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LATS1 Promotes B-ALL Tumorigenesis by Regulating YAP1 Phosphorylation and Subcellular Localization

Current Medical Science 2024年第1期44卷 81-92页

作者： Feng ZHANG Mohammed Awal Issah Hai-ying FU Hua-rong ZHOU Ting-bo LIU Jian-zhen SHEN Fujian Provincial Key laboratory on Hematology Fujian Medical Center of HematologyFujian Institute of HematologyClinical Research Center for Hematological Malignancies of Fujian ProvinceFujian Medical University Union HospitalFuzhou 350001China Tamale Technical University Faculty of Allied Health and Pharmaceutical SciencesDepartment of Medical Laboratory TechnologyTamale NS-011-2000Ghana Department of Hematology The Third Affiliated People's Hospital of Fujian University of Traditional Chinese MedicineThe Third People's Hospital of Fujian ProvinceFuzhou 350122China

Objective YAP1 plays a dual role as an oncogene and tumor suppressor gene in several tumors;differentiating between these roles may depend on the YAP1 phosphorylation *** specific function of YAP1 in B cell acute lymphoblastic leukemia(B-ALL),however,is currently ***,in the present study,the role of YAP1 in B-ALL was investigated using relevant cell lines and patient *** The effects of shRNA-mediated knockdown on YAP1 and LATS1 levels in the NALM6 and MOLT-4 cell lines were examined using Western blotting,quantitative real-time polymerase chain reaction,flow cytometry,immunostaining,and nude mouse subcutaneous tumorigenesis *** expression levels of Hippo pathway-related molecules before and after verteporfin(VP)treatment were compared using RNA-Seq to identify significant Hippo pathway-related genes in NALM6 *** Patients with ALL showing high YAP1 expression and low YAP1-Ser127 phosphorylation levels had worse prognoses than those with low YAP1 protein expression and high YAP1-Ser127 phosphorylation ***1-Ser127 phosphorylation levels were lower in NALM6 cells than in MOLT-4 and control cells;YAP1 was distributed in the nuclei in NALM6 *** of YAP1 inhibited MOLT-4 and NALM6 cell proliferation and arrested the NALM6 cell cycle in the G0/G1 *** and after VP treatment,the expression of the upstream gene LATS1 was upregulated;its overexpression promoted YAP1-Ser127 ***,YAP1 was distributed in the *** LATS1 may downregulate YAP1-Ser127 phosphorylation and maintain B-ALL cell function;thus,VP,which targets this axis,may serve as a new therapeutic method for improving the outcomes for B-ALL patients.

关键词： acute lymphoblastic leukemia large tumor suppressor kinase 1 phosphorylation RNA-Seq Yesl-associated protein

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Novel PIKfyve/Tubulin Dual-target Inhibitor as a Promising Therapeutic Strategy for B-cell Acute Lymphoblastic Leukemia

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Current Medical Science 2024年第2期44卷 298-308页

作者： Zhen LU Qian LAI Zhi-feng LI Meng-ya ZHONG Yue-long JIANG Li-ying FENG Jie ZHA Jing-wei YAO Yin LI Xian-ming DENG Bing XU Department of Hematology The First Affiliated Hospital of Xiamen University and Institute of HematologySchool of MedicineXiamen UniversityXiamen361005China Key laboratory of Xiamen for Diagnosis and Treatment of hematological Malignancy Xiamen361005China Department of Oncology The First Affiliated Hospital of Jinan UniversityJinan UniversityGuangzhou510630China State Key laboratory of Cellular Stress Biology Innovation Center for Cell Signaling NetworkSchool of Life SciencesXiamen UniversityXiamen361003China

Objective:In B-cell acute lymphoblastic leukemia(B-ALL),current intensive chemotherapies for adult patients fail to achieve durable responses in more than 50%of cases,underscoring the urgent need for new therapeutic regimens for this patient *** present study aimed to determine whether HZX-02-059,a novel dual-target inhibitor targeting both phosphatidylinositol-3-phosphate 5-kinase(PIKfyve)and tubulin,is lethal to B-ALL cells and is a potential therapeutic for B-ALL ***:Cell proliferation,vacuolization,apoptosis,cell cycle,and in-vivo tumor growth were *** addition,Genome-wide RNA-sequencing studies were conducted to elucidate the mechanisms of action underlying the anti-leukemia activity of HZX-02-059 in ***:HZX-02-059 was found to inhibit cell proliferation,induce vacuolization,promote apoptosis,block the cell cycle,and reduce in-vivo tumor *** of the p53 pathway and suppression of the phosphoinositide 3-kinase(PI3K)/AKT pathway and the downstream transcription factors c-Myc and NF-κB were responsible for these ***:Overall,these findings suggest that HZX-02-059 is a promising agent for the treatment of B-ALL patients resistant to conventional therapies.

关键词： B-cell acute lymphoblastic leukemia dual-target inhibitor NF-kB c-Myc PI3K/AKT p53

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Long non-coding RNA MALAT1 in hematological malignancies and its clinical applications

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Chinese Medical Journal 2024年第10期137卷 1151-1159页

作者： Chunlan Zhang Yun Qin Yu Wu Heng Xu Yang Shu Department of Hematology West China HospitalSichuan UniversityChengduSichuan 610041China Department of Radiology West China HospitalSichuan UniversityChengduSichuan 610041China Department of laboratory Medicine/research Center of Clinical laboratory Medicine West China HospitalSichuan UniversityChengduSichuan 610041China Department of Biotherapy State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversityChengduSichuan 610041China Institute of General Surgery West China HospitalSichuan UniversityChengduSichuan 610041China Department of General Surgery Gastric Cancer Center and Laboratory of Gastric CancerWest China HospitalSichuan UniversityChengduSichuan 610041China

Metastasis-associated lung adenocarcinoma transcript 1(MALAT1)is a well-established oncogenic long non-coding RNA,the higher expression of which is strongly correlated with cancer events such as tumorigenesis,progression,metastasis,drug resistance,and treatment outcome in solid ***,a series of studies has highlighted its potential role in hematological malignancies in terms of these *** to solid cancers,MALAT1 can regulate various target genes via sponging and epigenetic mechanisms,but the miRNAs sponged by MALAT1 differ from those identified in solid *** this review,we systematically describe the role and underlying mechanisms of MALAT1 in multiple types of hematological malignancies,including regulation of cell proliferation,metastasis,stress response,and ***,MALAT1 expression is related to poor treatment outcome and drug resistance,therefore exhibiting potential prognostic value in multiple myeloma,lymphoma,and ***,we discuss the evaluation of MALAT1 as a novel therapeutic target against cancer in preclinical studies.

关键词： Long non-coding RNA hematological malignancies Tumorigenesis Metastasis Drug resistance Prognostic biomarker

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Stepping forward:T-cell redirecting bispecific antibodies in cancer therapy

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2361-2377页

作者： Xiaojing Qin Wenjing Ning Han Liu Xue Liu Wenxin Luo Ningshao Xia State Key laboratory of Vaccines for Infectious Diseases Xiang An Biomedicine LaboratorySchool of Public HealthXiamen UniversityXiamen 361102China National Institute of Diagnostics and Vaccine Development in Infectious Diseases State Key Laboratory of Molecular Vaccinology and Molecular DiagnosticsNational Innovation Platform for IndustryeEducation Integration in Vaccine Researchthe Research Unit of Frontier Technology of Structural Vaccinology of Chinese Academy of Medical SciencesXiamen UniversityXiamen 361102China

T cell-redirecting bispecific antibodies are specifically designed to bind to tumor-associated antigens,thereby engaging with CD3 on the T cell *** linkage between tumor cells and T cells actively triggers T cell activation and initiates targeted killing of the identified tumor *** antibodies have emerged as one of the most promising avenues within tumor ***,despite success in treating hematological malignancies,significant advancements in solid tumors have yet to be *** this review,we aim to address the critical challenges associated with T cellredirecting bispecific antibodies and explore novel strategies to overcome these obstacles,with the ultimate goal of expanding the application of this therapy to include solid tumors.

关键词： Bispecific antibody(BsAbs) T-cell redirecting BsAbs Tumor-associated antigens Toxicity Cytokine release syndrome Tumor microenvironment Cancer immunotherapy Combination therapy strategies

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Hodgkin's lymphoma:2023 update on treatment

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Cancer Biology & Medicine 2024年第4期21卷 269-273页

作者： Sicong Zhang Xianming Liu Lanfang Li Lihua Qiu Zhengzi Qian Shiyong Zhou Xianhuo Wang Huilai Zhang Department of Lymphoma Tianjin Medical University Cancer Institute&HospitalNational Key Laboratory of Druggability Evaluation and Systematic Translational MedicineNational Clinical Research Center for CancerTianjin's Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinThe Sino-US Center for Lymphoma and Leukemia ResearchTianjin 300060China

Hodgkin's lymphoma(HL)is a common,malignant hematological tumor of the lymph nodes and lymphatic system,accounting for 10%of all *** comprises 2 main subtypes:classical HL(cHL)and nodular lymphocyte predominant HL.

关键词： lymphoma treatment predominant

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Preoperative prediction of lymphovascular and perineural invasion in gastric cancer using spectral computed tomography imaging and machine learning

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World Journal of Gastroenterology 2024年第6期30卷 542-555页

作者： Hui-Ting Ge Jian-Wu Chen Li-Li Wang Tian-Xiu Zou Bin Zheng Yuan-Fen Liu Yun-Jing Xue Wei-Wen Lin Department of Radiology Fujian Medical University Union HospitalFuzhou 350001Fujian ProvinceChina Fujian Key laboratory of Intelligent Imaging and Precision Radiotherapy for Tumors Fujian Medical UniversityFuzhou 350001Fujian ProvinceChina Digestive Hematological and Breast MalignanciesClinical Research Center for Radiology and Radiotherapy of Fujian ProvinceFuzhou 350001Fujian ProvinceChina Department of Radiation Oncology Fujian Medical University Union HospitalFuzhou 350001Fujian ProvinceChina Department of Diagnostic Radiology Fujian Medical University Union HospitalFuzhou 350001Fujian ProvinceChina School of Electrical and Computer Engineering University of OklahomaOklahomaOK 73019United States

BACKGROUND Lymphovascular invasion(LVI)and perineural invasion(PNI)are important prognostic factors for gastric cancer(GC)that indicate an increased risk of metastasis and poor *** preoperative prediction of LVI/PNI status could help clinicians identify high-risk patients and guide treatment ***,prior models using conventional computed tomography(CT)images to predict LVI or PNI separately have had limited *** CT provides quantitative enhancement parameters that may better capture tumor *** hypothesized that a predictive model combining clinical and spectral CT parameters would accurately preoperatively predict LVI/PNI status in GC *** To develop and test a machine learning model that fuses spectral CT parameters and clinical indicators to predict LVI/PNI status *** This study used a retrospective dataset involving 257 GC patients(training cohort,n=172;validation cohort,n=85).First,several clinical indicators,including serum tumor markers,CT-TN stages and CT-detected extramural vein invasion(CT-EMVI),were extracted,as were quantitative spectral CT parameters from the delineated tumor ***,a two-step feature selection approach using correlation-based methods and information gain ranking inside a 10-fold cross-validation loop was utilized to select informative clinical and spectral CT parameters.A logistic regression(LR)-based nomogram model was subsequently constructed to predict LVI/PNI status,and its performance was evaluated using the area under the receiver operating characteristic curve(AUC).RESULTS In both the training and validation cohorts,CT T3-4 stage,CT-N positive status,and CT-EMVI positive status are more prevalent in the LVI/PNI-positive group and these differences are statistically significant(P<0.05).LR analysis of the training group showed preoperative CT-T stage,CT-EMVI,single-energy CT values of 70 keV of venous phase(VP-70 keV),and the ratio of standardized iodine co

关键词： Spectral computed tomography Gastric cancer Lymphovascular invasion Perineural invasion

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Enhanced Precision Therapy of Multiple Myeloma Through Engineered Biomimetic Nanoparticles with Dual Targeting

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Engineering 2024年第5期36卷 178-192页

作者： Ruogu Qi Shanshan Wang Jiayi Yu Tianming Lu Zhiqiang Bi Weibo Liu Yuanyuan Guo Yong Bian Jianliang Shen Xuesong Zhang Wenhao Hu School of Medicine Nanjing University of Chinese MedicineNanjing 210023China laboratory Animal Center Nanjing University of Chinese MedicineNanjing 210023China Key laboratory of Carcinogenesis and Translational research Ministry of Education/BeijingDepartment of Radiation OncologyBeijing Cancer HospitalBeijing 100142China Department of Orthopedics The Fourth Medical CenterThe Chinese People’s Liberation Army General HospitalBeijing 100853China State Key laboratory of Ophthalmology Optometry and Vision ScienceSchool of Biomedical EngineeringWenzhou Medical UniversityWenzhou 325027China

Multiple myeloma(MM)is the second most prevalent hematological *** MM treatment strategies are hampered by systemic toxicity and suboptimal therapeutic *** study addressed these limitations through the development of a potent MM-targeting chemotherapy strategy,which capitalized on the high binding affinity of alendronate for hydroxyapatite in the bone matrix and the homologous targeting of myeloma cell membranes,termed T-PB@*** results from our investigations highlight the considerable bone affinity of T-PB@M,both in vitro and in ***,this material demonstrated a capability for drug release triggered by low pH ***,T-PB@M induced the generation of reactive oxygen species and triggered cell apoptosis through the poly(ADP-ribose)polymerase 1(PARP1)-Caspase-3-B-cell lymphoma-2(Bcl-2)pathway in MM ***,T-PB@M preferentially targeted bone-involved sites,thereby circumventing systemic toxic side effects and leading to prolonged survival of MM orthotopic ***,this designed target-MM nanocarrier presents a promising and potentially effective platform for the precise treatment of MM.

关键词： Multiple myeloma Bortezomib Drug delivery Dual targeting Controlled release

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The chemical characteristics of different sodium iron ethylenediaminetetraacetate sources and their relative bioavailabilities for broilers fed with a conventional corn‑soybean meal diet

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Journal of Animal Science and Biotechnology 2024年第2期15卷 826-843页

作者： Shengchen Wang Bingxin Wu Ling Zhu Weiyun Zhang Liyang Zhang We Wu Jiaqi Wu Yun Hu Tingting Li Xiaoyan Cui Xugang Luo College of Animal Science and Technology Yangzhou UniversityYangzhou 225000People’s Republic of China Mineral Nutrition research Division State Key Laboratory of Animal NutritionInstitute of Animal ScienceChinese Academy of Agricultural SciencesBeijing 100193China

Background Our previous studies demonstrated that divalent organic iron(Fe)proteinate sources with higher complexation or chelation strengths as expressed by the greater quotient of formation(Qf)values displayed higher Fe bioavailabilities for *** iron ethylenediaminetetraacetate(NaFeEDTA)is a trivalent organic Fe source with the strongest chelating ligand ***,the bioavailability of Fe when administered as NaFeEDTA in broilers and other agricultural animals remains ***,the chemical characteristics of 12 NaFeEDTA products were *** these,one feed grade NaFeEDTA(Qf=2.07×10^(8)),one food grade NaFeEDTA(Qf=3.31×10^(8)),and one Fe proteinate with an extremely strong chelation strength(Fe-Prot ES,Qf value=8,590)were *** bioavailabilities relative to Fe sulfate(FeSO_(4)·7H_(2)O)for broilers fed with a conventional corn-soybean meal diet were evaluated during d 1 to 21 by investigating the effects of the above Fe sources and added Fe levels on the growth performance,hematological indices,Fe contents,activities and gene expressions of Fe-containing enzymes in various tissues of *** NaFeEDTA sources varied greatly in their chemical *** Fe concentration(PI),transferrin saturation(TS),liver Fe content,succinate dehydrogenase(SDH)activities in liver,heart,and kidney,catalase(CAT)activity in liver,and SDH mRNA expressions in liver and kidney increased linearly(P<0.05)with increasing levels of Fe ***,differences among Fe sources were detected(P<0.05)only for PI,liver Fe content,CAT activity in liver,SDH activities in heart and kidney,and SDH mRNA expressions in liver and *** on slope ratios from multiple linear regressions of the above indices on daily dietary analyzed Fe intake,the average bioavailabilities of Fe-Prot ES,feed grade NaFeEDTA,and food grade NaFeEDTA relative to the inorganic FeSO_(4)·7H_(2)O(100%)for broilers were 139%,155%,and 166%,***

关键词： Broilers Chelation strengths Fe-containing enzymes NaFeEDTA Relative bioavailabilities

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Comparison of clinical features of nephrotic syndrome after haploidentical and matched donor hematopoietic stem cell transplantation

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Chinese Medical Journal 2024年第4期137卷 478-480页

作者： Wei Sun Yuanyuan Zhang Yuhong Chen Yuqian Sun Yifei Cheng Fengrong Wang Huan Chen Yao Chen Chenhua Yan Xiaodong Mo Wei Han Lanping Xu Yu Wang Xiaohui Zhang Kaiyan Liu Xiaojun Huang Peking University People’s Hospital Peking University Institute of HematologyNational Clinical Research Center for Hematologic DiseaseBeijing Key Laboratory of Hematopoietic Stem Cell TransplantationPeking UniversityBeijing 10004China

To the Editor:Allogeneic hematopoietic stem cell transplantation(allo-HSCT)is one of the most effective options for hematological ***,allo-HSCT treatment can cause serious ***-transplant kidney damage is an important *** this study,we retrospectively analyzed the frequency of nephrotic syndrome(NS)after allo-HSCT and compared the frequency and clinical characteristics of NS between haploidentical donor(HID)and matched donor(MD)HSCT(including matched sibling donors[MSD]and unrelated donors[URD]).

关键词： hematopoietic clinical matched

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Whole breast ultrafractionation radiotherapy after breast-conserving surgery in early breast cancer: A single-center, prospective, observational study from China

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Malignancy Spectrum 2024年第2期1卷 113-122页

作者： Rui-Zhi Zhao Cheng Huang Tian-Lan Tang Gui-Qing Shi Si-Lin Chen Yu-Ping Lin Ying Wang Liu-Qing Jiang Jin-Hua Chen Chun-Sen Xu Fang-Meng Fu Zhong-Hua Han Shun-Guo Lin Chuan Wang Yong Yang Department of Radiation Oncology Fujian Medical University Union HospitalFujian Key Laboratory of Intelligent Imaging and Precision Radiotherapy for Tumors(Fujian Medical University)Clinical Research Center for Radiology and Radiotherapy of Fujian Province(DigestiveHematological and Breast Malignancies)FuzhouFujianChina Department of Follow-Up Center Fujian Medical University Union HospitalFuzhouFujianChina Department of Breast Surgery Fujian Medical University Union HospitalFuzhouFujianChina

Objective:This single-center,prospective,observational study was designed to investigate the toxicities,patient-reported outcome(PRO),and dosimetric analysis of whole breast ultrafractionation radiotherapy(RT)after breast-conserving surgery(BCS)in early breast cancer(BC).Patients and methods:Patients diagnosed with BC stage I,II and treated with BCS were enrolled.A dose of 26 Gray(Gy)in five fractions was prescribed to the whole breast and tumor *** endpoints included toxicities,PRO,and dosimetric *** was measured by the European Organization for research and Treatment of Cancer general quality of life questionnaire(EORTC QLQ-C30)and the BC-specific questionnaire(EORTC QLQ-BR23)***:Between January 2022 and June 2023,62 female patients were *** median age was 45 *** patients(83.9%)were diagnosed with pathological stage I *** median planning target volume(PTV)was 456.4 *** minimum,maximum,and mean doses,and D95(dose of PTV irradiated volume more than 95%)to PTV were 20.2,28.8,27.2,and 26.3 Gy,*** median mean lung dose and percentage lung volume receiving 8 Gy(V8)were 3.6 Gy and 13.4%,*** median mean heart dose,V1.5(percentage of organ volume irradiated with 1.5 Gy or higher),and V7(percentage of organ volume irradiated with 7 Gy or higher)were 0.6 Gy,6.8%,and 0.4%,*** effects before RT showed no obvious differences compared to that post *** toxicities of grade 3 or higher *** patients had asymptomatic radiation pneumonia(grade 1),and 12 patients had radiation dermatitis(grade 1).No factor was significantly related to radiation dermatitis or radiation *** the EORTC QLQ-C30 and QLQ-BR23 questionnaires,all function and symptom scores before RT had no significant differences compared with that after RT,1−2 months after RT,and 3−4 months after *** RT did not worsen *** 1-year crude local control was 100%.Conclusion:Whole br

关键词： ultrafractionation radiotherapy breast cancer breast-conserving surgery toxicities patient-reported outcome

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