Página 7 dos resultados de 1094 itens digitais encontrados em 0.063 segundos
Resultados filtrados por Publicador: Nature Publishing Group

‣ Effects of proteasome inhibitors on bone cancer

Terpos, Evangelos; Christoulas, Dimitrios
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
Publicado em 14/08/2013 Português
Relevância na Pesquisa
349.00605%
Bone metastasis is a frequent complication of cancer, occurring in up to 70% of patients with advanced breast or prostate cancer, while bone disease is also the characteristic clinical feature of multiple myeloma. Skeletal-related events can be devastating, with major effect on the quality of life and survival. Bisphosphonates are the mainstay of therapeutic management of bone disease of solid tumors and myeloma, and denosumab has recently been approved for patients with bone metastases. Both act through inhibition of the osteoclast activity but do not restore bone formation. Proteasome inhibition has direct bone anabolic effects. Proteasome inhibitors have been used in the management of patients with multiple myeloma and mantle-cell lymphoma during the last decade. In multiple myeloma, bortezomib, the first-in-class proteasome inhibitor, has shown both in vitro and in vivo regulation of bone remodeling by inhibiting osteoclast function and promoting osteoblast activity. Bortezomib also reduces bone resorption but more importantly increases bone formation and bone mineral density, at least, in subsets of myeloma patients. Thus, bortezomib is recommended for myeloma patients with extended bone disease in combination with bisphosphonates. This review focuses on the effects of the proteasome system on bone metabolism and the implications into the better management of patients with cancer and bone disease.

‣ Variation in type I collagen fibril nanomorphology: the significance and origin

Fang, Ming; Holl, Mark M Banaszak
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
Publicado em 21/08/2013 Português
Relevância na Pesquisa
349.00605%
Although the axial D-periodic spacing is a well-recognized nanomorphological feature of type I collagen fibrils, the existence of a distribution of values has been largely overlooked since its discovery seven decades ago. Studies based on single fibril measurements occasionally noted variation in D-spacing values, but accredited it with no biological significance. Recent quantitative characterizations supported that a 10-nm collagen D-spacing distribution is intrinsic to collagen fibrils in various tissues as well as in vitro self-assembly of reconstituted collagen. In addition, the distribution is altered in Osteogenesis Imperfecta and long-term estrogen deprivation. Bone collagen is organized into lamellar sheets of bundles at the micro-scale, and D-spacings within a bundle of a lamella are mostly identical, whereas variations among different bundles contribute to the full-scale distribution. This seems to be a very general phenomenon for the protein as the same type of D-spacing/bundle organization is observed for dermal and tendon collagen. More research investigation of collagen nanomorphology in connection to bone biology is required to fully understand these new observations. Here we review the data demonstrating the existence of a D-spacing distribution...

‣ A bone to pick with zebrafish

Mackay, Eirinn W; Apschner, Alexander; Schulte-Merker, Stefan
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
Publicado em 13/11/2013 Português
Relevância na Pesquisa
349.00605%
The development of high-throughput sequencing and genome-wide association studies allows us to deduce the genetic factors underlying diseases much more rapidly than possible through classical genetics, but a true understanding of the molecular mechanisms of these diseases still relies on integrated approaches including in vitro and in vivo model systems. One such model that is particularly suitable for studying bone diseases is the zebrafish (Danio rerio), a small fresh-water teleost that is highly amenable to genetic manipulation and in vivo imaging. Zebrafish physiology and genome organization are in many aspects similar to those of humans, and the skeleton and mineralizing tissues are no exception. In this review, we highlight some of the contributions that have been made through the study of mutant zebrafish that feature bone and/or mineralization disorders homologous to human diseases, including osteogenesis imperfecta, fibrodysplasia ossificans progressiva and generalized arterial calcification of infancy. The genomic and phenotypic similarities between the zebrafish and human cases are illustrated. We show that, despite some systemic physiological differences between mammals and teleosts, and a relative lack of a history as a model for bone research...