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1.
Chin Med J (Engl) ; 132(15): 1765-1772, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31306219

RESUMO

BACKGROUND: Allogeneic stem-cell transplantation (SCT) is a well-established immunotherapeutic strategy for multiple myeloma (MM) with a potent and often sustained graft-vs.-myeloma effect. This multicenter investigation aimed to analyze the complications and survival of haploidentical SCT in patients with MM, and compare the main outcomes with matched-related donors (MRDs). METHODS: Haploidentical and MRD SCT was identified from a cohort of 97 patients with MM who received a myeloablative transplantation in 13 hospitals from May 2001 to December 2017. A matched-pair analysis was designed. For each haplo recipient, the recipients were randomly selected from the MRD group and were matched according to the following criteria: year of the hematopoietic SCT (±2 years), disease status at transplantation, and the length of follow-up. RESULTS: Seventy cases received MRD and 27 received haploidentical transplantation. The two groups showed no significant differences regarding age, gender, cytogenetic risk, and diagnostic stage. The cumulative incidences of non-relapse mortality (NRM) at 1 and 3 years based on donor type were 20.5% (95% confidence interval [CI], 10.90-30.10%) and 24.2% (95% CI, 13.81-34.59%) for the MRD group and 16.80% (95% CI, 1.71-31.89%) and 28.70% (95% CI, 8.71-48.69%) for the haplo group, respectively. Cumulative incidence of NRM did not differ significantly between the two groups (χ = 0.031, P = 0.861). The cumulative incidences of progression-free survival (PFS) and 1 year and 3 years by type of donors were 59.8% (95% CI, 48.24-71.36%) and 45.4% (95% CI, 33.44-57.36%), and 65.6% (95% CI, 47.18-84.02%) and 26.8% (95% CI, 7.59-46. 01%) for MRD and haploidentical donor, respectively. Cumulative incidence of PFS did not differ significantly between the two groups (χ = 0.182, P = 0.670). In multivariate analyses, no statistically significant differences were observed between haploidentical and MRD for relapse, NRM, PFS, and overall survival. There were no statistically differences on main outcomes after haploidentical and MRD. CONCLUSION: Haploidentical SCT could be performed safely and feasibly for patients with MM in need.

2.
Acta Haematol ; 142(3): 162-170, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31091521

RESUMO

Aplastic anemia (AA) is a hematologic disease characterized by pancytopenia and hypocellular bone marrow, potentially leading to chronic anemia, hemorrhage, and infection. The China Aplastic Anemia Committee and British Committee for Standards in Haematology guidelines recommend hematopoietic stem-cell transplantation (HSCT) or immunosuppressive therapy (IST) comprising antithymocyte globulin (ATG) with cyclosporine (CsA) as initial treatment for AA patients. With limited epidemiological data on the clinical management of AA in Asia, a prospective cohort registry study involving 22 AA treatment centers in China was conducted to describe the disease characteristics of newly diagnosed AA patients and investigate real-world treatment patterns and patient outcomes. Of 340 AA patients, 72.9, 12.6, and 3.5% were receiving IST, traditional Chinese medicine, and HSCT, respectively, at baseline; only 22.2% of IST-treated patients received guideline-recommended ATG with CsA initially. Almost all patients received supportive care (95.6%) as blood transfusion (97.8%), antibiotics (63.7%), and/or hematopoietic growth factors (58.2%). Overall, 64.8% achieved a partial or complete response, and 0.9% experienced relapse. No new safety concerns were identified; serious adverse events were largely unrelated to the treatment regimen. These results demonstrate the need to identify and minimize treatment barriers to standardize and align AA management in China with treatment guideline recommendations and further improve patient outcomes.

3.
Leuk Res ; 55: 49-54, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28122283

RESUMO

Angiopoietins play an important role in vascular endothelial function. Endothelial damage is an important pathogenesis relating with acute graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), protecting endothelial cells (ECs) from damage may be a potent prophylaxis and therapeutic strategy of acute GVHD (aGVHD). In this study, we explored changes in Angiopoietin-1 (Ang-1) and Ang-2 expression in a aGVHD mouse model and determined whether simvastatin prevents GVHD through regulating Ang-1 and Ang-2 expression. In vitro simvastatin administration increased Ang-1 production and release but conversely inhibited Ang-2 release from EA.hy926 ECs. Simvastatin improved the survival of aGVHD mice, attenuated the histopathological GVHD grades and plasma levels of Ang-2, and elevated the plasma levels of Ang-1 as well as the aortic endothelial levels of Ang-1 and Ang-2. In summary, simvastatin represents a novel approach to combat GVHD by increasing Ang-1 production while suppressing Ang-2 release to stabilize endothelial cells.


Assuntos
Doença Enxerto-Hospedeiro/prevenção & controle , Sinvastatina/farmacologia , Angiopoietina-1/análise , Angiopoietina-1/biossíntese , Angiopoietina-1/sangue , Angiopoietina-2/análise , Angiopoietina-2/biossíntese , Angiopoietina-2/sangue , Animais , Aorta/citologia , Modelos Animais de Doenças , Células Endoteliais/química , Células Endoteliais/patologia , Expressão Gênica/efeitos dos fármacos , Doença Enxerto-Hospedeiro/tratamento farmacológico , Camundongos , Sinvastatina/uso terapêutico
4.
J Hematol Oncol ; 10(1): 25, 2017 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-28107815

RESUMO

BACKGROUND: Haploidentical donor (HID) hematopoietic stem cell transplantation (HSCT) is an alternative treatment method for severe aplastic anemia (SAA) patients lacking suitable identical donors and those who are refractory to immunosuppressive therapy (IST). The current study evaluated the feasibility of upfront haploidentical HSCT in SAA patients. METHODS: We conducted a multicenter study based on a registry database. One hundred fifty-eight SAA patients who underwent upfront transplantation between June 2012 and September 2015 were enrolled. RESULTS: Eighty-nine patients had haploidentical donors (HIDs), and 69 had matched related donors (MRDs) for HSCT. The median times for myeloid engraftment in the HID and MRD cohorts were 12 (range, 9-20) and 11 (range, 8-19) days, with a cumulative incidence of 97.8 and 97.1% (P = 0.528), respectively. HID recipients had an increased cumulative incidence of grades II-IV acute graft-versus-host disease (aGVHD) (30.3 vs. 1.5%, P < 0.001), grades III-IV aGVHD (10.1 vs. 1.5%, P = 0.026), and chronic GVHD (cGVHD) (30.6 vs. 4.4%, P < 0.001) at 1 year but similar extensive cGVHD (3.4 vs. 0%, P = 0.426). The three-year estimated overall survival (OS) rates were 86.1 and 91.3% (P = 0.358), while the three-year estimated failure-free survival (FFS) rates were 85.0 and 89.8% (P = 0.413) in the HID and MRD cohorts, respectively. In multivariate analysis, survival outcome for the entire population was significantly adversely associated with increased transfusions and poor performance status pre-SCT. We did not observe differences in primary engraftment and survival outcomes by donor type. CONCLUSIONS: Haploidentical SCT as upfront therapy was an effective and safe option for SAA patients, with favorable outcomes in experienced centers.


Assuntos
Anemia Aplástica/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Histocompatibilidade/imunologia , Adolescente , Adulto , Anemia Aplástica/complicações , Anemia Aplástica/imunologia , Anemia Aplástica/mortalidade , Criança , Pré-Escolar , Feminino , Sobrevivência de Enxerto/imunologia , Doença Enxerto-Hospedeiro/imunologia , Haploidia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Taxa de Sobrevida , Fatores de Tempo , Adulto Jovem
5.
Br J Haematol ; 175(2): 265-274, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27352174

RESUMO

We conducted a prospective, multicentre study to confirm the feasibility of haplo-identical transplantation in treatment of severe aplastic anaemia (SAA) as salvage therapy, by analysing the outcomes of 101 patients who received haplo-identical transplantation between June 2012 and October 2015. All cases surviving for more than 28 d achieved donor myeloid engraftment. The median time for myeloid engraftment was 12 (range, 9-25) days and 15 (range, 7-101) days for platelets, with a cumulative platelet engraftment incidence of 94·1 ± 0·1%. With a median follow-up of 18·3 (3·0-43·6) months, recipients from haplo-identical transplantation had more cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD, 33·7% vs. 4·2%, P < 0·001), more chronic GVHD (22·4% vs. 6·6%, P = 0·014) at 1 year, but similar grade III-IV aGVHD (7·9% vs. 2·1%, P = 0·157), 3-year estimated overall survival (OS, 89·0% vs. 91·0%, P = 0·555) and failure-free survival (FFS, 86·8% vs. 80·3%, P = 0·659) when compared with 48 patients who received contemporaneous transplantation from matched related donors. Multivariate analysis showed no significant difference in engraftment and survival between the two cohorts. Both OS and FFS for the entire population correlated significantly with grades III-IV aGVHD. In conclusion, haplo-identical transplantation is a feasible choice for SAA with favourable outcomes.


Assuntos
Anemia Aplástica/diagnóstico , Anemia Aplástica/terapia , Haplótipos , Transplante de Células-Tronco Hematopoéticas , Doadores de Tecidos , Adolescente , Adulto , Anemia Aplástica/etiologia , Anemia Aplástica/mortalidade , Biomarcadores , Criança , Pré-Escolar , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Antígenos HLA/genética , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Retratamento , Índice de Gravidade de Doença , Análise de Sobrevida , Condicionamento Pré-Transplante , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
6.
Am J Physiol Cell Physiol ; 310(10): C821-35, 2016 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-27009877

RESUMO

Accumulating evidence suggests that endothelial microparticles (EMPs), a marker of endothelial damage, are elevated in acute graft-versus-host disease (aGVHD), and that endothelial damage is implicated in the pathogenesis of aGVHD, but the mechanisms remain elusive. In this study, we detected the plasma EMP levels and endothelial damage in patients and mice with aGVHD in vivo and then examined the effects of EMPs derived from injured endothelial cells (ECs) on endothelial damage and the role of hedgehog-interacting protein (HHIP) carried by EMPs in these effects in vitro. Our results showed that EMPs were persistently increased in the early posttransplantation phase in patients and mice with aGVHD. Meanwhile, endothelial damage was continuous in aGVHD mice, but was temporary in non-aGVHD mice after transplantation. In vitro, EMPs induced endothelial damage, including increased EC apoptosis, enhanced reactive oxygen species, decreased nitric oxide production and impaired angiogenic activity. Enhanced expression of HHIP, an antagonist for the Sonic hedgehog (SHH) signaling pathway, was observed in patients and mice with aGVHD and EMPs from injured ECs. The endothelial damage induced by EMPs was reversed when the HHIP incorporated into EMPs was silenced with an HHIP small interfering RNA or inhibited with the SHH pathway agonist, Smoothened agonist. This work supports a feasible vicious cycle in which EMPs generated during endothelial injury, in turn, aggravate endothelial damage by carrying HHIP into target ECs, contributing to the continuously deteriorating endothelial damage in the development of aGVHD. EMPs harboring HHIP would represent a potential therapeutic target for aGVHD.


Assuntos
Proteínas de Transporte/imunologia , Micropartículas Derivadas de Células/imunologia , Endotélio Vascular/imunologia , Endotélio Vascular/patologia , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/patologia , Glicoproteínas de Membrana/imunologia , Doença Aguda , Adolescente , Adulto , Animais , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Adulto Jovem
7.
J Huazhong Univ Sci Technolog Med Sci ; 35(5): 694-699, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26489624

RESUMO

Acute graft-versus-host disease (aGVHD) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the mechanisms of aGVHD are not well understood. We aim to investigate the roles of the three angiogenic factors: angiopoietin-1 (Ang-1), Ang-2 and vascular endothelial growth factor (VEGF) in the development of aGVHD. Twenty-one patients who underwent allo-HSCT were included in our study. The dynamic changes of Ang-1, Ang-2 and VEGF were monitored in patients before and after allo-HSCT. In vitro, endothelial cells (ECs) were treated with TNF-ß in the presence or absence of Ang-1, and then the Ang-2 level in the cell culture medium and the tubule formation by ECs were evaluated. After allo-HSCT, Ang-1, Ang-2 and VEGF all exhibited significant variation, suggesting these factors might be involved in the endothelial damage in transplantation. Patients with aGVHD had lower Ang-1 level at day 7 but higher Ang-2 level at day 21 than those without aGVHD, implying that Ang-1 may play a protective role in early phase yet Ang-2 is a promotion factor to aGVHD. In vitro, TNF-ß promoted the release of Ang-2 by ECs and impaired tubule formation of ECs, which were both weakened by Ang-1, suggesting that Ang-1 may play a protective role in aGVHD by influencing the secretion of Ang-2, consistent with our in vivo tests. It is concluded that monitoring changes of these factors following allo-HSCT might help to identify patients at a high risk for aGVHD.


Assuntos
Angiopoietina-1/genética , Angiopoietina-2/genética , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide/genética , Linfoma não Hodgkin/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Doença Aguda , Adolescente , Adulto , Indutores da Angiogênese/imunologia , Indutores da Angiogênese/metabolismo , Indutores da Angiogênese/farmacologia , Angiopoietina-1/imunologia , Angiopoietina-1/farmacologia , Angiopoietina-2/imunologia , Angiopoietina-2/farmacologia , Antineoplásicos/uso terapêutico , Feminino , Regulação Neoplásica da Expressão Gênica , Doença Enxerto-Hospedeiro/genética , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/patologia , Células Endoteliais da Veia Umbilical Humana/citologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/imunologia , Humanos , Leucemia Mieloide/imunologia , Leucemia Mieloide/patologia , Leucemia Mieloide/terapia , Linfoma não Hodgkin/imunologia , Linfoma não Hodgkin/patologia , Linfoma não Hodgkin/terapia , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Estudos Retrospectivos , Transdução de Sinais , Transplante Homólogo , Fator de Necrose Tumoral alfa/farmacologia , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/imunologia
8.
J Huazhong Univ Sci Technolog Med Sci ; 35(4): 477-484, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26223913

RESUMO

Although mesenchymal stem cells (MSCs) are increasingly used to treat graft-versus-host disease (GVHD), their immune regulatory mechanism in the process is elusive. The present study aimed to investigate the curative effect of third-party umbilical cord blood-derived human MSCs (UCB-hMSCs) on GVHD patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and their immune regulatory mechanism. Twenty-four refractory GVHD patients after allo-HSCT were treated with UCB-hMSCs. Immune cells including T lymphocyte subsets, NK cells, Treg cells and dendritic cells (DCs) and cytokines including interleukin-17 (IL-17) and tumor necrosis factor-alpha (TNF-α) were monitored before and after MSCs transfusion. The results showed that the symptoms of GVHD were alleviated significantly without increased relapse of primary disease and transplant-related complications after MSCs transfusion. The number of CD3(+), CD3(+)CD4(+) and CD3(+)CD8(+) cells decreased significantly, and that of NK cells remained unchanged, whereas the number of CD4(+) and CD8(+) Tregs increased and reached a peak at 4 weeks; the number of mature DCs, and the levels of TNF-α and IL-17 decreased and reached a trough at 2 weeks. It was concluded that MSCs ameliorate GVHD and spare GVL effect via immunoregulations.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Doença Enxerto-Hospedeiro/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Imunomodulação , Transplante Homólogo/efeitos adversos , Adolescente , Adulto , Citocinas/metabolismo , Células Dendríticas/metabolismo , Feminino , Doença Enxerto-Hospedeiro/imunologia , Humanos , Células Matadoras Naturais/metabolismo , Masculino , Subpopulações de Linfócitos T/metabolismo , Adulto Jovem
9.
Chin Med J (Engl) ; 126(19): 3750-3, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24112176

RESUMO

BACKGROUND: Many studies indicated the human cytochrome P450 2D6 (CYP2D6) gene polymorphism was associated with acute leukemia (AL) susceptibility, however, the results were inconsistent. So we performed this meta-analysis to evaluate the relationship between CYP2D6*3 or CYP2D6*4 polymorphism and AL susceptibility. METHODS: We searched PubMed database up to February 20, 2013, and finally yielded 9 case-control studies including 1343 cases and 1843 controls which tested the association between CYP2D6*3 or *4 polymorphism and AL. After data extraction, we conducted a meta-analysis using the Comprehensive Meta Analysis software. RESULTS: Overall, no significant association between CYP2D6*3 or *4 polymorphism and AL risk was found in this metaanalysis (+ vs. -: OR = 1.13, 95% CI = 0.79-1.63; +/+ vs. -/-: OR = 1.73, 95% CI = 0.99-3.02; -/+ vs. -/-: OR = 1.03, 95% CI = 0.68-1.56; (-/+ and +/+) vs. -/-: OR = 1.08, 95% CI = 0.72-1.63; +/+ vs. (-/+ and -/-): OR = 1.76, 95% CI = 0.98-3.17). Similar results were also been found in stratified subgroup analysis. There was no publication bias. CONCLUSION: CYP2D6*3 or *4 polymorphism might not be associated with AL susceptibility. However, the results need to be further confirmed by well-designed and high quality randomized controlled trials with larger sample sizes.


Assuntos
Citocromo P-450 CYP2D6/genética , Leucemia/genética , Polimorfismo Genético , Doença Aguda , Predisposição Genética para Doença , Humanos , Leucemia/etiologia , Risco
10.
Acta Pharmacol Sin ; 30(10): 1471-8, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19767767

RESUMO

AIM: To analyze the results of idarubicin (IDA)- versus etoposide (VP16)-intensified myeloablative conditioning regimen in allogeneic hematopoietic stem cell transplantation (allo-SCT) for high-risk acute leukemia. METHODS: From January 2005 to June 2008, 48 consecutive patients (male: n=29; median age: 30 years, range 14-51 years) with high-risk acute leukemia underwent allo-SCT following an IDA- or VP16-intensified conditioning regimen. The conditioning regimens were modified BUCY2 (busulfan+cyclophosphamide) consisting of IDA (15 mg/m2 per day, days -12 to -10) or VP16 (25 mg/kg per day, days -3 to -2) and CY/TBI (cyclophosphamide/total body irradiation) intensified with IDA (15 mg/m2 per day, days -6 to -5) or VP16 (25 mg/kg per day, days -3 to -2) for acute myeloid leukemia and acute lymphoblastic leukemia, respectively. RESULTS: Between the two groups, no significant differences in terms of baseline characteristics, incidence of acute or chronic graft-versus-host disease (GVHD) or transplant-related mortality (TRM) (P=0.50) were observed. However, the IDA group demonstrated higher incidences of mucositis and Aspergillus pneumonia (P<0.01 and P=0.03, respectively). For the IDA and VP16 groups, relapse rates were 28% and 50%, respectively (P=0.13). For the same groups, the 2-year probabilities of leukemia-free survival (LFS) and overall survival (OS) were 72% versus 51% (P=0.04) and 74% versus 53% (P=0.04), respectively. CONCLUSION: This retrospective analysis suggests that conditioning regimens intensified with IDA can achieve better outcomes than conditioning regimens with VP16 in patients preparing to undergo allo-SCT for high-risk acute leukemia.


Assuntos
Etoposídeo/administração & dosagem , Transplante de Células-Tronco Hematopoéticas/métodos , Idarubicina/administração & dosagem , Leucemia/terapia , Condicionamento Pré-Transplante/métodos , Doença Aguda , Protocolos de Quimioterapia Combinada Antineoplásica , Aspergillus/isolamento & purificação , Aspergillus/patogenicidade , Bussulfano/administração & dosagem , China , Terapia Combinada , Ciclofosfamida/administração & dosagem , Citarabina/administração & dosagem , Intervalo Livre de Doença , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/prevenção & controle , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Hidroxiureia/administração & dosagem , Imunossupressores/uso terapêutico , Leucemia/mortalidade , Leucemia Mieloide Aguda/terapia , Masculino , Metilprednisolona/administração & dosagem , Mucosite/induzido quimicamente , Pneumonia/induzido quimicamente , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Pré-Medicação , Estudos Retrospectivos , Fatores de Risco , Semustina/administração & dosagem , Condicionamento Pré-Transplante/efeitos adversos , Transplante Homólogo/efeitos adversos , Resultado do Tratamento , Irradiação Corporal Total
11.
Chin Med J (Engl) ; 122(17): 1969-73, 2009 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-19781379

RESUMO

BACKGROUND: Most patients with acute myelogenous leukemia (AML) suffer from disordered hemostasis. We have previously shown that annexin II (Ann II), a high-affinity co-receptor for plasminogen/tissue plasminogen activator, plays a central role in primary hyperfibrinolysis in patients with acute promyelocytic leukemia (APL). The expression of Ann II in cells from patients with major subtypes of AML and the effect of arsenic trioxide (As2O3) on Ann II expression in AML cells were investigated to determine whether As2O3-mediated downregulation of Ann II could restore hemostatic stability. METHODS: A total of 103 patients (48 females and 55 males; age, 19 - 58 years) were included. Plasma samples were collected before and after treatment as well as after complete remission. Ann II and plasminogen activation were measured in leukemic cells during treatment with 1 micromol/L As2O3. RESULTS: Before As2O3 treatment, Ann II mRNA expression (real-time PCR) was the highest in M3 cells (P < 0.05), higher in M5 cells than that in M1, M2, M4, and M6 cells (P < 0.001), and positively correlated with Ann II protein expression (flow cytometry) (r = 0.752, P < 0.01). Exposure for up to 120 hours to As2O3 (1 micromol/L) had no significant effect on Ann II protein in M1 and M2 leukemic cells, but decreased Ann II protein expression twofold within 48 hours of exposure in M3 cells (P < 0.05) and twofold within 96 hours in M5 cells (P < 0.05). The rate of plasmin generation was higher in APL, M5, and M4 cells than in M1, M2, and M6 cells. CONCLUSIONS: As2O3 may reduce hyperfibrinolysis in AML by downregulation of Ann II. Furthermore, As2O3 affects more than one form of AML (APL, M4 and M5), suggesting its potential role in their management.


Assuntos
Anexina A2/metabolismo , Arsenicais/farmacologia , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Regulação para Baixo/efeitos dos fármacos , Leucemia Promielocítica Aguda/metabolismo , Óxidos/farmacologia , Adulto , Trióxido de Arsênio , Células da Medula Óssea/citologia , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Feminino , Humanos , Leucemia Promielocítica Aguda/fisiopatologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto Jovem
12.
Chin Med J (Engl) ; 121(18): 1770-4, 2008 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-19080355

RESUMO

BACKGROUND: Relapse remains an obstacle to successful allogeneic haematopoietic stem cell transplantation (allo-HSCT) for patients with acute leukaemia and no standard treatment is available. We assessed fludarabine and cytarabine with transfusion of donor haematopoietic stem cell in treating the relapse of acute leukaemia after allo-HSCT. METHODS: Seven patients, median age 34 years, with relapse of acute leukaemia after allo-HSCT received combination chemotherapy of fludarabine with cytarabine for 5 days. Five patients suffered from acute myeloid leukaemia (2 refractory) and 2 refractory acute lymphoblastic leukaemia. After the transplantation, the median relapse time was 110 days (range, 38 - 185 days). Two days after chemotherapy, 5 patients received infusion of donor's peripheral blood stem cells, mobilized by granulocyte colony stimulating factor. No prophylactic agents of graft versus host diseases were administered. RESULTS: Six patients achieved haematopoietic reconstitution. DNA sequence analysis at day 30 after treatment identified all as full donor chimera type. The median observation time was 189 days. After the treatment, the median time for neutrophilic granulocyte value = 0.5 x 10(9)/L and for platelet value = 20 x 10(9)/L were 13 days (range, 10 - 18 days) and 15 days (range, 11 - 24 days), respectively. Graft versus host disease occurred in 2 patients (acute) and 3 (chronic). Five patients suffered from pulmonary fungal infection (2 died), 3 haemorrhagic cystitis and 2 cytomegalovirus viraemia. The other patients died of leukaemia related deaths. Three patients with chronic graft versus host disease who had received donor peripheral blood stem cells reinfusion have survived for 375 days, 232 days and 195 days, respectively. CONCLUSIONS: Fludarabine with cytarabine plus the donor haematopoietic stem cell should be considered as an effective therapeutic regimen for relapse of acute leukaemia after allo-HSCT. The disease free state of patients may increase, though with high risk of secondary fungal infection.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Antimetabólitos Antineoplásicos/administração & dosagem , Antineoplásicos/administração & dosagem , Citarabina/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transplante Homólogo , Vidarabina/administração & dosagem , Vidarabina/análogos & derivados
13.
Zhonghua Xue Ye Xue Za Zhi ; 28(6): 363-6, 2007 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-17939398

RESUMO

OBJECTIVE: To explore the role of PTEN gene in the regulation of tissue factor (TF) expression in human neuroblastoma cells. METHODS: Expression of PTEN or TF was determined by Western blotting. Transcription of TF was examined by RT-PCR. PTEN gene expressing vector pCMV-PTEN was transfected with Lipofectamine2000. Phosphorylation of AKT was inhibited by LY294002 and then examined by Western blotting. RESULTS: Human neuroblastoma cell line SK-N-SH was PTEN-positive and expressed low level TF, whereas an other neuroblastoma cell line SK-N-MC was PTEN-negative but expressed high level TF. TF level was downregulated in SK-N-MC cells by enforced expression of PTEN in a dose dependent manner. Inhibition of TF was achieved along with inactivation of AKT. Furthermore treatment with PI3K/AKT inhibitor LY294002 also resulted in decrease of TF expression in a dose-dependent manner. CONCLUSION: Expression of TF is inhibited by PTEN gene via inactivating PI3K/AKT pathway, loss of PTEN might be the explanation of aberrant high-level TF in human neuroblastoma. It may be at least one of the mechanisms by which loss of PTEN expression confers to cancer progression.


Assuntos
Neuroblastoma/metabolismo , PTEN Fosfo-Hidrolase/genética , Tromboplastina/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Vetores Genéticos , Humanos , Neuroblastoma/genética , PTEN Fosfo-Hidrolase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Tromboplastina/genética , Transfecção
14.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 15(2): 391-5, 2007 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-17493354

RESUMO

To investigate the effect of arsenic trioxide (As(2)O(3)) or all-trans retinoic acid (ATRA) on the mRNA and protein expression of tissue factor (TF) and thrombomodulin (TM) and procoagulant activity (PCA) in NB4 cells. The NB4 cells were cultured in vitro and treated with As(2)O(3) or ATRA, expression of TF and TM antigen, and PCA change of treated NB4 cells were detected with ELISA, TF and TM mRNA transcription on the NB4 cells was assayed with reversed transcription polymerase chain reaction (RT-PCR). The results showed that 1 micromol/L As(2)O(3) and 1 micromol/L ATRA both gradually downregulated the expression of TF antigen and mRNA on NB4 cells, a human promyelocytic leukemia cell line, in time-dependent manner, as compared with control. The levels of TF antigen expression in AS(2)O(3) group were 13.3 +/- 1.8, 8.6 +/- 1.9, 10.8 +/- 1.5, 2.0 +/- 0.6 and 2.6 +/- 0.9 ng/10(7) respectively; while the levels of TF antigen expression in ATRA group were 12.4 +/- 1.1, 11.3 +/- 1.8, 5.7 +/- 1.7, 2.8 +/- 0.8 and 2.0 +/- 0.6 ng/10(7) at 24, 48, 72, 96 and 120 hours respectively (P<0.05). The procoagulant activity (PCA) of NB4 cells was decreased, blood coagulation times were 123.5 +/- 10.5, 156.3 +/- 11.6, 179.3 +/- 15.3, 248.9 +/- 20.1, 312.0 +/- 29.8 seconds in As(2)O(3) groups, respectively; 76.4 +/- 5.6, 146.8 +/- 10.9, 198.2 +/- 15.6, 265.8 +/- 20.6 and 363.8 +/- 31.9 seconds in ATRA groups respectively at 24, 48, 72, 96 and 120 hours (P<0.05). ATRA upregulated TM antigen expression on NB4 cells. It is concluded that the As(2)O(3) and ATRA decrease mRNA transcription of TF, downregulate expression of TF and reduce procoagulant activity in NB4 cells. The TM transcription and expression upregulated by ATRA may alleviate dysfunction of coagulation in APL.


Assuntos
Arsenicais/farmacologia , Leucemia Promielocítica Aguda/metabolismo , Óxidos/farmacologia , Trombomodulina/biossíntese , Tromboplastina/biossíntese , Tretinoína/farmacologia , Antineoplásicos/farmacologia , Trióxido de Arsênio , Humanos , Leucemia Promielocítica Aguda/patologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Trombomodulina/genética , Tromboplastina/genética , Tromboplastina/metabolismo , Células Tumorais Cultivadas
15.
Zhonghua Xue Ye Xue Za Zhi ; 28(9): 594-7, 2007 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-18246814

RESUMO

OBJECTIVE: To investigate the regulation of tissue factor (TF) on doxorubicin-induced apoptosis in human neuroblastoma. METHOD: The expression of TF was examined by Western blotting. TF siRNA-pSUPER plasmid was constructed by inserting a specific 19-nt silencing sequence targeting TF gene into pSUPER vector. Transfection of TF siRNA-pSUPER was performed using lipofectamine 2000. The activation of caspase-3 and PARP induced by doxorubicin was tested by Western blotting. The apoptotic cells were stained by Hochest 33342 and counted under fluorescence inverted microscope. RESULTS: (1) Human neuroblastoma cell line SK-N-MC expressed high level of TF. (2) Downregulation of TF expression was achieved by transfection of TF siRNA-pSUPER into SK-N-MC cells in a dose-dependent manner. (3) Cleavage of caspase-3 and PARP was increased in transfected SK-N-MC cell with down-regulation of TF. (4) TF siRNA treatment at 1 microg/ml for 8 h significantly increased apoptotic cell number in transfected SK-N-MC cells compared to that in non-transfected cells (P < 0.05) while exposing to 1 microg/ml doxorubicin for 8 h. CONCLUSIONS: Downregulation of TF expression by specific siRNA vector could increase the cytotoxicity of doxorubicin and enhance doxorubicin-induced apoptosis in human neuroblastoma cells.


Assuntos
Apoptose/efeitos dos fármacos , Doxorrubicina/farmacologia , Neuroblastoma/patologia , Interferência de RNA , Tromboplastina/genética , Apoptose/genética , Caspase 3/metabolismo , Linhagem Celular Tumoral , Vetores Genéticos , Humanos , Neuroblastoma/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo , RNA Interferente Pequeno/genética , Tromboplastina/metabolismo , Transfecção
16.
Zhonghua Yi Xue Za Zhi ; 87(44): 3127-9, 2007 Nov 27.
Artigo em Chinês | MEDLINE | ID: mdl-18269872

RESUMO

OBJECTIVE: To investigate the clinical effect of peripheral blood progenitor (PBPC) selected CD34(+) cell autologous transplantation in non-Hodgin lymphoma (NHL) patients. METHODS: Peripheral blood was collected from 5 NHL patients, 3 males and 2 females, aged 29 (14 - 58), t3 with T cell NHL, 1 with diffused large B cell NHL and 1 with genuine histiocytic lymphoma, 2 at the IIA stage and 3 at the IVB stage, and 4 in their first complete remission (CR1) period, and 1 in partial remission (PR2). CD34(+) cells were collected by magnetic-activated cell sorting system, enriched, and re-infused after pretreatment with chemotherapy and granulocyte-colony stimulating factor. Follow-up was conducted for 1 - 44 months. RESULTS: Magnetic-activated cell sorting resulted in 3.3 log depletion of CD34(-) cells and a median yield of CD34(+) selected cells was reinfused with the dose of 2.0 x 10(6)/kg. The median recovery rate of CD34(+) was 52% and purity rate was 86%. The WBC count became > 0.5 x 10(9)/L and the platelet count became > 20 x 10(9)/L at day 12 and day 19 respectively. Both the event-free and overall survival rate were 80.0% (4/5). One-year survival rate and 5-year estimated survival rate were 80% and 75% respectively. CONCLUSION: Brings prompt and stable engraftment, autologous selected PBPC CD34(+) cells transplantation may safely improve the clinical outcome of the patients with NHL.


Assuntos
Antígenos CD34/sangue , Linfoma não Hodgkin/cirurgia , Transplante de Células-Tronco de Sangue Periférico/métodos , Adolescente , Adulto , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Linfoma não Hodgkin/sangue , Linfoma não Hodgkin/mortalidade , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Transplante Autólogo
17.
Zhonghua Xue Ye Xue Za Zhi ; 25(9): 523-7, 2004 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-15569528

RESUMO

OBJECTIVE: To explore the role of tissue factor/activated factor VII (TF/FVIIa) complex in human ovarian cancer invasion and metastasis. METHODS: (1) Constructed an expression vector of TF, pcDNA3-TF and established a human ovarian cell line A2780/TF expressing high level TF by using molecular cloning and gene transfection techniques. (2) By Boyden chamber assay to count the numbers of A2780 and A2780/TF cells that penetrated the matrigel to the back of PVPF membrane after FVIIa stimulation. (3) BALB/c nude mice were used to establish experimental model of metastasis with A2780 or A2780/TF and the lung tissue sections were examined by microscopy for cancer metastasis. RESULTS: (1) Compared with their parental A2780 cells, A2780/TF cells expressed high level of TF mRNA (3.99 +/- 0.15 vs 0.97 +/- 0.23, P < 0.01) and TF antigen on cell surface \[(48.56 +/- 9.53)% vs (2.73 +/- 1.15)%, P < 0.01\]. (2) After stimulation, the A2780/TF cell number on the back of PVPF membrane increased from basal level 157.3 +/- 19.2 to 447.7 +/- 39.4 (P < 0.01), which could decreased to basal level when coincubated with anti-TF antibody. (3) Cancer metastasis was found in 22.2% of nude mice transplanted with A2780 cells, while in 88.9% of those transplanted with A2780/TF cells. CONCLUSION: TF could promote the invasion and metastasis of human ovarian cancer cells through TF/FVIIa pathway.


Assuntos
Fator VIIa/genética , Neoplasias Ovarianas/patologia , Tromboplastina/genética , Animais , Linhagem Celular Tumoral , Movimento Celular , Clonagem Molecular , Fator VIIa/fisiologia , Feminino , Vetores Genéticos , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Metástase Neoplásica , Transplante de Neoplasias , Neoplasias Ovarianas/genética , Tromboplastina/fisiologia , Transfecção , Transplante Heterólogo
18.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 12(5): 590-4, 2004 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-15498116

RESUMO

This study was aimed to investigate the effects and the mechanism of mangiferin on chronic myeloid leukemia cell lines K562 cells in vitro. The antiproliferation effects of mangiferin on K562 leukemia cells were tested by tetrazolium salt (MTT) method; the apoptosis induced by mangiferin on K562 cell line was explored by means of cell morphology, DNA gel electrophoresis and flow cytometry. The changes in bcr/abl gene expression was detected by using reverse transcriptase (RT)-PCR. The results showed that five different concentrations of mangiferin (25 - 200 micromol/L) dose-dependently and time-dependently inhibited the proliferation of K562 cells, and induced apoptosis in K562 cell line. RT-PCR revealed that bcr/abl gene expression was down-regulated when K562 cells had been treated with different concentrations of mangiferin. In conclusion, mangiferin remarkably inhibits the proliferation of K562 leukemia cells in vitro, and induces apoptosis in K562 cell line probably through down-regulation of bcr/abl gene expression.


Assuntos
Apoptose/efeitos dos fármacos , Xantonas/farmacologia , Proliferação de Células/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Citometria de Fluxo , Genes abl , Humanos , Células K562
19.
Zhonghua Xue Ye Xue Za Zhi ; 25(3): 143-6, 2004 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-15182581

RESUMO

OBJECTIVE: To construct the expression vector of human tissue factor (TF), and investigate the influence of TF/coagulant factor VIIa (FVIIa) complex on the transcriptional expression of urokinase plasminogen activator (u-PA) and u-PA receptor (u-PAR) in human ovarian cancer. METHODS: The human TF cDNA was obtained from placenta by RT-PCR and then inserted into eukaryotic expression vector pcDNA3 to obtain the TF-pcDNA3 combinant. This combinant was transfected into human ovarian cancer cell line A2780 by lipofectamine. Stably-transfected cells A2780/TF were screened. A2780 and A2780/TF cell lines were stimulated by FVIIa respectively, and the transcriptional levels of u-PA and u-PAR were examined by RT-PCR. RESULTS: (1) The constructed product was identified as TF-pcDNA3 combinant by sequencing. (2) TF was highly expressed not only at transcriptional level in the stable-transfected A2780/TF cell (transfected cell 3.91 +/- 0.28, untransfected cell 0.97 +/- 0.23, P < 0.01), but also on the membrane of the cell surface [transfected cell (48.56 +/- 9.53)%, untransfected cell (2.73 +/- 1.15)%, P < 0.01]. (3) The u-PA and u-PAR mRNA levels in A2780 cell line did not change significantly after stimulated by FVIIa; (4) While stimulated by FVIIa, the u-PAR mRNA levels in A2780/TF cells increased significantly in both dose-dependent and time-dependent manner, while the u-PA mRNA levels did not change significantly; (5) In the A2780/TF cell line the enhanced expression of u-PAR mRNA by FVIIa was significantly inhibited by coincubated with anti-TF antibody. CONCLUSION: TF/FVIIa complex could up-regulate the transcription of u-PAR in human ovarian cancer cells so as to enhance tumor invasion and metastasis.


Assuntos
Fator VIIa/metabolismo , Neoplasias Ovarianas/genética , Receptores de Ativador de Plasminogênio Tipo Uroquinase/genética , Tromboplastina/metabolismo , Regulação para Cima , Linhagem Celular Tumoral , Fator VIIa/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Ovarianas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Tromboplastina/genética , Ativador de Plasminogênio Tipo Uroquinase/genética , Ativador de Plasminogênio Tipo Uroquinase/metabolismo
20.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 12(6): 730-2, 2004 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-15631649

RESUMO

This study was aimed to investigate coagulation factor VII level in uremic patients with chronic renal failure and to explore theirs influence factors. The plasma levels of coagulation factor VII were detected in 30 uremic patients with chronic renal failure before and after hemodialysis for 1 month, the factor VII activity (FVII:C) was determined by one-stage coagulation method, while activated factor VII (FVIIa) was measured by one-stage coagulation method using recombinant soluble tissue factor, and factor VII antigen was detected by ELISA. The results showed that: (1) The FVIIa, FVII:C and FVIIAg levels in chronic uremic patients before hemodialysis were 4.00 +/- 0.86 microg/L, (148.5 +/- 40.4)% and (99.8 +/- 21.1)% respectively, which were significantly increased, as compared with healthy controls [2.77 +/- 1.02 microg/L, (113.1 +/- 33.0)% and (73.7 +/- 18.3)% respectively, P < 0.05]. (2) After hemodialysis the FVIIa, FVII:C and FVIIAg levels in uremic patients significantly enhanced to 5.56 +/- 1.45 microg/L, (200.8 +/- 68.7)% and (124.1 +/- 19.3)% respectively (P < 0.05). (3) The abnormal increase of coagulation factor VII was positively correlated with levels of blood uria nitrogen and serum creatinine before hemodialysis but not after hemodialysis. It is concluded that the enhanced levels of coagulation factor VII in chronic uremic patients suggested abnormal activated state, herperactivity and elevated production of factor VII which correlated with renal functional injury. The abnormality of factor VII in uremia may be aggravated by hemodialysis. Coagulation factor (FVII) may be a risk factor for cardiovascular events in uremic patients who especially had been accepted long-term hemodialysis.


Assuntos
Fator VII/análise , Uremia/sangue , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/etiologia , Diálise Renal , Fatores de Risco , Uremia/complicações , Uremia/terapia
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