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Adaptive ultra-hypofractionated whole-pelvic radiotherapy in high-risk and very high-risk prostate cancer on 1.5-Tesla mR-Linac:Estimated delivered dose and early toxicity results

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Chronic diseases and Translational m.d.cine 2024年第1期10卷 51-61页

作者： Linrui Gao Ran Wei Shirui Qin Yuan Tian Wenlong Xia Yongwen Song Shulian Wang Hui Fang Yu Tang Hao Jing Yueping Liu Yuan Tang Shunan Qi Bo Chen Yexiong Li Nianzeng Xing Ningning Lu department of Radiation Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina GCP center/Clinical Research center National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina department of Urology State Key Laboratory of Molecular OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

Background: magnetic resonance(mR)-guided ultra-hypofractionated radiotherapy with whole-pelvic irradiation(UHF-WPRT)is a novel approach to radiotherapy for patients with high-risk(HR)and very high-risk(VHR)prostate cancer(PCa).However,the inherent complexity of adaptive UHF-WPRT might inevitably result in longer on-couch *** aim.d.to estimate the delivered dose,study the feasibility and safety of adaptive UHF-WPRT on a 1.5-Tesla ***: Ten patients with clinical stage T3a-4N0-1m0-1c PCa,who consecutively received UHF-WPRT,were enrolled *** contours of the target and organ-at-risks on the position verification-mR(PV-mR),beam-on 3d-mR(Bn-mR),and post-mR(after radiotherapy delivery)were derived from the pre-mR data by deformable image *** physician then manually adjusted them,and dose recalculation was perform.d.*** Prism 9(GraphPad Prism Software Inc.)was utilized for conducting statistical ***: In total,we collected 188 mR scans(50 pre-mR,50 PV-mR,44 Bn-mR,and 44 post-mR scans).With m.d.an 59 min,the mean prostate clinical target volume(CTV)-V_(100%)was 98.59%±2.74%,and the mean pelvic CTVp-V_(100%)relative percentages of all scans was 99.60%±1.18%.The m.d.an V29 Gy change in the rectal wall was−2%(−18%to 20%).With a m.d.an follow-up of 9 months,no patient had acute Common Terminology Criteria for Adverse Events(CTCAE)grade 2 or more severe genitourinary(GU)or gastrointestinal(GI)toxicities(0%).Conclusion: UHF-RT to the prostate and the whole pelvis with concomitant boost to positive nodes using an Adapt-To-Shape(ATS)workflow was technically feasible for patients with HR and VHR PCa,presenting only mild GU and GI *** estimated target dose during the beam-on phase was clinically acceptable based on the 3d-mR-based dosimetry *** trial registration Chinese Clinical Trial Registry ChiCTR2000033382.

关键词： dosimetry hypofractionation magnetic resonance imaging prostate cancer radiation dose radiotherapy

Aberrant epithelial cell interaction promotes esophageal squamous-cell carcinoma development and progression

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Signal Transduction and Targeted Therapy 2024年第1期9卷 279-294页

作者： Liping Chen Shihao Zhu Tianyuan Liu Xuan Zhao Tao Xiang Xiao Hu Chen Wu dongxin Lin department of Etiology and Carcinogenesis National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Key Laboratory of cancer Genomic Biology Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Collaborative Innovation center for cancer Personalized m.d.cine Nanjing Medical UniversityNanjing 211166China CAmS Oxford Institute Chinese Academy of Medical SciencesBeijing 100006China Sun Yat-sen University cancer center State Key Laboratory of Oncology in South ChinaGuangzhou 510060China

Epithelial-mesenchymal transition(EmT)and proliferation play important roles in epithelial cancer formation and progression,but what molecules and how they trigger EmT is largely *** we perform.d.spatial transcriptomic and functional analyses on samples of multistage esophageal squamous-cell carcinoma(ESCC)from mice and humans to decipher these critical *** investigating spatiotemporal gene expression patterns and cell–cell interactions,we demonstrated that the aberrant epithelial cell interaction via EFNB1-EPHB4 triggers EmT and cell cycle m.d.ated by downstream SRC/ERK/AKT *** aberrant epithelial cell interaction occurs within the basal layer at early precancerous lesions,which expands to the whole epithelial layer and strengthens along the cancer development and *** analysis revealed that the aberrant EFNB1-EPHB4 interaction is caused by overexpressedΔNP63 due to TP53 mutation,the culprit in human ESCC *** results shed new light on the role of TP53-TP63/ΔNP63-EFNB1-EPHB4 axis in EmT and cell proliferation in epithelial cancer formation.

关键词： esophageal TP53 squamous

The Functional Redundancy of Neddylation E2s and E3s in m.d.lating the Fitness of Regulatory T Cells

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Research 2024年第2期2023卷 373-387页

作者： di Wu Yi Sun cancer Institute(Key Laboratory of cancer Prevention and Intervention China National Ministry of Education)of the Second Affiliated Hospital and Institute of Translational MedicineZhejiang University School of MedicineHangzhou 310029China cancer center of Zhejiang University Hangzhou 310029China Zhejang Provincial Clinical Research center for cancer Zhejang ProvinceChina Key Laboratory of molecular Biology in m.d.cal Sciences Zhejang ProvinceChina Research center for Life Science and Human Health Binjiang Institute of Zhejiang UniversityHangzhou 310053China

Neddylation is necessary for activation of Cullin-RING ligases(CRLs),which degrade various immune regulatory *** recent study showed that while depletion of neddylation E2-E3 pair Ube2f-Sag in regulatory T(T_(reg))cells had no obvious phenotype,the same depletion of either Ube2m or Rbx1 caused inflammation disorders with different *** these E2s or E3s compensate each other in functional regulations of T_(reg)cells is,however,previously *** this report,we generated Foxp3^(Cre);Ube2m^(fl/fl);Ube2f^(fl/fl)or Foxp3^(Cre);Rbx1^(fl/fl);Sag^(fl/fl)double-null mice by simultaneous deletion of both neddylation E2s or E3s in T_(reg)cells,***,Ube2m&Ube2f double-null mice developed much severe autoimmune phenotypes than did Ube2m-null mice,indicating that Ube2m markedly compensates Ube2f in T_(reg)*** minor worsened autoimmune phenotypes seen at the very early stage in Rbx1&Sag double-null than Rbx1-null mice is likely due to already severe phenotypes of the later,indicating a minor compensation of Rbx1 for *** RNA profiling-based analyses revealed that up-and down-regulations of few signaling pathways in T_(reg)cells are associated with the severity of autoimmune ***,severer inflammation phenotypes seen in mice with double E3-null than with double E2-null T_(reg)cells indicate a neddylation-independent mechanism of 2 E3s,also known to serve as the RING component of CRLs in regulation of T_(reg)cell fitness.

关键词： Foxp3 inflammation markedly

Organoid co-culture m.d.ls of the tumor microenvironment promote precision m.d.cine

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cancer Innovation 2024年第1期3卷 79-103页

作者： Zhaoru Gu Quanyou Wu Bingqing Shang Kaitai Zhang Wen Zhang State Key Laboratory of molecular Oncology Department of Etiology and CarcinogenesisNational Cancer CenterNational Clinical Research Center for CancerCancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina department of Urology National Cancer CenterNational Clinical Research Center for CancerCancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina department of Immunology National Cancer CenterNational Clinical Research Center for CancerCancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

In recent years,the three-dimensional(3d)culture system has emerged as a promising preclinical m.d.l for tumor research owing to its ability to replicate the tissue structure and molecular characteristics of solid tumors in *** system offers several advantages,including high throughput,efficiency,and retention of tumor *** matrigel-submerged organoid cultures primarily support the long-term proliferation of epithelial *** solution for the exploration of the tumor microenvironment is a reconstitution approach involving the introduction of exogenous cell types,either in dual,triple or even multiple *** solution is a holistic approach including patient-derived tumor fragments,air-liquid interface,suspension 3d culture,and microfluidic tumor-on-chip *** co-culture m.d.ls have also gained popularity for studying the tumor microenvironment,evaluating tumor immunotherapy,identifying predictive biomarkers,screening for effective drugs,and m.d.ling *** leveraging these 3d culture systems,it is hoped to advance the clinical application of therapeutic approaches and improve patient outcomes.

关键词： air-liquid interface immunotherapy organoid tumor microenvironment tumor-on-chip

diabetes and pulmonary infection:how hyperglycaemia shapes the immune system

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1245-1246页

作者： Christian Herder michael Roden Nicolas Venteclef Institute for Clinical diabetology German Diabetes CenterLeibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf40225DüsseldorfGermany German center for diabetes Research(dZd) Partner Düsseldorf85764München-NeuherbergGermany department of Endocrinology and diabetology Medical Faculty and University Hospital DüsseldorfHeinrich Heine University Düsseldorf40225DüsseldorfGermany Institut Necker-Enfants malades(INEm) UniversitéParis CitéINSERM UMR-S1151CNRS UMR-S8253ParisFrance

In a recent study published in Nature,Nobs and colleagues aim.d.to identify novel mechanisms that may explain why diabetes is associated with an increased susceptibility to viral respiratory *** analyses revealed a central role of lung dendritic cells(dC)which exhibited several functional defects induced by hyperglycaemia and consequently result in impaired antiviral immune responses.

关键词： impaired lung respiratory

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 m.d.cine 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 rem.d.l 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 transform.d.cells and their ecosystem.d.ring 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

Heavy-atom engineered hypoxia-responsive probes for precisive photoacoustic imaging and cancer therapy

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Chinese Chemical Letters 2024年第4期35卷 316-320页

作者： Ling-Ling Wu Xiangchuan meng Qingyang Zhang Xiaowan Han Feiya Yang Qinghua Wang Hai-Yu Hu Nianzeng Xing department of Urology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China State Key Laboratory of Bioactive Substances and Function of Natural m.d.cine Institute of Materia MedicaPeking Union Medical College and Chinese Academy of Medical SciencesBeijing 100050China

Photoacoustic agents combining photodynamic therapy(PdT) and photothermal therapy(PTT) functions have emerged as potent theranostic agents for combating cancer. The molecular approaches for enhancing the near-infrared(NIR)-absorption and maximizing non-radiative energy transfer are essential for effective photoacoustic imaging(PAI) and therapy applications. In addition, such molecules with high specificity and affinity to cancer cells are urgently needed, which would further decrease the side effect during treatments. In this study, we applied a heavy-atom engineering strategy and introduced p-aminophenol,-thio, and-seleno moieties into NIR heptamethine cyanine(Cy7) skeleton(Cy7-X-NH_(2), X = O, S, Se) to significantly increase photothermal conversion efficiency for PTT and promote intersystem crossing for ***, we designed a series of nitroreductase(NTR)-activated photoacoustic probes(Cy7-X-NO_(2),X = O, S, Se), and target hypoxic tumors with NTR overexpression. Our prostate cancer targeting probe,Cy7-Se-NO_(2)-KUE, exhibited specific tumor photoacoustic signals and effective tumor killing through outstanding synergistic PTT/PdT in vivo. These findings highlighted a versatile strategy for cancer photoacoustic diagnosis and enhanced phototherapy.

关键词： Heavy-atom effect Phototherapy Photoacoustic imaging Hypoxia-responsive Prostate cancer

Situational Analysis of malaria Incidence Under Integrated malaria Service in Hotspot Township-minbya Township,Rakhine State,myanmar,2017–2020

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China CdC weekly 2024年第17期6卷 374-377页

作者： Aung Than Oo Hong Chen ASEAN Centre for Biodiversity Ringgold standard institution D.M.Lantican AvenueUniversity of the Philippines Los Baños LagunaLos BañosPhilippines center for Global Public Health Chinese Center for Disease Control and PreventionBeijingChina

Introduction:malaria is a significant public health concern and tropical disease,particularly affecting myanmar within the Greater mekong *** annual parasite index(API)exceeds 1 per 10,000 population in the northern seven townships of Rakhine State,with minbya Township designated as a highburden area for malaria by the World Health Organization(WHO)myanmar and the National malaria Control Programme(NmCP).Since 2017,the malaria reduction intensification plan has been in place in this township to combat the high disease transmission *** study aims to assess the malaria epidemiology in minbya Township from 2017 to 2020 under the intensification plan for elimination,as well as to evaluate the effectiveness of the integrated strategy in reducing cases in hotspot ***:The study utilized a surveillance study design to collect secondary data from the malaria surveillance system(mSS)and the epidemiologic monitoring dashboard of minbya Township,maruk-U district,located in Rakhine ***:Since 2017,the malaria prevention and control(P&C)Program in minbya Township has successfully decreased malaria morbidity,eliminated malaria-related deaths,and bolstered malaria testing capabilities through the participation of village health volunteers(VHVs).Approximately 87%of malaria prevention and control services are executed by the township’s malaria elimination and disease control programs,with additional support from *** API dropped from 13 in 2017 to 2.5 in 2020,with Plasm.d.um vivax being the most prevalent malaria species,accounting for 55%of ***:The study suggests that early diagnosis and promotion of artemisinin-based combination treatment(ACT),along with strategic planning including expanding active case detection in rural health centers and implementing a communitybasedcommunitybased integrated healthcare approach,are effective and efficient strategies for malaria elimination.

关键词： malaria prevention epidemiology

Spark plasma sintering of tungsten-based WTaVCr refractory high entropy alloys for nuclear fusion applications

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International Journal of minerals,metallurgy and materials 2024年第1期31卷 146-154页

作者： Yongchul Yoo Xiang Zhang Fei Wang Xin Chen Xing-Zhong Li michael Nastasi Bai Cui department of mechanical&materials Engineering University of Nebraska-LincolnLincolnNE 68588USA Nebraska center for materials and Nanoscience University of Nebraska-LincolnLincolnNE 68588USA department of Nuclear Engineering Texas A&M UniversityCollege StationTX 77843USA

W-based WTaVCr refractory high entropy alloys (RHEA) may be novel and promising candidate materials for plasma facing components in the first wall and diverter in fusion reactors. This alloy has been developed by a powder metallurgy process combining mechanical alloying and spark plasma sintering (SPS). The SPSed samples contained two phases, in which the matrix is RHEA with a body-centered cubic structure, while the oxide phase was most likely Ta2VO6through a combined analysis of X-ray diffraction (XRd),energy-dispersive spectroscopy (EdS), and selected area electron diffraction (SAEd). The higher oxygen affinity of Ta and V may explain the preferential formation of their oxide phases based on therm.d.namic calculations. Electron backscatter diffraction (EBSd) revealed an average grain size of 6.2μm. WTaVCr RHEA showed a peak compressive strength of 2997 mPa at room temperature and much higher micro-and nano-hardness than W and other W-based RHEAs in the literature. Their high Rockwell hardness can be retained to at least 1000°C.

关键词： refractory high entropy alloy plasma-facing material fusion reactor spark plasma sintering