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1.
Leukemia ; 25(3): 440-8, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21151022

RESUMO

Although glucocorticoid (GC) is widely used for treating hematopoietic malignancies including adult T-cell leukemia (ATL), the mechanism by which leukemic cells become resistant to GC in the clinical course remains unclear. Using a series of T-cell lines infected with human T lymphotropic virus type-I (HTLV-I), the causative virus of ATL, we have dissected the transformation from interleukin (IL)-2-dependent to -independent growth stage. The transformation associates the loss of thioredoxin-binding protein-2 (TBP-2), a tumor suppressor and regulator of lipid metabolism. Here we show that TBP-2 is responsible for GC-induced apoptosis in ATL cells. In the IL-2-dependent stage, dexamethasone induced TBP-2 expression and apoptosis, both of which were blocked by GC receptor (GR) antagonist RU486. Knockdown of TBP-2 consistently reduced the amount of GC-induced apoptosis. In IL-2-independent stage, however, expression of GR and TBP-2 was suppressed and GC failed to induce apoptosis. Forced expression of GR led the cells to mild sensitivity to GC, which was also accomplished by treatment with suberoylanilide hydroxamic acid, a TBP-2 inducer. A transfection experiment showed that TBP-2 expression induced apoptosis in IL-2-independent ATL cells. Thus, TBP-2 is likely to be one of the key molecules for GC-induced apoptosis and a potential target for treating the advanced stage of ATL.


Assuntos
Proteínas de Transporte/fisiologia , Transformação Celular Viral , Glucocorticoides/farmacologia , Vírus Linfotrópico T Tipo 1 Humano , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Linfócitos T/efeitos dos fármacos , Proteínas de Transporte/análise , Linhagem Celular , Humanos , Ácidos Hidroxâmicos/farmacologia , Receptores de Glucocorticoides/análise , Receptores de Glucocorticoides/fisiologia , Vorinostat
2.
Eur J Gastroenterol Hepatol ; 13(10): 1231-3, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11711781

RESUMO

BACKGROUND: It has been suggested that appendectomy may protect against ulcerative colitis (UC). However, the incidences of appendectomy and UC in developed countries have diverged over the last 50 years, possibly as a consequence of environmental factors. AIM: To determine whether the incidence of appendectomy is lower in patients with UC than in the general population. METHODS: Patients with UC (153), their relatives (116) and members of the general population (306) that had been matched for age, sex and educational status were studied. RESULTS: Six per cent of UC patients had undergone appendectomy. The corresponding figure for non-family controls was 20% (P < 0.0001; OR = 0.27; 95% CI = 0.15-0.45). The rate of appendectomy within families (cases plus siblings) was 17/269 (6.3%) and was similar to that for UC patients alone(P < 0.001). CONCLUSIONS: A negative association between appendectomy and UC exists in our patients with UC. In addition, the appendectomy rate in families of UC patients was lower than that in the general population, possibly implying that common environmental and genetic factors could play an important role in the divergent incidences of appendicitis and UC over the last 50 years.


Assuntos
Apendicectomia/estatística & dados numéricos , Apendicite/epidemiologia , Apendicite/genética , Colite Ulcerativa/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Apendicite/cirurgia , Estudos de Casos e Controles , Colite Ulcerativa/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Prevalência , Espanha/epidemiologia
3.
Rev Esp Enferm Dig ; 93(5): 303-14, 2001 May.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-11488108

RESUMO

UNLABELLED: There is some controversy regarding the prevalence of tonsillectomy and appendectomy among patients with Crohn's disease (CD) and a lower rate of appendectomy among patients with ulcerative colitis (UC). However, some environmental and familial factors that could alter those figures have not been studied. OBJECTIVE: To explore the prevalence of MALTectomy (appendectomy and tonsillectomy) among patients with IBD, stressing those factors that may be significantly associated to it. METHOD: Age-and-sex matched case-control study in patients with IBD, their relatives and the general population. Two hundred and eighty seven cases were IBD patients (153 UC, and 134 CD), the "family control" group included 203 siblings and the population-based control group included 570 individuals. Potential confounding factors, such as smoking, educational level, oral contraceptive use, place of birth and residence up to the age of 15 years, were ruled out. RESULTS: Appendectomy and UC: 7% of UC patients had undergone appendectomy versus 20% (OR: 0.23; 95% CI: 0.11-0.5; p < 0.0001) of controls. Appendectomy rates in families with at least one case of UC were 17/153 (6.3%) and 61/306 (20%) in the control group (p < 0.001). Appendectomy and CD: Twelve per cent of CD patients had undergone appendectomy six months before the onset of the disease versus 17% among the control population (OR: 0.43; 95% CI: 0.29-0.95; p < 0.01). The frequency of appendectomy in families with at least one case of CD was 22/221 (10%), which was significantly lower (p < 0.05) than among the control group 45/264 (17%). No differences were found between IBD patients and familial controls. Tonsillectomy and CD: Forty six per cent of CD patients had undergone tonsillectomy versus 39% of control patients (OR: 1.77; 95% CI: 0.92-2.05; p = ns). Tonsillectomy and UC: Twenty eight per cent of UC patients had undergone tonsillectomy versus 39% of the population control group (OR: 1.07; 95 CI: 0.57-1.25: p = ns). In fact, no differences were found regarding the prevalence of tonsillectomies within families with IBD cases as compared to population controls. CONCLUSIONS: Appendectomy is not only less frequent among CD and UC patients, but also among their relatives, thus suggesting the existence of environmental and genetic factors with opposed etiological roles in IBD and appendicitis.


Assuntos
Apendicectomia/estatística & dados numéricos , Colite Ulcerativa/cirurgia , Doença de Crohn/cirurgia , Tonsilectomia/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Colite Ulcerativa/genética , Doença de Crohn/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
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