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Sarcandra glabra, a medicinal plant in family Chloranthaceae, has been taken as an important raw material for multiple Chinese patent drugs due to its diverse indications. Considering the diversified chemical constituents and rich biological activities of S. glabra, numerous phytochemical and pharmacodynamic investigations were conducted to explore the material basis for its medicinal use. It has been found that its main chemical constituents were sesquiterpenoids, sesquiterpenoid polymers, phenolic acids, coumarins, and flavonoids. As revealed by pharmacological research, it possesses multiple biological activities like anti-inflammation, anti-bacteria, anti-tumor, anti-oxidation, and neuroprotection. Some unreported novel structures, including polymers of lindenane sesquiterpenes and monoterpenes, sesquiterpene trimers, and adducts of flavonoids and monoterpenes, have been identified from S. glabra in recent years. Moreover, biological studies relating to its anti-tumor, anti-inflammatory, and anti-oxidant activities have been deepened. This paper reviewed the chemical constituents and bioactivities of S. glabra explored over the past ten years, so as to provide a scientific basis for further development and utilization of this plant.
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Anti-Inflamatórios/farmacologia , Flavonoides , Compostos Fitoquímicos/farmacologia , Plantas Medicinais/química , SementesRESUMO
With repeated silica gel, octadecyl silica(ODS), and Sephadex LH-20 column chromatography, normal-phase and reverse-phase high performance liquid chromatography(HPLC), etc., a pair of new enantiomers and 5 known compounds were separated from the 95% ethanol extract of Chloranthus multistachys. These compounds were identified by the nuclear magnetic resonance spectroscopy(including 1 D-NMR and 2 D-NMR), single-crystal X-ray diffraction, circular dichroism(CD) spectroscopy, mass spectrometry(MS), and some other methods as(1R,4R,5R,8S,10R)-chloraeudolide H(1 a),(1S,4S,5S,8R,10S)-chloraeudolide H(1 b), hydroxyisogermafurenolide(2), 4α-hydroxy-5α,8β(H)-eudesm-7(11)-en-8,12-olide(3), chloraniolide A(4), chlorantene D(5), 4α,8β-dihydroxy-5α(H)-eudesm-7(11)-en-8,12-olide(6). Compounds 1 a and 1 b are a pair of new eudesmane-type sesquiterpene enantiomers, and compounds 2-4 were isolated from C. multistachys for the first time.
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Cromatografia Líquida de Alta Pressão , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Estrutura Molecular , Sesquiterpenos , EstereoisomerismoRESUMO
The genus Chloranthus has 13 species and 5 varieties in China, which can be found in the southwest and northeast regions. Phytochemical studies on Chloranthus plants have reported a large amount of terpenoids, such as diterpenoids, sesquiterpenoids, and sesquiterpenoid dimers. Their anti-inflammation, anti-tumor, antifungal, antivirus, and neuroprotection activities have been confirmed by previous pharmacological research. Herein, research on the chemical constituents from Chloranthus plants and their biological activities over the five years was summarized to provide scientific basis for the further development and utilization of Chloranthus plants.
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Diterpenos , Compostos Fitoquímicos/farmacologia , Plantas , Sesquiterpenos/farmacologia , TerpenosRESUMO
Eight sesquiterpenes were isolated and purified from the ethanol extract of Chloranthus henryi by column chromatographies over silica gel, ODS and Sephadex LH-20,and preparative HPLC. Their chemical structures were established by spectral data and physiochemical properties as(1S,6S,8S,10R)-8-ethoxy-10-methoxychlomultin C(1),tianmushanol(2),multistalide A(3),myrrhterpenoid N(4),1α,9α-dihydroxy-8,12-expoxy-eudesma-4,7,11-trien-6-one(5),4β,10α-aromadendranediol(6),oplopanone(7),10α-hydroxycadinan-4-en-3-one(8). Among them, compound(1) was a new compound, and compounds 2-8 were isolated from Chloranthus henryi for the first time.
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Cromatografia Líquida de Alta Pressão , Estrutura Molecular , SesquiterpenosRESUMO
Objective: To determine the association between pulse pressure and the risk of new-onset diabetes in hypertensive patients. Methods: In this prospective cohort study, hypertensive patients from the Kailuan Study, who were diagnosed in 2006-2007 check-up, were screened for enrollment. Participants who finished the biennial follow-up until December 31, 2017 were finally included in this analysis. The primary outcome was incident diabetes development. The pulse pressure variables were divided into quartiles (Q1-Q4), and the Kaplan-Meier curve was used to examine and estimate the cumulative incidence of new-onset diabetes among quartiles. Cox proportional hazards regression model was performed to explore the association between pulse pressure and the risk of new-onset diabetes in hypertensive patients. Results: During an average follow-up of 8.17 years, 6 617 new-onset diabetes were identified out of the 32 917 hypertensive patients with no history or evidence of diabetes in 2006-2007 check-up. Participants were classified into quartiles according to pulse pressure levels as follows: Q1 group(<41 mmHg (1mmHg=0.133kPa))(n=7 995); Q2 group(41-<51 mmHg) (n=8 196); Q3 group (51-<61 mmHg) (n= 8 270); Q4 group (≥61 mmHg) (n=8 456). The cumulative incidences of new-onset diabetes across the quartiles were 16.94%, 19.61%, 21.07%, and 22.33%, respectively, with the incidence density was 20.27, 23.20, 24.92, and 26.10 per 1 000 person-years, respectively. The cumulative incidence of new-onset diabetes increased in proportion with increasing pulse pressure levels (P<0.01 by the Log-rank test). After multivariate adjustment, compared with the first quartile, the hazard ratios for new-onset diabetes in the third and fourth quartiles were 1.13 (95%CI 1.04-1.22, P<0.01) and 1.14 (95%CI 1.05-1.24, P<0.01), respectively. The risk of new-onset diabetes increased 5%(HR=1.05, 95%CI 1.02-1.08, P<0.01) with the fractional pulse pressure increased per 1 SD (0.13). Findings from the three sensitivity analyses were consistent with the main results in this cohort. Conclusions: Pulse pressure at baseline is positively associated with the incidence of new-onset diabetes among hypertensive individuals, and pulse pressure is an independent risk factor for the development of diabetes in hypertensive patients.
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Five compounds were isolated from the alcohol extract of Olibanum by MCI, silica gel, ODS, and Sephadex LH-20 column chromatographies and preparative high-performance liquid chromatography(HPLC). On the basis of spectral data and literature data, the compounds were identified as:(1S,3R,4S,7R,11S,12R)-1:12,4:7-diepoxisonane-8(19)-ene-3,11-diol(1), boscartin A(2),(+)-resinolin(3),(+)-5-hydroxy-3,4-dimethyl-5-pentylfuran-2(5H)-one(4), and acerogenin A(5). Compound 1 is a new compound, and compounds 3-5 were isolated from Olibanum for the first time. The structure of compound 1 was determined by spectroscopic analysis and single-crystal X-ray diffraction. Compounds 1 and 2 were tested for PC12 neurotoxicity, and the results showed that they were both safe compounds.
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Cromatografia Líquida de Alta Pressão , Diterpenos , Franquincenso , Estrutura MolecularRESUMO
BackgroundSince late December 2019, the outbreak of the novel coronavirus disease, COVID-19, that began in Wuhan, has become endemic in China and more than 100 countries and regions in the world. So far, there is rare data on the prevalence of COVID-19 in patients with chronic myelogenous leukemia (CML). We aimed to describe the clinical course, outcomes of CML patients with COVID-19 and prevalence of COVID-19 in CML patients. MethodsIn this multicentre, cross-sectional survey, the clinical data of CML patients with COVID-19 in each center were collected. Simultaneously, an online survey was conducted for information about the CML patients under the management at each center by asking the CML patients to complete a questionnaire,from February 15, 2020 to February 21, 2020. The questionnaire includes demographic data, place of residence, smoking status, CML diagnosis and treatment, comorbidities, combined medications, epidemiological history, symptoms(fever, cough, shortness of breath, etc) during the epidemic. Additional clinical data was collected on respondents suspected or confirmed to have COVID-19. We described and analyzed the prevalence of COVID-19 in CML patients, and focus on the clinical characteristics and outcomes of COVID-19 patients. Data were compared between the CML patients with optimal response and those with non-optimal response. The primary outcome was prevalence of COVID-19 in CML patients, as of Feb 21, 2020. Secondary outcomes included the history of epidemiology of CML patients, the clinical characteristics and outcomes of CML patients with COVID-19. FindingsOf 392 respondents, 223(56.9%) were males, and 240(61.2%) were 50 years or younger. Only 10 patients took drugs irregularly due to the influence of the epidemic because of traffic control, pharmacies unable to operate normally, etc. In the history of epidemiology, there were 4 patients with definite contact with COVID-19, of which 3 were remote contact and 1 was close contact. 12 respondents had fever, cough or shortness of breath during the epidemic, 1 case (common type) was confirmed with COVID-19 and cured after treatment. 1 patient was clinically diagnosed and succumbed. 1 of 299 (0.3%) patients with an optimal response was diagnosed with COVID-19. Of the 50 patients who failed to respond to CML treatment or had a poor response, 1 patient (2%) had a clinical diagnosis of COVID-19. InterpretationWhile the 392 CML respondents required regular referrals to hospitals, they did not have much contact with COVID-19 patients during the outbreak. Patients who failed to achieved an optimal response to CML therapy appear more likely to have a symptomatic infection with SARS-CoV-2. Older patients with comorbidities are at increased risk of death. FundingThis work was supported by grants from the National Natural Science Foundation of China(NSFC)(81873440&81700142).
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This study examined the mechanism of the inhibitory effect of parthenolide (PTL) on the activity of NF-κB in multiple myeloma (MM). Human multiple myeloma cell line RPMI 8226 cells were treated with or without different concentrations of PTL for various time periods, and then MTT assay was used to detect cell proliferation. Cell cycle and apoptosis were flow cytometrically detected. The level of protein ubiquitination was determined by using immunoprecipitation. Western blotting was employed to measure the level of total protein ubiquitination, the expression of IκB-α in cell plasma and the content of p65 in nucleus. The content of p65 in nucleus before and after PTL treatment was also examined with immunofluorescence. Exposure of RPMI 8226 cells to PTL attenuated the level of ubiquitinated Nemo, increased the expression of IκB-α and reduced the level of p65 in nucleus, finally leading to the decrease of the activity of NF-κB. PTL inhibited cell proliferation, induced apoptosis and blocked cell cycle. Furthermore, the levels of ubiquitinated tumor necrosis factor receptor-associated factor 6 (TRAF6) and total proteins were decreased after PTL treatment. By using Autodock software package, we predicted that PTL could bind to TRAF6 directly and tightly. Taken together, our findings suggest that PTL inhibits the activation of NF-κB signaling pathway via directly binding with TRAF6, thereby suppressing MM cell proliferation and inducing apoptosis.
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Humanos , Apoptose , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Mieloma Múltiplo , Tratamento Farmacológico , Metabolismo , NF-kappa B , Sangue , Sesquiterpenos , Farmacologia , Fator 6 Associado a Receptor de TNF , Metabolismo , Fator de Transcrição RelA , Metabolismo , UbiquitinaçãoRESUMO
This study examined the mechanism of the inhibitory effect of parthenolide (PTL) on the activity of NF-κB in multiple myeloma (MM). Human multiple myeloma cell line RPMI 8226 cells were treated with or without different concentrations of PTL for various time periods, and then MTT assay was used to detect cell proliferation. Cell cycle and apoptosis were flow cytometrically detected. The level of protein ubiquitination was determined by using immunoprecipitation. Western blotting was employed to measure the level of total protein ubiquitination, the expression of IκB-α in cell plasma and the content of p65 in nucleus. The content of p65 in nucleus before and after PTL treatment was also examined with immunofluorescence. Exposure of RPMI 8226 cells to PTL attenuated the level of ubiquitinated Nemo, increased the expression of IκB-α and reduced the level of p65 in nucleus, finally leading to the decrease of the activity of NF-κB. PTL inhibited cell proliferation, induced apoptosis and blocked cell cycle. Furthermore, the levels of ubiquitinated tumor necrosis factor receptor-associated factor 6 (TRAF6) and total proteins were decreased after PTL treatment. By using Autodock software package, we predicted that PTL could bind to TRAF6 directly and tightly. Taken together, our findings suggest that PTL inhibits the activation of NF-κB signaling pathway via directly binding with TRAF6, thereby suppressing MM cell proliferation and inducing apoptosis.
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The cytokines of acute leukemia (AL) patients have certain expression patterns, forming a complex network involved in diagnosis, progression, and prognosis. We collected the serum of different AL patients before and after complete remission (CR) for detection of cytokines by using an antibody chip. The expression patterns of cytokines were determined by using bioinformatics computational analysis. The results showed that there were significant differences in the cytokine expression patterns between AL patients and normal controls, as well as between acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). In confirmatory test, ELISA revealed the expression of uPAR in AL. Moreover, the bioinformatic analysis showed that the differentially expressed cytokines among the AL groups were involved in different biological behaviors and were closely related with the development of the disease. It was concluded that the cytokine expression pattern of AL patients is significantly different from that of healthy volunteers. Also, differences of cytokine expression patterns exist between AML and ALL, and between before and after CR in the same subtype of AL, which holds important clinical significance for revealing disease progression.
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Humanos , Citocinas , Sangue , Diagnóstico Diferencial , Regulação Leucêmica da Expressão Gênica , Leucemia Mieloide Aguda , Sangue , Análise em Microsséries , Leucemia-Linfoma Linfoblástico de Células Precursoras , Sangue , Prognóstico , RNA Mensageiro , SangueRESUMO
This study was aimed to investigate a more convenient and efficient method to cultivate the human bone marrow mesenchymal stem cells by means of natural erythrocyte sedimentation principle, based on the whole bone marrow adherent method. The bone marrow was cultured with a six-well plate instead of the flasks.Firstly, the bone marrow specimen was cultivated with the MSC complete medium for 48 h, then the upper RBC-free supernatant layer was drawn and placed into the new wells to isolate MSC. Inverted microscope was used to observe the cell morphology and to record the adherent time of first cell passage, first passaging time. The traditional whole bone marrow adherent method was used as the control. The cell cycle and cell surface markers were detected by flow cytometry,and the differentiative capacity of MSC into osteocyte and adipocyte was identified by alkaline phosphatase kit and oil red O, respectively. Besides, the proliferative curve of P1,P3,P5 of BMSC was depicted by counting method. The results showed that MSC cultured by the modified method highly expressed CD90, CD105, CD13, CD44 and lowly expressed CD14, CD45, CD34. Concerning the cell cycle feature, it was found that most of the cells were in G0/G1 phase (88.76%) , followed by G2/M phase (3.04%) and S phase (8.2%), which was in accordance with stem cell cycle characteristics. The proliferative curve showed a typical "S" type, and both the oil red O and alkaline phosphatase staining of MSC were positive. Compared with the traditional method, the modified method had the advantage of high adherence rate (P = 0.0001) and shorter passaging time for the first passage (P = 0.001), with the statistically significant difference. It is concluded that there is a large number of adherent, active and suspended MSC in the RBC-free supernatant layer after the culture of bone marrow for 48 h. Isolating MSC by the modified method is more convenient and efficient than the traditional whole bone marrow adherent method.
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Humanos , Células da Medula Óssea , Biologia Celular , Técnicas de Cultura de Células , Métodos , Separação Celular , Células Cultivadas , Células-Tronco Mesenquimais , Biologia CelularRESUMO
The cytokines of acute leukemia (AL) patients have certain expression patterns, forming a complex network involved in diagnosis, progression, and prognosis. We collected the serum of different AL patients before and after complete remission (CR) for detection of cytokines by using an antibody chip. The expression patterns of cytokines were determined by using bioinformatics computational analysis. The results showed that there were significant differences in the cytokine expression patterns between AL patients and normal controls, as well as between acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). In confirmatory test, ELISA revealed the expression of uPAR in AL. Moreover, the bioinformatic analysis showed that the differentially expressed cytokines among the AL groups were involved in different biological behaviors and were closely related with the development of the disease. It was concluded that the cytokine expression pattern of AL patients is significantly different from that of healthy volunteers. Also, differences of cytokine expression patterns exist between AML and ALL, and between before and after CR in the same subtype of AL, which holds important clinical significance for revealing disease progression.
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The effects of granulocyte colony-stimulation-factor (G-CSF) on stem cell mobilization and its impact on the amplification of myeloid-derived suppressor cells (MDSCs) of donor mice were examined. A mouse model of stem cell mobilization was established by consecutive subcutaneous injection of 100 μg/kg G-CSF for 5 days. The blood from the donor mice was routinely examined during mobilization. Stem cells and MDSCs were analyzed by flow cytometry. The immunosuppressive molecules derived from MDSCs in serum and spleen, including hydrogen dioxide (H2O2) and nitric oxide (NO), and the activity of nitric oxide synthase (NOS) were determined during the mobilization. Apoptosis of T lymphocytes was assessed by using Annexin-V/PI. During stem cell mobilization, the number of lymphocytes and white blood cells in the peripheral blood was increased, and peaked on the 4th day. The number of stem cells in G-CSF-treated mice was significantly greater than that in controls (P<0.01). The expansions of MSDCs were also observed after G-CSF mobilization, with a more notable rate of growth in the peripheral blood than in the spleen. The activity of NOS and the production of NO were increased in the donor mice, and the serum H2O2 levels were approximately 4-fold greater than the controls. Consequently, apoptosis of T lymphocytes was increased and showed a positive correlation with the elevated percentage of MDSCs. It was concluded that G-CSF could provide sufficient peripheral blood stem cells for transplantation. Exogenous administration of G-CSF caused the accumulation of MDSCs in the peripheral blood and the spleen, which could lead to apoptosis of T lymphocytes and may offer a new strategy for the prevention and treatment of graft versus host disease.
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Animais , Camundongos , Apoptose , Fator Estimulador de Colônias de Granulócitos , Farmacologia , Mobilização de Células-Tronco Hematopoéticas , Peróxido de Hidrogênio , Metabolismo , Camundongos Endogâmicos C57BL , Células Progenitoras Mieloides , Biologia Celular , Metabolismo , Óxido Nítrico , Metabolismo , Óxido Nítrico Sintase , Metabolismo , Linfócitos T , Biologia Celular , MetabolismoRESUMO
The effects of granulocyte colony-stimulation-factor (G-CSF) on stem cell mobilization and its impact on the amplification of myeloid-derived suppressor cells (MDSCs) of donor mice were examined. A mouse model of stem cell mobilization was established by consecutive subcutaneous injection of 100 μg/kg G-CSF for 5 days. The blood from the donor mice was routinely examined during mobilization. Stem cells and MDSCs were analyzed by flow cytometry. The immunosuppressive molecules derived from MDSCs in serum and spleen, including hydrogen dioxide (H2O2) and nitric oxide (NO), and the activity of nitric oxide synthase (NOS) were determined during the mobilization. Apoptosis of T lymphocytes was assessed by using Annexin-V/PI. During stem cell mobilization, the number of lymphocytes and white blood cells in the peripheral blood was increased, and peaked on the 4th day. The number of stem cells in G-CSF-treated mice was significantly greater than that in controls (P<0.01). The expansions of MSDCs were also observed after G-CSF mobilization, with a more notable rate of growth in the peripheral blood than in the spleen. The activity of NOS and the production of NO were increased in the donor mice, and the serum H2O2 levels were approximately 4-fold greater than the controls. Consequently, apoptosis of T lymphocytes was increased and showed a positive correlation with the elevated percentage of MDSCs. It was concluded that G-CSF could provide sufficient peripheral blood stem cells for transplantation. Exogenous administration of G-CSF caused the accumulation of MDSCs in the peripheral blood and the spleen, which could lead to apoptosis of T lymphocytes and may offer a new strategy for the prevention and treatment of graft versus host disease.
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This study was aimed to observe the effects of siRNA on Livin expression and function in K562 cells. Livin siRNA were designed and synthesized, then were transfected into K562 cells by using AMAXA nucle transfactor. Expressions of Livin mRNA and protein in transfected K562 cells was detected by RT-PCR and Western blot respectively. Non-transfected cells were used as control. The enhanced green fluorescent protein plasmid was used as positive control and the transfection efficiency was detected by flow cytometry. Cell apoptosis was measured by flow cytometry with Annexin V-FITC/PI double staining. The results showed that the transfection efficiency of electroporation method was about 50. The synthesized siRNA inhibited livin expression at both mRNA and protein levels. The rate of K562 cell apoptosis increased from (9.63 ± 0.89) in control group to (12.07 ± 1.39) and (27.41 ± 2.30) at 24 h and 48 h after transfection, respectively (P < 0.05). It is concluded that the siRNA can inhibit anti-apoptosis of livin gene via down-regulating livin gene expression, which may provide the new method for anti-leukemia study.
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Humanos , Proteínas Adaptadoras de Transdução de Sinal , Genética , Apoptose , Genética , Regulação Leucêmica da Expressão Gênica , Proteínas Inibidoras de Apoptose , Genética , Células K562 , Proteínas de Neoplasias , Genética , RNA Interferente Pequeno , GenéticaRESUMO
Objective To assess the value of Montreal Cognitive Assessment(MoCA)in screening mild cognitive impairment(MCI)in elderly patients.Methods Thirty-two elderly patients with MCI and 50 healthy elderly subjects were examined with neuropsychological tests using Mini-mental State Examination(MMSE)and the MoCA. Results With a cut-off score of 26,the MoCA had a sensitivity of 96.87%and specificity of 76%for detecting MCI,and the sensitivity and specificity of MMSE were 56.25%and 96%,respectively.For the MoCA sub-items,the elderly patients with MCI had significantly lower scores than the healthy elderly in all the cognitive function measures (P<0.05)except for abstraction and fixed orientation.In MMSE sub-items,significant differgnces were found between the two groups in only calculation/attention and delayed recall(P<0.05).Conclusions The MoCA is a highiy sensitive scale for screening MCI in elderly patients,which allows comprehensive assessment of the cognitive function of MCI patients and is applicable in detecting MCI in patients with normal MMSE results.
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Mesenchymal stem cells (MSCs) have received much attention because of their capabilities of differentiating into multiple mesenchymal lineages and supporting hematopoiesis. Recently, MSCs have gained further interests after the demonstration of an immunosuppressive role. However, it's still unclear whether the immunosuppressive capability of MSCs will be altered with disease state. In this study, our results showed that MSCs derived from patients with lymphoblastic leukemia (ALL), Hodgkin disease (HD), and non-Hodgkin lymphoma (NHL) capable of suppressing the proliferation of T-lymphocyte stimulated in a mixed-lymphocyte reaction (MLR). The immunosuppressive effect of MSCs derived from ALL, HD and NHL on T-cell proliferation was dose-dependent. The supernatants of MSCs derived from ALL, HD and NHL had effect on T-cell proliferation. By using neutralising monoclonal antibodies, we found that transforming growth factor beta1 (TGFbeta1) and hepatocyte growth factor were major mediators of T-cell suppression by MSCs derived from ALL, HD and NHL. Although MSCs derived from patients with myelodysplastics syndromes (MDS) could inhibit T-cell proliferation stimulated with mitogen or in MLR, the inhibitory effect of MDS-MSCs was impaired. However, adherent cells derived from patients with acute myeloid leukemia (AML) showed abnormal immunomodulatory functions. Adherent cells derived from AML failed to suppress the proliferation of T-cell stimulated in MLR.
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Células da Medula Óssea/imunologia , Neoplasias Hematológicas/imunologia , Fator de Crescimento de Hepatócito/imunologia , Células-Tronco Mesenquimais/imunologia , Fator de Crescimento Transformador beta/imunologia , Doença de Hodgkin , Humanos , Fatores Imunológicos , Terapia de Imunossupressão , Teste de Cultura Mista de Linfócitos , Linfoma não Hodgkin , Leucemia-Linfoma Linfoblástico de Células Precursoras , Linfócitos T/imunologiaRESUMO
<p><b>BACKGROUND</b>Relapse remains an obstacle to successful allogeneic haematopoietic stem cell transplantation (allo-HSCT) for patients with acute leukaemia and no standard treatment is available. We assessed fludarabine and cytarabine with transfusion of donor haematopoietic stem cell in treating the relapse of acute leukaemia after allo-HSCT.</p><p><b>METHODS</b>Seven patients, median age 34 years, with relapse of acute leukaemia after allo-HSCT received combination chemotherapy of fludarabine with cytarabine for 5 days. Five patients suffered from acute myeloid leukaemia (2 refractory) and 2 refractory acute lymphoblastic leukaemia. After the transplantation, the median relapse time was 110 days (range, 38 - 185 days). Two days after chemotherapy, 5 patients received infusion of donor's peripheral blood stem cells, mobilized by granulocyte colony stimulating factor. No prophylactic agents of graft versus host diseases were administered.</p><p><b>RESULTS</b>Six patients achieved haematopoietic reconstitution. DNA sequence analysis at day 30 after treatment identified all as full donor chimera type. The median observation time was 189 days. After the treatment, the median time for neutrophilic granulocyte value = 0.5 x 10(9)/L and for platelet value = 20 x 10(9)/L were 13 days (range, 10 - 18 days) and 15 days (range, 11 - 24 days), respectively. Graft versus host disease occurred in 2 patients (acute) and 3 (chronic). Five patients suffered from pulmonary fungal infection (2 died), 3 haemorrhagic cystitis and 2 cytomegalovirus viraemia. The other patients died of leukaemia related deaths. Three patients with chronic graft versus host disease who had received donor peripheral blood stem cells reinfusion have survived for 375 days, 232 days and 195 days, respectively.</p><p><b>CONCLUSIONS</b>Fludarabine with cytarabine plus the donor haematopoietic stem cell should be considered as an effective therapeutic regimen for relapse of acute leukaemia after allo-HSCT. The disease free state of patients may increase, though with high risk of secondary fungal infection.</p>
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Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antimetabólitos Antineoplásicos , Antineoplásicos , Protocolos de Quimioterapia Combinada Antineoplásica , Usos Terapêuticos , Citarabina , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Terapêutica , Leucemia-Linfoma Linfoblástico de Células Precursoras , Terapêutica , Transplante Homólogo , VidarabinaRESUMO
The aim of this study was to investigate the effect of [(-)-epigallocatechin-3-gallate (EGCG)] on angiogenesis induced by multiple myeloma cell line KM3 and its mechanism. The effects of KM3 cell supernatant after being treated with EGCG in different concentrations on migration and vascular formation ability of endothelial cell line HUVEC were investigated through culture of MM cell line KM3 in vitro. The secretion level of vascular endothelial growth factor (VEGF) in KM3 cell supernatant and the expression level of VEGF mRNA in KM3 were detected by ELISA and RT-PCR respectively. The results indicated that the KM3 cell supernatant significantly induced endothelial cell migration and vascular formation in vitro. EGCG inhibited the effect of endothelial cell migration induced by KM3 cell supernatant, and the numbers of migrated cells were 414 +/- 27, 299 +/- 70, 202 +/- 42 and 116 +/- 13 at 5, 25, 50, 100 micromol/L respectively. The numbers of migrated cells showed negative correlation with the dose of EGCG (r = -0.952, p < 0.05). The areas of the capillary-like structures decreased while the concentrations of EGCG increased, 88343.9 +/- 3231.1 microm(2) at 25 micromol/L, 60897.5 +/- 914.1 microm2 at 50 micromol/L, which were significantly less than that in the control (p < 0.01) and showed negative correlation with the dose of EGCG (r = -0.888, p < 0.05). 48 hours after treatment with EGCG at concentrations of 5, 25, 50 and 100 micromol/L, the levels of VEGF in the culture supernatant were 1399.0 +/- 47.4, 660.1 +/- 5.7, 108.5 +/- 5.8 and 26.2 +/- 18.6 pg/ml respectively. Except 5 micromol/L, all the other groups showed significant changes while compared with the controls (p < 0.01). Furthermore, EGCG depressed the mRNA expression of VEGF in KM3 cells in a dose-dependent manner. It is concluded that the EGCG can significantly inhibit angiogenic ability of multiple myeloma KM3 cells, its pharmacological mechanism may be downregulation of VEGF mRNA expression and reduction of VEGF secretion.
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Humanos , Inibidores da Angiogênese , Farmacologia , Catequina , Farmacologia , Linhagem Celular Tumoral , Regulação para Baixo , Mieloma Múltiplo , Metabolismo , RNA Mensageiro , Metabolismo , Fator A de Crescimento do Endotélio Vascular , MetabolismoRESUMO
To investigate the As(2)O(3)-chemosensitization of Gö6976 in K562 cells by its abrogation of As(2)O(3)-induced G(2)/M cell cycle arrest, K562 cells were treated with As(2)O(3) (5 micromol/L) and Gö6976 with various concentrations, the distributions of cell cycles were detected by flow cytometry, the cell viability was observed by trypan blue exclusion test and cell proliferation was tested by MTT assay. The results indicated that having treated by As(2)O(3) for 24 h and 48 h, the proportion of K562 cells in G(2)/M phase were (38.02 +/- 7.70)% and (32.58 +/- 7.43)% respectively, and no obvious cell apoptosis appeared. 50 nmol/L Gö6976 combined with As(2)O(3) decrease the proportion of cells in G(2)/M phase to (23.24 +/- 2.93)% and (16.18 +/- 1.60)% respectively and increase the proportion of cells in subG(1) phase to (11.82 +/- 2.31)% and (27.80 +/- 2.89)% respectively. Gö6976 abrogated G(2)/M cell cycle arrest induced by As(2)O(3) and increased cell apoptosis in a concentration- and time-dependent manner. Additionally, comparing to the control group, Gö6976 combined with As(2)O(3) decreased the cell viability and depressed the cell proliferation, but Gö6976 alone showed no same effect on them. In conclusion, the effects of AS(2)O(3)-chemosensitization of Gö6976 on K562 cells is associated with its abrogation of As(2)O(3)-induced G(2)/M cell cycle arrest.