Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 27
Filtrar
1.
Korean J Intern Med ; 37(4): 841-850, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35811370

RESUMO

BACKGROUND/AIMS: We evaluated the feasibility and long-term efficacy of the combination of cytarabine, idarubicin, and all-trans retinoic acid (ATRA) for treating patients with newly diagnosed acute promyelocytic leukemia (APL). METHODS: We included 87 patients with newly diagnosed acute myeloid leukemia and a t(15;17) or promyelocytic leukemia/retinoic acid receptor alpha (PML-RARα) mutation. Patients received 12 mg/m2/day idarubicin intravenously for 3 days and 100 mg/m2/day cytarabine for 7 days, plus 45 mg/m2/day ATRA. Clinical outcomes included complete remission (CR), relapse-free survival (RFS), overall survival (OS), and the secondary malignancy incidence during a 20-year follow-up. RESULTS: The CR, 10-year RFS, and 10-year OS rates were 89.7%, 94.1%, and 73.8%, respectively, for all patients. The 10-year OS rate was 100% for patients that achieved CR. Subjects were classified according to the white blood cell (WBC) count in peripheral blood at diagnosis (low-risk, WBC < 10,000/mm3; high-risk, WBC ≥ 10,000/mm3). The low-risk group had significantly higher RFS and OS rates than the high-risk group, but the outcomes were not superior to the current standard treatment (arsenic trioxide plus ATRA). Toxicities were similar to those observed with anthracycline plus ATRA, and higher than those observed with arsenic trioxide plus ATRA. The secondary malignancy incidence after APL treatment was 2.7%, among the 75 patients that achieved CR, and 5.0% among the 40 patients that survived more than 5 years after the APL diagnosis. CONCLUSION: Adding cytarabine to anthracycline plus ATRA was not inferior to anthracycline plus ATRA alone, but it was not comparable to arsenic trioxide plus ATRA. The probability of secondary malignancy was low.


Assuntos
Leucemia Promielocítica Aguda , Antraciclinas/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Trióxido de Arsênio/efeitos adversos , Citarabina/efeitos adversos , Seguimentos , Humanos , Idarubicina/efeitos adversos , Leucemia Promielocítica Aguda/diagnóstico , Leucemia Promielocítica Aguda/tratamento farmacológico , Leucemia Promielocítica Aguda/genética , Recidiva , Indução de Remissão , Resultado do Tratamento , Tretinoína/efeitos adversos
2.
Genes Genomics ; 44(6): 659-670, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35377131

RESUMO

BACKGROUND: Polymorphisms of endothelial nitric oxide synthases (eNOS) have been associated with cancer susceptibility. Also, metabolic syndrome is associated with cancer malignancy. However, the effect of eNOS polymorphisms and metabolic syndrome on colorectal cancer (CRC) prognosis remains unclear. OBJECTIVE: To investigated whether three genetic polymorphisms (- 786 T > C rs2070744, 4a4b rs869109213, and 894G > T rs1799983) in the eNOS and metabolic syndrome (MetS) were associated with CRC patient survival. METHODS: We genotyped three polymorphisms of eNOS (- 786 T > C, 4a4b, and 894G > T) in 312 CRC cases from the Korean population by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: Although the three eNOS polymorphisms were not causative of MetS, the TT genotype of the 894G > T polymorphism was associated with a worse survival rate compared with the GG genotype in the CRC group with MetS than in the CRC group without MetS (5-years survival; adjusted HR = 54.777; 95% CI 5.073-591.487 and RFS; adjusted HR = 14.909; 95% CI 1.571-141.528). CONCLUSIONS: The eNOS polymorphisms were not associated with metabolic syndrome prevalence in CRC patients. However, our findings suggest that the eNOS 894G > T polymorphism with MetS was associated with poor clinical outcomes.


Assuntos
Neoplasias Colorretais , Síndrome Metabólica , Neoplasias Colorretais/complicações , Neoplasias Colorretais/genética , Humanos , Síndrome Metabólica/complicações , Síndrome Metabólica/genética , Óxido Nítrico Sintase Tipo III/genética , Polimorfismo Genético , Prognóstico
3.
Br J Ophthalmol ; 105(6): 829-837, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32727729

RESUMO

BACKGROUND: Although human embryonic stem cells (hESCs) have been considered a potential therapeutic option for regenerative medicine, there are some concerns regarding tumorigenicity, immunogenicity and ethical considerations. Stargardt macular dystrophy (SMD) is the most common form of juvenile macular degeneration that causes early onset blindness. Therapeutic options for SMD remain limited, although several treatment strategies are currently under investigation. Here, we report a 3-year assessment of a phase I clinical trial involving subretinal transplantation of hESC-retinal pigment epithelium (RPE) cells in patients with SMD. METHODS: This prospective, non-randomised clinical trial included three patients with SMD. All transplant recipients had central visual acuity no better than 20/400. Trans-pars plana vitrectomy was performed in the eye with poorer vision. RPE cells were reconstituted in balanced salt solution plus, then injected into the subretinal space using a semi-automated subretinal injection method. RESULTS: No serious adverse events occurred throughout the 3-year period following the injection of hESC-RPE cells. The functional and anatomical results were favourable, compared with the natural course of SMD reported in the ProgStar study. One patient showed best-corrected visual acuity improvement, while the other patients had stable best-corrected visual acuity during the 3-year follow-up period. CONCLUSION: These results suggest the long-term safety, tolerability, and feasibility of subretinal hESC-derived RPE cell transplantation in regenerative medicine. TRIAL REGISTRATION NUMBER: NCT01625559.


Assuntos
Células-Tronco Embrionárias/citologia , Epitélio Pigmentado da Retina/patologia , Doença de Stargardt/cirurgia , Transplante de Células-Tronco/métodos , Tomografia de Coerência Óptica/métodos , Adulto , Células-Tronco Embrionárias/transplante , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , República da Coreia/epidemiologia , Doença de Stargardt/diagnóstico , Doença de Stargardt/epidemiologia , Fatores de Tempo , Vitrectomia
5.
Cancer Res Treat ; 50(2): 590-598, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28602052

RESUMO

PURPOSE: The treatment strategy for elderly patients older than 80 years with diffuse large B-cell lymphoma (DLBCL) has not been established because of poor treatment tolerability and lack of data. MATERIALS AND METHODS: This multicenter retrospective study was conducted to investigate clinical characteristics, treatment patterns and outcomes of patients older than 80 years who were diagnosed with DLBCL at 19 institutions in Korea between 2005 and 2016. RESULTS: A total of 194 patients were identified (median age, 83.3 years). Of these, 114 patients had an age-adjusted International Prognostic Index (aaIPI) score of 2-3 and 48 had a Charlson index score of 4 or more. R-CHOP was given in 124 cases, R-CVP in 13 cases, other chemotherapy in 17 cases, radiation alone in nine cases, and surgery alone in two cases. Twenty-nine patients did not undergo any treatment. The median number of chemotherapy cycles was three. Only 37 patients completed the planned treatment cycles. The overall response rate from 105 evaluable patientswas 90.5% (complete response, 41.9%). Twentynine patients died due to treatment-related toxicities (TRT). Thirteen patients died due to TRT after the first cycle. Median overall survival was 14.0 months. The main causes of death were disease progression (30.8%) and TRT (27.1%). In multivariate analysis, overall survival was affected by aaIPI, hypoalbuminemia, elevated creatinine, and treatment. CONCLUSION: Age itself should not be a contraindication to treatment. However, since elderly patients show higher rates of TRT due to infection, careful monitoring and dose modification of chemotherapeutic agents is needed.


Assuntos
Linfoma Difuso de Grandes Células B/terapia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Linfoma Difuso de Grandes Células B/patologia , Masculino , República da Coreia , Estudos Retrospectivos , Resultado do Tratamento
6.
Exp Hematol ; 44(1): 3-13, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26325332

RESUMO

We compared the outcomes of patients with higher-risk diffuse large B-cell lymphoma (DLBCL) who were treated with either up-front autologous stem cell transplantation (ASCT) or salvage chemotherapy followed by delayed ASCT after relapse. Data for 122 DLBCL patients who underwent ASCT as up-front or salvage treatment were analyzed. The 3-year overall survival (OS) rate in DLBCL patients who underwent up-front ASCT was 76.6%, and the rate for those who underwent delayed ASCT was 60.9% (p = 0.017). In a subgroup analysis of patients with a high-intermediate/high-risk age-adjusted International Prognostic Index, achievement of complete remission translated into improved OS in the up-front ASCT group, whereas patients who achieved partial remission had similar OS rates in both groups. The up-front ASCT group had improved OS in patients aged <50 years or with good performance status, whereas the OS rates of both groups were similar in patients aged ≥ 60 years or with poor performance status. When the OS outcome is analyzed by the number of factors (no complete remission during R-CHOP induction chemotherapy, age ≥ 50 years, and performance status ≥ 2), the 3-year OS rates of patients with zero or one, two, and three clinical factors were 80.2%, 51.6%, and 0%, respectively (p < 0.001). In conclusion, in higher-risk DLBCL patients, induction chemotherapy followed by up-front ASCT may have a survival benefit compared with induction chemotherapy alone in highly selected patients who have achieved a complete remission, who are aged <50 years, and who have a good performance status at diagnosis.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linfoma Difuso de Grandes Células B/terapia , Transplante de Células-Tronco , Condicionamento Pré-Transplante , Adolescente , Adulto , Idoso , Anticorpos Monoclonais Murinos/administração & dosagem , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Estudos Retrospectivos , Rituximab , Análise de Sobrevida , Vincristina/administração & dosagem , Adulto Jovem
7.
Mol Clin Oncol ; 3(3): 639-648, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-26137281

RESUMO

Folate has essential roles in DNA synthesis, repair and methylation. Folate metabolism-related gene variants may modulate the levels of this vitamin and affect the cancer risk. Thus, whether these polymorphisms play an important role in carcinogenesis, particularly colorectal cancer (CRC) development, has been a subject interest. The present study investigated the association between polymorphisms in the methylenetetrahydrofolate reductase (MTHFR), thymidylate synthase (TS) and the reduced folate carrier 1 (RFC1) genes and CRC risk. Polymorphisms in MTHFR (677C>T and 1298A>C), TS [1494del6 and the TS enhancer region (TSER)] and RFC1 (-43T>C, 80G>A and 696C>T) were characterized using polymerase chain reaction-restriction fragment length polymorphism in 477 CRC cases and 514 controls. Although no polymorphisms were significantly associated with the CRC risk in the overall sample, significant associations between folate metabolism-related polymorphisms and CRC risk were identified in the stratified analyses. The MTHFR 677CT/1298AC and MTHFR 1298AC+CC/TSER 2R3R genotypes in the presence of plasma folate levels ≤4.12 ng/ml were associated with significantly increased CRC risk. In addition, individuals with the MTHFR 677TT/TSER 3R3R or MTHFR 677/TSER 3R3R/TS 1494 0bp6bp+6bp6bp genotypes and diabetes mellitus (DM) were at an increased risk for CRC. Therefore, the data suggest that i) MTHFR polymorphisms combined with low plasma folate levels and ii) polymorphisms in folate metabolism-related genes combined with metabolic syndrome risk factors (hypertension and DM) increase the odds of developing CRC.

8.
Stem Cell Reports ; 4(5): 860-72, 2015 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-25937371

RESUMO

Embryonic stem cells hold great promise for various diseases because of their unlimited capacity for self-renewal and ability to differentiate into any cell type in the body. However, despite over 3 decades of research, there have been no reports on the safety and potential efficacy of pluripotent stem cell progeny in Asian patients with any disease. Here, we report the safety and tolerability of subretinal transplantation of human embryonic-stem-cell (hESC)-derived retinal pigment epithelium in four Asian patients: two with dry age-related macular degeneration and two with Stargardt macular dystrophy. They were followed for 1 year. There was no evidence of adverse proliferation, tumorigenicity, ectopic tissue formation, or other serious safety issues related to the transplanted cells. Visual acuity improved 9-19 letters in three patients and remained stable (+1 letter) in one patient. The results confirmed that hESC-derived cells could serve as a potentially safe new source for regenerative medicine.


Assuntos
Células-Tronco Embrionárias/citologia , Degeneração Macular/terapia , Epitélio Pigmentado da Retina/transplante , Idoso , Povo Asiático , Diferenciação Celular , Eletrorretinografia , Feminino , Humanos , Degeneração Macular/congênito , Masculino , Pessoa de Meia-Idade , Epitélio Pigmentado da Retina/citologia , Epitélio Pigmentado da Retina/metabolismo , Doença de Stargardt , Acuidade Visual
9.
Ann Hematol ; 94(3): 481-9, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25417830

RESUMO

To gain insight into the natural history of cytomegalovirus (CMV) infection following unrelated cord blood transplantation (UCBT) in seropositive patients, we analyzed the data of 349 seropositive patients who received UCBT in Korea between 2000 and 2011. CMV reactivation occurred in 49 % (171/349) of the CMV-seropositive transplant recipients at a median of 31 days post UCBT. One hundred sixty-four out of 171 patients (96 %) received preemptive therapy. The median duration of CMV reactivation was 29 days. In multivariate analysis, weight >22 kg, use of total body irradiation, use of pre-transplant antithymocyte globulin, graft-versus-host disease (GVHD) prophylaxis with mycophenolate mofetil, and presence of grade II-IV acute GVHD were independent predictors of CMV reactivation. CMV reactivation did not impact transplantation-related mortality (TRM), leukemia relapse, or survival. CMV disease was diagnosed in 62 patients (17.8 %) at a median 55 days after UCBT. Longer duration of CMV reactivation was the only risk factor for progression to CMV disease (p = 0.01). CMV disease resulted in higher TRM (56.0 vs. 31.4 %, p < 0.01) and lower survival (36.1 vs. 55.1 %, p = 0.02).


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Infecções por Citomegalovirus/epidemiologia , Leucemia/epidemiologia , Leucemia/terapia , Transplantados/estatística & dados numéricos , Doadores não Relacionados , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Transplante de Células-Tronco de Sangue do Cordão Umbilical/estatística & dados numéricos , Citomegalovirus/imunologia , Citomegalovirus/fisiologia , Infecções por Citomegalovirus/complicações , Feminino , Humanos , Lactente , Leucemia/complicações , Leucemia/imunologia , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Estudos Soroepidemiológicos , Transplante Homólogo , Ativação Viral , Adulto Jovem
10.
BMC Cancer ; 14: 881, 2014 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-25423914

RESUMO

BACKGROUND: Polymorphisms in angiogenesis-related genes and metabolic syndrome (MetS) risk factors play important roles in cancer development. Moreover, recent studies have reported associations between a number of 3'-UTR polymorphisms and a variety of cancers. The aim of this study was to investigate the associations of three VEGF 3'-UTR polymorphisms (1451C > T [rs3025040], 1612G > A [rs10434], and 1725G > A [rs3025053]) and MetS with colorectal cancer (CRC) susceptibility in Koreans. METHODS: A total of 850 participants (450 CRC patients and 400 controls) were enrolled in the study. The genotyping of VEGF polymorphisms was performed by TaqMan allelic discrimination assays. Cancer risks of genetic variations and gene-environment interactions were assessed by adjusted odds ratios (AORs) and 95% confidence intervals (CIs) of multivariate logistic regression analyses. RESULTS: VEGF 1451C > T was significantly associated with rectal cancer risk (Dominant model; AOR =1.58; 95% CI = 1.09 - 2.28; p = 0.015) whereas VEGF 1725G > A correlated with MetS risk (Dominant model; AOR =1.61; 95% CI =1.06 - 2.46; p = 0.026). Of the gene-environment combined effects, the interaction of VEGF 1451C > T and MetS contributed to increased rectal cancer risk (AOR = 3.15; 95% CI = 1.74 - 5.70; p < .001) whereas the combination of VEGF 1725G > A and MetS was involved with elevated colon cancer risk (AOR = 2.68; 95% CI = 1.30 - 1.55; p =0.008). CONCLUSIONS: Our results implicate that VEGF 1451C > T and 1725G > A may predispose to CRC susceptibility and the genetic contributions may be varied with the presence of MetS.


Assuntos
Regiões 3' não Traduzidas , Povo Asiático/genética , Neoplasias Colorretais/genética , Síndrome Metabólica/genética , Polimorfismo de Nucleotídeo Único , Fator A de Crescimento do Endotélio Vascular/genética , Estudos de Casos e Controles , Feminino , Interação Gene-Ambiente , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , República da Coreia , Fatores de Risco
11.
Blood Res ; 49(1): 61-4, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24724069

RESUMO

Oxaliplatin is a platinum compound used in patients with gastrointestinal malignancies. It is known to evoke a drug-induced immune-mediated thrombocytopenia, which has not been reported in Korea. We describe a 53-year-old man who developed oxaliplatin-induced immune-mediated thrombocytopenia during chemotherapy for colon cancer. Oxaliplatin-dependent IgG platelet antibodies were detected in his serum on flow cytometry. He was treated with immunoglobulin and corticosteroids without any complications. Physicians should consider oxaliplatin-induced immune-mediated thrombocytopenia, when a sudden, isolated thrombocytopenia develops during chemotherapy with oxaliplatin.

12.
Oncol Rep ; 31(2): 995-1002, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24337371

RESUMO

The microRNA (miR)-34 family is a direct transcriptional target of tumor-suppressor TP53 and loss of miR-34 function may impair TP53-mediated cell cycle arrest and apoptosis. In the present study, we investigated whether the single nucleotide polymorphisms (SNPs) rs4938723 (T>C) in the promoter region of miR-34b/c and Arg72Pro (G>C) in codon 72 of TP53 are independently or complementarily associated with the risks and clinical outcomes of colorectal cancer (CRC) and whether the combined effect of these SNPs and metabolic risk factors are related to CRC. We evaluated the SNPs in 545 CRC patients and 428 healthy controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequence analysis. We found that the GC and GC/CC genotypes of TP53 Arg72Pro were associated with decreased risk of CRC (adjusted OR = 0.727 for GC; OR = 0.735 for GC/CC). The combined genotypes of TT-GC and CC-GG were significantly associated with reduced CRC risk (adjusted OR = 0.628 for TT-GC; OR = 0.381 for CC-GG, respectively). The SNP rs4938723 and diabetes mellitus (DM) together were associated with an increased CRC risk, but the SNP TP53 Arg72Pro CC with DM showed a protective effect against CRC. These findings indicate that rs4938723 in the promoter region of pri-miR-34b/c and the SNP in TP53 codon 72 were related to decreased risk of CRC in the population studied and those metabolic diseases and genetic variants influence each other with regard to CRC susceptibility.


Assuntos
Neoplasias Colorretais/genética , MicroRNAs/genética , Proteína Supressora de Tumor p53/genética , Apoptose/genética , Povo Asiático/genética , Sequência de Bases , Biomarcadores Tumorais/genética , Pontos de Checagem do Ciclo Celular/genética , Neoplasias Colorretais/mortalidade , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas/genética , República da Coreia , Estudos Retrospectivos , Risco , Análise de Sequência de DNA , Resultado do Tratamento
13.
Gene ; 533(2): 558-64, 2014 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-24100087

RESUMO

BACKGROUND: 5-Fluorouracil (5-FU) is a cornerstone of chemotherapy for colorectal cancer (CRC), and the major targets of 5-FU are thymidylate synthase (TS), methylenetetrahydrofolate reductase (MTHFR), and reduced folate carrier 1 (RFC1). We hypothesized that polymorphisms in the genes encoding these proteins would be associated with CRC patient survival. PATIENTS AND METHODS: We genotyped the following polymorphisms in 372 CRC patients: TS enhancer region (TSER), TS 1494del6, MTHFR 677C>T and 1298A>C, and RFC1 -43T>C, 80G>A, and 696C>T. Using Kaplan-Meier curves, log-rank tests, and Cox proportional hazard models, we evaluated associations between these polymorphisms and overall survival (OS). RESULTS: The combined TS 1494 0bp6bp+6bp6bp genotype was associated with reduced OS compared to the TS 1494 0bp0bp genotype. Among rectal cancer patients, the RFC1 -43CC and 80AA genotypes were associated with favorable OS. CONCLUSIONS: Our data suggest that TS and RFC1 polymorphisms are associated with CRC prognosis in Korean patients. Further studies are needed to verify these findings.


Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Ácido Fólico/metabolismo , Proteína Carregadora de Folato Reduzido/genética , Timidilato Sintase/genética , Idoso , Povo Asiático/genética , Neoplasias Colorretais/tratamento farmacológico , Feminino , Fluoruracila/farmacocinética , Fluoruracila/uso terapêutico , Humanos , Masculino , Redes e Vias Metabólicas/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Pessoa de Meia-Idade , Polimorfismo Genético , População/genética , República da Coreia/epidemiologia , Análise de Sobrevida
14.
Biol Blood Marrow Transplant ; 19(4): 640-6, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23380345

RESUMO

Pre-engraftment syndrome (PES) is poorly characterized, and its clinical significance and the prognostic impact after unrelated cord blood transplantation (CBT) are unclear. To address these issues, we retrospectively analyzed the incidence, risk factors, and clinical outcomes of PES in unrelated CBT recipients. Data of 381 patients who received unrelated CBT from 18 medical centers in Korea were reviewed. PES was defined as unexplained fever >38.3°C not associated with infection, and/or unexplained skin rash with or without evidence of fluid retention before neutrophil recovery. PES developed in 102 patients (26.8%) at a median of 7 days after CBT. Of these patients, 74 patients (72.5%) received intravenous corticosteroid at a median dose of 1 mg/kg/day, and of these, 95% showed clinical improvement. Risk factors for developing PES included low risk disease, myeloablative conditioning, graft-versus-host disease (GVHD) prophylaxis without methotrexate or corticosteroid, and >5.43 x 10(7)/kg infused nucleated cells. Absence of PES was one of the risk factors for graft failure in multivariate analysis. The cumulative incidence of grade II to grade IV acute GVHD by 100 days after CBT was higher in patients with PES than in those without PES (56.0% versus 34.4%, P < .01). PES was not associated with chronic GVHD, treatment-related mortality, relapse, or overall survival. PES seems to be common after CBT and may be associated with enhanced engraftment without significant morbidity.


Assuntos
Corticosteroides/uso terapêutico , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Sobrevivência de Enxerto/imunologia , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/terapia , Doença Aguda , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Rejeição de Enxerto/prevenção & controle , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Agonistas Mieloablativos/uso terapêutico , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Pele/imunologia , Pele/patologia , Análise de Sobrevida , Síndrome , Condicionamento Pré-Transplante , Transplante Homólogo , Doadores não Relacionados
15.
Gene ; 512(2): 275-81, 2013 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-23137631

RESUMO

BACKGROUND: Polymorphisms of endothelial nitric oxide synthases (eNOS) have been shown to be associated with cancer susceptibility. However, the results of such studies are conflicting to date. We investigated whether polymorphisms of the eNOS gene correlated with patients with colorectal cancer (CRC), relative to healthy individuals. PATIENTS AND METHODS: In the present study, we analyzed three polymorphisms of eNOS (-786T>C, 4a4b, and 894G>T) in 509 healthy controls and 528 patients with CRC. The genotyping of eNOS polymorphisms was performed using polymerase chain reaction or polymerase chain reaction-restriction fragment length polymorphism assays. RESULTS: We found that the TC+CC genotype of the -786T>C polymorphism was significantly associated with an increased risk of CRC compared with the TT genotype. Similarly, the GT+TT genotype of the 894G>T polymorphism was associated with an increased susceptibility to CRC. However, no evidence was found for any association between the 4a4b polymorphism and CRC risk. In addition, the C/4b/G (-786T>C/4a4b/894G>T) haplotype was significantly associated with increased risk of CRC and C/4b/T (-786T>C/4a4b/894G>T) haplotype was only detected in CRC patients. CONCLUSIONS: Our study suggests that the eNOS -786T>C and 894G>T polymorphisms may be associated with the development of CRC in the Korean population.


Assuntos
Neoplasias Colorretais/genética , Predisposição Genética para Doença , Óxido Nítrico Sintase Tipo III/genética , Polimorfismo de Fragmento de Restrição , Idoso , Povo Asiático , Neoplasias Colorretais/enzimologia , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia
16.
Int J Clin Oncol ; 18(6): 1032-41, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23132736

RESUMO

BACKGROUND: Angiogenesis plays an important role in tumor development, progression, and metastasis. Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis. However, the contribution of common VEGF polymorphisms to colorectal cancer (CRC) prognosis remains unclear. METHODS: We have genotyped four polymorphisms of VEGF (-2578C>A, -1154G>A, -634G>C, and 936C>T) in 350 CRC cases from the Korean population. The genotyping of VEGF polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism assay. RESULTS: Although not every VEGF polymorphism was significantly correlated with patient prognosis in overall 350 CRC patients, we found that the VEGF -2578CA genotype was associated with a significantly poor prognosis for rectal cancers compared to the CC genotype (HR = 2.156; 95 % CI 1.090-4.267; P = 0.028). In addition, we found that the -2578A/-1154G/-634G/+936C haplotype was significantly associated with a decreased overall survival (OS) rate in all 350 CRC patients (HR = 2.530; 95 % CI 1.340-4.780; P = 0.004). In combination analysis, we found that the combined VEGF -2578CA+AA/-1154GG genotype was associated with a poor OS rate in all 350 CRC patients (HR = 2.068; 95 % CI 1.159-3.693; P = 0.015). CONCLUSIONS: The VEGF gene polymorphisms investigated in this study were not found to be independent prognostic markers in Korean CRC populations. However, our results suggest that the VEGF -2578C>A variant may be a potential genetic marker for rectal cancer prognosis. Further large population studies are warranted to define whether the -2578C>A polymorphism is a prognostic marker of rectal cancer.


Assuntos
Neoplasias Colorretais/genética , Neovascularização Patológica/genética , Prognóstico , Fator A de Crescimento do Endotélio Vascular/genética , Idoso , Biomarcadores Tumorais/genética , Neoplasias Colorretais/patologia , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neovascularização Patológica/patologia , Polimorfismo de Nucleotídeo Único
17.
Acta Haematol ; 129(4): 197-206, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23257958

RESUMO

BACKGROUND AND AIMS: Immunomodulatory properties of mesenchymal stem cells (MSCs) have been applied to reduce the incidence of graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HSCT). Among the various sources of MSCs that have immunomodulatory effects in vitro, only placenta-derived MSCs (PD-MSCs) have not been evaluated in an in vivo model of GVHD. In this study, we investigated the immunomodulatory properties of PD-MSCs in vitro and evaluated their clinical potential for controlling GVHD in an animal model. METHODS: A GVHD animal model was established by transplanting C57BL/6 donor bone marrow cells and spleen cells into lethally irradiated BALB/c recipient mice. To control GVHD, human PD-MSCs were transplanted into recipient mice (5 × 10(5) or 1 × 10(6) cells). RESULTS: PD-MSCs suppressed mitogen-stimulated T cell proliferation in vitro in a dose-dependent manner. Moreover, PD-MSCs inhibited cytokine secretion (interleukin-12, tumor necrosis factor-α and interferon-γ) of activated T cells. In vivo, the survival rate in the PD-MSC group (transplanted with 1 × 10(6) cells) was higher than that in the control group and histological scores were low in the PD-MSC group. CONCLUSION: We present the first evidence that human PD-MSCs can efficiently control GVHD in an HSCT in vivo model.


Assuntos
Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/prevenção & controle , Imunomodulação , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/imunologia , Placenta/citologia , Animais , Transplante de Medula Óssea/imunologia , Diferenciação Celular , Modelos Animais de Doenças , Feminino , Fase G2 , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/patologia , Humanos , Interferon gama/metabolismo , Interleucina-12/metabolismo , Ativação Linfocitária/imunologia , Transplante de Células-Tronco Mesenquimais , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Gravidez , Taxa de Sobrevida , Linfócitos T/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
18.
Korean J Hematol ; 47(1): 74-6, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22479281

RESUMO

Pneumatosis intestinalis (PI) is a rare condition characterized by multiple pneumocysts in the submucosa or subserosa of the bowel. Here, we report a rare case of asymptomatic PI after chemotherapy induction in an 18-yr-old man with B lymphoblastic leukemia with recurrent genetic abnormalities. The patient was treated conservatively and recovered without complications. The possibility of PI should be considered as a complication during or after chemotherapy for hematologic malignancies. Conservative treatment should be considered unless there are complications, including peritonitis, bowel perforation, and severe sepsis.

19.
Mol Carcinog ; 51 Suppl 1: E65-73, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22161766

RESUMO

MicroRNAs (miRNAs) are small, 18- to 22-nucleotide non-coding RNAs that regulate target gene expression. Although recent studies focused on various diseases that harbor the miR-146aC>G (rs2910164), 149C>T (rs2292832), 196a2C>T (rs11614913), and 499A>G (rs3746444) polymorphisms, the role of miRNA genetic variants in colorectal cancer is still unknown. The present study aimed to evaluate the role of four miRNA polymorphisms in patients with colorectal cancer. We enrolled 446 colorectal cancer patients and 502 control subjects from the Korean population. We found a significantly increased colorectal cancer risk with the miR-196a2CC genotype compared with the TT/CT genotype (AOR = 1.50; 95% CI = 1.11-2.04; P = 0.01; FDR-P = 0.04). In the stratified analyses, we observed both weak and strong association data. We found stronger associations of the miR-196a2 variants in the non-diabetic and rectal cancer groups than other stratified groups. Our data suggest that the miRNA variants could affect the development of colorectal cancer in the Korean population.


Assuntos
Neoplasias Colorretais/genética , Predisposição Genética para Doença , MicroRNAs , Polimorfismo de Nucleotídeo Único , Idoso , Povo Asiático/genética , Estudos de Casos e Controles , Humanos , Masculino , Pessoa de Meia-Idade , Distribuição Aleatória
20.
Int J Hematol ; 95(1): 107-11, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22167655

RESUMO

Human herpesvirus 8-positive (HHV-8⁺) and Epstein-Barr virus-positive (EBV⁺) germinotropic lymphoproliferative disorder (GLD) is extremely rare and occurs most commonly in immunocompetent persons who are human immunodeficiency virus (HIV)-seronegative. It is also recognized as a favorable response to conventional chemotherapy. Here, we report a case of a 75-year-old man with an incidentally found mass in the neck, compatible with GLD, which was detected by positron emission tomography (PET). Computed tomography (CT) scan, PET, and bone marrow studies showed only the left neck mass and no evidence of metastasis. Excisional biopsy of the mass was performed. The patient received four courses of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) therapy. After these treatments, he remained disease-free for 19 months. To the best of our knowledge, only five cases of HHV-8⁺, EBV⁺ GLD have been documented. This is the first such case report in Asia.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Centro Germinativo/patologia , Infecções por Herpesviridae/complicações , Herpesvirus Humano 4/isolamento & purificação , Herpesvirus Humano 8/isolamento & purificação , Linfoma/complicações , Linfoma/tratamento farmacológico , Idoso , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Centro Germinativo/virologia , Neoplasias de Cabeça e Pescoço/complicações , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/virologia , Infecções por Herpesviridae/virologia , Humanos , Linfoma/patologia , Linfoma/virologia , Masculino , Prednisona/uso terapêutico , Vincristina/uso terapêutico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA