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1.
Leuk Lymphoma ; : 1-6, 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31858854

RESUMO

Hematological toxicity is a common adverse effect of tyrosine kinase inhibitors (TKIs) for the treatment of chronic myeloid leukemia (CML). We retrospectively investigated the incidence of hematological toxicity after TKI administration in 143 CML patients and parameters associated with hematological toxicity. Severe hematological toxicity (grade 3-4) existed in 26 (18.2%) patients. Marrow fibrosis (MF), age, Sokal score, and spleen enlargement were associated with severe hematological toxicity. Further multivariate analysis showed that only MF was an independent predictor. Complete cytogenetic response(CCyR) rates and major molecular response (MMR) rates with grade 3-4 hematological toxicity were 42.3% and 26.9%, respectively, significantly lower than patients with grade 1-2 and without hematological toxicity (p = .032 for CCyR and p = .044 for MMR). Similar results were observed regarding progression-free survival (PFS) and overall survival (OS) (p = .011 for PFS and p = .037 for OS). This study indicated that MF was an independent predictor of severe hematological toxicity of TKIs.

2.
Lancet Haematol ; 6(6): e328-e337, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31126528

RESUMO

BACKGROUND: Anthracycline dose optimisation in the treatment of diffuse large B-cell lymphoma has rarely been tested. We aimed to find out whether R-CEOP70 was non-inferior to R-CHOP50 with less cardiotoxicity, and whether R-CEOP90 had a superior efficacy to R-CHOP50 or R-CEOP70 with acceptable toxic effects. METHODS: In this multicentre, phase 3, randomised, controlled study (NHL-001), patients with newly diagnosed diffuse large B-cell lymphoma or follicular lymphoma grade 3B were enrolled from 20 centres of the Multicenter Hematology-Oncology Programs Evaluation System in China. Young patients (16-60 years) were randomly assigned 1:1:1 (block size of six) to six courses of R-CHOP50, R-CEOP70, or R-CEOP90, and older patients (61-80 years) were assigned 1:1 (block size of four) to R-CHOP50 or R-CEOP70. Patients were randomly assigned using computer-assisted permuted-block randomisation. Investigators and patients were not masked to treatment assignment. In the R-CHOP50 group, patients were given rituximab 375 mg/m2 intravenously on day 0, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and vincristine 1·4 mg/m2 (maximum dose 2 mg) intravenously on day 1, and prednisone 60 mg/m2 (maximum dose 100 mg) orally from day 1-5; in the R-CEOP70 group, epirubicin 70 mg/m2 replaced doxorubicin; and in the R-CEOP90 group, high dose epirubicin 90 mg/m2 replaced doxorubicin. All patients received two additional courses of rituximab 375 mg/m2 intravenously every 21 days. Consolidation radiotherapy was given to patients with bulky disease at diagnosis or residual disease at the end of treatment. The primary endpoint was 2-year progression-free survival. The non-inferiority margin for R-CEOP70 versus R-CHOP50 was defined by hazard ratio [HR] as the upper limit of its 95% CI being no greater than 1·50. Analysis of efficacy and safety were of the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01852435. FINDINGS: From May 15, 2013, to March 16, 2016, a total of 648 patients were enrolled, including 404 (62%) young patients (R-CHOP50 [n=135], R-CEOP70 [n=134], or R-CEOP90 [n=135]), and 244 (38%) older patients (R-CHOP50 [n=122] or R-CEOP70 [n=122]). Four patients were excluded from the study for consent withdrawal and one patient for misdiagnosis before treatment. The 2-year progression-free survival in the R-CHOP50 group was 72·5% (95% CI 66·6-77·6) and in the R-CEOP70 group was 72·4% ([66·5-77·5]; HR 1·00 [0·73-1·38]; p=0·99). The non-inferiority was met and adverse events were similar between the two groups. Fewer patients in the R-CEOP70 group (14 [13%] of 110) presented with over 10% decrease in left ventricular ejection fraction (LVEF) than those in the R-CHOP50 group (31 [29%] of 108) at 3 years after remission. For young patients, the 2-year progression-free survival in the R-CEOP90 group was 88·8% (82·1-93·1) and was significantly improved compared with the R-CHOP50 group (75·9% [67·7-82·3]; 0·44 [0·25-0·76]; p=0·0047) and the R-CEOP70 group (77·4% [69·4-83·7%]; 0·49 [0·27-0·86]; p=0·017). Grade 3-4 neutropenia occurred more frequently in the R-CEOP90 group (97 [72%] of 134) than in the R-CHOP50 group (87 [65%] of 133) and R-CEOP70 group (84 [63%] of 133) in young patients but without further increase of clinically significant infections. Fewer patients in the R-CEOP70 group (7 [11%] of 66) and in the R-CEOP90 group (10 [13%] of 79) presented with more than 10% decrease in LVEF than those in the R-CHOP50 group (17 [26%] of 66) at 3 years after remission. INTERPRETATION: R-CEOP70 could serve as an alternative regimen to R-CHOP50 with mild long-term cardiotoxicity. Young patients with diffuse large B-cell lymphoma might benefit from high-dose epirubicin. Epirubicin is an alternative drug to doxorubicin in regular R-CHOP with mild long-term cardiotoxicity. FUNDING: National Natural Science Foundation of China, National Key Research and Development Program, Shanghai Commission of Science and Technology, Shanghai Municipal Education Commission Gaofeng Clinical Medicine Grant Support, Multicenter Clinical Research Project by Shanghai Jiao Tong University School of Medicine, Clinical Research Plan of Shanghai Hospital Development Center, and Chang Jiang Scholars Program.


Assuntos
Antraciclinas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antraciclinas/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/administração & dosagem , Feminino , Humanos , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Neutropenia/etiologia , Modelos de Riscos Proporcionais , Rituximab/administração & dosagem , Taxa de Sobrevida , Resultado do Tratamento , Vincristina/administração & dosagem , Adulto Jovem
3.
Oncol Rep ; 41(1): 415-426, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30365089

RESUMO

The Snail family transcriptional repressor 1 gene (Snail1) was screened in multiple myeloma cells (MMCs) from bortezomib-resistant MM patients and was found to be significantly associated with the development of drug-resistance mechanisms. In the present study, we first confirmed that the protein expression of Snail1 in bortezomib-resistant MMCs was significantly higher than that in MMCs without bortezomib resistance. The mechanistic studies confirmed that the enhancement of Snail1 expression in bortezomib-resistant MMCs directly upregulated transcription of the intracellular MDR1 gene to immediately develop multiple drug resistance mechanisms and inhibited P53 protein expression through the Snail1/hsa-miRNA-22-3p/P53 pathway to inhibit tumor cell apoptosis. By upregulating MDR1 and downregulating P53, Snail1 induced the drug resistance of MMCs to bortezomib, while Snail1 gene silencing effectively improved the drug sensitivity of MMCs to bortezomib chemotherapy. The present study further elucidated the drug resistance mechanisms of MMCs and provides evidence for increased clinical efficacy of bortezomib in MM patients.


Assuntos
Bortezomib/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/genética , Fatores de Transcrição da Família Snail/genética , Adulto , Idoso , Apoptose/genética , Linhagem Celular Tumoral , Resistência a Múltiplos Medicamentos/genética , Feminino , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Transdução de Sinais/genética , Ativação Transcricional/genética , Proteína Supressora de Tumor p53/genética , Regulação para Cima/genética
4.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 25(5): 1300-1306, 2017 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-29070099

RESUMO

OBJECTIVE: To study the expression of stromal cell derived factor-1α (SDF-1α) receptor CXCR7 in acute monocytic leukemia (AML-M5), and its effects on proliferation, apoptosis, invasion of acute monocytic leukemia cell line THP-1. METHODS: CXCR7 protein and mRNA expression levels in THP-1 cells and peripheral blood mononuclear cells (PBMNC) from the newly diagnosed AML-M5 patients and normal individuals were detected by flow cytometry, Western blot and RT-PCR respectively. CCK8, Annexin V/PI double staining and Transwell assay were used to observe the effects of CXCR7 on the proliferation, apoptosis, and invasion of THP-1 cells in vitro. RESULTS: The expression of CXCR7 on immature cell surface of the newly diagnosed AML-M5 patients was significantly higher than that in the control group (P<0.05). CXCR7 was also highly expressed on THP-1 cells surface. The CXCR7 protein and mRNA levels in THP-1 cells and PBMNC of AML-M5 patients were significantly higher than those in the control group (P<0.05). The THP-1 cell proliferation activity was higher in SDF-1α-treated group, but this activity could be inhibited by CXCR7 antibody (P<0.01). CXCR7 antibody did not affect THP-1 cell apoptosis (P>0.05). CXCR7 antibody could inhibit SDF-1α -induced THP-1 cell invasiveness (P<0.01). CONCLUSION: CXCR7 highly expresses in AML-M5 patients and THP-1 cells, and involves in cell proliferation and invasion. The blocking CXCR7 expression can reduce the risk of AML-M5 cell infiltration.


Assuntos
Leucemia Monocítica Aguda/imunologia , Receptores CXCR/metabolismo , Células THP-1/imunologia , Apoptose , Proliferação de Células , Quimiocina CXCL12 , Humanos , Leucócitos Mononucleares , Receptores CXCR/imunologia , Receptores CXCR4 , Transdução de Sinais
5.
Clin Lab ; 63(4): 765-771, 2017 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-28397467

RESUMO

BACKGROUND: Complement activation is critically involved in multiple autoimmune diseases. Immune thrombocytopenia (ITP) is a hemorrhagic condition with enhanced platelet clearance caused by antiplatelet autoantibodies. However, the roles of complements C3a, C5a, and soluble C5b-9 (sC5b-9) in the hemorrhage of ITP remain unknown. METHODS: Plasma C3a, C5a, and sC5b-9 levels in ITP patients were measured by enzyme-linked immunosorbent assay (ELISA). Antiplatelet autoantibodies (anti-GPIIb/IIIa and anti-GPIbα) were evaluated by modified monoclonal antibody immobilization of platelet antigen (MAIPA) assay. The severity of bleeding was assessed using the validated bleeding score for each ITP patient at onset. RESULTS: Levels of C3a, C5a, and sC5b-9 were significantly increased in active ITP patients, compared with those in controls (p < 0.001). However, levels of C3a, C5a, and sC5b-9 were not changed by treatment of HD-DXM. In addition, the C3a levels were correlated with the increase in bleeding scores from the patients with ITP (p < 0.05, r = 0.256). In contrast, neither platelet counts nor antiplatelet autoantibodies (anti-GPIIb/IIIa and anti-GPIbα) showed any correlation with levels of C3a, C5a, and sC5b-9. CONCLUSIONS: Levels of C3a, C5a, and sC5b-9 are increased in patients with ITP, suggesting a hyperactive complement system. Certain complement components, such as C3a, may contribute to hemorrhage of patients with ITP.


Assuntos
Púrpura Trombocitopênica Idiopática , Autoanticorpos , Plaquetas , Complemento C3a , Ensaio de Imunoadsorção Enzimática , Humanos , Contagem de Plaquetas
6.
J Hematol Oncol ; 10(1): 69, 2017 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-28298231

RESUMO

The efficacy and safety of chidamide, a new subtype-selective histone deacetylase (HDAC) inhibitor, have been demonstrated in a pivotal phase II clinical trial, and chidamide has been approved by the China Food and Drug Administration (CFDA) as a treatment for relapsed or refractory peripheral T cell lymphoma (PTCL). This study sought to further evaluate the real-world utilization of chidamide in 383 relapsed or refractory PTCL patients from April 2015 to February 2016 in mainland China. For patients receiving chidamide monotherapy (n = 256), the overall response rate (ORR) and disease control rate (DCR) were 39.06 and 64.45%, respectively. The ORR and DCR were 51.18 and 74.02%, respectively, for patients receiving chidamide combined with chemotherapy (n = 127). For patients receiving chidamide monotherapy and chidamide combined with chemotherapy, the median progression-free survival (PFS) was 129 (95% CI 82 to 194) days for the monotherapy group and 152 (95% CI 93 to 201) days for the combined therapy group (P = 0.3266). Most adverse events (AEs) were of grade 1 to 2. AEs of grade 3 or higher that occurred in ≥5% of patients receiving chidamide monotherapy included thrombocytopenia (10.2%) and neutropenia (6.2%). For patients receiving chidamide combined with chemotherapy, grade 3 to 4 AEs that occurred in ≥5% of patients included thrombocytopenia (18.1%), neutropenia (12.6%), anemia (7.1%), and fatigue (5.5%). This large real-world study demonstrates that chidamide has a favorable efficacy and an acceptable safety profile for refractory and relapsed PTCL patients. Chidamide combined with chemotherapy may be a new treatment choice for refractory and relapsed PTCL patients but requires further investigation.


Assuntos
Aminopiridinas/administração & dosagem , Benzamidas/administração & dosagem , Linfoma de Células T Periférico/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Aminopiridinas/efeitos adversos , Aminopiridinas/uso terapêutico , Anemia/induzido quimicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Benzamidas/efeitos adversos , Benzamidas/uso terapêutico , China , Intervalo Livre de Doença , Fadiga/induzido quimicamente , Feminino , Inibidores de Histona Desacetilases/uso terapêutico , Humanos , Linfoma de Células T Periférico/complicações , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Recidiva , Indução de Remissão/métodos , Terapia de Salvação/efeitos adversos , Terapia de Salvação/métodos , Trombocitopenia/induzido quimicamente , Adulto Jovem
7.
J Hematol Oncol ; 10(1): 46, 2017 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-28179000

RESUMO

Immune thrombocytopenia (ITP) is a common autoimmune bleeding disorder. Despite considerable investigation, the pathogenesis of ITP remains incompletely understood, and for many patients, effective therapy is still unavailable. Using murine models and in vitro studies of human blood samples, we recently identified a novel Fc-independent platelet clearance pathway, whereby antibody-mediated desialylated platelets can be cleared in the liver via asialoglycoprotein receptors, leading to decreased response to standard first-line therapies targeting Fc-dependent platelet clearance. Here, we evaluated the significance of this finding in 61 ITP patients through correlation of levels of platelet desialylation with the efficacy of first-line therapies. We found that desialylation levels between different responses to treatment groups were statistically significant (p < 0.01). Importantly, correlation analysis indicated response to treatment and platelet desialylation were related (p < 0.01), whereby non-responders had significantly higher levels of platelet desialylation. Interestingly, we also found secondary ITP and certain non-ITP thrombocytopenias also exhibited significant platelet desialylation compared to healthy controls. These findings designate platelet desialylation as an important biomarker in determining response to standard treatment for ITP. Furthermore, we show for the first time platelet desialylation in other non-ITP thrombocytopenias, which may have important clinical implications and deserve further investigation.


Assuntos
Assialoglicoproteínas/imunologia , Plaquetas/imunologia , Púrpura Trombocitopênica Idiopática/diagnóstico , Adulto , Animais , Anticorpos/imunologia , Receptor de Asialoglicoproteína/imunologia , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Oligossacarídeos/imunologia , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/imunologia , Complexo Glicoproteico GPIb-IX de Plaquetas/imunologia , Indução de Remissão , Resultado do Tratamento
8.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 24(2): 427-32, 2016 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-27151004

RESUMO

OBJECTIVE: To investigate the predictive value of neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) for the patients with diffuse large B-cell lymphoma (DLBCL). METHODS: The clinical data of 57 DLBCL patients admitted in the First Affiliated hospital of Anhui Medical University were analyzed retrospectively. According to ROC curve, the cut-off value for NLR and PLR was deterimined, and the patients were divided into high and low NLR/PLR groups before first chamotherapy. Then the relation of NLR and PLR with overall survival (OS) and progression-free survival (PFS) was analyzed by univariate and multivariate COX regression. RESULTS: The optimal cut-off value for NLR and PLR was 2.915 and 270.27, respectively. NLR at the diagnosis was found to be an independent predictor for OS and PFS by univariate and multivariate analysis, while the PLR was an independent predictor for PFS, but did not affect the OS. CONCLUSION: NLR and PLR may provide additional prognostic information for DLBCL patients.


Assuntos
Plaquetas/citologia , Linfócitos/citologia , Linfoma Difuso de Grandes Células B/diagnóstico , Neutrófilos/citologia , Intervalo Livre de Doença , Humanos , Contagem de Linfócitos , Análise Multivariada , Prognóstico , Estudos Retrospectivos
9.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 23(5): 1380-5, 2015 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-26524042

RESUMO

OBJECTIVE: To investigate the influence of divalent cation chelator EDTA and heparin sodium on the detection of ITP platelet-specific autoantibodies by the modified monoclonal antibody immobilization of platelet antigen assay (MAIPA) and to explore the relationship between types of platelet specific autoantibodies and glucocorticoid efficacy. METHODS: The samples were obtained from EDTA- and heparin- anticoagulant ITP patients, respectively, so as to detect the platelet-specific autoantibodies (GPIIb/IIIa and GPIbα) in 140 ITP samples by modified MAIPA, then the differences between these two methods were compared. RESULTS: Out of 140 cases in EDTA group, 55 cases were positive for GPIIb/IIIa, while 76 cases in heparin group were positive for GPIIb/IIIa, 42 cases in both group were repeatable; among them 13 cases were positive in EDTA group and negative in heparin group, while 34 cases were positive in heparin group and negative in EDTA group, there was significant difference between them (x (2) = 9.38, P < 0.05), 62 cases in 140 cases of EDTA group were positive for GPIba, while 51 cases in heparin group were positive for GPIba, 42 cases in both group were repeatabe; among them 20 cases were positive in EDTA group and negative in heparin group, while 9 cases were positive in heparin group and negative in EDTA group, there was no significant difference between them (x (2) = 3.44, P > 0.05). A total of 320 cases received a standard glucocorticoid treatment, out of them 143 cases were positive for GPIbα with effective rate 39.9%, 177 cases were negative for GPIbα with effective rate 79.7%, there was statisticalty significant difference between them (x (2) = 53.115, P < 0.05). CONCLUSION: EDTA anticoagulant (a divalent cation chelator) has a significant influence on detection of ITP platelet-specific autoantibodies (GPIIb/IIIa) by a modified MAIPA method and the GPIbα antibody positive may be one of the important factors that results in un-sensitivity of ITP patients to glucocorticoid treatment.


Assuntos
Anticoagulantes/uso terapêutico , Autoanticorpos/sangue , Plaquetas/imunologia , Glucocorticoides/uso terapêutico , Púrpura Trombocitopênica Idiopática/imunologia , Anticorpos Monoclonais , Antígenos de Plaquetas Humanas , Fibrinolíticos , Heparina , Humanos , Complexo Glicoproteico GPIIb-IIIa de Plaquetas , Púrpura Trombocitopênica Idiopática/sangue
10.
Nat Commun ; 6: 7737, 2015 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-26185093

RESUMO

Immune thrombocytopenia (ITP) is a common bleeding disorder caused primarily by autoantibodies against platelet GPIIbIIIa and/or the GPIb complex. Current theory suggests that antibody-mediated platelet destruction occurs in the spleen, via macrophages through Fc-FcγR interactions. However, we and others have demonstrated that anti-GPIbα (but not GPIIbIIIa)-mediated ITP is often refractory to therapies targeting FcγR pathways. Here, we generate mouse anti-mouse monoclonal antibodies (mAbs) that recognize GPIbα and GPIIbIIIa of different species. Utilizing these unique mAbs and human ITP plasma, we find that anti-GPIbα, but not anti-GPIIbIIIa antibodies, induces Fc-independent platelet activation, sialidase neuraminidase-1 translocation and desialylation. This leads to platelet clearance in the liver via hepatocyte Ashwell-Morell receptors, which is fundamentally different from the classical Fc-FcγR-dependent macrophage phagocytosis. Importantly, sialidase inhibitors ameliorate anti-GPIbα-mediated thrombocytopenia in mice. These findings shed light on Fc-independent cytopenias, designating desialylation as a potential diagnostic biomarker and therapeutic target in the treatment of refractory ITP.


Assuntos
Anticorpos Monoclonais Murinos/imunologia , Integrina beta3/imunologia , Neuraminidase/imunologia , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/imunologia , Complexo Glicoproteico GPIb-IX de Plaquetas/imunologia , Púrpura Trombocitopênica Idiopática/imunologia , Animais , Plaquetas , Western Blotting , Citometria de Fluxo , Hepatócitos/metabolismo , Humanos , Imuno-Histoquímica , Camundongos , Camundongos Knockout , Neuraminidase/antagonistas & inibidores
11.
Med Princ Pract ; 24(5): 458-64, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26111958

RESUMO

OBJECTIVE: We aimed to investigate the expression of interleukin 12 (IL-12) family cytokines (IL-12, IL-23, IL-27 and IL-35) and their relevant cytokines (IFN-γ, IL-4, IL-17A and IL-10) in patients with chronic immune thrombocytopenia (cITP) as well as the effect of high-dose dexamethasone (HD-DXM) treatment on this expression. MATERIALS AND METHODS: DXM was administered orally at a dose of 40 mg per day for 4 consecutive days to 38 patients with cITP. We measured the plasma levels of IL-12p70, IL-23, IL-27, IFN-γ, IL-4 and IL-17A before and after treatment and also in 36 matched healthy controls, by means of FlowCytomix™ technology. The plasma levels of IL-10 and IL-35 were measured by enzyme-linked immunosorbent assay. RESULTS: Significantly higher plasma levels of IL-12p70, IL-23, IL-27, IFN-γ and IL-17A were observed in cITP patients than in controls (p < 0.01), and after HD-DXM treatment, these levels decreased significantly (p < 0.01). However, significantly lower plasma levels of IL-4, IL-10 and IL-35 were observed in cITP patients than in controls (p < 0.01); after the HD-DXM treatment, these levels had increased significantly in the cITP patients (p < 0.01). Moreover, the cytokine levels of patients who attained a complete response returned to the levels of normal controls (p > 0.05) but were not corrected in the patients who had no response (p < 0.01). CONCLUSIONS: The patients with cITP had abnormal expression of the IL-12 family cytokines and their relevant cytokines levels, and HD-DXM treatment corrected the derangement of plasma cytokines. Measuring cytokine levels may help in the clinical assessment of cITP.


Assuntos
Citocinas/biossíntese , Dexametasona/uso terapêutico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/imunologia , Citocinas/sangue , Citocinas/classificação , Dexametasona/administração & dosagem , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Interleucina-12/biossíntese , Interleucina-12/sangue , Masculino , Púrpura Trombocitopênica Idiopática/sangue
12.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 23(2): 460-4, 2015 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-25948205

RESUMO

OBJECTIVE: To detect desialylation of platelets in primary immune thrombocytopenia(ITP) patients with FITC-labelled ECL and RCA-1, and compare the correlation of the desialylation level and the efficacy of first-line therapy for ITP. METHODS: Before treatment, 48 ITP patients were selected and their levels of ECL and RCA-1 were detected with flow cytometry. RESULTS: The desialylation level in the different efficacy groups by using the first-line therapy of corticosteroids and (or) intravenous immunoglobulin G (IVIG) had a statistically significant difference (P<0.05). The correlation analysis showed negative relation of the therapeutic efficacy with desialylation level, that is to say, the more high of desialylation level, the more poor therapeutic efficacy of the first-line therapy. CONCLUSION: The desialylation level of platelets in ITP patients is related with the first-line therapeutic efficacy, the efficacy for patients with high desialylation level is poor, suggesting that the FcR-independent pathway exists in clearance of platelets in ITP patients. Therefore, the desialylation level of platelets may suggest the first-line therapeutic efficacy for ITP patients to a certain degree, and may be used as a potential target for the treatment of refractory ITP.


Assuntos
Plaquetas , Púrpura Trombocitopênica Idiopática , Corticosteroides , Citometria de Fluxo , Humanos , Imunoglobulina G , Imunoglobulinas Intravenosas
13.
Zhonghua Xue Ye Xue Za Zhi ; 36(3): 202-5, 2015 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-25854462

RESUMO

OBJECTIVE: To investigate the different outcomes by dexamethasone in adults immune thrombocytopenia purpura (ITP) with different types of platelet specific-autoantibodies. METHODS: A total of 185 ITP were enrolled, 61 males and 124 females, with a median age of 42 (18-83) years, including 117 newly diagnosed, 35 persistent, and 33 chronic cases. All the patients received the dexamethasone at an initial dose of 40 mg per day for 4 days and a low dose of 5-10 mg for 3-4 weeks. The platelet specific-autoantibodies were identified by the modified monoclonal antibody-specific immobilization of platelet antigen (MAIPA) assay. RESULTS: Among the IgG positive patients, the response rates in anti-GPIIb/IIIa antibody, anti-GPIbα antibody, both antibody positive, and both antibody negative were 87.5%, 50.0%, 68.0%, and 72.3% (χ²=11.489, P<0.05), respectively. Among the IgM positive patients, the response rates in the four groups were 82.1%, 71.4%, 61.9%, and 68.9% (χ²=2.719, P=0.437), respectively. Among the GPIbα antibody positive patients, the response rates in IgG alone, IgM alone, both positive, and both negative were 52.4%, 59.1%, 76.1%, and 77.9% (χ²=10.811, P<0.05), respectively. Among the GPIIb/IIIa antibody positive patients, the response rates in the four groups were 73.3%, 71.0%, 78.6%, and 66.3% (χ²=1.374, P=0.719), respectively. CONCLUSION: ITP patients with GPIbα-IgG antibody have worse response to dexamethasone treatment.


Assuntos
Púrpura Trombocitopênica Idiopática , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais , Autoanticorpos , Plaquetas , Dexametasona , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complexo Glicoproteico GPIIb-IIIa de Plaquetas , Adulto Jovem
14.
J Pediatr Hematol Oncol ; 36(8): 617-23, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25072364

RESUMO

Bone marrow-derived mesenchymal stem cells (BM-MSCs) in the marrow stroma provide a scaffold for hematopoiesis. Chemokine stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 have been shown to affect the engraftment of hematopoietic stem cells. However, little is known about SDF-1/CXCR4's functions in regulating BM-MSCs in humans. As an initial step toward this issue, we have evaluated expression of SDF-1/CXCR4 in the BM-MSCs from a cohort of adolescents and young adults with acute lymphoblastic leukemia (ALL). We found a decrease of the CXCR4 level and an increase of the SDF-1 level in these MSCs of ALL. Moreover, cell migration appeared to be impaired in the MSCs of ALL. These changes were reversed by chemotherapy. Taken together, alteration of SDF-1/CXCR4 expression could be potentially developed as biomarkers for monitoring the effectiveness of chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Quimiocina CXCL12/genética , Monitoramento de Medicamentos/métodos , Células-Tronco Mesenquimais/efeitos dos fármacos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Receptores CXCR4/genética , Adolescente , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/fisiologia , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Movimento Celular/efeitos dos fármacos , Movimento Celular/fisiologia , Células Cultivadas , Quimiocina CXCL12/metabolismo , Dipeptidil Peptidase 4/genética , Dipeptidil Peptidase 4/metabolismo , Expressão Gênica/efeitos dos fármacos , Hematopoese/efeitos dos fármacos , Hematopoese/fisiologia , Humanos , Células-Tronco Mesenquimais/fisiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Receptores CXCR4/metabolismo , Adulto Jovem
15.
Cardiovasc Hematol Disord Drug Targets ; 13(1): 50-8, 2013 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-23082940

RESUMO

Phagocytes were first described by Dr. Metchnikoff in 1873. The roles of phagocytes in innate and adaptive immunity have been well established to date, although the molecular mechanisms involved in initiating phagocytosis (through Fc or other receptors) remain to be further explored. Phagocytes in the reticuloendothelial system, particularly macrophages, have been implicated in the clearance of senescent blood cells. The destruction of these cells may be primarily mediated via an Fc-independent pathway. Fc-independent phagocytosis may also play an important role in platelet clearance, including in autoimmune thrombocytopenia (ITP), and in clearance of platelet-rich emboli detached from sites of vascular injury. In ITP, the two major platelet auto-antigens have been located on glycoprotein (GP)IIbIIIa and the GPIb complex. It has been demonstrated that anti-GPIb antibodies, in contrast to anti-GPIIbIIIa, can induce thrombocytopenia in an Fc-independent manner. We further demonstrated in an animal model that intravenous IgG (IVIG) is unable to ameliorate thrombocytopenia caused by most anti-GPIb antibodies, despite its efficacy in anti- GPIIbIIIa-mediated thrombocytopenia. Our data was supported by subsequent retrospective studies with ITP patients by several independent groups. Most recently, we found that anti-GPIb-mediated ITP was also resistant to steroid therapy and that platelet activation and apoptosis induced by anti-GPIb antibodies may be involved in the Fc-independent platelet clearance. Therefore, identification of antibody specificity in patients, e.g. anti-GPIIbIIIa (Fc-dependent) versus anti-GPIb (Fc-independent), may be important for therapies against ITP, as well as other immune-mediated thrombocytopenias.


Assuntos
Imunoglobulinas Intravenosas/uso terapêutico , Fagocitose/imunologia , Trombocitopenia/tratamento farmacológico , Trombocitopenia/imunologia , Animais , Modelos Animais de Doenças , Humanos , Imunoglobulinas Intravenosas/imunologia , Fagocitose/efeitos dos fármacos , Estudos Retrospectivos
16.
Zhonghua Xue Ye Xue Za Zhi ; 33(3): 183-6, 2012 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-22781603

RESUMO

OBJECTIVE: To evaluate the relationship between plasma trough level of imatinib and clinical outcomes in Chinese CML patients. METHODS: Plasma trough levels in 416 CML patients who received imatinib orally in six general hospitals were assessed. The correlations of imatinib plasma trough level with baseline characteristics including age, weight and BSA, and clinical response were evaluated. RESULTS: (1) Effects of age, body weight and BSA on imatinib plasma trough levels were not to be clinically significant. (2) Median imatinib plasma trough levels was 1271 (109-4329). Imatinib plasma trough level was related to dose of imatinib administration. Plasma trough levels at imatinib of dose < 400, 400 and > 400 mg were (969 ± 585), (1341 ± 595) and (1740 ± 748) µg/L (P < 0.01), respectively. (3) There was no statistic difference in imatinib plasma trough level with complete cytogenetic response [CCyR (1337 ± 571) µg/L vs no CCyR (1354 ± 689) µg/L, P = 0.255]. (4) Imatinib plasma trough level might be important for a good clinical response in some CML patients. CONCLUSION: There was a large interpatient variability in imatinib plasma concentration in Chinese CML patients. No correlation of imatinib plasma trough level with CCyR was observed. However, higher doses of imatinib were shown to attain greater trough plasma concentration, suggesting that imatinib plasma trough level might be important for a good clinical response in some CML patients.


Assuntos
Benzamidas/sangue , Benzamidas/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/sangue , Piperazinas/sangue , Piperazinas/uso terapêutico , Pirimidinas/sangue , Pirimidinas/uso terapêutico , Adolescente , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , Feminino , Humanos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
17.
Am J Hematol ; 87(2): 206-8, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22139961

RESUMO

Immune thrombocytopenia (ITP) is characterized by platelet clearance mediated primarily by autoantibodies against the platelet GPIIbIIIa and/or GPIbα. Steroid therapy is a first-line treatment for ITP. However, some patients are refractory to this therapy and currently no method can predict which patients will respond. To evaluate whether steroids are equally efficacious in treating patients with ITP caused by anti-GPIIbIIIa versus anti-GPIbα antibodies, we performed a retrospective study on 176 newly diagnosed patients with acute ITP who had severe bleeding symptoms and were admitted as resident patients to the hospital. The patients were treated first with intravenous administration of high-dose dexamethasone (DXM), followed by oral administration of prednisone. Response to therapy was observed in a majority of patients with antibodies specific for GPIIbIIIa (31/43) or without detectable antibodies against either GPIIbIIIa or GPIbα (36/45). In contrast, the steroid response was significantly lower in patients with anti-GPIbα antibodies (9/34) or with antibodies against both GPIbα and GPIIbIIIa (16/54). The preliminary findings of this study suggest that in future prospective clinical trials including corticosteroids, the anti-GPIbα, and -GPIIbIIIa status should be assessed in order to test its potential relevance in deciding future treatments.


Assuntos
Autoanticorpos/imunologia , Dexametasona/uso terapêutico , Glucocorticoides/uso terapêutico , Glicoproteínas de Membrana/imunologia , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/imunologia , Prednisona/uso terapêutico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Plaquetas/efeitos dos fármacos , Plaquetas/imunologia , Plaquetas/patologia , Dexametasona/farmacologia , Esquema de Medicação , Monitoramento de Medicamentos , Feminino , Glucocorticoides/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Complexo Glicoproteico GPIb-IX de Plaquetas , Prednisona/farmacologia , Púrpura Trombocitopênica Idiopática/imunologia , Púrpura Trombocitopênica Idiopática/patologia , Estudos Retrospectivos , Resultado do Tratamento
18.
Zhonghua Zhong Liu Za Zhi ; 33(5): 345-8, 2011 May.
Artigo em Chinês | MEDLINE | ID: mdl-21875462

RESUMO

OBJECTIVE: To investigate the effect of total astragalosides (TA) on proliferation and apoptosis in human leukemia NB4 cells in vitro. METHODS: The NB4 cells were treated with TA at different concentrations for 48 h in culture. Growth inhibition rates were measured by CCK-8 method. Flow cytometry was used to explore the cell apoptosis and the activity of NF-κB and Akt during apoptosis. RESULTS: TA at different concentrations (200, 400, 600, 800 mg/L) inhibited proliferation of NB4 cells in a dose-dependent manner (P < 0.05), and the inhibitory rates of TA on NB4 cells were (14.54 ± 3.20)%, (24.79 ± 3.98)%, (57.28 ± 4.71)% and (88.28 ± 4.65)%, respectively. In terms of the induction of apoptosis, there was a significant difference between the TA group and blank control [(1.80 ± 1.24)%, P < 0.05]. At TA doses of 200, 400 and 600 mg/L, the apoptotic rates of NB4 cells were (10.03 ± 3.31)%, (14.87 ± 3.65)%, (23.45 ± 1.90)%, respectively. Besides, TA induced apoptosis of NB4 cells in a dose-dependent manner in the groups of 200 mg/L, 400 mg/L, 600 mg/L (P < 0.05). But there was no significant difference in apoptotic rates between the groups of 800 mg/L and 600 mg/L [(23.45 ± 1.90)%, P > 0.05]. In the group of 800 mg/L, the necrotic cells increased highly and the necrotic rate reached (45.65 ± 3.16)%. After TA treatment of NB4 cells at different concentrations (200, 400, 600 mg/L), the expression of NF-κB protein was significantly decreased compared with that of the blank control (9.79 ± 0.95, P < 0.05), while Akt protein was not significantly decreased (P > 0.05). CONCLUSION: TA can inhibit the growth of NB4 cells and induce apoptosis in NB4 cells through an Akt-independent NF-κB signaling pathway.


Assuntos
Apoptose/efeitos dos fármacos , Astragalus propinquus/química , Medicamentos de Ervas Chinesas/farmacologia , Leucemia Promielocítica Aguda/patologia , Saponinas/farmacologia , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/isolamento & purificação , Humanos , Leucemia Promielocítica Aguda/metabolismo , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Saponinas/administração & dosagem , Saponinas/isolamento & purificação
19.
Zhonghua Xue Ye Xue Za Zhi ; 31(9): 590-3, 2010 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-21122317

RESUMO

OBJECTIVE: To investigate the frequency and clinical implication of JAK2 mutation in patients with myeloproliferative neoplasm(MPN)and the correlation between the mutation and thrombosis. METHODS: The clinical and laboratory data of 107 MPN patients was retrospectively analyzed. JAK2 mutation were detected with allele-specific polymerase chain reaction (AS-PCR) and sequencing. The significance of the mutation in disease diagnosis and molecular pathogenesis and the correlation between the mutation and thrombosis was analysed. RESULTS: JAK2 mutation was detected in 71 (66.4%) and thrombosis in 34 (31.8%) of the 107 MPN patients. Thrombosis occurred in 34.8% (16/46) of polycythemia vera (PV), 32.6% (14/43) of essential thrombocythemia (ET), and 22.2% (4/18) of primany myelofibrosis (PMF) patients. The difference among the 3 groups was not significant (χ(2) = 0.96, P > 0.05). The frequency of thrombosis in JAK2(+) MPN patients (82.4%, 28/34) was higher than that in JAK2(-) MPN patients (17.6%, 6/34) (χ(2) = 5.71, P < 0.05). The frequency of thrombosis in MPN patients > 60 years was higher (41.5%, 27/65) than that in patients < 60 years (16.7%, 7/42) (χ(2) = 7.28, P < 0.01). CONCLUSION: JAK2 V617F mutation occurs in significant percentage of Chinese patients with MPN. Patients with JAK2 mutation and older age are more succeptible to thrombosis. JAK2 mutation screening in patients with unknown thrombosis is helpful to reveal the underlying latent-MPN.


Assuntos
Transtornos Mieloproliferativos , Neoplasias , Humanos , Mutação , Transtornos Mieloproliferativos/genética , Trombocitemia Essencial/genética , Trombose
20.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 18(1): 49-53, 2010 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-20137117

RESUMO

This study was purposed to evaluate ABL tyrosine kinase point mutations in imatinib-treated chronic myeloid leukemia (CML) patients and their clinical significance. 51 bone marrow samples from 28 imatinib-resistant patients and 10 newly diagnosed CML patients were collected. ABL kinase domain of bcr-abl allele was amplified by nested reverse transcription-polymerase chain reaction, followed by purifying, directly sequencing and sequence homology analysis of amplified products in order to determine the existence and type of point mutation. The results showed that the point mutations were found in 12 of 38 patients, and all the 12 ones progressed to advanced disease or death. 2 patients showed Met351Thr mutation, 7 patients showed Glu252His, 2 patients showed Glu279Lys, the other types were Glu255Val and Glu355Gly, each of which was tested in one patient. The incidence of the point mutation was 17.6%, 45.5% and 44.4% in chronic, accelerated and blast phase respectively. The incidences of point mutation in hematologically and genetically resistant patients were 50% (5/10) and 44.4% (8/18), and the 95% confidence interval (CI) was 12.3% - 87.7% and 19% - 69.9% respectively. It is concluded that ABL kinase point mutation is an important mechanism of imatinib resistance, monitoring the ABL kinase domain point mutation is helpful to estimating the prognosis and adjusting the therapeutic strategy.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Mutação Puntual , Proteínas Tirosina Quinases/genética , Adulto , Idoso , Benzamidas , Feminino , Humanos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Resultado do Tratamento , Adulto Jovem
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