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1.
Biosci Rep ; 41(12)2021 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-34750607

RESUMO

BACKGROUND: Cell-surface proteins have been widely used as diagnostic and prognostic markers in cancer research and as targets for the development of anticancer agents. So far, very few attempts have been made to characterize the surfaceome of patients with breast cancer, particularly in relation with the current molecular breast cancer (BRCA) classification. In this view, we developed a new computational method to infer cell-surface protein activities from transcriptomics data, termed 'SURFACER'. METHODS: Gene expression data from GTEx were used to build a normal breast network model as input to infer differential cell-surface proteins activity in BRCA tissue samples retrieved from TCGA versus normal samples. Data were stratified according to the PAM50 transcriptional subtypes (Luminal A, Luminal B, HER2 and Basal), while unsupervised clustering techniques were applied to define BRCA subtypes according to cell-surface proteins activity. RESULTS: Our approach led to the identification of 213 PAM50 subtypes-specific deregulated surface genes and the definition of five BRCA subtypes, whose prognostic value was assessed by survival analysis, identifying a cell-surface activity configuration at increased risk. The value of the SURFACER method in BRCA genotyping was tested by evaluating the performance of 11 different machine learning classification algorithms. CONCLUSIONS: BRCA patients can be stratified into five surface activity-specific groups having the potential to identify subtype-specific actionable targets to design tailored targeted therapies or for diagnostic purposes. SURFACER-defined subtypes show also a prognostic value, identifying surface-activity profiles at higher risk.

2.
Comput Struct Biotechnol J ; 19: 4092-4100, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34306570

RESUMO

Motivation: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (coronavirus disease, 2019; COVID-19) is associated with adverse outcomes in patients. It has been observed that lethality seems to be related to the age of patients. While ageing has been extensively demonstrated to be accompanied by some modifications at the gene expression level, a possible link with COVID-19 manifestation still need to be investigated at the molecular level. Objectives: This study aims to shed out light on a possible link between the increased COVID-19 lethality and the molecular changes that occur in elderly people. Methods: We considered public datasets of ageing-related genes and their expression at the tissue level. We selected human proteins interacting with viral ones that are known to be related to the ageing process. Finally, we investigated changes in the expression level of coding genes at the tissue, gender and age level. Results: We observed a significant intersection between some SARS-CoV-2 interactors and ageing-related genes, suggesting that those genes are particularly affected by COVID-19 infection. Our analysis evidenced that virus infection particularly involves ageing molecular mechanisms centred around proteins EEF2, NPM1, HMGA1, HMGA2, APEX1, CHEK1, PRKDC, and GPX4. We found that HMGA1 and NPM1 have different expressions in the lung of males, while HMGA1, APEX1, CHEK1, EEF2, and NPM1 present changes in expression in males due to ageing effects. Conclusion: Our study generated a mechanistic framework to clarify the correlation between COVID-19 incidence in elderly patients and molecular mechanisms of ageing. We also provide testable hypotheses for future investigation and pharmacological solutions tailored to specific age ranges.

3.
Methods Protoc ; 4(2)2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-34066513

RESUMO

Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq) is a recently established multimodal single cell analysis technique combining the immunophenotyping capabilities of antibody labeling and cell sorting with the resolution of single-cell RNA sequencing (scRNA-seq). By simply adding a 12-bp nucleotide barcode to antibodies (cell hashing), CITE-seq can be used to sequence antibody-bound tags alongside the cellular mRNA, thus reducing costs of scRNA-seq by performing it at the same time on multiple barcoded samples in a single run. Here, we illustrate an ideal CITE-seq data analysis workflow by characterizing the transcriptome of SH-SY5Y neuroblastoma cell line, a widely used model to study neuronal function and differentiation. We obtained transcriptomes from a total of 2879 single cells, measuring an average of 1600 genes/cell. Along with standard scRNA-seq data handling procedures, such as quality checks and cell filtering procedures, we performed exploratory analyses to identify most stable genes to be possibly used as reference housekeeping genes in qPCR experiments. We also illustrate how to use some popular R packages to investigate cell heterogeneity in scRNA-seq data, namely Seurat, Monocle, and slalom. Both the CITE-seq dataset and the code used to analyze it are freely shared and fully reusable for future research.

4.
J Med Virol ; 93(9): 5638-5643, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33951211

RESUMO

Several severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have emerged, posing a renewed threat to coronavirus disease 2019 containment and to vaccine and drug efficacy. In this study, we analyzed more than 1,000,000 SARS-CoV-2 genomic sequences deposited up to April 27, 2021, on the GISAID public repository, and identified a novel T478K mutation located on the SARS-CoV-2 Spike protein. The mutation is structurally located in the region of interaction with human receptor ACE2 and was detected in 11,435 distinct cases. We show that T478K has appeared and risen in frequency since January 2021, predominantly in Mexico and the United States, but we could also detect it in several European countries.


Assuntos
COVID-19/virologia , Genoma Viral , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/fisiologia , Europa (Continente) , Humanos , México , Mutação , Filogenia , Glicoproteína da Espícula de Coronavírus/genética , Estados Unidos
5.
ChemMedChem ; 16(15): 2315-2329, 2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-33890721

RESUMO

Copper is an essential transition metal frequently increased in cancer known to strongly influence essential cellular processes. Targeted therapy protocols utilizing both novel and repurposed drug agents initially demonstrate strong efficacy, before failing in advanced cancers as drug resistance develops and relapse occurs. Overcoming this limitation involves the development of strategies and protocols aimed at a wider targeting of the underlying molecular changes. Receptor Tyrosine Kinase signaling pathways, epigenetic mechanisms and cell metabolism are among the most common therapeutic targets, with molecular investigations increasingly demonstrating the strong influence each mechanism exerts on the others. Interestingly, all these mechanisms can be influenced by intracellular copper. We propose that copper chelating agents, already in clinical trial for multiple cancers, may simultaneously target these mechanisms across a wide variety of cancers, serving as an excellent candidate for targeted combination therapy. This review summarizes the known links between these mechanisms, copper, and copper chelation therapy.

6.
Biomolecules ; 11(2)2021 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-33525507

RESUMO

Neuroblastoma (NBL) is a pediatric cancer responsible for more than 15% of cancer deaths in children, with 800 new cases each year in the United States alone. Genomic amplification of the MYC oncogene family member MYCN characterizes a subset of high-risk pediatric neuroblastomas. Several cellular models have been implemented to study this disease over the years. Two of these, SK-N-BE-2-C (BE2C) and Kelly, are amongst the most used worldwide as models of MYCN-Amplified human NBL. Here, we provide a transcriptome-wide quantitative measurement of gene expression and transcriptional network activity in BE2C and Kelly cell lines at an unprecedented single-cell resolution. We obtained 1105 Kelly and 962 BE2C unsynchronized cells, with an average number of mapped reads/cell of roughly 38,000. The single-cell data recapitulate gene expression signatures previously generated from bulk RNA-Seq. We highlight low variance for commonly used housekeeping genes between different cells (ACTB, B2M and GAPDH), while showing higher than expected variance for metallothionein transcripts in Kelly cells. The high number of samples, despite the relatively low read coverage of single cells, allowed for robust pathway enrichment analysis and master regulator analysis (MRA), both of which highlight the more mesenchymal nature of BE2C cells as compared to Kelly cells, and the upregulation of TWIST1 and DNAJC1 transcriptional networks. We further defined master regulators at the single cell level and showed that MYCN is not constantly active or expressed within Kelly and BE2C cells, independently of cell cycle phase. The dataset, alongside a detailed and commented programming protocol to analyze it, is fully shared and reusable.


Assuntos
Regulação Neoplásica da Expressão Gênica , Proteína Proto-Oncogênica N-Myc/genética , Neuroblastoma/metabolismo , Análise de Célula Única/métodos , Transcrição Genética , Ciclo Celular , Linhagem Celular Tumoral , Amplificação de Genes , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Genoma Humano , Humanos , Proteínas Oncogênicas/genética , RNA Mensageiro/genética , RNA-Seq , Transcriptoma , Regulação para Cima
7.
J Biomol Struct Dyn ; : 1-11, 2021 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-33583326

RESUMO

SARS-CoV-2 entry in human cells is mediated by the interaction between the viral Spike protein and the human ACE2 receptor. This mechanism evolved from the ancestor bat coronavirus and is currently one of the main targets for antiviral strategies. However, there currently exist several Spike protein variants in the SARS-CoV-2 population as the result of mutations, and it is unclear if these variants may exert a specific effect on the affinity with ACE2 which, in turn, is also characterized by multiple alleles in the human population. In the current study, the GBPM analysis, originally developed for highlighting host-guest interaction features, has been applied to define the key amino acids responsible for the Spike/ACE2 molecular recognition, using four different crystallographic structures. Then, we intersected these structural results with the current mutational status, based on more than 295,000 sequenced cases, in the SARS-CoV-2 population. We identified several Spike mutations interacting with ACE2 and mutated in at least 20 distinct patients: S477N, N439K, N501Y, Y453F, E484K, K417N, S477I and G476S. Among these, mutation N501Y in particular is one of the events characterizing SARS-CoV-2 lineage B.1.1.7, which has recently risen in frequency in Europe. We also identified five ACE2 rare variants that may affect interaction with Spike and susceptibility to infection: S19P, E37K, M82I, E329G and G352V.Communicated by Ramaswamy H. Sarma.

8.
Brief Bioinform ; 22(2): 690-700, 2021 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-33057582

RESUMO

The current outbreak of COVID-19 has generated an unprecedented scientific response worldwide, with the generation of vast amounts of publicly available epidemiological, biological and clinical data. Bioinformatics scientists have quickly produced online methods to provide non-computational users with the opportunity of analyzing such data. In this review, we report the results of this effort, by cataloguing the currently most popular web tools for COVID-19 research and analysis. Our focus was driven on tools drawing data from the fields of epidemiology, genomics, interactomics and pharmacology, in order to provide a meaningful depiction of the current state of the art of COVID-19 online resources.


Assuntos
COVID-19/prevenção & controle , Pandemias , COVID-19/virologia , Biologia Computacional , Humanos , Internet , SARS-CoV-2/isolamento & purificação
9.
J Med Virol ; 93(5): 3238-3245, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33205830

RESUMO

The avalanche of genomic data generated from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus requires the development of tools to detect and monitor its mutations across the world. Here, we present a webtool, coronapp, dedicated to easily processing user-provided SARS-CoV-2 genomic sequences and visualizing the current worldwide status of SARS-CoV-2 mutations. The webtool allows users to highlight mutations and categorize them by frequency, country, genomic location and effect on protein sequences, and to monitor their presence in the population over time. The tool is available at http://giorgilab.unibo.it/coronannotator/ for the annotation of user-provided sequences. The full code is freely shared at https://github.com/federicogiorgi/giorgilab/tree/master/coronannotator.


Assuntos
Genoma Viral , Mutação , SARS-CoV-2/genética , Sequência de Aminoácidos , COVID-19/virologia , Genômica , Humanos
10.
Cancer Res ; 80(19): 4129-4144, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32816860

RESUMO

Therapeutic checkpoint antibodies blocking programmed death receptor 1/programmed death ligand 1 (PD-L1) signaling have radically improved clinical outcomes in cancer. However, the regulation of PD-L1 expression on tumor cells is still poorly understood. Here we show that intratumoral copper levels influence PD-L1 expression in cancer cells. Deep analysis of the The Cancer Genome Atlas database and tissue microarrays showed strong correlation between the major copper influx transporter copper transporter 1 (CTR-1) and PD-L1 expression across many cancers but not in corresponding normal tissues. Copper supplementation enhanced PD-L1 expression at mRNA and protein levels in cancer cells and RNA sequencing revealed that copper regulates key signaling pathways mediating PD-L1-driven cancer immune evasion. Conversely, copper chelators inhibited phosphorylation of STAT3 and EGFR and promoted ubiquitin-mediated degradation of PD-L1. Copper-chelating drugs also significantly increased the number of tumor-infiltrating CD8+ T and natural killer cells, slowed tumor growth, and improved mouse survival. Overall, this study reveals an important role for copper in regulating PD-L1 and suggests that anticancer immunotherapy might be enhanced by pharmacologically reducing intratumor copper levels. SIGNIFICANCE: These findings characterize the role of copper in modulating PD-L1 expression and contributing to cancer immune evasion, highlighting the potential for repurposing copper chelators as enhancers of antitumor immunity. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/19/4129/F1.large.jpg.


Assuntos
Antígeno B7-H1/metabolismo , Neoplasias Encefálicas/imunologia , Cobre/metabolismo , Neuroblastoma/imunologia , Evasão Tumoral/fisiologia , Animais , Antígeno B7-H1/genética , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Quelantes/farmacologia , Transportador de Cobre 1/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/imunologia , Humanos , Imunoterapia/métodos , Células Matadoras Naturais , Linfócitos do Interstício Tumoral/patologia , Camundongos Endogâmicos BALB C , Neuroblastoma/tratamento farmacológico , Neuroblastoma/metabolismo , Trietilenofosforamida/farmacologia , Evasão Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Front Microbiol ; 11: 1800, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32793182

RESUMO

The novel respiratory disease COVID-19 has reached the status of worldwide pandemic and large efforts are currently being undertaken in molecularly characterizing the virus causing it, SARS-CoV-2. The genomic variability of SARS-CoV-2 specimens scattered across the globe can underly geographically specific etiological effects. In the present study, we gather the 48,635 SARS-CoV-2 complete genomes currently available thanks to the collection endeavor of the GISAID consortium and thousands of contributing laboratories. We analyzed and annotated all SARS-CoV-2 mutations compared with the reference Wuhan genome NC_045512.2, observing an average of 7.23 mutations per sample. Our analysis shows the prevalence of single nucleotide transitions as the major mutational type across the world. There exist at least three clades characterized by geographic and genomic specificity. In particular, clade G, prevalent in Europe, carries a D614G mutation in the Spike protein, which is responsible for the initial interaction of the virus with the host human cell. Our analysis may facilitate custom-designed antiviral strategies based on the molecular specificities of SARS-CoV-2 in different patients and geographical locations.

12.
Toxicology ; 441: 152531, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32593706

RESUMO

Gene-regulatory networks reconstruction has become a very popular approach in applied biology to infer and dissect functional interactions of Transcription Factors (TFs) driving a defined phenotypic state, termed as Master Regulators (MRs). In the present work, cutting-edge bioinformatic methods were applied to re-analyze experimental data on leukemia cells (human myelogenous leukemia cell line THP-1 and acute myeloid leukemia MOLM-13 cells) treated for 6 h with two different Ribosome-Inactivating Proteins (RIPs), namely Shiga toxin type 1 (400 ng/mL) produced by Escherichia coli strains and the plant toxin stenodactylin (60 ng/mL), purified from the caudex of Adenia stenodactyla Harms. This analysis allowed us to identify the common early transcriptional response to 28S rRNA damage based on gene-regulatory network inference and Master Regulator Analysis (MRA). Both toxins induce a common response at 6 h which involves inflammatory mediators triggered by AP-1 family transcriptional factors and ATF3 in leukemia cells. We describe for the first time the involvement of MAFF, KLF2 and KLF6 in regulating RIP-induced apoptotic cell death, while receptor-mediated downstream signaling through ANXA1 and TLR4 is suggested for both toxins.


Assuntos
Redes Reguladoras de Genes/efeitos dos fármacos , Leucemia/metabolismo , Proteínas Inativadoras de Ribossomos/farmacologia , Linhagem Celular Tumoral , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Humanos , Lectinas/farmacologia , Proteínas de Membrana/efeitos dos fármacos , Proteínas de Membrana/metabolismo , N-Glicosil Hidrolases/farmacologia , Toxina Shiga I/farmacologia , Fatores de Transcrição/metabolismo
13.
Front Pharmacol ; 11: 630, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32457623

RESUMO

Stenodactylin, a highly toxic type 2 ribosome-inactivating protein purified from the caudex of Adenia stenodactyla Harms, is a potential anticancer drug candidate. Previous studies demonstrated that stenodactylin induces apoptosis and necroptosis in treated cells, involving the production of reactive oxygen species. We analyzed the effect of stenodactylin on Raji and Ramos (Human Burkitt's lymphoma cells) and MOLM-13 (acute myeloid leukemia cells). Moreover, we focused on the early events in MOLM-13 cells that characterize the cellular response to the toxin by whole-genome microarray analysis of gene expression. Treatment with stenodactylin induced the depurination of 28S rRNA within 4 h and increased the phosphorylation of p38 and JNK. A time-dependent activation of caspase 1, 2, 8, 9, 3/7 was also observed. Genome-wide gene expression microarray analysis revealed early changes in the expression of genes involved in the regulation of cell death, inflammation and stress response. After 4 h, a significant increase of transcript level was detectable for ATF3, BTG2, DUSP1, EGR1, and JUN. Increased upstream JUN signaling was also confirmed at protein level. The early response to stenodactylin treatment involves inflammatory and apoptotic signaling compatible with the activation of multiple cell death pathways. Because of the above described properties toward acute myeloid leukemia cells, stenodactylin may be a promising candidate for the design of new immunoconjugates for experimental cancer treatment.

14.
Genes (Basel) ; 11(5)2020 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-32429325

RESUMO

Histone deacetylases (HDACs) are evolutionary conserved enzymes which operate by removing acetyl groups from histones and other protein regulatory factors, with functional consequences on chromatin remodeling and gene expression profiles. We provide here a review on the recent knowledge accrued on the zinc-dependent HDAC protein family across different species, tissues, and human pathologies, specifically focusing on the role of HDAC inhibitors as anti-cancer agents. We will investigate the chemical specificity of different HDACs and discuss their role in the human interactome as members of chromatin-binding and regulatory complexes.


Assuntos
Inibidores de Histona Desacetilases/uso terapêutico , Histona Desacetilases/genética , Neoplasias/genética , Fatores de Transcrição/genética , Antineoplásicos/uso terapêutico , Histonas/genética , Humanos , Neoplasias/terapia , Especificidade por Substrato/genética
15.
Bioinformatics ; 36(12): 3916-3917, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32232425

RESUMO

MOTIVATION: Gene network inference and master regulator analysis (MRA) have been widely adopted to define specific transcriptional perturbations from gene expression signatures. Several tools exist to perform such analyses but most require a computer cluster or large amounts of RAM to be executed. RESULTS: We developed corto, a fast and lightweight R package to infer gene networks and perform MRA from gene expression data, with optional corrections for copy-number variations and able to run on signatures generated from RNA-Seq or ATAC-Seq data. We extensively benchmarked it to infer context-specific gene networks in 39 human tumor and 27 normal tissue datasets. AVAILABILITY AND IMPLEMENTATION: Cross-platform and multi-threaded R package on CRAN (stable version) https://cran.r-project.org/package=corto and Github (development release) https://github.com/federicogiorgi/corto. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Redes Reguladoras de Genes , Neoplasias , Humanos , Software , Transcriptoma
16.
J Clin Med ; 9(4)2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32244779

RESUMO

The recent epidemic outbreak of a novel human coronavirus called SARS-CoV-2 causing the respiratory tract disease COVID-19 has reached worldwide resonance and a global effort is being undertaken to characterize the molecular features and evolutionary origins of this virus. In this paper, we set out to shed light on the SARS-CoV-2/host receptor recognition, a crucial factor for successful virus infection. Based on the current knowledge of the interactome between SARS-CoV-2 and host cell proteins, we performed Master Regulator Analysis to detect which parts of the human interactome are most affected by the infection. We detected, amongst others, affected apoptotic and mitochondrial mechanisms, and a downregulation of the ACE2 protein receptor, notions that can be used to develop specific therapies against this new virus.

17.
Biochim Biophys Acta Gene Regul Mech ; 1863(6): 194430, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31678629

RESUMO

Transcriptional regulation is a fundamental molecular mechanism involved in almost every aspect of life, from homeostasis to development, from metabolism to behavior, from reaction to stimuli to disease progression. In recent years, the concept of Gene Regulatory Networks (GRNs) has grown popular as an effective applied biology approach for describing the complex and highly dynamic set of transcriptional interactions, due to its easy-to-interpret features. Since cataloguing, predicting and understanding every GRN connection in all species and cellular contexts remains a great challenge for biology, researchers have developed numerous tools and methods to infer regulatory processes. In this review, we catalogue these methods in six major areas, based on the dominant underlying information leveraged to infer GRNs: Coexpression, Sequence Motifs, Chromatin Immunoprecipitation (ChIP), Orthology, Literature and Protein-Protein Interaction (PPI) specifically focused on transcriptional complexes. The methods described here cover a wide range of user-friendliness: from web tools that require no prior computational expertise to command line programs and algorithms for large scale GRN inferences. Each method for GRN inference described herein effectively illustrates a type of transcriptional relationship, with many methods being complementary to others. While a truly holistic approach for inferring and displaying GRNs remains one of the greatest challenges in the field of systems biology, we believe that the integration of multiple methods described herein provides an effective means with which experimental and computational biologists alike may obtain the most complete pictures of transcriptional relationships. This article is part of a Special Issue entitled: Transcriptional Profiles and Regulatory Gene Networks edited by Dr. Federico Manuel Giorgi and Dr. Shaun Mahony.


Assuntos
Redes Reguladoras de Genes , Software , Sítios de Ligação , Imunoprecipitação da Cromatina , Bases de Dados de Ácidos Nucleicos , Humanos , Motivos de Nucleotídeos , Mapeamento de Interação de Proteínas , Análise de Sequência de DNA , Fatores de Transcrição/metabolismo
19.
Front Genet ; 10: 671, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31379928

RESUMO

Cancer is a disease often characterized by the presence of multiple genomic alterations, which trigger altered transcriptional patterns and gene expression, which in turn sustain the processes of tumorigenesis, tumor progression, and tumor maintenance. The links between genomic alterations and gene expression profiles can be utilized as the basis to build specific molecular tumorigenic relationships. In this study, we perform pan-cancer predictions of the presence of single somatic mutations and copy number variations using machine learning approaches on gene expression profiles. We show that gene expression can be used to predict genomic alterations in every tumor type, where some alterations are more predictable than others. We propose gene aggregation as a tool to improve the accuracy of alteration prediction models from gene expression profiles. Ultimately, we show how this principle can be beneficial in intrinsically noisy datasets, such as those based on single-cell sequencing.

20.
Pediatr Radiol ; 49(9): 1209-1216, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31129699

RESUMO

BACKGROUND: Osteoid osteoma is a benign and painful musculoskeletal tumour that usually affects children. Current standard treatment is CT-guided radiofrequency ablation, a minimally invasive percutaneous procedure, with clinical success rates ranging between 85% and 98%. Though minimally invasive, however, this type of procedure is not free from complications. OBJECTIVE: To investigate the efficacy and safety of magnetic resonance (MR)-guided focused ultrasound (MRgFUS), a needleless procedure of thermal ablation employed in the treatment of non-spinal osteoid osteoma in paediatric patients. MATERIALS AND METHODS: We report the results of 33 procedures of ablation of osteoid osteoma performed with MRgFUS in three university hospitals. To ablate a lesion on the bone surface, MRgFUS employs the ultrasound energy transduced along the soft tissue. The follow-up studies lasted 24 months and were performed combining clinical and imaging data. RESULTS: Mean age of the children was 13.8 years. The clinical outcome showed a primary success of 97%. One case alone was submitted to repeat treatment because the first one failed (secondary success). No major or minor complications were recorded. During the investigation time, no relapse of symptomatology or delayed complications were observed. CONCLUSION: Although our study is preliminary and limited by a low number of patients, our data show that MRgFUS is effective. This suggests that it might be useful as the first-line treatment in paediatric patients with osteoid osteoma.


Assuntos
Neoplasias Ósseas/cirurgia , Ablação por Ultrassom Focalizado de Alta Intensidade , Imagem por Ressonância Magnética Intervencionista , Osteoma Osteoide/cirurgia , Adolescente , Neoplasias Ósseas/diagnóstico por imagem , Criança , Feminino , Humanos , Masculino , Osteoma Osteoide/diagnóstico por imagem
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