Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 60
Filtrar
1.
Br J Haematol ; 200(5): 608-621, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36370064

RESUMO

In a prospective, explorative study, the donor-source difference of haploidentical family (HF), matched sibling (MS), and unrelated donors (UD) was evaluated for the outcome of haematopoietic cell transplantations (HCT) in 101 patients with acute myeloid leukaemia (AML) in complete remission (CR). To eliminate compounding effects, a uniform conditioning regimen containing antithymocyte globulin (ATG) was used. After transplantation, there was a significantly higher cumulative incidence of acute graft-versus-host disease (GVHD) in HF-HCT patients (49%, 7%, and 16% for HF-, MS- and UD-HCT respectively; p < 0.001). A quarter of acute GVHD cases observed in HF-HCT patients occurred within three days of engraftment and were characterized by diffuse skin rash, fever, weight gain, and hypoalbuminaemia. This peri-engraftment acute GVHD was not observed in MS-HCT or UD-HCT patients. Additionally, a significantly higher proportion of HF-HCT patients achieved complete donor chimaerism in the peripheral mononuclear cells at one month (88%, 46%, and 69% for HF-, MS- and UD-HCT respectively; p = 0.001). There was no significant difference in engraftment, chronic GVHD, leukaemia recurrence, non-relapse mortality, and patient survival. In patients with AML in CR who received HCT using ATG-containing conditioning, stronger donor-patient alloreactivity was observed in HF-HCT, in terms of increased acute GVHD and higher likelihood of complete donor chimaerism.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Humanos , Bussulfano/uso terapêutico , Soro Antilinfocitário/uso terapêutico , Doadores não Relacionados , Irmãos , Estudos Prospectivos , Recidiva Local de Neoplasia , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Leucemia Mieloide Aguda/terapia , Condicionamento Pré-Transplante
2.
Phytother Res ; 37(12): 5904-5915, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37654104

RESUMO

Schizophrenia is a chronic brain disorder characterized by positive symptoms (delusions or hallucinations), negative symptoms (impaired motivation or social withdrawal), and cognitive impairment. In the present study, we explored whether D-pinitol could ameliorate schizophrenia-like behaviors induced by MK-801, an N-methyl-D-aspartate receptor antagonist. Acoustic startle response test was conducted to evaluate the effects of D-pinitol on sensorimotor gating function. Social interaction and novel object recognition tests were employed to measure the impact of D-pinitol on social behavior and cognitive function, respectively. Additionally, we examined whether D-pinitol affects motor coordination. Western blotting was conducted to investigate the mechanism of action of D-pinitol. Single administration of D-pinitol at 30, 100, or 300 mg/kg improved the sensorimotor gating deficit induced by MK801 in the acoustic startle response test. D-Pinitol also reversed social behavior deficits and cognitive impairments induced by MK-801 without causing any motor coordination deficits. Furthermore, D-pinitol reversed increased expression levels of pNF-kB induced by MK-801 treatment and consequently increased expression levels of TNF-α and IL-6 in the prefrontal cortex. These results suggest that D-pinitol could be a potential candidate for treating sensorimotor gating deficits and cognitive impairment observed in schizophrenia by down-regulating transcription factor NF-κB and pro-inflammatory cytokines in the prefrontal cortex.


Assuntos
Disfunção Cognitiva , Esquizofrenia , Camundongos , Animais , Maleato de Dizocilpina/efeitos adversos , Reflexo de Sobressalto/fisiologia , Esquizofrenia/induzido quimicamente , Esquizofrenia/tratamento farmacológico , Esquizofrenia/metabolismo , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológico
3.
Clin Transplant ; 35(3): e14199, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33349948

RESUMO

The prognosis of patients with acute leukemia relapsed after allogeneic hematopoietic stem cell transplantation (HSCT) is dismal. We aimed to evaluate the outcomes and prognostic factors of the second HSCT (HSCT2) in acute leukemia patients relapsed after the first HSCT (HSCT1). We analyzed 80 patients who received HSCT2 for relapsed acute leukemia in two Korean institutes. All but four patients received HSCT2 from a donor other than matched sibling donor: an unrelated donor (URD) in 30 and a familial haploidentical donor (FHD) in 46. Forty-four patients (55.0%) were in complete remission (CR) or CR with incomplete count recovery (CRi) at HSCT2, and the median time from HSCT1 to relapse was 9 months. The 2-year overall survival (OS) and event-free survival (EFS) were 21.0% and 17.5%, respectively. The outcomes were similar between URD and FHD. Multivariate analysis demonstrated that disease status (active disease vs. CR/CRi) at HSCT2 and remission duration after HSCT1 were independent prognostic factors for OS and EFS after HSCT2. HSCT2 from URD or FHD was feasible in patients with acute leukemia relapsed after allogeneic HSCT. Also, our study confirmed two critical prognostic factors; disease status at HSCT2 and remission duration after HSCT1.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Doença Aguda , Humanos , Leucemia Mieloide Aguda/terapia , Indução de Remissão , Estudos Retrospectivos , Doadores não Relacionados
4.
J Korean Med Sci ; 36(23): e151, 2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34128593

RESUMO

BACKGROUND: This study presents outcomes of management in graft failure (GF) after allogeneic hematopoietic stem cell transplantation (HCT) and provides prognostic information including rare cases of autologous reconstitution (AR). METHODS: We analyzed risk factors and outcomes of primary and secondary GF, and occurrence of AR in 1,630 HCT recipients transplanted over period of 18 years (January 2000-September 2017) at our center. RESULTS: Primary and secondary GF occurred in 13 (0.80%), and 69 patients (10-year cumulative incidence, 4.5%) respectively. No peri-transplant variables predicted primary GF, whereas reduced intensity conditioning (RIC) regimen (relative risk [RR], 0.97-28.0, P < 0.001) and lower CD34⁺ cell dose (RR, 2.44-2.84, P = 0.002) were associated with higher risk of secondary GF in multivariate analysis. Primary GF demonstrated 100% mortality, in the secondary GF group, the 5-year Kaplan-Meier survival rate was 28.8%, relapse ensued in 18.8%, and AR was observed in 11.6% (n = 8). In survival analysis, diagnosis of aplastic anemia (AA), chronic myeloid leukemia and use of RIC had a positive impact. There were 8 patients who experienced AR, which was rarely reported after transplantation for acute leukemia. Patient shared common characteristics such as young age (median 25 years), use of RIC regimen, absence of profound neutropenia, and had advantageous survival rate of 100% during follow period without relapse. CONCLUSION: Primary GF exhibited high mortality rate. Secondary GF had 4.5% 10-year cumulative incidence, median onset of 3 months after HCT, and showed 5-year Kaplan-Meier survival of 28.8%. Diagnosis of severe AA and use of RIC was both associated with higher incidence and better survival rate in secondary GF group. AR occurred in 11.6% in secondary GF, exhibited excellent prognosis.


Assuntos
Rejeição de Enxerto/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Condicionamento Pré-Transplante/métodos , Transplante Homólogo/efeitos adversos , Adolescente , Adulto , Idoso , Feminino , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Condicionamento Pré-Transplante/efeitos adversos , Falha de Tratamento , Adulto Jovem
5.
Biol Blood Marrow Transplant ; 25(6): 1116-1121, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30508593

RESUMO

Our previous research indicated that a reduced-intensity conditioning regimen (fludarabine and melphalan at 100 mg/m2) was useful in allogeneic hematopoietic cell transplantation (HCT) for patients with lymphoma. This retrospective study evaluated the reduced-intensity conditioning regimen in allogeneic HCT for adult patients with hemophagocytic lymphohistiocytosis (HLH). Sixteen patients with HLH were evaluated, including 6 patients who were enrolled in a prospective clinical trial (NCT00772811) and 10 patients who received the same conditioning regimen (fludarabine at 30 mg/m2/day on days -6 to -2 and melphalan at 100 mg/m2 on day -2). The median age was 42 years (range, 18 to 64), and 12 patients had Epstein-Barr virus (EBV)-associated HLH. Donors were an HLA matched sibling for 10 patients, an unrelated matched volunteer for 4 patients, and a mismatched family member for 2 patients. After excluding 3 patients who died soon after HCT, 12 patients achieved an engraftment (neutrophil median, day 12; platelet median, day 16). Five patients experienced acute graft-versus-host disease (GVHD), including 1 case of grade II and 4 cases of grades III to IV. Chronic GVHD occurred in 3 patients (moderate, 1 case; severe, 2 cases). After a median follow-up of 33.8 months 1 patient progressed, 3 patients relapsed, and 9 patients died. Five deaths were unrelated to relapse or progression and were caused by infection (n = 3), bleeding (n = 1), and GVHD (n = 1). No deaths or relapses were observed at >124 days post-transplant. The overall survival rate was 48.6%, and significant differences were observed according to pretransplant ferritin level (P = .007) and cytopenia lineage (P = .021). Before allogeneic HCT 10 of 12 patients still tested positive for EBV DNA: 6 patients tested negative for EBV DNA after HCT, 2 patients had persistent EBV DNA, and 2 patients were unassessable because of early death. Conditioning therapy using a lower dose of melphalan combined with fludarabine appears to be promising in allogeneic HCT for adults with HLH. However, strategies are needed to reduce the risk of early death.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Melfalan/uso terapêutico , Agonistas Mieloablativos/uso terapêutico , Condicionamento Pré-Transplante/métodos , Transplante Homólogo/métodos , Vidarabina/análogos & derivados , Adolescente , Adulto , Feminino , Humanos , Linfo-Histiocitose Hemofagocítica/mortalidade , Masculino , Melfalan/farmacologia , Pessoa de Meia-Idade , Agonistas Mieloablativos/farmacologia , Análise de Sobrevida , Vidarabina/farmacologia , Vidarabina/uso terapêutico , Adulto Jovem
6.
Rapid Commun Mass Spectrom ; 32(11): 897-905, 2018 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-29572989

RESUMO

RATIONALE: In addition to the development of adequate screening methods for multiple compounds, the World Anti-Doping Agency (WADA) requires anti-doping laboratories to analyze prohibited substances and their metabolites from various classes. This task presents a difficult challenge for all agencies and interests involved in the field of doping control. METHODS: A screening method is reported in which hybrid sample preparation was performed using a combination of weak cation-exchange solid-phase extraction (WCX-SPE) and the 'Dilute and Shoot' strategy in order to take advantage of both the methodologies. Target substances were extracted using a WCX cartridge and reconstituted with a diluted sample aliquot that included 20% of an untreated urine sample. The target substances were further analyzed by high-performance liquid chromatography/triple quadrupole mass spectrometry (LC/MS). RESULTS: The SPE procedure was optimized using a cartridge-washing step, elution conditions, and elution volume. The cartridge-washing step, which was performed using 10% methanol, improved the overall recovery of target substances. Since the recovery was observed to vary according to the pH of the eluting solution, we applied an elution step using both an acid and a basic organic solvent to achieve complementary recovery. Reconstitution of the diluted aliquot sample was performed to recover the polar substances. CONCLUSIONS: The method was validated and applied to real samples in accordance with the external quality assessment scheme of WADA and to the previously reported samples that had provided positive test results. This novel method using hybrid sample preparation and LC/MS could be useful to screen multiple classes of the 264 targeted substances in anti-doping analysis.


Assuntos
Dopagem Esportivo , Substâncias para Melhoria do Desempenho/análise , Extração em Fase Sólida/métodos , Betametasona/urina , Cromatografia Líquida de Alta Pressão , Humanos , Concentração de Íons de Hidrogênio , Limite de Detecção , Substâncias para Melhoria do Desempenho/urina , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Solventes/química , Espectrometria de Massas por Ionização por Electrospray/métodos , Trimetazidina/urina
7.
Acta Haematol ; 139(4): 220-227, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29860259

RESUMO

The prognosis of adult acute lymphoblastic leukemia is much worse than that of pediatric acute lymphoblastic leukemia, even when patients achieve complete remission. Early response to treatment can be an important alternative indicator of treatment outcomes. The purpose of our current study was to identify the prognostic value of the blast percentage of the induction interim bone marrow, which might predict relapse-free survival and overall survival in patients with adult acute lymphoblastic leukemia. A retrospective analysis was performed on 80 adult patients diagnosed with Philadelphia chromosome-negative acute lymphoblastic leukemia from 1994 to 2011. Complete remission was observed in 75 (93.8%) patients after induction chemotherapy. On multivariate analysis, a reduction of blasts to a level of 5% or less in the induction interim bone marrow and CD20 positivity were significant prognostic predictors of relapse-free survival (hazard ratio, HR = 2.88, p = 0.006, and HR = 2.67, p = 0.010) and overall survival (HR = 2.10, p = 0.033, and HR = 2.39, p = 0.013). The blast percentage of the induction interim bone marrow may be a useful prognostic factor to predict outcome.


Assuntos
Medula Óssea/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores , Biópsia , Exame de Medula Óssea , Terapia Combinada , Análise Citogenética , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Imunofenotipagem , Quimioterapia de Indução , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Prognóstico , Análise de Sobrevida , Transplante Homólogo , Resultado do Tratamento
8.
Biol Blood Marrow Transplant ; 23(9): 1555-1566, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28552421

RESUMO

To investigate the role of antithymocyte globulin (ATG)-containing reduced-intensity conditioning (RIC) in hematopoietic cell transplantation (HCT) from unrelated (UD) or haploidentical family donors (HFD), we conducted a phase 2 trial of 237 patients (age range, 16 to 69 years) with acute myeloid leukemia (AML) in remission. Patients undergoing UD-HCT (n = 93) or HFD-HCT (n = 59) received RIC comprising busulfan, fludarabine, and ATG, 9 mg/kg, whereas those undergoing HCT from matched sibling donors (MSD, n = 85) received myeloablative busulfan and cyclophosphamide conditioning or aforementioned RIC with ATG, 4.5 mg/kg. For graft-versus-host disease (GVHD) prophylaxis, cyclosporine and methotrexate were administered. The median follow-up period was 44.7 months after HCT for 161 survivors. For UD-HCT versus HFD-HCT, there were no significant differences in leukemia recurrence, nonrelapse mortality, relapse-free survival, grades 2 to 4 acute GVHD, and moderate-to-severe chronic GVHD. Furthermore, when the outcomes of UD-HCT and HFD-HCT were combined and compared with those of MSD-HCT, there were no significant differences in leukemia recurrence (3-year cumulative incidence, 30% versus 29%), nonrelapse mortality (3-year cumulative incidence, 7% versus 8%), relapse-free survival (3-year estimate, 63% versus 63%), and grades 2 to 4 acute GVHD (120-day cumulative incidence, 16% versus 13%). Moderate-to-severe chronic GVHD, however, occurred less frequently in UD/HFD-HCT (2-year cumulative incidence, 22% versus 40%; P = .006). The addition of ATG to conditioning regimen was a significant predictor for less chronic GVHD (subdistribution hazard ratio, .59). In AML in remission, UD/HFD-HCT after ATG-containing RIC achieved leukemia control equivalent to that of MSD-HCT. Despite HLA disparity in UD/HFD-HCT, chronic GVHD occurred less frequently after ATG-containing RIC, suggesting a strong GVHD-modulating effect of ATG.


Assuntos
Soro Antilinfocitário/uso terapêutico , Bussulfano/uso terapêutico , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas , Imunossupressores/uso terapêutico , Mieloma Múltiplo/terapia , Vidarabina/análogos & derivados , Doença Aguda , Adolescente , Adulto , Idoso , Doença Crônica , Ciclofosfamida/uso terapêutico , Ciclosporina/uso terapêutico , Feminino , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/patologia , Teste de Histocompatibilidade , Humanos , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Mieloma Múltiplo/imunologia , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/patologia , Agonistas Mieloablativos/uso terapêutico , Estudos Prospectivos , Recidiva , Indução de Remissão , Irmãos , Análise de Sobrevida , Condicionamento Pré-Transplante/métodos , Transplante Haploidêntico , Doadores não Relacionados , Vidarabina/uso terapêutico
9.
J Org Chem ; 82(21): 11566-11572, 2017 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-29019238

RESUMO

The first total synthesis and biological evaluation of penchinone A and its structural analogues are described. The key steps for the preparation of penchinone A derivatives involve the oxime-directed palladium(II)-catalyzed oxidative acylation, Claisen rearrangement, and base-mediated olefin migration. This transformation efficiently provides a range of allyl-substituted biaryl ketones with site-selectivity and functional group compatibility. In addition, all synthetic compounds were screened for anti-inflammatory activity against nitric oxide (NO), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6) with lipopolysaccharide (LPS)-induced RAW264.7 cells. Generally, a range of penchinone A derivatives potently inhibited NO, TNF-α, and IL-6 productions, compared to dexamethasone as a positive control. Notably, penchinone A (8g) and its derivatives (8e and 8f) were found to exhibit anti-inflammatory activity stronger than that of dexamethasone.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Interleucina-6/antagonistas & inibidores , Lignanas/farmacologia , Óxido Nítrico/antagonistas & inibidores , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Animais , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Interleucina-6/biossíntese , Lignanas/síntese química , Lignanas/química , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Camundongos , Estrutura Molecular , Óxido Nítrico/biossíntese , Células RAW 264.7 , Fator de Necrose Tumoral alfa/biossíntese
10.
Biol Blood Marrow Transplant ; 22(11): 2065-2076, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27530969

RESUMO

The optimum method of donor natural killer cell infusion (DNKI) after allogeneic hematopoietic cell transplantation (HCT) remains unclear. Fifty-one patients (age range, 19 years to 67 years) with refractory acute leukemia underwent HLA-haploidentical HCT and underwent DNKI on days 6, 9, 13, and 20 of HCT. Median DNKI doses were .5, .5, 1.0, and 2.0 × 108/kg cells, respectively. During DNKI, 33 of the 45 evaluated patients (73%) developed fever (>38.3°C) along with weight gain (median, 13%; range, 2% to 31%) and/or hyperbilirubinemia (median, 6.2 mg/dL; range, 1.0 mg/dL to 35.1 mg/dL); the toxicity was reversible in 90% of patients. After transplantation, we observed cumulative incidences of neutrophil engraftment (≥500/µL), grade 2 to 4 acute graft-versus-host disease (GVHD), chronic GVHD, and nonrelapse mortality of 84%, 28%, 30%, and 16%, respectively. The leukemia complete remission rate was 57% at 1 month after HCT and 3-year cumulative incidence of leukemia progression was 75%. When analyzed together with our historical cohort of 40 patients with refractory acute leukemia who underwent haploidentical HCT and DNKI on days 14 and 21 only, higher expression of NKp30 (>90%) on donor NK cells was an independent predictor of higher complete remission (hazard ratio, 5.59) and less leukemia progression (hazard ratio, .57). Additional DNKI on days 6 and 9 was not associated with less leukemia progression (75% versus 55%).


Assuntos
Células Matadoras Naturais/transplante , Leucemia/terapia , Transplante Haploidêntico/métodos , Doença Aguda , Adulto , Idoso , Feminino , Antígenos HLA , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Imunoterapia Adotiva/métodos , Masculino , Pessoa de Meia-Idade , Terapia de Salvação/métodos , Doadores de Tecidos , Adulto Jovem
11.
Ann Hematol ; 95(7): 1151-61, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27106699

RESUMO

Reduced-intensity conditioning (RIC) regimens can cause decreased non-relapse mortality (NRM) but lead to higher relapse rates in higher-risk myelodysplastic syndrome (MDS). However, relapse is not the main problem after hematopoietic cell transplantation (HCT) in lower-risk MDS, and post-transplant outcomes may therefore improve with less intense non-myeloablative conditioning (NMC) regimens. We here report the results of a single-center feasibility study of NMC with cyclophosphamide-fludarabine-antithymocyte globulin (CyFluATG) in MDS patients with bone marrow blasts <5 %. We compared post-transplant outcomes between CyFluATG and a RIC regimen, busulfan-fludarabine-antithymocyte globulin (BuFluATG). Fifteen MDS patients received allogeneic HCT after CyFluATG conditioning comprising cyclophosphamide (100 mg/kg), fludarabine (150 mg/m(2)), and ATG, and 30 MDS historical control patients received BuFluATG conditioning which contained busulfan (8 [oral] or 6.4 [i.v.] mg/kg), fludarabine, and ATG. The 4-year overall survival (OS) and NRM rates were 80.0 and 20.0 % for CyFluATG and 73.3 and 20.0 % for BuFluATG, respectively. Neutrophil and platelet engraftment was significantly faster with CyFluATG than BuFluATG (median 12 vs. 14 days, P = 0.005 for neutrophils; median 15 vs. 21 days, P = 0.032 for platelets). CyFluATG produced a faster immune reconstitution of T-cells at 1 month after HCT than BuFluATG. Fertility was maintained after HCT with CyFluATG. In conclusion, the CyFluATG regimen is feasible in lower-risk MDS patients in terms of adequate engraftment and low NRM.


Assuntos
Células da Medula Óssea/patologia , Transplante de Células-Tronco Hematopoéticas/métodos , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/terapia , Condicionamento Pré-Transplante/métodos , Adolescente , Adulto , Soro Antilinfocitário/administração & dosagem , Células da Medula Óssea/efeitos dos fármacos , Bussulfano/administração & dosagem , Ciclofosfamida/administração & dosagem , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transplante Homólogo/métodos , Vidarabina/administração & dosagem , Vidarabina/análogos & derivados , Adulto Jovem
12.
J Org Chem ; 81(20): 9878-9885, 2016 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-27680096

RESUMO

The rhodium(III)-catalyzed direct C-H functionalization of various indolines with 1,4,2-dioxazol-5-ones as new amidating agents is described. This transformation provides efficient preparation of C7-amidated indolines known to display potent anticancer activity. The synthetic compounds were evaluated for in vitro anticancer activity against human prostate adenocarcinoma cells (LNCaP), human endometrial adenocarcinoma cells (Ishikawa), and human ovarian carcinoma cells (SKOV3). Compound 4f was found to be highly cytotoxic, with activity competitive with that of anticancer agent doxorubicin.


Assuntos
Amidas/química , Indicadores e Reagentes/química , Indóis/química , Ródio/química , Catálise , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Indóis/farmacologia , Masculino , Análise Espectral/métodos
13.
J Org Chem ; 81(11): 4771-8, 2016 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-27187625

RESUMO

The rhodium(III)-catalyzed γ-trifluoromethylallylation of various heterocyclic C-H bonds with CF3-substituted allylic carbonates is described. These reactions provide direct access to linear CF3-containing allyl frameworks with complete trans-selectivity via C-H bond activation followed by a formal SN-type reaction pathway.

14.
J Org Chem ; 81(22): 11353-11359, 2016 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-27794608

RESUMO

The rhodium(III)-catalyzed olefination of various carboxamides with α-CF3-substituted allylic carbonate is described. This reaction provides direct access to linear CF3-allyl frameworks with complete trans-selectivity. In particular, a rhodium catalyst provided Heck-type γ-CF3-allylation products via the ß-O-elimination of rhodacycle intermediate and subsequent olefin migration process.

15.
Ann Hematol ; 94(5): 795-801, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25563594

RESUMO

Monosomal karyotype (MK) in acute myeloid leukemia (AML) is associated with an extremely poor outcome. The clinical significance of MK and the role of allogeneic hematopoietic cell transplantation (HCT) were evaluated in 749 Korean patients with newly diagnosed AML. MK was found in 9.3% of patients and was more frequent in patients with advanced age or secondary AML. Patients with MK had significantly lower blood leukocyte counts and bone marrow blast percentages, and they had lower complete remission (CR) rate (43%) and shorter median overall survival (OS) (6.5 months) and relapse-free survival (RFS) (10.0 months) than any other prognostic group. MK+ patients who received allogeneic HCT at the first CR had higher OS [hazard ratio (HR) 0.344, P = 0.018], RFS (HR 0.257, P = 0.006), and lower relapse probability (HR 0.264, P = 0.008) than those not receiving. This study's results confirmed poor outcomes for AML patients with MK and suggest that allogeneic HCT at the first CR may improve outcome.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide Aguda/genética , Transplante Homólogo/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Cariotipagem , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
16.
Psychooncology ; 24(8): 871-7, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25382562

RESUMO

OBJECTIVE: This study aimed to understand factors related to post-traumatic growth (PTG) in patients who received allogeneic hematopoietic stem cell transplantation (HSCT), building baseline data for developing intervention programs to enhance PTG in HSCT survivors. METHODS: A self-report survey was administered to 100 patients who received HSCT within the last 5 years. The Post-traumatic Growth Inventory, Impact of Event Scale-Revised, Perceived Social Support Scale, and Healthcare Professional's Support Scale were used, as well as items on demographic and clinical characteristics. Standard deviations of frequency and percentage, Chi-squared test between genders, independent t-test, correlation analysis between independent variables and extent of PTG, and regression analysis were conducted. RESULTS: The PTG levels of HSCT survivors were statistically significantly higher when participants were women, carried out more religious activities, had higher educational levels, or utilized nurse counseling. The 'intrusive thinking' traumatic impact subcategory, as well as social support and support from healthcare professionals, were found to be highly related to PTG scores. Upon multiple regression analysis, factors with greatest influence on PTG in HSCT survivors were support from healthcare professionals, followed in order, by social support, utilization of nurse counseling, intrusive thinking, and frequency of religious activities. CONCLUSIONS: We suggest implementing programs for HSCT patients to enhance support from healthcare professionals and to increase post-traumatic growth through greater utilization of nurse counseling, self-help meetings, and writing.


Assuntos
Adaptação Psicológica , Transplante de Células-Tronco Hematopoéticas/psicologia , Apoio Social , Adulto , Aconselhamento , Escolaridade , Análise Fatorial , Feminino , Transplante de Células-Tronco Hematopoéticas/enfermagem , Humanos , Pessoa de Meia-Idade , Enfermeiras e Enfermeiros , Religião , Autorrelato , Fatores Sexuais , Sobreviventes/psicologia , Transplante Homólogo , Adulto Jovem
17.
Acta Haematol ; 133(2): 183-92, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25323649

RESUMO

In patients with secondary acute myeloid leukemia (s-AML) arising from the myelodysplastic syndrome (MDS), treatment outcome is unsatisfactory. We compared up-front allogeneic hematopoietic cell transplantation (HCT) to induction chemotherapy (IC) as an initial treatment in patients with s-AML arising from MDS. This retrospective study included 85 patients who were diagnosed with s-AML arising from MDS; 11 patients proceeded to up-front HCT without IC (HCT group) and 74 received IC (IC group) as an initial treatment for s-AML, 28 of whom subsequently underwent HCT. In the IC group, 41.9% achieved complete remission (CR) compared to 81.8% in the HCT group (p = 0.013). The HCT group showed a significantly longer event-free survival (EFS) than the IC group (median 29.2 vs. 5.2 months, p = 0.042). Overall survival of the HCT group was higher than that of the IC group, but the difference was not statistically significant (median 34.6 vs. 7.6 months, p = 0.149). After adjustment for other clinical factors, outcome in the HCT group was significantly better than in the IC group in terms of CR rate (hazard ratio, HR, 11.195; p = 0.007) and EFS (HR, 0.384; p = 0.029). Up-front HCT is a viable option in s-AML arising from MDS if an appropriate donor is available.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/terapia , Adolescente , Adulto , Idoso , Aloenxertos , Intervalo Livre de Doença , Feminino , Humanos , Leucemia Mieloide Aguda/diagnóstico , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/complicações , Síndromes Mielodisplásicas/diagnóstico , Indução de Remissão , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
18.
Biol Blood Marrow Transplant ; 20(5): 696-704, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24525278

RESUMO

The doses of donor-derived natural killer (NK) cells that can be given safely after human leukocyte antigen (HLA)-haploidentical hematopoietic cell transplantation (HCT) remain to be defined. Forty-one patients (ages 17 to 75 years) with hematologic malignancy underwent HLA-haploidentical HCT after reduced-intensity conditioning containing busulfan, fludarabine, and antithymocyte globulin. Cell donors (ages 7 to 62 years) underwent growth factor-mobilized leukapheresis for 3 to 4 days. Cells collected on the first 2 to 3 days were used for HCT, whereas those collected on the last day were CD3-depleted and cultured into NK cells using human interleukins-15 and -21. These NK cells were then infused into patients twice at 2 and 3 weeks after HCT at an escalating doses of .2 × 10(8) cells/kg of body weight (3 patients), .5 × 10(8) cells/kg (3 patients), 1.0 × 10(8) cells/kg (8 patients), and ≥ 1.0 × 10(8) cells/kg or available cells (27 patients). At all dose levels, no acute toxicity was observed after NK cell infusion. After HLA-haploidentical HCT and subsequent donor NK cell infusion, when referenced to 31 historical patients who had undergone HLA-haploidentical HCT after the same conditioning regimen but without high-dose NK cell infusion, there was no significant difference in the cumulative incidences of major HCT outcomes, including engraftment (absolute neutrophil count ≥ 500/µL, 85% versus 87%), grade 2 to 4 acute graft-versus-host disease (GVHD, 17% versus 16%), moderate to severe chronic GVHD (15% versus 10%), and transplantation-related mortality (27% versus 19%). There was, however, a significant reduction in leukemia progression (74% to 46%), with post-transplantation NK cell infusion being an independent predictor for less leukemia progression (hazard ratio, .527). Our findings showed that, when given 2 to 3 weeks after HLA-haploidentical HCT, donor-derived NK cells were well tolerated at a median total dose of 2.0 × 10(8) cells/kg. In addition, they may decrease post-transplantation progression of acute leukemia.


Assuntos
Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Células Matadoras Naturais/transplante , Agonistas Mieloablativos/uso terapêutico , Condicionamento Pré-Transplante/métodos , Adolescente , Adulto , Idoso , Soro Antilinfocitário/uso terapêutico , Bussulfano/uso terapêutico , Criança , Progressão da Doença , Feminino , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/patologia , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/patologia , Teste de Histocompatibilidade , Humanos , Células Matadoras Naturais/imunologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Transplante Homólogo , Vidarabina/análogos & derivados , Vidarabina/uso terapêutico
20.
J Nanosci Nanotechnol ; 14(3): 2343-51, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24745230

RESUMO

Various SBA-15-based catalysts, Si-SBA-15, Pt/Si-SBA-15, Al-SBA-15, and Pt/Al-SBA-15, were applied to the catalytic pyrolysis of miscanthus. Pt nanoparticles with three different sizes, 1.7 nm, 2.9 nm, and 7.1 nm, were used to synthesize Pt/Si-SBA-15 and Pt/Al-SBA-15. Pyrolysis-gas chromatography/mass spectrometry was used for the pyrolysis experiments. The catalysts were characterized by X-ray diffraction patterns, transmittance electron microscopy, N2 adsorption-desorption, and Brunaure-Emmett-Teller surface area. The product species distribution of pyrolysis of miscanthus was significantly affected by the acid property of the catalyst and the presence of Pt. In particular, Pt/Al-SBA-15, which has both acid sites and Pt, changed the product species distribution to the largest extent; the main products were phenolics and furans. The effect of Pt particle size on the species distribution of pyrolysis product was negligible.


Assuntos
Poaceae/metabolismo , Dióxido de Silício/química , Adsorção , Alumínio/química , Fontes de Energia Bioelétrica , Biomassa , Carbono/química , Catálise , Cromatografia Gasosa-Espectrometria de Massas , Nanopartículas Metálicas/química , Microscopia Eletrônica de Transmissão , Oxigênio/química , Tamanho da Partícula , Fenol/química , Platina/química , Silício/química , Propriedades de Superfície , Difração de Raios X
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA