RESUMO
Despite the benefits of first generation drug eluting stents (DES), concerns have been raised over their long term safety in particular the risk of stent thrombosis. As a result, the current generation and novel DES have been developed, the latter includes DES with biocompatible and biodegradable polymers, polymer free DES and completely bioresorbable stent platforms. Many of these stents are currently under evaluation in clinical trials, and early results are promising. This paper reviews the progress thus far in DES technology and aims to highlight the impact of recent DES innovations on clinical efficacy and safety.
Assuntos
Stents Farmacológicos , Implantes Absorvíveis , Previsões , Humanos , Polímeros , Desenho de PróteseRESUMO
BACKGROUND: Angiogenic factors have an essential role in normal and pathologic angiogenesis. However, the clinical implication of angiogenic factor expression in myelodysplastic syndromes (MDS) remains unclear. METHODS: In this study, we sought to investigate the prognostic impact of the expression of genes encoding angiopoietin-1 (Ang-1), Ang-2, the receptor Tie2, vascular endothelial growth factor-A (VEGF-A) and VEGF-C in the bone marrow (BM) in 208 patients with newly diagnosed primary MDS. RESULTS: BM Ang-1 expression was significantly higher in MDS patients, especially those with higher-risk subtypes, than in normal controls. With a median follow-up time of 32.9 months, the disease transformed to acute leukaemia more frequently in the patients bearing higher Ang-1 expression than in those with lower expression (31.5% vs 18.6%, P=0.023). The MDS patients with higher Ang-1 expression had shorter overall survival than those with lower expression (median 20.8±4.5 months vs 63.3±17.8 months, P<0.001). Multivariate analyses showed that higher Ang-1 expression was an independent unfavourable prognostic factor for overall survival. There was no impact of the expression of other angiogenic factors on survival. CONCLUSION: BM Ang-1 expression may serve as a new biomarker to predict clinical outcome in MDS patients.
Assuntos
Angiopoietina-1/metabolismo , Medula Óssea/metabolismo , Síndromes Mielodisplásicas/metabolismo , Síndromes Mielodisplásicas/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Angiopoietina-1/genética , Angiopoietina-2/genética , Angiopoietina-2/metabolismo , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Técnicas Imunoenzimáticas , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/genética , Prognóstico , RNA Mensageiro/genética , Receptor TIE-2/genética , Receptor TIE-2/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de Sobrevida , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator C de Crescimento do Endotélio Vascular/genética , Fator C de Crescimento do Endotélio Vascular/metabolismo , Adulto JovemRESUMO
Hepatitis B virus (HBV) infection is one of the main concerns in blood and marrow transplantation (BMT) patients for possible breakthrough hepatitis. Active recipient immunization against HBV was found to be ineffective and many studies had showed that the adoptive transfer of immunity against hepatitis B virus would be possible by BMT with unknown duration and mechanism. A 46-year-old female patient with chronic hepatitis B had persistent detectable HBV DNA and positive serum hepatitis B e antigen (HBeAg), even while on long-term lamivudine and adefovir therapy. She received allogeneic matched unrelated donor peripheral blood stem cell transplantation (allo-MUD-PBSCT) for her refractory acute myeloid leukemia (AML). The HBV DNA became undetectable and she developed HBeAg seroconversion after PBSCT. Her hepatitis B surface antigen (HBsAg) remained positive, which disappeared later, along with the development of antibody to HBsAg after one shot of donor lymphocyte infusion (DLI) as a boost against her AML. In summary, BMT from an immunized donor would probably bring adoptive immunity against HBV. This adoptive immunity might be further enhanced by the subsequent DLI.
Assuntos
Transferência Adotiva , Vírus da Hepatite B/imunologia , Hepatite B Crônica/imunologia , Leucemia Mieloide Aguda/terapia , Transfusão de Linfócitos , Transplante de Células-Tronco de Sangue Periférico , Adenina/análogos & derivados , Adenina/uso terapêutico , Antivirais/uso terapêutico , DNA Viral/análise , Combinação de Medicamentos , Feminino , Anticorpos Anti-Hepatite B/sangue , Anticorpos Anti-Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/sangue , Antígenos de Superfície da Hepatite B/imunologia , Antígenos E da Hepatite B/sangue , Antígenos E da Hepatite B/imunologia , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/terapia , Humanos , Lamivudina/uso terapêutico , Pessoa de Meia-Idade , Organofosfonatos/uso terapêutico , Taiwan , Resultado do Tratamento , Doadores não RelacionadosRESUMO
Embryonic stem (ES) cells are considered to have potentials for tissue regeneration and treatment of diverse human diseases. ES cells are capable of indefinite renewal and proliferation, which can be induced to differentiate into tissues of all three germ lines. Despite these exciting potential, it remains unclear as to how the renewal and differentiation programs are operated and regulated at the genetic level. Genetic manipulation such as delivery of exogenous gene expression or knockdown with small interfering RNA (siRNA) is commonly used in most of cancer or transformed cells but relatively rare in ES cells. In this study, we compare the transfection efficacies of several liposome-based transfection methods by introduction of a plasmid encoding enhanced green fluorescent protein (EGFP) into mouse ES (mES) cells. Our results show that transfection by Effectene achieves the efficiency of >98% in CCE and >80% in D3 cells. The optimal ratio of DNA:Effectene for EGFP transfection is between 1:4 and 1:8. Transient-expressed EGFP or endogenous protein kinase A (PKA) were significantly knocked down by Effectene transfection of specific siRNA. High EGFP level expression and accumulation in mES cells induces minor cytotoxicity but can be reduced by introducing siRNA of EGFP. Further, this transfection method did not significantly affect mES properties of proliferation or differentiation. Our results provide an optimal protocol to achieve an efficient transfection for mES cells.
Assuntos
Células-Tronco Embrionárias/metabolismo , Transfecção/métodos , Animais , Células Cultivadas , Proteínas Quinases Dependentes de AMP Cíclico/genética , Expressão Gênica , Proteínas de Fluorescência Verde/genética , Lipídeos/administração & dosagem , Lipossomos , Camundongos , Interferência de RNA , RNA Interferente Pequeno/administração & dosagemRESUMO
Between 1993 and July 2008, a total of 354 leukaemic patients received either allogeneic bone marrow transplantation (BMT) [n = 180] or peripheral blood stem cell transplantation (PBSCT) [n = 174] from human leukocyte antigen-matched sibling donors. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporin A and methotrexate. When comparing with BMT group, patients in the PBSCT group received much higher nucleated cells and CD34+ cells, and had much faster recovery of the neutrophil and platelet counts. The probability of developing acute GVHD was slightly higher in PBSCT patients (P = 0.02). The probability of chronic GVHD (cGVHD) in PBSCT was much higher in PBSCT (70 +/- 5.4%, extensive 48 +/- 6.5%) than in BMT (25 +/- 4.7%, extensive 10 +/- 3.4%; P < 0.001). Chronic GVHD was associated with long-term impairment of life quality and decreased quality-adjusted survival. In standard-risk leukaemia, use of PBSCT was associated with higher cGVHD, transplant-related mortality and a trend for decreased overall survival. The results suggest that allogeneic PBSCT is associated with high incidence of cGVHD in Chinese patients and its long-term risk and benefit remains to be defined in early stage of leukaemia.
Assuntos
Doença Enxerto-Hospedeiro/etiologia , Leucemia/terapia , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Irmãos , Doença Enxerto-Hospedeiro/epidemiologia , Hospitais Universitários , Humanos , Incidência , Estimativa de Kaplan-Meier , Qualidade de Vida , Sobreviventes , Taiwan/epidemiologia , Tempo , Transplante Homólogo/efeitos adversosRESUMO
In this study, the effect of degree of the grafting and crosslinking on the morphology of the crystalline domain in poly(vinylbenzyl chloride)-grafted poly(ethylene-co-tetrafluoroethylene) [ETFE-g-PVBC] films was investigated using a SANS (small-angle neutron scattering) analysis. The grafted films can be used as a precursor for ion-exchange membrane. ETFE-g-PVBC films with various degrees of cross-linking were prepared by a simultaneous irradiation grafting of vinylbenzyl chloride (VBC) and divinylbenzene (DVB) onto an ETFE film. The SEM-EDX (scanning electron microscopy-energy dispersive X-ray spectroscopy) results of a cross-sectional distribution of ETFE-g-PVBC films showed that the chlorine atoms were well-distributed throughout the films. SANS profiles of the PVBC-grafted films in the absence of a DVB crosslinker showed that the crystalline domain peaks were observed and the peak maximum position shifted significantly from 0.032 Å-(-1) to 0.02 Å(-1) with an increase in the degree of grafting. However, peak maximum positions of the PVBC-grafted films in the presence of a DVB crosslinker shifted slightly from 0.02 Å(-1) to 0.024 Å(-1) with an increase in the amount of DVB monomer at same degree of grafting. These results indicate that the degree of grafting and crosslinking affect the morphology of the crystalline domain in the ETFE-g-PVBC films.
RESUMO
A number of patient-specific and leukemia-associated factors are related to the poor outcome in older patients with acute myeloid leukemia (AML). However, comprehensive studies regarding the impact of genetic alterations in this group of patients are limited. In this study, we compared relevant mutations in 21 genes between AML patients aged 60 years or older and those younger and exposed their prognostic implications. Compared with the younger patients, the elderly had significantly higher incidences of PTPN11, NPM1, RUNX1, ASXL1, TET2, DNMT3A and TP53 mutations but a lower frequency of WT1 mutations. The older patients more frequently harbored one or more adverse genetic alterations. Multivariate analysis showed that DNMT3A and TP53 mutations were independent poor prognostic factors among the elderly, while NPM1 mutation in the absence of FLT3/ITD was an independent favorable prognostic factor. Furthermore, the status of mutations could well stratify older patients with intermediate-risk cytogenetics into three risk groups. In conclusion, older AML patients showed distinct genetic alterations from the younger group. Integration of cytogenetics and molecular mutations can better risk-stratify older AML patients. Development of novel therapies is needed to improve the outcome of older patients with poor prognosis under current treatment modalities.
Assuntos
Leucemia Mieloide Aguda/genética , Mutação , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Citogenética , DNA (Citosina-5-)-Metiltransferases/genética , DNA Metiltransferase 3A , Feminino , Genes p53/genética , Humanos , Leucemia Mieloide Aguda/diagnóstico , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Proteínas Nucleares/genética , Nucleofosmina , Prognóstico , Medição de Risco , Tirosina Quinase 3 Semelhante a fms/genéticaRESUMO
All-trans retinoic acid (ATRA) is now a standard agent for remission induction of acute promyelocytic leukemia (APL). Recently, extramedullary relapse, which was a rare condition in APL patients after chemotherapy alone, was reported with an increased frequency after ATRA treatment. However, it is not yet clear whether ATRA truly increases the risk of extramedullary recurrence and what are the risk factors. In this study, three of 13 patients with recurrent APL after prior treatment of ATRA were found to have extramedullary involvement, compared with none in 11 recurrent patients previously treated with chemotherapy alone (estimated relative risk 2.100, 95% confidence interval 1.341-3.289). Furthermore, in the former group of patients, the development of retinoic acid (RA) syndrome during prior induction treatment was significantly associated with extramedullary involvement at relapse (three in five patients with RA syndrome vs none in eight without the syndrome, estimated relative risk 5.000, 95% confidence interval 1.448-17.271). In conclusion, ATRA may predispose APL patients to extramedullary involvement at relapse and the occurrence of RA syndrome is a risk factor for it. Further studies are needed to confirm these findings. It also remains to be clarified whether treatment modification is necessary in patients who develop RA syndrome during ATRA treatment.
Assuntos
Hematopoese Extramedular/efeitos dos fármacos , Leucemia Promielocítica Aguda/tratamento farmacológico , Indução de Remissão/métodos , Tretinoína/uso terapêutico , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Recidiva , Estudos Retrospectivos , Fatores de Risco , SíndromeRESUMO
The TP53 mutation is frequently detected in acute myeloid leukemia (AML) patients with complex karyotype (CK), but the stability of this mutation during the clinical course remains unclear. In this study, TP53 mutations were identified in 7% of 500 patients with de novo AML and 58.8% of patients with CK. TP53 mutations were closely associated with older age, lower white blood cell (WBC) and platelet counts, FAB M6 subtype, unfavorable-risk cytogenetics and CK, but negatively associated with NPM1 mutation, FLT3/ITD and DNMT3A mutation. Multivariate analysis demonstrated that TP53 mutation was an independent poor prognostic factor for overall survival and disease-free survival among the total cohort and the subgroup of patients with CK. A scoring system incorporating TP53 mutation and nine other prognostic factors, including age, WBC counts, cytogenetics and gene mutations, into survival analysis proved to be very useful to stratify AML patients. Sequential study of 420 samples showed that TP53 mutations were stable during AML evolution, whereas the mutation was acquired only in 1 of the 126 TP53 wild-type patients when therapy-related AML originated from different clone emerged. In conclusion, TP53 mutations are associated with distinct clinic-biological features and poor prognosis in de novo AML patients and are rather stable during disease progression.
Assuntos
Leucemia Mieloide Aguda/genética , Proteína Supressora de Tumor p53/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/patologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Mutação , Nucleofosmina , Modelos de Riscos Proporcionais , Adulto JovemRESUMO
Recently, mutations of the additional sex comb-like 1 (ASXL1) gene were identified in patients with myelodysplastic syndrome (MDS), but the interaction of this mutation with other genetic alterations and its dynamic changes during disease progression remain to be determined. In this study, ASXL1 mutations were identified in 106 (22.7%) of the 466 patients with primary MDS based on the French-American-British (FAB) classification and 62 (17.1%) of the 362 patients based on the World Health Organization (WHO) classification. ASXL1 mutation was closely associated with trisomy 8 and mutations of RUNX1, EZH2, IDH, NRAS, JAK2, SETBP1 and SRSF2, but was negatively associated with SF3B1 mutation. Most ASXL1-mutated patients (85%) had concurrent other gene mutations at diagnosis. ASXL1 mutation was an independent poor prognostic factor for survival. Sequential studies showed that the original ASXL1 mutation remained unchanged at disease progression in all 32 ASXL1-mutated patients but were frequently accompanied with acquisition of mutations of other genes, including RUNX1, NRAS, KRAS, SF3B1, SETBP1 and chromosomal evolution. On the other side, among the 80 ASXL1-wild patients, only one acquired ASXL1 mutation at leukemia transformation. In conclusion, ASXL1 mutations in association with other genetic alterations may have a role in the development of MDS but contribute little to disease progression.
RESUMO
Conventionally, acute myeloid leukemia (AML) patients are categorized into good-, intermediate- and poor-risk groups according to cytogenetic changes. However, patients with intermediate-risk cytogenetics represent a largely heterogeneous population regarding treatment response and clinical outcome. In this study, we integrated cytogenetics and molecular mutations in the analysis of 318 patients with de novo non-M3 AML who received standard chemotherapy. According to the mutation status of eight genes, including NPM1, CEBPA, IDH2, RUNX1, WT1, ASXL1, DNMT3A and FLT3, that had prognostic significance, 229 patients with intermediate-risk cytogenetics could be refinedly stratified into three groups with distinct prognosis (P<0.001); patients with good-risk genotypes had a favorable outcome (overall survival, OS, not reached) similar to those with good-risk cytogenetics, whereas those with poor-risk genotypes had an unfavorable prognosis (OS, 10 months) similar to those with poor-risk cytogenetics (OS, 13.5 months), and the remaining patients with other genotypes had an intermediate outcome (OS, 25 months). Integration of cytogenetic and molecular profiling could thus reduce the number of intermediate-risk AML patients from around three-fourth to one-fourth. In conclusion, integration of cytogenetic and molecular changes improves the prognostic stratification of AML patients, especially those with intermediate-risk cytogenetics, and may lead to better decision on therapeutic strategy.
Assuntos
Aberrações Cromossômicas , Leucemia Mieloide Aguda/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Nucleofosmina , Fatores de Risco , Adulto JovemAssuntos
Peptídeos e Proteínas de Sinalização Intracelular/genética , Síndromes Mielodisplásicas/genética , Proteínas Tirosina Fosfatases/genética , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Progressão da Doença , Feminino , Humanos , Lactente , Janus Quinase 2 , Masculino , Pessoa de Meia-Idade , Mutação , Síndromes Mielodisplásicas/diagnóstico , Proteína Tirosina Fosfatase não Receptora Tipo 11 , Fatores de RiscoRESUMO
Although the clinical features of the Isocitrate dehydrogenase 2 (IDH2) mutation in acute myeloid leukemia (AML) have been characterized, its prognostic significance remains controversial and its stability has not been investigated. We analyzed 446 adults with primary non-M3 AML and found IDH2 R172, R140 and IDH1 R132 mutations occurred at a frequency of 2.9, 9.2 and 6.1%, respectively. Compared with wild-type IDH2, mutation of IDH2 was associated with higher platelet counts, intermediate-risk or normal karyotype and isolated +8, but was inversely correlated with expression of HLA-DR, CD34, CD15, CD7 and CD56, and was mutually exclusive with WT1 mutation and chromosomal translocations involving core-binding factors. All these correlations became stronger when IDH1 and IDH2 mutations were considered together. Multivariate analysis revealed IDH2 mutation as an independent favorable prognostic factor. IDH2(-)/FLT3-ITD(+) genotype conferred especially negative impact on survival. Compared with IDH2 R140 mutation, IDH2 R172 mutation was associated with younger age, lower white blood cell count and lactate dehydrogenase level, and was mutually exclusive with NPM1 mutation. Serial analyses of IDH2 mutations at both diagnosis and relapse in 121 patients confirmed high stability of IDH2 mutations. In conclusion, IDH2 mutation is a stable marker during disease evolution and confers favorable prognosis.
Assuntos
Isocitrato Desidrogenase/genética , Leucemia Mieloide Aguda/genética , Mutação , Progressão da Doença , Estabilidade Enzimática/genética , Evolução Molecular , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/enzimologia , Nucleofosmina , PrognósticoRESUMO
EBV-induced post transplant lymphoproliferative disorder (PTLD) continues to be a major complication after transplantation. Between January 1993 and April 2006, 12 cases of B-cell lymphoproliferative disorder were identified among 577 patients after allogeneic hematopoietic SCT (HSCT) with an overall incidence of 2.51% at 1 year. Grades II-IV acute GVHD, CMV antigenemia and the use of antithymocyte globulin (ATG) were independent risk factors for PTLD. At diagnosis, all of the tumors were CD20-positive and 11 (92%) were EBV-encoded RNA (EBER)-positive. Of the 12 patients with B-cell lymphoproliferative disorder, 8 had pulmonary involvement and 10 had extranodal involvement. Eleven patients received weekly rituximab therapy at a dose of 375 mg/m(2); the median interval between the onset of symptoms and rituximab therapy was 6 days. The overall mortality rate was 92% and seven (64%) of the deaths were directly attributable to disseminated PTLD within days or weeks of presentation. In our series, pulmonary PTLD followed an extremely aggressive course and poor response to current therapy, even though rituximab was included in the therapeutic regimens.
Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Pneumopatias/etiologia , Transtornos Linfoproliferativos/etiologia , Adolescente , Adulto , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Murinos , Criança , Pré-Escolar , Estudos de Coortes , Infecções por Vírus Epstein-Barr/etiologia , Infecções por Vírus Epstein-Barr/imunologia , Infecções por Vírus Epstein-Barr/terapia , Feminino , Humanos , Lactente , Pneumopatias/imunologia , Pneumopatias/terapia , Transtornos Linfoproliferativos/imunologia , Transtornos Linfoproliferativos/terapia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores de Risco , Rituximab , Transplante Homólogo , Resultado do Tratamento , Adulto JovemRESUMO
Acute myeloid leukemia (AML) with t(7;11)(p15;p15), which results in a NUP98-HOXA9 fusion, is a distinct entity, but this subtype has not been characterized in detail. In a comprehensive study comparing 11 such patients with another 482 adult patients, we found that those with t(7;11) were younger (P=0.0076) and female (P=0.0111), with almost all having the M2-subtype of AML (P<0.0001). Even when those with low-risk karyotypes were excluded, patients with t(7;11) had poorer overall survival than the other AML group (median 13.5 and 20 months, respectively, P=0.045) and poorer relapse-free survival (median 6 and 12 months, respectively, P=0.003). The NUP98-HOXA9 fusion was strongly associated with KRAS and WT1 mutations (P=0.015 and P=0.0018, respectively). We characterized four varieties of this fusion, among which NUP98 exon 12/HOXA9 exon 1b was present in all 11 patients. We developed a highly sensitive and specific assay to quantify the abundance of leukemic cells, and found that the fusion remained detectable in morphological complete remission, even after allogeneic stem cell transplantation, suggesting that this disease was highly refractory to very intensive treatment. AML with NUP98-HOXA9 fusion therefore appears to have a distinct clinical and biological profile, and should be regarded as a poor prognostic group.
Assuntos
Cromossomos Humanos Par 15 , Cromossomos Humanos Par 7 , Leucemia Mieloide Aguda/genética , Translocação Genética , Sequência de Bases , Primers do DNA , Humanos , Reação em Cadeia da PolimeraseRESUMO
The differences in clinical features and prognosis between hypoplastic myelodysplastic syndrome (h-MDS) and normo-/hypercellular MDS (NH-MDS) remain unsettled. In this study, the characteristics of 37 h-MDS patients and 152 NH-MDS patients were compared. Peripheral-blood white blood cell counts and bone marrow blast percentage were lower in h-MDS patients than in NH-MDS patients (P=0.012 and 0.016, respectively). Refractory anemia (RA) was predominant (56.8%) in h-MDS, whereas RA with excess of blast (RAEB) was most common (44.7%) in NH-MDS. Chromosomal abnormalities -7/7q- occurred less frequently in h-MDS patients than in NH-MDS patients (0 vs 18.3%, P=0.022). There was no significant difference in the prevalence of mutations of RAS, AML1, JAK2, PTPN11, FLT3/ITD, and hypermethylation of SOCS1 and SHP1 between these two groups. International Prognostic Scoring System (IPSS) was ideal for predicting prognoses in h-MDS patients (P=0.002). In low- or intermediate-1 (Int-1)-risk MDS patients, h-MDS patients had a superior survival than NH-MDS patients (P=0.01). In conclusion, distinct from NH-MDS, h-MDS patients have different patterns of hemogram, distribution of French-American-British subtypes, cytogenetic changes and prognoses. IPSS is applicable in h-MDS as in NH-MDS. In patients with low- or Int-1-risk MDS, h-MDS patients have a better prognosis than NH-MDS patients.
Assuntos
Síndromes Mielodisplásicas/patologia , Índice de Gravidade de Doença , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia Refratária/epidemiologia , Anemia Refratária com Excesso de Blastos/epidemiologia , Medula Óssea/patologia , Criança , Pré-Escolar , Aberrações Cromossômicas , Metilação de DNA , Análise Mutacional de DNA , Humanos , Hiperplasia , Lactente , Contagem de Leucócitos , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/classificação , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/mortalidade , Prognóstico , Análise de SobrevidaAssuntos
Isocitrato Desidrogenase/genética , Leucemia Mieloide Aguda/genética , Mutação , Sequência de Bases , Células da Medula Óssea/metabolismo , Células da Medula Óssea/patologia , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Proteínas Nucleares/genética , Nucleofosmina , Indução de RemissãoRESUMO
In order to elucidate the structure-activity relationship of griseofulvin (1), (+/-)-6-demethyl analog (3), 2-demethoxy-6-demethyldihydro analog (4), (+/-)-dechloro-6-ethyl analog (5), (+/-)-dechloro-6-epi-ethyl analog (6), (+/-)6-ethyl analog (7) and (+/-)-6-epi-ethyl analog (8) were synthesized by a Diels-Alder cycloaddition of alkylidene ketones (16, 17 18, 19 and 20) with modified 1,3-butadienes (21 or 22). Their biological activities were examined against fungi.
Assuntos
Griseofulvina/análogos & derivados , Fungos Mitospóricos/efeitos dos fármacos , Griseofulvina/síntese química , Griseofulvina/química , Griseofulvina/farmacologia , Relação Estrutura-AtividadeRESUMO
By bioactivity-guided fractionation, a new flavanone triglycoside, naringenin 7-O-(2",6"-di-O-alpha-rhamnopyranosyl)-beta-glucopyranoside (1), as well as hesperetin 7-O-(2", 6"-di-O-alpha-rhamnopyranosyl)-beta-glucopyranoside (2), hesperidin (3) and narirutin (4) have been isolated from the fruits of Citrus junos Tanaka (Rutaceae). In addition, hesperetin 7-O-(2",6"-di-O-alpha-rhamnopyranosyl)-beta-glucopyranoside (2) is reported for the first time from this plant and inhibits the influenza A virus.
Assuntos
Antivirais/isolamento & purificação , Citrus/química , Flavanonas , Glicosídeos/farmacologia , Vírus da Influenza A/efeitos dos fármacos , Antivirais/química , Antivirais/farmacologia , Sequência de Carboidratos , Flavonoides/química , Flavonoides/isolamento & purificação , Glicosídeos/química , Glicosídeos/isolamento & purificação , Espectroscopia de Ressonância Magnética , Dados de Sequência MolecularRESUMO
The synthesis and biological activity of the novel series of 1 beta-methylcarbapenems, 1 and 2 were described. Most compounds displayed high potent antibacterial activity. The best compound in this series, 2a (IH201; R2 = NH2) showed an excellent and a broad spectrum as well as high renal DHP-I stability. It also possessed good in vivo efficacy and high safety.