RESUMO
Cholangiocarcinoma (CCA) is an aggressive malignancy that originates from the epithelial cells of the biliary duct system. Depending on the anatomical location, CCA can be considered extrahepatic (eCCA) or intrahepatic (iCCA) (1). Two thirds of CCAs involve the extrahepatic biliary system, whereas the rest are confined within the liver parenchyma, beyond the secondary biliary radicals (2). Due to its biological aggressiveness and difficulty in diagnosis, the majority of patients with CCA are unresectable at presentation and the overall 5-year survival is approximately five percent (4). This article focuses on the genetic and epigenetic alterations present in cholangiocarcinomas, their occasional relationship to external stimuli, and with an emphasis on those unanswered questions about cholangiocarcinogenesis and future directions in the comprehension of epigenetic DNA methylation in patients with CCA.
Assuntos
Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologia , Colangiocarcinoma/patologia , Transformação Genética/genética , Animais , Neoplasias dos Ductos Biliares/genética , Ductos Biliares Intra-Hepáticos/metabolismo , Colangiocarcinoma/genética , Humanos , Transdução de SinaisRESUMO
BACKGROUND: The objectives of this study were to assess the incidence of clinical allergy and end-induction antiasparaginase (anti-ASNase) antibodies in children with high-risk acute lymphoblastic leukemia treated with pegylated (PEG) Escherichia coli ASNase and to determine whether they carry any prognostic significance. METHODS: Of 2057 eligible patients, 1155 were allocated to augmented arms in which PEG ASNase replaced native ASNase postinduction. Erwinia chrysanthemi (Erwinia) ASNase could be used to replace native ASNase after allergy, if available. Allergy and survival data were complete for 990 patients. End-induction antibody titers were available for 600 patients. RESULTS: During the consolidation phase, 289 of 990 patients (29.2%) had an allergic reaction. There were fewer allergic reactions to Erwinia ASNase than to native ASNase (odds ratio, 4.33; P < .0001) or PEG ASNase (odds ratio, 3.08; P < .0001) only during phase 1 of interim maintenance. There was no significant difference in 5-year event-free survival (EFS) between patients who received PEG ASNase throughout the entire study postinduction versus those who developed an allergic reaction to PEG ASNase during consolidation phase and subsequently received Erwinia ASNase (80.8% ± 2.8% and 81.6% ± 3.8%, respectively; P = .66). Patients who had positive antibody titers postinduction were more likely to have an allergic reaction to PEG ASNase (odds ratio, 2.4; P < .001). The 5-year EFS rate between patients who had negative versus positive antibody titers (80% ± 2.6% and 77.7% ± 4.3%, respectively; P = .68) and between patients who did not receive any ASNase postconsolidation and those who received PEG ASNase throughout the study (P = .22) were significantly different. CONCLUSIONS: The current results demonstrate differences in the incidence rates of toxicity between ASNase preparations but not in EFS. The presence of anti-ASNase antibodies did not affect EFS.
Assuntos
Antineoplásicos/efeitos adversos , Asparaginase/efeitos adversos , Hipersensibilidade a Drogas/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Anticorpos/sangue , Antineoplásicos/química , Antineoplásicos/imunologia , Asparaginase/química , Asparaginase/imunologia , Criança , Pré-Escolar , Dickeya chrysanthemi/enzimologia , Dickeya chrysanthemi/imunologia , Hipersensibilidade a Drogas/imunologia , Escherichia coli/enzimologia , Escherichia coli/imunologia , Humanos , Quimioterapia de Indução , Lactente , Polietilenoglicóis/química , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Análise de Sobrevida , Resultado do TratamentoRESUMO
The Advanced Trauma Life Support (ATLS) protocol is a successful course offered by the American College of Surgeons. Once based on didactic lectures and seminars taught by experts in the field, trauma training has evolved to become a set of standardized assessment and treatment protocols based on evidence rather than expert opinion. As the ATLS expands, indices to predict outcome, morbidity, and mortality have evolved to guide management and treatment based on retrospective data. This historical, perspective article attempts to tell the story of ATLS from its inception to its evolution as an international standard for the initial assessment and management of trauma patients.
Assuntos
Cuidados para Prolongar a Vida/história , Cuidados para Prolongar a Vida/normas , Guias de Prática Clínica como Assunto , Traumatologia/história , Traumatologia/normas , Ferimentos e Lesões/história , Ferimentos e Lesões/terapia , História do Século XX , História do Século XXI , Humanos , Estados UnidosRESUMO
Using transgenic mice expressing human cystatin C (encoded by CST3), we show that cystatin C binds soluble amyloid-beta peptide and inhibits cerebral amyloid deposition in amyloid-beta precursor protein (APP) transgenic mice. Cystatin C expression twice that of the endogenous mouse cystatin C was sufficient to substantially diminish amyloid-beta deposition. Thus, cystatin C has a protective role in Alzheimer's disease pathogenesis, and modulation of cystatin C concentrations may have therapeutic implications for the disease.