RESUMO
Lumbar spondylolysis is a unilateral or bilateral defect of the pars interarticularis, an isthmus of bone connecting the superior and inferior facet surfaces in the lumbar spine at a given level. Spondylolysis is common in young athletes participating in sports, particularly those requiring repetitive hyperextension movements. The majority of young athletes are able to return to full sport participation following accurate diagnosis and conservative management, including a structured treatment program. Surgical intervention for isolated pars injuries is seldom necessary. A progressive physical therapy (PT) program is an important component of recovery after sustaining an acute pars fracture. However, there is a paucity of literature detailing PT programs specific to spondylolysis. Here, we provide an overview of the epidemiology, natural history, radiographic evaluation, and management of pars fractures in young athletes. In addition, a detailed description of a physiotherapy program for this population that was developed at a spine center within an academic medical center is provided.
RESUMO
Herpes simplex virus-1 (HSV-1), like all herpesviruses, is a large complex DNA virus containing up to 16 different viral membrane proteins in its envelope. The assembly of HSV-1 particles occurs by budding/wrapping at intracellular membranes producing infectious virions contained within the lumen of cytoplasmic membrane-bound compartments that are then released by secretion. To ensure incorporation of all viral membrane proteins into the envelope, they need to be localized to the appropriate intracellular membranes either via the endocytic pathway or by direct targeting to assembly sites from the biosynthetic secretory pathway. Many HSV-1 envelope proteins encode targeting motifs that direct their endocytosis and targeting, while others do not, including the essential entry proteins gD and the gH/gL complex, and so it has been unclear how these envelope proteins reach the appropriate assembly compartments. We now show that efficient endocytosis of gD and gH/gL and their incorporation into mature virions relies upon the presence of the HSV-1 envelope proteins gM and the gK/pUL20 complex. Our data demonstrate both redundant and synergistic roles for gM and gK/pUL20 in controlling the targeting of gD and gH/L to the appropriate intracellular virus assembly compartments.
Assuntos
Herpesvirus Humano 1/fisiologia , Proteínas do Envelope Viral/metabolismo , Montagem de Vírus , Animais , Transporte ProteicoRESUMO
Chemotherapy resistance frequently drives tumour progression. However, the underlying molecular mechanisms are poorly characterized. Epithelial-to-mesenchymal transition has been shown to correlate with therapy resistance, but the functional link and signalling pathways remain to be elucidated. Here we report that microRNA-30c, a human breast tumour prognostic marker, has a pivotal role in chemoresistance by a direct targeting of the actin-binding protein twinfilin 1, which promotes epithelial-to-mesenchymal transition. An interleukin-6 family member, interleukin-11 is identified as a secondary target of twinfilin 1 in the microRNA-30c signalling pathway. Expression of microRNA-30c inversely correlates with interleukin-11 expression in primary breast tumours and low interleukin-11 correlates with relapse-free survival in breast cancer patients. Our study demonstrates that microRNA-30c is transcriptionally regulated by GATA3 in breast tumours. Identification of a novel microRNA-mediated pathway that regulates chemoresistance in breast cancer will facilitate the development of novel therapeutic strategies.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Resistencia a Medicamentos Antineoplásicos/genética , Interleucina-11/metabolismo , MicroRNAs/metabolismo , Proteínas dos Microfilamentos/metabolismo , Proteínas Tirosina Quinases/metabolismo , Animais , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Análise por Conglomerados , Citoesqueleto/efeitos dos fármacos , Citoesqueleto/genética , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Feminino , Fator de Transcrição GATA3/metabolismo , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Interleucina-11/genética , Camundongos , Proteínas dos Microfilamentos/genética , Prognóstico , Proteínas Tirosina Quinases/genética , Reação em Cadeia da Polimerase em Tempo Real , Supressão Genética/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Metastasis remains a significant challenge in treating cancer. A better understanding of the molecular mechanisms underlying metastasis is needed to develop more effective treatments. Here, we show that human breast tumor biomarker miR-30c regulates invasion by targeting the cytoskeleton network genes encoding twinfilin 1 (TWF1) and vimentin (VIM). Both VIM and TWF1 have been shown to regulate epithelial-to-mesenchymal transition. Similar to TWF1, VIM also regulates F-actin formation, a key component of cellular transition to a more invasive mesenchymal phenotype. To further characterize the role of the TWF1 pathway in breast cancer, we found that IL-11 is an important target of TWF1 that regulates breast cancer cell invasion and STAT3 phosphorylation. The miR-30c-VIM/TWF1 signaling cascade is also associated with clinical outcome in breast cancer patients.
