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The regulatory roles and clinical significance of glycolysis in tumor

Cancer Communications 2024年第7期44卷 761-786页

作者： Qiqi Qiao Shunfeng Hu Xin Wang department of hematology Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinanShandongP.R.China department of hematology Shandong Provincial HospitalShandong UniversityJinanShandongP.R.China Taishan Scholars Program of Shandong Province JinanShandongP.R.China Branch of National Clinical Research Center for Hematologic Diseases JinanShandongP.R.China National Clinical Research Center for Hematologic Diseases the First Affiliated Hospital of Soochow UniversitySuzhouJiangsuP.R.China

Metabolic reprogramming has been demonstrated to have a significant impact on the biological behaviors of tumor cells,among which glycolysis is an important *** research has revealed that the heightened glycolysis levels,the abnormal expression of glycolytic enzymes,and the accumulation of glycolytic products could regulate the growth,proliferation,invasion,and metastasis of tumor cells and provide a favorable microenvironment for tumor development and *** on the distinctive glycolytic characteristics of tumor cells,novel imaging tests have been developed to evaluate tumor proliferation and *** addition,glycolytic enzymes have been found to serve as promising biomarkers in tumor,which could provide assistance in the early diagnosis and prognostic assessment of tumor *** glycolytic enzymes have been identified as potential therapeutic targets for tumor treatment,and various small molecule inhibitors targeting glycolytic enzymes have been developed to inhibit tumor development and some of them are already applied in the *** this review,we systematically summarized recent advances of the regulatory roles of glycolysis in tumor progression and highlighted the potential clinical significance of glycolytic enzymes and products as novel biomarkers and therapeutic targets in tumor treatment.

关键词： glycolysis tumor development biomarkers targeted therapy

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PRC2 primes bivalent genes for transcription induction independent of histone methyltransferase activity

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Science China(Life Sciences) 2024年第9期67卷 2033-2035页

作者： Meihan Gong Ye Yuan Zhongye Dai Xuejiao Lv Jiacheng Su Dawei Huo Lin Niu Xu Chen Xudong Wu State Key Laboratory of Experimental hematology The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical EpigeneticsKey Laboratory of Immune Microenvironment and Disease(Ministry of Education)Department of Cell BiologySchool of Basic Medical SciencesTianjin Medical UniversityTianjin 300070China Bone Marrow Transplantation Center the First Affiliated HospitalZhejiang University School of MedicineLiangzhu LaboratoryInstitute of HematologyZhejiang UniversityHangzhou 311113China

Dear Editor,Polycomb group proteins,conserved epigenetic transcriptional repressors,are crucial for orchestrating diverse developmental gene expression programs(Schuettengruber et al.,2017).The polycomb repressive complex 2(PRC2)catalyzes H3 lysine-27 trimethylation(H3K27me3)to establish a delicate balance with H3K4me3,forming a bivalent chromatin state at target gene promoters and thereby poising them for subsequent transcription activation(Bernstein et al.,2006).

关键词： valent thereby subsequent

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Advances and clinical applications of immune checkpoint inhibitors in hematological malignancies

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Cancer Communications 2024年第9期44卷 1071-1097页

作者： Wenyue Sun Shunfeng Hu Xin Wang department of hematology Shandong Provincial HospitalShandong UniversityJinanShandongP.R.China department of hematology Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinanShandongP.R.China Taishan Scholars Program of Shandong Province JinanShandongP.R.China Branch of National Clinical Research Center for Hematologic Diseases JinanShandongP.R.China National Clinical Research Center for Hematologic Diseases the First Affiliated Hospital of Soochow UniversitySuzhouJiangsuP.R.China

Immune checkpoints are differentially expressed on various immune cells to regulate immune responses in tumor *** cells can activate the immune checkpoint pathway to establish an immunosuppressive tumor microenvironment and inhibit the anti-tumor immune response,which may lead to tumor progression by evading immune *** coinhibitory signaling pathways with immune checkpoint inhibitors(ICIs)could reinvigorate the anti-tumor immune response and promote immune-mediated eradication of tumor *** a milestone in tumor treatment,ICIs have been firstly used in solid tumors and subsequently expanded to hematological malignancies,which are in their ***,immune checkpoints have been investigated as promising biomarkers and therapeutic targets in hematological malignancies,and novel immune checkpoints,such as signal regulatory proteinα(SIRPα)and tumor necrosis factor-alpha-inducible protein 8-like 2(TIPE2),are constantly being *** ICIs have received clinical approval for clinical application in the treatment of hematological malignancies,especially when used in combination with other strategies,including oncolytic viruses(OVs),neoantigen vaccines,bispecific antibodies(bsAb),bio-nanomaterials,tumor vaccines,and cytokine-induced killer(CIK)***,the proportion of individuals with hematological malignancies benefiting from ICIs remains lower than expected due to multiple mechanisms of drug resistance and immune-related adverse events(irAEs).Close monitoring and appropriate intervention are needed to mitigate irAEs while using *** review provided a comprehensive overview of immune checkpoints on different immune cells,the latest advances of ICIs and highlighted the clinical applications of immune checkpoints in hematological malignancies,including biomarkers,targets,combination of ICIs with other therapies,mechanisms of resistance to ICIs,and irAEs,which can provide novel insight into the future

关键词： Immune checkpoint hematological malignancies biomarkers therapeutic targets drug resistance

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Identification of cell surface markers for acute myeloid leukemia prognosis based on multi-model analysis

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Journal of Biomedical Research 2024年第4期38卷 397-412页

作者： Jiaqi Tang Lin Luo Bakwatanisa Bosco Ning Li Bin Huang Rongrong Wu Zihan Lin Ming Hong Wenjie Liu Lingxiang Wu Wei Wu Mengyan Zhu Quanzhong Liu Peng Xia Miao Yu Diru Yao Sali Lv Ruohan Zhang Wentao Liu Qianghu Wang Kening Li department of Bioinformatics School of Biomedical Engineering and InformaticsNanjing Medical UniversityNanjingJiangsu 211166China department of hematology of the Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University Northern Jiangsu Institute of Clinical MedicineHuai'anJiangsu 223300China Collaborative Innovation Center for Personalized Cancer Medicine Jiangsu Key Lab of Cancer BiomarkersPrevention and TreatmentNanjing Medical UniversityNanjingJiangsu 211166China department of hematology the First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjingJiangsu 210029China Key Laboratory of hematology of Nanjing Medical University NanjingJiangsu 210029China department of Pharmacology School of Basic Medical SciencesNanjing Medical UniversityNanjingJiangsu 211166China The Affiliated Cancer Hospital of Nanjing Medical University Jiangsu Cancer HospitalJiangsu Institute of Cancer ResearchNanjingJiangsu 210002China

Given the extremely high inter-patient heterogeneity of acute myeloid leukemia(AML),the identification of biomarkers for prognostic assessment and therapeutic guidance is *** surface markers(CSMs)have been shown to play an important role in AML leukemogenesis and *** the current study,we evaluated the prognostic potential of all human CSMs in 130 AML patients from The Cancer Genome Atlas(TCGA)based on differential gene expression analysis and univariable Cox proportional hazards regression *** using multi-model analysis,including Adaptive LASSO regression,LASSO regression,and Elastic Net,we constructed a 9-CSMs prognostic model for risk stratification of the AML *** predictive value of the 9-CSMs risk score was further validated at the transcriptome and proteome *** Cox regression analysis showed that the risk score was an independent prognostic factor for the AML *** AML patients with high 9-CSMs risk scores had a shorter overall and event-free survival time than those with low ***,single-cell RNA-sequencing analysis indicated that patients with high 9-CSMs risk scores exhibited chemotherapy ***,PI3K inhibitors were identified as potential treatments for these high-risk *** conclusion,we constructed a 9-CSMs prognostic model that served as an independent prognostic factor for the survival of AML patients and held the potential for guiding drug therapy.

关键词： acute myeloid leukemia cell surface markers prognosis drug sensitivity multi-model analysis

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Red blood cell membrane-coated FLT3 inhibitor nanoparticles to enhance FLT3-ITD acute myeloid leukemia treatment

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Chinese Chemical Letters 2024年第9期35卷 303-308页

作者： Jisheng Liu Junli Chen Xifeng Zhang Yin Wu Xin Qi Jie Wang Xiang Gao department of Neurosurgery and Institute of Neurosurgery State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalWest China Medical SchoolSichuan UniversityChengdu 610041China West China School of Basic Medical Sciences&Forensic Medicine Sichuan UniversityChengdu 610041China department of hematology West China HospitalSichuan UniversityChengdu 610041China

FMS-like tyrosine kinase 3(FLT3)is a viable and important therapeutic target for acute myeloid leukemia(AML).FLT3 internal tandem duplication(FLT3-ITD)mutations have been identified in approximately 30%of AML patients,and are associated with unfavorable prognosis,higher risk of relapse,drug resistance,and poor clinical *** FLT3 inhibitors have demonstrated promising efficacy,they cannot cure AML or even significantly extend the lives of patients with FLT3-ITD *** is partly because of poor water solubility,insufficient membrane penetration and short half-life of small molecule ***,the presence of enzymes like CYP3A4 in bone marrow accelerate the elimination and metabolism of FLT3 inhibitors,resulting in low plasma concentrations and side *** we report the erythrocyte membrane-camouflaged FLT3 inhibitor nanoparticles to enhance FLT3-ITD AML ***,we physically coextruded red blood cell(RBC)membrane vesicles with nanoparticles derived from FLT3 inhibitor F30 to obtain F30@RBC-M,which exhibited comparable potent FLT3-ITD inhibitory effects compared to free F30 in vitro,while displaying a higher potent antitumor efficacy in xenograft models due to the prolonged circulation ***,administration of F30@RBC-M significantly extended the survival of mice in a transplanted mouse model than F30 free *** findings suggest that RBC membrane-coated nanoparticles derived from FLT3 inhibitors hold promise as a tool to enhance the therapeutic efficacy to treat FLT3-ITD AML.

关键词： FLT3-ITD Acute myeloid leukemia AML Red blood cell membrane Biomimetics

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Mitochondrial diseases and mtDNA editing

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Genes & Diseases 2024年第3期11卷 303-310页

作者： Min Song Lingqun Ye Yongjin Yan Xuechun Li Xinglong Han Shijun Hu Miao Yu department of Cardiovascular Surgery of the First Affiliated Hospital&Institute for Cardiovascular Science Collaborative Innovation Center of HematologyState Key Laboratory of Radiation Medicine and ProtectionSuzhou Medical CollegeSoochow UniversitySuzhouJiangsu 215000China Hai'an People's Hospital NantongJiangsu 226600China

Mitochondrial diseases are a heterogeneous group of inherited disorders character-ized by mitochondrial dysfunction,and these diseases are often severe or even ***-chondrial diseases are often caused by mitochondrial DNA ***,there is no curative treatment for patients with pathogenic mitochondrial DNA *** the rapid development of traditional gene editing technologies,such as zinc finger nucleases and tran-scription activator-like effector nucleases methods,there has been a search for a mitochon-drial gene editing technology that can edit mutated mitochondrial DNA;however,there are still some problems hindering the application of these *** discovery of the DddA-derived cytosine base editor has provided hope for mitochondrial gene *** this paper,we will review the progress in the research on several mitochondrial gene editing technologies with the hope that this review will be useful for further research on mitochondrial gene editing technologies to optimize the treatment of mitochondrial diseases in the future.

关键词： Gene editing Mitochondrialdisease MitochondrialDNA mutation Transcription activator-like effectornucleases Zinc finger nucleases

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Gene mutations in newly diagnosed multiple myeloma patients detected by next-generation sequencing technology

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Cancer Pathogenesis and Therapy 2024年第3期2卷 205-211页

作者： Yutong Wang Mengzhen Wang Bin Chu Minqiu Lu Lei Shi Shan Gao Yuan Chen Qin Yan Na Ji Li Bao department of hematology Beijing Jishuitan HospitalCapital Medical UniversityBeijing 100035China

Background:Multiple myeloma(MM)is a heterogeneous plasma-derived hematopoietic malignancy with complex genetic mutation contributing to the *** gene sequencing has been applied in MM,genetic features from Chinese MM patients are reported *** investigated the genetic mutation of newly diagnosed multiple myeloma(NDMM)patients and explore its correlation with cytogenetic abnormalities detected by fluorescence in situ hybridization(FISH).Methods:A total of 206 patients with NDMM were *** enriching plasma cells with CD138 magnetic beads,92 MM-related target gene mutations were detected by the Illumina sequencing platform,and six common genetic abnormalities were detected by ***:162 cases(78.6%)had at least one gene mutation detected by *** top 5 mutated genes were KRAS,NRAS,TRAF3,BRAF,and *** abnormalities detected by FISH have a certain correlation with gene mutations,t(11;14)translocations are often accompanied by CCND1 and TP53 mutations,KLHL6 in t(4;14),SP140,CDKN1B and PRKD2 in t(14;16)and t(14;20)*** mutation ratio was higher for EGR1,while lower of CCND1 in patients with gain *** TP53 mutation was more likely in patients with 17p *** gene mutation affects the pathway of the RNA process is more frequently occurring in males and age less than 70 years *** International Staging System(ISS)Stage Ⅲ correlated with gene mutations in the NK-κB pathway while Revised ISS(R-ISS)Stage Ⅲ correlated with the DNA damage repair ***:There are various gene mutations in NDMM patients,mainly RAS/MAPK and NF-κB pathway gene pathways.

关键词： Multiple myeloma Next-generation sequencing Genetics mutation

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Galectin 3-binding protein(LGALS3BP)depletion attenuates hepatic fibrosis by reducing transforming growth factor-β1(TGF-β1)availability and inhibits hepatocarcinogenesis

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Cancer Communications 2024年第10期44卷 1106-1129页

作者： Dae-Hwan Kim Minjeong Sung Myong-Suk Park Eun-Gene Sun Sumin Yoon Kyung Hyun Yoo Kamalakannan Radhakrishnan Sung Yun Jung Woo-Kyun Bae Sang-Hee Cho Ik-Joo Chung department of Internal Medicine Division of Hematology and OncologyChonnam National University Medical SchoolHwasunSouth Korea department of Internal Medicine Division of Hematology and OncologyChonnam National University Hwasun HospitalHwasunSouth Korea Combinatorial Tumor Immunotherapy MRC Center Chonnam National University Medical SchoolHwasunSouth Korea National Immunotherapy Innovation Center HwasunSouth Korea BioMedical Sciences Graduate Program Chonnam National UniversityHwasunSouth Korea department of Biological Science SookmyungWomen’s UniversitySeoulSouth Korea Clinical Vaccine R&D Center Chonnam National UniversityHwasunSouth Korea department of Biochemistry and Molecular Pharmacology Baylor College of MedicineHoustonTexasUSA

Background:Increased Galectin 3-binding protein(LGALS3BP)serum levels have been used to assess hepatic fibrosis stages and the severity of hepatocellular carcinoma(HCC).Considering the crucial role of transforming growth factor-β1(TGF-β1)in the emergence of these diseases,the present study tested the hypothesis that LGALS3BP regulates the TGF-β1 signaling ***:The expression levels of LGALS3BP and TGFB1 were analyzed in patients with metabolic dysfunction-associated steatohepatitis(MASH)and *** omics techniques,such as RNA-sequencing,transposaseaccessible chromatin-sequencing assay,and liquid chromatography-tandem mass spectrometry proteomics,were used to identify the regulatory mechanisms for the LGALS3BP-TGF-β1 *** effects of altered TGF-β1 signaling by LGALS3BP were investigated in conditional LGALS3BP-knockin and LGALS3BP-knockout ***:In patients with MASH and HCC,the levels of LGALS3BP and TGFB1 exhibited positive *** of LGALS3BP by the inflammatory cytokine interferonαin HCC cells or ectopic overexpression of LGALS3BP in hepatocytes promoted the expression levels of *** fibrosis was observed in the livers of hepatocyte-specific LGALS3BP-knockin mice,with increased TGFB1 ***3BP directly bound to and assembled integrinαV,an integral mediator required for releasing active TGF-β1 from extracellular latent complex with the rearranged F-actin *** released TGF-β1 activated JunB transcription factor,which in turn promoted the TGF-β1 positive feedback ***3BP deletion in the hepatocytes downregulated TGF-β1 signaling and CCl4 induced ***,LGALS3BP depletion hindered hepatocarcinogenesis by limiting the availability of fibrogenic TGF-β***:LGALS3BP plays a crucial role in hepatic fibrosis and carcinogenesis by controlling the TGF-β1 signaling pathway,making it a promising therapeutic target in TGF-β1-related diseases.

关键词： F-actin FAK hepatic carcinogenesis IntegrinαV Interferonα JunB LGALS3BP metabolic dysfuntion-associated steatohepatitis tensile force TGF-β1

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Lyophilized lymph nodes:A paradigm shift in CAR T-cell delivery for solid tumor therapy

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3774-3776页

作者： Qiuhua Luo Xiaojing Yan Hong-Xu Liu Heran Li department of Pharmacy the First Hospital of China Medical UniversityShenyang 110001China School of Pharmacy China Medical UniversityShenyang 110122China department of hematology the First Hospital of China Medical UniversityShenyang 110001China Liaoning Cancer Hospital&Institute Cancer Hospital of Dalian University of TechnologyShenyang 110042China

CAR T(chimeric antigen receptor T-cell)therapy represents a paradigm shift in cancer *** empowering immune cells to target malignant cells directly,it opens another door to precision medicine,promising cures for once refractory ***,the extension of CAR T therapy to solid tumors confronts formidable *** physical and biochemical barriers within the tumor microenvironment,such as dense extracellular matrices and immunosuppressive factors,impede CAR T cell infiltration and function,leading to diminished success rates in solid tumor treatment2.

关键词： CAR therapy tumor

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Silencing of Jumonji domain-containing 1C inhibits the osteogenic differentiation of bone marrow mesenchymal stem cells via nuclear factor-κB signaling

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World Journal of Stem Cells 2024年第2期16卷 151-162页

作者： Jing-Yi Li Ting-Ting Wang Li Ma Yu Zhang Di Zhu department of Medical Cosmetology Beijing Tiantan HospitalCapital Medical UniversityBeijing 100070China department of General Gerontology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina department of Plastic Surgery China-Japan Friendship HospitalBeijing 100029China Senior department of hematology The Fifth Medical CentreGeneral Hospital of Chinese People’s Liberation ArmyBeijing 100071China department of Orthopaedic Surgery Beijing Tiantan HospitalCapital Medical UniversityBeijing 100070China

BACKGROUND Osteoporosis is a common metabolic bone disorder induced by an imbalance between osteoclastic activity and osteogenic *** osteoporosis,bone mesenchymal stem cells(BMSCs)exhibit an increased ability to differentiate into adipocytes and a decreased ability to differentiate into osteoblasts,resulting in bone *** domain-containing 1C(JMJD1C)has been demonstrated to suppress *** To examine the effect of JMJD1C on the osteogenesis of BMSCs and the potential underlying *** BMSCs were isolated from mouse bone marrow *** Red O staining,Alizarin red staining,alkaline phosphatase staining and the expression of adipo-genic and osteogenic-associated genes were assessed to determine the differen-tiation of *** marrow-derived macrophages(BMMs)were incubated with receptor activator of nuclear factor-kappaΒligand to induce osteoclast differentiation,and osteoclast differen-tiation was confirmed by tartrate-resistant acid phosphatase *** related genes were measured via reverse transcription coupled to the quantitative polymerase chain reaction and western ***-linked immunosorbent assays were used to measure the levels of inflammatory cytokines,including tumor necrosis factor alpha,interleukin-6 and interleukin-1 *** The osteogenic and adipogenic differentiation potential of BMSCs isolated from mouse bone marrow samples was ***1C mRNA and protein expression was upregulated in BMSCs after osteoblast induction,while p-nuclear factor-κB(NF-κB)and inflammatory cytokines were not significantly *** of JMJD1C repressed osteogenic differentiation and enhanced NF-κB activation and inflammatory cytokine release in ***,JMJD1C expression decreased during BMM osteoclast *** The JMJD1C/NF-κB signaling pathway is potentially involved in BMSC osteogenic differentiation and may play vital roles in the pathogenesis of osteoporosis.

关键词： Osteoporosis Mesenchymal stem cells Osteogenesis Jumonji domain-containing 1C Nuclear factor-κB

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