FAK (Phospho-Tyr576) ELISA Kit

Although osteosarcoma is the most common bone malignancy, the molecular and cellular mechanisms influencing its pathogenesis have remained elusive. Prion proteins (PRNP and PRND), known mostly for its involvement in neurodegenerative spongiform encephalopathies, have been recently demonstrated to be involved in resistance to apoptosis, tumorigenesis, proliferation, and metastasis. The main aim of research was to study whether prion proteins were over-expressed in human osteosarcoma, and if prion proteins could have a role also in osteosarcomas. We evaluated differential gene expression between 22 cases of osteosarcoma and 40 cases of normal bone specimens through cDNA microarray analysis spanning a substantial fraction of the human genome. PRNP and PRND are significantly over-expressed in osteosarcoma. PRNP and PRND appear involved with some important genes related to tumorigenesis and apoptosis. PRNP is linked to PTK2, RBBP9, and TGFB1 while PRND is linked to TNFSF10, BCL2A1, NFKB2, and TP53RK. Increased expression on Affymetrix arrays of prion proteins seems to be associated with the development of osteosarcoma. Prions seem to induce a negative regulation of apoptosis, thus promoting osteosarcoma development and progression. Osteosarcoma is a very aggressive tumor and even after modern chemotherapy and excision of tumors efforts are needed to improve clinical outcome. Since Prion proteins seem to be related to osteosarcoma development, their inhibition could represent a new approach to the molecular treatment of osteosarcoma. (c) 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:10041012, 2012

A multiple-functionalized targeting delivery system was prepared by self-assembly for efficient delivery of Cas9/sgRNA plasmids to targeted tumor cell nuclei. The Cas9/sgRNA plasmids were compacted by protamine in the presence of calcium ions to form nanosized cores, which were further decorated by peptide and aptamer conjugated alginate derivatives. With the help of the nuclear location signal peptide and AS1411 aptamer with specific affinity for nucleolin in the tumor cell membrane and nuclei, the delivery vector can specifically deliver the plasmid to the nuclei of tumorous cells for knocking out the protein tyrosine kinase 2 (PTK2) gene to down-regulate focal adhesion kinase (FAK). The tumor cell apoptosis induced by genome editing is mitochondrial-dependent. In addition, FAK knockout results in negative regulation on the PI3K/AKT signaling pathway. Meanwhile, favorable modulation on various proteins involved in tumor progression can be realized by genome editing. The enhanced E-cadherin and decreased MMPs, vimentin, and VEGF imply the desirable effects of genome editing on suppression of tumor development. Wound healing and transwell assays confirm that the genome editing system can suppress tumor invasion and metastasis in edited cells efficiently. The investigation provides a facile and effective strategy to fabricate multiple-functionalized delivery vectors for genome editing.