RESUMO
BACKGROUND: Ec peptide (PEc), resulting from the proteolytic cleavage of the IGF-1Ec isoform, is involved in prostate cancer progression and metastasis, whereas in muscle tissue, it is associated with the mobilization of satellite cells prior to repair. Our aim is to determine the physiological conditions associated to the IGF-1Ec upregulation and PEc secretion in prostate tumors, as well as, the effect of tumor PEc on tumor repair. METHODS: IGF-1 (mature and isoforms) expression was examined by qRT-PCR, both in prostate cancer cells co-incubated with cells of the immune response (IR) and in tumors. PEc secretion was determined by Multiple Reaction Monitoring. The effect of PEc, on mesenchymal stem cell (MSC) mobilization and repair, was examined using migration and invasion assays, FISH and immunohistochemistry (IHC). The JAK/STAT signaling pathway leading to the IGF1-Ec expression was examined by western blot analysis. Determination of the expression and localization of IL-6 and IGF-1Ec in prostate tumors was examined by qRT-PCR and by IHC. RESULTS: We documented that IL-6 secreted by IR cells activates the JAK2 and STAT3 pathway through IL-6 receptor in cancer cells, leading to the IGF-1Ec upregulation and PEc secretion, as well as to the IL-6 expression and secretion. The resulting PEc, apart from its oncogenic role, also mobilizes MSCs towards the tumor, thus promoting tumor repair. CONCLUSIONS: IL-6 leads to the PEc secretion from prostate cancer cells. Apart from its oncogenic role, PEc is also involved in the mobilization of MSCs resulting in tumor repair.
Assuntos
Fator de Crescimento Insulin-Like I/metabolismo , Interleucina-6/metabolismo , Peptídeos/metabolismo , Neoplasias da Próstata/metabolismo , Adulto , Animais , Linhagem Celular Tumoral , Células Cultivadas , Humanos , Fator de Crescimento Insulin-Like I/genética , Interleucina-6/farmacologia , Janus Quinase 2/metabolismo , Linfócitos/imunologia , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/fisiologia , Camundongos SCID , Peptídeos/farmacologia , Neoplasias da Próstata/imunologia , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Fator de Transcrição STAT3/metabolismoRESUMO
BACKGROUND: Retraction pockets are collapsed segments of the tympanic membrane. Their formation is associated with a disruption in middle-ear ventilation pathways, leading to the loss of organised collagen of the tympanic membrane. There are several approaches in treating retraction pockets, which aim either to improve ventilation or repair the retraction pockets themselves. METHODS: A review of the literature regarding the classification and associated management of retraction pockets was conducted, using Medline and Cochrane Library databases, with the addition of our institution's experience in undertaking novel techniques. RESULTS: All the current classification systems fail to guide treatment or prognosticate the disease. Commonly, an initial conservative approach is suggested for early stages, with no clear indication regarding when a surgical solution should be offered. There are conflicting data concerning the effectiveness of these treatments in terms of disease prevention, recurrence and hearing outcomes. CONCLUSION: Minimally invasive approaches utilising novel techniques may be key to reducing peri-operative morbidity and improving the overall patient experience.
Assuntos
Colesteatoma da Orelha Média , Otopatias , Colesteatoma da Orelha Média/complicações , Colágeno , Bases de Dados Factuais , Otopatias/diagnóstico , Otopatias/cirurgia , Humanos , Ventilação da Orelha Média , Membrana Timpânica/cirurgiaRESUMO
OBJECTIVE: Sinonasal inverted papillomas are challenging benign tumours of the nasal cavity because of their high recurrence rates and the lifetime malignant transformation risk of 10 per cent as well as their locally aggressive behaviour. This study aimed to describe treatment strategies for inverted papillomas with intracranial or intraorbital involvement. METHOD: This was a prospective case series study of 18 patients with inverted papilloma with intracranial or intraorbital involvement. Patient demographic data, imaging, pathology, surgical technique and recurrences were recorded prospectively over a period of seven years. RESULTS: A total of 83 per cent of the patients in this study had been previously operated on, consisting of 8 cases with intracranial involvement, 1 case with intraorbital involvement and 9 with both. During follow up with a medium of 37 months (range, 13-115 months) there were two recurrences. CONCLUSION: It was postulated that intracranial or intraorbital involvement observed in this series was the result of multiple revisions. However, using accurate imaging protocols and the pedicle-oriented approach for tumour excision, complete tumour removal was achieved in most cases with minimal post-operative complications.