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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.
Cell Cycle ; 18(14): 1635-1645, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31213131

RESUMO

Cutaneous T-cell lymphoma (CTCL) is associated with the downregulation of miR-337 expression, although the exact underlying mechanism is unknown. In the present work, we investigated the molecular mechanism and function of miR-337 in regulating CTCL cell viability and invasion. We observed that miR-337 expression was downregulated in both CTCL tumors and cell lines. Furthermore, CCK assay, BrdU incorporation assay, and flow cytometry revealed that transfection with the miR-337 mimic resulted in decreased proliferation and increased apoptotic levels in CTCL cells. Results of the Transwell migration assay indicated that the miR-337 mimic decreased CTCL cell invasion in vitro. Both bioinformatics prediction and the dual-luciferase reporter assay revealed that miR-337 targets the 3'-UTR of STAT3 for silencing. Overexpression of STAT3 counteracted the pro-apoptotic influence of miR-337 in CTCL cell lines and restored their invasion properties. The results thus indicate that the miR-337-STAT3 axis inhibits the proliferation of malignant T cells and that miR-337 may serve as a promising therapeutic target for CTCL.

3.
Nanoscale ; 11(16): 7813-7824, 2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-30958488

RESUMO

In this work, we prepared ultrathin MoS2 nanosheets with exposed active edge sites and high electric conductivity that can sufficiently absorb light in the visible region to enable solar energy conversion. The gold nanocrystal-decorated MoS2 nanosheets facilitate sufficiently enhanced photoelectrochemical water splitting in the UV-visible region. Different Au nanostructures, such as Au nanoparticles and nanorods, were modified on the surface of MoS2 nanosheets to promote photoelectrochemical water decomposition. By spin-coating a synthetic gold-modified MoS2 hybrid photoanode on a FTO substrate, the efficiency of photoelectrochemical water oxidation was significantly enhanced, by 2 times (nanorods) and 3.5 times (nanoparticles) in the visible-infrared region; furthermore, the average optical resistance was reduced by a factor of two compared to the MoS2 photoanode without Au, and the photocurrent increases exponentially when the system bias was greater than 0.7 volts. The Au-MoS2 metal-semiconductor interface plays an important role in studying the surface plasmon interactions, charge transfer mechanism, and electric field amplification. This rational design for such a unique hybrid nanostructure explains the plasmon-enhanced photoelectrochemical water splitting. This current contribution provides a new path for using the plasmonic metal/semiconductor heterostructure to effectively harvest UV-visible light for solar fuel generation.

4.
Cancer Biol Ther ; 20(6): 877-885, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30894066

RESUMO

BCR fused ABL kinase is the critical driving oncogene for chronic myeloid leukemia (CML) and has been extensively studied as the drug discovery target in the past decade. The successful introduction of tyrosine kinase inhibitors (TKI) such as Imatinib, Dasatinib and Bosutinib has greatly improved the CML patient survival rate. However, upon the chronic treatment, a variety of TKI resistant mutants, such as the V299L mutant which has been found in more and more patients with the high-throughput sequencing technology, are observed, although the incidence is still considered rare compared to the more prevalent gatekeeper T315I mutant. However, with the progress of the precision medicine concept, the rare mutation (or the orphan drug target) has attracted more and more attention. Here we report a novel type II BCR-ABL kinase inhibitor, CHMFL-ABL-039, which not only displayed great potency (IC50: 7.9 nM) and selectivity (S score (1) = 0.02) against native ABL kinase among other kinases in the kinome, but also exhibited great potency (IC50: 27.9 nM) and selectivity against Imatinib-resistant V299L mutant among other frequently observed ABL kinase mutants. CHMFL-ABL-039 has demonstrated greater efficacies than Imatinib regarding to the anti-proliferation, inhibition of the signaling pathway, arrest of cell cycle progression, induction of apoptosis in vitro and suppression of the tumor progression in vivo in the native and V299L mutated BCR-ABL kinase-driven cells/xenograft models. It would be a useful pharmacological tool to study the TKI resistant ABL V299L mutant-mediated pathology and provide a potential precise treatment approach for this orphan CML subtype in the precision medicine era.

5.
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
6.
J Med Chem ; 62(2): 875-892, 2019 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-30565931

RESUMO

Most of the current FMS-like tyrosine kinase 3 (FLT3) inhibitors lack selectivity between FLT3 kinase and cKIT kinase as well as the FLT3 wt and internal tandem duplication (ITD) mutants. We report a new compound 27, which displays GI50 values of 30-80 nM against different ITD mutants and achieves selectivity over both FLT3 wt (8-fold) and cKIT kinase in the transformed BaF3 cells (>300-fold). 27 potently inhibits the proliferation of the FLT3-ITD-positive acute myeloid leukemia cancer lines through suppression of the phosphorylation of FLT3 kinase and downstream signaling pathways, induction of apoptosis, and arresting the cell cycle into the G0/G1 phase. 27 also displays potent antiproliferative effect against FLT3-ITD-positive patient primary cells, whereas it does not apparently affect FLT3 wt primary cells. In addition, it also exhibits a good therapeutic window to PBMC compared to PKC412. In the in vivo studies, 27 demonstrates favorable PK profiles and suppresses the tumor growth in the MV4-11 cell inoculated mouse xenograft model.


Assuntos
Acetamidas/química , Inibidores de Proteínas Quinases/química , Tirosina Quinase 3 Semelhante a fms/antagonistas & inibidores , Acetamidas/farmacologia , Acetamidas/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Sítios de Ligação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Feminino , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/patologia , Camundongos , Camundongos Nus , Simulação de Dinâmica Molecular , Mutagênese , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Estrutura Terciária de Proteína , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-Atividade , Tirosina Quinase 3 Semelhante a fms/genética , Tirosina Quinase 3 Semelhante a fms/metabolismo
7.
Eur J Med Chem ; 160: 61-81, 2018 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-30317026

RESUMO

There is still a great demand in the clinic for the drugs which can overcome a variety of imatinib resistant ABL mutants. Starting from a type I inhibitor axitinib, which has been reported to overcome ABL-T315I mutant induced resistance, through a structure guided drug design approach and binding mode switch strategy, we have discovered a novel type II ABL inhibitor 24 (CHMFL-ABL-121), which significantly improved the inhibitory activity against ABL wt and a broad spectrum of mutants including the most prevalent imatinib-resistant gatekeeper mutant T315I. 24 exhibited IC50 values of 2 nM and 0.2 nM against purified inactive ABL wt and T315I kinase protein respectively and inhibited the proliferation of the established CML cell lines with GI50 at single digit nM. In cellular context, 24 strongly affected BCR-ABL mediated signaling pathways and induced apoptosis as well as arrested cell cycle at G0/G1 phase. In the in vivo study, 50 mg/kg/day dosage of 24 displayed TGI of 52% in the TEL-ABLT315I-BaF3 cell inoculated allograft mouse model without obvious toxicity.


Assuntos
Antineoplásicos/farmacologia , Descoberta de Drogas , Proteínas de Fusão bcr-abl/antagonistas & inibidores , Indazóis/farmacologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Piperazinas/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Piridinas/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Proteínas de Fusão bcr-abl/genética , Proteínas de Fusão bcr-abl/metabolismo , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Camundongos , Camundongos Nus , Modelos Moleculares , Estrutura Molecular , Mutação , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Relação Estrutura-Atividade
8.
Biochem Biophys Res Commun ; 503(1): 385-390, 2018 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-29902450

RESUMO

Circular RNA (circRNA) belongs to the non-coding RNA family and is involved in various human cancers, such as lung cancer and colorectal cancer. Nevertheless, whether circRNA expression is related to chronic lymphocytic leukemia (CLL) progression remains largely unclear. In our study, we investigated the role of circ-CBFB in CLL. We found that circ-CBFB was markedly overexpressed in CLL cells compared to normal controls. Furthermore, we found that circ-CBFB could serve as a diagnostic and prognostic biomarker for CLL patients. We also explored the physiological function of circ-CBFB. We found that circ-CBFB knockdown significantly suppressed CLL cell proliferation, arrested cell cycle progression, and induced cellular apoptosis. In terms of its mechanism, we identified circ-CBFB as a sponge of miR-607, which targeted FZD3. By inhibiting miR-607 availability, circ-CBFB promoted FZD3 expression, leading to the activation of the Wnt/ß-catenin pathway and consequent CLL progression. Taken together, our findings revealed that the circ-CBFB/miR-607/FZD3/Wnt/ß-catenin regulatory signaling cascade contributes to CLL progression.


Assuntos
Subunidade beta de Fator de Ligação ao Core/genética , Receptores Frizzled/genética , Regulação Leucêmica da Expressão Gênica , Leucemia Linfocítica Crônica de Células B/genética , MicroRNAs/metabolismo , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Leucemia Linfocítica Crônica de Células B/metabolismo , Leucemia Linfocítica Crônica de Células B/patologia , Via de Sinalização Wnt
9.
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
10.
J Med Chem ; 60(20): 8407-8424, 2017 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-28956923

RESUMO

FLT3-ITD mutant has been observed in about 30% of AML patients and extensively studied as a drug discovery target. On the basis of our previous study that ibrutinib (9) exhibited selective and moderate inhibitory activity against FLT3-ITD positive AML cells, through a structure-guided drug design approach, we have discovered a new type II FLT3 kinase inhibitor, compound 14 (CHMFL-FLT3-213), which exhibited highly potent inhibitory effects against FLT3-ITD mutant and associated oncogenic mutations (including FLT3-D835Y/H/V, FLT3-ITD-D835Y/I/N/A/G/Del, and FLT3-ITD-F691L). In the cellular context 14 strongly affected FLT3-ITD mediated signaling pathways and induced apoptosis by arresting cell cycle into G0/G1 phase. In the in vivo studies 14 demonstrated an acceptable bioavailability (F = 19%) and significantly suppressed the tumor growth in MV4-11 cell inoculated xenograft model (15 mg kg-1 day-1, TGI = 97%) without exhibiting obvious toxicity. Compound 14 might be a potential drug candidate for FLT3-ITD positive AML.


Assuntos
Descoberta de Drogas , Compostos de Fenilureia/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Pirazóis/farmacologia , Tirosina Quinase 3 Semelhante a fms/antagonistas & inibidores , Animais , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Marcação In Situ das Extremidades Cortadas , Camundongos , Camundongos Nus , Compostos de Fenilureia/química , Inibidores de Proteínas Quinases/química , Espectroscopia de Prótons por Ressonância Magnética , Pirazóis/química , Espectrometria de Massas por Ionização por Electrospray , Ensaios Antitumorais Modelo de Xenoenxerto
11.
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
12.
Medicine (Baltimore) ; 96(52): e9424, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29384919

RESUMO

This study aimed to explore the association between the percentage of reticulated platelets (RP%) and infection, and analyze the value of combined measurement of RP% with other inflammatory indicators in diagnosing infection. A total of 190 patients with signs and symptoms suspicious of infection were included in the infection group, and 70 healthy subjects with comparable percentages of gender and age were included in the control group. Peripheral white blood cell (WBC) count, percentage of neutrophils (N%), platelet count, C-reactive protein (CRP), procalcitonin (PCT), RP%, and axillary temperature were recorded. Dynamic changes in RP% with infection were measured to analyze the association between RP% and infection. The receiver operating characteristic curve was used to evaluate the value of each inflammatory indicator in diagnosing infection and analyze the diagnostic value of the combined adoption of multiple inflammatory indicators. RP% was significantly higher in the infection group than in the noninfection and control groups. The sensitivity and specificity for diagnosing infection were, respectively, 91.78% and 93.18% when RP% and CRP were used in combination, 90.41% and 90.90% when RP% and PCT were used in combination, and 100% and 100% when RP%, CRP, and PCT were used in combination. RP% changed dynamically with the progression of infection and recovered to lower than 5.5% at 2 to 7 days before the body temperature recovered to a normal level. The diagnostic value of RP% was the highest. A combined use with CRP/PCT could improve the sensitivity and specificity in the early diagnosis of infectious diseases.


Assuntos
Doenças Transmissíveis/sangue , Doenças Transmissíveis/diagnóstico , Contagem de Plaquetas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Temperatura Corporal , Proteína C-Reativa/metabolismo , Calcitonina/sangue , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Adulto Jovem
13.
ACS Appl Mater Interfaces ; 8(37): 24826-36, 2016 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-27575872

RESUMO

Attention on semiconductor nanocrystals have been largely focused because of their unique optical and electrical properties, which can be applied as light absorber and luminophore. However, the band gap and structure engineering of nanomaterials is not so easy because of their finite size. Here we demonstrate an approach for preparing ternary AgInS2 (AIS), quaternary AgZnInS (AZIS), AgInS2/ZnS and AgZnInS/ZnS nanocompounds based on cation exchange. First, pristine Ag2S quantum dots (QDs) with different sizes were synthesized in one-pot, followed by the partial cation exchange between In(3+) and Ag(+). Changing the initial ratio of In(3+) to Ag(+), reaction time and temperature can control the components of the obtained AIS QDs. Under the optimized conditions, AIS QDs were obtained for the first time with a cation disordered cubic phase and high photoluminescence (PL) quantum yield (QY) up to 32% in aqueous solution, demonstrating the great potential of cation exchange in the synthesis for nanocrystals with excellent optical properties. Sequentially, Zn(2+) ions were incorporated in situ through a second exchange of Zn(2+) to Ag(+)/In(3+), leading to distinct results under different reaction temperature. Addition of Zn(2+) precursor at room temperature produced AIS/ZnS core/shell NCs with successively enhancement of QY, while subsequent heating could obtain AZIS homogeneous alloy QDs with a successively blue-shift of PL emission. This allow us to tune the PL emission of the products from 483 to 675 nm and fabricate the chemically stable QDs core/ZnS shell structure. Based on the above results, a mechanism about the cation exchange for the ternary nanocrystals of different structures was proposed that the balance between cation exchange and diffusion is the key factor of controlling the band gap and structure of the final products. Furthermore, photostability and in vitro experiment demonstrated quite low cytotoxicity and remarkably promising applications in the field of clinical diagnosis.

14.
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
15.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 24(1): 25-9, 2016 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-26913388

RESUMO

OBJECTIVE: To explore the clinical efficacy and safety of rituximab combined with fludarabine and cyclophosphamide for the treatment of the chronic lymphocytic leukemia (CLL). METHODS: Forty cases of CLL patients treated in our hospital from March 2010 to March 2014 years were selected and divided into the observation group (20 cases) and control group (20 cases) by random number table method. The patients in control group were treated with CHOP chemotherapy, the patients in observation group were treated with rituximab combined with fludarabine, cyclophosphamide treatment. The therapeutic efficacy of patients in 2 groups was analyzed according to the peripheral hemogram indexes, symptom and sign disappeared time as well as adverse reaction incidence. RESULTS: the remission rate in observation group was 90.00%, which was significantly higher than that in control group (70.00%) (P < 0.05); the peripheral hemogram indexes in 2 groups before treatment showed no significant difference (P > 0.05), and were significantly improved after treatment, but the white blood cell count and lymphocyte absolute number were significantly lower in observation group as compared to the control group (P < 0.05); symptom and sign disappeared time in observation group were significantly shorter as compared with the control group (P < 0.05); adverse reaction incidence in obseovation group was significantly lower as compared with control group (P < 0.05). CONCLUSION: application of rituximab combined with fludarabine and cyclophosphamide in the treatment of CLL shows the higher curative effect, can effectively improve the symptoms and reduce the incidence of adverse reactions. It is worthy to be popularized.


Assuntos
Ciclofosfamida/uso terapêutico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Rituximab/uso terapêutico , Vidarabina/análogos & derivados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/administração & dosagem , Doxorrubicina/uso terapêutico , Humanos , Prednisona/uso terapêutico , Rituximab/administração & dosagem , Resultado do Tratamento , Vidarabina/administração & dosagem , Vidarabina/uso terapêutico , Vincristina/uso terapêutico
16.
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
17.
Int J Clin Exp Pathol ; 8(8): 9133-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26464657

RESUMO

B cell lymphoma (BCL) has a higher degree of malignancy and complicated pathogenic mechanism. Regulatory T cells (Treg cells) are known to exert certain immune suppression functions, in addition to immune mediating effects. Recent studies have revealed the role of Treg cells in pathogenesis and progression of multiple malignant tumors. This study therefore investigated the functional role and related mechanism of Treg cells in BCL. A cohort of thirty patients who were diagnosed with BCL in our hospital between January 2013 and December 2014. Another thirty healthy individuals were recruited. Peripheral blood mononuclear cells (PBMCs) were separated and analyzed for the ratio of CD4+/CD25+ Treg cells. The mRNA expression levels of Foxp3, transforming growth factor (TGF)-ß1 and interleukin (IL)-10 genes were quantified by real-time PCR, while their serum levels were determined by enzyme-linked immunosorbent assay (ELISA). Meanwhile all laboratory indexes for patients were monitored during the complete remission (CR) stage. BCL patients significantly elevated ratio of CD4+/CD25+ Treg cells, which were decreased at CR stage. mRNA levels of Foxp3, TGF-ß1 and IL-10, in addition to protein levels of TGF-ß1 and IL-10 were potentiated in lymphoma patients but decreased in CR patients (P<0.05 in all cases). CD4+/CD25+ Treg cells exert immune suppressing functions in BCL via regulating cytokines, thereby facilitating the pathogenesis and progression of lymphoma.


Assuntos
Linfoma de Células B/patologia , Linfócitos T Reguladores/patologia , Adolescente , Adulto , Feminino , Fatores de Transcrição Forkhead/metabolismo , Humanos , Interleucina-10/metabolismo , Linfoma de Células B/imunologia , Linfoma de Células B/metabolismo , Masculino , Pessoa de Meia-Idade , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Adulto Jovem
18.
ACS Appl Mater Interfaces ; 7(39): 21985-94, 2015 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-26371629

RESUMO

Despite the fact that Au-Ag hollow nanoparticles (HNPs) have gained much attention as ablation agents for photothermal therapy, the instability of the Ag element limits their applications. Herein, excess Au atoms were deposited on the surface of a Au-Ag HNP by improving the reduction power of l-ascorbic acid (AA) and thereby preventing the reaction between HAuCl4 and the Ag element in the Au-Ag alloy nanostructure. Significantly, the obtained Au-Ag@Au HNPs show excellent chemical stability in an oxidative environment, together with remarkable increase in extinction peak intensity and obvious narrowing in peak width. Moreover, finite-difference time-domain (FDTD) was used to simulate the optical properties and electric field distribution of HNPs. The calculated results show that the proportion of absorption cross section in total extinction cross section increases with the improvement of Au content in HNP. As predicted by the theoretical calculation results, Au-Ag@Au nanocages (NCs) exhibit a photothermal transduction efficiency (η) as high as 36.5% at 808 nm, which is higher than that of Au-Ag NCs (31.2%). Irradiated by 808 nm laser at power densities of 1 W/cm(2), MCF-7 breast cancer cells incubated with PEGylated Au-Ag@Au NCs were seriously destroyed. Combined together, Au-Ag@Au HNPs with enhanced chemical stability and improved photothermal transduction efficiency show superior competitiveness as photothermal agents.


Assuntos
Antineoplásicos/química , Ouro/química , Nanopartículas Metálicas/química , Nanoestruturas/química , Prata/química , Ligas , Antineoplásicos/farmacologia , Ácido Ascórbico , Sobrevivência Celular/efeitos dos fármacos , Estabilidade de Medicamentos , Ouro/farmacologia , Humanos , Células MCF-7 , Neoplasias/tratamento farmacológico , Fototerapia , Prata/farmacologia
19.
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
20.
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
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