Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 33
Filtrar
1.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(5): 1463-1468, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31607299

RESUMO

OBJECTIVE: To investigate the transcriptional regulation of transcription factor MZF-1 on acute monocytic leukemia-related gene MLAA-34. METHODS: The effect of MZF-1 on the transcriptional activity of MLAA-34 gene promoter was analyzed by luciferase reporter gene detection system and site-directed mutation technique. The EMSA and ChIP assay were used to verify whether MZF-1 directly and specifically binds to the core region of MLAA-34 promoter. The over-expression vector and interference vector of MZF-1 were constructed to transfect U937 cells, and RT-PCR and Western blot were used to detect the transcription and expression changes of MLAA-34 gene. RESULTS: The transcription factor MZF-1 had a regulatory effect on MLAA-34 gene expression, and the relative luciferase activity was decreased after MZF-1 binding point mutation (P<0.01). EMSA and ChIP experiments demonstrated that MZF-1 could directly bind to MLAA-34 promoter and play a regulatory role. In the over-expression test, the increase of MZF-1 could up-regulate the expression of MLAA-34 (P<0.05). In the interference test, the decrease of MZF-1 could down-regulate the expression of MLAA-34 (P<0.05). CONCLUSION: Transcription factor MZF-1 can bind to the transcriptional regulatory region on the promoter of MLAA-34 gene and promote the transcription of MLAA-34 gene in acute monocytic leukemia.


Assuntos
Antígenos de Neoplasias/genética , Proteínas Reguladoras de Apoptose/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Leucemia Monocítica Aguda , Regulação Neoplásica da Expressão Gênica , Genes Reporter , Fator 1-alfa Nuclear de Hepatócito , Humanos , Regiões Promotoras Genéticas , Transcrição Genética
2.
Acta Haematol ; : 1-10, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31597158

RESUMO

BACKGROUND: The aim of this study was to detect the expression of long noncoding RNA small nucleolar RNA host gene 18 (SNHG18) andsemaphorin 5A (SEMA5A) genes in multiple myeloma (MM) patients and to explore the correlation of the expression of these genes with the clinical characteristics and prognosis of MM patients. METHODS: Forty-seven newly diagnosed MM, 18 complete remission MM, 13 refractory/relapse MM, and 22 iron deficiency anemia (serving as control) samples were extracted at the Department of Hematology, Second Affiliated Hospital of Xian Jiaotong University between January 2015 and December 2016. The clinical features of the MM patients are summarized. Real-time quantitative PCR was performed to analyze the relative expression levels of the SNHG18 and SEMA5Agenes. The clinical characteristics and overall survival (OS) of the MM patients were statistically analyzed while measuring different levels of SNHG18 and SEMA5Agene expression. At the same time, the correlation between the expression of SNHG18 and SEMA5A was also analyzed. RESULTS: The analysis confirmed that SNHG18 and its possible target gene SEMA5A were both highly expressed in newly diagnosed MM patients. After analyzing the clinical significance of SNHG18 and SEMA5A in MM patients, we found that the expression of SNHG18 and SEMA5A was related to the Durie-Salmon (DS), International Staging System (ISS), and Revised International Staging System (R-ISS) classification systems, and the Mayo Clinic Risk Stratification for Multiple Myeloma (mSMART; p < 0.05). Moreover, we observed a significant difference in OS between the SNHG18/SEMA5A high expression group and the low expression group. We found a positive correlation between SNHG18 and SEMA5A expression (r = 0.709, p < 0.01). Surprisingly, the expected median OS times of both the SNHG18 and SEMA5Ahigh expression groups were significantly decreased, which was in contrast to those of both the SNHG18 and SEMA5Alow expression groups and the single-gene high expression group (p < 0.05). CONCLUSION: High expression of both SNHG18 and SEMA5A is associated with poor prognosis in patients with MM.

3.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(3): 641-645, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31204911

RESUMO

OBJECTIVE: To clone the promoter sequence of acute monocytic leukemia new antigen gene.MLAA-34 and identify its promoter core region. METHODS: The full-length fragment of MLAA-34 gene promoter region was amplified by PCR, then was ligated into pGL3-Basic vector, and the recombinant plasmid was cloned. Constructed a series of MLAA-34 gene promoter 5' flanking region truncated plasmid. These recombinant plasmids were transfected into U937 and HEK293 cells, and the dual luciferase reporter gene was used to detect the promoter activity of each fragment to determine the minimum active region. Transcription factor binding sites were analyzed by bioinformatics methods. RESULTS: The recombinant plasmid containing MLAA-34 promoter sequence and its truncated plasmid were successfully constructed, and the promoter activity was significantly increased as compared with the empty vector (P<0.001). The minimal active region of MLAA-34 located between 402 bp and 200 bp. It contained multiple transcription factor binding sites such as E2F1, MZF-1, SP1, USF2 and STAT3. CONCLUSION: The promoter of luciferase reporter gene has been successfully constructed with different deletion fragments of MLAA-34, and its core promoter region may contain multiple transcription factor sequence.


Assuntos
Antígenos de Neoplasias/genética , Proteínas Reguladoras de Apoptose/genética , Leucemia Monocítica Aguda , Adulto , Clonagem Molecular , Genes Reporter , Células HEK293 , Humanos , Leucemia Monocítica Aguda/genética , Luciferases , Regiões Promotoras Genéticas
4.
J Hematol Oncol ; 11(1): 141, 2018 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-30572922

RESUMO

BACKGROUND: Chimeric antigen receptor (CAR) T cell therapy has demonstrated proven efficacy in some hematologic cancers. We evaluated the safety and efficacy of LCAR-B38M, a dual epitope-binding CAR T cell therapy directed against 2 distinct B cell maturation antigen epitopes, in patients with relapsed/refractory (R/R) multiple myeloma (MM). METHODS: This ongoing phase 1, single-arm, open-label, multicenter study enrolled patients (18 to 80 years) with R/R MM. Lymphodepletion was performed using cyclophosphamide 300 mg/m2. LCAR-B38M CAR T cells (median CAR+ T cells, 0.5 × 106 cells/kg [range, 0.07 to 2.1 × 106]) were infused in 3 separate infusions. The primary objective is to evaluate the safety of LCAR-B38M CAR T cells; the secondary objective is to evaluate the antimyeloma response of the treatment based on the general guidelines of the International Myeloma Working Group. RESULTS: At data cutoff, 57 patients had received LCAR-B38M CAR T cells. All patients experienced ≥ 1 adverse events (AEs). Grade ≥ 3 AEs were reported in 37/57 patients (65%); most common were leukopenia (17/57; 30%), thrombocytopenia (13/57; 23%), and aspartate aminotransferase increased (12/57; 21%). Cytokine release syndrome occurred in 51/57 patients (90%); 4/57 (7%) had grade ≥ 3 cases. One patient reported neurotoxicity of grade 1 aphasia, agitation, and seizure-like activity. The overall response rate was 88% (95% confidence interval [CI], 76 to 95); 39/57 patients (68%) achieved a complete response, 3/57 (5%) achieved a very good partial response, and 8/57 (14%) achieved a partial response. Minimal residual disease was negative for 36/57 (63%) patients. The median time to response was 1 month (range, 0.4 to 3.5). At a median follow-up of 8 months, median progression-free survival was 15 months (95% CI, 11 to not estimable). Median overall survival for all patients was not reached. CONCLUSIONS: LCAR-B38M CAR T cell therapy displayed a manageable safety profile and demonstrated deep and durable responses in patients with R/R MM. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03090659 ; Registered on March 27, 2017, retrospectively registered.


Assuntos
Antígeno de Maturação de Linfócitos B/metabolismo , Mieloma Múltiplo/tratamento farmacológico , Receptores de Antígenos Quiméricos/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Indução de Remissão , Adulto Jovem
5.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 26(1): 97-104, 2018 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-29397825

RESUMO

OBJECTIVE: To investigate the correlation of all exone mutation in MLAA-34 gene with chemotherapeutic efficacy for leukemia. METHODS: The expression level of MLAA-34 gene in 40 patients with AML-M5 and 5 healthy volunteers as control was detected by RT-PCR and its effect on chemotherapeutic efficacy were analyzed by RT-PCR; the effect of MLAA-34 gene mutation on overall survival (OS) and progression-free survival (PFS) of AML-M5 patients was analyzed by sequencing of all 12 exoues in MLAA-34 gene, the correlation between the mutation of prognostic genes important to leukemia and the mutation of MLAA-34 gene was explored. RESULTS: The expression level of MLAA-34 gene was significantly up-regulated as compared with that of healthy volunteers, moreover this up-regulation was related with a C59T SNP site located in second exon of MLAA-34 gene, meanswhile this SNP site is affinitive to the well-known mdecular markers of AML, inclinding Fms-like tyrosine kinase (FLT-3) and DNA methyltransferase-3A(DNAMT3A). The AML-M5 patients with high expression of MLAA-34 gene poorly responded to chemotherapy, the AML-M5 patients with MLAA-34 C59T mulation had even more high expression of MLAA-34 gene and significantly short OS and PFS in comparison with those of patients without C59T mutation. CONCLUSION: The C59T mutation in MLAA-34 gene is a high risk factor for recurrence of AML, and may be a cadidate target for treatment of AML.


Assuntos
Leucemia Monocítica Aguda , Antígenos de Neoplasias , Éxons , Humanos , Leucemia Mieloide Aguda , Mutação , Prognóstico , Tirosina Quinase 3 Semelhante a fms
6.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 25(5): 1466-1470, 2017 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-29070126

RESUMO

OBJECTIVE: To screen serum peptide associated with renal impairment in patients with multiple myeloma(MM) and search early biomarker of MM renal impairment. METHODS: The weak cation exchange magnetic bead combined with matrix assisted laser desorption/ionization time of flight mass spectrometry was used to compare and analyze serum peptidome of MM with or without renal impairment. RESULTS: There were 18 peptide peaks with statistical significance in the molecular weight range from 700 to 10 000 Da(P<0.05), among them 7 peptides were upregulated and 11 were downregulated. The Quick Classifier diagnostic model composed of 3 peptides, which can strongly distinguish MM patients with or without renal impairment by means of Embedded Software. Its sensitivity and specificity were 97.14% and 94.12%, respectively. Peptides with molecular weight of 3908.85 Da and 3216.06 Da were significantly upregulated in MM patients with renal impairment, while the peptide with molecular weight of 2990.08 Da was significantly downregulated in MM patients with renal impairment. CONCLUSION: Peptides associated with MM renal impairment obtained by serum peptidome technology can provide a new clue for early assessment and diagnosis of clinical MM renal impairment.


Assuntos
Biomarcadores/análise , Nefropatias/etiologia , Mieloma Múltiplo/complicações , Peptídeos/análise , Humanos , Nefropatias/diagnóstico , Mieloma Múltiplo/diagnóstico , Proteômica , Sensibilidade e Especificidade , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
7.
Leuk Res ; 48: 57-61, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27497340

RESUMO

As sensitization of leukemia cells with granulocyte colony-stimulating factor (G-CSF) can enhance the cytotoxicity of chemotherapy in myeloid malignancies, a pilot study was conducted in order to evaluate the effect of G-CSF priming combined with low-dose chemotherapy in patients with higher risk myelodysplastic syndrome (MDS). The regimen, G-HA, consisted of cytarabine (Ara-C) 7.5mg/m(2)/12h by subcutaneous injection, days 1-14, homoharringtonine (HHT) 1.5mg/m(2)/day by intravenous continuous infusion, days 1-14, and G-CSF 150mg/m(2)/day by subcutaneous injection, days 0-14. 56 patients were enrolled, 34 patients (61%, 95% confidence interval: 51.44-70.56%) achieved complete remission (CR). Median duration of neutropenia was 7days (ranging from 2 to 16days). Grade 1-2 nonhematologic toxicities were documented, including nausea and vomiting (5%), liver function abnormality (5%), and heart function abnormality (2%). No central nervous system toxicity was found. Mortality within the first 4 weeks was 4%. The G-HA regimen is effective in remission induction for higher risk MDS patients and well tolerated due to the acceptable toxicity in maintenance therapy in the patients who cannot undergo Hematopoietic cell transplantation (HCT).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Síndromes Mielodisplásicas/tratamento farmacológico , Adulto , Idoso , Citarabina/administração & dosagem , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Harringtoninas/administração & dosagem , Mepesuccinato de Omacetaxina , Humanos , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/prevenção & controle , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/complicações , Neutropenia/induzido quimicamente , Projetos Piloto , Indução de Remissão/métodos , Risco , Adulto Jovem
8.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 24(4): 1044-50, 2016 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-27531772

RESUMO

OBJECTIVE: To analyze the clinical characteristics and prognostic factors of patients with non-Hodgkin's lymphoma (NHL) in single center of the Northwest area in China for 10 years, so as to provide the evidences for early diagnosis, stratified treatmetn, evaluation of therapeutic efficacy and prognosis, as well as early prevation and so on. METHODS: The clinical data of 254 patients with NHL were analyzed retrospectively, the clinical characteristics were evaluated by unvariate analysis; then the single factors affecting prognosis were enrolled in multivariate analysis and the independent prognostic factors affecting the survival of patients were summarized. RESULTS: A total of 182 cases achieved CR(71.6%), PR 30 cases(11.8%), SD 22 cases(8.7%), PD 20 cases(7.9%), and RR 212 cases(83.5%). The statistically significant unfavorable prognostic factors for NHL revealed by univariate analysis included age, invasive, Ann Arbor stage, relapse, and total course of chemotherapy. Cox regression model analysis showed that the Ann Arbor stage, IPI, ECOG, B symptoms, peripheral blood cell levels, short-term efficacy, course to achieve CR, and total course of chemotherapy all were the independent prognostic factors. CONCLUSION: The incidence characteristics of NHL in this center displayed mainly middle and high-risk B cell type with attacks at young age, aggression and in lymph nodes. For aggressive lymphoma, the single and multiple prognostic factors may provide the significant guides for the treatment, individualized plan and evaluation of prognosis. The course number of chemotherapy is one of the important factors for survival and prognosis, possessed clinical significance, and worth further clinical research for aggressive lymphoma.


Assuntos
Linfoma não Hodgkin , Linfócitos B , China , Humanos , Linfonodos , Análise Multivariada , Prognóstico , Recidiva , Estudos Retrospectivos
9.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 24(3): 788-94, 2016 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-27342511

RESUMO

OBJECTIVE: To analyze the serum protein fingerprints of immune thrombocytopenia (ITP) patients and healthy controls by using weak cation exchange nanometer magnetic beads and MALDI-TOF-MAS technology, to identify the proteins with different expression, to establish the diagnostic model for ITP and to explore the pathogenesis of ITP. METHODS: A total of 40 patients with ITP and 40 healthy controls were selected, the serum protein components were captured by using weak cation exchange nanaometer magnetic beads, the protein spectra of all specimens were detected by Autoflex II matrix assisted laser desorption/ionization time of flight mass spectrometry (MALDI- TOF-MS) and then the data were analyzed by CliprotoolsTM2.2 software, by which the distinct protein molecules were screened to set up ITP diagnostic model. To identify the established model, the sera of 20 ITP patients and 20 healthy controls were selected to make category and cross validations. RESULTS: The detection of Clinprot system and the analysis of CliprotoolsTM2.2 software showed that about 55 protein peaks were detected with the range of 700 Da to 10 000 Da of molecular weight in the protein spectrum of serum speciments from 40 ITP patients and 40 healthy controls. Compared with healthy controls, 19 protein expression peaks with statistically significant difference were found in ITP patients (P < 0.05), among them 5 expressions were up-regulated and 14 expressions were down-regulated. The diagnostic model on basis of Supervised Neural Network Algorithm (SNN) was established through 10 MS peaks with strongest capability in ITP group and control group automatically distinguished by software, and it is expected that the sensitivity of model group reached to 100%, and the specificity to 100%. The category validation showed that this diagnostic model correctly identificed all 20 ITP patients and 20 healthy controls, and in cross validation, the model sensitivity was 100% and the specificity was 100%. CONCLUSION: The ITP SNN model ertablished by using ChinProt System with high flax and good repetition is composed of 10 protein peaks with significant difference, this model can effectively distinguish ITP patients and healthy controls.


Assuntos
Biomarcadores/sangue , Proteínas Sanguíneas/análise , Púrpura Trombocitopênica Idiopática/sangue , Estudos de Casos e Controles , Humanos , Peso Molecular , Mapeamento de Peptídeos , Proteômica , Sensibilidade e Especificidade , Software , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
10.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 24(2): 405-10, 2016 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-27151000

RESUMO

OBJECTIVE: To explore the effectiveness and safety of combined chemotherapy with pegasparaginase (PEG-Asp) for treatment of patients with acute lymphoblastic leukemia (ALL) and T cell non-Hodgkin's lymphoma (T-NHL) patients. METHODS: A total of 62 ALL or T-NHL patients were diagnosed and treated in our department and were enrolled in this study. Among them, 22 patients received the combined chemotherapy with PEG-Asp, while the other 40 patients received the standard chemotherapy with L-asparaginase (L-Asp) as the control. Therapeutic effectiveness, adverse effects, duration and expense of hospitalization, treatment-related mortality and survival were evaluated and compared in 2 different groups. RESULTS: In group of combined chemotherapy with PEG-Asp, the overall response rate was 90.91% (20 cases), among them CR rate and PR rate are 77.27% (17 cases) and 13.64% (3 cases), respectively. In the group of standard chemotherapy with L-Asp, the overall response rate was 87.5% (35 cases), among them CR rate and PR rate were 72.5% (29 cases) and 15% (6 cases), respectively. The difference neither between PEG-Asp and L-Asp chemotherapy groups nor between ALL and T-NHL subgroups was significant (P > 0.05). The 6-month and 12-month overall survival rates were not significantly different between the PEG-Asp and L-Asp chemotherapy groups, respectively (P > 0.05). The adverse effects were identified as degree 1-2 according to the WHO criteria of drug toxicity. Neither the adverse effects identified as degree 3-4 nor the treatment-related death were observed. Expect for allergy and hyperglycaemia, the difference of side-effect incidence between the two groups were not significant (P > 0.05). The treatment for all the patients in PEG-Asp chemotherapy group was completed, while the treatment with L-Asp was completed only in 29 cases. Moreover, both average duration and expense of hospitalization after the combined chemotherapy were less than the control. CONCLUSION: With higher response rate, lower drug toxicity and allergy incidence, the combined chemotherapy with PEG-Asp can replace the standard chemotherapy with L-Asp in the treatment of ALL and T-NHL. The optimization of the combined chemotheropeutic protocols for more cases and long-term survival rates need to further and deeply explorate.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Células T/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Asparaginase/uso terapêutico , Humanos , Polietilenoglicóis/uso terapêutico , Taxa de Sobrevida
11.
Nan Fang Yi Ke Da Xue Xue Bao ; 36(3): 303-8, 2016 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-27063153

RESUMO

OBJECTIVE: To compare the efficacy of porcine and rabbit antithymocyte globulins (ATG) in the treatment of severe aplastic anemia (SAA). METHODS: We reviewed the clinical data of 43 SAA patients receiving porcine ALG treatment and 32 patients receiving rabbit ATG treatment between 2004 and 2013 in our hospital. The overall response rates of the patients at 6 month were compared, and the patients' survival in the two groups was analyzed using Kaplan-Meier survival curves. RESULTS: The overall response rates at 6 months was significantly higher in porcine ALG group than in rabbit ATG group (79.07% vs 56.25%, P=0.034). The 5-year overall survival was also higher in porcine ALG group than in rabbit ATG group, but this difference was not statistically significant (86.047% vs 72.878%, P=0.190). CONCLUSIONS: Porcine ALG is superior over rabbit ATG in terms of hematological response but is comparable with rabbit ATG in view of the patients' survival and safety.


Assuntos
Anemia Aplástica/terapia , Soro Antilinfocitário/uso terapêutico , Animais , Humanos , Estimativa de Kaplan-Meier , Coelhos , Estudos Retrospectivos , Suínos
12.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 23(6): 1612-7, 2015 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-26708881

RESUMO

OBJECTIVE: To study the non-Hodgkin's lymphoma treated with enhanced chemotherapy regimen and increase of treatment courses, including number of treatment courses, short-term efficacy, long-term survival and safety. METHODS: All the 254 cases of NHL in our hospital from January 2004 to February 2014 received a variety of intensive enhanced chemotherapy regimen, such as CHOPE, MAED, MMED and TAED. The median number of treatment course was 14, including 8 in the 1st year, 4 in the 2nd and 2 in the 3rd. RESULTS: (1) In 254 assessable patients, 182 patients (71.7%) achieved complete responses (CR), 30 patients (11.8%) achieved partial responses (PR), 22 patients (8.7%) achieved stable disease (SD), 20 patients (7.9%) achieved progressive disease (PD), 212 patients (83.5%) achieved response rate (RR). The median time of following-up was 56.5 months, the overall survivals (OS) of 1, 3 and 5 years were 90.1%, 74.5% and 61.1% respectively, the median survival time was 69 months, and the disease-free survivals (DFS) were 81.8%, 65.4% and 54.7% respectively, the median DFS was 65 months. (2) In therapeutic effects at early phase, the 3-year OS of patients who achieved CR, PR, SD and PD were 92.2%, 56.0%, 20.2% and 0% respectively; The 5-year OS of patients who achieved CR through ≤4 cycle treatments and the 5-year OS of patients who achieved CR through >4 cycles treatments were 83.1% and 6.8%, their DFS were 72.4% and 0% respectively. (3) The relapse rates of patients who received < 6, 6-8, 9-10, 11-13, 14, 15 and 20 cycle treatments were 82.5%, 78.9%, 71.9%, 65.8%, 41.8%, 30.4% and 16.7%. The response rate (RR) of patients who received 6-8 traditional chemotherapy cycle as CHOP or CHOP-like regimen were 50%-60% and relapse rate > 70%. CONCLUSION: Compared with traditional chemotherapy regimens, the dose-escalated, intensive and modified chemotherapy regimen can significatly improve the therapeutic efficiency for patients with NHL, including CR, long-term survival rate, and a good tolerance for patients. The chemotherapy intensity has been confirmed to be an important factor that associated with therapeutic efficiency. On the conditions tolerated by patients, the number of treatment cycles for NHL patients can be increased at lest 14, with 8 in the first year, 4 in the second year and 2 in the third year. The increase of chemotherapy cycle can obviously reduce the relapse rate and improve the long-term prognosis of patients. It is worth to further explore.


Assuntos
Linfoma não Hodgkin , Protocolos de Quimioterapia Combinada Antineoplásica , Ciclofosfamida , Intervalo Livre de Doença , Doxorrubicina , Etoposídeo , Humanos , Prednisona , Prognóstico , Recidiva , Indução de Remissão , Vincristina
13.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 23(5): 1341-5, 2015 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-26524034

RESUMO

OBJECTIVE: To explore the change of T help cell 17 (Th17) in the peripheral blood of patients with multiple myeloma (MM) before and after treatment with thalidomide. METHODS: A total of 35 MM patients treated with thalidomide and 35 healthy controls were enrolled in this study. The percentage of Th17 cells were detected by flow cytometry. The mRNA levels of retinoid-related orphan receptor gamma-t (RORγt) were detected by real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) and the plasm IL-17 levels were measured by enzyme linked immunosorbent assay (ELISA). RESULTS: The percentage of Th17 cells, the mRNA expression of RORγt and the plasm IL-17 levels in patients with MM were statistically higher than those in normal controls (P < 0.05). The percentage of Th17 cells was not correlate with the sex, age, disease type, globulin, immune globulin, light chain, M-protein and the proportion of plasmocytes (P > 0.05), but correlated with ISS stage, the level of ß2-microglobulin and the plasm IL-17 levels (P < 0.05). The percentage of Th17 cells, the mRNA expression of RORγt and the plasm IL-17 levels in patients with response to thalidomide were statistically lower than those in patients before treatment (P < 0.05). CONCLUSION: The Th17 cells increase in the peripheral blood of patients with MM, the Th17 cells may participate in the occurrence of MM. Thalidomide may exert anti-MM through down-regulating Th17 cells.


Assuntos
Mieloma Múltiplo/tratamento farmacológico , Células Th17/efeitos dos fármacos , Talidomida/farmacologia , Estudos de Casos e Controles , Regulação para Baixo , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Humanos , Interleucina-17/sangue , Mieloma Múltiplo/imunologia , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , RNA Mensageiro , Reação em Cadeia da Polimerase em Tempo Real
14.
Int J Clin Exp Med ; 8(8): 12064-75, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26550118

RESUMO

OBJECTIVES: The aim of the article is to critically appraise and synthesize available evidence regarding the efficacy and regimen-related toxicity (RRT) of Busulfan plus fludarabine (BuFlu) compared to busulfan plus cyclophosphamide (BuCy) as a conditioning regimen, prior to allogeneic hematopoietic stem cell transplantation (HSCT) in patients with hematologic neoplasms. METHODS: A meta-analysis was attempted on clinical controlled trials (CCTs), randomized or non-randomized controlled trials (RCTs or non-RCTs), comparing BuCy with BuFlu. We did a systematic search of the indexed medical literature using appropriate keywords to identify potentially relevant articles. The primary outcome of interest was efficacy measured by overall survival (OS) and event-free survival (EFS), acute graft-versus-host-disease (aGVHD). Chronic GVHD (extensive) and other toxicity were secondary endpoints. A relative risk or risk ratio (RR) and 95% confidence interval (CI) was calculated for each outcome in the meta-analysis. RESULTS: Nine clinical controlled trials were included, of which 4 tries were RCTs involving 584 patients and the other 5 were non-RCTs involving 571 patients. The cumulative incidences of OS, EFS, acute graft-versus-host disease (aGVHD) were not significantly different between the two regimens. The non-relapse mortality was higher in BuCy but non-significant increment (RR=1.48, 95% CI: [0.97-2.26]). Liver related toxicity was significantly higher with BuCy compared to BuFlu (RR=1.90, 95% CI: [1.00-3.61]). CONCLUSION: Liver related toxicity is significantly lesser with BuFlu, but BuFlu regimen has no significant benefits compared with BuCy in OS, EFS, aGVHD. For all this, the weight of evidence favors BuFlu over BuCy as a first choice-conditioning regimen for patients with hematologic neoplasms, especially for people who have poor liver function.

15.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 23(2): 369-74, 2015 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-25948187

RESUMO

OBJECTIVE: To explore the clinical efficacy and adverse effects of GHA(G-CSF+homoharringtonin+cytarabine C) and new combined priming chemotherapeutic regimens(GHAA/GHTA) with high efficacy and low toxicity for treatment of relapsed and refractory acute myeloid leukemia(AML) and myelodysplastic syndrome(MDS), and to analyze the relation of above-mentioned regimens with the expression of co-stimuolating molecule B7.1. METHODS: Standard GHA regimen consisting of G-CSF: 100 µg/(m2·d) subcutaneous injection, d 0-14; homoharringtonine: 1.0 mg/(m2·d) intravenous drip, d 1-14; Ara-C: 7.5-10 mg/(m2·d) subcutaneous injection, q12h, d 1-14. Other regimens as GHAA/GHTA were combined respectively with aclarubicin 20 mg d 1-7, or pirarubicin 20 mg d 1-7. 74 patients with refractory AML and 46 patients with MDS received these priming chemotherapy. The clinical efficacy and toxicity of above-mentioned priming chemotherapy were compared with 56 patients received routine chemotherapy (MA/TAE) respectively. And the expression of costimulatory molecule B7.1 on leukemia cells in patients of different subtypes was also detected by immunofluoressence and its relationship with clinical efficiency was explored. RESULTS: (1) for AML patients treated with priming chemotherapy, the total remission was 67.56% (CR 54.05%, PR 13.51%), which was much higher than that of patients received routine chemotherapy (P<0.05). The CR rate of AML-M2 and AML-M5 group (65.51%, 61.90% respectively) was much higher than that of AML other subtypes (P<0.05), and the longest remission period lasted for 4 years; (2) for MDS patients treated with priming chemotherapy, the total remission was 60.87% (CR 45.65%, PR 15.22%), which was also significantly higher than that of patients received routine chemotherapy (P<0.05); (3) in comparison with patients received standard GHA priming regimen, the remission rate of combined priming chemotherapy GHAA/GHTA was significantly higher both in patients with AML (85.18%) and MDS (81.25%); (4) side effects after chemotheropy, including granulocyte deficiency, thrombocytopenia and anemia etc, lasted for 7-14 days; the severe infection rate was 1%, there were no severe bleeding, digest effect and damage of function in heart, liver and kidney. The therapy-related mortality was zero. Compared with routine chemotherapy, priming chemotherapy proved significantly safe and effective (P<0.05); (5) the expression rate of costimulatory molecule B7.1 showed large variance between AML and MDS, it was higher in AML-M2/AML-M5 and lower in AML of other subtypes (P<0.05). In the same case, B7.1 expression was positive correlated with efficiency of priming chemotherapy. CONCLUSION: GHA priming chemotherapy, as well as other combination regimens GHAA/GHTA, are well-tolerated, effective regimens for refractory AML and advanced MDS, without severe side effects and therapy-related mortality. Especially the new regimens GHAA/GHTA has better efficacy, which are proved more efficient than conventional GHA. Efficiency of priming chemotherapy is positive correlated with B7.1 expression, its mechanism will be further explored.


Assuntos
Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Aclarubicina/análogos & derivados , Protocolos de Quimioterapia Combinada Antineoplásica , Antígeno B7-1 , Estudos de Coortes , Citarabina , Doxorrubicina/análogos & derivados , Fator Estimulador de Colônias de Granulócitos , Granulócitos , Harringtoninas , Mepesuccinato de Omacetaxina , Humanos , Recidiva , Trombocitopenia
16.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 23(2): 471-6, 2015 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-25948207

RESUMO

OBJECTIVE: To evaluate the short and long term therapeutic efficacy of the immunosuppressive therapy(IST) for adult severe aplastic anemia(SAA), and to analysis the relationship between the clinical factors(age, typing, lymphocyte percentage, reticulocyte percentage, neutrophil count) and the response to IST. METHODS: The response rate of 39 patients received the IST between September 2009 and September 2013 in our hospital was assayed, the effective time in which all patients had hematologic response, and the survival rate at the first year were analyzed. The survival rates, the average amounts of the RBC and Plt transfusion per month in the first year were compared by using χ2 test between the IST group and the non-IST group; the multinomial logistic regression was used to analyze the relationship between the clinical factors and the response to IST. RESULTS: The response rates of the 39 SAA patients at the first month, the third month, the sixth month and the first year were 29.73%, 70.27%, 75.68%, 86.49%, respectively. The median effective time of hematologic response in all patients had was 61.5 d(10 d-344 d). The survival rate of the IST group was 92.31%, which was much higher than that of the non-IST group (P<0.05). The average amounts of the RBC and Plt transfusion per month at the first year in the IST group were 1.04(0.13-2.78)×400 ml and 1.38(0.17-5.10)×200 ml, respectively, which were much lower than those in the non-IST group (P<0.01). Among the five clinical factors, the age, lymphocyte percentage and neutrophil count related to the response of IST (P<0.05). CONCLUSION: The response rate of the 39 SAA patients received IST is 86.49% at the first year, and their long term survival is better than that of non-IST group. The age, lymphocyte percentage and neutrophil count relate to the response of IST.


Assuntos
Anemia Aplástica , Adulto , Transfusão de Sangue , Ciclosporina , Humanos , Imunossupressores , Contagem de Leucócitos , Modelos Logísticos , Neutrófilos , Reticulócitos , Taxa de Sobrevida
17.
Int J Clin Exp Med ; 7(12): 4720-33, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25663969

RESUMO

Interleukin-10 (IL-10) single nucleotide polymorphisms (SNPs) have been indicated to be correlated with Non-Hodgkin's lymphoma (NHL) susceptibility. However, the results of these studies on the association remain inconsistent. This meta-analysis was conducted to derive a more accuracy estimation of the association between the common SNPs (rs1800890, rs1800896, rs1800871 and rs1800872) in IL-10 and NHL risk. Meta-analyses were performed on 21 studies with 7,749 cases and 8584 controls. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the NHL risk. Meta-analyses showed that rs1800890, rs1800871 and rs1800872 polymorphisms had no association with NHL risk. However, rs1800896 polymorphism has association with NHL risk based on the following comparison models (G vs. A: OR = 1.14, 95% CI = 1.00-1.29; AG vs. AA: OR = 1.20, 95% CI = 1.05-1.37; GG+AG vs. AA: OR = 1.22, 95% CI = 1.08-1.39). In the ethnic subgroup analysis, rs1800896 had an increased NHL risk in Caucasians based on the heterozygote model (OR = 1.21, 95% CI = 1.04-1.41) and dominant model (OR = 1.22, 95% CI = 1.00-1.48). When stratified by subtypes, rs1800890, rs1800896 and rs1800872 polymorphisms were found significant association with an increased risk of diffuse large B-cell Lymphoma (DLBCL) in different comparison models, whereas negative results were obtained for Follicular Lymphoma (FL) and chronic lymphocytic Leukemia/small lymphocytic Lymphoma (CLL/SLL) in all genetic models. Our meta-analysis suggested that the rs1800896 polymorphism had an increased risk with NHL susceptibility, where as the rs1800890, rs1800871 and rs1800872 had no association with NHL risk. Among the common subtypes of NHL, three polymorphisms (rs1800890, rs1800896 and rs1800872) had significant association with DLBCL risk.

18.
Oncol Rep ; 29(2): 491-506, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23135622

RESUMO

MLAA-34 is a novel acute monocytic leukemia (M5)-associated antigen (MLAA) that plays a role in the apoptosis of U937 cells. However, the expression and molecular mechanism of MLAA-34 in U937 cells remain largely unclear. Here, we utilized three strategies to gain insight into the expression and molecular functions of MLAA-34 and to identify its interacting proteins and pathways involved in the fine-tuning of the MLAA-34 response. Western blot analysis was performed to assess the expression of MLAA-34 in 41 cell lines and five mixed cell types, which revealed that MLAA-34 is most strongly expressed in U937 cells. Immunostaining indicated that MLAA-34 is localized in the cytoplasm and cell membrane. Furthermore, lentivirus-mediated overexpression of MLAA-34 in the U937 cell line led to significant suppression of apoptosis and increased the potential of tumorigenicity. Co-immunoprecipitation (Co-IP), shotgun and bioinformatic analysis identified 256 proteins and 225 of them were annotated by gene ontology categories. This analysis revealed 71 proteins involved in cell apoptosis or proliferation of biological processes and signaling pathways. Moreover, the effect of MLAA-34 apoptosis may be through interaction with the Ras, Wnt, calcium and chemokine signaling pathways and thirteen of the annotated proteins may interact with MLAA-34 and participate in carcinogenesis directly. This study provides a basis for a better understanding of the molecular mechanism and proteomics in the inhibition of apoptosis by MLAA-34 in U937 cells and indicates that MLAA-34 may be a potential candidate for the early diagnosis and therapeutic application of M5.


Assuntos
Antígenos de Neoplasias/genética , Antígenos de Neoplasias/metabolismo , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Apoptose , Membrana Celular , Proliferação de Células , Citoplasma , Vetores Genéticos , Humanos , Lentivirus , Leucócitos Mononucleares/metabolismo , Fosfoglicerato Quinase/metabolismo , Proteômica , Transdução de Sinais/genética , Transfecção , Células U937 , Regulação para Cima/genética , beta Catenina/metabolismo , Proteínas rab3 de Ligação ao GTP/metabolismo , Proteínas rap de Ligação ao GTP/metabolismo
19.
J Cancer Res Clin Oncol ; 137(6): 997-1003, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21152934

RESUMO

BACKGROUND: To explore the effect of low dose of homoharringtonine (HHT) and cytarabine (Ara-c) combined with granulocyte colony-stimulating factor (G-CSF) priming (HAG regimen) on relapsed or refractory acute myeloid leukemia (AML). METHODS: Sixty-seven patients with relapsed or refractory acute myeloid leukemia (AML) were enrolled. All the patients were treated with HAG regimen (HHT 1.5 mg/m(2)/day, 1-14d; Ara-C 7.5 mg/m(2)/12 h, 1-14d; G-CSF 150 µg/m(2)/day, according to the counting of the peripheral white blood cells). Blood cell counting, liver, kidney function, ECG and myocardial enzymes were monitored regularly. RESULTS: Thirty-five of 67 (52.2%) patients achieved complete remission (CR) and 8/67 (11.9%) partial remission (PR). The overall response rate was 64.1%. Myelosuppression was the most frequently observed adverse effect. Sixty of 67 (89.5%) patients suffered from grade 1-4 adverse effects of hematologic toxicity (according to World Health Organization criteria) and non-hematologic toxicity was mild. CONCLUSION: In conclusion, HAG regimen was effective and tolerated well in refractory or relapsed AML. As a promising regimen for relapse or refractory AML, further observations should be made.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Citarabina/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Harringtoninas/administração & dosagem , Leucemia Mieloide Aguda/tratamento farmacológico , Adolescente , Adulto , Idoso , Citarabina/efeitos adversos , Citarabina/uso terapêutico , Feminino , Harringtoninas/efeitos adversos , Harringtoninas/uso terapêutico , Mepesuccinato de Omacetaxina , Humanos , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Receptores CXCR4/análise , Recidiva
20.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 18(5): 1132-7, 2010 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-21129246

RESUMO

This study was purposed to preliminarily screen characteristic tumor markers of acute myeloid leukemia (AML) and to investigate the serum proteomics characteristics of patients with AML and their significance in pathogenesis. 14 patients with AML and 28 healthy controls were enrolled in this study. The serum protein components were captured by weak cation exchange nanometer magnetic beads, the protein mass-spectra of all samples were detected by Autoflex II matrix-assisted laser desorption/ionization time of flight mass spectrometer, and the detection data were analyzed by means of CliprotoolsTM2.2 software, then the differential protein molecules were screened and the diagnostic model was established. Sera of 7 AML patients and 14 healthy controls were selected to verify the established model by using blind test. The results indicated that about 69 protein peaks could be detected within the range of 0.7-10 kD in protein spectra of serum samples from AML patients and controls. Compared with healthy controls, there were 44 statistically differential expression peaks in AML group (p<0.0001). Among them, 10 protein peaks were upregulated protein peaks and 34 protein peaks were downregulated. Diagnostic model was established on the basis of Quick Classifier Algorithm (QC), and the three mass peaks had the strongest power for software to automatically distinguish AML group from control group. Mass charge ratios (m/z) were 3216.57, 4089.7, and 7762.87 respectively. Sensitivity was expected as 86.4% while 82.8% in this established model group. Category validation showed that this diagnostic model correctly identified all 6 cases out of AML and 12 cases out of 14 healthy controls. In cross validation, the model sensitivity and specificity both were 85.7%. It is concluded that the AML QC model is composed of three protein peaks, which can effectively distinguish AML patients from healthy controls. Owing to higher sensitivity and specificity, they may act as serum tumor markers of AML. Among the three proteins, the one with m/z 7762.87 is the platelet-derived protein chemokine (PF4) protein. This finding will probably provide significant experimental evidence for understanding pathogenesis, molecular type, prognosis and treatment effect of AML.


Assuntos
Biomarcadores Tumorais/sangue , Leucemia Mieloide Aguda/sangue , Adulto , Idoso , Biomarcadores , Estudos de Casos e Controles , Feminino , Humanos , Leucemia Mieloide Aguda/diagnóstico , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise Serial de Proteínas/métodos , Proteômica , Sensibilidade e Especificidade , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA