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1.
Anticancer Res ; 41(10): 4929-4936, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34593440

RESUMO

BACKGROUND/AIM: A new set of LQB-nitrones and analogues was synthesized to evaluate anticancer activity based on the substitution of the terpenyl moiety of the antileukemic compound LQB-278 by the conformationally restricted cinnamyl ether. MATERIALS AND METHODS: A structure-activity relationship study was performed in vitro on Jurkat cells to screen the antileukemic activity of LQB-nitrones and analogues and elucidate the mechanisms of action of the most active derivatives. RESULTS: The cynamyl ramification and its ortho position aldehyde substitution improved the antileukemic activity. Three compounds showed an in vitro antiproliferative action, but only 5b induced apoptosis. Analysis of the molecular mechanisms showed increased expression of the cell cycle inhibitor p21CIP1/WAF1/Sdi1, caspase 3, Fas receptor, and Bax/Bcl-2 ratio. CONCLUSION: The cinnamyl derivative 5b (LQB-461) presented higher antileukemic effects than the prototype terpenyl nitrone, inducing Jurkat cell death by activating both extrinsic and intrinsic pathways of apoptosis. Therefore, this compound is a new promising candidate drug against leukemia.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Leucemia/tratamento farmacológico , Óxidos de Nitrogênio/química , Óxidos de Nitrogênio/farmacologia , Apoptose , Proliferação de Células , Humanos , Leucemia/patologia , Células Tumorais Cultivadas
2.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(5): 1387-1393, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34627415

RESUMO

OBJECTIVE: To investigate the inhibitory effects of novel phosphodiesterase 4 inhibitor ZL-n-91 to the proliferation of leukemia cells L1210 and K562. METHODS: CCK-8 method was used to detect the effect of ZL-n-91 to the proliferation of L1210 and K562 cells, and the proliferation rate, IC50 were calculated. The effects of ZL-n-91 to the cycle of L1210 and K562 cells was detected by PE single staining, and the effects of ZL-n-91 to the apoptosis of L1210 and K562 cells was detected by PE/7AA-D double staining. Western blot was used to detect the effect of ZL-n-91 to the expression levels of apoptosis related proteins. Subcutaneous tumor transplantation model of acute lymphoblastic leukemia L1210 was established in the nude mice, and the inhibitory effect of oral administration of ZL-n-91 to the xenograft was observed. RESULTS: ZL-n-91 showed a significant inhibitory effect to the proliferation of leukemia cells L1210 and K562 in a dose-dependent manner (P<0.001). After treated by ZL-n-91, the leukemia cells L1210 and K562 in the S-phase in cell cycle decreased significantly compared with those in control group (P<0.01). The apoptosis of leukemia cells L1210 and K562 could be induced by ZL-n-91 (P<0.001), and the expression level of apoptosis related protein BAX significantly increased. In the animal experiment, the result showed that ZL-n-91 could significantly inhibit the growth of subcutaneously transplantation tumor (P<0.05). CONCLUSION: The novel phosphodiesterase 4 inhibitor ZL-n-91 can effectively inhibit the proliferation of leukemia cells L1210 and K562, which has the potential of anti-leukemia drug development.


Assuntos
Leucemia , Inibidores da Fosfodiesterase 4 , Animais , Proliferação de Células , Humanos , Células K562 , Camundongos , Camundongos Nus , Inibidores da Fosfodiesterase 4/farmacologia
3.
Gen Physiol Biophys ; 40(5): 397-407, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34602453

RESUMO

The present study was conducted to explore the anti-acute myeloid leukaemia (AML) effects of leonurine. HL-60 and U-937 cells were used to assess the antileukaemia effect of leonurine in vitro, and HL-60 and U-937 xenograft nude mice were used to evaluate its antitumour effect in vivo. Leonurine inhibited the proliferation of HL-60 and U-937 cells in a time- and dose-dependent manner. Moreover, leonurine therapy prevented the growth of tumours in both xenograft animal models. Leonurine could induce apoptosis in HL-60 and U-937 cells. The cytotoxic effects of leonurine on HL-60 and U-937 cells were associated with an increased ratio of Bax/Bcl-2, activation of caspase-3, caspase-8 and caspase-9, and increased expression of cytochrome c in the cytoplasm. Leonurine inhibited activation of the PI3K/Akt pathway in HL-60 and U-937 cells by lowering the phosphorylation levels of PI3K and Akt. Our results indicate that leonurine is a potential anti-AML agent, and this activity may be associated with its repression of the phosphorylation of PI3K and Akt.


Assuntos
Leucemia , Fosfatidilinositol 3-Quinases , Animais , Ácido Gálico/análogos & derivados , Células HL-60 , Humanos , Camundongos , Camundongos Nus
4.
Nat Commun ; 12(1): 5773, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34599159

RESUMO

Protein localisation and translocation between intracellular compartments underlie almost all physiological processes. The hyperLOPIT proteomics platform combines mass spectrometry with state-of-the-art machine learning to map the subcellular location of thousands of proteins simultaneously. We combine global proteome analysis with hyperLOPIT in a fully Bayesian framework to elucidate spatiotemporal proteomic changes during a lipopolysaccharide (LPS)-induced inflammatory response. We report a highly dynamic proteome in terms of both protein abundance and subcellular localisation, with alterations in the interferon response, endo-lysosomal system, plasma membrane reorganisation and cell migration. Proteins not previously associated with an LPS response were found to relocalise upon stimulation, the functional consequences of which are still unclear. By quantifying proteome-wide uncertainty through Bayesian modelling, a necessary role for protein relocalisation and the importance of taking a holistic overview of the LPS-driven immune response has been revealed. The data are showcased as an interactive application freely available for the scientific community.


Assuntos
Inflamação/metabolismo , Leucemia/metabolismo , Leucemia/patologia , Lipopolissacarídeos/farmacologia , Proteômica , Algoritmos , Anti-Infecciosos/metabolismo , Anti-Inflamatórios/metabolismo , Apresentação do Antígeno , Autofagossomos/metabolismo , Teorema de Bayes , Pontos de Checagem do Ciclo Celular , Membrana Celular/metabolismo , Núcleo Celular/metabolismo , Forma Celular , Humanos , Imunidade , Inflamação/patologia , Leucemia/imunologia , Ativação Linfocitária/imunologia , Lisossomos/metabolismo , Proteínas de Neoplasias/metabolismo , Transporte Proteico , Proteoma/metabolismo , Transdução de Sinais , Linfócitos T/imunologia , Células THP-1 , Fatores de Tempo , Vesículas Transportadoras/metabolismo , Regulação para Cima , Proteínas rho de Ligação ao GTP/metabolismo
5.
Rinsho Ketsueki ; 62(8): 988-997, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34497239

RESUMO

Leukemia is caused by uncontrolled proliferation of immature hematopoietic progenitors. MLL fusion proteins, generated by chromosomal translocations, activate a broad range of previously transcribed genes to achieve the same expression profile as that of the parent cell in the daughter cells, thereby promoting self-renewal. Normally, replication of the expression profile only occurs in the hematopoietic stem cells (HSCs). A transactivation system comprised of MLL and AF4/ENL/P-TEFb (AEP) complexes promotes it by reactivating CpG-rich promoters. In the normal hematopoietic development, this system is tightly regulated and progressively suppressed during the course of hematopoietic differentiation so that non-HSC hematopoietic cells would not self-renew. Genetic mutations such as fusions of MLL and AEP components generate a constitutively active form of the MLL transcriptional machinery, which aberrantly promotes self-renewal even in non-HSC hematopoietic cells. In this review, I depict a molecular mechanism of MLL fusion-mediated leukemogenesis from a standpoint that leukemogenesis is driven by aberrant self-renewal that is mediated by hyper-active transcriptional machinery, and introduce several molecularly targeted therapies in the making which specifically perturb this transactivation system.


Assuntos
Leucemia , Proteína de Leucina Linfoide-Mieloide , Carcinogênese , Células-Tronco Hematopoéticas , Humanos , Leucemia/genética , Leucemia/terapia , Proteína de Leucina Linfoide-Mieloide/genética , Proteínas de Fusão Oncogênica/genética
6.
Comput Intell Neurosci ; 2021: 2167670, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34497637

RESUMO

In reliability studies, the best fitting of lifetime models leads to accurate estimates and predictions, especially when these models have nonmonotone hazard functions. For this purpose, the new Exponential-X Fréchet (NEXF) distribution that belongs to the new exponential-X (NEX) family of distributions is proposed to be a superior fitting model for some reliability models with nonmonotone hazard functions and beat the competitive distribution such as the exponential distribution and Frechet distribution with two and three parameters. So, we concentrated our effort to introduce a new novel model. Throughout this research, we have studied the properties of its statistical measures of the NEXF distribution. The process of parameter estimation has been studied under a complete sample and Type-I censoring scheme. The numerical simulation is detailed to asses the proposed techniques of estimation. Finally, a Type-I censoring real-life application on leukaemia patient's survival with a new treatment has been studied to illustrate the estimation methods, which are well fitted by the NEXF distribution among all its competitors. We used for the fitting test the novel modified Kolmogorov-Smirnov (KS) algorithm for fitting Type-I censored data.


Assuntos
Leucemia , Modelos Estatísticos , Simulação por Computador , Humanos , Reprodutibilidade dos Testes , Distribuições Estatísticas
7.
Ann Ital Chir ; 102021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34569474

RESUMO

Mucormycosis is an opportunistic and aggressive fungal infection that mainly affects immunocompromised patients who generally suffer from diabetes mellitus, immune impairment, hematological disease. It is a life-threatening infection and the management is not standardized. The literature proposes aggressive and early surgical approach, even at the expense of mutilation. We report a case of rhino-orbital mucormycosis in a child with myeloblastic leukemia and the successful treatment using the instill negative pressure wound therapy combined with reconstructive surgery in order to reduce mortality and to avoid disfigurement. KEY WORDS: Amphotericin B, Apex syndrome, Forehead flap, Instill NPWT, Myeloaplasia Mucormycosis.


Assuntos
Leucemia , Mucormicose , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Criança , Humanos , Leucemia/tratamento farmacológico , Mucormicose/complicações , Mucormicose/cirurgia
8.
Pan Afr Med J ; 39: 150, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34527166

RESUMO

Blastoid variant of mantle cell lymphoma (MCL) is an aggressive and incurable form of B-cell lymphoma. Various chemo-immunotherapy regimens have been used with a limited success. Autologous stem cell transplant (ASCT) is being increasingly recommended in first remission for patients with blastoid variant MCL. Here, we describe the case of a 45-year-old lady suffering from blastoid variant of MCL. Patient was administered R-CHOP and underwent autologous stem cell transplant (ASCT). Currently, patient is disease-free and is on a regular follow up for 26 months now. This is an extremely rare case documented in the Indian literature with a long survival post-transplant.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linfoma de Célula do Manto/diagnóstico , Transplante de Células-Tronco/métodos , Terapia Combinada , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Humanos , Leucemia/diagnóstico , Linfoma de Célula do Manto/terapia , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Rituximab/administração & dosagem , Transplante Autólogo , Resultado do Tratamento , Vincristina/administração & dosagem
10.
Hematology ; 26(1): 637-647, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34474663

RESUMO

OBJECTIVES: The objective of the current study was to investigate the relationship between changes in vital signs and intensive care unit (ICU) admission. Windsor Regional Hospital treats 15-20 new patients a year with acute leukemia. These patients are at increased risk of neutropenic fevers and admission to the ICU following induction chemotherapy. METHODS: Retrospective review examined the correlation between acute leukemia patient vitals and ICU admission. The analysis included 37 patients: 7 ICU versus 30 controls. Changes were compared to baseline over 24 hours prior to ICU admission or 5 days after the initiation of induction chemotherapy in the following vital signs: heart rate (HR), mean arterial pressure (MAP), temperature (T), respiratory rate (RR), and fraction of inspired oxygen (FiO2) required to maintain a stable oxygen saturation. RESULTS: RR and FiO2 demonstrated significant change over baseline leading up to ICU admission within the ICU group. T, HR and MAP did not demonstrate significant changes over time in either group. RR, FiO2 and HR were significantly higher in the ICU group at time zero compared with the control group. RR was recorded least frequently in the 24 hours leading up to ICU admission. DISCUSSION: Changes in RR and FiO2 predicted clinical deterioration requiring ICU admission in acute leukemia patients. This is consistent with the predominant reason for ICU admission which was respiratory failure. CONCLUSION: We present preliminary evidence to support enhanced monitoring of RR and FiO2 in acute leukemia patients following induction chemotherapy with early intervention if identified.


Assuntos
Unidades de Terapia Intensiva , Leucemia , Admissão do Paciente , Sinais Vitais , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Leucemia/metabolismo , Leucemia/fisiopatologia , Leucemia/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
11.
Gene ; 804: 145903, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34411647

RESUMO

Traditional methods to understand leukemia stem cell (LSC)'s biological characteristics include constructing LSC-like cells and mouse models by transgenic or knock-in methods. However, there are some potential pitfalls in using this method, such as retroviral insertion mutagenesis, non-physiological level gene expression, non-physiological expansion, and difficulty to construct. The mRNAsi index for each sample of the Cancer Genome Atlas (TCGA) could avoid these potential pitfalls by machine learning. In this work, we aimed to construct a network of LSC genes utilizing the mRNAsi. First, mRNAsi value was analyzed with expressions distributions, survival analysis, age, and gender in acute myeloid leukemia (AML) samples. Then, we used the weighted gene co-expression network analysis (WGCNA) to construct modules of stemness genes. The correlation of the LSC genes transcription and interplay among LSC proteins was analyzed. We performed functional and pathway enrichment analysis to annotate stemness genes. Survival analysis further identified prognostic biomarkers by clinical data of TCGA and the Gene Expression Omnibus (GEO) database. We found that the result of mRNAsi overall survival is not significant, which may be due to the heterogeneity of AML in the stage of myeloid differentiation, French-American-British (FAB) classification systems. Enrichment analysis indicated that the stemness genes were biologically clustered as a group and mainly associated with cell cycle and mitosis. Moreover, 10 key genes (SNRNP40, RFC4, RFC5, CDC6, HSPE1, PA2G4, SNAP23P, DARS2, MIS18A, and HPRT1) were screened by survival analysis with the data from TCGA and GEO. Among them, RFC4 and RFC5 were the distinguished biomarkers for their double-validated prognostic value in both databases. Additionally, the expression of RFC4 and RFC5 had the same trend as mRNAsi score in FAB subtypes. In conclusion, our result demonstrated that mRNAsi based LSC-related genes were found to have strong interactions as a cluster. These genes, especially RFC4 and RFC5, could be the therapeutic targets for inhibiting the stemness characteristics of AML. This work is also a comprehensive pipeline for future cancer stem cell studies.


Assuntos
Leucemia/metabolismo , Leucemia/patologia , Aprendizado de Máquina , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Adulto , Biomarcadores Tumorais/genética , Bases de Dados Genéticas , Feminino , Redes Reguladoras de Genes , Humanos , Leucemia/genética , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Masculino , Prognóstico , RNA Mensageiro/genética , Proteínas de Ligação a RNA/genética , Transcriptoma
12.
Biomolecules ; 11(8)2021 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-34439817

RESUMO

Epstein-Barr virus (EBV) and cytomegalovirus (CMV) are viruses globally distributed that have been associated with the development and prognosis of many pathologies, including hematological diseases. This study aimed to characterize the epidemiological profile of EBV infection and the infection-correlated hepatic manifestations in patients with hematological diseases of the northern Brazilian state of Amazonas. A total of 228 patients were serologically tested for the presence of anti-EBV and anti-CMV IgG antibodies through an enzyme-linked immunosorbent assay. The coinfection with CMV, sociodemographic and laboratory records of all patients were also assessed. The overall prevalence observed among the study population for EBV infection and EBV/CMV coinfection was 85.09% (95% CI: 0.80-0.90) and 78.51% (95% CI: 0.73-0.84), respectively. The age group 31-40 years old were more susceptible to EBV/CMV coinfection (95% CI: 1.59-93.41, p = 0.011), while young people aged 1-10 years old were less affected for both EBV infection (CI 95%; 0.66-0.91, p = 0.001) and EBV/CMV coinfection (95% CI: 0.52-0.81, p < 0.0001). High serum levels of the liver biomarker ferritin were associated with EBV infection (95% CI: 1.03-1.54, p = 0.031) and EBV/CMV coinfection (95% CI: 1.02-1.70, p = 0.038). Our findings indicated that the elevated prevalence of EBV infection is not associated with the hematological diseases or transfusion rates, but with the socioeconomic status of the study population. Also, this study suggests that the EBV infection and its coinfection with CMV are related to the increase of serum ferritin levels.


Assuntos
Anemia/epidemiologia , Anticorpos Antivirais/sangue , Infecções por Citomegalovirus/epidemiologia , Infecções por Vírus Epstein-Barr/epidemiologia , Ferritinas/sangue , Leucemia/epidemiologia , Linfoma/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia/imunologia , Anemia/patologia , Anemia/virologia , Biomarcadores/sangue , Transfusão de Sangue/estatística & dados numéricos , Brasil/epidemiologia , Criança , Pré-Escolar , Coinfecção , Citomegalovirus/crescimento & desenvolvimento , Citomegalovirus/patogenicidade , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/patologia , Infecções por Citomegalovirus/virologia , Infecções por Vírus Epstein-Barr/imunologia , Infecções por Vírus Epstein-Barr/patologia , Infecções por Vírus Epstein-Barr/virologia , Feminino , Herpesvirus Humano 4/crescimento & desenvolvimento , Herpesvirus Humano 4/patogenicidade , Humanos , Imunoglobulina G/sangue , Lactente , Recém-Nascido , Leucemia/imunologia , Leucemia/patologia , Leucemia/virologia , Fígado/imunologia , Fígado/patologia , Fígado/virologia , Linfoma/imunologia , Linfoma/patologia , Linfoma/virologia , Masculino , Pessoa de Meia-Idade , Prevalência , Classe Social
13.
Int J Mol Sci ; 22(16)2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34445701

RESUMO

Chimeric antigen receptor (CAR) T-cells (CAR T-cells) are a promising therapeutic approach in treating hematological malignancies. CAR T-cells represent engineered autologous T-cells, expressing a synthetic CAR, targeting tumor-associated antigens (TAAs) independent of major histocompatibility complex (MHC) presentation. The most common target is CD19 on B-cells, predominantly used for the treatment of lymphoma and acute lymphocytic leukemia (ALL), leading to approval of five different CAR T-cell therapies for clinical application. Despite encouraging clinical results, treatment of other hematological malignancies such as acute myeloid leukemia (AML) remains difficult. In this review, we focus especially on CAR T-cell application in different hematological malignancies as well as strategies for overcoming CAR T-cell dysfunction and increasing their efficacy.


Assuntos
Neoplasias Hematológicas/terapia , Imunoterapia Adotiva/métodos , Imunoterapia Adotiva/tendências , Antígenos de Neoplasias/imunologia , Neoplasias Hematológicas/metabolismo , Neoplasias Hematológicas/patologia , Humanos , Imunoterapia/métodos , Leucemia/imunologia , Leucemia/terapia , Linfoma/imunologia , Linfoma/terapia , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos Quiméricos/imunologia , Linfócitos T/imunologia
15.
Elife ; 102021 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-34431785

RESUMO

Leukemic oncoproteins cause uncontrolled self-renewal of hematopoietic progenitors by aberrant gene activation, eventually causing leukemia. However, the molecular mechanism underlying aberrant gene activation remains elusive. Here, we showed that leukemic MLL fusion proteins associate with the HBO1 histone acetyltransferase (HAT) complex through their trithorax homology domain 2 (THD2) in various human cell lines. MLL proteins associated with the HBO1 complex through multiple contacts mediated mainly by the ING4/5 and PHF16 subunits in a chromatin-bound context where histone H3 lysine 4 tri-methylation marks were present. Of the many MLL fusions, MLL-ELL particularly depended on the THD2-mediated association with the HBO1 complex for leukemic transformation. The C-terminal portion of ELL provided a binding platform for multiple factors including AF4, EAF1, and p53. MLL-ELL activated gene expression in murine hematopoietic progenitors by loading an AF4/ENL/P-TEFb (AEP) complex onto the target promoters wherein the HBO1 complex promoted the association with AEP complex over EAF1 and p53. Moreover, the NUP98-HBO1 fusion protein exerted its oncogenic properties via interaction with MLL but not its intrinsic HAT activity. Thus, the interaction between the HBO1 complex and MLL is an important nexus in leukemic transformation, which may serve as a therapeutic target for drug development.


Assuntos
Carcinogênese/genética , Histona Acetiltransferases/genética , Histona-Lisina N-Metiltransferase/genética , Leucemia/genética , Proteína de Leucina Linfoide-Mieloide/genética , Animais , Transformação Celular Neoplásica , Feminino , Células HEK293 , Histona Acetiltransferases/metabolismo , Histona-Lisina N-Metiltransferase/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Proteína de Leucina Linfoide-Mieloide/metabolismo
16.
J Vis Exp ; (174)2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-34398156

RESUMO

Tumor-associated macrophages (TAM) can switch their expression and cytokine profile according to external stimuli. This remarkable plasticity enables TAM to adapt to ongoing changes within the tumor microenvironment. Macrophages can have either primarily pro-inflammatory (M1-like) or anti-inflammatory (M2-like) attributes and can continually switch between these two main states. M2-like macrophages within the tumor environment are associated with cancer progression and poor prognosis in several types of cancer. Many different methods for inducing differentiation and polarization of THP-1 cells are used to investigate cellular and intercellular mechanisms and the effects of TAM within the microenvironment of tumors. Currently, there is no established model for M2-like macrophage polarization using the THP-1 cell line, and the results of expression and cytokine profiles of macrophages due to certain in vitro stimuli vary between studies. This protocol serves as detailed guidance to differentiate THP-1 monocyte-like cells into M0 macrophages and to further polarize cells into an M2-like phenotype within 14 days. We demonstrate the morphological changes of THP-1 monocyte-like cells, differentiated macrophages, and polarized M2-like macrophages using light microscopy. This model is the basis for cell line models investigating the anti-inflammatory effects of TAM and their interactions with other cell populations of the tumor microenvironment.


Assuntos
Leucemia , Monócitos , Diferenciação Celular , Linhagem Celular Tumoral , Humanos , Macrófagos , Fenótipo , Células THP-1 , Microambiente Tumoral
17.
Cancer Radiother ; 25(6-7): 603-606, 2021 Oct.
Artigo em Francês | MEDLINE | ID: mdl-34462212

RESUMO

The management of myeloid and lymphoid disease is essentially based on chemotherapy and targeted therapies. Since radiotherapy could be responsible for severe late toxicities, essentially due to conventional bidimensional irradiation techniques, many trials have attempted to omit radiotherapy or to scale down the dose in their therapeutic strategy. Nevertheless, radiotherapy still plays a role for curative or symptomatic purposes.


Assuntos
Leucemia/radioterapia , Linfoma/radioterapia , Neoplasias Cutâneas/radioterapia , Doença Aguda , Doença de Hodgkin/patologia , Doença de Hodgkin/radioterapia , Humanos , Leucemia/patologia , Linfoma não Hodgkin/patologia , Linfoma não Hodgkin/radioterapia , Mieloma Múltiplo/radioterapia , Plasmocitoma/radioterapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/radioterapia , Sarcoma/radioterapia , Neoplasias Cutâneas/patologia
18.
Ann Palliat Med ; 10(7): 7872-7883, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34353075

RESUMO

BACKGROUND: meta-analysis was performed to study the therapeutic effect of hematopoietic stem cell transplantation combined with killer cells (important immune cells of the body) on leukemia, hoping to enhance the postoperative therapeutic efficiency. METHODS: literatures were searched with "Hematopoietic stem cell transplantation", "killer cell", "leukemia", "Cytokine induction", etc. as search terms using Boolean logic search. Review Manager was utilized for meta-analysis after literature screening. RESULTS: eleven literatures were included, most of which were of low-risk bias (medium-high quality). Through meta-analysis, statistical heterogeneity was found in non-recurring mortality (NRM) between control group and experimental group (Chi2 =15.69, I2=62%, P=0.02). The leukemia-free survival rate between two groups was not heterogeneous (Chi2 =13.16, I2=32%, P=0.16), without considerable difference between groups (Z=1.52, P=0.13). The incidence of graft-versus-host disease (GvHD) between the two groups was statistically heterogeneous (Chi2 =21.38, I2=67%, P=0.003). The incidence of graft-versus-host disease in experimental group was greatly inferior to controls (Z=3.87, P=0.0001). DISCUSSION: hematopoietic stem cell transplantation combined with killer cells can effectively reduce the incidence of GvHD after stem cell transplantation in patients. The prognosis of transplantation was good, and it had no obvious effect on the overall survival rate and recurrence rate.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia , Células-Tronco Hematopoéticas , Humanos , Incidência , Leucemia/terapia
19.
Rinsho Ketsueki ; 62(7): 733-738, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34349056

RESUMO

Despite the challenges involved in studying the epidemiology of a rare disease, the last two decades have provided considerable information regarding the probable causes of childhood leukemia, in which current evidence suggests an important role for genetic susceptibility and external factors originating from the environment. The genome-wide association study approach has led to the identification of several associated genes, thereby confirming the polygenic nature of childhood leukemia. Ongoing studies have shown that many of these loci, which were originally identified in populations of European ancestry, are also important in the Japanese population. Regarding potential external exposures, increasing evidence is becoming available to elucidate the role of infectious agents and the influence of immune maturation in early life. Epidemiological evidence supports the prevailing hypotheses related to the effect of population mixing on transient increases in the childhood leukemia rates, as well as the role of delayed exposures to common infections in propagating an aberrant immune response and subsequent leukemia risk. Future advances in the investigation of childhood leukemia and other rare diseases along with coordinated studies and collaborations are needed, owing to stringent sample size requirements to support statistically robust comparisons and opportunities for independent validation.


Assuntos
Estudo de Associação Genômica Ampla , Leucemia , Biometria , Predisposição Genética para Doença , Humanos , Leucemia/epidemiologia
20.
Rinsho Ketsueki ; 62(7): 739-743, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34349057

RESUMO

Recent studies have revealed that the gut microbiota play a critical role in the regulation of hematopoiesis at multiple stages. Accumulated evidence of the relationship between the clinical outcome of allogeneic hematopoietic stem cell transplantation and diversity of the microbiota demonstrates the importance of the microbiota in the physiological and pathological regulation of hematopoiesis. In addition, recent studies have shown that aberrant diet-related changes in the microbiota may cause abnormal hematopoiesis and contribute to the progression of myeloproliferative neoplasm in combination with RAS-MAPK activation. Ten-eleven translocation 2 (Tet2) mutation in myeloid cells causes dysfunction of the small-intestinal barrier, which leads to induction of preleukemic myeloproliferation. Proliferation of leukemia cells is associated with reduced insulin secretion and enhancement of insulin resistance, partly due to microbiota-derived metabolites. Thus, the microbiota affects normal and malignant hematopoiesis mediated by multiple factors. Further analyses may contribute to the identification of critical environmental factors, which may lead to the discovery of novel diagnostic and therapeutic strategies for hematopoietic neoplasms.


Assuntos
Microbioma Gastrointestinal , Transplante de Células-Tronco Hematopoéticas , Leucemia , Hematopoese , Homeostase , Humanos
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