المؤلفون: Hisayuki Amano, Masahiko Honda, Akiyoshi Komuro, Takeshi Ueda, Masahito Kawazu, Akinori Kanai, Kazushige Ota, Hitoshi Okada

المصدر: FASEB BioAdvances, Vol 3, Iss 12, Pp 1020-1033 (2021)
FASEB BioAdvances

مصطلحات موضوعية: Cancer Research, gene expression analysis, Physiology, QH301-705.5, Myeloid leukemia, Gene targeting, Biology, acute myeloid leukemia, Biochemistry, Genetics and Molecular Biology (miscellaneous), Aml1 eto, Chromatin, gene targeting, chromatin accessibility, hemic and lymphatic diseases, Gene expression, Cancer research, Molecular Medicine, Biology (General), Research Articles, Research Article

الوصف: Epigenetic alterations of chromatin structure affect chromatin accessibility and collaborate with genetic alterations in the development of cancer. Lysine demethylase 4B (KDM4B) has been identified as a JmjC domain‐containing epigenetic modifier that possesses histone demethylase activity. Although recent studies have demonstrated that KDM4B positively regulates the pathogenesis of multiple types of solid tumors, the tissue specificity and context dependency have not been fully elucidated. In this study, we investigated gene expression profiles established from clinical samples and found that KDM4B is elevated specifically in acute myeloid leukemia (AML) associated with chromosomal translocation 8;21 [t(8;21)], which results in a fusion of the AML1 and the eight‐twenty‐one (ETO) genes to generate a leukemia oncogene, AML1‐ETO fusion transcription factor. Short hairpin RNA‐mediated KDM4B silencing significantly reduced cell proliferation in t(8;21)‐positive AML cell lines. Meanwhile, KDM4B silencing suppressed the expression of AML1‐ETO‐inducible genes, and consistently perturbed chromatin accessibility of AML1‐ETO‐binding sites involving altered active enhancer marks and functional cis‐regulatory elements. Notably, transduction of murine KDM4B orthologue mutants followed by KDM4B silencing demonstrated a requirement of methylated‐histone binding modules for a proliferative surge. To address the role of KDM4B in leukemia development, we further generated and analyzed Kdm4b conditional knockout mice. As a result, Kdm4b deficiency attenuated clonogenic potential mediated by AML1‐ETO and delayed leukemia progression in vivo. Thus, our results highlight a tumor‐promoting role of KDM4B in AML associated with t(8;21).

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::24841aa5aeb1ee4572bc9c2b7e2c5426Test
https://doaj.org/article/5926bec7943c4cc888c811f78ca73aa2Test

المؤلفون: Goshi Shiota, Hiroyuki Tsuchiya

المصدر: Tsuchiya, Hiroyuki. Shiota, Goshi. Immune evasion by cancer stem cells. Regenerative Therapy. 17. 20-33. doi:10.1016/j.reth.2021.02.006
Regenerative Therapy, Vol 17, Iss, Pp 20-33 (2021)
Regenerative Therapy

مصطلحات موضوعية: PD-L1/2, ligands 1/2, 0301 basic medicine, Medicine (General), Immune checkpoint inhibitors, Cell, LAG3, lymphocyte activation gene 3, Review, NK cells, Tumor initiation, HNSCC, head and neck squamous cell carcinoma, MIC, MHC class I polypeptide-related sequence, DC, dendritic cell, 0302 clinical medicine, AML, acute myeloid leukemia, ARID3B, AT-rich interaction domain-containing protein 3B, OCT4, octamer-binding transcription factor 4, TCR, T cell receptor, Cancer stem cells, Immune evasion, CCR7, C–C motif chemokine receptor 7, KDM4, lysine-specific demethylase 4C, medicine.anatomical_structure, TAM, tumor-associated macrophage, EMT, epithelial–mesenchymal transition, NK, natural killer, ULBP, UL16 binding protein, LILR, leukocyte immunoglobulin-like receptor, NGF, nerve growth factor, T cells, Biomedical Engineering, Treg, regulatory T cell, Tumor immunity, CTL, cytotoxic T lymphocytes, NOD, nonobese diabetic, Biomaterials, 03 medical and health sciences, R5-920, Immune system, ALDH, alcohol dehydrogenase, EV, extracellular vesicle, MDSC, myeloid-derived suppressor cell, Cancer stem cell, medicine, MHC, major histocompatibility complex, KIR, killer immunoglobulin-like receptor, TAP, transporter associated with antigen processing, SCID, severe combined immunodeficient, QH573-671, business.industry, LMP, low molecular weight protein, CIK, cytokine-induced killer cell, LOX, lysyl oxidase, CTLA-4, cytotoxic T-cell-associated antigen-4, CMV, cytomegalovirus, SOX2, sex determining region Y-box 2, NSG, NOD/SCID IL-2 receptor gamma chain null, Evasion (ethics), CSC, cancer stem cell, 030104 developmental biology, DNMT, DNA methyltransferase, Cancer cell, Immune checkpoints, Cancer research, PI9, protease inhibitor 9, ADCC, antibody-dependent cell mediated cytotoxicity, uPAR, urokinase-type plasminogen activator receptor, Cytology, business, ETO, fat mass and obesity associated protein, 030217 neurology & neurosurgery, PD-1, programmed death receptor-1, PSME3, proteasome activator subunit 3, Developmental Biology

الوصف: Tumor immunity represents a new avenue for cancer therapy. Immune checkpoint inhibitors have successfully improved outcomes in several tumor types. In addition, currently, immune cell-based therapy is also attracting significant attention. However, the clinical efficacy of these treatments requires further improvement. The mechanisms through which cancer cells escape the immune response must be identified and clarified. Cancer stem cells (CSCs) play a central role in multiple aspects of malignant tumors. CSCs can initiate tumors in partially immunocompromised mice, whereas non-CSCs fail to form tumors, suggesting that tumor initiation is a definitive function of CSCs. However, the fact that non-CSCs also initiate tumors in more highly immunocompromised mice suggests that the immune evasion property may be a more fundamental feature of CSCs rather than a tumor-initiating property. In this review, we summarize studies that have elucidated how CSCs evade tumor immunity and create an immunosuppressive milieu with a focus on CSC-specific characteristics and functions. These profound mechanisms provide important clues for the development of novel tumor immunotherapies.
Highlights • Cancer stem cells (CSCs) play a central role in multiple aspects of malignant tumors. • Immune evasion is a fundamental feature of CSCs. • Immune evasion mechanisms must be precisely clarified to improve tumor immunotherapy. • CSCs are promising targets for tumor immunotherapy.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4f6054a82a446a6f8b0b1100401e59a6Test
https://doi.org/10.1016/j.reth.2021.02.006Test

المؤلفون: Min Yang, Bide Zhao, Jinghan Wang, Yi Zhang, Chao Hu, Lixia Liu, Jiayue Qin, Feng Lou, Shanbo Cao, Chengcheng Wang, Wenjuan Yu, Hongyan Tong, Haitao Meng, Jian Huang, Honghu Zhu, Jie Jin

المصدر: Frontiers in Oncology, Vol 11 (2022)
Frontiers in Oncology

مصطلحات موضوعية: Cancer Research, Oncology, hemic and lymphatic diseases, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, next-generation sequencing, AML-ETO, prognosis, acute myeloid leukemia, LASSO Cox regression, RC254-282, Original Research

الوصف: Core Binding Factor (CBF)-AML is one of the most common somatic mutations in acute myeloid leukemia (AML). t(8;21)/AML1-ETO-positive acute myeloid leukemia accounts for 5-10% of all AMLs. In this study, we consecutively included 254 AML1-ETO patients diagnosed and treated at our institute from December 2009 to March 2020, and evaluated molecular mutations by 185-gene NGS platform to explore genetic co-occurrences with clinical outcomes. Our results showed that high KIT VAF(≥15%) correlated with shortened overall survival compared to other cases with no KIT mutation (3-year OS rate 26.6% vs 59.0% vs 69.6%, HR 1.50, 95%CI 0.78-2.89, P=0.0005). However, no difference was found in patients’ OS whether they have KIT mutation in two or three sites. Additionally, we constructed a risk model by combining clinical and molecular factors; this model was validated in other independent cohorts. In summary, our study showed that c-kit other than any other mutations would influence the OS in AML1-ETO patients. A proposed predictor combining both clinical and genetic factors is applicable to prognostic prediction in AML1-ETO patients.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9d21ae5bacd8d38a53726a89714d4087Test
https://www.frontiersin.org/articles/10.3389/fonc.2021.783114/fullTest

المؤلفون: Qing Du, Hongxing Liu, Hui Wang, Minjing Fu, Man Chen, Ping Wu, Tong Wang, Aixian Wang, Junyi Zhen, Xueying Wu, Meiwei Gong

المصدر: International Journal of Laboratory Hematology. 43

مصطلحات موضوعية: Text mining, business.industry, Biochemistry (medical), Clinical Biochemistry, Rare case, Cancer research, Medicine, Myeloid leukemia, Hematology, General Medicine, business, Aml1 eto

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::4d07ecaceb7a0208fb531f94db100a09Test
https://doi.org/10.1111/ijlh.13558Test

المؤلفون: Meihui Yi, Chao Liu, Xiao-Yan Chen, Xiaofan Zhu, Yongjuan Duan, Wenyu Yang, Min Ruan, Yumei Chen, Ye Guo, Tianyuan Hu, Bingrui Wang, Li Zhang, Xiaojuan Chen, Xuelian Cheng, Yingchi Zhang, Suyu Zong, Tao Cheng, Yao Zou

المصدر: Translational Oncology
Translational Oncology, Vol 14, Iss 8, Pp 101119-(2021)

مصطلحات موضوعية: 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Fusion gene, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, hemic and lymphatic diseases, Medicine, Digital polymerase chain reaction, Gene, RC254-282, Original Research, Acute myeloid leukemia, AML1-ETO fusion gene, business.industry, Childhood Acute Myeloid Leukemia, Breakpoint, Myeloid leukemia, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Minimal residual disease, Aml1 eto, body regions, 030104 developmental biology, Droplet digital PCR, 030220 oncology & carcinogenesis, business

الوصف: Highlights l Performed DNA-based ddPCR to accurately monitor the MRD of AE (+) AML. l Identified quantification of the fusion gene correlates strongly with clinical prognosis.
Relapse of childhood AML1-ETO (AE) acute myeloid leukemia is the most common cause of treatment failure. Optimized minimal residual disease monitoring methods is required to prevent relapse. In this study, we used next-generation sequencing to identify the breakpoints in the fusion gene and the DNA-based droplet digital PCR (ddPCR) method was used for dynamic monitoring of AE-DNA. The ddPCR technique provides more sensitive and precise quantitation of the AE gene during disease progression and relapse. Quantification of the AE fusion gene by ddPCR further contributes to improved prognosis. Our study provides valuable methods for dynamic surveillance of AE fusion DNA and assistance in determining the prognosis.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5a3f94ddf1cb175ec3660ff8a971705dTest
https://pubmed.ncbi.nlm.nih.gov/34000643Test

المؤلفون: Wenjuan Yu, Xiang Zhang, Jie Jin

المصدر: Annals of Hematology. 98:2621-2623

مصطلحات موضوعية: Adult, Male, medicine.medical_specialty, Myeloid, Adolescent, Oncogene Proteins, Fusion, Oncogene Proteins, Young Adult, RUNX1 Translocation Partner 1 Protein, Internal medicine, medicine, Humans, Aged, Aged, 80 and over, Hematology, business.industry, Myeloid leukemia, Neoplasms, Second Primary, Exons, General Medicine, Middle Aged, medicine.disease, Aml1 eto, Repressor Proteins, Leukemia, Myeloid, Acute, Leukemia, medicine.anatomical_structure, Core Binding Factor Alpha 2 Subunit, Mutation, Mutation (genetic algorithm), Cancer research, Female, business

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3900b4843e51c58fc045847c2214114fTest
https://doi.org/10.1007/s00277-019-03804-wTest

المؤلفون: Yanhong Qiao, Mingming Xue, Wei Zhou, Shuling Zhang, Shuili Yu, Yanchun Li, Jinli Jian, Bei Liu, Degui Wang

المصدر: Leukemia & Lymphoma. 60:1316-1319

مصطلحات موضوعية: Regulation of gene expression, Cancer Research, Myeloid, business.industry, viruses, De novo acute, virus diseases, Myeloid leukemia, Chromosomal translocation, Hematology, medicine.disease, Aml1 eto, 03 medical and health sciences, Leukemia, 0302 clinical medicine, medicine.anatomical_structure, Immunophenotyping, Oncology, hemic and lymphatic diseases, 030220 oncology & carcinogenesis, medicine, Cancer research, business, neoplasms, 030215 immunology

الوصف: Coexistence of AML1-ETO and PML-RARa has rarely been reported, and there is limited information on a special subtype of AML characterized by co-expression of AML1-ETO and PML-RARa. Herein, we prese...

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::177848b1dbdf41ce7f044b8bb879224cTest
https://doi.org/10.1080/10428194.2018.1520991Test

المؤلفون: Guendalina Zuccari, Silvana Alfei, Cinzia Domenicotti, Barbara Marengo, Giulia Elda Valenti

المصدر: The 2nd International Online-Conference on Nanomaterials.

مصطلحات موضوعية: protracted release, Response to therapy, Human neuroblastoma, etoposide (ETO), gallic acid (GA), ROS-mediated anticancer effect, polyester dendrimers, dendrimer nanoformulations, synergistic action, Chemistry, Nanoparticle, Pediatric Tumor, medicine.disease, Neuroblastoma cell, Neuroblastoma, Dendrimer, medicine, Cancer research, Cytotoxic T cell, neoplasms

الوصف: Human neuroblastoma (NB) is a pediatric tumor, which, after an initial response to therapy, usually develops resistance [...]

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c2b835924fb230b9e27c39d674bcf69dTest
https://doi.org/10.3390/iocn2020-07970Test

المؤلفون: Xue Xiang, Xin Wang, Cheng-Cheng Ma, Ying Gao, Wan Li Hu, Huiling Chen, Ye Chai

المصدر: Journal of International Medical Research, Vol 48 (2020)
The Journal of International Medical Research

مصطلحات موضوعية: Medicine (General), Oncogene Proteins, Fusion, medicine.drug_class, Fusion Proteins, bcr-abl, Abnormal Karyotype, Case Report, Biochemistry, Somatic evolution in cancer, Translocation, Genetic, Tyrosine-kinase inhibitor, 03 medical and health sciences, RUNX1 Translocation Partner 1 Protein, 0302 clinical medicine, R5-920, chronic myeloid leukemia, Bone Marrow, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, hemic and lymphatic diseases, medicine, AML1-ETO, Humans, BCR-ABL, Gene, Chromosome Aberrations, Clonal evolution, business.industry, Biochemistry (medical), additional chromosome, Myeloid leukemia, Chromosome, Cell Biology, General Medicine, Middle Aged, blast crisis, Aml1 eto, Transformation (genetics), medicine.anatomical_structure, Karyotyping, 030220 oncology & carcinogenesis, Core Binding Factor Alpha 2 Subunit, Cancer research, Female, Bone marrow, business, Biomarkers, 030215 immunology

الوصف: Blast crisis develops in a minority of patients with chronic myeloid leukemia even in the era of tyrosine kinase inhibitor (TKI) therapy. Reports suggest that we know little about the mechanism of BCR-ABL and AML1-ETO co-expression in blast crisis of chronic myeloid leukemia, and that other chromosomal abnormalities also coexist. Here, we document an unusual and interesting case of a 51-year-old female diagnosed in the chronic phase of chronic myeloid leukemia. After undergoing TKI treatment for 3 months, her bone marrow aspirates in the chronic phase had transformed to blast crisis. Molecular genetic testing indicated she was positive for p210 form of BCR-ABL (copy number decreased from 108.91% to 56.96%) and AML1-ETO fusion (copy number, 5.65%) genes and had additional chromosomal abnormalities of t(8; 21)(q22; q22)/t(9; 22)(q34; q11), t(2; 5)(p24; q13) and an additional +8 chromosome.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9523c5e817cf6492ee12c69247c76e67Test
https://doaj.org/article/8a39b2cf875e417dbffb1b795bf88e63Test

المؤلفون: Diego Rodríguez-Puyol, Laura García-Bermejo, Ricardo Luiz Ramos, Santiago Lamas, Verónica Miguel

المساهمون: Ministerio de Ciencia e Innovación (España), Instituto de Salud Carlos III, Comunidad de Madrid, Sociedad Española de Nefrología, Fundación Renal Íñigo Álvarez de Toledo, Fundación Ramón Areces

المصدر: Digital.CSIC. Repositorio Institucional del CSIC
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Redox Biology
Redox Biology, Vol 40, Iss, Pp 101851-(2021)

مصطلحات موضوعية: 0301 basic medicine, MMP, mitochondrial membrane potential, Clinical Biochemistry, Eto, etomoxir, Mitochondrion, Kidney, Biochemistry, CPT1A, 0302 clinical medicine, Fibrosis, OCR, oxygen consumption rate, Beta oxidation, lcsh:QH301-705.5, lcsh:R5-920, TFAM, mitochondrial transcription factor A, Extracellular matrix, ECM, extracellular matrix, Mitochondria, medicine.anatomical_structure, Fatty acid oxidation, lcsh:Medicine (General), Myofibroblast, Research Paper, Ureteral Obstruction, ITS, insulin-transferrin-selenium, FDR, false discovery rate, Fatty acid oxidation Extracellular matrix, ETC, electron transport chain, Biology, AKI, acute kidney injury, SPF, specific pathogen free, Nephropathy, Transforming Growth Factor beta1, 03 medical and health sciences, MicroRNAS, Kidney fibrosis, FBS, fetal bovine serum, TGF-β, transforming growth factor-β, medicine, Renal fibrosis, miRNAs, microRNAs, Humans, UUO, unilateral ureteral obstruction, ECAR, extracellular acidification rate, Organic Chemistry, CKD, chronic kidney disease, TFAM, medicine.disease, Oxidative Stress, 030104 developmental biology, lcsh:Biology (General), Cancer research, FAN, folic acid nephropathy, 030217 neurology & neurosurgery, FAO, fatty acid oxidation, EMT, epithelial-to-mesenchymal transition

الوصف: Excessive accumulation of extracellular matrix (ECM) is the hallmark of fibrotic diseases. In the kidney, it is the final common pathway of prevalent diseases, leading to chronic renal failure. While cytokines such as TGF-β play a fundamental role in myofibroblast transformation, recent work has shown that mitochondrial dysfunction and defective fatty acid oxidation (FAO), which compromise the main source of energy for renal tubular epithelial cells, have been proposed to be fundamental contributors to the development and progression of kidney fibrosis. MicroRNAs (miRNAs), which regulate gene expression post-transcriptionally, have been reported to control renal fibrogenesis. To identify miRNAs involved in the metabolic derangement of renal fibrosis, we performed a miRNA array screen in the mouse model of unilateral ureteral obstruction (UUO). MiR-150-5p and miR-495-3p were selected for their link to human pathology, their role in mitochondrial metabolism and their targeting of the fatty acid shuttling enzyme CPT1A. We found a 2- and 4-fold upregulation of miR-150-5p and miR-495-5p, respectively, in both the UUO and the folic acid induced nephropathy (FAN) models, while TGF-β1 upregulated their expressions in the human renal tubular epithelial cell line HKC-8. These miRNAs synergized with TGF-β regarding its pro-fibrotic effect by enhancing the fibrosis-associated markers Acta2, Col1α1 and Fn1. Bioenergetics studies showed a reduction of FAO-associated oxygen consumption rate (OCR) in HKC-8 cells in the presence of both miRNAs. Consistently, expression levels of their mitochondrial-related target genes CPT1A, PGC1α and the mitochondrial transcription factor A (TFAM), were reduced by half in renal epithelial cells exposed to these miRNAs. By contrast, we did not detect changes in mitochondrial mass and transmembrane potential (ΔѰm) or mitochondrial superoxide radical anion production. Our data support that miR-150 and miR-495 may contribute to renal fibrogenesis by aggravating the metabolic failure critically involved in tubular epithelial cells, ultimately leading to fibrosis.
Graphical abstract MiR-150-5p and miR-495-3p exert pro-fibrotic effects by synergizing with TGF-β in the fibrotic response and contributing to the mitochondrial impairment associated to renal fibrosis.Image 1
Highlights • MiR-150-5p and miR-495-3p were upregulated both in the UUO and FAN models. • MiR-150-5p and miR-495-3p synergized with TGF-β profibrotic effects and reduced FAO-associated OCR in renal epithelial cells. • MiR-150-5p and miR-495-3p did not alter mitochondrial transmembrane potential and superoxide radical anion production. • MiRNAs 150-5p and 495-3p are contributors to the metabolic impairment leading to renal fibrosis.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::25f21a82192fc7b9a84acd0c9fd1b1d9Test
http://hdl.handle.net/10261/270587Test