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Bone marrow microRNA-34a is a good indicator for response to treatment in acute myeloid leukemia

Oncology Research 2024年第3期32卷 577-584页

作者： MONA SA BDELLATEIF NAGLAA MHASSAN MAHMOUD MKAMEL YOMNA MEL-MELIGUI Department of Cancer Biology Medical Biochemistry and Molecular BiologyNational Cancer InstituteCairo UniversityCairo11976Egypt Department of Cinical pathology National Cancer InstituteCairo UniversityCairo11976Egypt

Background:microRNA 34a(miR 34a)had been reported to have a diagnostic role in acute myeloid leukemia(AML).However,its value in the bone marrow(BM)of AML patients,in addition to its role in response to therapy is still *** current study was designed to assess the diagnostic,prognostic,and predictive significance of miR 34a in the BM of AML ***:The miR.34a was assed in BM aspirate of 82 AML patients in relation to 12 normal control subjects using *** data were assessed for correlation with the relevant dinical critenia,response to therapy,disease-free survival(DFS),and overall survival(OS)***:miR.34a was significantly downregulated in AML patients[0.005(3.3×10^(-6)-1.32)],compared to the control subjects[0.108(3.2× 10^(-4)-1.64),p=0.021].*** relative quantification(RQ)of miR-34a was 0.106(range;0-32.12).The specifaity,sensitivity,and area under the curve(AUC)for the diagnosis of AML were(58.3%,69.5%,0.707,respectively,p=0.021).patients with upregulated miR-34a showed decreased platelets count<34.5 × 10^(9)/L,and achieved early complete remission(CR,p=0.031,p=0.044,respectively).Similarly,patients who were refractory to therapy showed decreased miR 34a levels in comparison to those who achieved CR[0.002(0-0.01)and 0.12(0-32.12),respectively,p=0.002].Therefore,miR 34a could significantly identify patients with CR with a specificity of 75%and sensitivity of 100%at a cut-off of 0.014(AUC=0.927,p=0.005).There was no considerable association between miR-34a expression and survival rates of the induded AML ***:miR-34a could be a beneficial diagnostic biomarker for AML *** addition,it serves as a good indicator for response to therapy,which could possibly identify patients who are refractory to treatment with 100%sensitivity and 75%specificity.

关键词： AML miR 34a microRNA Leukemia

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RANKL inhibition reduces lesional cellularity and Gαs variant expression and enables osteogenic maturation in fibrous dysplasia

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Bone Research 2024年第1期12卷 165-179页

作者： Luis F.de Castro Jarred M.Whitlock Zachary Michel Kristen Pan Jocelyn Taylor Vivian Szymczuk Brendan Boyce Daniel Martin Vardit Kram Rebeca Galisteo Kamran Melikov Leonid V.Chernomordik Michael T.Collins Alison M.Boyce Skeletal Disorders and Mineral Homeostasis Section National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA Section on Membrane Biology Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Institutes of HealthBethesdaMDUSA Metabolic Bone Disorders Unit National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA Department of Plastic and Reconstructive Surgery The Johns Hopkins Medical InstitutionsBaltimoreMDUSA Department of pathology and Laboratory Medicine University of Rochester Medical CenterRochesterNYUSA NIDCR Genomics and Computational Biology Core National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA

Fibrous dysplasia(FD)is a rare,disabling skeletal disease for which there are no established *** evidence supports inhibiting the osteoclastogenic factor receptor activator of nuclear kappa-B ligand(RANKL)as a potential treatment *** this study,we investigated the mechanisms underlying RANKL inhibition in FD tissue and its likely indirect effects on osteoprogenitors by evaluating human FD tissue pre-and post-treatment in a phase 2 clinical trial of denosumab(NCT03571191)and in murine in vivo and ex vivo preclinical *** analysis of human and mouse tissue demonstrated increased osteogenic maturation,reduced cellularity,and reduced expression of the pathogenic Gαs variant in FD lesions after RANKL *** sequencing of human and mouse tissue supported these *** interaction between osteoclasts and mutant osteoprogenitors was further assessed in an ex vivo lesion model,which indicated that the proliferation of abnormal FD osteoprogenitors was dependent on *** results from this study demonstrated that,in addition to its expected antiosteoclastic effect,denosumab reduces FD lesion activity by decreasing FD cell proliferation and increasing osteogenic maturation,leading to increased bone formation within *** findings highlight the unappreciated role of cellular crosstalk between osteoclasts and preosteoblasts/osteoblasts as a driver of FD pathology and demonstrate a novel mechanism of action of denosumab in the treatment of bone disease.

关键词： dysplasia treatment finding

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The evolution of cancer genomic medicine in Japan and the role of the national Cancer Center Japan

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Cancer Biology & Medicine 2024年第1期21卷 29-44页

作者： Teruhiko Yoshida Yasushi Yatabe Ken Kato Genichiro Ishii Akinobu Hamada Hiroyuki Mano Kuniko Sunami Noboru Yamamoto Takashi Kohno Department of Genetic Medicine and Services National Cancer Center HospitalTokyo 104-0045Japan Department of Diagnostic pathology National Cancer Center HospitalTokyo 104-0045Japan Clinical Research Support Offce Clinical Research Coordinating SectionBiobank Translational Research Support SectionNational Cancer Center HospitalTokyo 104-0045Japan Department of pathology and Clinical Laboratories National Cancer Center Hospital EastChiba 277-8577Japan Division of Molecular Pharmacology National Cancer Center Research InstituteTokyo 104-0045Japan national Cancer Center Research institute Tokyo 104-0045Japan Department of Laboratory Medicine National Cancer Center HospitalTokyo 104-0045Japan Department of Experimental Therapeutics National Cancer Center HospitalTokyo 104-0045Japan Division of Genome Biology National Cancer Center Research InstituteTokyo 104-0045Japan

The journey to implement cancer genomic medicine(CGM)in oncology practice began in the 1980s,which is considered the dawn of genetic and genomic cancer *** the time,a variety of activating oncogenic alterations and their functional significance were unveiled in cancer cells,which led to the development of molecular targeted therapies in the 2000s and *** CGM is still a relatively new discipline and it is difficult to predict to what extent CGM will benefit the diverse pool of cancer patients,the national Cancer Center(NCC)of Japan has already contributed considerably to CGM advancement for the conquest of *** back at these past achievements of the NCC,we predict that the future of CGM will involve the following:1)A biobank of paired cancerous and non-cancerous tissues and cells from various cancer types and stages will be *** quantity and quality of these samples will be compatible with omics *** biobank samples will be linked to longitudinal clinical information.2)New technologies,such as whole-genome sequencing and artificial intelligence,will be introduced and new bioresources for functional and pharmacologic analyses(e.g.,a patient-derived xenograft library)will be systematically deployed.3)Fast and bidirectional translational research(bench-to-bedside and bedside-to-bench)performed by basic researchers and clinical investigators,preferably working alongside each other at the same institution,will be implemented;4)Close collaborations between academia,industry,regulatory bodies,and funding agencies will be established.5)There will be an investment in the other branch of CGM,personalized preventive medicine,based on the individual's genetic predisposition to cancer.

关键词： Cancer genomic medicine biobank patient-derived xenograft multi-gene panel test whole genome sequencing

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Survival benefit of concurrent chemoradiotherapy for advanced ampulla of Vater cancer

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World Journal of Clinical Cases 2024年第2期12卷 267-275页

作者： Chae Hwa Kwon Hyung Il Seo Dong Uk Kim Sung Yong Han Suk Kim Nam Kyung Lee Seung Baek Hong Ji Hyun Ahn Young Mok Park Byeong Gwan Noh BioMedical Research institute Pusan National University HospitalBusan 49241South Korea Department of Surgery Pusan National University School of Medicine and Biomedical Research InstitutePusan National University HospitalBusan 49241South Korea Department of Internal Medicine Pusan National University School of Medicine and Biomedical Research InstitutePusan National University HospitalBusan 49241South Korea Department of Radiology Pusan National University School of Medicine and Biomedical Research InstitutePusan National University HospitalBusan 49241South Korea Department of pathology and Biomedical Research institute Pusan National University HospitalBusan 49241South Korea

BACKGROUND Currently,there is no standard adjuvant therapy for patients with resected ampulla of Vater(AoV)*** To evaluate the effectiveness of adjuvant concurrent chemoradiotherapy(CCRT)in patients with advanced AoV cancer who underwent curative *** This single-centered,retrospective study included 29 patients with advanced AoV cancer who underwent pancreaticoduodenectomy between 2006 and *** impact of CCRT on advanced AoV cancer was *** The 1-,3-,and 5-yr recurrence-free survival(RFS)rates for patients with advanced AoV cancer were 82.8%,48.3%,and 40.8%,respectively,and the overall survival(OS)rates were 89.7%,62.1%,and 51.7%,***-cular invasion was found to be a significant risk factor for RFS and OS in patients with advanced AoV cancer in the univariate analysis,whereas T stage and lymph node metastasis were significantly associated with OS in the multivariate *** to the patients who did not receive adjuvant CCRT,those who received adjuvant CCRT did not show statistically significant improvements in the RFS and OS,although they had a significantly lower average age and significantly higher platelet-to-lymphocyte *** Adjuvant CCRT did not improve survival outcomes in patients with advanced AoV *** findings contribute to existing knowledge on the effectiveness of CCRT in this patient population and provide important insights for clinical decision-making.

关键词： Advanced ampulla of Vater cancer Adjuvant concurrent chemoradiotherapy Recurrence Survival Vater cancer

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A strategy for mechanically integrating robust hydrogeltissue hybrid to promote the anti-calcification and endothelialization of bioprosthetic heart valve

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Regenerative Biomaterials 2024年第2期3卷 123-136页

作者： Haoshuang Wu Nuoya Chen Tiantian Zheng Li Li Mengyue Hu Yumei Qin Gaoyang Guo Li Yang Yunbing Wang national Engineering Research Center for Biomaterials Sichuan UniversityChengdu 610065China institute of Clinical pathology West China Hospital of Sichuan UniversityChengdu 610041China College of Polymer Science and Engineering Sichuan UniversityChengdu 610065China

Bioprosthetic heart valve(BHV)replacement has been the predo-minant treatment for severe heart valve diseases over *** clinically available BHVs are crosslinked by glutaraldehyde(GLUT),while the high toxicity of residual GLUT could initiate calcification,severe thrombosis,and delayed ***,we construed a mechanically integrating robust hydrogel-tissue hybrid to improve the performance of *** particular,recombinant humanized coilagen type Ⅲ(rhCOLⅢ),which was precisely customized with anti-coagulant and pro-endothelialization bioactivity,was first incorporated into the polyvinyl alcohol(PVA)-based hydrogel via hydrogen bond ***,tannic acid was introduced to enhance the mechanicalperfo of PVA-based hvdrogel and interfacial bonding between the hydrogel layer and bio-derived tissue due to the strong affinity for a wide range of *** vitro and in vivo experimental results confirmed that the GLUT-crosslinked BHVs modified by the robust PVA-based hydrogel embedded rhCOLII and TA possessed long-term anti-coagulant,accelerated endothelialization,mild inflammatory response and anti-calcification ***,our mechanically integrating robust hydrogel-tissue hybrid strategy showed the potential to enhance the service function and prolong the service life of the BHVs after implantation.

关键词： bioprosthetic heart valves recombinant humanized collagen typeⅢ endothelialization anti-calcification anti-coagulation

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Inflammatory myofibroblastic tumor from molecular diagnostics to current treatment

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Oncology Research 2024年第7期32卷 1141-1162页

作者： PAULINA CHMIEL ALEKSANDRA SŁOWIKOWSKA ŁUKASZ BANASZEK ANNA SZUMERA-CIEĆKIEWICZ BARTŁOMIEJ SZOSTAKOWSKI MATEUSZ J.SPAŁEK TOMASZŚWITAJ PIOTR RUTKOWSKI ANNA M.CZARNECKA Department of Soft Tissue/Bone Sarcoma and Melanoma Maria Sklodowska-Curie National Research Institute of OncologyWarsaw02-781Poland Faculty of Medicine Medical University of WarsawWarsaw02-091Poland Department of pathology Maria Sklodowska Curie National Research Institute of OncologyWarsaw02-781Poland Department of Radiotherapy Maria Sklodowska-Curie National Research Institute of OncologyWarsaw02-781Poland

Inﬂammatory myoﬁbroblastic tumor(IMT)is a rare neoplasm with intermediate malignancy characterized by a propensity for recurrence but a low metastatic *** challenges arise from the diverse pathological presentation,variable symptomatology,and lack of different imaging ***,IMT is identiﬁed by the fusion of the anaplastic lymphoma kinase(ALK)gene,which is present in approximately 70%of cases,with various fusion partners,including ran-binding protein 2(RANBP2),which allows conﬁrmation of the *** surgery is the preferred approach for localized tumors,the optimal long-term treatment for advanced or metastatic disease is difﬁcult to deﬁ*** therapies are crucial for achieving sustained response to treatment within the context of genetic alteration in ***,an ALK tyrosine kinase inhibitor(TKI),was ofﬁcially approved by the US Food and Drug Administration(FDA)in 2020 to treat IMT with ALK ***,most patients face resistance and disease progression,requiring consideration of sequential *** radiotherapy with targeted therapy appears to be beneﬁcial in this *** promising results have also been achieved with immunotherapy,indicating potential for combined therapy ***,deﬁned recommendations are still *** review analyzes the available research on IMT,including genetic disorders and their impact on the course of the disease,data on the latest targeted therapy regimens and the possibility of developing immunotherapy in this indication,as well as summarizing general knowledge about prognostic and predictive factors,also in terms of resistance to systemic therapy.

关键词： Inﬂammatory myoﬁbroblastic tumor(IMT) Epithelioid inﬂammatory myoﬁbroblastic sarcoma Tyrosine kinase inhibitors(TKI) Anaplastic lymphoma kinase(ALK)

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Genomic medicine in clinical practice:national genomic medicine program in Japan

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Cancer Biology & Medicine 2024年第1期21卷 4-9页

Cancer statistics in Japan Cancer is the most common cause of death in Japan based on Statistics 2021~*** statistics were first gathered,infectious diseases,such as tuberculosis,and cerebrovascular disease have been the main causes of death in *** surpassed cerebrovascular disease as the main cause of death in 1981,and the number of cancer deaths has *** 38,000 people died of cancer in *** national Cancer Center(NCC)reported that the 5-year survival rate for patients with cancer was improving(62%for males and 66.9%for females)in a population-based cancer registry.

关键词： Cancer cancer death

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Efficient cold atom source from a single-layer atom chip

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Chinese Optics Letters 2024年第6期22卷 108-113页

作者： Petr Skakunenko Darya Bykova Anton Afanasiev Alexey Kalmykov Roman Kirtaev victor Balykin institute of Spectroscopy Russian Academy of Sciences Moscow institute of Physics and Technology Skolkovo institute of Science and Technology national Research University Higher School of Economics Emerging Technologies Research Center XPANCEO

We developed a new single-layer atom chip with an additional U-shaped current-carrying *** new U-shaped microwire creates optimized magnetic field distribution,which increases the trapping volume of a magneto-optical trap（MOT） near the *** approach allows one to localize more atoms,while a setup remains relatively simple （single-layer approach） and consumes low current （up to 10 A）. The total number of trapped87Rb atoms in our setup is 5×10～7.

关键词： Bose Einstein condensates Laser beams Laser cooling Optical clocks Quantum noise Rubidium

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Influence of biomass burning on ozone levels in the Megalopolis of Central Mexico during the COVID-19 lockdown

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Journal of Environmental Sciences 2024年第9期143卷 99-115页

作者： victor Almanza Luis Gerardo Ruiz-Suárez Ricardo Torres-Jardón Agustín García-Reynoso Iván Y.Hernández-Paniagua institute for Atmospheric Sciences and Climate Change National Autonomous University of MexicoCoyoacan 04510Mexico CityMexico

The massive reductions in anthropogenic emissions resulting from the COVID-19 lockdown provided a unique opportunity to evaluate the effect of mitigation measures aiming to abate air *** Mexico,the total lockdown period took place during the dry-hot season when biomass burning activity is ***,we investigate the role of biomass burning emissions on regional ozone levels in the Megalopolis of Central *** studied period covers the lockdown phases 2 and 3,and the first month of the New *** applied a factor separation technique and process analysis to estimate the pure and synergistic contributions of emission reductions under lockdown and that from biomass burning to daily ozone maximum concentrations in 7 metropolitan areas of different states in the *** results revealed that biomass burning plumes likely masked the effect of massive reductions from mobile emissions,impacted the PBL development during phase 3 and favored transition and mixed NO_(x)-limited and VOC-limited regional *** contributed to increased ozone production in the middle to lower PBL by changing the regional background levels which potentially could bias high ozone production efficiency *** the Megalopolis contribution to economic and societal development at national scale,our study suggests that ozone mitigation measures during the dry-hot season targeting mainly mobile emissions will likely be offset by biomass burning plumes.A regional and synergic policy aiming to control biomass burning would help to reduce the occurrence of high ozone levels in Central Mexico with the co-benefit of tackling short-lived climate pollutants.

关键词： COVID-19 Mexico Megalopolis Ozone Factor Separation Process Analysis

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Bruton’s tyrosine kinase inhibitors in primary central nervous system lymphoma:New hopes on the horizon

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World Journal of Clinical Oncology 2024年第5期15卷 587-590页

作者： Leonardo S Lino-Silva Sabrina B Martínez-Villavicencio Luisa Fernanda Rivera-Moncada Department of pathology Oncology National Cancer Institute(Mexico)TlalpanMexico City 14080Mexico

In this editorial,we comment on the article by Wang et *** manuscript explores the potential synergistic effects of combining zanubrutinib,a novel oral inhibitor of Bruton’s tyrosine kinase,with high-dose methotrexate(HD-MTX)as a therapeutic intervention for primary central nervous system lymphoma(PCNSL).The study involves a retrospective analysis of 19 PCNSL patients,highlighting clinicopathological characteristics,treatment outcomes,and genomic *** results indicate the combination’s good tolerance and strong antitumor activity,with an 84.2%overall response *** authors emphasize the potential of zanubrutinib to modulate key genomic features of PCNSL,particularly mutations in myeloid differentiation primary response 88 and cluster of differentiation ***,the study investigates the role of circulating tumor DNA in cerebrospinal fluid for disease surveillance and treatment response *** essence,the study provides valuable insights into the potential of combining zanubrutinib with HD-MTX as a frontline therapeutic regimen for *** findings underscore the importance of exploring alternative treatment modalities and monitoring genomic and liquid biopsy markers to optimize patient *** the findings suggest promise,the study’s limitations should be considered,and further research is needed to establish the clinical relevance of this therapeutic approach for PCNSL.

关键词： Primary central nervous system lymphoma Zanubrutinib Bruton’s tyrosine kinase Prognosis Myeloid differentiation primary response 88 gene Cluster of differentiation 79B gene

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