom...


    pub_type: 杂志文章


    authors: Huang J,Wu Y,Zeng F,Wu S

    更新日期:2019-09-25 00:00:00

  • ROS-Responsive Mitochondria-Targeting Blended Nanoparticles: Chemo- and Photodynamic Synergistic Therapy for Lung Cancer with On-Demand Drug Release upon Irradiation with a Single Light Source.

    abstract::Mitochondria in cancer cells maintain a more negative membrane potential than normal cells. Mitochondria are the primary source of cellular reactive oxygen species (ROS), which are necessary for photodynamic therapy. Thus, the strategy of targeting mitochondria can maximize the photodynamic therapeutic efficiency for ...


    pub_type: 杂志文章


    authors: Yue C,Yang Y,Zhang C,Alfranca G,Cheng S,Ma L,Liu Y,Zhi X,Ni J,Jiang W,Song J,de la Fuente JM,Cui D

    更新日期:2016-10-01 00:00:00

  • A novel Granzyme B nanoparticle delivery system simulates immune cell functions for suppression of solid tumors.

    abstract::Cell-based immunotherapy for the treatment of hematologic malignancies, such as leukemia and lymphoma, has seen much success and played an increasingly important role in clinical studies. Nevertheless, the efficacy of immunotherapy in solid tumors still needs improvements due to the immunosuppressive properties of tum...


    pub_type: 杂志文章


    authors: Qian X,Shi Z,Qi H,Zhao M,Huang K,Han D,Zhou J,Liu C,Liu Y,Lu Y,Yuan X,Zhao J,Kang C

    更新日期:2019-10-14 00:00:00

  • Soyasaponin II protects against acute liver failure through diminishing YB-1 phosphorylation and Nlrp3-inflammasome priming in mice.

    abstract::Acute liver failure is characterized by the rapid development of liver dysfunction and remarkably high mortality. Accumulating evidence suggests that soyasaponin possesses potential anti-inflammatory activities. Here, we aimed to investigate the potential role of soyasaponin II in acute liver failure and establish the...


    pub_type: 杂志文章


    authors: Wang F,Gong S,Wang T,Li L,Luo H,Wang J,Huang C,Zhou H,Chen G,Liu Z,Zhang Q,Jiang Y,Chen P

    更新日期:2020-02-03 00:00:00