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Assessment of HER2 status in extramammary Paget disease and its implication for disitamab vedotin,a novel humanized anti-HER2 antibody-drug conjugate therapy

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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

Designing macrophage membrane-engineered ruthenium/selenium nanoparticles to block bone metastasis of breast cancer

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Nano research 2024年第8期17卷 7504-7512页

作者： Meijin Yang Zhiying Tang Xiaoying Li Yanzi Yu Lizhen He Tianfeng Chen College of Chemistry and Materials Science Department of Oncology of The First Affiliated HospitalJinan UniversityGuangzhou 510632China

Bone metastasis along with osteolysis is a common complication of advanced breast cancer,which directly destroys bone function and becomes one of the major causes of cancer-related *** is crucial to develop a new strategy to achieve effective cancer therapy and inhibition of osteolytic bone *** ruthenium(Ru)complexes exhibit therapeutic potential in cancer ***,the clinical applications of Ru complexes were limited by poor bioavailability,lacking targeting,nonspecific ***,in this study,engineering of cell membrane biomimetic modification was used to construct a highly biocompatible nanoplatform with carrying Ru metal complex of RuPOP and Se nanoparticles(SeNPs).Strikingly,the obtained RPSR nanoparticles can efficiently inhibit the proliferation,invasion and migration of breast cancer cells(MDA-MB-231 cells)in *** importantly,RPSR nanoparticles can induce cycle arrest,apoptosis by generating excessive intracellular(reactive oxygen species,ROS)to disrupt the normal redox balance and induce DNA damage in tumor ***,RPSR nanoparticles can also reshape bone microenvironment by regulating selenoproteins to inhibit osteoclasts and avoid osteolytic bone metastasis induced by tumor *** together,this study not only provides an effective cell membrane biomimetic strategy to enhance the shortcomings of metal complexes,but also demonstrates potential clinical significance for the combined treatment of anti-cancer and bone metastasis inhibition.

关键词： cell membrane nanoparticles biomimetic modification ruthenium complexes selenium nanoparticles tumor bone metastasis

Single-atom alloys prepared by two-step thermal evaporation

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Nano research 2024年第4期17卷 2808-2813页

作者： Honglin Wang Jing Li Meirong Huang Jizhe Cui Zhiying Cheng Rong Yu Hongwei Zhu State Key lab of New Ceramics and Fine Processing School of Materials Science and EngineeringTsinghua UniversityBeijing 100084China State Key lab of Solid Waste Reuse for Building Materials Beijing Building Materials Academy of Science ResearchBeijing 100041China

Single-atom alloys(SAAs)have gained significant attention due to their remarkable atomic utilization efficiency,interactions between single atoms(SAs)and metal supports,and free-atom-like electronic structure of dopant *** this work,we observed the formation of SAs in pre-deposited metal particles by a two-step thermal evaporation technique,thereby establishing the first instance of discovering SAAs by thermal *** discovery of SAAs by thermal evaporation extends the range of SAAs preparation methods to include this traditional synthetic technique,which offers convenience,cost-efficiency,and *** formation mechanism of SAAs prepared using this technique was elucidated by density functional theory *** was demonstrated that thermal evaporation can be utilized to prepare SAAs with multiple SAs,further highlighting its universal applicability.

关键词： single-atom alloys thermal evaporation density functional theory

Precise nano-system-based drug delivery and synergistic therapy against androgen receptor-positive triple-negative breast cancer

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2685-2697页

作者： Fangyan Gao Yueyao Wu Runtian Wang Yuhui Yao Yiqiu Liu Lingling Fan Jingtong Xu Jian Zhang Xin Han Xiaoxiang Guan Department of oncology the First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization School of Medicine&Holistic Integrative MedicineNanjing University of Chinese MedicineNanjing 210023China Department of oncology the Second Hospital of NanjingNanjing University of Chinese MedicineNanjing 210023China Department of Medical oncology Fudan University Shanghai Cancer CenterShanghai 200032China Jiangsu Key lab of Cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjing 211166China

Targeting androgen receptor(AR)has shown great therapeutic potential in triple-negative breast cancer(TNBC),yet its efficacy remains ***,we aimed to identify promising targeted agents that synergize with enzalutamide,a second-generation AR inhibitor,in *** using a strategy for screening drug combinations based on the Sensitivity Index(SI),we found that MK-8776,a selective checkpoint kinase1(CHK1)inhibitor,showed favorable synergism with enzalutamide in AR-positive *** combination of enzalutamide and MK-8776 was found to exert more significant anti-tumor effects in TNBC than the single application of enzalutamide or MK-8776,***,a nanoparticle-based on hyaluronic acid(HA)-modified hollow-manganese dioxide(HMnO_(2)),named HMnE&M@H,was established to encapsulate and deliver enzalutamide and *** HA-modified nanosystem managed targeted activation via pH/glutathione ***&M@H repressed tumor growth more obviously than the simple addition of enzalutamide and MK-8776 without a ***,our study elucidated the synergy of enzalutamide and MK-8776 in TNBC and developed a novel tumor-targeted nano drug delivery system HMnE&M@H,providing a potential therapeutic approach for the treatment of TNBC.

关键词： Triple-negative breast cancer Androgen receptor Checkpoint kinase 1 Enzalutamide MK-8776 Synergy HMnO_(2) Nanodrug delivery system

Ultrasound-responsive spherical nucleic acid against c-Myc/PD-L1 to enhance anti-tumoral macrophages in triple-negative breast cancer progression

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Science China(Life Sciences) 2024年第4期67卷 698-710页

作者： Runtian Wang Gaigai Li Fangyan Gao Feng Xu Xintong Li Jian Zhang Jinbo Li Xiaoxiang Guan Department of oncology The First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China State Key laboratory of Analytical Chemistry for Life Sciences Jiangsu Key Laboratory of Advanced Organic MaterialsSchool of Chemistry and Chemical EngineeringChemistry and Biomedicine Innovation Center(ChemBIC)Nanjing UniversityNanjing 210023China Department of Medical oncology Fudan University Shanghai Cancer CenterDepartment of OncologyShanghai Medical CollegeFudan UniversityShanghai 200032China Jiangsu Key lab of Cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjing 211166China

Triple-negative breast cancer(TNBC)is the most challenging breast cancer subtype because of its aggressive behavior and limited therapeutic targets.c-Myc is hyperactivated in the majority of TNBC tissues,however,it has been considered an“undruggable”target due to its disordered ***,we developed an ultrasound-responsive spherical nucleic acid(SNA)against c-Myc and PD-L1 in *** is a self-assembled and carrier-free system composed of a hydrophilic small-interfering RNA(si RNA)shell and a hydrophobic core made of a peptide nucleic acid(PNA)-based antisense oligonucleotide(ASO)and a *** accomplished significant enrichment in the tumor by enhanced permeability and retention(EPR)effect,the controllable release of effective elements by ultrasound activation,and the combination of targeted therapy,immunotherapy and *** study demonstrated significant anti-tumoral effects in vitro and in *** cytometry showed an invigorated tumor microenvironment(TME)characterized by a significant alteration in the composition of tumor-associated macrophages(TAM)and decreased proportion of PD-1-positive(PD-1+)T effector cells after appropriate treatment of the ultrasound-responsive SNA(USNA).Further experiments verified that tumor-conditioned macrophages residing in the TME were transformed into the anti-tumoral *** finding offers a novel therapeutic strategy against the“undruggable”c-Myc,develops a new targeted therapy for c-Myc/PD-L1 and provides a treatment option for the TNBC.

关键词： triple-negative breast cancer c-Myc spherical nucleic acid self-assembly

Palmitic acid reduces the methylation of the FOXO1 promoter to suppress the development of diffuse large B-cell lymphoma via modulating the miR-429/DNMT3A axis

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Chinese Journal of Natural Medicines 2024年第6期22卷 554-567页

作者： LI Weiming GAO Ming XUE Weili LI Xiaoli CHANG Yu ZHANG Kaixin WEN Chenyu ZHANG Mingzhi Department of oncology Henan University of Traditional Chinese MedicineZhengzhou 450000China Department of oncology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450000China

Diffuse large B-cell lymphoma(DLBCL)is characterized by significant treatment *** acid(PA)has shown promising antitumor *** study aims to elucidate the molecular mechanisms by which PA influences DLBCL *** quantified the expression levels of microRNAs(miRNAs),Forkhead box protein O1(FOXO1),and DNA methyltransferase 3A(DNMT3A)in both untreated and PA-treated DLBCL tumors and cell *** were made of cell viability,apoptosis,and autophagy-related protein expression following PA *** analyses among miR-429,DNMT3A,and FOXO1 were conducted using luciferase reporter assays and methylation-specific(MSP)Polymerase chain reaction(PCR).After transfecting the miR-429 inhibitor,negative control(NC)inhibitor,shRNA against DNMT3A(sh-DNMT3A),shRNA negative control(sh-NC),over-expression vector for DNMT3A(oe-DNMT3A),or overexpression negative control(oe-NC),we evaluated the effects of miR-429 and DNMT3A on cell viability,mortality,and autophagy-related protein expression in PA-treated DLBCL cell *** efficacy of PA was also tested in vivo using DLBCL tumor-bearing mouse ***-429 and FOXO1 expression levels were downregulated,whereas DNMT3A was upregulated in DLBCL compared to the control *** treatment was associated with enhanced autophagy,mediated by the upregulation of miR-429 and downregulation of *** luciferase reporter assay and MSP confirmed that miR-429 directly inhibits DNMT3A,thereby reducing FOXO1 *** experiments demonstrated that PA promotes autophagy and inhibits DLBCL progression by upregulating miR-429 and modulating the DNMT3A/FOXO1 *** vivo PA signific-antly reduced the growth of xenografted tumors through its regulatory impact on the miR-429/DNMT3A/FOXO1 *** acid may modulate autophagy and inhibit DLBCL progression by targeting the miR-429/DNMT3A/FOXO1 signaling pathway,suggesting a novel therapeutic target for DLBCL management.

关键词： Palmitic acid Diffuse large B-cell lymphoma MiR-429 DNMT3A FOXO1 Autophagy

Circular RNAs in breast cancer diagnosis,treatment and prognosis

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oncology research 2024年第2期32卷 241-249页

作者： XIAOJIA HUANG CAILU SONG JINHUI ZHANG LEWEI ZHU HAILIN TANG Department of Breast oncology Surgery Affiliated Cancer Hospital&Institute of Guangzhou Medical UniversityGuangzhou510095China State Key laboratory of oncology in South China Guangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou510060China Department of Breast Surgery The First People’s Hospital of FoshanFoshan528000China

Breast cancer has surpassed lung cancer to become the most common malignancy *** incidence rate and mortality rate of breast cancer continue to rise,which leads to a great burden on public *** RNAs(circRNAs),a new class of noncoding RNAs(ncRNAs),have been recognized as important oncogenes or suppressors in regulating cancer initiation and *** breast cancer,circRNAs have significant roles in tumorigenesis,recurrence and multidrug resistance that are mediated by various ***,circRNAs may serve as promising targets of therapeutic strategies for breast cancer *** study reviews the most recent studies about the biosynthesis and characteristics of circRNAs in diagnosis,treatment and prognosis evaluation,as well as the value of circRNAs in clinical applications as biomarkers or therapeutic targets in breast *** the mechanisms by which circRNAs function could help transform basic research into clinical applications and facilitate the development of novel circRNA-based therapeutic strategies for breast cancer treatment.

关键词： CircRNA Breast cancer Diagnosis Treatment Biomarker

Clinicopathological significance and immunotherapeutic outcome of claudin 18.2 expression in advanced gastric cancer:A retrospective study

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Chinese Journal of Cancer research 2024年第1期36卷 78-89页

作者： Changsong Qi Xiaoyi Chong Ting Zhou Mingyang Ma Jifang Gong Miao Zhang Jian Li Jun Xiao Xiaohui Peng Zhen Liu Zonghai Li Lin Shen Xiaotian Zhang State Key laboratory of Holistic Integrative Management of Gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchDepartment of Gastrointestinal OncologyPeking University Cancer Hospital&InstituteBeijing 100142China Key laboratory of Carcinogenesis and Translational research(Ministry of Education/Beijing) Department of Gastrointestinal OncologyPeking University Cancer Hospital&InstituteBeijing 100142China CARsgen Therapeutics Co. LtdShanghai 200231China CARsgen Life Sciences Co. LtdShanghai 200131China

Objective: Immunotherapeutic outcomes and clinical characteristics of claudin 18 isoform 2 positive(CLDN18.2-positive) gastric cancer(GC) vary in different clinical studies, making it difficult to optimize antiCLDN18.2 therapy. We conducted a retrospective analysis to explore the association of CLDN18.2 expression with clinicopathological characteristics and immunotherapeutic outcomes in ***: A total of 536 advanced GC patients from 2019 to 2021 in the CT041-CG4006 and CT041-ST-01clinical trials were included in the analysis. CLDN18.2 expression on ≥40% of tumor cells(2+, 40%) and CLDN18.2 expression on ≥70% of tumor cells(2+, 70%) were considered the two levels of positively expressed GC. The clinicopathological characteristics and immunotherapy outcomes of GC patients were analyzed according to CLDN18.2 expression ***: CLDN18.2 was expressed in 57.6%(cut-off: 2+, 40%) and 48.9%(cut-off: 2+, 70%) of *** death-ligand 1(PD-L1) and CLDN18.2 were co-expressed in 19.8% [combined positive score(CPS)≥1, CLDN18.2(cut-off: 2+, 40%)] and 17.2% [CPS≥5, CLDN18.2(cut-off: 2+, 70%)] of ***18.2 expression positively correlated with younger age, female sex, non-gastroesophageal junction(nonGEJ), and diffuse phenotype(P<0.001). HER2 and PD-L1 expression were significantly lower in CLDN18.2-positive GC(both P<0.05). Uterine adnexa metastasis(P<0.001) was more frequent and liver metastasis(P<0.001)was less common in CLDN18.2-positive GC. Overall survival and immunotherapy-related progression-free survival(ir PFS) were inferior in the CLDN18.2-positive ***: CLDN18.2-positive GC is associated with poor prognosis and worse immunotherapeutic outcomes. The combination of anti-CLDN18.2 therapy, anti-PD-L1/PD-1 therapy, and chemotherapy for GC requires further investigation.

关键词： Gastric cancer claudin18.2 CT041 PD-L1 immunotherapy

The E3 ubiquitin ligase TRAF6 controls CTLA-4 turnover and promotes T-cell-mediated antitumor immunity

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Cellular & Molecular Immunology 2024年第1期21卷 97-99页

作者： Xiao-Liang Jie Hua Guo Guang-Biao Zhou State Key laboratory of Molecular oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College100021 BejingChina

Yu et al.[1]reported that the tumor necrosis factor(TNF)receptor OX40(CD134)-TNF receptor-associated factor 6(TRAF6)axis mediates Lys63-linked ubiquitination and subsequent lysosomal degradation of cytotoxic T-lymphocyte antigen 4(CTLA-4),leading to the enhancement of CD8^(+)T-cell-mediated antitumor *** findings unveil a previously unknown mechanism in controlling the stability of the immune checkpoint CTLA-4 and provide a potential therapeutic target for the improvement of Tcell-based immunotherapy.

关键词： immunity OX40 ubiquitin