RESUMEN
A retrospective analysis was conducted based on the clinical data from 60 patients older than 16 years from January 2016 to January 2021. All the patients were newly diagnosed with severe aplastic anemia (SAA) with an absolute neutrophil count (ANC) of zero. We compared the hematological response and survival of haploidentical-allogeneic hematopoietic stem cell transplantation (HID-HSCT) (n = 25) and intensive immunosuppressive therapy (IST) (n = 35) treatments. At six months, the overall response rate and complete response were significantly higher in the HID-HSCT group than those in the IST group (84.0% vs. 40.0%, P = 0.001; 80.0% vs. 17.1%, P = 0.001). With a median follow-up of 18.5 months (4.3~30.8 months), patients in the HID-HSCT group had longer overall survival and event-free survival (80.0% vs. 47.9%, P = 0.0419; 79.2% vs. 33.5%, P = 0.0048). These data suggested that HID-HSCT might be an effective alternative treatment option for adult patients with SAA with an ANC of zero, which requires further validation in an additional prospective study.
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Anemia Aplásica , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Adulto , Humanos , Estudios Retrospectivos , Neutrófilos , Estudios Prospectivos , Enfermedad Injerto contra Huésped/etiología , Terapia de Inmunosupresión , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Acondicionamiento PretrasplanteRESUMEN
BACKGROUND: Transfusion strategies are involving the survival and prognosis of patients with malignant neoplasm and the rational utilization of medical resources, but there are still controversy between different transfusion strategies. The aim of this article is to compare the benefit and harm of restrictive and liberal red blood cell(RBC) transfusion strategies in patients with malignant tumors. METHODS: We searched articles in the databases of PubMed, Cochrane Library, Web of Science, Embase and major conference proceedings, identified all randomized controlled trials (RCTs) and compared restrictive transfusion strategies with those that are liberal until MARCH 18, 2019. We used risk ratio (RR) and and 95 % confidence interval (95 %CI) to calculate the results of dichotomous variables, and the study heterogeneity was assessed by using the I2 statistics. Also, we did sensitivity analysis and quality assessment. RESULTS: Restrictive transfusion policies appear to have no effect on all-cause mortality (RR 1.33; 95 % CI 0.74-2.38; P = 0.34), compared with liberal policies. 2 trials including 498 patients were included of renal replacement therapy (RR 1.38; 95 % CI, 0.73-2.59; P = 0.32; I2 = 0%). Myocardial infarction (RR 1.17; 95 % CI, 0.33-4.1; P = 0.81; I2 = 0%) and ICU readmission were also mentioned in these articles (RR 1.19; 95 % CI, 0.7-2.04; P = 0.52; I2 = 0%). However, the RR of hospital length can't be evaluated. CONCLUSION: Restrictive transfusion strategies were not associated with all-cause mortality and other clinical outcomes in malignant tumors, and may be more suitable for patients' quality of life and medical economy than liberal.
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Transfusión Sanguínea/métodos , Neoplasias/terapia , Calidad de Vida/psicología , Humanos , Neoplasias/mortalidad , Proyectos Piloto , Ensayos Clínicos Controlados Aleatorios como Asunto , Análisis de SupervivenciaRESUMEN
OBJECTIVE: To study Chinese medicine (CM) syndrome types of chronic aplastic anemia (CAA) patients and the distribution laws of typical CM symptoms in different genders. METHODS: From June 2002 to June 2012, 220 CAA outpatients/inpatients at Department of Hematology, Zhejiang Chinese Medical Hospital were recruited. Patients' symptoms and signs, as well as four diagnostic information at the first onset were collected. CM syndrome differentiation was performed. The syndrome types and typical symptoms were analyzed. RESULTS: (1) In the 220 CAA patients, there were 121 cases of Shen yang deficiency syndrome (55.0%), 18 of Shen yin deficiency syndrome type (8.18%), 81 cases of Shen yin-yang deficiency syndrome (36.82%). (2) The distribution of typical symptoms: fatigue and shortness of breath (77.12% males and 73.53% females), pale complexion (64.41% males and 57.84% females), low temperature of four limbs (12.71% males and 26.47% females), spontaneous perspiration and night sweating (32.20% males and 26.47% females), dry mouth and throat (6.78% males and 6.86% females), feverish feelings in palms and soles (14.41% males and 20.59% females), loose stool (6.78% males and 2.94% females), petechiae and ecchymosis (42.37% males and 43.14% females). CONCLUSIONS: Shen yang deficiency syndrome was most often seen in CAA patients at the initial diagnosis, followed by Shen yin-yang deficiency syndrome. Shen yin deficiency syndrome was the least seen. In CM symptoms, fatigue and shortness of breath were most common seen, followed by pale complexion, skin petechia and ecchymosis.
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Anemia Aplásica/diagnóstico , Medicina Tradicional China/métodos , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Deficiencia Yang/diagnóstico , Deficiencia Yin/diagnóstico , Adulto JovenRESUMEN
OBJECTIVE: To observe the clinical characteristics and impact on mortality of carbapenem-resistant Pseudomonas aeruginosa (CRPA) colonized or infected patients with hematological disorders in order to provide evidence for the prevention and treatment of CRPA. METHODS: The patients who were colonized or infected with CRPA in the Department of Hematology of The First Affiliated Hospital of Zhejiang Chinese Medical University from January 2020 to March 2021 were selected as the research subjects, the clinical data such as hospitalization time, primary disease treatment regimen, granulocyte count, previous infection and antibiotic regimen of these patients were analyzed, meanwhile, antibiotic regimen and efficacy during CRPA infection, 30-day and long-term survival were also analyzed. RESULTS: A total of 59 patients were included in this study, and divided into CRPA infection group (43 cases) and CRPA colonization group (16 cases). Univariate logistic regression analysis showed that ECOG score (P =0.003), agranulocytosis (P <0.001), and exposure to upper than 3rd generations of cephalosporins and tigecycline within 30 days (P =0.035, P =0.017) were the high-risk factors for CRPA infection. Multivariate logistic regression analysis showed that ECOG score of 3/4 ( OR=10.815, 95%CI: 1.260-92.820, P =0.030) and agranulocytosis ( OR=13.82, 95%CI: 2.243-85.176, P =0.005) were independent risk factors for CRPA infection. There was a statistically significant difference in cumulative survival rate between CRPA colonization group and CRPA infection group ( χ2=14.134, P < 0.001). Kaplan-Meier survival analysis showed that the influencing factors of 30-day survival in patients with CRPA infection were agranulocytosis (P =0.022), soft tissue infection (P =0.03), and time of hospitalization before CRPA infection (P =0.041). Cox regression analysis showed that agranulocytosis was an independent risk factor affecting 30-day survival of patients with CRPA infection (HR=3.229, 95%CI :1.093-3.548, P =0.034). CONCLUSIONS: Patients with hematological disorders have high mortality and poor prognosis after CRPA infection. Bloodstream infection and soft tissue infection are the main causes of death. Patients with high suspicion of CRPA infection and high-risk should be treated as soon as possible.
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Enfermedades Hematológicas , Infecciones de los Tejidos Blandos , Humanos , Carbapenémicos/uso terapéutico , Pseudomonas aeruginosa , Infecciones de los Tejidos Blandos/tratamiento farmacológico , Antibacterianos/uso terapéutico , Análisis de SupervivenciaRESUMEN
OBJECTIVE: To explore the inhibition of Hedyotis diffusa Willd Injection (HDI) on the proliferation of RPMI 8226 cells and its mechanisms. METHODS: The inhibition of HDI on the proliferation of RPMI 8226 cells was detected by MTT and the drug concentrations for further researches were screened out. The apoptosis rate was detected using Annexin V-PI of flow cytometry. The cell cycle distribution was detected by PI. The expressions of adhesion molecule FITC-CD44 and PE-CD49d were detected. The IL-6 and VEGF concentrations of cell supernatants were tested by ELISA. The mRNA expressions of Bax, Bcl-2, Caspase-3, Survivin, IL-6, and VEGF were detected by RT-PCR. RESULTS: HDI could inhibit the proliferation of RPMI 8226 cells. Meanwhile, it induced their early apoptosis, arresting them at G1 phase in a concentration-dependent manner. The VEGF concentrations were down-regulated after acted by 0, 20, 40, and 60 microL/mL HDI in a dose-dependent manner (P< 0.01). The IL-6 content increased (P<0.01). The expressions of CD44 and CD49d were up-regulated in a concentration-dependent manner. After acted by 40 microL/mL HDI, the Survivin mRNA level was significantly downregulated (P<0.01), the mRNA levels of Bcl-2, IL-6, and VEGF were significantly up-regulated (P<0.01), but the up-regulation of Bax and Caspase-3 mRNA levels were not so obvious (P>0.05). CONCLUSIONS: HDI could inhibit the proliferation of RPMI 8226 cells. Its mechanisms might be correlated with early apoptosis induction, G1 phase arresting, VEGF secretion lowering, and Survivin mRNA transcription level down-regulating.
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Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Hedyotis , Línea Celular Tumoral , Humanos , Proteínas Inhibidoras de la Apoptosis/metabolismo , Interleucina-6/metabolismo , Survivin , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
BACKGROUND: Hepatitis-associated aplastic anemia (HAAA) is a rare condition. Patients with HAAA usually present with acute hepatitis, jaundice and significantly increased transaminase. After 1-2 mo, hepatitis gradually improves, but progressive hemocytopenia, bone marrow hematopoietic failure, and severe or extremely severe aplastic anemia are manifest. Most cases of HAAA are fulminant and usually lethal if left untreated. The literature on Epstein-Barr virus (EBV)-associated HAAA is sparse. CASE SUMMARY: We report a 30-year-old man who was admitted to our hospital because of pale yellow urine and skin with a simultaneous decrease in peripheral blood ternary cells. We made a diagnosis of EBV-associated HAAA. The treatment strategy for this patient included eltrombopag, an immunosuppressive regimen of rabbit anti-human thymocyte immunoglobulin, cyclosporine, and supportive care. The patient was discharged in normal physical condition after five months. A hemogram performed on follow-up revealed that he had achieved a complete response. CONCLUSION: Eltrombopag plus anti-thymocyte globubin and cyclosporine may be a therapeutic option for EBV-associated HAAA.Larger studies are warranted to confirm.
RESUMEN
Severe aplastic anemia (SAA) is a life-threatening bone marrow failure disease. Allogeneic hematopoietic stem cell transplantation from a matched sibling donor (MSD-HSCT) and intensive immunosuppressive therapy (IST) are 2 major comparable treatments for SAA. As the addition of eltrombopag (EPAG) to standard IST therapy has greatly improved the survival prognosis of SAA, whether MSD-HSCT or IST/EPAG is the better choice has become a matter of debate. A study was performed involving 99 patients with newly diagnosed acquired SAA from 5 medical centers, including 48 MSD-HSCT cases and 51 IST/EPAG cases, which consisted of rabbit antithymocyte globulin or porcine-antilymphocyte globulin, cyclosporine plus eltrombopag. The results suggested that patients treated with MSD-HSCT or IST/EPAG had similar overall survival (OS) rates exceeding 95% (Pâ¯=â¯.97). However, the event-free survival rate (EFS) of IST/EPAG (71.0%) was significantly lower than that of MSD-HSCT (89.6%), Pâ¯=â¯.04. Subgroup analysis indicated that the OS of the MSD-HSCT group was superior to that of the IST/EPAG group (100% versus 85.7%, Pâ¯=â¯.04) among those with very severe aplastic anemia (VSAA). Both the complete response rate (CR) and overall response rate (OR) with MSD-HSCT were significantly higher than those with IST/EPAG (CR: 79.2% versus 15.7%, P < .001; OR: 97.9% versus 72.6%, Pâ¯=â¯.001). In conclusion, IST/EPAG or MSD-HSCT treatment achieves an equally high OS in SAA, but MSD-HSCT leads to a better OS in patients with VSAA and shows advantages in improving EFS and accelerating hematopoietic reconstruction in patients with SAA.
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Anemia Aplásica , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Animales , Benzoatos , Humanos , Hidrazinas , Terapia de Inmunosupresión , Pirazoles , Hermanos , PorcinosRESUMEN
OBJECTIVE: To probe the effects of qi-supplementing and yin-nourishing therapy (blood-increasing decoction and blood generating powder) on chronic thrombocytopenia. METHODS: Two hundred patients with chronic thrombocytopenia were randomly divided into control (n = 100) and test groups (n = 100) with Amino-polypeptide as a basic treatment for both. Test group patients consumed a blood-increasing decoction and blood-generating powder for 1-3 months. Improvements in platelet counts and TCM syndrome were observed. RESULTS: One hundred and sixty-four (80 in the test group and 84 in the control group) of 189 total participants were treated for 3 months. The total effective rate in improving TCM syndrome was 95.00% in the test group and 79.76% in the control group (P < 0.05). There was significant difference (P < 0.05) in the accumulated score of TCM syndrome between the two groups treated at different time points. The total effective rate of platelet counts was 86.25% in the test group and 59.52% in the control group (P < 0.05). There was a significant difference in platelet counts before and after treatment in the two groups (P < 0.05). There was no significant differences in platelet count between the two groups treated for 1-2 months; however, a significant difference was found between the two groups after treatment for 3 months (P < 0.05). CONCLUSIONS: After a 3-month treatment of chronic thrombocytopenia patients with qi-supplementing and yin-nourishing therapy, TCM syndrome was improved and platelet counts increased with no obvious side effects, and the quality of life of the participants was enhanced with noticeable long-term curative effects.
Asunto(s)
Medicamentos Herbarios Chinos/uso terapéutico , Qi , Trombocitopenia/tratamiento farmacológico , Deficiencia Yin/tratamiento farmacológico , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Péptidos/uso terapéutico , Recuento de Plaquetas , Trombocitopenia/sangre , Deficiencia Yin/sangre , Adulto JovenRESUMEN
OBJECTIVE: To study the therapeutic effect of combined therapy with Chinese drugs and immuno-suppressors, mainly anti-lymphocyte globulin/anti-thymus globulin (ALG/ATG), for the treatment of severe aplastic anemia (SAA), the efficacy associated factors and adverse effects as well. METHODS: A retrospective analysis was conducted on 65 patients with SAA treated by combined therapy which was supplemented with cyclosporin A, androgen, hematopoietic growth factor, etc. RESULTS: Of the 57 patients followed-up, 26 (45.6%) were basically cured, 15 (26.3%) remitted, and 8 (14.0%) improved markedly, the total effective rate being 85.9%. By separately comparing with a single item of clinical data, it was shown that the therapeutic effectiveness was correlated, to a certain extent, with age, illness duration, neutrophil count, and bone marrow proliferation in patients before treatment, as well as with infection that occurred in the follow-up period. It was obviously higher in patients with peripheral neutrophil count > 0.5 x 10 10(9)/L (P<0.05). Various degrees of serum sickness-like reactions occurred in the treatment of 36 patients, including fever in 36 (63.2%), skin rash in 8 (14.0%), and musculoskeletal pain in 5 (8.8%). CONCLUSIONS: The therapeutic effect of combined therapy with Chinese drugs and ALG/ATG in treating SAA could be affirmed, showing some superiority as compared with Western medicine alone. The patients' age, duration of illness, neutrophil count, and bone marrow proliferation before treatment, and degree of infection that occurred could affect the therapeutic efficacy to a certain extent. Adverse reactions resulting from the combined therapy are less, showing the toxicity reducing and effect enhancing action of Chinese drugs.
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Anemia Aplásica/tratamiento farmacológico , Suero Antilinfocítico/uso terapéutico , Medicamentos Herbarios Chinos/uso terapéutico , Inmunosupresores/uso terapéutico , Adolescente , Adulto , Anemia Aplásica/patología , Suero Antilinfocítico/administración & dosificación , Suero Antilinfocítico/efectos adversos , Niño , Terapia Combinada , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/efectos adversos , Femenino , Estudios de Seguimiento , Humanos , Inmunosupresores/administración & dosificación , Inmunosupresores/efectos adversos , Linfocitos/efectos de los fármacos , Linfocitos/inmunología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Timo/efectos de los fármacos , Timo/inmunología , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: To evaluate the regulation of VEGF-Notch signaling pathway on proliferation and apoptosis of mesenchymal stem cells (MSC) in the patients with aplastic anemia (AA). METHODS: The bone marrow specimens of AA patients were collected for isolation and identification of BM MSC. Westen blot was used to detect the expression of VEGF-Notch signaling pathway-related proteins (VEGF, VEGFR, Notch 1, Jagged 1, Delta-like 1 and Hes1). The VEGF (100 ng/ml) and DAPT (γ-secretase inhibitor, 10 µmol/L) were respectively added into MSC culture system in oder to activate and inhibit the signaling transduction of VEGF-Notch in BM MSC. The proliferation, apoptosis and cell cycle of MSC in AA patients were detected by CCK8 assay and flow cyfometry. The adipogenic differentiation of BM MSC was detected by oil red O staining. RESULTS: The VEGF-Notch signaling pathway was significantly inhibited in AA BM tissues and AA MSC (Pï¼0.05) detected by Western blot. The intervention of VEGF and DAPT significantly activated and inhibited VEGF-Notch signaling in AA MSC, respectively. CCK8 assay showed that VEGF intervention significantly promoted the proliferation of MSC in AA patients (Pï¼0.05). Flow cytometry showed that VEGF significantly inhibited apoptosis of MSCs by blocking S phase cells (Pï¼0.05). CONCLUSION: The activation of VEGF-Notch can restore the proliferation function of MSC in AA patients.
Asunto(s)
Anemia Aplásica , Células Madre Mesenquimatosas , Apoptosis , Médula Ósea , Proliferación Celular , Humanos , Transducción de Señal , Factor A de Crecimiento Endotelial VascularRESUMEN
Objectives: To evaluate the prognosis of adult severe aplastic anemia (SAA) patients with absolute neutrophil count (ANC) values of zero prior to immunosuppressive therapy (IST). Methods: Patients with ANC values of zero prior to IST were separated from very SAA and analyzed in a prospective study. All patients received IST with rabbit anti-thymocyte globulin (ATG) and cyclosporine (CsA). Results: A significantly lower response rate (RR) was identified in patients with ANC = 0 prior to IST when compared to patients with SAA after both 3 and 6 month periods or compared to those with vSAA at 3 months only. The efficacy of IST was inversely related to ANC = 0. The overall survival rate of the 'zero' group was significantly lower than that of the vSAA or SAA groups. Overall survival was closely associated with response to IST, and was inversely related to ANC = 0. Discussion: In SAA patients, ANC is associated with prognosis, the elucidated overall survival improvement in patients without ANC = 0 occurred in conjunction with decreased infection-related mortality. Our study revealed that adult patients with ANC = 0 prior to IST responded poorly to IST, suggesting that having a very low number of neutrophils was a highly predictive factor for efficacy and survival of SAA patients treated with IST. Conclusion: Adult SAA patients with ANC = 0 had a very poor prognosis and new therapeutic regimens may result in better outcome for these patients.
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Anemia Aplásica/terapia , Inmunosupresores/uso terapéutico , Adolescente , Adulto , Anciano , Suero Antilinfocítico/uso terapéutico , Ciclosporina/uso terapéutico , Femenino , Humanos , Infecciones/etiología , Infecciones/mortalidad , Estimación de Kaplan-Meier , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Neutrófilos , Pronóstico , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
To understand the risks associated with aplastic anemia (AA) in 4 cities of Zhejiang Province, China, with special focus on the joint contributions of multiple risks.Based on an Electronic Data Capture (EDC), a case control study was carried out. Data regarding socio-demographic, diseases history, living habits, and exposures to toxic substances, etc., were collected through survey questionnaires. t Test, chi-square test, or non-parametric rank sum test, and univariate and multivariate Logistic regression analysis were conducted to analyze data.The univariate logistic regression analysis results indicated that among all study participants (nâ=â1802), AA was associated with over 30 risks, in terms of their individual behaviors, daily and environmental exposures, diseases history, and family history. Multivariate logistic regression analysis further confirmed that the independent risks related to AA included presence of chemical factory within 3âkm of living residence (odds ratio [OR]â=â8.73, 95% CI: 1.42-53.74, Pâ=â.019), living in a newly decorated house/apartment (ORâ=â25.37, 95% CI: 4.44-144.81, Pâ<â.001), vegetarian diet (ORâ=â131.60, 95% CI: 3.45-5020.16, Pâ=â.009), preference of sugar (ORâ=â89.38, 95% CI: 7.22-1106.44, Pâ<â.001), preference of oily food (ORâ=â55.68, 95% CI: 5.12-605.26, Pâ=â.001), drinking lake water or pond water (ORâ=â58.05, 95% CI: 3.21-1049.81, Pâ<â.001), habit of staying up late (ORâ=â11.87, 95% CI: 3.43-41.02, Pâ<â.001), infection history (ORâ=â10.08, 95% CI: 2.75-36.93, Pâ<â.001). Result of receiver operating characteristic curve (ROC) analysis on the joint contribution of multiple risks indicated that AA was 13.835 times likely to occur when exposed to ≥1 risks than those exposed to 0 risks (95% CI: 9.995-19.149).Our study results demonstrated a comprehensive epidemiological pattern, in which the joint contributions of individual inherited health status, environment exposure, and individual behaviors lead to the occurrence of AA.
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Anemia Aplásica/etiología , Medición de Riesgo/métodos , Adolescente , Adulto , Anciano , Anemia Aplásica/epidemiología , Estudios de Casos y Controles , Niño , Preescolar , China/epidemiología , Exposición a Riesgos Ambientales/efectos adversos , Femenino , Conductas Relacionadas con la Salud/etnología , Humanos , Lactante , Masculino , Persona de Mediana Edad , Factores de Riesgo , Encuestas y Cuestionarios , Adulto JovenRESUMEN
OBJECTIVE: To investigate the potential effect of pure total flavonoids from Citrus paradisi Macfad peel (PTFC) on the proliferation of human myeloid leukemia cells Kasumi-1, HL-60 and K562, and the underlying mechanisms. METHODS: PTFC was extracted from Citrus paradisi Macfad peel and was identified by high performance liquid chromatography. The effect of PTFC on the proliferation and apoptosis of leukemia cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, fluorescent microscopy and flow cytometry, respectively. The effect of PTFC on the expression levels of apoptosis-related regulators was determined by Western blot assay. RESULTS: Treatment with PTFC inhibited leukemia cell proliferation in a dose- and time-dependent manner and triggered Kasumi-1 cell apoptosis. Treatment with PTFC significantly increased the levels of activated poly adenosine diphosphate-ribosepolymerase and caspase-3/-9, but reduced the levels of Mcl-1 expression in Kasumi-1 cells. However, PTFC did not obviously induce HL-60 cell apoptosis. CONCLUSION: PTFC inhibited leukemia cell proliferation and induced their apoptosis by modulating apoptosisrelated regulator expression in leukemia cells in vitro.
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Apoptosis/efectos de los fármacos , Citrus paradisi/química , Flavonoides/uso terapéutico , Leucemia/tratamiento farmacológico , Leucemia/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Flavanonas/farmacología , Flavanonas/uso terapéutico , Flavonoides/farmacología , Hesperidina/análogos & derivados , Hesperidina/farmacología , Hesperidina/uso terapéutico , Humanos , Linfocitos/efectos de los fármacosRESUMEN
OBJECTIVE: To explore the feasibility of human leucocyte antigen (HLA) haploidentical related T-cell undepleted allogeneic bone marrow transplantation (Allo-BMT) combined with Chinese medicine for the treatment of leukaemia. METHODS: Four patients with chronic myeloblastic leukemia (CML) and 4 with acute myeloid leukemia (AML) received allo-BMT with graft from 1 - 3 HLA-mismatched related donors. All patients were pre-treated with standardized conditioning regimen consisting of high dose Ara-c, cyclophosphamide (CY) and total body irradiation (TBI) or busulfan. Donors were given G-CSF 250 microg/d for 7 days prior to marrow harvest. To prevent GVHD, besides application of CSA and MTX, ATG 2.5 mg/kg was given everyday for 4 days before transplantation, and MMF 1.0 g per day starting from the 7th day after transplantation. Chinese medicine for replenishing qi and yin and strengthening Pi and Wei was administrated orally after transplantation. RESULTS: Successful haematopoietic reconstruction was seen in all patients. The median days for reaching of granulocyte >0.5 X 10(9)/L and platelet > 20 x 10(9)/L were 12 (range 10-14) and 20 (range 18-25) days respectively. GVHD of skin in various grade was seen in 7 patients, among whom only one advanced to grade IV; besides, 2 accompanied with GVHD of gut, one with hemorrhagic cystitis, one died for concurrent infection on the 81st day, and one left hospital of his own accord on the 46th day. The median follow-up duration was 18 (range 2-32) months, during this period six patients were alive in a disease-free situation. CONCLUSION: Combined therapy of HLA haploidentical related T-cell undepleted Allo-BMT and Chinese medicine plus immunosuppressants with pre-harvest G-CSF application in doner could effectively reduce the incidence of acute severe GVHD and raise the disease-free survival rate in treating leukaemia.
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Trasplante de Médula Ósea , Antígenos HLA/inmunología , Haplotipos , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Leucemia Mieloide Aguda/terapia , Fitoterapia , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Combinada , Medicamentos Herbarios Chinos/uso terapéutico , Femenino , Enfermedad Injerto contra Huésped/prevención & control , Antígenos HLA/genética , Prueba de Histocompatibilidad , Humanos , Masculino , Persona de Mediana EdadRESUMEN
To investigate the potential effects of pure total flavonoid compounds (PTFCs) from Citrus paradisi Macfadyen separately or combined with arsenic trioxide on the proliferation of human myeloid leukemia cells and the mechanisms underlying the action of PTFCs. The effects of PTFCs separately or combined with arsenic trioxide on the proliferation and apoptosis of leukemia cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), fluorescence microscopy, and flow cytometry. Their effects on the expression levels of apoptosis-related regulators were determined by Western blot assay. PTFCs combined with arsenic trioxide significantly inhibited the growth of Kasumi-1 cells, and apoptosis was confirmed by flow cytometry analysis. Hoechst 33258 staining showed more significant morphological changes and more apoptosis following the combined treatment. Western blots showed changes in the expression of genes for poly ADP-ribose polymerase (PARP), caspase 3/9, and P65. The results indicated that PTFCs separately or combined with arsenic trioxide inhibited proliferation of leukemia cells in vitro and induced their apoptosis by modulating the expression of apoptosis-related regulator genes.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Apoptosis/efectos de los fármacos , Arsenicales/administración & dosificación , Flavonoides/administración & dosificación , Leucemia Mieloide Aguda/tratamiento farmacológico , Óxidos/administración & dosificación , Extractos Vegetales/administración & dosificación , Antineoplásicos/administración & dosificación , Trióxido de Arsénico , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Sinergismo Farmacológico , Humanos , Leucemia Mieloide Aguda/patología , Resultado del TratamientoRESUMEN
OBJECTIVE: To explore the proliferation inhibition and apoptosis effects of polysaccharides extracts from Hedyotis diffusa (PEHD) on multiple myeloma (MM) cell line RPMI 8226 cells in vitro, so as to provide experimental theory for the clinical application in the treatment of MM. METHODS: MTT assay was used to examine the effects of PEHD on cell growth. The apoptotic cells were analyzed by flow cytometry with Annexinâ ¤/PI staining. Hoechst staining was used to observe the morphological changes of RPMI 8226 cell apoptosis. The expression levels of caspase-3,-8,-9, PARP, nucleoprotein NF-κB protein and other channel protein were assayed by Western blotting method. RESULTS: The growth of RPMI 8226 cells were suppressed after treatment with PEHD, the highest inhibition rate reached to 92.3%, the results in the doses from 1 to 4 mg/ml showed a dose-and-time-dependent manner. The proportion of apoptotic cells in 1, 2 and 3 mg/ml PEHD treatment groups for 24 h were 22.52%, 62.31% and 69.94%, respectively, and significantly higher than that of control 8.93%. After treated with PEHD, apoptotic body appeared in RPMI 8226 cells nucleus and the number of apoptotic body increased in a dose-dependent manner. With the increasing of PEHD concentration, the expression of caspase-8,-9,-3 and PARP protein increased. The expression of Mcl-1, Bcl-xl, Bid and Bim protein decreased gradually, but the expression of Bax, Bak and Bad protein increased, and the expression of p-AKT protein (60 kDa) and NF-κB obviously decreased. CONCLUSION: PEHD could inhibited the growth of RPMI 8226 cells and displayed a dose-and-time-dependent manner, its mechanism may involve cell apoptosis induction, which was associated with the activation of caspase-8, caspase-9, and caspase-3 protein and the down-regulation of p-AKT and NF-κB protein expression.
Asunto(s)
Apoptosis/efectos de los fármacos , Hedyotis/química , Mieloma Múltiple/patología , Polisacáridos/farmacología , Caspasa 3/metabolismo , Caspasa 8/metabolismo , Caspasa 9/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Humanos , Mieloma Múltiple/metabolismo , FN-kappa B/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismoRESUMEN
OBJECTIVE: To explore differences in bone marrow angiogenesis seen in aplastic anemia (AA) patients presenting with differential Chinese medicine (CM) syndrome, and to correlate these differences with clinical pathology. METHODS: Thirty-five patients were enrolled, including 18 with "yang deficiency syndrome" and 17 with "yin deficiency syndrome." Bone marrow biopsies and serum were collected. Microvessel density (MVD) and positive expression of vascular endothelial-derived growth factor (VEGF) were detected by immunohistochemisty. Hypoxia inducible factor -1α (HIF-1α), and VEGF expression were assayed by enzyme-linked immunoabsorbent assay (ELISA), serum lactate dehydrogenase (LDH) was tested by enzyme method and liquid chip technology was used to detected the expression of interleukin (IL)-2, IL-4, IL-6, IL-10, interferon (IFN)-γ and tumor necrosis factor (TNF)-α. RESULTS: Counts for leukocytes, absolute neutrophils and platelets in "yin deficiency syndrome" were lower than those found in "yang deficiency syndrome" (P<0.05). MVD and VEGF expression, and the positive rate of CD34 and VEGF in bone marrow were lower in AA, especially in "yin deficiency syndrome" (P<0.01 or P<0.05). "Yin deficiency syndrome" displayed decreased VEGF and LDH expression, and enhanced expression of HIF-1α as compared to "yang deficiency syndrome" (P<0.05). Levels of IL-4 and IL-6 were higher in AA (P<0.01), but IL-10 was decreased (P<0.05). High TNF-α expression was seen in "yang deficiency syndrome" and IFN-γ expression was decreased in "yin deficiency syndrome" as compared with normals (P <0.01 and P<0.05, respectively). CONCLUSION: AA patients have lower MVD than normals, especially in "yin deficiency syndrome." MVD might differentially correlate to disease severity, and could be dependent on bone marrow or serum VEGF expression and LDH. Additionally, IL-2, IL-10, IL-4 and IFN-γ were negatively associated while IL-6 and TNF-α were positively associated with MVD.