Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 48.321
Filtrar
1.
Nat Commun ; 12(1): 223, 2021 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-33431820

RESUMO

Enhancers are DNA sequences that enable complex temporal and tissue-specific regulation of genes in higher eukaryotes. Although it is not entirely clear how enhancer-promoter interactions can increase gene expression, this proximity has been observed in multiple systems at multiple loci and is thought to be essential for the maintenance of gene expression. Bromodomain and Extra-Terminal domain (BET) and Mediator proteins have been shown capable of forming phase condensates and are thought to be essential for super-enhancer function. Here, we show that targeting of cells with inhibitors of BET proteins or pharmacological degradation of BET protein Bromodomain-containing protein 4 (BRD4) has a strong impact on transcription but very little impact on enhancer-promoter interactions. Dissolving phase condensates reduces BRD4 and Mediator binding at enhancers and can also strongly affect gene transcription, without disrupting enhancer-promoter interactions. These results suggest that activation of transcription and maintenance of enhancer-promoter interactions are separable events. Our findings further indicate that enhancer-promoter interactions are not dependent on high levels of BRD4 and Mediator, and are likely maintained by a complex set of factors including additional activator complexes and, at some sites, CTCF and cohesin.


Assuntos
Elementos Facilitadores Genéticos , Regiões Promotoras Genéticas , Transcrição Genética , Fator de Ligação a CCCTC/metabolismo , Carcinogênese/efeitos dos fármacos , Carcinogênese/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Cromatina/metabolismo , Proteínas Cromossômicas não Histona/metabolismo , Proteínas de Ligação a DNA/metabolismo , Glicóis/farmacologia , Histonas/metabolismo , Humanos , Leucemia/genética , Leucemia/patologia , Modelos Genéticos , Ligação Proteica/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-myc/genética , Transcrição Genética/efeitos dos fármacos
2.
Medicine (Baltimore) ; 100(1): e24014, 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33429764

RESUMO

INTRODUCTION: As a hematopoietic carcinogen, benzene induces human leukemia through its active metabolites such as benzoquinone, which may cause oxidative damage to cancer-related nuclear genes by increasing reactive oxygen species (ROS). Mitochondrion is the main regulatory organelle of ROS, genetic abnormality of mitochondrion can impede its regulation of ROS, leading to more severe oxidative damage. Mutations have been related to certain types of cancer in several mitochondrial genes, but they have never been completely analyzed genome-wide in leukemia. PATIENT CONCERNS: The patient was a 52-year-old female who had chronic exposure to benzene for several years. Her symptoms mainly included recurrent dizziness, fatigue, and they had lasted for nearly 8 years and exacerbated in recent weeks before diagnosis. DIAGNOSIS: Samples of peripheral blood were taken from the patient using evacuated tubes with EDTA anticoagulant on the second day of her hospitalization. At the same time blood routine and BCR/ABL genes of leukemic phenotype were tested. Platelets were isolated for mitochondrial DNA (mtDNA) extraction. The genetic analysis of ATP synthase Fo subunit 8 (complex V), ATP synthase Fo subunit 6 (complex V), cytochrome c oxidase subunit 1 (complex IV), cytochrome c oxidase subunit 2 (complex IV), cytochrome c oxidase subunit 3, Cytb, NADH dehydrogenase subunit 1 (complex I) (ND) 1, ND2, ND3, ND4, ND5, ND6, 12S-RNA, 16S-RNA, tRNA-Cysteine, A, N, tRNA-Leucine, E, displacement loop in platelet mtDNA were performed. All the detected gene mutations were validated using the conventional Sanger sequencing method. INTERVENTIONS: The patient received imatinib, a small molecule kinase inhibitor, and symptomatic treatments. OUTCOMES: After 3 months treatment her blood routine test indicators were restored to normal. CONCLUSION: A total of 98 mutations were found, and 25 mutations were frame shift. The ND6 gene mutation rate was the highest among all mutation points. Frame shifts were identified in benzene-induced leukemia for the first time. Many mutations in the platelet mitochondrial genome were identified and considered to be potentially pathogenic in the female patient with benzene-induced leukemia. The mutation rate of platelet mitochondrial genome in the benzene-induced leukemia patient is relatively high, and the complete genome analysis is helpful to fully comprehend the disease characteristics.


Assuntos
Plaquetas/patologia , Leucemia/etiologia , Leucemia/genética , Mitocôndrias/genética , Antineoplásicos/uso terapêutico , Benzeno/efeitos adversos , Exposição Ambiental/efeitos adversos , Feminino , Genoma Mitocondrial/genética , Genoma Mitocondrial/fisiologia , Humanos , Mesilato de Imatinib/uso terapêutico , Pessoa de Meia-Idade , Mitocôndrias/fisiologia
3.
Virol J ; 18(1): 1, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33397387

RESUMO

BACKGROUND: Virus neutralization by antibodies is an important prognostic factor in many viral diseases. To easily and rapidly measure titers of neutralizing antibodies in serum or plasma, we developed pseudovirion particles composed of the spike glycoprotein of SARS-CoV-2 incorporated onto murine leukemia virus capsids and a modified minimal murine leukemia virus genome encoding firefly luciferase. This assay design is intended for use in laboratories with biocontainment level 2 and therefore circumvents the need for the biocontainment level 3 that would be required for replication-competent SARS-CoV-2 virus. To validate the pseudovirion assay, we set up comparisons with other available antibody tests including those from Abbott, Euroimmun and Siemens, using archived, known samples. RESULTS: 11 out of 12 SARS-CoV-2-infected patient serum samples showed neutralizing activity against SARS-CoV-2-spike pseudotyped MLV viruses, with neutralizing titers-50 (NT50) that ranged from 1:25 to 1:1,417. Five historical samples from patients hospitalized for severe influenza infection in 2016 tested negative in the neutralization assay (NT50 < 25). Three serum samples with high neutralizing activity against SARS-CoV-2/MLV pseudoviruses showed no detectable neutralizing activity (NT50 < 25) against SARS-CoV-1/MLV pseudovirions. We also compared the semiquantitative Siemens SARS-CoV-2 IgG test, which measures binding of IgG to recombinantly expressed receptor binding domain of SARS-CoV-2 spike glycoprotein with the neutralization titers obtained in the pseudovirion assay and the results show high concordance between the two tests (R2 = 0.9344). CONCLUSIONS: SARS-CoV-2 spike/MLV pseudovirions provide a practical means of assessing neutralizing activity of antibodies in serum or plasma from infected patients under laboratory conditions consistent with biocontainment level 2. This assay offers promise also in evaluating immunogenicity of spike glycoprotein-based candidate vaccines in the near future.


Assuntos
/imunologia , Leucemia/imunologia , Testes de Neutralização/métodos , Glicoproteína da Espícula de Coronavírus/imunologia , Vírion/imunologia , /imunologia , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Células HEK293 , Humanos , Imunoglobulina G/sangue , Camundongos
4.
Crit Rev Oncol Hematol ; 157: 103170, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33316638

RESUMO

Resistance of extramedullary leukemia growth post-transplant prevents cure. Review of its behavior detailed in 585 published cases should lead to better treatment. Leukemic tumors were found up to 13 years after transplant, most in sites inaccessible to physical exam. In 83%, marrow was not in morphologic relapse; next relapse was most often extramedullary. Induction protocols alone produced few durable responses in acute leukemias and fatal marrow aplasia in 17 %. Overall, 120 patients survived over 2 years, 43 relapse-free up to 18 years, the majority after combined tumor-directed and systemic therapy. Overall median survival was 9 months. This review highlights how results can improve: by defining extent of leukemia involvement with scans before transplant, and emergently when leukemic tumor is found after, ablating tumor directly to abort metastasis, and determining dosing of systemic chemotherapy that protects, without ablating, donor marrow. Monitoring total body remission with body scans should increase transplant cures.


Assuntos
Leucemia , Biologia , Medula Óssea , Transplante de Medula Óssea , Humanos , Leucemia/terapia , Recidiva
5.
Ecotoxicol Environ Saf ; 207: 111490, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33120278

RESUMO

Benzene is a ubiquitous, occupational, and environmental hematotoxic and leukemogen. Damage to hematopoietic stem cells (HSCs) induced by benzene and its metabolites is a key event in bone marrow (BM) depression and leukemogenesis. There are no reports on transcriptome profiles of HSCs following benzene exposure. Here, Smart-seq2 single-cell transcriptome sequencing was used to detect transcriptomic alternations in BM HSCs and peripheral blood HSCs (PBSCs) in male C57B/6 mice exposed to benzene. We found that benzene caused hematotoxicity which was confirmed by routine blood test, pathological examination, and HSCs percentage analysis. A total of 1514 differentially expressed genes (DEGs) in BM HSCs and 1703 DEGs in PBSCs were screened after treatment with benzene. Weighted gene correlation network analysis revealed that pathways in cancer, transcriptional misregulation in cancer, and hematopoietic cell lineage are vital pathways involved in benzene-induced toxicity in BM HSCs, whereas hematopoietic cell lineage and leukocyte transendothelial migration are critical pathways in PBSCs. Of note, there were 164 common DEGs in both HSCs, out of which 53 genes were co-regulated in both types of HSCs. Subsequent pathway analysis of these 53 genes indicated that the most relevant pathways involved neutrophil degranulation and CD93 localized in the core of the network of the 53 genes, which are known to regulate leukemia stem cell self-renewal and quiescence. Our results could enhance our understanding of HSC responses to benzene, facilitate the identification of potential molecular biomarkers and future studies on its mechanism of toxicity toward HSCs.


Assuntos
Benzeno/toxicidade , Poluentes Ambientais/toxicidade , Testes de Toxicidade , Animais , Apoptose/genética , Medula Óssea/metabolismo , Células da Medula Óssea/metabolismo , Células-Tronco Hematopoéticas/metabolismo , Leucemia , Masculino , Camundongos , Neoplasias , Transcriptoma
6.
Chemosphere ; 263: 128242, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33297189

RESUMO

Perfluorooctanesulfonate (PFOS) is a persistent pollutant that can induce toxic effects, including leukemia, on blood cells. Vitamin C (VC), a functional nutrient, has been found to possess potent cytoprotective effects. However, there are currently no reports on its ability to treat PFOS-associated leukemia. This study used a molecular networking analysis to reveal the functional action and pharmacological mechanism of VC against PFOS-associated leukemia. The biological informatics findings revealed a total of 17 intersection targets against PFOS-associated leukemia. In addition, seven core-functional targets, including tumor protein p53 (TP53), mitogen-activated protein kinase 1 (MAPK1), estrogen receptor 1 (ESR1), sirtuin 1 (SIRT1), nitric oxide synthase 3 (NOS3), myeloid cell leukemia-1 (MCL1), and telomerase reverse transcriptase (TERT), were screened and identified. Notably, the molecular docking findings indicated that TP53, MAPK1, and ESR1 were potent pharmacological targets of VC against PFOS-associated leukemia. Moreover, the pharmacological functions including biological processes, cell components, and molecular pathways of VC against PFOS-associated leukemia were determined. According to the computational findings, we conclude that VC protects against PFOS-associated leukemia action by suppressing leukemia-associated cell proliferation and tumor growth. The validated genes of TP53, MAPK1, ESR1 may become potential biomarkers for monitoring and treating PFOS-associated leukemia.


Assuntos
Ácidos Alcanossulfônicos , Fluorcarbonetos , Leucemia , Ácidos Alcanossulfônicos/toxicidade , Ácido Ascórbico , Fluorcarbonetos/toxicidade , Humanos , Leucemia/induzido quimicamente , Simulação de Acoplamento Molecular , Transdução de Sinais
7.
Phytomedicine ; 80: 153383, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33091855

RESUMO

BACKGROUND: Caffeic acid 3,4-dihydroxyphenethyl ester (CADPE) is a natural polyphenolic ester isolated as a minor component from a water extract of the Chinese medicine Zhongjiefeng [Sarcandra glabra (Thunb.) Nakai (Chloranthaceae)] and has previously shown to have activity against solid tumors through the modulation of multiple targets or signal pathways. However, the activity and potential mechanism of CADPE against leukemia cells have not yet been characterized. PURPOSE: To investigate whether and how CADPE kills leukemia cells. METHOD: (1) The activity of CADPE inhibiting the growth of different leukemia cell lines was evaluated by MTT assay; (2) Cell cycle arrest and apoptosis induced by CADPE were determined by flow cytometry with FlowJo software for quantification; (3) The protein levels were analyzed by Western blot and ubiquitin-binding c-Myc was acquired by co-immunoprecipitation. RESULTS: CADPE exerted potent activity against different leukemia cell lines with low toxicity in normal cells. In terms of mechanism of action, CADPE promoted ubiquitin-proteasome-dependent degradation of c-Myc through activating glycogen synthase kinase-3ß (GSK3ß) and downregulating deubiquitinating enzyme USP28 to trigger the interaction of c-Myc with ubiquitin ligase Fbw7, resulting in the downregulation of cell cycle regulators and anti-apoptotic proteins and consequently, cell cycle arrest and cell apoptosis. CONCLUSION: CADPE is a novel c-Myc inhibitor with high activity and a unique mechanism for killing leukemia cells.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Ácidos Cafeicos/farmacologia , Leucemia/tratamento farmacológico , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proteínas F-Box/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Leucemia/metabolismo , Leucemia/patologia , Proteínas Proto-Oncogênicas c-myc/metabolismo , Transdução de Sinais/efeitos dos fármacos , Ubiquitina/metabolismo , Ubiquitina Tiolesterase/metabolismo
8.
J Healthc Eng ; 2020: 6648574, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33343851

RESUMO

For the last few years, computer-aided diagnosis (CAD) has been increasing rapidly. Numerous machine learning algorithms have been developed to identify different diseases, e.g., leukemia. Leukemia is a white blood cells- (WBC-) related illness affecting the bone marrow and/or blood. A quick, safe, and accurate early-stage diagnosis of leukemia plays a key role in curing and saving patients' lives. Based on developments, leukemia consists of two primary forms, i.e., acute and chronic leukemia. Each form can be subcategorized as myeloid and lymphoid. There are, therefore, four leukemia subtypes. Various approaches have been developed to identify leukemia with respect to its subtypes. However, in terms of effectiveness, learning process, and performance, these methods require improvements. This study provides an Internet of Medical Things- (IoMT-) based framework to enhance and provide a quick and safe identification of leukemia. In the proposed IoMT system, with the help of cloud computing, clinical gadgets are linked to network resources. The system allows real-time coordination for testing, diagnosis, and treatment of leukemia among patients and healthcare professionals, which may save both time and efforts of patients and clinicians. Moreover, the presented framework is also helpful for resolving the problems of patients with critical condition in pandemics such as COVID-19. The methods used for the identification of leukemia subtypes in the suggested framework are Dense Convolutional Neural Network (DenseNet-121) and Residual Convolutional Neural Network (ResNet-34). Two publicly available datasets for leukemia, i.e., ALL-IDB and ASH image bank, are used in this study. The results demonstrated that the suggested models supersede the other well-known machine learning algorithms used for healthy-versus-leukemia-subtypes identification.


Assuntos
Aprendizado Profundo , Diagnóstico por Computador , Internet das Coisas , Leucemia/classificação , Leucemia/diagnóstico , Reconhecimento Automatizado de Padrão , Algoritmos , Computação em Nuvem , Bases de Dados Factuais , Diagnóstico por Imagem , Humanos , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mieloide Aguda/diagnóstico , Aprendizado de Máquina , Redes Neurais de Computação , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Telemedicina
9.
BMC Bioinformatics ; 21(Suppl 21): 581, 2020 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-33371887

RESUMO

BACKGROUND: The estimation of microbial networks can provide important insight into the ecological relationships among the organisms that comprise the microbiome. However, there are a number of critical statistical challenges in the inference of such networks from high-throughput data. Since the abundances in each sample are constrained to have a fixed sum and there is incomplete overlap in microbial populations across subjects, the data are both compositional and zero-inflated. RESULTS: We propose the COmpositional Zero-Inflated Network Estimation (COZINE) method for inference of microbial networks which addresses these critical aspects of the data while maintaining computational scalability. COZINE relies on the multivariate Hurdle model to infer a sparse set of conditional dependencies which reflect not only relationships among the continuous values, but also among binary indicators of presence or absence and between the binary and continuous representations of the data. Our simulation results show that the proposed method is better able to capture various types of microbial relationships than existing approaches. We demonstrate the utility of the method with an application to understanding the oral microbiome network in a cohort of leukemic patients. CONCLUSIONS: Our proposed method addresses important challenges in microbiome network estimation, and can be effectively applied to discover various types of dependence relationships in microbial communities. The procedure we have developed, which we refer to as COZINE, is available online at https://github.com/MinJinHa/COZINE .


Assuntos
Biologia Computacional/métodos , Microbiota , Humanos , Leucemia/microbiologia
10.
Medicine (Baltimore) ; 99(50): e23569, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33327316

RESUMO

The SET nuclear proto-oncogene (SET)-nucleoporin (NUP) 214 fusion gene (SET-NUP214) is a rare leukemia fusion gene. Due to the limited number of samples with SET-NUP214 fusion gene in previous studies, the significance of SET-NUP214 for measurable residual disease (MRD) monitoring in patients with acute leukemia (AL) is still unclear. Our study aimed to observe the dynamic changes in SET-NUP214 expression before and after allogeneic hematopoietic stem cell transplantation (allo-HSCT), and analyzed whether SET-NUP214 could be used to evaluate MRD status. Our study included 24 AL patients who were newly diagnosed with SET-NUP214 fusion gene and they all received allo-HSCT. Their MRD was evaluated by monitoring SET-NUP214 fusion gene and leukemia-associated immunophenotype (LAIP). The median follow-up time was 501 days (56-2208 days). Of the enrolled patients, 6 (25%) patients died, including 3 (12.5%) patients died of leukemia relapse. Total 5 (20.8%) patients experienced hematological relapse at a median of 225 days (56-1057 days) post-transplantation. The SET-NUP214 median expression level at diagnosis was 405.1% (14.6%-1482.4%). SET-NUP214 gene expression generally became positive prior to flow cytometry results. In addition, the Kaplan-Meier survival curves analysis showed that those who had SET-NUP214 positive (SET-NUP214+) post-transplantation had a higher 2-year cumulative incidence of leukemia relapse (CIR) of 43.7 ±â€Š18.8% (P < .05). However, there was no significant difference between SET-NUP214 positive and SET-NUP214 negative patients with regard to their 2-year overall survival (OS) (82.5 ±â€Š11.3 vs 64.6 ±â€Š17.5%, respectively, P = .271). ROC curve analysis turned out that the area under the ROC curve (AUC) was 0.916 (95% CI: 0.784-1.0; P = .005). In conclusion, SET-NUP214 fusion gene determined by real-time quantitative reverse transcriptase polymerase chain reaction (RQ-PCR) could be used to evaluate MRD status after allo-HSCT. Patients with positive SET-NUP214 expression after transplantation will have a poor prognosis.


Assuntos
Proteínas de Ligação a DNA/genética , Transplante de Células-Tronco Hematopoéticas/métodos , Chaperonas de Histonas/genética , Leucemia/genética , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Fusão Oncogênica/genética , Adolescente , Adulto , Feminino , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Estimativa de Kaplan-Meier , Leucemia/diagnóstico , Leucemia/mortalidade , Leucemia/terapia , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Prognóstico , Curva ROC , Estudos Retrospectivos , Análise de Sobrevida , Adulto Jovem
11.
Gan To Kagaku Ryoho ; 47(10): 1415-1420, 2020 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-33130732

RESUMO

Current adoptive T cell therapies conducted in an autologous setting are costly, time consuming, and depend on the quality of the patient's T cells. To address these issues, we developed a strategy in which T cells are regenerated from induced pluripotent stem cells (iPSCs) that were originally derived from T cells, and succeeded in regenerating cytotoxic T lymphocytes (CTLs) specific for the WT1 antigen, which exhibited therapeutic efficacy in a xenograft model of leukemia. We recently have extended our strategy to solid tumors. To make our method more generally applicable, we developed an allogeneic approach by transducing HLA-haplotype homozygous iPSCs with WT1-specific TCR α/ß genes that had been tested clinically. The regenerated CTLs antigen-specifically suppressed tumor growth in a patient-derived xenograft model of renal cell carcinoma, demonstrating the feasibility of our strategy against solid tumors.


Assuntos
Células-Tronco Pluripotentes Induzidas , Leucemia , Neoplasias , Humanos , Linfócitos T Citotóxicos
12.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1534-1538, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067950

RESUMO

OBJECTIVE: To explore the effect of nuclear factor kappa-B (NF-κB) inhibitor pyrrolidine dithiocarbamate (PDTC) on the proliferation and apoptosis of acute leukemia cell HL-60. METHODS: HL-60 cells were cultured with PDTC of 0, 25, 50, 100 µmol/L for 24, 48, 72 h. The inhibition rate of cell proliferation was detected by CCK-8 assay. Cell apoptosis was detected by Hoechst staining. Cell cycle was detected by flow cytometry. The expression of B-cell lymphoma-2 (BCL-2), BCL-2 associated X protein (BAX), cyclinD1, activated cysteinyl aspartate specific proteinase (cleaved caspase 3), cleaved caspase 8 and activation of NF-κB signal pathway related protein was detected by Western blot. RESULTS: After the HL-60 cells were cultured with PDTC of 25, 50, 100 µmol/L for 24, 48, 72 h, the inhibition rate of cell proliferation increased with the enhancement of PDTC concentration at the same time point (r=0.924, P<0.01). At the same PDTC concentration, the inhibition rate of cell proliferation increased with prolonging of time (r=0.952, P<0.01). After HL-60 cell was cultured with PDTC of 25, 50, 100 µmol/L for 48 h, compared with control group, PDTC of 25, 50, 100 µmol/L increased the cell apoptotic rate, arrested cell cycle at G1 phase (P<0.01), the expression of BCL-2, cyclinD1 and p-NF-κB p65 was down-regulated(P<0.05), the expression of BAX, cleaved caspase 3, cleaved caspase 8 was up-regulated(P<0.01). PDTC of 50, 100 µmol/L down-regulated the expression of p-inhibitor of NF-κB (p-IκBα)(P<0.01). CONCLUSION: PDTC can inhibit acute leukemia HL-60 cell proliferation and induce cell apoptosis.


Assuntos
Apoptose , Leucemia , Proliferação de Células , Células HL-60 , Humanos , NF-kappa B , Pirrolidinas , Tiocarbamatos
13.
PLoS One ; 15(10): e0239967, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33002084

RESUMO

Our objective was to further the understanding of the process of reintegration of childhood cancer patients after treatment and to identify factors influencing that process. Using a qualitative approach, we conducted 49 interviews with parents (n = 29 mothers, n = 20 fathers) from 31 families with a child (<18 years) with leukemia or CNS tumor. Interviews were conducted about 16 to 24 months after the end of the treatment. We used a semi-structured interview guideline and analyzed the data using content analysis. Average age of pediatric cancer patients was 5.5 years at the time of diagnosis; mean time since diagnosis was 3.5 years. Parents reported immediate impact of the disease on their children. Reintegration had gone along with delayed nursery/school enrollment or social challenges. In most cases reintegration was organized with a gradual increase of attendance. Due to exhaustion by obligatory activities, reintegration in leisure time activities was demanding and parents reported a gradual increase of activity level for their children. Parents described several barriers and facilitators influencing the reintegration process into nursery/school and leisure time activities (structural support, social support, health status, intrapersonal aspects). Although many children reintegrate well, the process takes lots of effort from parents and children. Childhood cancer survivors and their families should be supported after the end of intensive treatment to facilitate reintegration.


Assuntos
Neoplasias Encefálicas/psicologia , Sobreviventes de Câncer/educação , Leucemia/psicologia , Pais/psicologia , Ajustamento Social , Adulto , Idoso , Atitude , Neoplasias Encefálicas/reabilitação , Sobreviventes de Câncer/psicologia , Criança , Feminino , Humanos , Leucemia/reabilitação , Masculino , Pessoa de Meia-Idade , Instituições Acadêmicas/estatística & dados numéricos , Inquéritos e Questionários
14.
Medicine (Baltimore) ; 99(44): e23006, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33126384

RESUMO

Interleukin-10(IL-10) is an immunosuppressive cytokine and plays an important role in inflammation and cancers. Numerous studies have explored the association between single nucleotide polymorphisms of IL-10 and leukemia, but their results were conflicting, so we performed this meta-analysis to elucidate the association between 3 common single nucleotide polymorphisms of IL-10 (rs1800896, rs1800871 and rs1800872) and risk of leukemia.We conducted a comprehensive research in Pubmed, Chinese Biomedical Literature Database disc and Embase using related terms. After strict selection, 18 studies with 2264 cases and 3846 controls were included into this meta-analysis. Odds ratio and 95% confidence interval were used to evaluate the strength of the association.We found that polymorphism of IL-10 -1082A/G was associated with decreased risk of leukemia both in overall analysis and in stratified analysis according to ethnicity and cancer type. A strong relationship was also uncovered between polymorphism of IL-10 -592C/A and increased risk of leukemia in non-Chinese.GG genotype of IL-10 -1082A/G is associated with decreased risk of leukemia, especially chronic lymphocytic leukemia. CC genotype of -592C/A is associated with decreased risk of leukemia in non-Chinese.


Assuntos
Predisposição Genética para Doença , Interleucina-10/genética , Leucemia/genética , Estudos de Casos e Controles , Grupos Étnicos , Humanos , Polimorfismo de Nucleotídeo Único , Risco
15.
Med Oral Patol Oral Cir Bucal ; 25(6): e791-e798, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33037810

RESUMO

BACKGROUND: Oropharyngeal mucositis (OM) is one of the main side-effects of oncological therapy. There is no treatment to prevent its occurrence, but some zinc-based therapies have been proven to help in decreasing its intensity. The objective of this study was to determine the effect of zinc in OM in children with acute leukemia in the early stages of oncological treatment. MATERIAL AND METHODS: This quasi-experimental study evaluated OM in 2 groups (control group: conventional hospital management, and experimental group: administration of 50 mg of zinc gluconate daily plus conventional hospital management). OM severity was recorded at a two-month follow-up. RESULTS: Forty-nine patients (26 in the control group and 23 in the experimental group) were included. The mean age of the patients was 11.1 ± 2.7 years; 65.3% had a diagnosis of pre-B acute lymphoblastic leukemia. The incidences of OM in the control group and the experimental group were 46.2% and 26.1%, respectively, but the difference was not significant. Based on a negative binomial regression model, females had, on average, 1.5 more days with OM (p = 0.002), and patients assigned to the experimental group had, on average, 2 less days with OM than the control group (p = 0.001). The pain score was higher in the control group (p = 0.0009), as was the mean score on the WHO scale (p = 0.0012). CONCLUSIONS: Zinc facilitated a reduction in the severity and duration of OM; further studies focusing on children are needed to confirm the effects of this trace element.


Assuntos
Antineoplásicos , Leucemia , Mucosite , Estomatite , Adolescente , Antineoplásicos/efeitos adversos , Criança , Feminino , Humanos , Leucemia/tratamento farmacológico , Estomatite/induzido quimicamente , Estomatite/tratamento farmacológico , Estomatite/prevenção & controle , Zinco
16.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 5464-5467, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33019216

RESUMO

In vitro cytotoxicity screening is a crucial step of anticancer drug discovery. The application of deep learning methodology is gaining increasing attentions in processing drug screening data and studying anticancer mechanisms of chemical compounds. In this work, we explored the utilization of convolutional neural network in modeling the anticancer efficacy of small molecules. In particular, we presented a VGG19 model trained on 2D structural formulae to predict the growth-inhibitory effects of compounds against leukemia cell line CCRF-CEM, without any use of chemical descriptors. The model achieved a normalized RMSE of 15.76% on predicting growth inhibition and a Pearson Correlation Coefficient of 0.72 between predicted and experimental data, demonstrating a strong predictive power in this task. Furthermore, we implemented the Layer-wise Relevance Propagation technique to interpret the network and visualize the chemical groups predicted by the model that contribute to toxicity with human-readable representations.Clinical relevance-This work predicts the cytotoxicity of chemical compounds against human leukemic lymphoblast CCRF-CEM cell lines on a continuous scale, which only requires 2D images of the structural formulae of the compounds as inputs. Knowledge in the structure-toxicity relationship of small molecules will potentially increase the hit rate of primary drug screening assays.


Assuntos
Descoberta de Drogas , Leucemia , Avaliação Pré-Clínica de Medicamentos , Humanos , Leucemia/tratamento farmacológico , Aprendizado de Máquina , Redes Neurais de Computação
17.
Arch. argent. pediatr ; 118(5): e468-e475, oct 2020. tab, ilus
Artigo em Espanhol | LILACS, BINACIS | ID: biblio-1122525

RESUMO

El trasplante de médula ósea es una terapia potencialmente curativa para múltiples enfermedades; el alogénico es el más indicado en leucemias. La enfermedad injerto versus huésped (EIVH) constituye la principal complicación del trasplante de médula ósea alogénico. Tanto en la EIVH aguda como crónica, la piel es el órgano más frecuentemente comprometido. El objetivo fue analizar las manifestaciones cutáneas de esta entidad. Trabajo retrospectivo y descriptivo, que incluyó a 59 pacientes trasplantados de edades entre 0 y 20 años. En 50 casos, se realizó trasplante de médula ósea alogénico. Veinticinco pacientes desarrollaron EIVH (17, la forma aguda, y 8, la forma crónica), y 24 tuvieron compromiso cutáneo. En concordancia con lo comunicado se encontró que las manifestaciones cutáneas fueron la manifestación clínica más común de EIVH. El hallazgo principal en EIVH aguda en nuestra serie fue el rash eritematoso maculopapular y, en EIVH crónica, las lesiones escleróticas símil morf


Bone marrow transplant is a potentially curative therapy for several diseases, and allogeneic bone marrow transplant is the most commonly indicated type for leukemias. Graft versus host disease (GVHD) is the main complication of allogeneic bone marrow transplant. In both acute and chronic GVHD, the skin is the most frequently involved organ. The objective of this study was to analyze cutaneous manifestations of this disease. Retrospective and descriptive study that included 59 transplanted patients aged 0 to 20 years. In 50 cases allogeneic bone marrow transplant was performed. Twenty-five patients developed GVHD (17 acute disease and 8 chronic disease) and 24 of them had cutaneous involvement. According to the literature, skin compromise was the commonest clinical manifestation of GVHD. Main finding in acute GVHD in our series was the erythematous maculopapular rash, while in chronic GVHD they were sclerotic lesions resembling morphe


Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Doença Enxerto-Hospedeiro/diagnóstico , Manifestações Cutâneas , Transplante Homólogo , Leucemia , Epidemiologia Descritiva , Estudos Retrospectivos , Transplante de Medula Óssea , Exantema
18.
PLoS Pathog ; 16(9): e1008811, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32903274

RESUMO

Damage-associated molecular patterns (DAMPs) are endogenous molecules activating the immune system upon release from injured cells. Here we show that the IFI16 protein, once freely released in the extracellular milieu of chronically inflamed tissues, can function as a DAMP either alone or upon binding to lipopolysaccharide (LPS). Specifically, using pull-down and saturation binding experiments, we show that IFI16 binds with high affinity to the lipid A moiety of LPS. Remarkably, IFI16 DAMP activity is potentiated upon binding to subtoxic concentrations of strong TLR4-activating LPS variants, as judged by TLR4-MD2/TIRAP/MyD88-dependent IL-6, IL-8 and TNF-α transcriptional activation and release in stimulated monocytes and renal cells. Consistently, using co-immunoprecipitation (co-IP) and surface plasmon resonance (SPR) approaches, we show that IFI16 is a specific TLR4-ligand and that IFI16/LPS complexes display a faster stimulation turnover on TLR4 than LPS alone. Altogether, our findings point to a novel pathomechanism of inflammation involving the formation of multiple complexes between extracellular IFI16 and subtoxic doses of LPS variants, which then signal through TLR4.


Assuntos
Inflamação/imunologia , Neoplasias Renais/imunologia , Leucemia/imunologia , Lipopolissacarídeos/metabolismo , Proteínas Nucleares/metabolismo , Fosfoproteínas/metabolismo , Receptor 4 Toll-Like/metabolismo , Humanos , Inflamação/metabolismo , Inflamação/patologia , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Leucemia/metabolismo , Leucemia/patologia , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais , Células Tumorais Cultivadas
20.
Med. clín (Ed. impr.) ; 155(4): 152-158, ago. 2020. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-195761

RESUMO

ANTECEDENTES Y OBJETIVO: La mielofibrosis es una neoplasia mieloproliferativa crónica infrecuente. Nuestro objetivo fue describir las características clínico-biológicas, el tratamiento y el curso evolutivo de los pacientes con mielofibrosis en España. MATERIAL Y MÉTODOS: Se analizaron 1.000 pacientes del Registro Español de Mielofibrosis diagnosticados de mielofibrosis primaria (n=641) o secundaria (n=359). RESULTADOS: La mediana de edad era de 68 años. La frecuencia de sintomatología constitucional, anemia moderada o severa (Hb<10g/dl) y esplenomegalia sintomática fue del 35, 36 y 17%, respectivamente. La incidencia de trombosis y hemorragia fue de 1,96 y 1,6 eventos por 100 años-paciente, respectivamente. La incidencia acumulada de leucemia fue del 15% a los 10 años. Para la anemia se emplearon principalmente agentes eritropoyéticos y danazol. A partir del 2010 se observó un incremento significativo del uso de ruxolitinib. Un 7,5% de los pacientes fue trasplantado. El 42% de los enfermos falleció, debido principalmente al deterioro clínico provocado por la mielofibrosis y a la transformación leucémica. La supervivencia mediana de la serie fue de 5,7 años. El IPSS identificó 4 grupos de riesgo: la supervivencia mediana no se alcanzó en el de bajo riesgo, mientras que fue de 8,8 años, 5,3 años y 2,8 años en los de riesgo intermedio-1, intermedio-2 y alto, respectivamente. CONCLUSIONES: la mielofibrosis es una enfermedad invalidante que afecta sobre todo a personas de edad avanzada y cuyo tratamiento es fundamentalmente sintomático. A pesar de su heterogeneidad clínica se dispone de modelos pronósticos útiles para la selección de candidatos a trasplante


Background and objective Myelofibrosis: is an infrequent chronic myeloproliferative neoplasm. We aimed to describe the clinico-biological characteristics, treatment, and evolutive course of myelofibrosis patients in Spain. MATERIAL AND METHODS: A total of 1,000 patients from the Spanish Registry of Myelofibrosis diagnosed with primary (n=641) or secondary (n=359) myelofibrosis were analysed. RESULTS: Median age was 68 years. The frequency of constitutional symptoms, moderate to severe anaemia (Hb<10g/dL), and symptomatic splenomegaly was 35%, 36%, and 17%, respectively. The rate of thrombosis and haemorrhage was 1.96 and 1.6 events per 100 patient-years, respectively. The cumulative incidence of leukaemia at 10 years was 15%. The most frequent therapies for the anaemia were the erythropoiesis stimulating agents and danazol. From 2010, a progressive increase in the use of ruxolitinib was noticed. A total of 7.5% of patients were transplanted. During the observation period, 42% of patients died mainly due to the clinical deterioration caused by myelofibrosis or leukaemic transformation. The median survival of the series was 5.7 years. Four different risk categories were identified by the IPSS: median survival was not reached in the low risk group and was 8.8 years, 5.3 years, and 2.8 years in the intermediate-1, intermediate-2, and high-risk groups, respectively. CONCLUSIONS: Myelofibrosis is a disabling condition mainly affecting elderly people. Its treatment is mostly driven by symptom control. Despite its clinical heterogeneity, several prognostic models are useful to select candidates for transplantation


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Mielofibrose Primária/epidemiologia , Mielofibrose Primária/patologia , Espanha/epidemiologia , Registros , Trombose/epidemiologia , Hemorragia/epidemiologia , Leucemia/epidemiologia , Anemia/tratamento farmacológico , Anemia/epidemiologia , Prognóstico , Grupos de Risco , Taxa de Sobrevida
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA