Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 19 de 19
Filtrar
Mais filtros










Base de dados
Tipo de estudo
Intervalo de ano de publicação
1.
Leuk Lymphoma ; : 1-6, 2020 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-32476519

RESUMO

In order to explore the prognostic value of CD2, CD4, and human leucocyte antigen-DR (HLA-DR) expression and Fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutation in leukemia cells in the bone marrow of patients with acute promyelocytic leukemia (APL), we retrospectively collected and analyzed the immunophenotype, molecular features and clinical characteristics of 219 newly diagnosed adult patients with APL in Henan Provincial People's Hospital from January 2010 to December 2019. It turned out that the relapse rates of patients with CD2, CD4, or HLA-DR expression and the early mortality rates of patients with CD2 expression, HLA-DR expression, or FLT3-ITD mutation were higher than those of their counterparts. Moreover, reduced overall survival was found for patients who showed CD2 expression, HLA-DR expression or FLT3-ITD mutation. Therefore, CD2 expression, HLA-DR expression and FLT3-ITD mutation were adverse prognostic factors in adults with APL.

2.
Clin Lymphoma Myeloma Leuk ; 20(7): e382-e391, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32336675

RESUMO

INTRODUCTION: The purpose of this study was to explore the outcomes of all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) plus idarubicin (IDA) as a frontline treatment in adult patients with acute promyelocytic leukemia (APL). PATIENTS AND METHODS: We analyzed the outcomes of ATRA and intravenous ATO plus IDA as a frontline induction therapy in 118 patients with APL with high-risk (HR) and standard-risk (SR) disease from January 2008 to December 2017. The medical records of 118 patients with APL (HR, n = 45; SR, n = 73) who received the frontline triple combination regimen at Henan Provincial People's Hospital and Tongji Hospital were retrospectively reviewed. Consolidation therapy comprised 6 cycles of ATO and ATRA plus IDA, and IDA was administered in 1 to 4 cycles of consolidation therapy based on the comparable clinical efficacy compared with 6 cycles and fewer side effects to myocardium without subsequent maintenance therapy. RESULTS: Of 118 patients, there were 3 (2.5%) early deaths and 115 (97.5%) hematologic complete remissions; 102 (88.7%) of 115 patients achieved molecular complete remission following induction therapy, and all patients were polymerase chain reaction-negative for promyelocytic leukemia-retinoic acid receptor alpha after the first cycle of consolidation therapy. The 5-year overall survival (OS) and event-free survival (EFS) were 93.0% ± 2.9% and 92.4% ± 3.0%, respectively. Early death, hematologic complete remissions, molecular complete remissions, and toxicities were comparable between the HR and SR groups. The cumulative incidence of relapse in the HR group was 4.7% (n = 2), and the cumulative incidence of relapse in the SR group was 0. The OS and EFS of the SR and HR groups were comparable (92.3% ± 4.5% vs. 92.8% ± 4.0%; X2 = 0.263; P = .608; 92.3% ± 4.5% vs. 91.1% ± 4.2%, X2 = 0.917; P = .338). The total dosage of IDA was approximately 181 to 258 mg, and no patient experienced cardiotoxicity. OS and EFS were not influenced by fms-related tyrosine kinase 3 internal tandem duplication mutation status (P = .405 and P = .528, respectively). CONCLUSION: The triple combination of ATRA and ATO plus IDA as both an induction and consolidation therapy for the HR and SR groups attained excellent outcomes, and this regimen was effective, safe, and easy, without maintenance therapy. The triple combination treatment might be a preferred frontline therapy for patients with APL, especially for those with HR or the APL fms-related tyrosine kinase 3 internal tandem duplication mutation.

3.
Cancer Cell ; 37(3): 403-419.e6, 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32183952

RESUMO

Natural killer/T cell lymphoma (NKTCL) is an aggressive and heterogeneous entity of non-Hodgkin lymphoma, strongly associated with Epstein-Barr virus (EBV) infection. To identify molecular subtypes of NKTCL based on genomic structural alterations and EBV sequences, we performed multi-omics study on 128 biopsy samples of newly diagnosed NKTCL and defined three prominent subtypes, which differ significantly in cell of origin, EBV gene expression, transcriptional signatures, and responses to asparaginase-based regimens and targeted therapy. Our findings thus identify molecular networks of EBV-associated pathogenesis and suggest potential clinical strategies on NKTCL.

4.
Leuk Lymphoma ; 61(1): 128-137, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31530212

RESUMO

Myeloid-derived suppressor cells (MDSCs) are considered to be a strong contributor to the immunosuppressive tumor microenvironment. In our study, the counts of MDSCs were correlated with the remission status of CML patients, especially the M-MDSCs. M-MDSCs promoted the proliferation of K562 cells or CD34+ cells from newly diagnosed CML patients, no matter in cells or mice experiments. We also established a TKI discontinuation model using the K562 cell line for examining the effect of microvesicles (MVs) derived from K562 cells before and after TKI discontinuation on MDSCs. We found a mutual promotion of proliferation of tumor cells and MDSCs. Moreover, MVs derived from K562 cells after TKI discontinuation significantly improved the proliferation of MDSCs compared with MVs from before TKI discontinuation. The bidirectional interaction results in a vicious cycle, by providing a protective niche against immune attacks. Therapeutic interventions modulating this interaction might accelerate the success of TFR.

5.
J Cell Physiol ; 235(4): 3790-3797, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31613009

RESUMO

Acute myelocytic leukemia (AML) is an aggressive malignant tumor and typically fatal without treatment. Identification and development of novel biomarkers could be beneficial for the diagnosis and prognosis of AML patients. Here, we aimed to identify the accurate DNA methylation prognostic signatures for AML patients. The DNA methylation data of AML patients and corresponding clinical information were retrieved from The Cancer Genome Atlas database. CPG sites that correlates closely with the survival of the AML patients were identified and further combined into CPG sites pairs to screen the survival-related pairs. The prognostic signatures were identified by the C-index and forward search algorithms and validated by the verification group. Finally, the functional enrichment analysis was performed on these CPG sites. As a result, a total of 498 CPG sites associated with the overall survival of AML patients was obtained. A prognostic signature composed of 10 CPG sites pairs was obtained and validated. The functional enrichment analysis showed prognostic genes were mainly enriched in tumor protein processing, cell differentiation, blood leukocyte immunity, and platelet growth factor pathways. In summary, we identified two accurate prognostic methylation signatures (NDRG2 and TLR7), which would be served as a novel therapy target for AML.

6.
Int J Oncol ; 56(1): 7-17, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31789408

RESUMO

Although the majority of patients with follicular lymphoma (FL) harbor the t(14;18)(q32;q21) IGH/BCL2 gene rearrangement that leads to the overexpression of BCL2 protein, approximately 20% of FL cases lack t(14;18)(q32;q21). It is considered that BCL2 overexpression underscores the development of the majority of cases of FL and their transformation to more aggressive lymphoma [known as transformed FL (tFL)]. However, FL cases lacking the t(14;18)(q32;q21) translocation exhibit symptoms analogous to their t(14;18)­positive counterparts. An important goal of recent research on FL has been to clarify the distinctions between the two different forms of FL. Numerous studies have shed light onto the genetic and molecular features of t(14;18)­negative FL and the related clinical manifestations. In this review, we summarize the current knowledge of t(14;18)­negative FL occurring in the lymph nodes with an emphasis on the underlying molecular and clinical features. In addition, novel treatment directions are discussed.

7.
Cell Cycle ; 18(14): 1660-1669, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31204563

RESUMO

Background: Nowadays, microRNAs (miRNAs) attract much attention in regulating anticancer drug resistance in cancers including multiple myeloma (MM). Bortezomib is the first-line choice in MM treatment, and bortezomib resistance caused by aberrant DNA repair leads to the recurrence and therapeutic failure of MM. Objective: Our study aims to identify a miRNA that overcomes bortezomib resistance in MM. Methods: We established bortezomib-resistant MM cell lines, and screened several miRNAs that have aberrant expressions in MM cell lines. The expression of DNA-repair-related proteins were assessed by western blot, and cell viability was determined by the MTT assay in bortezomib-resistant cell lines. The binding between miRNAs and 3'-UTR of APE1 mRNA was confirmed by luciferase reporter assay. The mouse bortezomib-resistant xenograft was established to verify the therapeutic effect of miRNA overexpression. Results: miR-520g and miR-520h were significantly downregulated in bortezomib-resistant MM cell lines, and overexpression of miR-520g and miR-520h together inhibited expression of homologous recombination-related protein Rad51 and cell viability of bortezomib-resistant MM cells in vitro by binding with 3'-UTR of APE1 mRNA. Combined overexpression of miR-520g and miR-520h inhibited bortezomib-resistant MM tumor growth in vivo. Conclusion: Our findings demonstrated that combined overexpression of miR-520g and miR-520h overcomes bortezomib resistance in MM through inhibition of DNA repair, offering a promising therapeutic target for MM treatment.

8.
Biol Blood Marrow Transplant ; 25(5): 975-980, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30658223

RESUMO

We compared the outcomes of immunosuppressive therapy (IST) with those of T cell-replete haploidentical donor hematopoietic stem cell transplantation (haplo-HSCT) in children and adolescents with severe aplastic anemia (SAA). The medical records of 49 patients with SAA who received frontline IST (n = 29) or frontline haplo-HSCT (n = 20) between 2012 and 2016 were analyzed retrospectively. Fourteen patients responded after the first IST, and 1 patient responded after the second IST in the frontline IST group; 12 patients underwent salvage HSCT after IST failure. Sixteen of the 20 patients who underwent frontline haplo-HSCT survived without treatment failure. The 3-year overall survival of the frontline IST group was comparable to that of the frontline haplo-HSCT group (79.3 ± 7.5% versus 85.0 ± 8.0%; χ2 = 0.110; P = .740). The 3-year failure-free survival was lower in the frontline IST group compared with the frontline haplo-HSCT group (35.9 ± 10.9% versus 80.0 ± 8.9%; χ2 = 4.089; P = .043). Five patients of the IST group who underwent salvage HSCT achieved long survival without event. The event-free survival was lower in the salvage HSCT group compared with the haplo-HSCT group (41.7 ± 14.2% versus 80.0 ± 8.9%; χ2 = 3.992; P = .046), and the incidences of acute GVHD, grade II-IV acute GVHD, chronic GVHD, and severe infection were comparable between the 2 groups. Our results suggest that frontline haplo-HSCT may be a better treatment than IST for children and adolescents with SAA who lack an HLA age-matched familial donor.


Assuntos
Anemia Aplástica/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Imunossupressão/métodos , Terapia de Salvação/métodos , Transplante Haploidêntico/métodos , Adolescente , Anemia Aplástica/mortalidade , Criança , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Imunossupressão/mortalidade , Estudos Retrospectivos , Análise de Sobrevida , Transplante Haploidêntico/mortalidade , Transplante Haploidêntico/normas , Resultado do Tratamento
9.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 26(3): 784-788, 2018 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-29950220

RESUMO

OBJECTIVE: To analyze the factors affecting survival and prognosis of patients with high-risk refractory lymphoma treated with autologous peripheral blood hematopoietic stem cell transplantation (auto-PBHSCT). METHODS: A total of 96 cases of high-risk refractory lymphoma received auto-PBHSCT were selected. The total survival rate after the treatment was analyzed by using Kaplan-Meier curve and long rank test, and the prognosis-related factors were analyzed by univariate analysis and COX regression analysis. RESULTS: The median survival time of 96 patients was 30.67 months, and the overall survival rate of 3 and 5 years after treatment was 81.25% and 71.88% respectively. Univariate analysis showed that the patients with high lactate dehydrogenase(LDH) level (>245 U/L), 3-5 scores of international prognostic index(IPI), hepatitis B virus (HBV) infection, high expression of Ki-67 (≥65%) and bone marrow infiltration had lower survival rate (P<0.05). COX regression analysis showed that the complete remission wasn't reached before auto-PBHSCT and the consolidation therapy was not carried out after auto-PBHSCT, both of them were the risk factors affecting the prognosis (OR=0.46, 0.12, 95% CI: 0.22-0.95, 0.02-0.82, P<0.05). CONCLUSION: Auto-PBHSCT in the treatment of patients with high-risk refractory lymphoma can significantly improve the survival status and prognosis, and the consolidotion therapy should be performed after auto-PBHSCT so as to further improve the long-term survival rate and prolong the survival time.


Assuntos
Linfoma , Protocolos de Quimioterapia Combinada Antineoplásica , Transplante de Células-Tronco Hematopoéticas , Humanos , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Transplante Autólogo , Resultado do Tratamento
10.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 26(3): 854-858, 2018 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-29950232

RESUMO

OBJECTIVE: To investigate the effect of ATO on the proportion of Treg in the peripheral blood of patients with severe aplastic anemia (SAA) in vitro. METHODS: The peripheral blood of 20 newlydiagnosed patients were collected, and the peripheral blood monomuclear cells (PBMNC) were extracted. After the PBMNC were treated with ATO of different concentrotions (0, 1, 2.5 and 5 µmol/L) for 96 hours, the proportion of CD44+ CD25+CD127low regulatatory T cells (Treg) were detected by flow cytometry. The expression levels of Foxp3 mRNA were detected by RT-PCR, and the levels of IFN-γ,IL-4,IL-17 and TGF-ß1 were detected by ELTSA to verify the results of flow cytomery. RESULTS: ATO significantly increased the proportion of Treg (P<0.01) at the concentration of 2.5 and 5 µmol/L, and the rising degree of Treg proportion improved with the increasing ATO concentration(r= 0.524). Treg proportion increased at a concentration of 1 µmol/L, but without statistical significance (P>0.05). At 1(P<0.05), 2.5(P<0.01) and 5 µmol/L(P<0.01), ATO significantly up-regulated the expression of Foxp3 mRNA, and the increase of Foxp3 mRNA positively and linearly correlated with the increase of Treg cell-frequency(r=0.523). ATO significantly reduced the levels of IFN-γ (at ATO 1,2.5 and 5 µmol/L, P<0.01), IL-4 (at ATO 2.5 µmol/L, P<0.01; at ATO 5 µmol/L, P<0.01) and IL-17(at ATO 2.5 µmol/L, P<0.05; at ATO 5 µmol/L, P<0.01). ATO had no significant effect on TGF-ß1 at 1(P>0.05) and 2.5 µmol/L (P>0.05), but significantly reduced TGF-ß1 level at 5 µmol/L (P<0.05). CONCLUSION: ATO can mediate the immune regulation through up-regulating the proportion of Treg in peripheral blood of patients with SAA and reducing the levels of IFN-γ, IL-4 and IL-17.


Assuntos
Arsenicais , Óxidos , Anemia Aplástica , Trióxido de Arsênio , Fatores de Transcrição Forkhead , Humanos , RNA Mensageiro , Linfócitos T Reguladores
11.
Oncoimmunology ; 7(7): e1448330, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29900066

RESUMO

T cell function in cancer patients is usually impaired due to the constitutive activation of immune checkpoint inhibitors. This state is known as 'exhaustion' and is often associated with the inefficient control of tumors or persistent infections. In this work, we investigated the role of leukemia cell-derived microvesicles (MVs) in T cell exhaustion. Following incubation with MVs from various sources, all T cell subtypes exhibited the exhaustion phonotype and impaired cytokine secretion in vitro. Mice models also showed the connection between immune checkpoint inhibitors and MV injection. Sequencing and bioinformatics analyses indicated that a number of transcription factors and microRNAs (miRNAs) were attributable to the dysregulation of pathways and exhaustion in T cells. Further work revealed that functional miR-92a-3p, miR-21-5p, miR-16-5p, miR-126 and miR-182-5p in MVs could be delivered into T cells to induce the exhaustion phenotype. SerpinB2, IL-1ß and CXCL5, which are mediators of the NF-κB pathway, were identified as the targets of the miRNAs mentioned above. We demonstrated that leukemia-derived MVs could initiate T cell exhaustion via the progressive temporal delivery of multiple exogenous miRNAs into T cells and the subsequent interaction of these miRNAs with their targets. Therefore, MVs can be expected not only to become new indicators of the T cell status in patients but also to be used as novel targets for personalized patient treatment.

12.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 26(2): 470-476, 2018 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-29665918

RESUMO

OBJECTIVE: To explore the anti-myeloma effect of suberoylanilide hydroxamic acid (SAHA) and on mouse myeloma cell line SP2/0 in vitro and in vivo and its mechanism. METHODS: The inhibitory effect of SAHA on SP2/0 cells was measured by CCK-8 assay,and the apoptosis and cell cycle were analyzed by flow cytometry FACS. The protein expression of Caspase-3 and p53 of SP2/0 cells treated with SAHA were examined by Western blot. Annexin V/7-AAD double staining was performed to detect the apoptosis of SP2/0 induced by SAHA in vitro. SP2/0 cells (1×106) resuspended in 200 µl PBS were inoculated subcutaneously and intravenously into BALB/c mice, so as to establish aggressive or non-aggressive myeloma-bearing mouse models respectively. On day 3 after modeling, mice received SAHA or vehicle control treatment by intraperitoneal injection. The dose of SAHA was 60 mg/kg·d, 5 times a week for 3 weeks. RESULTS: In SAHA-treated SP2/0 cells, the proliferation inhibition rate and apoptotic cells increased in a dose dependent manner. Also, SAHA significantly increased the ratio of cells in G2 phase and decreased in S phase. Molecular mechanisms of apoptosis and cell cycle arrest of SP2/0 induced by SAHA partly correlated with up-regulating the expression level of Caspase-3 and p53. In the non-aggressive myeloma-bearing mice, SP2/0 cells disappeared in peripheral blood after SAHA treatment. In the aggressive myeloma-bearing mice, inhibition of tumor growth and prolongation of the cell survival were observed after SAHA treatment. CONCLUSION: SAHA inhibited SP2/0 cell proliferation, this effect associates with inducing apoptosis and cell cycle arrest, the mechanism of SAHA ralates partly with activating Caspase-3 and p53 pathway.


Assuntos
Mieloma Múltiplo , Animais , Antineoplásicos , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Inibidores de Histona Desacetilases , Ácidos Hidroxâmicos , Camundongos , Camundongos Endogâmicos BALB C
14.
Anticancer Drugs ; 28(10): 1097-1105, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28885268

RESUMO

N1-guanyl-1,7-diaminoheptane (GC7), a deoxyhypusine synthase inhibitor, has been shown to exert antiproliferation effects in many solid tumors by regulating eukaryotic translation initiation factor 5a2 (eif5a-2). However, little is known about the role of GC7 and eif5a-2 in drug resistance in acute lymphoblastic leukemia (ALL). In the present study, we investigated the effect of GC7 on drug-resistant ALL and its potential mechanism. We found that using the CCK-8 assay that combined treatment with GC7 and vincristine (VCR) significantly inhibited the cell viability of two ALL cell lines. Using EdU incorporation assays and flow cytometry, we also showed that GC7 could markedly enhance the VCR sensitivity of ALL cells by suppressing cell proliferation and promoting apoptosis. Furthermore, we showed that GC7 could downregulate eif5a-2 and myeloid cell leukemia-1 (Mcl-1) expression. Knockdown of eif5a-2 inhibited the expression of Mcl-1 and significantly enhanced the VCR sensitivity. Moreover, eif5a-2 knockdown decreased the regulatory role of GC7 in increasing VCR sensitivity. Thus, our findings indicate that combined treatment with GC7 could enhance VCR sensitivity of ALL cells by regulating the eif5a-2/Mcl-1 axis. Together, our results highlight the potential clinical application of GC7 in VCR-based chemotherapy for the treatment of ALL.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Guanina/análogos & derivados , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Vincristina/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos , Sinergismo Farmacológico , Técnicas de Silenciamento de Genes , Guanina/administração & dosagem , Guanina/farmacologia , Humanos , Células Jurkat , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Fatores de Iniciação de Peptídeos/antagonistas & inibidores , Fatores de Iniciação de Peptídeos/genética , Fatores de Iniciação de Peptídeos/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Proteínas de Ligação a RNA/antagonistas & inibidores , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Vincristina/administração & dosagem
15.
Oncotarget ; 8(18): 30395-30409, 2017 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-28418922

RESUMO

DNA methyltransferase 3A (DNMT3A) mutations occurred in 18%~23% of acute myeloid leukemia (AML) patients, and were considered to be an adverse prognostic factor for adult de novo AML cases. However, the relevant molecular mechanism of the mutation in AML pathogenesis remains obscure. In this study, we established K562 and SKM1 cell model carrying the DNMT3A R882H mutation via transcription activator-like effector nuclease (TALEN) and Clustered regularly interspaced short palindromic repeats (CRISPR/Cas9) technology, and discovered that mutated DNMT3A could promote the proliferative capability of malignant cell clones. Further RNA microarray analysis revealed that some genes crucial for glutathione (GSH) synthesis, including CTH, PSPH, PSAT1 and especially SLC7A11 (the cysteine/glutamate transporter) were significantly up-regulated, which resulted in significant elevation of intracellular GSH levels. A subsequent experiment demonstrated that the mutant clones are resistant to chemotherapy as well as SLC7A11-inhibitorsBy shRNA induced SLC7A11 silencing, we discovered profoundly decreased cellular GSH and cell proliferative ability of DNMT3A mutated clones. Our results provided novel insight into the role of the DNMT3A R882H mutation in AML pathogenesis and suggested that targeting the cellular GSH synthetic pathway could enhance the current therapy for AML patients with the DNMT3A R882H mutation.


Assuntos
DNA (Citosina-5-)-Metiltransferases/genética , DNA (Citosina-5-)-Metiltransferases/metabolismo , Glutationa/metabolismo , Mutação , Nucleases dos Efetores Semelhantes a Ativadores de Transcrição/metabolismo , Alelos , Substituição de Aminoácidos , Sequência de Bases , Sistemas CRISPR-Cas , Proliferação de Células/genética , Sobrevivência Celular , Biologia Computacional/métodos , Análise Mutacional de DNA , Resistencia a Medicamentos Antineoplásicos , Perfilação da Expressão Gênica , Genótipo , Humanos , Células K562 , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Reprodutibilidade dos Testes , Transcriptoma
16.
Xenobiotica ; 47(12): 1121-1129, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27937048

RESUMO

1. Polymorphisms of cytochrome P450 2C19 (CYP2C19) is an important factor contributing to variability of voriconazole pharmacokinetics. Polymorphisms of CYP3A4, CYP3A5, CYP2C9 and non-genetic factors such as age, gender, body mass index (BMI), transaminase levels, concomitant medications might also affect voriconazole initial steady serum trough concentration (VICmin) in haematological patients, but the effects were not clear. 2. Eighteen single-nucleotide polymorphisms in CYP2C19, CYP3A4, CYP3A5, CYP2C9 were genotyped. Patients were stratified into two groups according to CYP2C19 genotype. Group 1 were patients with CYP2C19*2 or CYP2C19*3, and Group 2 were homozygous extensive metabolizers. The effects were studied in different groups. VICmin was adjusted on daily dose (VICmin/D) for overcoming effect of dose. 3. A total of 106 blood samples from 86 patients were included. In final optimal scaling regression models, polymorphisms of rs4646437 (CYP3A4), age, BMI was identified to be factors of VICmin/D in Group 1 (R2 = .255, p < .001). Only age was confirmed as a factor of VICmin/D in Group 2 (R2 = 0.144, p = .021). 4. Besides polymorphisms of CYP2C19, in individualized medication of voriconazole in haematological patients, polymorphisms of CYP3A4, and non-genetic factors as BMI, age should also be taken into account, especially for individuals with CYP2C19*2 or CYP2C19*3.


Assuntos
Antifúngicos/sangue , Citocromo P-450 CYP3A/genética , Voriconazol/sangue , Citocromo P-450 CYP2C19/genética , Humanos , Polimorfismo de Nucleotídeo Único
18.
Zhonghua Xue Ye Xue Za Zhi ; 34(1): 8-11, 2013 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-23597456

RESUMO

OBJECTIVE: To investigate the value of the HCT-CI score in chemotherapy risk assessment and prognosis of elderly patients with acute myeloid leukemia (AML). METHODS: The clinical data of 116 AML patients older than 60 years in the department of Hematology, Henan Provincial People's Hospital from January 2000 to December 2010 were analyzed retrospectively. All patients received cytarabine-based regimens, including protocol DA, MA, IA, AA or CAG, followed by cytarabine-based postremission treatment. (1) Comorbidities were evaluated by using HCT-CI score, the early death rates and median survival time were compared among these different groups. (2) These prognostic factors were analyzed by univariate and multivariate analyses. RESULTS: (1) All 116 cases were followed-up. The patient cohort was divided into those with HCT-CI scores of 0, 1 or 2, or ≥ 3. Early death rates were 3.7%, 12.1% and 23.21% in above three groups, respectively (P < 0.01). Overall survival were 345, 225 and 113 days, respectively (P < 0.01). (2) HCT-CI score ≥ 3 (P < 0.01), antecedent MDS history (P = 0.035), high-risk karyotype (P = 0.018), white blood cells at diagnosis ≥ 100×10(9)/L (P = 0.041) were independent adverse prognostic factors with multivariate analysis. CONCLUSION: (1) The HCT-CI score can objectively assess elderly AML patients with comorbidities and predict chemotherapy risk in older patients receiving AML induction therapy. (2) Antecedent MDS history, high-risk karyotype, high white blood cell, and HCT-CI score ≥ 3 are independent adverse prognostic factors of elderly AML patients.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia Mieloide Aguda/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Resultado do Tratamento
19.
Zhonghua Xue Ye Xue Za Zhi ; 33(8): 657-9, 2012 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-23134863

RESUMO

OBJECTIVE: To evaluate the diagnostic value and safety of percutaneous lung biopsy in hematologic patients with lung infection. METHODS: 28 cases hematologic patients received CT-guided percutaneous lung biopsy when they developed a fever associated with pulmonary nodules or lumps in CT scan whose clinical diagnosis were unclear during or after chemotherapy. Sample of each lesion were drawn twice. The lung tissue was re-scanned after lung biopsy to check up in order to discover bleeding and pneumothorax. Biopsy tissue was examined by bacteria culture, acid-fast staining and pathology. Pathological examination contained HE staining, acid-fast stain, PAS stain, TB-DNA, methenamine silver and others. RESULTS: 28 cases contain 24 males and 4 females. Median age was 40 15 - 77 years old. Blood tests were as follows: 3 cases with HGB > 110 g/L, 9 with HGB 90 - 110 g/L, 12 with HGB 60 - 89 g/L, 4 with HGB < 60 g/L. 8 with WBC > 10×10(9)/L, 6 with WBC (4 - 10)×10(9)/L, 13 with WBC < 4×10(9)/L, 1 with WBC < 2×10(9)/L; 14 with PLT > 100×10(9)/L, 5 with PLT (50 - 100)×10(9)/L, 5 with PLT < 50×10(9)/L, 4 with PLT < 30×10(9)/L. 4 cases had mild extended PT, 3 mild extended APTT, 3 FIB lower than normal. Lung CT scans were as follows: 4 cases with simply lesion in right lung, 4 with simply lesion in left lung, 20 with lesions in bilateral lung. 8 cases were diagnosed as fungal infection, 3 as tuberculosis infection, 1 as lung cancer, 1 as pulmonary infiltration of lymphoma, 1 as pulmonary infiltration of leukemia, and 14 as inflammatory changes with no specific diagnosis. 4 cases came with pneumothorax during lung biopsy, mild to moderate in 3 cases and severe in 1 case. Severe patient turned better after CT-guided suction. 3 cases with mild hemoptysis turned better after treatment. CONCLUSION: When hematopathy patients are with pulmonary nodules or lumps in CT scan whose clinical diagnosis is unclear, CT-guided percutaneous lung biopsy is safe and conducive to early diagnosis and conducive to early rehabilitation of patients if the coagulation function is basically normal and platelet count is not too low.


Assuntos
Biópsia , Doenças Hematológicas/patologia , Pulmão/patologia , Pneumonia/diagnóstico , Adolescente , Adulto , Idoso , Feminino , Doenças Hematológicas/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA