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Chemotherapy-induced small extracellular vesicles prime the pre-metastatic niche to accelerate neuroblastoma metastasis

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Genes & Diseases 2024年第4期11卷 65-68页

作者： Carson A.Wills Xiaoming Liu Longgui Chen Yuanjun Zhao Zhenqiu Liu Vladimir S.Spiegelman Jeffrey Sundstrom Hong-Gang Wang department of Pediatrics Division of Pediatric Hematology and OncologyThe Pennsylvania State University Collegeof MedicinePA 17033USA department of Ophthalmology The Pennsylvania State University College of MedicinePA 17033USA department of Public Health Sciences The Pennsylvania StateUniversityCollegeofMedicinePA 17033USA

Neuroblastoma is the most common extracranial solid tumor in children,accounting for more than 10%of cancerrelated deaths in this *** standard of care for patients diagnosed with medium-to high-risk neuroblastoma,incl... 详细信息

关键词： neuroblastoma metastatic metastasis

Resistance mechanisms and potential therapeutic strategies in relapsed or refractory natural killer/T cell lymphoma

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中华医学杂志(英文版) 2024年第19期137卷 2024 Aug 23页

作者： Wang Chengji Wang Liang department of hematology Beijing Tongren Hospital Capital Medical University Beijing China

Natural killer/T cell lymphoma (NKTCL) is a malignant tumor originating from NK or T cells, characterized by its highly aggressive and heterogeneous nature. NKTCL is predominantly associated with Epstein–Barr virus infection, disproportionately affecting Asian and Latin American populations. Owing to the application of asparaginase and immunotherapy, clinical outcomes have improved significantly. However, for patients in whom first-line treatment fails, the prognosis is exceedingly poor. Overexpression of multidrug resistance genes, abnormal signaling pathways, epigenetic modifications and active Epstein–Barr virus infection may be responsible for resistance. This review summarized the mechanisms of resistance for NKTCL and proposed potential therapeutic approaches.

关键词： Natural killer/T cell lymphoma Epstein–Barr virus Chemotherapy resistance Asparaginase Immunotherapy

Converting“cold”to“hot”:epigenetics strategies to improve immune therapy effect by regulating tumor-associated immune suppressive cells

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Cancer Communications 2024年第6期44卷 601-636页

作者： Yijia Tang Guangzu Cui Haicong Liu Ying Han Changjing Cai Ziyang Feng Hong Shen Shan Zeng department of Oncology Xiangya HospitalCentral South UniversityChangshaHunanP.R.China National Clinical Resaerch Center for geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunanChina

Significant developments in cancer treatment have been made since the advent of immune ***,there are still some patientswithmalignant tumors who do not benefit from *** without immunogenicity are called“cold”tumors which are unresponsive to immunotherapy,and the opposite are“hot”*** suppressive cells(ISCs)refer to cells which can inhibit the immune response such as tumor-associated macrophages(TAMs),myeloid-derived suppressor cells(MDSCs),regulatory T(Treg)cells and so *** more ISCs infiltrated,the weaker the immunogenicity of the tumor,showing the characteristics of“cold”*** dysfunction of ISCs in the tumor microenvironment(TME)may play essential roles in insensitive therapeutic *** studies have found that epigeneticmechanisms play an important role in the regulation of *** ISCs may be a new approach to transforming“cold”tumors into“hot”***,we focused on the function of ISCs in the TME and discussed how epigenetics is involved in regulating *** addition,we summarized the mechanisms by which the epigenetic drugs convert immunotherapy-insensitive tumors into immunotherapy-sensitive tumors which would be an innovative tendency for future immunotherapy in“cold”tumor.

关键词： DNA methylation epigenetics strategy histone modification immune suppressive cell noncoding RNA

TRIANGLE operation,combined with adequate adjuvant chemotherapy,can improve the prognosis of pancreatic head cancer:A retrospective study

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 1773-1786页

作者： Jia-Hao Chen Li-Yong Zhu Zhi-Wei Cai Xiao Hu Abousalam Abdoulkader Ahmed Jie-Qiong Ge Xiao-Yan Tang Chun-Jing Li Yun-Long Pu Chong-Yi Jiang department of Hepato-Biliary-Pancreatic Surgery Huadong Hospital Affiliated to Fudan UniversityShanghai 200040China Shanghai Key Laboratory of Clinical geriatric Medicine Fudan UniversityShanghai 200040China department of Nursing Huadong Hospital Affiliated to Fudan UniversityShanghai 200040China

BACKGROUND The TRIANGLE operation involves the removal of all tissues within the triangle bounded by the portal vein-superior mesenteric vein,celiac axis-common hepatic artery,and superior mesenteric artery to improve patient *** previously promising in patients with locally advanced pancreatic ductal adenocarcinoma(PDAC),data are limited regarding the long-term oncological outcomes of the TRIANGLE operation among resectable PDAC patients undergoing pancreaticoduodenectomy(PD).AIM To evaluate the safety of the TRIANGLE operation during PD and the prognosis in patients with resectable *** This retrospective cohort study included patients who underwent PD for pancreatic head cancer between January 2017 and April 2023,with or without the TRIANGLE *** were divided into the PD_(TRIANGLE)and PD_(non-TRIANGLE)*** and survival outcomes were compared between the two *** adjuvant chemotherapy was defined as adjuvant chemotherapy≥6 *** The PD_(TRIANGLE)and PD_(non-TRIANGLE) groups included 52 and 55 patients,*** were no significant differences in the baseline characteristics or perioperative indexes between the two ***,the recurrence rate was lower in the PD_(TRIANGLE) group than in the PD_(non-TRIANGLE) group(48.1%vs 81.8%,P<0.001),and the local recurrence rate of PDAC decreased from 37.8%to 16.0%.Multivariate Cox regression analysis revealed that PD_(TRIANGLE)(HR=0.424;95%CI:0.256-0.702;P=0.001),adequate adjuvant chemotherapy≥6 months(HR=0.370;95%CI:0.222-0.618;P<0.001)and margin status(HR=2.255;95%CI:1.252-4.064;P=0.007)were found to be independent factors for the recurrence *** The TRIANGLE operation is safe for PDAC patients undergoing ***,it reduces the local recurrence rate of PDAC and may improve survival in patients who receive adequate adjuvant chemotherapy.

关键词： TRIANGLE operation Pancreatic ductal adenocarcinoma Heidelberg triangle Adjuvant chemotherapy Prognosis Pancreaticoduodenectomy

Therapeutic strategies of targeting nonapoptotic regulated cell death (RCD) with smallmolecule compounds in cancer

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Acta Pharmaceutica Sinica B 2024年第7期14卷 2815-2853页

作者： Xin Jin Wenke Jin Linlin Tong Jia Zhao Lan Zhang Na Lin department of Ultrasound Department of Medical Oncology and Department of Hematologythe First Hospital of China Medical UniversityChina Medical UniversityShenyang 110001China Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs School of Life Science and EngineeringSouthwest Jiaotong UniversityChengdu 610031China

Regulated cell death(RCD)is a controlled form of cell death orchestrated by one or more cascading signaling pathways,making it amenable to pharmacological *** subroutines can be categorized as apoptotic or non-apoptotic and play essential roles in maintaining homeostasis,facilitating development,and modulating *** evidence has recently revealed that RCD evasion is frequently the primary cause of tumor *** non-apoptotic RCD subroutines have garnered attention as promising cancer therapies due to their ability to induce tumor regression and prevent relapse,comparable to ***,they offer potential solutions for overcoming the acquired resistance of tumors toward apoptotic *** an increasing understanding of the underlying mechanisms governing these non-apoptotic RCD subroutines,a growing number of small-molecule compounds targeting single or multiple pathways have been discovered,providing novel strategies for current cancer *** this review,we comprehensively summarized the current regulatory mechanisms of the emerging non-apoptotic RCD subroutines,mainly including autophagy-dependent cell death,ferroptosis,cuproptosis,disulfidptosis,necroptosis,pyroptosis,alkaliptosis,oxeiptosis,parthanatos,mitochondrial permeability transition(MPT)-driven necrosis,entotic cell death,NETotic cell death,lysosome-dependent cell death,and immunogenic cell death(ICD).Furthermore,we focused on discussing the pharmacological regulatory mechanisms of related small-molecule *** brief,these insightful findings may provide valuable guidance for investigating individual or collaborative targeting approaches towards different RCD subroutines,ultimately driving the discovery of novel small-molecule compounds that target RCD and significantly enhance future cancer therapeutics.

关键词： Regulated cell death(RCD) Non-apoptotic RCD subroutine Autophagy Ferroptosis Necroptosis Regulatory mechanism Small-molecule compound Cancer therapy

Decitabine in combination with idarubicin within a modified busulfan/cyclophosphamide conditioning regimen for patients with advanced myelodysplastic syndrome:A prospective multicenter clinical cohort study

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Chinese Medical Journal 2024年第9期137卷 1115-1117页

作者： Yigeng Cao Mingyang Wang Fuxu Wang Wenwen Guo Yueshen Ma Xiaoyun Li Yi He Aiming Pang Rongli Zhang Weihua Zhai Xin Chen Qiaoling Ma Jialin Wei Donglin Yang Yong Huang Dan Feng Jia Liu Xin Gao Shupeng Wen Wen Wang Tao Wang Ying Li Xiaosheng Fang Yingchun Li Xiaohan Zhang Yun Cai Yongqi Wang Weijie Cao Runqing Lu Sizhou Feng Rong Guo Yuewen Fu Xin Du Zhuogang Liu Xin Wang Ling Wang Liangming Ma Chuanfang Liu Xuejun Zhang Mingzhe Han Erlie Jiang department of Hematopoietic Stem Cell Transplantation Center State Key Laboratory of Experimental HematologyNational Clinical Research Center for Blood DiseasesHaihe Laboratory of Cell EcosystemInstitute of HematologyBlood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300000China department of hematology Second Hospital of Hebei Medical UniversityHebei Key Laboratory of HematologyShijiazhuangHebei 050000China Center for Information and Resource State Key Laboratory of Experimental HematologyNational Clinical Research Center for Blood DiseasesHaihe Laboratory of Cell EcosystemInstitute of HematologyBlood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300000China department of hematology Qilu Hospital of Shandong UniversityJinanShandong 250000China department of hematology Shanxi Bethune HospitalThird Hospital of Shanxi Medical UniversityTaiyuanShanxi 030032China department of hematology Qingdao Central HospitalUniversity of Health and Rehabilitation SciencesQingdaoShandong 266042China department of hematology Shandong Provincial HospitalCheeloo College of MedicineShandong UniversityJinanShandong 250000China department of hematology Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinanShandong 250000China department of hematology Shengjing Hospital of China Medical UniversityShenyangLiaoning 110000China department of hematology Shenzhen Second People’s HospitalThe First Affiliated Hospital of Shenzhen UniversityShenzhen University School of MedicineShenzhenGuangdong 518000China department of hematology Henan Cancer HospitalCancer Hospital Affiliated Zhengzhou UniversityZhengzhouHenan 450000China department of hematology Department of HematologyThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450000China

To the Editor:Allogeneic hemopoietic stem cell transplantation(allo-HSCT)represents the only long-term survival treatment choice for patients with myelodysplastic syndromes(MDS)and MDS/myeloproliferative neoplasm(MPN).Unfortunately,post-hemopoietic stem cell transplantation(HSCT)relapse remains a cause of treatment failure and the results of salvage treatments are *** better conditioning regimens is urgently *** studies have shown synergistic antileukemic effects between decitabine(DEC)and idarubicin(IDA).[1]In an attempt to design a conditioning strategy with very low toxicity but considerable myelosuppressive activity and potential immune-enhancing effects for patients with high-risk MDS and MDS/MPN,we combined DEC and IDA with busulfan,cyclophosphamide,andudarabine for a modied myeloablative regimen in this prospective,multicenter cohort study(hereafter referred to as the“DEC/IDA study”).

关键词： regimen myelo patients

New perspectives on biology,disease progression,and therapy response of head and neck cancer gained from single cell RNA sequencing and spatial transcriptomics

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Oncology Research 2024年第1期32卷 1-17页

作者： GERWIN HELLER THORSTEN FUEREDER ALEXANDER MICHAEL GRANDITS ROTRAUD WIESER Division of Oncology Department of Medicine IMedical University of ViennaVienna1090Austria Ludwig Boltzmann Institute for hematology and Oncology Medical University of ViennaVienna1090Austria

Head and neck squamous cell carcinoma(HNSCC)is one of the most frequent cancers *** main risk factors are consumption of tobacco products and alcohol,as well as infection with human papilloma *** therapeutic options comprise surgery,radiation,chemotherapy,targeted therapy through epidermal growth factor receptor inhibition,and immunotherapy,but outcome has remained unsatisfactory due to recurrence rates of~50%and the frequent occurrence of second *** availability of the human genome sequence at the beginning of the millennium heralded the omics era,in which rapid technological progress has advanced our knowledge of the molecular biology of malignant diseases,including HNSCC,at an unprecedented ***,microarray-based methods,followed by approaches based on next-generation sequencing,were applied to study the genetics,epigenetics,and gene expression patterns of bulk *** recently,the advent of single-cell RNA sequencing(scRNAseq)and spatial transcriptomics methods has facilitated the investigation of the heterogeneity between and within different cell populations in the tumor microenvironment(e.g.,cancer cells,fibroblasts,immune cells,endothelial cells),led to the discovery of novel cell types,and advanced the discovery of cell-cell communication within *** review provides an overview of scRNAseq,spatial transcriptomics,and the associated bioinformatics methods,and summarizes how their application has promoted our understanding of the emergence,composition,progression,and therapy responsiveness of,and intercellular signaling within,HNSCC.

关键词： Head and neck squamous cell carcinoma Tumor microenvironment Immunotherapy Gene expression Omics

Clinical characteristics and impactof comorbidities on the prognosis of senileepilepsy in Southwest China:a retrospectivecohort study

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Acta Epileptologica 2024年第2期7卷 100-109页

作者： Zhen Cao Yinping Li Shengyi Liu Zihua He Jinmei Li department of Neurology West China HospitalSichuan UniversityChengdu 610041China department of geriatric The Second People’s Hospital of YibinYibin 644000China department of Neurology Chengdu Shangjin Nanfu HospitalChengdu 610000China

Background Senile epilepsy and its comorbidities pose a tremendous burden on patients and the *** was aimed to investigate the clinical characteristics and comorbidities of senile epilepsy,as well as the impactof comorbidities on the prognosis of senile *** Information of patients with senile epilepsy was retrospectively collected from three tertiary hospitalsin Southwest China between December 2014 and December 2022.A total of 154 patients met the inclusion criteriaand were divided into two groups based on the presence or absence of *** prevalence,type,charac-teristics,and impacts of the comorbidities were *** characteristics of patients with and without comor-bidities were also *** Eighty-one percent of patients with senile epilepsy had at least one comorbidity,and 36%had three or *** different types of comorbidities were *** most common comorbidities were neu-rological(61%),followed by cardiovascular(45%)and psychiatric(26%)*** than one-third of patientshad bidirectional comorbidities,whereas more than half of the patients had additional causal *** types of comorbidities,neurological and psychiatric comorbidities were found to be associated with an increasedrisk of recurrent *** to patients without bidirectional comorbidities,those with at least one bidirec-tional comorbidity had a lower rate of achieving seizure *** higher the number of bidirectional comor-bidities,the lower the seizure-free *** analysis revealed that patients with neurological comorbidities hada higher risk of *** This study revealed a high comorbidity rate and a low seizure-freedom rate among patients with *** particular,neuropsychiatric comorbidities can increase the risk of seizures and affect the survival rateof patients with senile ***,preventing and managing these comorbidities may

关键词： Senile epilepsy Elderly Epilepsy Comorbidity Prognosis

Subcutaneous daratumumab in Chinese patients with relapsed or refractory multiple myeloma:an open-label,multicenter,phase 1 study(MMY1010)

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Blood Science 2024年第3期6卷 42-47页

作者： Gang An Zheng Ge Hongmei Jing Jing Liu Guoping Yang Ru Feng Zhongyuan Xu Ming Qi Jianping Wang Juanjuan Song Wei Zhou Binbin Sun Dian Zhu Xi Chen Canchan Cui Lugui Qiu National Clinical Research Center for Hematological Disorders State Key Laboratory of Experimental HematologyInstitute of Hematology and Blood Diseases HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeTianjin 300020China department of hematology Zhongda Hospital Southeast UniversityNanjing 210009China Peking University Third Hospital Beijing 100191China department of hematology The Third Xiangya Hospital of Central South UniversityChangsha 410013China department of hematology Nanfang Hospital of Southern Medical UniversityGuangzhou 510515China Phase 1 Clinical Trial department Nanfang Hospital of Southern Medical UniversityGuangzhou 510515China Janssen Research&Development LLCSpring HousePA 19477USA Janssen Research&Development LLCBeijing 100025China Janssen Research&Development LLCShanghai 200231Chin

Despite recent progress in multiple myeloma(MM)treatments,most patients will relapse and require additional *** daratumumab,a human IgGκmonoclonal antibody targeting CD38,has shown good efficacy in the treatment of MM.A subcutaneous version of daratumumab was formulated to reduce the burden of intravenous *** aimed to investigate the efficacy and safety of subcutaneous daratumumab in Chinese patients with relapsed/refractory MM based on the demonstrated noninferiority of subcutaneous daratumumab to intravenous daratumumab,with a shorter administration time and reduced infusion-related reaction rate in global *** phase 1,multicenter study(MMY1010;*** Identifier:NCT04121260)evaluated subcutaneous daratumumab in Chinese patients with relapsed/refractory MM after 1 prior line(n=1)or≥2 prior lines(n=20)of therapy,including a proteasome inhibitor and an immunomodulatory *** endpoints were pharmacokinetics and ***(standard deviation)maximum trough concentration of daratumumab was 826(335)μg/mL,which was consistent with prior studies of subcutaneous daratumumab and intravenous *** was consistent with safety profiles observed in other daratumumab studies,with no new safety concerns *** of infusion-related reactions and injection-site reactions were low and consistent with other subcutaneous daratumumab *** a median follow-up of 7.5 months,the overall response rate was 57.1%,with a very good partial response or better rate of 38.1%and complete response or better rate of 19.0%.Our results demonstrate a favorable benefit/risk profile of subcutaneous daratumumab in Chinese patients with relapsed/refractory MM,potentially impacting clinical administration of daratumumab in this population.

关键词： Chinese Daratumumab Multiple myeloma Pharmacokinetic Relapse/refractory Safety Subcutaneous