RESUMO
Epidemiological studies indicate that longterm aspirin usage reduces the incidence of colorectal cancer (CRC) and may protect against other nonCRC associated adenocarcinomas, including oesophageal cancer. A number of hypotheses have been proposed with respect to the molecular action of aspirin and other nonsteroidal antiinflammatory drugs in cancer development. The mechanism by which aspirin exhibits toxicity to CRC has been previously investigated by synthesising novel analogues and derivatives of aspirin in an effort to identify functionally significant moieties. Herein, an early effect of aspirin and aspirinlike analogues against the SW480 CRC cell line was investigated, with a particular focus on critical molecules in the epidermal growth factor (EGF) pathway. The present authors proposed that aspirin, diaspirin and analogues, and diflunisal (a salicylic acid derivative) may rapidly perturb EGF and EGF receptor (EGFR) internalisation. Upon longer incubations, the diaspirins and thioaspirins may inhibit EGFR phosphorylation at Tyr1045 and Tyr1173. It was additionally demonstrated, using a qualitative approach, that EGF internalisation in the SW480 cell line may be directed to endosomes by fumaryldiaspirin using early endosome antigen 1 as an early endosomal marker and that EGF internalisation may also be perturbed in oesophageal cell lines, suggestive of an effect not only restricted to CRC cells. Taken together and in light of our previous findings that the aspirinlike analogues can affect cyclin D1 expression and nuclear factorκB localisation, it was hypothesized that aspirin and aspirin analogues significantly and swiftly perturb the EGFR axis and that the protective activity of aspirin may in part be explained by perturbed EGFR internalisation and activation. These findings may also have implications in understanding the inhibitory effect of aspirin and salicylates on wound healing, given the critical role of EGF in the response to tissue trauma.
Assuntos
Aspirina/farmacologia , Neoplasias Colorretais/metabolismo , Salicilatos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Aspirina/análogos & derivados , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ciclina D1/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais , Família de Proteínas EGF/metabolismo , Receptores ErbB/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , NF-kappa B/metabolismo , Fosforilação/efeitos dos fármacosRESUMO
Dentinogenesis imperfecta type 2 (DI-2), also known as hereditary opalescent dentin, is a rare, genetically linked condition that affects both primary and permanent teeth. Severe attrition requiring full-mouth rehabilitation is a common finding associated with DI-2. Dental rehabilitation options include a variety of invasive and noninvasive restorative techniques dictated by the age of the patient. Growth and development must be considered and may result in a restorative challenge for the dental practitioner, particularly when the patient in question is a child. This case report describes the fabrication of an overdenture to reestablish function, esthetics, and self-esteem in a 12-year-old patient. A 2-stage restorative treatment was followed by a satisfactory 6-month recall examination, indicating that the prostheses provided a successful outcome until more definitive restorative treatment can be accomplished in adulthood.