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Major histocompatibility complex class II (MHC-II) trans-activator (CII TA) has been shown to be required for constitutive and IFN-gamma-induced MHC-II transcription. This study investigated the inhibitory effect of anti-CII TA M1-RNA on expression of MHC-II in chondrocytes in response to IFN-gamma. M1-RNAs with different guide sequence (GS) recognizing 452 or 3408 sites in CII TA (M1-452-GS and M1-3408-GS, respectively) were cloned into pUC19 vector. Target mRNA (3176-3560) in CII TA was obtained from Raji cell and inserted into pGEM-7zf(+) plasmid. The recombinant M1-RNAs and their target mRNA were incubated in a cell-free condition. It showed that only M1-3408-GS could cleave the target mRNA exclusively. M1-3408-GS was also cloned into psNAV vector (named pA3408). Chondrocytes was stably transfected with pA3408 and expressions of classical MHC-II (HLA-DR, -DP, -DQ) were analyzed by Flow Cytometry. The level of CII TA mRNA was measured by RT-PCR. Peripheral blood mono-nucleated cells (PBMNCs) were stimulated by pA3408-positive chondrocytes in mixed lymphocyte reaction, and proliferation of PBMNCs and IL-2 mRNA were detected. The expression of HLA-DR and HLA-DP on pA3408-positive chondrocytes in response to IFN-gamma decreased 73.00%+/-5.24%, 88.47%+/-2.02%, respectively (P<0.05); So did the content of CII TA mRNA (70.11%+/-5.79%, P<0.05). Proliferation of PBMNCs and production of IL-2 mRNA were both inhibited by pA3408 in mixed lymphocyte reaction. This is the first description that anti-CII TA M1-RNA could prevent IFN-gamma-induced CII TA transcription and results in a decreased MHC-II expression in chondrocytes.
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Condrocitos/inmunología , Proteínas de Escherichia coli/genética , Antígenos de Histocompatibilidad Clase II/metabolismo , Interferón gamma/antagonistas & inhibidores , Proteínas Nucleares/antagonistas & inhibidores , Ribonucleasa P/genética , Transactivadores/antagonistas & inhibidores , Células Cultivadas , Condrocitos/efectos de los fármacos , Antígenos de Histocompatibilidad Clase I/genética , Antígenos de Histocompatibilidad Clase I/metabolismo , Antígenos de Histocompatibilidad Clase II/genética , Humanos , Interferón gamma/farmacología , Prueba de Cultivo Mixto de Linfocitos , Proteínas Nucleares/genética , ARN Mensajero/antagonistas & inhibidores , ARN Mensajero/metabolismo , Transactivadores/genéticaRESUMEN
OBJECTIVE: To quantify peripheral blood mononuclear cell JAK3 mRNA levels after allogeneic haematopoietic stem cell (allo-HSCT) transplantation, and to explore its relationship with graft vs host disease (GVHD). METHODS: Serial monitoring of JAK3 mRNA levels by fluorescent quantitative reverse transcriptase polymerase chain reaction (FQ-RT-PCR) technique was performed on 26 cases (83 samples) after allo-HSCT. RESULTS: The mean JAK3/ABL expression levels was 8.71 in 14 patients without GVHD; the JAK3/ABL expression level was 31.94 in one patient with acute GVHD (aGVHD); the mean JAK3/ABL expression levels was 19.23 in 11 patients with chronic GVHD (cGVHD), and the cGVHD was diagnosed at the mean time of six months (3 - 12 months). The JAK3/ABL expression levels did not change in 4 patients one month after allo-HSCT, however, the levels increased again when GVHD were diagnosed in these 4 patients, and the JAK3/ABL expression levels decreased again when GVHD was remitted. CONCLUSION: The JAK3 expression level related to the remission and relapse in patients with GVHD.
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Enfermedad Injerto contra Huésped/genética , Janus Quinasa 3/genética , ARN Mensajero/metabolismo , Adolescente , Adulto , Femenino , Expresión Génica , Trasplante de Células Madre Hematopoyéticas , Humanos , Masculino , Trasplante de Células Madre de Sangre Periférica , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Adulto JovenRESUMEN
OBJECTIVE: To evaluate the safety of domestically produced idarubicin in the treatment of acute leukemia by a multicenter randomized control trial. METHODS: This trial was carried out in the hemotologica department of five hospitals throughout China, with hospitalized patients who suffered from acute myelogenous leukemia ( AML except M3 type) , acute lymphocytic leukemia ( ALL) , chronic myelogenous leukemia-blast (CML-blast) , totally 155 patients. Those with severely cardial, hepatic or renal disfunction or those who had ever treated with > or = 200 mg/m(2) idarubicin were excluded from the trial. All patients signed the letter of consent as required by the Ethics Committee of our government. In this study, 155 leukemia patients were randomly grouped into: 1. test group treated using domestic idarubicin, 2. control group using imported idarubicin. The acute myelogenous leukemia regimen included idarubicin 8 mg/m(2), dl -3 plus cytosine arabinoside 100 mg/m(2), dl - 7 for 1-2 cycles. The regimen for acute lymphocytic leukemia was idarubicin 8 mg/m2, dl - 3; vincristine 2 mg/mr, dl; cyclophosphamide 750 mg/m2, dl ; plus prednisone 60 mg/m(2),dl - 14 for 1-2 cycles. RESULTS: Clinical response rate of the tested group treated with domestic idarubicin and control group treated with imported idarubicin was 78. 1% (50/64) vs. 76.9% (50/65) without any statistically significant difference between the two groups(P >0. 05). Grade Ill - IV hematological toxicity rate of the domestic idarubicin group and imported idarubicin group was 74. 0% vs. 73. 1% , respectively (P = 0. 73). Drug-related death was observed in 3 of 77 patients in the domestic idarubicin group (3.9%) due to cerebral hemorrage or septic infection. The incidence of non-hematological toxicities in domestic idarubicin group and imported idarubicin group was 84. 4% vs. 79. 5% for nausea or vomiting, 70. 1% vs. 71. 8% for infection, 42. 9% vs. 41. 0% for mucositis, 33. 8% vs. 33. 3% for alopecia, 28.6% vs. 28. 2% for serum glutamicoxalacetic transaminase abnormalitis, 16. 9% vs. 10. 3% for cardiac toxicity, all without statistically significant differences between these two groups (P > 0. 05). Discontinuation of treatment due to non-hematological toxicity was not neccessary. CONCLUSION: Domestic idarubicin is comparable to imported counterpart in efficiency and safety for the treatment of acute leukemia. The most severe side effects of domestic idarubicin is hematological toxicity, which should be closely observed and treated in time, while its non-hematological toxicity is tolerable.
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Antibióticos Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Idarrubicina/administración & dosificación , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Adolescente , Adulto , Anciano , Agranulocitosis/inducido químicamente , Antibióticos Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Crisis Blástica/tratamiento farmacológico , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Citarabina/administración & dosificación , Citarabina/efectos adversos , Femenino , Humanos , Idarrubicina/efectos adversos , Masculino , Persona de Mediana Edad , Mucositis/inducido químicamente , Náusea/inducido químicamente , Prednisona/administración & dosificación , Prednisona/efectos adversos , Inducción de Remisión , Resultado del Tratamiento , Vincristina/administración & dosificación , Vincristina/efectos adversosRESUMEN
OBJECTIVE: To explore the clinical efficacy and toxicity of CLAT protocol (cladribine, cytarabine and topotecan) for treating patients with refractory acute myeloid leukemia (R-AML). METHODS: A total of 18 patients with R-AML (median age 37 years, range 18 to 58 years; male n = 16, female n = 2) were treated with CLAT protocol, which consisted of cladribine 5 mg/m(2)/d, i.v. on days 1-5, cytarabine 1.5 g/m(2)/d, i.v. on days 1-5, topotecan 1.25 mg/m(2)/d, i.v. on days 1-5 and G-CSF 300 µg/d subcutaneous injection on day 6 until neutrophile granulocyte recovery. RESULTS: Out of 18 patients 2 died of severe infection before the assessment. Among 16 evaluated patients, 10 (55.6%) achieved complete remission (CR), and 2 (11.1%) achieved partial remission (PR), the overall response rate was 66.7%, the rest 4 patients did not respond (NR). The median overall survival time and DFS for the CR patients was 9.5 months (95%CI: 6.7-16.64) and 9.5 months (95%CI: 6.1-16.7) respectively. The 1 year OS and DFS rates were 45% and 46.9%, respectively. All patients developed grade 4 of granulocytopenia and thrombocytopenia, the median duration was 13 (range 2 to 21) days and 12 days (range 2 to 21), respectively, all patients developed infection, 2 patients died of severe infection. The most common non-hematological side effects included nausea, vomiting, diarrhoea, rash, aminotransferase or bilirubin elevation and were grade 1 to 2. CONCLUSION: The CLAT protocol seems to have promising for the treatment of refractory AML patients, and patients well tolerated. This CLAT protocol offers an alternative treatment for R-AML patients who received severe intensive treatment, especially with anthracycline-containing chemotherapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Adolescente , Adulto , Agranulocitosis , Cladribina/uso terapéutico , Citarabina/uso terapéutico , Femenino , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Inducción de Remisión , Trombocitopenia , Topotecan/uso terapéutico , Adulto JovenRESUMEN
OBJECTIVE: To evaluate the efficacy and safety of IDA (Haizheng Parmacy, China) in the treatment of acute leukemia. METHODS: A multi-institutional single-blind randomized controlled clinical trial was carried out. A total of 155 newly diagnosed patients with AML and ALL were enrolled. The patients were randomly divided into two groups, one was given IDA (n = 77) and the other given zevodas (Pharnacia & Upjohn, n = 78) for comparison. RESULTS: All the patients enrolled in this trial were eligible for assessment of side effects, and 129 patients for evaluation of overall response rate. In patients treated with IDA vs zevodas, the overall response rate (OR) was 78.1% vs 76.9%, CR was 68.8% vs 67.7%; in AML patients, OR was 82.4% vs 71.8%, and CR was 76.5% vs 64.1%; in ALL patients, OR was 80.0% vs 81.8%, and CR was 68.0% vs 68.2%. There was no sitatistically significant difference in hematologic and non-hematologic toxicities between the two groups. CONCLUSION: The efficacy of IDA in the treatment of acute leukemia is comparable to that of zevodas. Both have similar toxic side effects.
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Antibióticos Antineoplásicos/uso terapéutico , Idarrubicina/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Adolescente , Adulto , Anciano , Antibióticos Antineoplásicos/efectos adversos , China , Femenino , Humanos , Idarrubicina/efectos adversos , Masculino , Persona de Mediana Edad , Método Simple CiegoRESUMEN
BACKGROUND: Manumycin exhibits an antitumor effect in a variety of cancer cell lines, including prostate cancer cell lines (DU145 and PC-3). Our previous studies demonstrated that manumycin induced the apoptosis of anaplastic thyroid cancer cells and leukemia cells via the intrinsic apoptosis pathway. In the current study, we further evaluated the effect of manumycin in two prostate cancer cell lines (LNCaP and 22Rv1), and here we elucidate some of the underlying mechanisms. MATERIALS AND METHODS: The cell viability of prostate cancer cells was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay after treatment with manumycin for 48 hours. Apoptosis was detected by flow cytometry using annexin V and propidium iodide. The expressions of B-cell lymphoma (Bcl)-2 family members and the activations of caspase-9 and caspase-3 were detected by Western blotting. RESULTS: Manumycin treatment resulted in significant decreases in the viabilities of the two prostate cancer cell lines in a dose-dependent manner through apoptosis, and this apoptosis involved caspase-9 activation. A specific inhibitor of caspase-9 protected cells from caspase-3 activation, apoptosis, and cytotoxicity induced by manumycin. We also found that manumycin downregulated Bcl-2 expression and upregulated Bax expression. CONCLUSION: Our data suggest that manumycin induces apoptosis in prostate cancer cells through regulation of the Bcl-2 family involving caspase-9 activation. These results suggest that manumycin may be beneficial for the treatment of prostate cancer.
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This study was aimed to investigate the c-kit mutation in acute myeloid leukemia (AML) patients with AML1-ETO and analyze its relation with clinical and laboratorial features and prognosis. PCR and sequencing methods were used to detect the c-kit 17 exon mutations in 31 AML patients with AML1-ETO. The relation of the c-kit mutation with clinical features, results of laboratorial examination and prognosis of disease were analyzed. The results showed that the c-kit mutation was found in 14 out of 31 AML patients and the mutation frequency was 45.16%. Male patients had a higher incidence of c-kit mutation than that of female patients (P = 0.020). The proportion of patients with newly diagnosed white blood cell>10×10(9)/L and with extramedullary infiltration in mutated group were higher than those in unmutated group respectively. No significant difference was observed at the age (P = 0.437) and the rate of bone marrow blasts(P = 0.510) between the above mentioned two groups. The difference in complete remission rate (64.29% vs 80%, P = 0.344)and relapse rate (58.33% vs 21.43%, P = 0.054) between c-kit mutated and c-kit unmutated groups were not significant. While the c-kit mutated group had a significant higher death rate as compared with c-kit unmutated group (57.14% vs 20%, P = 0.039). It is concluded that the c-kit mutation is frequent in AML patients with AML1-ETO and the c-kit mutated patients have a poor prognosis. It is important to detect c-kit mutation in routine clinical practice for patient's risk stratification, evaluation of prognosis and selection of effective treatment.
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Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Leucemia Mieloide Aguda/genética , Proteínas de Fusión Oncogénica/genética , Proteínas Proto-Oncogénicas c-kit/genética , Adolescente , Adulto , Anciano , Análisis Mutacional de ADN , Femenino , Humanos , Leucemia Mieloide Aguda/patología , Masculino , Persona de Mediana Edad , Mutación , Pronóstico , Proteína 1 Compañera de Translocación de RUNX1 , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: To understand the predictive value of early monitoring BCR-ABL transcripts in patients with chronic myeloid leukemia (CML) after treatment with tyrosine kinase inhibitor (TKI), and to provides the information for early assessment of prognosis and treatment options. METHODS: BCR-ABL transcripts of 53 CML patients before and after TKI treatment were detected by using real-time quantitative RT-PCR. The relationship between BCR-ABL transcripts level after TKI treatment for 3 months and the later molecular response, progression and mutation was analyzed. RESULTS: The median values of BCR-ABL transcripts in peripheral blood samples from 30 newly diagnosed patients were 43.99%, which was used as a baseline of BCR-ABL transcripts for molecular response evaluation. Of 53 patients, 31 (58.49%) had a BCR-ABL mRNA ≤ 4.40% (reduced more than 1 log) and 22 (41.51%) greater than 4.40% (reduced to less than 1 log) after 3 months of TKI treatment. The former 31 patients had a significantly higher 18-months cumulative incidence of major molecular response (MMR) (90.32% vs 18.18%, P=0.000) and 3-year cumulative incidence of complete molecular response (CMR) (48.39% vs 0, P=0.000) compared with the latter 22 patients. The lower BCR-ABL level was, the earlier MMR reached. The proportion of patients with a mutation in group of BCR-ABL mRNA>4.40% was significantly higher than that of BCR-ABL mRNA ≤ 4.40% (22.73% vs 0, P=0.021). The incidence of progression increased in group of BCR-ABL mRNA>4.40%, but the difference was not statistically significant (P=0.052). CONCLUSION: It is important for the prognosis evaluation of the patients to monitor the level of BCR-ABL transcripts at 3 months after TKI treatment, which might help to early optimization of treatment and to improve curative effect of CML patients.
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Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Adulto , Anciano , Femenino , Proteínas de Fusión bcr-abl/sangre , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , ARN Mensajero/genética , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: To analyze the specificity, sensitivity and receiver operating characteristic (ROC) curve of plasma elafin for diagnosis of skin acute graft-versus-host disease (aGVHD), and to explore its clinical diagnostic value. METHODS: Incidence of skin aGVHD from fifty-three patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT) were observed prospectively in Guangdong General Hospital from Apr 2010 to Aug 2011. The plasma concentrations of elafin were detected by enzyme-linked immunosorbent assay (ELISA). Skin biopsies were taken from 28 patients with skin rash, and elafin expression in the skin was detected by immunohistochemistry. Positive expression was defined as significant staining of at 50% of the depth of the epidermis, excluding the granular cell layer and the acrosyringium. RESULTS: Among 28 patients with skin rash, twenty-five were considered as skin aGVHD by clinical diagnosis, seventeen were confirmed as skin aGVHD by pathological biopsy. 11 cases were elafin positive by immunohistochemical staining. Elafin protein was overexpressed in aGVHD skin tissue (P = 0.001). Plasma concentrations of elafin were significantly higher in patients with skin aGVHD (positive) group than in those without skin aGVHD (negative) group (P = 0.005), among which there being no statistically significant difference in plasma elafin level between patients with grade I skin aGVHD group and negative group(P = 0.971), but being statistically significant difference compared patients with grade II-IV skin aGVHD group with those with grade I skin aGVHD group (P = 0.02) and with negative group (P = 0.008). Using the pathological diagnosis as the gold standard, the estimated specificity and the sensitivity of clinical diagnosis criteria were 27.3% and 100%, respectively, and those of tissue elafin protein level were 100% and 64.7%, respectively. The area under the ROC curve was 0.909 (0.797 - 1.021) when plasma concentrations of elafin was used in diagnosis of skin aGVHD. The sensitivity was 82.4% and the specificity was 81.8 % when the critical value was set at 1456.043 µg/L. CONCLUSION: Plasma concentration of elafin is significantly higher at the onset of skin aGVHD. It can be used as biochemical marker of skin aGVHD and has higher value in diagnosis of skin aGVHD.
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Elafina/sangre , Enfermedad Injerto contra Huésped/sangre , Enfermedad Injerto contra Huésped/diagnóstico , Enfermedades de la Piel/sangre , Adolescente , Adulto , Femenino , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Curva ROC , Sensibilidad y Especificidad , Enfermedades de la Piel/diagnóstico , Enfermedades de la Piel/etiología , Adulto JovenRESUMEN
The aim of this study was to investigate the renal function in 149 patients receiving myeloablative allogeneic hematopoietic stem cell transplantation (allo-HSCT) from June 2005 to June 2010 in our hospital, and analyze the risk factors resulting in kidney insufficiency and experience in diagnose and therapy. The creatinine clearance (CrCL) and serial creatinine level were evaluated before and after allo-HSCT within 100 days and 1 year. Non-radiation conditioning regimens were used for any patients. The acute kidney insufficiency (AKI) was defined as at least a 1.5-fold rise in serum creatinine level after allo-HSCT within the first 100 days. The chronic kidney insufficiency (CKI) was defined as the creatinine clearance < basal level within 3 months to 1 year after allo-HSCT. The results showed that the kidney insufficiency was found in 41 patients, in which the incidence of AKI was 32/149 (21.5%). CsA, amphotericin B (P = 0.025) and ES (P = 0.022) were defined as risk factors for AKI. The incidence of CKI was 18/138 (13%). cGVHD (P = 0.013) and TA-TMA (P = 0.012) were associated with the development of CKI. The 2-year survival was lower in patients with kidney dysfunction than that in patients without kidney dysfunction (39% vs 74.1%, P < 0.001). The main factors resulting in kidney insufficiency were defined as infection (52%), GVHD (20%), TA-TMA (12%) and tumor relapse (12%). It is concluded that kidney insufficiency is an important complication of allo-HSCT. Careful monitoring kidney function, minimizing the use of amphotericin B, prophylaxis and effective treatment of fungal infection, GVHD and TA-TMA may be effective preventive measures to decrease the incidence of kidney insufficiency.
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Trasplante de Células Madre Hematopoyéticas/efectos adversos , Insuficiencia Renal/etiología , Lesión Renal Aguda/etiología , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Trasplante Homólogo , Adulto JovenRESUMEN
This study was purposed to investigate the efficacy and safety of intravenous injecting itraconazole (ITCZ) as empirical antifungal therapy in the patients with hematological malignancies. According to recommendation in IDSA guidebook, the patients suffered from fever during neutropenia and inefficacy of treatment using broad-spectrum antibiotics for 4 days should receive intravenous injection of ITCZ as empirical antifungal therapy. The results showed that the overall clinical response rate to ITCZ injection was 62.9% (22/35), and the success rate of achieving composite endpoints was 54.3% (19/35). Mild adverse reactions were observed in 6 patients (17.1%). The injection of ITCZ was stopped in 2 patents (5.7%) due to adverse reaction. Further analysis revealed that the response rate was higher in patients with fever prior to the start of ITCZ within five days than beyond five days (P = 0.031). The response rate was higher in patients with possible invasive fungus infection (IFI) than that in patients with probable and confirmed IFI (P = 0.002). The prophylactic antifungal treatment during neutropenia displayed no significant influence on efficacy of empirical antifungal therapy with itraconazole (P = 0.054). It is concluded that the good efficacy and safety of empirical ITCZ injection for hematological malignancies patients is efficient and safe.
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Antifúngicos/uso terapéutico , Neoplasias Hematológicas/tratamiento farmacológico , Itraconazol/uso terapéutico , Adolescente , Adulto , Anciano , Antifúngicos/administración & dosificación , Femenino , Humanos , Inyecciones Intravenosas , Itraconazol/administración & dosificación , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: To analyze the promoter methylation levels of p15, CDH1, DAPK and HICI genes of patients with myelodysplastic syndrome (MDS) and explore the relationship between the level of methylation and clinical features. METHODS: DNA methylation levels of p15, CDH1, DAPK and HICI in peripheral blood (PB) or bone marrow (BM) samples from 52 MDS patients were detected by real-time quantitative PCR. The correlation of the methylation level with clinical features and hematological findings was analyzed. 38 de novo AML patients and 46 normal individuals served as controls. RESULTS: The methylation levels of p15, CDH1, DAPK and HICI were 16.23 ± 21.69, 6.59 ± 9.39, 0.14 ± 0.11 and 7.81 ± 9.70 in BM, and 14.96 ± 20.16, 6.00 ± 9.26, 0.12 ± 0.14 and 6.74 ± 9.72 in PB, respectively from 18 MDS patients, and the difference between BM and PB was not statistically significant (P > 0.05). The methylation levels of p15 (14.70 ± 18.17) and CDH1 (6.61 ± 8.79) genes in high risk (RAEBI/II) MDS were significantly higher than in low risk (RCMD/RARS/5q-, p15: 1.99 ± 1.59, CDH1: 1.23 ± 1.14 and RCMD, p15: 3.02 ± 3.42, CDH1:1.53 ± 2.06) MDS or control (p15: 1.69 ± 1.82, CDH1: 1.01 ± 1.12) (P < 0.05). The methylation levels of DAPK gene had no difference among subtypes of MDS, and that of HIC1 gene only differed between RAEB I/II (9.16 ± 11.95) and control (2.49 ± 2.26) (P = 0.042). The difference of methylation levels of p15, CDH1, DAPK and HICI in BM was statistically significant among subtypes of MDS (P = 0.001, 0.003, 0.039, 0.023, respectively). And so did of p15 and DAPK in PB (P = 0.013, 0.006, respectively). The methylation level of p15 and CDH1 was significantly correlated with IPSS classification and blasts percentage in BM. CONCLUSIONS: p15 and CDH1 genes are special hypermethylation genes in MDS. Methylation level of HIC1 gene showed an upward tendency from low risk to high risk MDS.
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Metilación de ADN , Síndromes Mielodisplásicos/genética , Síndromes Mielodisplásicos/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Cadherinas/genética , Cadherinas/metabolismo , Proteínas Quinasas Dependientes de Calcio-Calmodulina/genética , Proteínas Quinasas Dependientes de Calcio-Calmodulina/metabolismo , Estudios de Casos y Controles , Inhibidor p15 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p15 de las Quinasas Dependientes de la Ciclina/metabolismo , Proteínas Quinasas Asociadas a Muerte Celular , Femenino , Humanos , Factores de Transcripción de Tipo Kruppel/genética , Factores de Transcripción de Tipo Kruppel/metabolismo , Masculino , Persona de Mediana Edad , Regiones Promotoras Genéticas , Reacción en Cadena en Tiempo Real de la Polimerasa , Adulto JovenRESUMEN
The purpose of this study was to investigate the influence of nitro oxide (NO) from mesenchymal stem cells (MSC) on the proliferative responses of allogeneic lymphocytes and its mechanism. MSCs were isolated and cultured from human bone marrow. Selected surface antigens of MSCs were detected by flow cytometry and their morphologic characteristics were determined by microscopy. Mitomycin C-treated MSCs were plated in dishes and then mixed lymphocyte cultures (MLC) were set up. After 4 days, lymphocyte proliferation was determined by CCK-8 assays; NO secretion in coculture supernatant was determined by Griess reagent kit; the level of FOXP3 mRNA expression was detected by real-time quantitative PCR. The results indicated that in MSC/MLC coculture experiment, the lymphocyte proliferation decreased significantly with of IOD value 0.49+/-0.03, NO production increased obviously (21.05+/-1.14 micromol/L) and FOXP3 mRNA expression was increased [(1.56+/-0.34)%] as compared with MLC coculture without MSC. There were significant difference between these two groups. It is concluded that NO production in human MSC culture up-regulates FOXP3 mRNA expression and thus inhibits lymphocyte proliferation response.
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Células de la Médula Ósea/citología , Proliferación Celular , Linfocitos/citología , Células Madre Mesenquimatosas/citología , Óxido Nítrico/metabolismo , Adulto , Células Cultivadas , Factores de Transcripción Forkhead/metabolismo , Humanos , Recuento de Linfocitos , Prueba de Cultivo Mixto de Linfocitos , Linfocitos/inmunología , Linfocitos/metabolismoRESUMEN
This study was aimed to investigate the aven mRNA expression level of leukocytes from peripheral blood(PB)of de novo patients with acute myeloid leukemia (AML) and analyze its clinical significance, so as to provide a experimental basis for evaluating prognosis. The aven mRNA expression levels in PB samples from 69 de novo AML patients were detected by using real-time quantitative PCR. The relation of aven mRNA level with clinical and hematological characteristics (age, sex, WBC, Hb, Plt, LDH, Blast% in PB and BM, FAB subtype) and treatment outcome (CR rate and relapse rate) were analyzed. 21 normal individuals served as controls. The results showed that the expression level of aven mRNA was between 11.72% and 178.93% (median 37.2%) in de novo AML and between 10.81% and 50.98% (median 28.81%) in normal individuals. Aven mRNA expression level was higher in the AML group than that in the controls (p = 0.006). As aven mRNA expression level was compared with other clinical and hematological parameters, there were significant correlations between aven mRNA expression level and age (r = 0.25, p = 0.039), and between hemoglobin level (r = 0.29, p = 0.019), FAB subtype(r = 0.253, p = 0.036). The median expression level (50.08%) of aven mRNA in older patients (> or = 44 years) was higher then that (32.41%) in younger patients (< 44 years) (p = 0.018). The complete remission (CR) rate after two cycles of chemotherapy in patients with lower aven mRNA level (25/30, 83.33%) was higher than that in patients with higher aven mRNA level(21/30, 70%), but the difference was not significant(p = 0.22). The difference of aven mRNA expression level between AML patients with relapse and AML patents without relapse was not significant (p = 0.076). It is concluded that the expression level of aven mRNA in de novo AML patients obviously increases, the overexpression of aven mRNA likely involves in genesis of AML. The definite relation of aven mRNA expression level with treatment outcome and relapse was not been found.
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Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Reguladoras de la Apoptosis/genética , Leucemia Mieloide Aguda/genética , Proteínas de la Membrana/genética , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , ARN Mensajero/genética , Análisis de Secuencia , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND AND OBJECTIVE: Chemotherapy regimen containing anthracyclines has been used as the standard treatment for acute myeloid leukemia (AML). This study was to compare the efficacy and toxicity of the chemotherapy regimen containing perarubicin (THP) with that containing mitoxantrone (MIT) for young patients with newly diagnosed AML. METHODS: A total of 129 patients with newly diagnosed AML, aged 16 to 60 years olds, were assigned for induction chemotherapy containing one to two courses with standard-dose cytarabine (Ara-C) and an anthracycline antibiotic, THP or MIT. When complete remission was achieved after induction therapy, the patients received two courses of consolidation therapy identical to the induction regimen. From then, the patients were alternately given four courses of consolidation therapy consisting of Ara-C/THP or Ara-C/MIT every three weeks. Maintenance treatment continued for three years when patients were in continuous complete remission (CCR). RESULTS: Twenty-six out of 42 patients (61.90%) receiving THP therapy, and 48 out of 73 patients (65.75%) treated by MIT achieved CR (P>0.05). Nine (34.61%) and 11 (22.92%) out of CR patients treated by THP and MIT, respectively, relapsed within one year (P=0.28). Moreover, the incidences of toxicities, such as infection, nausea/vomiting and cardiac events, were similar in these two groups (P>0.05) except for alopecie, which was 26.19% in the THP group compared to 42.47% in the MIT group (P<0.01). CONCLUSIONS: Regimen containing THP plus Ara-C can be used for young adults with newly diagnosed AML for remission induction, but it is not superior to the regimen with MIT. Consolidation chemotherapy with THP or MIT is feasible for young adults with AML after CR.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Doxorrubicina/análogos & derivados , Leucemia Mieloide Aguda/tratamiento farmacológico , Adolescente , Adulto , Agranulocitosis/inducido químicamente , Alopecia/inducido químicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Citarabina/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Humanos , Leucemia Mieloide Aguda/patología , Masculino , Persona de Mediana Edad , Mitoxantrona/administración & dosificación , Náusea/inducido químicamente , Recurrencia , Inducción de Remisión , Adulto JovenRESUMEN
OBJECTIVE: To screen the molecular markers for refractory anemia with excess blasts in transformation (RAEB) in myelodysplastic syndromes (MDS) by serum proteome profiling. METHODS: The serum protein were isolated from patients with RAEB, acute myeloid leukemia or normal subjects by 2-dimensional electrophoresis (2-DE), and the electrophoresis gels were obtained to identify the differentially reacting protein spots. The replica gels of the differentially reacting proteins were analyzed to locate the matching protein spots, which were identified by peptide mass fingerprint based on matrix-assisted laser desorption/ionization time of-flight mass spectrometry (MALDI-TOF-MS) and database searching. RESULTS: Seven differentially expressed proteins in RAEB were found by 2-DE. Of the 7 proteins, 4 were identified by MALDI-TOF-MS to have significantly differential expression in RAEB, including dipeptidyl peptidase (DPP/CD26), polymerase (DNA directed) kappa, PRO2044 and an albumin-like protein. CONCLUSION: 2-DE-based serum proteome profiling helps identify serum proteomic biomarkers related to MDS. DDP/CD26 has increased expression in the serum in RAEB subtype MDS, suggesting its possible role in advanced MDS.