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circT P63-N suppresses the proliferation and metastasis of nasopharyngeal carcinoma via engaging with HSP90AB1 to modulate the YAP1/Hippo signaling pathway

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Science China Life Sciences 2025年第03期 689-705页

作者： Dan Wang Sicheng Zuo Junshang Ge Hongke Qu Jie Wu Na Yi Lei Shi Yumin Wang Yongzhen Mo Chunmei Fan Yi He Pan Chen Ming Zhou Bo Xiang Wei Xiong Wenjia Guo Zhaoyang Zeng Can Guo NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of cancer Metabolism Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine Central South University Key Laboratory of Carcinogenesis and cancer Invasion of the Chinese Ministry of Education Cancer Research Institute and School of Basic Medicine Sciences Central South University Furong Laboratory cancer Research Institute Affiliated Cancer Hospital of Xinjiang Medical University Xinjiang Key Laboratory of Translational Biomedical Engineering

Circular RNAs(circRNAs) play pivotal roles in the development and progression of various diseases, including malignant tumors. However,the biological functions and the underlying mechanisms of many circRNAs remain elusive. In this study, we identified a novel circRNA,circTP63-N, generated through the splicing of exons 2–4 of the TP63 gene in nasopharyngeal carcinoma(NPC). circTP63-N was found to be downregulated in clinical samples of NPC. Both in vitro and in vivo experiments unequivocally demonstrated that circTP63-N inhibits the proliferation and metastasis of NPC cells. Further investigations revealed that circTP63-N interacted with the HSP90AB1 protein, leading to the recruitment of LATS/YAP1 proteins. This, in turn, induced phosphorylation and ubiquitination-dependent degradation of YAP1, resulting in reduced nuclear translocation of YAP1 and inhibition of the transcriptional activation of downstream oncogenic genes, including INHBA, MMP3, and CCNE2. Our findings highlight the identification of circTP63-N, a novel circRNA encoded by an important tumor-relevant gene TP63 and elucidate its molecular mechanism as a tumor suppressor in NPC. These insights offer novel potential molecular markers and therapeutic targets for the clinical diagnosis and treatment of NPC.

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Irreversible electroporation combined with anti-programmed cell death protein 1 therapy promotes tumor antigen-specific CD8+T cell response

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World Journal of Gastrointestinal Oncology 2025年第3期17卷 237-245页

作者： Yang-Yang Ma Xiao-Hua Wang Jian-Ying Zeng Ji-Bing Chen Li-Zhi Niu Guangzhou Fuda cancer Hospital Guangzhou 510665Guangdong ProvinceChina Department of Oncology Guangzhou Fuda Cancer HospitalGuangzhou 510665Guangdong ProvinceChina

BACKGROUND Irreversible electroporation(IRE)is a novel local tumor ablation approach with the potential to activate the host’s immune ***,this approach is insufficient to prevent cancer progression,and complementary approaches are required for effective *** To assess the immunomodulatory effects and mechanism of IRE combined antiprogrammed cell death protein 1(PD-1)treatment in subcutaneous pancreatic cancer *** C57BL-6 tumor-bearing mice were randomly divided into four groups:Control group;IRE group;anti-PD-1 group;and IRE+anti-PD-1 ***-infiltrating T,B,and natural killer cell levels and plasma concentrations of T helper type 1 cytokines(interleukin-2,interferon-γ,and tumor necrosis factor-α)were ***-time PCR was used to determine the expression of CD8(marker of CD8+T cells)in tumor tissues of the mice of all groups at different points of *** growth curves of tumors were *** The results demonstrated that the IRE+anti-PD-1 group exhibited significantly higher percentages of T lymphocyte infiltration,including CD4+and CD8+T cells compared with the control ***,the IRE+anti-PD-1 group showed increased infiltration of natural killer and B cells,elevated cytokine levels,and higher CD8 mRNA *** volume was significantly reduced in the IRE+anti-PD-1 group,indicating a more pronounced therapeutic *** The combination of IRE and anti-PD-1 therapy promotes CD8+T cell immunity responses,leading to a more effective reduction in tumor volume and improved therapeutic outcomes,which provides a new direction for ablation and immunotherapy of pancreatic cancer.

关键词： Irreversible electroporation Pancreatic cancer programmed cell death protein 1 blockade CD8+T cell Anticancer immunity

Establishment and validation of a nomogram for predicting esophagogastric variceal bleeding in patients with liver cirrhosis

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World Journal of Gastroenterology 2025年第9期31卷 54-67页

作者： Lun-Xi Liang Xiao Liang Ya Zeng Fen Wang Xue-Ke Yu Department of Gastroenterology The Third Xiangya HospitalCentral South UniversityChangsha 410013Hunan ProvinceChina Department of Gastroenterology The Affiliated Changsha Central HospitalHengyang Medical SchoolUniversity of South ChinaChangsha 410008Hunan ProvinceChina Hunan Key Laboratory of Nonresolving inflammation and cancer The Third Xiangya HospitalCentral South UniversityChangsha 410006Hunan ProvinceChina School of Clinical Medicine Changsha Medical UniversityChangsha 410200Hunan ProvinceChina

BACKGROUND Patients with decompensated liver cirrhosis suffering from esophagogastric variceal bleeding(EGVB)face high *** To investigate the risk factors for EGVB in patients with liver cirrhosis and establish a diagnostic *** Patients with liver cirrhosis who met the inclusion criteria were randomly divided into training and validation cohorts in a 6:4 ratio in this retrospective *** analysis,least absolute shrinkage and selection operator regression,and multivariate analysis were employed to establish the nomogram *** curve,the area under the receiver operating characteristic curve(AUC),and decision curve analysis(DCA)were applied to assess the discrimination,accuracy,and clinical practicability of the nomogram,*** A total of 1115 patients were enrolled in this *** nomogram was established based on white blood cells(P<0.001),hemoglobin(P<0.001),fibrinogen(P<0.001),total bilirubin(P=0.007),activated partial thromboplastin time(P=0.002),total bile acid(P=0.012),and ascites(P=0.006).The calibration curve indicated that the actual observation results were in good agreement with the prediction results of the *** AUC values of the diagnostic model were 0.861 and 0.859 in the training and validation cohorts,respectively,which were higher than that of the aspartate aminotransferase-to-platelet ratio index,fibrosis index based on 4 factors,and aspartate aminotransferase-to-alanine aminotransferase ***,DCA indicated that the net benefit value of the model was higher than that of the other *** This research constructed and validated a nomogram with perfect performance for predicting EGVB events in patients with liver cirrhosis,which could help clinicians with timely diagnosis,individualized treatment,and follow-up.

关键词： Liver cirrhosis Esophagogastric variceal bleeding Diagnostic model Nomogram Retrospective study

Research landmarks on the 60th anniversary of Epstein-Barr virus

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Science China(Life Sciences) 2025年第2期68卷 354-380页

作者： Lan-Yi Zhong Chu Xie Le-Le Zhang Yan-Lin Yang Yuan-Tao Liu Ge-Xin Zhao Guo-Long Bu Xian-Shu Tian Zi-Ying Jiang Bo-Yu Yuan Peng-Lin Li Pei-Huang Wu Wei-Hua Jia Christian Münz Benjamin E.Gewurz Qian Zhong Cong Sun Mu-Sheng Zeng State Key Laboratory of Oncology in South China Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and TherapyGuangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou 510060China Viral Immunobiology Institute of Experimental ImmunologyUniversity of ZürichZürich 8092Switzerland Division of Infectious Diseases Department of MedicineBrigham and Women’s HospitalBoston MA 02115USA Department of Microbiology Harvard Medical SchoolBoston MA 02115USA Harvard program in Virology Boston MA 02115USA Broad Institute of Harvard and MIT Cambridge MA 02142USA

Epstein-Barr virus(EBV),the first human oncovirus discovered in 1964,has become a focal point in virology,immunology,and oncology because of its unique biological characteristics and significant role in human *** we commemorate the 60th anniversary of EBV's discovery,it is an opportune moment to reflect on the major advancements in our understanding of this complex *** this review,we highlight key milestones in EBV research,including its virion structure and life cycle,interactions with the host immune system,association with EBV-associated diseases,and targeted intervention strategies.

关键词： Epstein-Barr virus oncovirus immune response epidemiology vaccines antibodies

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Clinicopathological and molecular features of HR+/HER2- breast cancer patients with distinct endocrine resistance patterns

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Chinese Journal of cancer Research 2025年第01期 48-72页

作者： Siwei Zhang Han Wang Hang Zhang Qingyuan Zhuang Xiaohui Zhu Yi Xiao Yizhou Jiang Key Laboratory of Breast cancer in Shanghai Department of Breast Surgery Fudan University Shanghai Cancer Center Department of Oncology Shanghai Medical College Fudan University

Objective: Recurrence continues to be a pivotal challenge among hormone receptor-positive（HR+）/human epidermal growth factor receptor 2-negative（HER2-） breast cancers. In the international consensus guidelines,HR+/HER2-breast cancer relapse patterns are divided into three distinct types: primary resistant, secondary resistant, and endocrine sensitive. However, owing to the lack of cohorts with treatment and follow-up data, the heterogeneity among different recurrence patterns remains uncharted. Current treatments still lack ***: This analysis included data from a large-scale multiomics study of a HR+/HER2-breast cancer cohort（n=314）. Through the analysis of transcriptomics（n=312）, proteomics（n=124）, whole-exome sequencing（n=290）,metabolomics（n=217）, and digital pathology（n=228） data, we explored distinctive molecular features and identified putative therapeutic targets for patients experiencing ***: We explored distinct clinicopathological characteristics, biological heterogeneity, and potential therapeutic strategies for recurrence. Based on a shared relapse signature, we stratified patients into high-and lowrecurrence-risk groups. Patients with different relapse patterns presented unique molecular features in primary tumors. Specifically, receptor tyrosine kinase（RTK） pathway activation in the primary resistant group suggested the utility of RTK inhibitors, whereas mammalian target of rapamycin（mTOR） and cell cycle pathway activation in the secondary resistant group highlighted the potential of mTOR and CDK4/6 inhibitors. Interestingly, the endocrine-sensitive group displayed a quiescent state and high genomic instability, suggesting that targeting quiescent cells and using poly-ADP-ribose polymerase（PARP） inhibitors could be effective ***: These findings illuminate the clinicopathological and molecular landscape of HR+/HER2-breast cancer patients with distinct recurrence patterns, highlighting potential targeted the

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Reduced graphene oxide-mediated electron-hole separation using titanium dioxide increases the photocatalytic antibacterial activity of bone scaffolds

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Bio-Design and Manufacturing 2025年第1期8卷 100-115,I0044页

作者： Pei Feng Haifeng Tian Feng Yang Shuping Peng Hao Pan Cijun Shuai State Key Laboratory of Precision Manufacturing for Extreme Service Performance College of Mechanical and Electrical EngineeringCentral South UniversityChangsha 410083China NHC Key Laboratory of Carcinogenesis of Hunan cancer Hospital and the Affiliated cancer Hospital of Xiangya School of Medicine Cancer Research InstituteSchool of Basic Medical ScienceCentral South UniversityChangsha 410013China RESEARCH ARTICLE The Key Laboratory of Carcinogenesis and cancer Invasion of the Chinese Ministry of Education of Xiangya Hospital and School of Basic Medical Science Central South UniversityChangsha 410013China Department of Periodontics&Oral Mucosal Section Xiangya Stomatological Hospital&Xiangya School of StomatologyCentral South UniversityChangsha 410013China Institute of Additive Manufacturing Jiangxi University of Science and TechnologyNanchang 330013China College of Mechanical Engineering Xinjiang UniversityUrumqi 830017China

Fast electron-hole recombination issues during titanium dioxide(TiO_(2))photocatalysis limit its application in preventing bacterial infection during bone defect *** this study,TiO_(2)@reduced graphene oxide(rGO)composites were synthesized using a hydrothermal method in which rGO,which possesses very high electrical conductivity,promotes the separation of photoelectron-hole pairs of TiO_(2),thus improving the efficiency of photocatalytic production of reactive oxygen species(ROS).Subsequently,TiO_(2)@rGO composites were introduced into poly-L-lactic acid(PLLA)to prepare bone scaffolds with photocatalytic antibacterial function via selective laser *** results showed that TiO_(2)grew on the surface of rGO and formed a covalent bond connection(Ti-O-C)with rGO.A decreased electrochemical impedance of TiO_(2)@rGO composites was observed,and the transient photocurrent intensity increased from 0.05 to 0.5μA/cm^(2).Analysis of electron spin resonance found that the photocatalytic products of TiO_(2)were·OH and·O^(2-),two kinds of ROS capable of killing bacteria via disrupting the structure of the bacterial membrane in *** experiments showed that the PLLA/TiO_(2)@rGO scaffolds had good antibacterial properties against Escherichia coli and Staphylococcus ***,we report that these scaffolds exhibited both enhanced mechanical properties due to the addition of TiO_(2)@rGO as a reinforcement material and good biocompatibility during cell proliferation.

关键词： Reduced graphene oxide Photocatalysis Reactive oxygen species Antibacterial properties Bone scaffold

Fighting hypoxia to improve photodynamic therapy-driven immunotherapy: Alleviating, exploiting and disregarding

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Chinese Chemical Letters 2025年第2期36卷 57-68页

作者： Liangliang Jia Ye Hong Xinyu He Ying Zhou Liujiao Ren Hongjun Du Bin Zhao Bin Qin Zhe Yang Di Gao The Key Laboratory of Biomedical Information Engineering of Ministry of Education School of Life Science and Technology Xi'an Jiaotong University Center of Digestive Endoscopy Shaanxi Provincial Cancer Hospital Department of Ophthalmology Xijing Hospital Department of Epidemiology Shaanxi Provincial Cancer Hospital Department of Gastroenterology Second Affiliated Hospital Xi'an Jiaotong University Research Institute of Xi'an Jiaotong University

Innovative anti-cancer therapies that activate the immune system show promise in combating cancers resistant to conventional treatments. Photodynamic therapy (PDT) is one such treatment, which not only directly eliminates tumor cells but also functions as an in situ tumor vaccine by enhancing tumor immunogenicity and triggering anti-tumor immune responses through immunogenic cell death (ICD). However, the effectiveness of PDT in enhancing immune responses is influenced by factors, such as photosensitizers and the tumor microenvironment, particularly hypoxia. Current clinically used PDT heavily relies on oxygen (O2) availability and can be limited by tumor hypoxia. Additionally, the tumor immunosuppressive microenvironment induced by hypoxia affects the anti-tumor immunity of tumor-infiltrating effector T cells. Meanwhile, the immunosuppressive myeloid-lineage cells are recruited to the hypoxic tumor tissue and exhibit higher immunosuppressive capabilities under hypoxia conditions. Consequently,numerous strategies have been developed to modulate tumor hypoxia or to create hypoxia-compatible PDT, aiming to reduce the effects of tumor hypoxia on PDT-driven immunotherapy. This review investigates these strategies, including approaches to alleviate, exploit, and disregard tumor hypoxia within the context of PDT/immunotherapy. It also emphasizes the role of advanced nanomedicine and its benefits in these strategies, while outlining current challenges and future prospects in the field.

关键词： Immunogenic cell death Immunotherapy Nanomedicine Photodynamic therapy Photosensitizers Tumor hypoxia

Advances in basic and translational research into nasopharyngeal carcinoma

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Oncology and Translational Medicine 2025年第1期11卷 10-16页

作者： Zhe Li Yupei Chen Jun Ma Department of Radiation Oncology State Key Laboratory of Oncology in South ChinaGuangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and TherapyGuangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhouChina

According to the International cancer Research Institute of the World Health Organization data,nasopharyngeal carcinoma(NPC)remains a significant health concern,particularly in regions such as Southeast Asia and southern ***,substantial progress has been made in the field of basic and translational research on NPC,enhancing our understanding of the molecular mechanisms underlying the disease and paving the way for precise therapeutic *** review summarizes the advances in NPC research,focusing on key areas that include radiotherapy and chemotherapy resistance and tumor metastasis,microenvironment,metabolism,microbiome,and ***,future research directions in NPC are discussed to provide valuable insights to advance the field further.

关键词： Nasopharyngeal carcinoma Treatment resistance Tumor biomarkers Tumor microenvironment

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Genetics and genomics of prostate cancer

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Asian Journal of Andrology 2013年第3期15卷 309-313页

作者： Michael Dean Hong LOU cancer and inflammation program National Cancer Institute National Institutes of Health Frederick MD 21702 USA Basic Science program SAIC-Frederick Nationa Cancer Institute National Institutes of Health Frederick MD 21702 USA

Prostate cancer （PCa） is one of the most common malignancies in the world with over 890 000 cases and over 258 000 deaths worldwide each year. Nearly all mortalities from PCa are due to metastatic disease, typically through tumors that evolve to be hormone-refractory or castrate-resistant. Despite intensive epidemiological study, there are few known environmental risk factors, and age and family history are the major determinants. However, there is extreme heterogeneity in PCa incidence worldwide, suggesting that major determining factors have not been described. Genome-wide association studies have been performed and a considerable number of significant, but low-risk loci have been identified. In addition, several groups have analyzed PCa by determination of genomic copy number, fusion gene generation and targeted resequencing of candidate genes, as well as exome and whole genome sequencing. These initial studies have examined both primary and metastatic tumors as well as murine xenografts and identified somatic alterations in TP53and other potential driver genes, and the disturbance of androgen response and cell cycle pathways. It is hoped that continued characterization of risk factors as well as gene mutation and misregulation in tumors will aid in understanding, diagnosing and better treating PCa.

关键词： androgen receptor cancer progression chromatin remodeling metastasis prostate cancer (PCa) risk factor somaticmutation tumor heterogeneity