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Frontiers of Medicine 2024年第3期18卷 565-569页

作者： Jia Jia Lili Mao Jing Lin Wenyu Li Pei Yuan Lei Guo Jie Dai Caili Li Xue Bai Zhongwu Li Yu Chen Jun Guo Jianming Ying Lu Si State Key Laboratory of Molecular Oncology Department of PathologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100021China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of Melanoma and SarcomaPeking University Cancer Hospital&InstituteBeijing100142China Department of Medical Oncology Clinical Oncology School of Fujian Medical UniversityFujian Cancer HospitalFuzhou350014China Department of Pathology Peking University Cancer Hospital&InstituteBeijing100142China

Dear Editor,Extramammary Paget disease(EMPD)is a rare adenocarcinoma that originates in the apocrine gland-rich skin and usually affects the perineal skin(primary EMPD)or represents the intraepithelial spread of an underlying visceral carcinoma(secondary EMPD).Approximately half of EMPD cases are confined to the epidermis,which was defined as intraepithelial EMPD.

关键词： Paget HER2 adenocarcinoma

Lack of evidence for germline WWP1 pathogenic variants in gastrointestinal polyposis and other phenotypes suggestive of PTEN-hamartoma-tumor syndrome

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Genes & Diseases 2024年第2期11卷 524-527页

作者： Noemi Gonzalez-Abuin Tirso Pons Teresa Fuster Isabel Quintana Mariona Terradas Gemma Aiza Joan Brunet Gabriel Capellá Heather Hampel Laura Valle Hereditary cancer Program Catalan Institute of OncologyOncobell ProgramIDIBELLHospitalet de LlobregatBarcelona 08908Spain Department of Immunology and Oncology National Center for BiotechnologySpanish National Research Council (CNB-CSIC)Madrid 28049Spain Centro de Investigación Biomédica en Red de Cáncer (CIBERONC) Madrid 28029Spain Catalan institute of Oncology IDIBGiGirona 17007Spain Division of Clinical cancer Genomics Department of Medical Oncology & Therapeutic ResearchCity of Hope National Cancer CenterDuarteCA 91010USA

Germline activating variants in WWP1,which encodes an E3 ubiquitin ligase that antagonizes PTEN tumor suppressive function,have been proposed as an alternative mechanism of PTEN inactivation in PTEN-hamartoma-tumor syndrome(PHTS)-like patients with wildtype PTEN.1 More specifically,heterozygous,potentially activating wwP1 variants were first identified by Lee et al in patients affected with gastrointestinal oligopolyposis,including adenomatous,hyperplastic/serrated,and hamartomatous polyps,and occasionally with colorectal cancer(Table 1).Subsequently,based on the PHTS phenotypic features,wWP1 mutational screening was performed in patients with thyroid nodules,2 or normocephalic autism spectrum disorder(ASD),3 where germline WWP1 variants were also identified(Table S1).

关键词： WWP1 gastrointestinal polyposis

Targeting lncRNA16 by GalNAc-siRNA conjugates facilitates chemotherapeutic sensibilization via the HBB/NDUFAF5/ROS pathway

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Science China(Life Sciences) 2024年第4期67卷 663-679页

作者： Yanfang Liu Yan Wang Bing Liu Wenzhong Liu Yuanyuan Ma Yiren Cao Shi Yan Panpan Zhang Lixin Zhou Qimin Zhan Nan Wu Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of Thoracic Surgery IIPeking University Cancer Hospital and InstituteBeijing 100142China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Laboratory of Molecular OncologyPeking University Cancer Hospital and InstituteBeijing 100142China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of Thoracic Oncology IIPeking University Cancer Hospital and InstituteBeijing 100142China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education) Department of PathologyPeking University Cancer Hospital and InstituteBeijing 100142China Peking University International cancer institute Beijing 100191China institute of cancer Research Shenzhen Bay LaboratoryShenzhen 518132China

Chemoresistance is a significant barrier to effective cancer *** mechanisms for chemoresistance include reactive oxygen species(ROS)accumulation and expression of chemoresistance-promoting ***,we report a novel function of lncRNA16 in the inhibition of ROS generation and the progression of *** analyzing the serum levels of lncRNA16 in a cohort of 35 patients with non-small cell lung cancer(NSCLC)and paired serum samples pre-and post-treatment from 10 NSCLC patients receiving neoadjuvant platinum-based chemotherapy,performing immunohistochemistry(IHC)assays on 188 NSCLC tumor samples,using comprehensive identification of RNA-binding proteins by mass spectrometry(ChIRP-MS)assays,as well as RNA immunoprecipitation(RIP)and RNA pull-down analyses,we discovered that patients with increased serum levels of lncRNA16 exhibited a poor response to platinum-based *** expression of hemoglobin subunit beta(HBB)and NDUFAF5 significantly increases with the development of ***16 binds to HBB and promotes HBB accumulation by inhibiting ***16 can also inhibit ROS generation via the HBB/NDUFAF5 axis and function as a scaffold to facilitate the colocalization of HBB and NDUFAF5 in the ***,preclinical studies in mouse models of chemo-resistant NSCLC have suggested that lncRNA16 targeting by trivalent N-acetylgalactosamine(GalNAc)-conjugated siRNA restores chemosensitivity and results in tumor growth inhibition with no detectable toxicity in ***,lncRNA16 is a promising therapeutic target for overcoming chemoresistance,and the combination of first-line platinum-based chemotherapy with lncRNA16 intervention can substantially enhance anti-tumor efficacy.

关键词： chemoresistance lncRNARNA interference ROs chemosensitizer

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Somatic CDKN2A copy number variations are associated with the prognosis of esophageal squamous cell dysplasia

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Chinese Medical Journal 2024年第8期137卷 980-989页

作者： Zhiyuan Fan Jing Zhou Yuan Tian Yu Qin Zhaojun Liu Liankun Gu Sanford M.Dawsey Wenqiang Wei Dajun Deng national Central cancer Registry National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Key Laboratory of Carcinogenesis and Translational Research(MOE/Beijing) Division of EtiologyPeking University Cancer Hospital and InstituteBeijing 100142China Division of cancer Epidemiology and Genetics National Cancer InstituteBethesdaMDUSA Collaborative Innovation Center for cancer Personalized Medicine Nanjing Medical UniversityNanjingJiangsu 211166China

Background:Somatic copy number variations(SCNVs)in the CDKN2A gene are among the most frequent events in the dysplasia-carcinoma sequence of esophageal squamous cell ***,whether CDKN2A SCNVs are useful biomarkers for the risk stratification and management of patients with esophageal squamous cell dysplasia(ESCdys)is *** study aimed to investigate the characteristics and prognostic value of CDKN2A SCNVs in patients with mild or moderate(m/M)***:This study conducted a prospective multicenter study of 205 patients with a baseline diagnosis of m/M ESCdys in five high-risk regions of China(Ci County,Hebei Province;Yanting,Sichuan Province;Linzhou,Henan Province;Yangzhong,Jiangsu Province;and Feicheng,Shandong Province)from 2005 to *** DNA was extracted from paraffin biopsy samples and paired peripheral white blood cells from patients,and a quantitative polymerase chain reaction assay,P16-Light,was used to detect CDKN2A copy *** cumulative regression and progression rates of ESCdys were evaluated using competing risk ***:A total of 205 patients with baseline m/M ESCdys were *** proportion of ESCdys regression was significantly lower in the CDKN2A deletion cohort than in the diploid and amplification cohorts(18.8%[13/69]vs.35.0%[28/80]vs.51.8%[29/56],P<0.001).In the univariable competing risk analysis,the cumulative regression rate was statistically significantly lower(P=0.008),while the cumulative progression rate was higher(P=0.017)in ESCdys patients with CDKN2A deletion than in those without CDKN2A ***2A deletion was also an independent predictor of prognosis in ESCdys(P=0.004)in the multivariable ***:The results indicated that CDKN2A SCNVs are associated with the prognosis of ESCdys and may serve as potential biomarkers for risk stratification.

关键词： Somatic copy number variations Esophageal squamous cell carcinoma Esophageal neoplasms Squamous intraepithelial lesions DNA copy number variations Prognosis Prospective study

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A novel metal-free porous covalent organic polymer for efficient room-temperature photocatalytic CO2 reduction via dry-reforming of methane

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Green Energy & Environment 2024年第9期9卷 1407-1418页

作者： Sheng-Yan Yin Ziyi Li Yingcai Hu Xiao Luo Jishan Li College of Chemistry and Chemical Engineering Hunan University institute of Basic Medicine and cancer (IBMC) Chinese Academy of Sciences

At room temperature,the conversion of greenhouse gases into valuable chemicals using metal-free catalysts for dry reforming of methane（DRM） is quite promising and ***,we developed a novel covalent organic porous polymer （TPE-COP） with rapid charge separation of the electron–hole pairs for DRM driven by visible light at room temperature,which can efficiently generate syngas （CO and H2）.Both electron donor (tris（4-aminophenyl）amine,TAPA) and acceptor (4,4',4'',4'''-(（1 E,1'E,1''E,1'''E）-(ethene-1,1,2,2-tetrayltetrakis （benzene-4,1-diyl）)tetrakis （ethene-2,1-diyl）)tetrakis (1-（4-formylbenzyl）quinolin-1-ium),TPE-CHO) were existed in TPE-COP,in which the push–pull effect between them promoted the separation of photogenerated electron–hole,thus greatly improving the photocatalytic *** functional theory （DFT） simulation results show that TPE-COP can form charge-separating species under light irradiation,leading to electrons accumulation in TPE-CHO unit and holes in TAPA,and thus efficiently initiating *** 20 h illumination,the photocatalytic results show that the yields reach 1123.6 and 30.8μmol g-1for CO and H2,respectively,which are significantly higher than those of TPE-CHO small *** excellent result is mainly due to the increase of specific surface area,the enhancement of light absorption capacity,and the improvement of photoelectron-generating efficiency after the formation of ***,this work contributes to understanding the advantages of COP materials for photocatalysis and fundamentally pushes metal-free catalysts into the door of DRM field.

关键词： Metal-free Photocatalytic CO 2 reduction Covalent organic polymer Dry-reforming of methane Electron donor and acceptor

Engineering biomimetic nanosystem targeting multiple tumor radioresistance hallmarks for enhanced radiotherapy

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Science China(Life Sciences) 2024年第7期67卷 1398-1412页

作者： Shuxiang Wang Hongmei Cao Cui-Cui Zhao Qian Wang Dianyu Wang Jinjian Liu Lijun Yang Jianfeng Liu State Key Laboratory of Advanced Medical Materials and Devices Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear MedicineKey Laboratory of Radiopharmacokinetics for Innovative DrugsTianjin Institutes of Health ScienceInstitute of Radiation MedicineChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300192China Tianjin Medical University cancer institute and Hospital National Clinical Research Center for CancerTianjin’s Clinical Research Center for CancerKey Laboratory of Cancer Prevention and Therapy(Tianjin)Key Laboratory of Breast Cancer Prevention and TherapyTianjin Medical UniversityMinistry of EducationTianjin 300060China

Tumor cells establish a robust self-defense system characterized by hypoxia,antioxidant overexpression,DNA damage repair,and so forth to resist *** one of these features is insufficient to overcome radioresistance due to the feedback mechanisms initiated by tumor cells under ***,we herein developed an engineering biomimetic nanosystem(M@HHPt)masked with tumor cell membranes and loaded with a hybridized protein-based nanoparticle carrying oxygens(O_(2))and cisplatin prodrugs(Pt(Ⅳ))to target multiple tumor radioresistance hallmarks for enhanced *** administration,M@HHPt actively targeted and smoothly accumulated in tumor cells by virtue of its innate homing abilities to realize efficient co-delivery of O_(2)and Pt(Ⅳ).O_(2)introduction induced hypoxia alleviation cooperated with Pt(Ⅳ)reduction caused glutathione consumption greatly amplified radiotherapy-ignited cellular oxidative ***,the released cisplatin effectively hindered DNA damage repair by crosslinking with radiotherapy-produced DNA ***,M@HHPt-sensitized radiotherapy significantly suppressed the proliferation of lung cancer H1975 cells with an extremely high sensitizer enhancement ratio of 1.91 and the progression of H1975 tumor models with an excellent tumor inhibition rate of 94.7%.Overall,this work provided a feasible strategy for tumor radiosensitization by overcoming multiple radioresistance mechanisms.

关键词： biomimetic nanosystem hypoxia alleviation glutathione consumption oxidative stress amplification DNA damage fixation radiosensitization

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Tumor initiation and early tumorigenesis:molecular mechanisms and interventional targets

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Signal Transduction and Targeted Therapy 2024年第7期9卷 2900-2935页

作者： Shaosen Zhang Xinyi Xiao Yonglin Yi Xinyu Wang Lingxuan Zhu Yanrong Shen Dongxin Lin Chen Wu Department of Etiology and Carcinogenesis National Cancer Center/National Clinical Research Center/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College100021 BeijingChina Key Laboratory of cancer Genomic Biology Chinese Academy of Medical Sciences and Peking Union Medical College100021 BeijingChina Changping Laboratory 100021 BeijingChina Collaborative Innovation Center for cancer Personalized Medicine Nanjing Medical UniversityNanjing 211166China Sun Yat-sen University cancer Center State Key Laboratory of Oncology in South ChinaGuangzhou 510060China CAMS Oxford institute Chinese Academy of Medical Sciences100006 BeijingChina

Tumorigenesis is a multistep process,with oncogenic mutations in a normal cell conferring clonal advantage as the initial ***,despite pervasive somatic mutations and clonal expansion in normal tissues,their transformation into cancer remains a rare event,indicating the presence of additional driver events for progression to an irreversible,highly heterogeneous,and invasive ***,researchers are emphasizing the mechanisms of environmental tumor risk factors and epigenetic alterations that are profoundly influencing early clonal expansion and malignant evolution,independently of inducing ***,clonal evolution in tumorigenesis reflects a multifaceted interplay between cell-intrinsic identities and various cell-extrinsic factors that exert selective pressures to either restrain uncontrolled proliferation or allow specific clones to progress into ***,the mechanisms by which driver events induce both intrinsic cellular competency and remodel environmental stress to facilitate malignant transformation are not fully *** this review,we summarize the genetic,epigenetic,and external driver events,and their effects on the co-evolution of the transformed cells and their ecosystem during tumor initiation and early malignant evolution.A deeper understanding of the earliest molecular events holds promise for translational applications,predicting individuals at high-risk of tumor and developing strategies to intercept malignant transformation.

关键词： alterations mechanisms restrain

Can patients with mild non-neoplastic lesions diagnosed at baseline screening be safely exempt from surveillance: evidence from multicenter community-based cohorts

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Science China Life Sciences 2024年

作者： Siyi He Zhiyi Zhang Guohui Song Zhenhai Wang Chunyun Dai Shipeng Yan Kun Jiang Bingbing Song He Li Maomao Cao Dianqin Sun Fan Yang Xinxin Yan Shaoli Zhang Yi Teng Qianru Li Changfa Xia Wanqing Chen Office of cancer Screening National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Department of Gastroenterology Gansu Wuwei Tumor Hospital Cixian cancer institute Linzhou cancer Hospital Center for Disease Control and Prevention of Sheyang County Department of cancer Prevention and Control Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine Central South University Luoshan Center for Disease Control and Prevention Office for cancer Control and Research Affiliated Cancer Hospital of Harbin Medical University

Surveillance recommendations for gastric cancer(GC) in current guidelines focused on advanced precancerous lesions and were based on precise diagnosis of severity/extent of baseline lesions. We aimed to develop a less endoscopy-related equipment-dependent risk-stratification tool, and assessed whether mild-precursor-lesion patients can be safely exempt from surveillance. In the multicenter communitybased cohort, 75,051 participants receiving baseline endoscopy were enrolled during 2015–2017 and followed-up until 2021. Cumulative incidence rates(CIRs) of GC for precancerous-conditions were calculated by Kaplan-Meier method and compared by Log-rank tests. Mixedeffects Cox regression models were used to detect potential factors for progression towards GC. A risk score was calculated as counts of selected factors. An independent cohort, including 26,586 participants was used for external validation. During a median follow-up of6.25 years, CIRs of GC were 0.302%, 0.436%, and 4.756% for normal group, non-neoplastic(atrophic gastritis/intestinal metaplasia) and neoplastic lesions(low-grade/high-grade dysplasia), respectively(Ptrend<0.001). Four predictors, including male, ≥60 years, smoking, and limited vegetable consumption, were selected for risk-stratification. High-risk patients(≥3 risk factors) with non-neoplastic lesions showed higher GC risks(adjusted HR=7.73, 95%CI: 4.29–13.92), and their four-year CIR reached the one-year CIR of neoplastic lesions. Further categorizing non-neoplastic lesions by histological grade, both patients with moderate-to-severe lesions(aHR=3.07, 95%CI: 1.67–5.64) and high-risk patients with mild lesions(aHR=7.29, 95%CI: 3.58–14.86) showed higher risks. Consistent trends were observed in validation cohort. High-risk mild-precursor-lesion patients should receive surveillance within 3–5 years after baseline screening. Our study provides evidence on supplementing current guideline recommendations.

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Lipid metabolism analysis in esophageal cancer and associated drug discovery

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Journal of Pharmaceutical Analysis 2024年第1期14卷 1-15页

作者： Ruidi Jiao Wei Jiang Kunpeng Xu Qian Luo Luhua Wang Chao Zhao Bionic Sensing and Intelligence Center Institute of Biomedical and Health EngineeringShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong518000China Department of Radiation Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital&Shenzhen HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhenGuangdong518116China School of Medicine Southern University of Science and TechnologyShenzhenGuangdong518000China University of Chinese Academy of Sciences Beijing100049China Shenzhen Key Laboratory of Precision Diagnosis and Treatment of Depression Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong518000China

Esophageal cancer is an upper gastrointestinal malignancy with a bleak *** is still being explored in depth due to its complex molecular mechanisms of occurrence and *** play a crucial role in cells by participating in energy supply,biofilm formation,and signal transduction processes,and lipid metabolic reprogramming also constitutes a significant characteristic of malignant *** and more studies have found esophageal cancer has obvious lipid metabolism abnormalities throughout its beginning,progress,and treatment *** inhibition of tumor growth and the enhancement of antitumor therapy efficacy can be achieved through the regulation of lipid ***,we reviewed and analyzed the research results and latest findings for lipid metabolism and associated analysis techniques in esophageal cancer,and comprehensively proved the value of lipid metabolic reprogramming in the evolution and treatment resistance of esophageal cancer,as well as its significance in exploring potential therapeutic targets and biomarkers.

关键词： Lipid metabolism Esophageal cancer Progression Treatment resistance New therapeutic targets

Single-cell RNA-seq reveals the transcriptional program underlying tumor progression and metastasis in neuroblastoma

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Frontiers of Medicine 2024年第4期18卷 690-707页

作者： Zhe Nian Dan Wang Hao Wang Wenxu Liu Zhenyi Ma Jie Yan Yanna Cao Jie Li Qiang Zhao Zhe Liu Department of Immunology School of Basic Medical SciencesTianjin Medical UniversityTianjin300070China Zhejiang Key Laboratory of Medical Epigenetics Department of Cell BiologySchool of Basic Medical SciencesHangzhou Normal UniversityHangzhou311121China Department of Pediatric Oncology Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjin’s Clinical Research Center for CancerTianjin300060China Collaborative Innovation Center for cancer Personalized Medicine Nanjing Medical UniversityNanjing211166China

Neuroblastoma(NB)is one of the most common childhood *** percent of patients present with widely disseminated clinical signs at diagnosis and exhibit poor ***,the molecular mechanisms triggering NB metastasis remain largely *** this study,we generated a transcriptomic atlas of 15447 NB cells from eight NB samples,including paired samples of primary tumors and bone marrow *** used time-resolved analysis to chart the evolutionary trajectory of NB cells from the primary tumor to the metastases in the same patient and identified a common‘starter’subpopulation that initiates tumor development and ***‘starter’population exhibited high expression levels of multiple cell cycle-related genes,indicating the important role of cell cycle upregulation in NB tumor *** addition,our evolutionary trajectory analysis demonstrated the involvement of partial epithelial-to-mesenchymal transition(p-EMT)along the metastatic route from the primary site to the bone *** study provides insights into the program driving NB metastasis and presents a signature of metastasis-initiating cells as an independent prognostic indicator and potential therapeutic target to inhibit the initiation of NB metastasis.

关键词： single-cell RNA sequencing metastasis neuroblastoma epithelial-to-mesenchymal transition