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1.
Leukemia ; 33(10): 2454-2465, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30953029

RESUMO

New prognostic factors are needed to establish indications for haematopoietic stem cell transplantation (HSCT) in first complete remission (CR1) for T-cell lymphoblastic lymphoma (T-LBL) patients. We used microarray to compare T-LBL tissue samples (n = 75) and fetal thymus tissues (n = 20), and identified 35 differentially expressed miRNAs. Using 107 subjects as the training group, we developed a five-miRNA-based classifier to predict patient survival with LASSO Cox regression: lower risk was associated with better prognosis (disease-free survival (DFS): hazard ratio (HR) 4.548, 95% CI 2.433-8.499, p < 0.001; overall survival (OS): HR 5.030, 95% CI 2.407-10.513, p < 0.001). This classifier displayed good performance in the internal testing set (n = 106) and the independent external set (n = 304). High risk was associated with more favorable response to HSCT (DFS: HR 1.675, 95% CI 1.127-2.488, p = 0.011; OS: HR 1.602, 95% CI 1.055-2.433, p = 0.027). When combined with ECOG-PS and/or NOTCH1/FBXW7 status, this classifier had even better prognostic performance in patients receiving HSCT (DFS: HR 2.088, 95% CI 1.290-3.379, p = 0.003; OS: HR 1.996, 95% CI 1.203-3.311, p = 0.007). The five-miRNA classifier may be a useful prognostic biomarker for T-LBL adults, and could identify subjects who could benefit from HSCT.

2.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 24(2): 399-404, 2016 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-27150999

RESUMO

OBJECTIVE: To explore the clinical efficacy and toxicity of CLAT protocol (cladribine, cytarabine and topotecan) for treating patients with refractory acute myeloid leukemia (R-AML). METHODS: A total of 18 patients with R-AML (median age 37 years, range 18 to 58 years; male n = 16, female n = 2) were treated with CLAT protocol, which consisted of cladribine 5 mg/m(2)/d, i.v. on days 1-5, cytarabine 1.5 g/m(2)/d, i.v. on days 1-5, topotecan 1.25 mg/m(2)/d, i.v. on days 1-5 and G-CSF 300 µg/d subcutaneous injection on day 6 until neutrophile granulocyte recovery. RESULTS: Out of 18 patients 2 died of severe infection before the assessment. Among 16 evaluated patients, 10 (55.6%) achieved complete remission (CR), and 2 (11.1%) achieved partial remission (PR), the overall response rate was 66.7%, the rest 4 patients did not respond (NR). The median overall survival time and DFS for the CR patients was 9.5 months (95%CI: 6.7-16.64) and 9.5 months (95%CI: 6.1-16.7) respectively. The 1 year OS and DFS rates were 45% and 46.9%, respectively. All patients developed grade 4 of granulocytopenia and thrombocytopenia, the median duration was 13 (range 2 to 21) days and 12 days (range 2 to 21), respectively, all patients developed infection, 2 patients died of severe infection. The most common non-hematological side effects included nausea, vomiting, diarrhoea, rash, aminotransferase or bilirubin elevation and were grade 1 to 2. CONCLUSION: The CLAT protocol seems to have promising for the treatment of refractory AML patients, and patients well tolerated. This CLAT protocol offers an alternative treatment for R-AML patients who received severe intensive treatment, especially with anthracycline-containing chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Adolescente , Adulto , Agranulocitose , Cladribina/uso terapêutico , Citarabina/uso terapêutico , Feminino , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Trombocitopenia , Topotecan/uso terapêutico , Adulto Jovem
3.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 21(4): 839-42, 2013 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-23998570

RESUMO

This study was aimed to investigate the c-kit mutation in acute myeloid leukemia (AML) patients with AML1-ETO and analyze its relation with clinical and laboratorial features and prognosis. PCR and sequencing methods were used to detect the c-kit 17 exon mutations in 31 AML patients with AML1-ETO. The relation of the c-kit mutation with clinical features, results of laboratorial examination and prognosis of disease were analyzed. The results showed that the c-kit mutation was found in 14 out of 31 AML patients and the mutation frequency was 45.16%. Male patients had a higher incidence of c-kit mutation than that of female patients (P = 0.020). The proportion of patients with newly diagnosed white blood cell>10×10(9)/L and with extramedullary infiltration in mutated group were higher than those in unmutated group respectively. No significant difference was observed at the age (P = 0.437) and the rate of bone marrow blasts(P = 0.510) between the above mentioned two groups. The difference in complete remission rate (64.29% vs 80%, P = 0.344)and relapse rate (58.33% vs 21.43%, P = 0.054) between c-kit mutated and c-kit unmutated groups were not significant. While the c-kit mutated group had a significant higher death rate as compared with c-kit unmutated group (57.14% vs 20%, P = 0.039). It is concluded that the c-kit mutation is frequent in AML patients with AML1-ETO and the c-kit mutated patients have a poor prognosis. It is important to detect c-kit mutation in routine clinical practice for patient's risk stratification, evaluation of prognosis and selection of effective treatment.


Assuntos
Subunidade alfa 2 de Fator de Ligação ao Core/genética , Leucemia Mieloide Aguda/genética , Proteínas de Fusão Oncogênica/genética , Proteínas Proto-Oncogênicas c-kit/genética , Adolescente , Adulto , Idoso , Análise Mutacional de DNA , Feminino , Humanos , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Proteína 1 Parceira de Translocação de RUNX1 , Resultado do Tratamento , Adulto Jovem
4.
Nan Fang Yi Ke Da Xue Xue Bao ; 31(5): 854-5, 2011 May.
Artigo em Chinês | MEDLINE | ID: mdl-21602141

RESUMO

OBJECTIVE: To investigate the expression of CD133 in the bone marrow of patients with myelodysplastic syndrome (MDS) and explore its clinical significance. METHODS: The expression of CD133 and CD34/CD38 in the bone marrow was detected using flow cytometry in 31 cases of refractory anemia with excess blasts (RAEB), 10 cases of refractory cytopenia with multilineage dysplasia (RCMD) and 11 cases of aplastic anemia (AA). RESULTS: The percentage of CD133-expressing cells was 6.75% in patients with RAEB, significantly higher than that in patients with RCMD (1.41%) and AA (2.70%) (P<0.05); the percentage of CD133-positive cells were similar between the latter two patient groups (P>0.05). The percentage of CD34(+)/CD38- cells was similar in the 3 groups (P>0.05), all lower than 1%. CONCLUSIONS: Advanced MDS patients are characterized by an increase of CD133-expressing cells, suggesting the value of CD133 in the diagnosis of RAEB. CD34(+)/CD38- cells do not show a significant value in the diagnosis of MDS.


Assuntos
Antígenos CD/metabolismo , Glicoproteínas/metabolismo , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/metabolismo , Peptídeos/metabolismo , Antígeno AC133 , Anemia Aplástica/metabolismo , Antígenos CD34/metabolismo , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade
5.
Zhonghua Xue Ye Xue Za Zhi ; 32(4): 254-8, 2011 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-21569709

RESUMO

OBJECTIVE: To analyze the promoter methylation levels of p15, CDH1, DAPK and HICI genes of patients with myelodysplastic syndrome (MDS) and explore the relationship between the level of methylation and clinical features. METHODS: DNA methylation levels of p15, CDH1, DAPK and HICI in peripheral blood (PB) or bone marrow (BM) samples from 52 MDS patients were detected by real-time quantitative PCR. The correlation of the methylation level with clinical features and hematological findings was analyzed. 38 de novo AML patients and 46 normal individuals served as controls. RESULTS: The methylation levels of p15, CDH1, DAPK and HICI were 16.23 ± 21.69, 6.59 ± 9.39, 0.14 ± 0.11 and 7.81 ± 9.70 in BM, and 14.96 ± 20.16, 6.00 ± 9.26, 0.12 ± 0.14 and 6.74 ± 9.72 in PB, respectively from 18 MDS patients, and the difference between BM and PB was not statistically significant (P > 0.05). The methylation levels of p15 (14.70 ± 18.17) and CDH1 (6.61 ± 8.79) genes in high risk (RAEBI/II) MDS were significantly higher than in low risk (RCMD/RARS/5q-, p15: 1.99 ± 1.59, CDH1: 1.23 ± 1.14 and RCMD, p15: 3.02 ± 3.42, CDH1:1.53 ± 2.06) MDS or control (p15: 1.69 ± 1.82, CDH1: 1.01 ± 1.12) (P < 0.05). The methylation levels of DAPK gene had no difference among subtypes of MDS, and that of HIC1 gene only differed between RAEB I/II (9.16 ± 11.95) and control (2.49 ± 2.26) (P = 0.042). The difference of methylation levels of p15, CDH1, DAPK and HICI in BM was statistically significant among subtypes of MDS (P = 0.001, 0.003, 0.039, 0.023, respectively). And so did of p15 and DAPK in PB (P = 0.013, 0.006, respectively). The methylation level of p15 and CDH1 was significantly correlated with IPSS classification and blasts percentage in BM. CONCLUSIONS: p15 and CDH1 genes are special hypermethylation genes in MDS. Methylation level of HIC1 gene showed an upward tendency from low risk to high risk MDS.


Assuntos
Metilação de DNA , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Caderinas/genética , Caderinas/metabolismo , Proteínas Quinases Dependentes de Cálcio-Calmodulina/genética , Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Estudos de Casos e Controles , Inibidor de Quinase Dependente de Ciclina p15/genética , Inibidor de Quinase Dependente de Ciclina p15/metabolismo , Proteínas Quinases Associadas com Morte Celular , Feminino , Humanos , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas , Reação em Cadeia da Polimerase em Tempo Real , Adulto Jovem
6.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 17(6): 1424-8, 2009 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-20030919

RESUMO

This study was aimed to investigate the aven mRNA expression level of leukocytes from peripheral blood(PB)of de novo patients with acute myeloid leukemia (AML) and analyze its clinical significance, so as to provide a experimental basis for evaluating prognosis. The aven mRNA expression levels in PB samples from 69 de novo AML patients were detected by using real-time quantitative PCR. The relation of aven mRNA level with clinical and hematological characteristics (age, sex, WBC, Hb, Plt, LDH, Blast% in PB and BM, FAB subtype) and treatment outcome (CR rate and relapse rate) were analyzed. 21 normal individuals served as controls. The results showed that the expression level of aven mRNA was between 11.72% and 178.93% (median 37.2%) in de novo AML and between 10.81% and 50.98% (median 28.81%) in normal individuals. Aven mRNA expression level was higher in the AML group than that in the controls (p = 0.006). As aven mRNA expression level was compared with other clinical and hematological parameters, there were significant correlations between aven mRNA expression level and age (r = 0.25, p = 0.039), and between hemoglobin level (r = 0.29, p = 0.019), FAB subtype(r = 0.253, p = 0.036). The median expression level (50.08%) of aven mRNA in older patients (> or = 44 years) was higher then that (32.41%) in younger patients (< 44 years) (p = 0.018). The complete remission (CR) rate after two cycles of chemotherapy in patients with lower aven mRNA level (25/30, 83.33%) was higher than that in patients with higher aven mRNA level(21/30, 70%), but the difference was not significant(p = 0.22). The difference of aven mRNA expression level between AML patients with relapse and AML patents without relapse was not significant (p = 0.076). It is concluded that the expression level of aven mRNA in de novo AML patients obviously increases, the overexpression of aven mRNA likely involves in genesis of AML. The definite relation of aven mRNA expression level with treatment outcome and relapse was not been found.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Reguladoras de Apoptose/genética , Leucemia Mieloide Aguda/genética , Proteínas de Membrana/genética , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , RNA Mensageiro/genética , Análise de Sequência , Resultado do Tratamento , Adulto Jovem
7.
Nan Fang Yi Ke Da Xue Xue Bao ; 29(9): 1799-801, 2009 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-19778794

RESUMO

OBJECTIVE: To screen the molecular markers for refractory anemia with excess blasts in transformation (RAEB) in myelodysplastic syndromes (MDS) by serum proteome profiling. METHODS: The serum protein were isolated from patients with RAEB, acute myeloid leukemia or normal subjects by 2-dimensional electrophoresis (2-DE), and the electrophoresis gels were obtained to identify the differentially reacting protein spots. The replica gels of the differentially reacting proteins were analyzed to locate the matching protein spots, which were identified by peptide mass fingerprint based on matrix-assisted laser desorption/ionization time of-flight mass spectrometry (MALDI-TOF-MS) and database searching. RESULTS: Seven differentially expressed proteins in RAEB were found by 2-DE. Of the 7 proteins, 4 were identified by MALDI-TOF-MS to have significantly differential expression in RAEB, including dipeptidyl peptidase (DPP/CD26), polymerase (DNA directed) kappa, PRO2044 and an albumin-like protein. CONCLUSION: 2-DE-based serum proteome profiling helps identify serum proteomic biomarkers related to MDS. DDP/CD26 has increased expression in the serum in RAEB subtype MDS, suggesting its possible role in advanced MDS.


Assuntos
Anemia Refratária com Excesso de Blastos/sangue , DNA Polimerase Dirigida por DNA/sangue , Dipeptidil Peptidases e Tripeptidil Peptidases/sangue , Síndromes Mielodisplásicas/sangue , Proteômica , Anemia Refratária com Excesso de Blastos/genética , Medula Óssea/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/classificação , Síndromes Mielodisplásicas/genética
8.
Ai Zheng ; 28(6): 619-25, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19635200

RESUMO

BACKGROUND AND OBJECTIVE: Chemotherapy regimen containing anthracyclines has been used as the standard treatment for acute myeloid leukemia (AML). This study was to compare the efficacy and toxicity of the chemotherapy regimen containing perarubicin (THP) with that containing mitoxantrone (MIT) for young patients with newly diagnosed AML. METHODS: A total of 129 patients with newly diagnosed AML, aged 16 to 60 years olds, were assigned for induction chemotherapy containing one to two courses with standard-dose cytarabine (Ara-C) and an anthracycline antibiotic, THP or MIT. When complete remission was achieved after induction therapy, the patients received two courses of consolidation therapy identical to the induction regimen. From then, the patients were alternately given four courses of consolidation therapy consisting of Ara-C/THP or Ara-C/MIT every three weeks. Maintenance treatment continued for three years when patients were in continuous complete remission (CCR). RESULTS: Twenty-six out of 42 patients (61.90%) receiving THP therapy, and 48 out of 73 patients (65.75%) treated by MIT achieved CR (P>0.05). Nine (34.61%) and 11 (22.92%) out of CR patients treated by THP and MIT, respectively, relapsed within one year (P=0.28). Moreover, the incidences of toxicities, such as infection, nausea/vomiting and cardiac events, were similar in these two groups (P>0.05) except for alopecie, which was 26.19% in the THP group compared to 42.47% in the MIT group (P<0.01). CONCLUSIONS: Regimen containing THP plus Ara-C can be used for young adults with newly diagnosed AML for remission induction, but it is not superior to the regimen with MIT. Consolidation chemotherapy with THP or MIT is feasible for young adults with AML after CR.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doxorrubicina/análogos & derivados , Leucemia Mieloide Aguda/tratamento farmacológico , Adolescente , Adulto , Agranulocitose/induzido quimicamente , Alopecia/induzido quimicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Citarabina/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Humanos , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Mitoxantrona/administração & dosagem , Náusea/induzido quimicamente , Recidiva , Indução de Remissão , Adulto Jovem
9.
Zhonghua Yi Xue Za Zhi ; 85(17): 1195-7, 2005 May 11.
Artigo em Chinês | MEDLINE | ID: mdl-16029595

RESUMO

OBJECTIVE: To evaluate the therapeutic effects of chemotherapeutic regimen containing pirarubicin (THP) on the treatment of high-risk or refractory and relapsed acute leukemia (AL) in adults. METHODS: Forty patients with high-risk or refractory and relapsed AL, 26 males and 14 females, aged 33 (14-63) received treatment regimens with THP: TA regimen [THP + cytosine-arabinoside (Ara-C)] for acute myeloid leukemia (AML) and TAOP regimen [THP + Ara-C + vincristine (VCR) + prednisone (Pred)] for acute lymphocytic leukemia (ALL) or biphenotype-AL. Forty matched patients received mitoxantron (MIT) + Ara-C for AML or MIT + Ara-C + VCR + Pred for ALL and biphenotype AL as controls. The therapeutic effects were observed. RESULTS: The complete remission (CR) rate was 47.5% vs 45% (P > 0.05), partial response (PR) rate was 25% vs 20% (P > 0.05), and overall response (OR) rate was 72.5% vs 65% (P > 0.05) in the treatment group and control group. The continuous CR time was 528 days in the treatment group, significantly longer than in the control group (463 days, P < 0.05). Marrow suppression was more serious in the treatment group. The patients in the treatment group had higher incidence of infections (P < 0.05). The time with sustained recovery of platelet number was 13.9 days in the treatment group, significantly longer than in the control group (P < 0.05). CONCLUSION: Regimens with THP are more effective on treatment of high-risk or refractory and relapsed AL in adults, however, with more serious marrow suppression and higher incidence of infection.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doxorrubicina/análogos & derivados , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Adulto , Citarabina/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Vincristina/administração & dosagem
10.
Ai Zheng ; 22(8): 852-5, 2003 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-12917034

RESUMO

BACKGROUND & OBJECTIVE: Cell proliferation and differentiation are directed by cell cycle mechanism. When tumor cells proliferate abnormally, cyclins, which are positive agents of cell cycle, may be expressed abnormally at the same time. Now many references proved that cyclins are highly expressed in solid tumors. This study was designed to investigate the relationship between expression of cyclins and prognosis of acute leukemia. METHODS: Sixty-eight cases of acute leukemia were enrolled. Reverse transcription polymerase chain reaction (RT-PCR) was performed on tumor samples to examine the expression of cyclin A, cyclin D, cyclin E. All samples were divided into three groups: acute leukemia in complete remission (12 cases), newly diagnosed acute leukemia (16 cases) and refractory leukemia (40 case). Samples of benign hemopoietic patients were used as normal control (15 cases). RESULTS: All the 15 cases in the control group were negative of cyclin mRNA. No difference of cyclin A mRNA expression was shown between control group and the three experiment groups (P >0.05). But expression of cyclin D and cyclin E mRNA was significantly different between them (P< 0.01). There was no difference of expression of cyclin D and cyclin E mRNA among CR patients with acute leukemia(P >0.05), while the expression of cyclin D mRNA is significantly higher than that of cyclin E in refractory leukemia group. Furthermore the expression of cyclin D mRNA in recurrent refractory leukemia patients is significantly higher than that newly diagnosed cases (P< 0.05). All cyclins mRNA positive cases were divided into single cyclin gene expressed group and multiple cyclins gene expressed group. The positive rates of them were counted. No difference was found between complete remission group and refractory leukemia group (P >0.05). CONCLUSION: Cyclin D may act as a prognostic marker for acute leukemia. The amount of cyclins expressed cannot be used as a prognostic factor for acute leukemia.


Assuntos
Ciclinas/genética , Leucemia/metabolismo , RNA Mensageiro/análise , Doença Aguda , Adolescente , Adulto , Idoso , Ciclina A/genética , Ciclina D , Ciclina E/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
11.
Ai Zheng ; 22(8): 861-6, 2003 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-12917036

RESUMO

BACKGROUND & OBJECTIVE: Acute lymphocytic leukemia(ALL), which is sensitive to tumor necrosis factor (TNF) is one of hematological malignances derived from lymphoid tissue. Genetic polymorphisms in the tumor necrosis factor (TNF) locus can affect transcription and expression of TNF genes. This study was designed to investigate the relationship between -308 bp polymorphism in tumor necrosis factor-alpha(TNFalpha) gene and +252 bp in lymphotoxin-alpha(LTalpha) gene and the pathogenesis, clinical course, and outcome of ALL. METHODS: The single base mutation polymorphism in TNFalpha gene and LTalpha gene were analyzed among 29 Chinese patients with ALL and 72 normal controls using polymerase chain reaction (PCR)-restrictive fragment length polymorphism (RFLP). The clinical data were collected and survival analysis was performed. RESULTS: The difference of distribution of genotypes, alleles of TNFalpha(-308), LTalpha(+252), and TNF/LT polymorphic extended haplotypes between the ALL patients and control group were not statistically significant (P >0.05). In patients, no statistically significant association was found between the presence of a given TNF/LT haplotype status and clinical characters such as sex, white blood cell (WBC) counts, central nervous system involvement, and the response to therapy(P >0.05). The estimated 1-year overall survival rates in the groups of patients carrying high-risk and low-risk haplotypes were not statistically significant (P >0.05) using Kaplan-Meier method. In multivariate Cox regression models the TNF/LT haplotype status was not found to be a risk factor for outcome (P >0.05). CONCLUSION: These data suggest that genetic polymorphisms in the TNFalpha(-308) and LTalpha(+252) are not crucial in the pathogenesis, clinical course, and outcome of ALL patients.


Assuntos
Polimorfismo Genético , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Fator de Necrose Tumoral alfa/genética , Adolescente , Adulto , Idoso , Criança , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Taxa de Sobrevida
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