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Primary cutaneous follicle center lymphoma (PCFCL) differs from follicular lymphoma in biological behavior and molecular profile and is treated as a distinct entity, according to the 5th edition of the World Health Organization classification of hematolymphoid tumors. It is an uncommon cutaneous B-cell lymphoma that is considerably rare in children and adolescents. To date, only 13 cases of individuals younger than 20 years of age have been reported in the literature. The lack of relevant clinical epidemiological data in this population has hampered the investigation of its clinical and diagnostic aspects. Here we report the case of a 17-year-old male with PCFCL, who may be the first PCFCL patient under 20 years of age reported in China. He was admitted to the hospital with a solitary nodule on his face. After complete surgical excision, the patient's facial mass was histologically identified as PCFCL. The patient's prognosis was favorable, with no recurrence at 17 months of follow-up after the surgical resection. We present a case of an adolescent PCFCL patient and systematically review the literature with a view to increase the awareness of the disease and inform the diagnosis and treatment of this age group.
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Background: Multiple trials have confirmed that romiplostim could increase platelet count in individuals with primary immune thrombocytopenia (ITP), but no related study has assessed Chinese patients. Objectives: To assess the effectiveness of romiplostim as a second-line treatment of persistent or chronic ITP in Chinese adults. Methods: This phase III multicenter, randomized, placebo-controlled, double-blind, then open-label clinical trial (NCT02868099, CTR20150395) was conducted at 28 investigational sites in China. The patients were randomly assigned (3:1) to romiplostim (starting and maximum doses of 1 and 10 µg/kg, respectively) or placebo for 9 weeks (double-blind period), followed by the open-label period (both groups administered romiplostim) to week 22. The primary endpoint was the time (in weeks) during which platelet counts were ≥50 × 109/L in the double-blind period. Results: In this study, 202 patients (romiplostim, n = 151; placebo, n = 51) started the treatment. The median (range) numbers of weeks with platelet response after 6 weeks of treatment were 2 (0-6) and 0 (0-2) in patients administered romiplostim and placebo, respectively (P < .001). During the double-blind period, the proportions of patients with treatment-emergent adverse events were comparable between the romiplostim and placebo groups (82.8% vs 82.4%). The treatment-emergent adverse event with ≥10% difference in incidence between these 2 groups was injection site bleeding (1.3% vs 11.8%). Conclusion: Romiplostim significantly increased the time with maintained platelet response in patients with persistent or chronic ITP in comparison with placebo. No new safety signal was observed. Trial registration: ClinicalTrials.gov, NCT02868099. www.chinadrugtrials.org.cn/clinicaltrials.searchlist.dhtml, CTR20150395.
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OBJECTIVES: To retrospectively investigate the clinical characteristics, prognosis, treatment, and therapy outcome of Chinese patients with primary testicular lymphoma (PTL). METHODS: we collected data of 49 PTL patients from four hospitals over 13 years. The median age was 63 years old. We described the clinical characteristics of the patients including the laterality, serum lactate dehydrogenase (LDH), pathology classification, stage, International prognostic index (IPI) scores and more. RESULTS: Complete remission (CR) was achieved in 34 patients and partial remission (PR) in 3 patients; Progressive disease (PD) was detected in 11 patients, and 10 patients died. The average progression-free survival (PFS) of all patients was 43.92 months, and the average overall survival (OS) was 47.55 months. The Ann Arbor stage, IPI score, and LDH were associated with OS, while Ann Arbor stage, IPI score, LDH, and histotype were significantly associated with PFS. Chemotherapy and radiotherapy following orchiectomy was associated with a significantly longer PFS. CONCLUSION: Most patients can achieve CR after induced therapy or orchiectomy. However, there are many associated prognostic factors.
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Linfoma Difuso de Grandes Células B , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Intervalo Livre de Doença , Humanos , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Indução de Remissão , Estudos RetrospectivosRESUMO
Objectives: Primary breast diffuse large B-cell lymphoma (PB-DLBCL) and primary breast high-grade B-cell lymphoma (PB-HGBCL) are rare extranodal aggressive B-cell lymphomas with distinct characteristics. Reliable data regarding appropriate treatment of these specific entities are lacking due to their rarity.Methods: We reviewed 36 patients diagnosed at four Chinese medical centres between January 2008 and December 2018. Data regarding clinicopathological features, therapeutic evaluation and central nervous system (CNS) relapse were collected, and overall survival (OS) and progression-free survival (PFS) were calculated.Results: Among the 36 patients, there were 29 PB-DLBCL patients and 7 PB-HGBCL patients. The 5-year OS for PB-DLBCL and PB-HGBCL was 75.9% and 28.6%, respectively. The 5-year PFS for PB-DLBCL and PB-HGBCL was 69.0% and 14.3%, respectively. The R-DAEPOCH regimen was significantly more effective in PB-DLBCL patients than the R-CHOP regimen (5-year OS: 78.9% vs 62.5%, P=0.024; 5-year PFS: 73.7% vs 50.0%, P=0.037) but resulted in more severe myelosuppression (P=0.025). The rate of CNS relapse was 17.2% in PB-DLBCL patients and 28.6% in PB-HGBCL patients; the difference was not significant (P=0.602). The R-DAEPOCH regimen did not predominantly reduce CNS recurrence as expected (P=0.616). The Cox proportional hazards model revealed that risk stratification and triple expression were independent prognostic factors.Conclusion: Current treatments, including more intensive chemotherapy regimens, achieve good control of the disease. Novel drugs combined with cellular immunotherapy initially show promising therapeutic effects, and more clinical trials are required to confirm these effects further.
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Linfoma de Células B/terapia , Linfoma Difuso de Grandes Células B/terapia , Adulto , Idoso , Feminino , Humanos , Linfoma de Células B/mortalidade , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
Acquired haemophilia A (AHA) is a rare haemorrhagic disorder caused by autoantibodies directed against the functional epitopes of coagulation factor VIII (FVIII). Its management relies on prompt diagnosis, control of bleeding and eradication of the inhibitor by immunosuppression. China Acquired Hemophilia Registry (CARE), a nationwide multicentre registry, was intended to survey the status of AHA and standardize its diagnosis and therapy in China. One hundred and eighty-seven registered patients had an average age of 52 years. Diagnosis was delayed in 46·5% patients. There was a significant delay from diagnosis to immunosuppressive therapy in 68·3% patients. Bleeding control was significantly higher in patients treated with prothrombin complex concentrate (PCC) versus FVIII replacement therapy (84·6% vs. 34·4%; P < 0·001). Inhibitor eradication with a combination of steroids and cyclophosphamide showed a higher partial remission (PR) rate (92·2% vs. 70·3%) and stable complete remission (CR) rate (82·8% vs. 48·6%) than with steroids alone. Logistic regression model showed age and malignancy were significantly related to survival at final follow-up. The mean age for the survivors [51 years (IQR, 35-65 years)] was significantly lower than that of the non-survivors [79 years (IQR, 67-86 years)] (P < 0·001). Overall survival was higher in non-malignancy group than malignancy group (94·9% vs. 70%) (OR = 1·313; 95% CI, 0·913-1·889, P = 0·015).
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Hemofilia A/diagnóstico , Hemofilia A/tratamento farmacológico , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/sangue , Doenças Autoimunes/complicações , Doenças Autoimunes/epidemiologia , Fatores de Coagulação Sanguínea/efeitos adversos , Fatores de Coagulação Sanguínea/uso terapêutico , China/epidemiologia , Bases de Dados Factuais , Quimioterapia Combinada , Fator VIII/imunologia , Feminino , Glucocorticoides/uso terapêutico , Hemofilia A/epidemiologia , Hemofilia A/etiologia , Hemorragia/tratamento farmacológico , Hemorragia/epidemiologia , Hemorragia/etiologia , Hemostáticos/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/epidemiologia , Recidiva , Sistema de Registros , Indução de Remissão , Resultado do Tratamento , Adulto JovemRESUMO
The current study aimed to explore the levels of leptin (LEP) and LEP receptor (LEP-R) on the progression of aplastic anemia (AA) with bone marrow fat conversion. An AA model was developed by infusing C57BL/6 lymph node cells into BALB/c mice. At 0, 3, 6, 9, 12, 15 and 18 days after modeling, routine blood counts, bone marrow biopsy slides, lymphocyte subsets (CD4+ and CD8+ T cells) and cytokine levels [including interleukin (IL)-2, IL-4, IL-5 and interferon-γ] were assessed. LEP and LEP-R levels in peripheral blood serum, mesenchymal stem cells (MSCs) and bone marrow were also analyzed by enzyme-linked immunosorbent assay, polymerase chain reaction and immunohistochemistry. The relevance of LEP, LEP-R and other factors was analyzed by Pearson's correlation analysis. Peripheral pancytopenia (reduced count of white blood cells, red blood cells, hemoglobin and platelets), abnormal immune factor levels and histological changes in bone marrow sections were detected in the AA model mice, suggesting that these mice mimicked the pathological changes commonly observed in AA. In addition, following the establishment of AA, the LEP level was gradually increased and the LEP-R level was reduced in the mice over time (P<0.05). The expression of adipogenic genes, including CCAAT/enhancer-binding protein (C/EBP)α, C/EBPß and peroxisome proliferator-activated receptor γ, was markedly increased, while the expression of the osteogenic gene runt-related transcription factor 2 was reduced compared with the levels in the control group (P<0.05). Taken together, damage to LEP-R may lead to dysregulation of LEP and the enhancement of MSCs to differentiate into adipocytes, resulting in excessive fat in bone marrow of AA patients.
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Diffuse large B-cell lymphoma (DLBCL) contributes to the cancer-related mortality. Increasing evidence have reported the crucial role of long non-coding RNAs (lncRNAs) in tumorigenesis. Microarray analysis was used to screen out the differentially expressed lncRNAs. qRT-PCR proved that lncRNA functional intergenic repeating RNA element (FIRRE) was up-regulated in DLBCL tissues and cells. Based on Kaplan-Meier analysis, high FIRRE level was associated with the poor overall survival. Subsequently, cell functional assays further revealed that FIRRE functioned as an oncogene by promoting cell proliferation and reducing cell apoptosis in DLBCL. The upstream mechanism of FIRRE was analyzed in accordance with the bioinformatics analysis and mechanism experiments. The results showed that MYC proto-oncogene (MYC) contributed to the transcriptional activation of FIRRE in DLBCL cells. Further mechanism investigation prompted us to determine the association between Wnt/ß-catenin signaling pathway and FIRRE. Subcellular fractionation assay and western blot assay demonstrated that FIRRE activated Wnt/ß-catenin signaling pathway by promoting nuclear translocation of ß-catenin. Taken together, FIRRE activated Wnt/ß-catenin signaling pathway to facilitate DLBCL cell growth via modulation of the nuclear translocation of ß-catenin. Our findings reveals the novel molecular mechanism of FIRRE in DLBCL.
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Carcinogênese/genética , Linfoma Difuso de Grandes Células B/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , RNA Longo não Codificante/genética , Via de Sinalização Wnt , Transporte Ativo do Núcleo Celular , Carcinogênese/metabolismo , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Linfoma Difuso de Grandes Células B/metabolismo , Proto-Oncogene Mas , Ativação Transcricional , beta Catenina/metabolismoRESUMO
Three dimensional (3D) culture has gradually become a research hotspot in the field of drug screening, stem cell research, and tissue engineering due to its more physiological-like morphology and function. In this study, we compared the differences of cell proliferation, population, protein expression and chemoresistance profiles between two dimensional (2D) and 3D culture of acute lymphoblastic leukemia (ALL) Jurkat cell line. Polycaprolactone (PCL) is used for 3D culture owing to its biochemical properties and compatibility. Culturing of ALL Jurkat cell line in collagen type I coated polycaprolactone scaffold for 168 h increased cell proliferation, attachment, as well as the drug resistance to cytarabine (Ara-C) and daunorubicin (DNR) without changing the original CD2+CD3+CD4+dimCD8-CD34-CD45+dim phenotype, compared to uncoated PCL scaffold and tissue culture plate systems. Molecularly, increased chemoresistance is associated with the upregulation of discoidin domain receptor 1 (DDR1) and transcription factor STAT3. Inhibition of DDR1 activity by DDR1-specific inhibitor DDR-IN-1 accelerated cell death in the presence of Ara-C, DNR or their combination. These results demonstrated that 3D culture enhances chemoresistance of ALL Jurkat cell line by increasing DDR1 expression. Importantly, the cell adhesion-mediated drug resistance induced by DDR1 in the scaffold was similar to the clinical situation, indicating the 3D culture of cancer cells recapitulate the in vivo tumor environment and this platform can be used as a promising pre-clinic drug-screen system.
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The aim of this study was to determine the safety and efficacy of recombinant human thrombopoietin (rhTPO) for the management of immune thrombocytopenia (ITP) during pregnancy. Pregnant patients with ITP were enrolled in the study if they had a platelet count less than 30 × 109/L, were experiencing bleeding manifestations, had failed to respond to corticosteroids and/or intravenous immunoglobulin (IVIG), and had developed refractoriness to platelet transfusion. Thirty-one patients received rhTPO at an initial dose of 300 U/kg once daily for 14 days. Twenty-three patients responded (74.2%), including 10 complete responders (>100 × 109/L) and 13 responders (30-100 × 109/L). It appears that rhTPO ameliorated the bleeding symptoms remarkably, even in the nonresponders. rhTPO was well tolerated. Dizziness, fatigue, and pain at an injection site were reported in 1 patient each. No congenital disease or developmental delays were observed in the infants in a median follow-up of 53 (range, 39-68) weeks. In conclusion, rhTPO is a potentially safe and effective treatment choice for patients with ITP during pregnancy. Our work has paved the way for further study on the clinical application of rhTPO and other thrombopoietic agents for the management of ITP during pregnancy. This study is registered at www.clinicaltrials.gov as NCT02391272.
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Complicações Hematológicas na Gravidez/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Proteínas Recombinantes/uso terapêutico , Trombopoetina/uso terapêutico , Adulto , Feminino , Hemorragia/tratamento farmacológico , Humanos , Recém-Nascido , Contagem de Plaquetas , Gravidez , Complicações Hematológicas na Gravidez/sangue , Púrpura Trombocitopênica Idiopática/sangue , Proteínas Recombinantes/efeitos adversos , Trombopoetina/efeitos adversos , Trombopoetina/sangueRESUMO
Philadelphia chromosome-positive acute myeloid leukemia is controversial and difficult to distinguish from the blast phase of chronic myeloid leukemia. As a myeloid neoplasm, rare cases of this leukemia manifest multiple soft-tissue tumors or bone lytic lesions. In this paper, we describe a 49-year-old male patient who had an abrupt onset with sharp chest pain, fever, fatigue, emaciation, and splenomegaly. 18F-fluoro-deoxy-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) result showed diffuse and uneven hypermetabolic lesions in the bone marrow with peripheral bone marrow expansion, multiple soft tissue neoplasms with high 18F-FDG uptake, and lytic bone lesions. Bone marrow smear and biopsy detected aberrant blast cells expressing myeloid rather than lymphoid immunophenotype marker. For the existence of Philadelphia chromosome and BCR-ABL1 fusion gene together with complex chromosome abnormalities, a diagnosis of Philadelphia-positive acute myeloid leukemia was made, although the type (de novo or blast crisis) remained unclear.
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Medula Óssea/patologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico por imagem , Leucemia Mieloide Aguda/diagnóstico por imagem , Osteólise/diagnóstico por imagem , Neoplasias de Tecidos Moles/diagnóstico por imagem , Fluordesoxiglucose F18 , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia ComputadorizadaRESUMO
OBJECTIVE: To investigate HOXB4, PRDM16 and HOXA9 gene expression in patients with acute myeloid leukemia (AML) and its clinical significance. METHODS: Real-time quantitative PCR (RT-qPCR) with SYBR Green assay was used to detect the expression of HOXB4, PRDM16 and HOXA9 gene in AML patients (40 cases), the patients with complete remission (9 cases) and patients with non-malignant hematologic diseases as control (10 cases). The relationship between the expression levels of gene HOXB4, PRDM16, HOXA9 and clinical features was investigated by statistical analysis. RESULTS: The gene expression levels of HOXB4, PRDM16, HOXA9 in newly diagnosed or relapsed AML patients were significantly higher than those in patients with non-malignant hematologic disease (P < 0.05). It was observed that the expression of HOXB4 gene in newly diagnosed or relapsed patients positively correlates with leukemic blasts in bone marrow (r = 0.39). The expression levels of HOXB4, PRDM16 and HOXA9 positively correlate with each other. There was statistical significance among gene expressions in different phases (newly diagnosed, relapse, remission). No correlation was observed between expression levels of HOXB4, PRDM16, HOXA9 and chromosome risk status. It was noticed that expression levels of HOXB4, PRDM16, HOXA9 genes were lower in the patients achieved remission after two courses of chemotherapy than those in the other. And high expression group of each gene had a lower remission rate than that in the low expression group. CONCLUSION: The expression level of HOXB4, PRDM16, HOXA9 genes and leukemic blasts somewhat correlate with curative effect and prognosis. The expression of HOXB4, PRDM16, HOXA9 genes is higher in newly diagnosed and relapsed leukemia patients, and lower in the patients acquired CR/PR. High expression of HOXB4, PRDM16, HOXA9 genes predicts an adverse prognosis.
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Proteínas de Ligação a DNA/metabolismo , Proteínas de Homeodomínio/metabolismo , Leucemia Mieloide Aguda/metabolismo , Fatores de Transcrição/metabolismo , Medula Óssea , Estudos de Casos e Controles , Proteínas de Ligação a DNA/genética , Expressão Gênica , Proteínas de Homeodomínio/genética , Humanos , Leucemia Mieloide Aguda/genética , Prognóstico , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Recidiva , Indução de Remissão , Fatores de Transcrição/genéticaRESUMO
OBJECTIVE: To evaluate efficacy and safety of second-generation tyrosine kinase inhibitors (TKI) dasatinib, nilotinib and imatinib in treatment of newly diagnosed patients with chronic-phase chronic myeloid leukemia (CML). METHODS: The clinical data and follow-up results of 163 patients with chronic-phase chronic myeloid lenkemia(CP-CML) who were treated in our hospital during the nearly 3 years were analysed retrospectively, among 163 patients 47 received dasatinib, 43 received nilotinib and 73 received imatinib. The efficacy, disease progression and safety were evaluated. RESULTS: After treatment for 3 months, the rate of complete hematologic response(CHR) in three treatment groups were 77%, 79% and 67%, respectivily, CHR at 12 months in three treatment groups were 92%, 91% and 90%, respectively. By 3 months, the rates of complete cytogenetic response(CCyR) with dasatinib and nilotinib were higher than that with imatinib (55%, 53% vs 33%)(P<0.05 for both comparisons), CCyR at 12 months in three treatment groups were 86%, 88% vs 69% (P<0.05 for both comparisons). The rates of major molecular response(MMR) for dasatinib (11%) and nilotinib (9%) by 3 months were significantly higher than that for imatinib (1%) (P<0.05 for both comparisons), MMR at 12 months in three treatment groups were 49%, 50% and 28%, respectively (P<0.05 for both comparison). Progression to the accelerated or blast phase of CML occurred in 2 (4%) patients received dasatinib, 2 (5%) received nilotinib and 6 (8%) received imatinib. The safety profiles of these 3 second-generation TKI treatments were similar. CONCLUSION: Both dasatinib and nilotinib induced strikingly higher and faster rates of complete cytogenetic response and major molecular response, with a statistically significant difference from imatinib.
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Leucemia Mielogênica Crônica BCR-ABL Positiva , Protocolos de Quimioterapia Combinada Antineoplásica , Crise Blástica , Dasatinibe , Progressão da Doença , Humanos , Mesilato de Imatinib , Inibidores de Proteínas Quinases , Pirimidinas , Estudos Retrospectivos , Resultado do TratamentoRESUMO
This study aimed to compare the efficacy and safety of rituximab (RTX) plus recombinant human thrombopoietin (rhTPO) with RTX alone in patients with immune thrombocytopenia (ITP) who had failed to respond to corticosteroids or relapsed. Recruited patients were randomized at a ratio of 2:1 into 2 groups: the combination group (RTX + rhTPO, n = 77) and the monotherapy group (RTX, n = 38). Overall response was achieved in 79.2% of patients in the combination group vs 71.1% in the monotherapy group (P = .36), and the complete response (CR) rate was 45.4% in the combination group compared with 23.7% in the monotherapy group (P = .026). The combination group had significantly shorter time to response (TTR; median and range, 7 and 4-28 days) compared with the monotherapy group (28 and 4-90 days) (P < .01). There was no difference between these 2 groups in terms of the long-term response (P = .12). Our findings demonstrated that the combination of RTX and rhTPO significantly increased the CR rate and shortened TTR compared with RTX monotherapy in the treatment of corticosteroid-resistant or relapsed ITP but failed to show a beneficial effect on the long-lasting response. This study is registered at www.clinicaltrials.gov as #NCT01525836.
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Anticorpos Monoclonais Murinos/administração & dosagem , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/terapia , Trombopoetina/administração & dosagem , Adolescente , Corticosteroides/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/efeitos adversos , Autoanticorpos/sangue , Criança , Terapia Combinada , Resistência a Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Púrpura Trombocitopênica Idiopática/sangue , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Recidiva , Rituximab , Trombopoetina/efeitos adversos , Resultado do Tratamento , Adulto JovemRESUMO
This study was aimed to investigate the effects of the DNA methylation inhibitor 5-aza-2'-deoxycytidine (5-Aza-CdR) and histone deacetylase inhibitor trichostatin A (TSA) on DLC-1 gene transcription regulation and molecular biological behaviours in the human multiple myeloma RPMI-8226 cells. The cells were treated respectively with 5-Aza-CdR and TSA alone, or the both combination; the cell proliferation and apoptosis, DLC-1 expression, the protein expression of Ras homolog family member A (RhoA) and Ras-related C3 botulinum toxin substrate 1 (Rac1) were examined by CCK-8 method, RT-PCR and ELISA, respectively. The results showed that the 5-Aza-CdR and TSA had cell growth inhibitory and apoptosis-inducing effects in dose-dependent manner (P < 0.05). Compared with a single drug (5-Aza-CdR or TSA alone), the effects were significantly enhanced after treatment with the combination of 5-Aza-CdR and TSA (P < 0.05). DLC-1 was weakly expressed in the control group; the treatment with 5-Aza-CdR alone enhanced its re-expression dose-dependently (P < 0.05). Compared with 5-Aza-CdR alone, 5-Aza-CdR plus TSA enhanced DLC-1 re-expression significantly.Compared with the control, 5-Aza-CdR and TSA significantly decreased RhoA and Rac1 protein expression (P < 0.05). It is concluded that 5-Aza-CdR and TSA can effectively reverse DLC-1 expression of RPMI-8226 cells; TSA has a synergistic effect on its re-expression. 5-Aza-CdR and TSA have significant cell growth inhibitory and apoptosis-inducing effects on RPMI-8226 cells. These effects may be related to the inhibition of Rho/Rho kinase signalling pathway.
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Apoptose/efeitos dos fármacos , Azacitidina/análogos & derivados , Proteínas Ativadoras de GTPase/metabolismo , Ácidos Hidroxâmicos/farmacologia , Mieloma Múltiplo/patologia , Proteínas Supressoras de Tumor/metabolismo , Antimetabólitos Antineoplásicos/farmacologia , Azacitidina/administração & dosagem , Azacitidina/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Decitabina , Expressão Gênica/efeitos dos fármacos , Humanos , Ácidos Hidroxâmicos/administração & dosagem , Mieloma Múltiplo/genéticaRESUMO
The purpose of this study was to evaluate the cytotoxicity of human multiple myeloma cells (RPMI-8226) treated with graphene oxide (GO), doxorubicin (DOX), and GO loaded with DOX (GO/DOX). Cell viability was determined using the Cell Counting Kit-8 assay and analyzing the cell cycle and cell apoptosis. Cells treated with GO, GO/DOX, and pure DOX for 24 hours showed a decrease in proliferation. GO/DOX significantly inhibited cell proliferation as compared with pure DOX (P<0.01). When the effects of GO were removed, there was no observed difference between GO/DOX and pure DOX (P>0.05). Flow cytometry analysis of untreated and GO-, DOX-, and GO/DOX-treated cells found no significant differences in the G0/G1 phase (P>0.05), while significant differences were observed in the total apoptotic rates (P<0.05). No significant differences existed in the total apoptotic rates of GO-treated and untreated cells (P>0.05). These findings suggest that GO caused low cytotoxicity and did not induce cell apoptosis or change the cell cycle in multiple myeloma cells. Moreover, GO did not affect the antitumor activity of DOX. In conclusion, GO would be suitable as an anticancer drug nanocarrier and used to treat hematological malignancies.
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Doxorrubicina/administração & dosagem , Doxorrubicina/química , Grafite/química , Mieloma Múltiplo/tratamento farmacológico , Nanocápsulas/administração & dosagem , Nanocápsulas/química , Óxidos/química , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Difusão , Humanos , Mieloma Múltiplo/patologia , Resultado do TratamentoRESUMO
BACKGROUND: The management of patients with refractory immune thrombocytopenia (ITP) is challenging, as there is no standard treatment option. The aim of this study was to investigate the efficacy of recombinant human thrombopoietin (rhTPO) in combination with cyclosporin A (CsA) for the management of patients with corticosteroid-resistant primary ITP. METHODS: Thirty-six patients with corticosteroid-resistant ITP were randomly divided into an observation group and control group. In the observation group, 19 patients received subcutaneous injection of rhTPO at a dose of 1 µg/kg (300 U/kg) once daily up to day 14. Simultaneously they also received oral CsA at a dose of 1.5-2.0 mg/kg twice daily for three months. In the control group, rhTPO alone was administered subcutaneously at 1 µg/kg once daily in the other 17 ITP patients for 14 consecutive days and then the treatment was withdrawn. RESULTS: There was no significant difference in the response rate at the end of the first week after treatment initiation between the observation group and the control group (63.2% vs. 58.8%, P > 0.05), neither was there at the end of the second week (89.5% vs. 94.1%, P > 0.05). However, the relapse rate in the observation group was significantly lower than that in control group at the end of the first (17.7% vs. 50.0%, P < 0.05), second (29.4% vs. 68.8%, P < 0.05) and the third month (29.4% vs. 87.5%, P < 0.01). In addition, rhTPO plus CsA were well tolerated and adverse events recorded were mild. CONCLUSIONS: Combination therapy with rhTPO and CsA was effective in the management of patients with corticosteroidresistant ITP, with a relatively short time to response and low recurrence rate. It might be considered as a potential secondline treatment regimen for ITP.
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Corticosteroides/uso terapêutico , Ciclosporina/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Trombocitopenia/tratamento farmacológico , Trombopoetina/uso terapêutico , Adolescente , Adulto , Idoso , Ciclosporina/administração & dosagem , Resistência a Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Trombopoetina/efeitos adversos , Resultado do Tratamento , Adulto JovemRESUMO
To investigate the effect of vitamin D in pathogenesis and clinical treatment of patients with immune thrombocytopenic (ITP), ELISA was used to detect the level of 25-hydroxylate vitamin D3[25(OH)D3] and 1,25-dihydroxyvitamin D3[1,25(OH)2D3] in peripheral blood from 45 ITP patients and 30 normal controls. Vitamin D receptor (VDR) mRNA expression was detected by RT-PCR. The results showed that the levels of 25(OH)D3 (10.6 ± 7.7 ng/ml) and 1,25(OH)2D3 (69.9 ± 29.0 pg/ml) in peripheral blood of the initial ITP patients were lower than those in peripheral blood of normal controls (13.7 ± 9.1 ng/ml, 87.3 ± 19.9 pg/ml) (P < 0.05). The expression of VDR gene obviously increased in peripheral blood of initial ITP patients (1.588 ± 0.127), as compared with that in peripheral blood of normal controls (1.055 ± 0.734) (P < 0.05). It is concluded that vitamin D level and its receptor expression may play an important role in ITP, and vitamin D and its similarities may be a new agent to treat patients with ITP.
Assuntos
Receptores de Calcitriol/sangue , Trombocitopenia/sangue , Vitamina D/sangue , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Células Cultivadas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , Adulto JovemRESUMO
This study was aimed to investigate the changes of the platelet particle membrane protein (GMP-140), platelet activating factor (PAF) and platelet parametes in the patients with hyperuricemia (HUA), ELISA was used to detect the levels of GMP-140 and PAF in 55 patients with HUA and 30 healthy individuals. Platelet parameters were measured with automatic blood cell analyzer, and the biochemical indexes were detected at the same time. The results showed that the levels of serum uric acid, triglycerides (TG) and low density lipoprotein cholesterol (LDL-C) in HUA patients were higher than that in the normal group (P < 0.01). Serum uric acid level of HUA group was higher in men than that in women. The levels of GMP-140 and PAF in HUA patients were much higher than that in the normal group (P < 0.01), the indexes of platelet distribution width (PDW) and platelet-large cell ratio (P-LCR) in HUA patients were higher than that in the normal group (P < 0.01), there was no statistically significant difference in platelet count, plateletcrit (PCT), mean platelet volume (MPV) between the two groups. There was positive correlation between serum uric acid and levels of GMP-140, PAF, P-LCR and PDW, respectively (r = 0.667, 0.879, 0.310, 0.460, P < 0.01 or P < 0.05). Multivariate stepwise regression analysis revealed that serum uric acid, creatinine, P-LCR, urea nitrogen contributed to GMP-140 level (adjusted R(2) = 0.822). Serum uric acid and LDL-C also contributed to PAF level (adjusted R(2) = 0.451). It is concluded that a close relationship exists between HUA and the change of platelet function, and HUA plays a certain role in cardiovascular disease thrombosis complications.
Assuntos
Hiperuricemia/sangue , Selectina-P/metabolismo , Fator de Ativação de Plaquetas/metabolismo , Adulto , Idoso , Plaquetas/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de PlaquetasRESUMO
OBJECTIVE: To investigate the efficacy and safety of a schedule of 2 cycles' high-dose dexamethasone (HD-DXM) as an initial therapy in adults immune thrombocytopenia (ITP), and compare with conventional dose prednisone therapy. METHOD: A total of 59 newly diagnosed ITP patients were divided into 2 groups randomly. In 30 patients (Dexamethasone group), oral HD-DXM was administered at 40 mg/d for 4 consecutive days, repeated one week later, and then failed to maintain. In the remaining 29 patients (Prednisone group), prednisone was administered orally at 1.0 - 1.5 mg×kg(-1)×d(-1) for 4 weeks, and then gradually tapered. RESULTS: For short-term efficacy, after 1 and 2 weeks of treatment, the response rate in Dexamethasone group was significantly higher than that in Prednisone group (50.0% vs 24.1%, P < 0.01; 73.3% vs 55.2%, P < 0.05), while 3 weeks later, there was no remarkable difference between the two groups (83.3% vs 68.9%, P > 0.05), though the response rate in Dexamethasone group remained higher. For long-term effect, at the end of the 2nd and 3rd months of follow-up, the relapse rate in Dexamethasone group was significantly lower than that in Prednisone group (24.0% vs 40.0%, P < 0.05; 32.0% vs 65.0%, P < 0.01), while at the end of the 1(st) month of follow-up, there was no significant difference (16.0% vs 20.0%, P > 0.05). In addition, it's well tolerated and no complications such as severe infection or Cushing syndrome were complained in Dexamethasone group. CONCLUSION: HD-DXM possesses an advantage over conventional dose prednisone therapy in efficacy and safety.
Assuntos
Dexametasona/administração & dosagem , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Adolescente , Adulto , Idoso , Dexametasona/efeitos adversos , Dexametasona/uso terapêutico , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prednisona/uso terapêutico , Resultado do Tratamento , Adulto JovemRESUMO
This study was aimed to explore the expression of erythropoietin receptor (EPOR) on acute leukemia cells and its clinical significance. Bone marrow of 40 patients with acute leukemia (AL) and 24 patients with normal bone marrow as control group were collected. Samples came from outpatients and inpatients in our hospital. EPOR mRNA was detected by reverse transcription-PCR. The results showed that there was EPOR expression on AL cells, the expression rate was 57.5%, and the average expression level (Gray value) was 0.3549 ± 0.2800, but both were lower than that in control group (p < 0.05). There was no significant statistic difference of expression rate between acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL) (p > 0.05), and expression level of AML EPOR was higher than that of ALL (p < 0.05). It is concluded that there is EPOR expression on AL cells, while the expression rate and expression level are lower than those in control group (p < 0.05). There is no significant statistic difference of the expression rate between AML and ALL (p > 0.05), and the expression level of AML EPOR is higher than that of ALL (p < 0.05).