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Casual associations between blood metabolites and colon cancer

World Journal of Gastrointestinal oncology 2024年第5期16卷 1995-2005页

作者： Ke-Yue Hu Yi-Quan Cheng Zhi-Long Shi Fu-Peng Ren Gang-Feng Xiao Department of hematology and oncology Ningbo No.2 HospitalNingbo 315000Zhejiang ProvinceChina

BACKGROUND Limited knowledge exists regarding the casual associations linking blood metabolites and the risk of developing colorectal *** To investigate causal associations between blood metabolites and colon *** The study utilized a two-sample Mendelian randomization(MR)analysis to investigate the causal impact of 486 blood metabolites on colorectal *** primary method of analysis used was the inverse variance weighted *** further validate the results several sensitivity analyses were performed,including Cochran's Q test,MR-Egger intercept test,and MR robust adjusted profile *** additional analyses were conducted to ensure the reliability and robustness of the *** After rigorous selection for genetic variation,486 blood metabolites were included in the MR *** found Mannose[odds ratio(OR)=2.09(1.10-3.97),P=0.024],N-acetylglycine[OR=3.14(1.78-5.53),P=7.54×10^(-8)],X-11593-O-methylascorbate[OR=1.68(1.04-2.72),P=0.034],1-arachidonoylglycerophosphocholine[OR=4.23(2.51-7.12),P=6.35×10^(-8)]and 1-arachidonoylglycerophosphoethanolamine 4[OR=3.99(1.17-13.54),P=0.027]were positively causally associated with colorectal cancer,and we also found a negative causal relationship between Tyrosine[OR=0.08(0.01-0.63),P=0.014],Urate[OR=0.25(0.10-0.62),P=0.003],N-acetylglycine[0.73(0.54-0.98),P=0.033],X-12092[OR=0.89(0.81-0.99),P=0.028],Succinylcarnitine[OR=0.48(0.27-0.84),P=0.09]with colorectal cancer.A series of sensitivity analyses were performed to confirm the rigidity of the *** This study showed a causal relationship between 10 blood metabolites and colorectal cancer,of which 5 blood metabolites were found to be causal for the development of colorectal cancer and were confirmed as risk *** other five blood metabolites are protective factors.

关键词： Metabolites Colon cancer Mendelian randomization Genome-wide association studies Casual

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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

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RNF6 promotes chronic myelogenous leukemia cell proliferation and migration by stabilizing vimentin via multiple atypical ubiquitinations

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Genes & Diseases 2024年第1期11卷 87-90页

作者： Hongxia Zhang Yueya Zhong Yuanming He Yujia Xu Ying Ren Haixia Zhuang Tong Sun Zhigang Zhu Xinliang Mao Institute of Clinical Pharmacology Science and Technology Innovation CenterGuangzhou University of Chinese MedicineGuangzhouGuangdong 510403China Guangdong Provincial Key Laboratory of Protein Modification and Degradation School of Basic Medical SciencesGuangzhou Medical UniversityGuangzhouGuangdong 511436China Department of Pharmacology College of Pharmaceutical SciencesSoochow UniversitySuzhouJiangsu 215123China Division of hematology&oncology Department of GeriatricsGuangzhou First People's HospitalCollege of MedicineSouth China University of TechnologyGuangzhouGuangdong 510180China

Chronic myelogenous leukemia(CML)is a malignancy from bone marrow myeloid stem cells mainly driven by the fusion gene *** addition to BCR-ABL,other genes including RNF6 are also dysregulated in CML cells.1 RNF6,a ubiquitin ligase of the RING family,promotes various cancer cell proliferation,chemoresistance,and tumor growth in vivo by targeting various proteins for ubiquitination and degradation,including SHP1,TLE3,FOXA1,and MAD1.^(2) However,its specific mechanism in CML is not known.

关键词： ubiquitin myelogenous leukemia

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Preclinical evaluation of cyclophosphamide and fludarabine combined with CD19 CAR-T in the treatment of B-cell hematologic malignancies in vivo

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oncology Research 2024年第6期32卷 1109-1118页

作者： ZHIGANG XIA MENGYAO TIAN YUCAI CHENG WENFANG YI ZEFAN DU TIANWEN LI YUCHEN WEN LINDI LI YONG LIU CHUN CHEN Pediatric hematology Laboratory Division of Hematology/OncologyDepartment of PediatricsThe Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China Scientific Research Center The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China

Background:Chimeric antigen receptor T(CAR-T)cell therapy has achieved marked therapeutic success in ameliorating hematological ***,there is an extant void in the clinical guidelines concerning the most effective chemotherapy regimen prior to chimeric antigen receptor T(CAR-T)cell therapy,as well as the optimal timing for CAR-T cell infusion *** and Methods:We employed cell-derived tumor xenograft(CDX)murine models to delineate the optimal pre-conditioning chemotherapy regimen and timing for CAR-T cell ***,transcriptome sequencing was implemented to identify the therapeutic targets and elucidate the underlying mechanisms governing the treatment ***:Our preclinical in vivo evaluation determined that a combination of cyclophosphamide and fludarabine,followed by the infusion of CD19 CAR-T cells five days subsequent to the chemotherapy,exerts the most efficacious therapeutic effect in B-cell hematological ***,RNA-seq data indicated that the therapeutic efficacy predominantly perturbs tumor cell metabolism,primarily through the inhibition of key mitochondrial targets,such as C-Jun Kinase enzyme(C-JUN).Conclusion:In summary,the present study offers critical clinical guidance and serves as an authoritative reference for the deployment of CD19 CAR-T cell therapy in the treatment of B-cell hematological malignancies.

关键词： CD19 CAR-T B-cell hematologic malignancies Metabolism In vivo

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Clinical study of chemotherapy-related cognitive impairment in patients with non-Hodgkin lymphoma

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World Journal of Psychiatry 2024年第7期14卷 1062-1067页

作者： Qiang-Li Wang Hai-Yan Xu Yi Wang Yin-Ling Wang Pei-Nan Lin Zhong-Lei Chen Department of oncology and hematology Suzhou Kowloon HospitalShanghai Jiao Tong University School of MedicineSuzhou 215000Jiangsu ProvinceChina

BACKGROUND Chemotherapy for malignant tumors can cause brain changes and cognitive impairment,leading to chemotherapy-induced cognitive impairment(CICI).Current research on CICI has focused on breast cancer and Hodgkin’s *** patients with non-Hodgkin’s lymphoma(NHL)undergoing chemo-therapy have cognitive impairment has not been fully *** have cognitive impairment has not been fully *** To investigate whether NHL patients undergoing chemotherapy had cognitive *** The study included 100 NHL patients who were required to complete a compre-hensive psychological scale including the Brief Psychiatric Examination Scale(MMSE)at two time points:before chemotherapy and within 2 wk of two chemo-therapy courses.A language proficiency test(VFT),Symbol Number Pattern Test(SDMT),Clock Drawing Test(CDT),Abbreviated Daily Cognition Scale(ECog-12),Prospective and Retrospective Memory Questionnaire,and Karnofsky Perfor-mance Status were used to assess cognitive changes before and after *** The VFT scores for before treatment(BT)and after treatment(AT)groups were 45.20±15.62,and 42.30±17.53,respectively(t-2.16,P<0.05).The CDT scores were 8(3.5-9.25)for BT and 7(2.5-9)for AT groups(Z-2.1,P<0.05).Retrospective memory scores were 13.5(9-17)for BT and 15(13-18)for AT(Z-3.7,P<0.01).The prospective memory scores were 12.63±3.61 for BT and 14.43±4.32 for AT groups(t-4.97,P<0.01).The ECog-12 scores were 1.71(1.25-2.08)for BT and 1.79(1.42-2.08)for AT groups(Z-2.84,P<0.01).The SDMT and MMSE values did not show a significant difference between BT and AT *** Compared to the AT group,the BT group showed impaired language,memory,and subjective cognition,but objec-tive cognition and execution were not significantly affected.

关键词： Non-Hodgkin’s lymphoma Hodgkin lymphoma Lymphoma cognitive impairment Chemotherapy-related cogni-tive impairment Clinical study

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A multicenter prospective study on the management of hepatoblastoma in children:a report from the Chinese Children's Cancer Group

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World Journal of Pediatrics 2024年第6期20卷 590-601页

作者： Meng-Jie Tang Xiao-Li Ma Xiang-Ling He Wei-Hua Pan Xiao-Hong Zhang Sha-Yi Jiang Ju Gao Fu Lie Wei Yao Song Gu Wei-Ling Zhang Qiang Zhao Shi-Hao Huang Yong-Jun Fang Wei Liu Hui-Zhong Niu Chun-Mei Wang Li-Rong Sun Hui Gao Yun-Peng Dai Shun-Gen Huang Zhi-Yong Zhong Xi-Ge Wang Zhong-Rong Li Liang-Chun Yang Ye-Ming Wu Huan-Min Wang Xin Sun Xiao-Jun Yuan Department of Pediatric hematology/oncology Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineNo.1665Kongjiang RoadYangpu DistrictShanghai 200092China Medical oncology Department Pediatric Oncology CenterBeijing Children's HospitalCapital Medical UniversityNational Center for Children's HealthBeijing 100045China Department of hematology/oncology Children's Medical CenterHunan Provincial People's HospitalThe First Affiliated Hospital of Hunan Normal UniversityChangsha 41005China Department of Pediatric Surgery Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China Department of hematology/oncology Guangzhou Women and Children's Medical CenterNational Children's Medical Center for South Central RegionGuangzhou 510623China Department of hematology Shanghai Children's HospitalShanghai Jiao Tong UniversityShanghai 200062China Department of Pediatrics West China Second University HospitalSichuan UniversityChengdu 610041China Department of hematology/oncology Qilu Children's Hospital of Shandong UniversityJinan 250022China Department of Pediatric Surgery Children's Hospital of Fudan UniversityShanghai 201102China Department of General Surgery Shanghai Children's Medical Center(National Children's Medical Center-Shanghai)Shanghai Jiao Tong University School of MedicineShanghai 200127China Department of Pediatrics Beijing Tongren HospitalCapital Medical UniversityBeijing 100730China Department of Pediatric oncology Tianjin Medical University Cancer Institute and HospitalTianjin 300060China Department of hematology/oncology Children's Hospital of Nanjing Medical UniversityNanjing 210008China Department of hematology/oncology Henan Children's HospitalZhengzhou 450018China Department of Pediatric General Surgery Hebei Children's Hospital of Hebei Medical UniversityShijiazhuang City 050031China Children's Hospital the First Affliated Hospital of Zhengzhou UniversityZhengzhou 450052China Department of Paediatric

Background This study aimed to identify survival risk factors in Chinese children with hepatoblastoma(HB)and assess the effectiveness of the new treatment protocol proposed by the Chinese Children's Cancer Group(CCCG)in *** A multicenter,prospective study that included 399 patients with HB from January 2015 to June 2020 was *** demographics,treatment protocols,and other related information were *** regression models and Kaplan-Meier curve methods were *** The 4-year event-free survival(EFS)and overall survival(OS)were 76.9 and 93.5%,*** 4-year EFS rates for the very-low-risk,low-risk,intermediate-risk,and high-risk groups were 100%,91.6%,81.7%,and 51.0%,*** 4-year 0S was 100%,97.3%,94.4%,and 86.8%,*** regression analysis found that age,tumor rupture(R+),and extrahepatic tumor extension(E+)were independent prognostic factors.A total of 299 patients had complete remission,and 19 *** with declining alpha-fetoprotein(AFP)>75%after the first two cycles of neoadjuvant chemotherapy had a better EFS and OS than those≤75%.Conclusions The survival outcome of HB children has dramatically improved since the implementation of CCCG-HB-2016 ***≥8 years,R+,and E+were independent risk factors for *** with a declining AFP>75%after the first two cycles of neoadjuvant chemotherapy had better EFS and OS.

关键词： Alpha-fetoprotein Hepatoblastoma Multicenter Prospective study Survival

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Phase II study of novel orally PI3Kα/δinhibitor TQ-B3525 in relapsed and/or refractory follicular lymphoma

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2193-2201页

作者： Huaqing Wang Jifeng Feng Yanyan Liu Zhengzi Qian Da Gao Xuehong Ran Hui Zhou Lihong Liu Binghua Wang Meiyun Fang Hebing Zhou Zhenqian Huang Shi Tao Zhuowen Chen Liping Su Hang Su Yu Yang Xiaobao Xie Huijing Wu Ping Sun Guoyu Hu Aibin Liang Zhiming Li Department of oncology Tianjin Union Medical Center of Nankai UniversityTianjin 300121PR China The Institute of Translational Medicine Tianjin Union Medical Center of Nankai UniversityTianjin 300121PR China Department of Medical oncology Jiangsu Cancer HospitalThe Affiliated Cancer Hospital of Nanjing Medical UniversityNanjing 210009PR China Department of Medical oncology Henan Cancer HospitalThe Affiliated Cancer Hospital of Zhengzhou UniversityZhengzhou 450003PR China Department of Medical oncology Tianjin Medical University Cancer Institute and HospitalTianjin 300060PR China Department of hematology The Affiliated Hospital of Inner Mongolia Medical College010050 HohhotPR China Department of hematology Weifang People’s HospitalThe First Affiliated Hospital of Weifang Medical University261000 WeifangPR China Department of Lymphoma&hematology Hunan Cancer HospitalThe Affiliated Cancer Hospital of Xiangya School of MedicineCentral South University410013 ChangshaPR China Department of hematology The Fourth Hospital of Hebei Medical University and Hebei Tumor Hospital050011 ShijiazhuangPR China Department of Lymphoma Weihai Central Hospital264400 WeihaiPR China Department of hematology and Rheumatology The Affiliated Zhongshan Hospital of Dalian University116001 DalianPR China Department of hematology Beijing Luhe Hospital101199 BeijingPR China Department of hematology The First Affiliated Hospital of Guangzhou Medical University510120 GuangzhouPR China Department of hematology The First Affiliated Hospital of Hainan Medical College570102 HaikouPR China Department of hematology The First People’s Hospital of Foshan528000 FoshanPR China Department of hematology Shanxi Cancer Hospital030013 TaiyuanPR China Department of Lymphoma Senior Department of HematologyThe Fifth Medical Center of Chinese PLA General Hospital100039 BeijingPR China Department of Lymphoma and Head and Neck Cancer Fujian Cancer Hospital350014 FuzhouPR China Department of hematology The First People’s Hospit

This registration study assessed clinical outcomes of TQ-B3525,the dual phosphatidylinositol-3-kinase(PI3K)α/δinhibitor,in relapsed and/or refractory follicular lymphoma(R/R FL).This phase II study(*** *** March 27,2020)comprised run-in stage and stage 2.R/R FL patients after≥2 lines therapies received oral 20 mg TQ-B3525 once daily in a 28-day cycle until intolerable toxicity or disease *** endpoint was independent review committee(IRC)-assessed objective response rate(ORR).Based on results(ORR,88.0%;duration of response[DOR],11.8 months;progression-free survival[PFS],12.0 months)in 25 patients at run-in stage,second stage study was initiated and included 82 patients for efficacy/safety *** received prior-line(median,3)therapies,with 56.1%refractory to previous last therapies;73.2%experienced POD24 at *** stage 2,ORR was 86.6%(71/82;95%CI,77.3-93.1%),with 28(34.2%)complete *** control rate was 95.1%due to 7(8.5%)stable *** time to response was 1.8 *** 71 responders,median DOR was not reached;18-month DOR rate was 51.6%.with median follow-up of 13.3 months,median PFS was 18.5(95%CI,10.2-not estimable)*** overall survival(OS)was not reached by cutoff date;24-month OS rate was estimated as 86.1%.Response rates and survival data were consistent across all *** 3 or higher treatment-related adverse events were observed in 63(76.8%)cases,with neutropenia(22.0%),hyperglycemia(19.5%),and diarrhea(13.4%)being ***-B3525 showed favorable efficacy and safety for R/R FL patients after≥2 lines prior therapies.

关键词： lymphoma assessed initiated

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Parenteral iron therapy in children with iron deficiency anemia

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World Journal of Clinical Cases 2024年第13期12卷 2138-2142页

作者： Jelena Roganovic Department of Pediatric hematology and oncology Children’s Hospital Zagreb10000 ZagrebCroatia Faculty of Biotechnology and Drug Development University of RijekaRijeka 51000Croatia

Iron deficiency anemia(IDA)continues to be a global public health *** iron is the universally accepted first-line therapy,and most children have a prompt and favorable response to oral *** subsets of children who fail to respond due to intolerance,poor adherence,or inadequate intestinal absorption,parenteral iron is *** numerous studies in adults with IDA of diverse etiologies,pediatric studies on parenteral iron use are very *** mostly retrospective and small,these studies have documented the efficacy and safety profile of intravenous iron *** this editorial the author comments on the most important published data and underscores the need to seriously consider parenteral iron use in children unresponsive to oral therapy.

关键词： Anemia Iron deficiency Intravenous iron Iron deficiency anemia Children

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Low-dose immune tolerance induction for severe hemophilia A inhibitor patients:Immunosuppressants are generally not necessary for inhibitor-titer below 200 BU/mL

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Pediatric Investigation 2024年第2期8卷 91-100页

作者： Zhengping Li Jie Sun Zekun Li Zhenping Chen Guoqing Liu Wanru Yao Xiaoling Cheng Gang Li Yingzi Zhen Di Ai Yaohan Zhou Qianqian Mao Man-Chiu Poon Runhui Wu Hemophilia Comprehensive Care Center Hematology DepartmentHematology CenterBeijing Key Laboratory of Pediatric Hematology-OncologyKey Laboratory of Major Diseases in ChildrenNational Key Discipline of Pediatrics(Capital Medical University)Ministry of EducationBeijing Children’s HospitalCapital Medical UniversityNational Center for Children’s HealthBeijingChina Hematologic Disease Laboratory Hematology DepartmentHematology CenterBeijing Key Laboratory of Pediatric Hematology-OncologyKey Laboratory of Major Diseases in ChildrenNational Key Discipline of Pediatrics(Capital Medical University)Ministry of EducationBeijing Pediatric Research InstituteBeijing Children’s HospitalCapital Medical UniversityNational Center for Children’s HealthBeijingChina Department of Pharmacy Beijing Children’s HospitalCapital Medical UniversityNational Center for Children’s HealthBeijingChina Departments of Medicine Pediatrics and OncologyUniversity of Calgary Cumming School of MedicineCalgaryCanada

Importance:It remained unclear that the efficacy comparison between low-dose immune tolerance induction(LD-ITI)incorporating immunosuppressants(IS)when severe hemophilia A(SHA)patients had inhibitor-titer≥200 Bethesda Units(BU)/mL(LD-ITI-IS200 regimen)and LD-ITI combining with IS when SHA patients had inhibitor-titer≥40 BU/mL(LD-ITI-IS40 regimen).Objective:To compare the efficacy of the LD-ITI-IS200 regimen with that of the LD-ITI-IS40 regimen for SHA patients with high-titer ***:A prospective cohort study on patients receiving LD-ITI-IS200 compared to those receiving LD-ITI-IS40 from January 2021 to December *** received LD-ITI[FVIII 50 IU/kg every other day].IS(rituximab+prednisone)was added when peak inhibitor tier≥200 BU/mL in the LD-ITI-IS200 regimen and≥40 BU/mL in the LD-ITI-IS40 *** is defined as a negative inhibitor plus FVIII recovery≥66%of the ***:We enrolled 30 patients on LD-ITI-IS200 and 64 patients on LD-ITI-IS40,with similar baseline clinical characteristics.A lower IS-use rate was discovered in the LD-ITI-IS200 regimen compared to the LD-ITI-IS40 regimen(30.0%vs.62.5%).The two regimens(LD-ITI-IS200 ***-ITI-IS40)had similar success rate(70.0%vs.79.7%),median time to success(9.4 vs.10.6 months),and annualized bleeding rate during ITI(3.7 vs.2.8).The cost to success was lower for LD-ITI-IS200 than for LD-ITI-IS40(2107 vs.3256 US Dollar/kg).Among patients with peak inhibitor-titer 40-199 BU/mL,10 non-IS-using(on LD-ITI-IS200 regimen)and 28 IS-using(on LD-ITI-IS40 regimen)had similar success rates(70.0%vs.78.6%)and time to success(9.0 vs.8.8 months).Interpretation:In LD-ITI,IS are not necessary for inhibitor titer<200 BU/mL.

关键词： Hemophilia A High-titer inhibitor Immune tolerance induction Immunosuppressant Low-dose

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Mechanism and application of feedback loops formed by mechanotransduction and histone modifications

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Genes & Diseases 2024年第5期11卷 198-218页

作者： Han Sun Yafang Gao Xinyu Ma Yizhou Deng Lintao Bi Lisha Li Department of hematology and oncology China-Japan Union HospitalJilin UniversityChangchunJilin 130021China The Key Laboratory of Pathobiology Ministry of EducationCollege of Basic Medical SciencesJilin UniversityChangchunJilin 130021China

Mechanical stimulation is the key physical factor in cell *** acts as a fundamental regulator of cell behavior,regulating cell proliferation,differentiation,apoptosis,and exhibiting specific signature alterations during the pathological *** research continues,the role of epigenetic science in mechanotransduction is attracting ***,the molecular mechanism of the synergistic effect between mechanotransduction and epigenetics in physiological and pathological processes has not been *** focus on how histone modifications,as important components of epigenetics,are coordinated with multiple signaling pathways to control cell fate and disease ***,we propose that histone modifications can form regulatory feedback loops with signaling pathways,that is,histone modifications can not only serve as downstream regulators of signaling pathways for target gene transcription but also provide feedback to regulate signaling *** and epigenetic changes could be potential markers and therapeutic targets in clinical practice.

关键词： FAK Histone modifications MAPK Mechanotransduction RhoA WNT/b-catenin YAP/TAZ

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