Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Osteosarcoma is major cause of cancer-related death in the pediatric age group, and this is due to the development of pulmonary metastases that fail to be eradicated with current treatment regimes. Although there have been significant improvements in the long-term survival of such patients, 25-50% with initially non-metastatic disease, subsequently develop metastases and this remains the major cause of death for these patients. In this study, we report the multimodal activity of pigment epithelium-derived factor (PEDF) in inhibiting osteosarcoma growth, angiogenesis and metastasis. In vitro, we found that administration of recombinant PEDF (rPEDF) on two osteosarcoma cell lines (rat UMR 106-01 and human SaOS-2) significantly reduced tumor cell proliferation and increased apoptosis, as well as decreased cell invasion, angiogenesis, and increased adhesion to collagen type-1. Administration of rPEDF upregulated the mRNA expression of phenotypic osteoblast differentiation markers (ALP, pro-alpha(1) collagen and osteocalcin) in a pre-osteoblastic cell line, UMR 201, and also increased mineralized nodule formation in both UMR 106-01 and SaOS-2. In vivo, rPEDF dramatically suppressed primary osteosarcoma growth and the development of macroscopic pulmonary metastases in an orthotopic model of human osteosarcoma (SaOS-2). Interestingly, no activity was seen in tumors grown subcutaneously, suggesting a paracrine interaction between PEDF and the bone microenvironment. Preliminary pharmacoevaluation studies demonstrated rPEDF stability within media containing serum and osteosarcoma cells, and no gross systemic toxicity was observed in vivo with rPEDF administration. These results suggest that PEDF is emerging as an attractive and clinically appealing drug candidate for the treatment of osteosarcoma.
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PMID:Inhibition of orthotopic osteosarcoma growth and metastasis by multitargeted antitumor activities of pigment epithelium-derived factor. 1745 11

Osteosarcoma (OS) is a disease that afflicts teenagers and adolescents in the prime of their lives. In spite of surgery and therapies currently used, there is a 1/3 chance of relapse. As for other cancers, current research is largely devoted to elucidating the molecular basis of the disease, with the anticipation that such research will lead to discovery and development of biological therapies. The major advantage of utilising such therapy is the relative lack of toxicity to normal tissues. One such enterprising candidate molecule, pigment epithelium-derived factor (PEDF), has recently been implicated to be involved in control of OS in orthotopic spontaneously metastasising models of the disease, whether administered as recombinant protein, overexpressed or administered as short peptides derived from the parent molecule. Expression of PEDF is inversely proportional to expression of vascular endothelial growth factor (VEGF) at the growth plate cartilage layer of growing bone in both mice and man. PEDF, originally discovered for its potent antiangiogenic activity, is now established as an anticancer factor with multiple mechanisms at its disposal for tumour inhibition. Current efforts are devoted to develop drug delivery systems, such as controlled release nanoparticles, that can be used to progress this potential drug candidate closer towards clinical trials for OS.
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PMID:PEDF as an emerging therapeutic candidate for osteosarcoma. 1907 91

Osteosarcoma (OS) is the most common type of malignant bone cancer, and the sixth most common type of cancer in children and young adults. Currently, gene therapy is being evaluated as a novel method for OS treatment. Here we report on an in situ gelling chitosan-based hydrogel system that sustains the release of a potential anti-cancer gene (pigment epithelium-derived factor) to the tumor site. A significant reduction of the primary OS in a clinically relevant orthotopic model was measured. The combination of plasmid treatment and chemotherapy together with the use of this delivery system led to the highest suppression of tumor growth without side effects. The results obtained from this study demonstrate the potential application of a biodegradable hydrogel technology as an anti-cancer drug delivery system for successful chemo-gene therapy.
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PMID:A chitosan hydrogel delivery system for osteosarcoma gene therapy with pigment epithelium-derived factor combined with chemotherapy. 1950 19

Bone homeostasis is maintained through a balance between bone formation and resorption. Bone resorption is mainly carried out by a specific type of cell called the osteoclast (OCL). Previously, expression of pigment epithelium-derived factor (PEDF), the most potent endogenous inhibitor of angiogenesis, has been demonstrated in bone tissue and it known to induce differentiation in osteoblastic cells. Furthermore, therapeutic effects of PEDF on osteosarcoma, a prevalent primary bone tumor, with inhibition of bone destruction has been shown. Thus, PEDF is possibly involved in bone homeostasis as an inhibitor of bone resorption. To address this involvement, we studied the effect of PEDF on OCL function. OCL differentiation, RANKL-mediated survival and bone resorption activity were inhibited by PEDF in a dose-dependent manner. PEDF upregulated osteoprotegerin (OPG), which naturally blocks OCL maturation, in primary osteoblasts and OCL precursor cells. These results suggest that PEDF inhibits OCL function via regulating OPG expression, and thereby contributes to the maintenance of bone homeostasis.
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PMID:PEDF regulates osteoclasts via osteoprotegerin and RANKL. 1994 27

The potent antiangiogenic pigment epithelium-derived factor (PEDF) has shown promise against osteosarcoma, a tumour that originates in the bone and metastasises to the lungs. Neurotrophic, antiangiogenic, antiproliferative, and antimetastatic properties of PEDF have been attributed to a number of functional epitopes on the PEDF glycoprotein. StVOrth-2 (residues 78-102) and StVOrth-3 (residues 90-114) are two PEDF-derived peptides based on these functional epitopes. StVOrth-2 has previously been shown to inhibit osteosarcoma cell proliferation, while StVOrth-3 increased osteosarcoma cell adhesion to collagen I in vitro. In this paper, we have evaluated systemically and continuously delivered StVOrth-2 and StVOrth-3 using a clinically relevant murine model of osteosarcoma with spontaneous metastasis. Treatment with StVOrth-2 or StVOrth-3 with microosmotic pumps was initiated after primary osteosarcoma was established in the tibia. While treatment with StVOrth-2 and StVOrth-3 did not appear to affect local tumour invasion, tumour necrosis or apoptosis, StVOrth-2 predominantly restricted the growth of primary tumours, while StVOrth-3 restricted the burden of pulmonary metastatic disease. No peptide caused gross toxicity in mouse tissues as assessed by measuring weight of animals, serum biochemistry, and gross tissue observation. The differential effects exhibited by StVOrth-2 and StVOrth-3 in this orthotopic model of osteosarcoma may be related to the functional epitopes on the PEDF glycoprotein that they represent.
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PMID:Efficacy of continuously administered PEDF-derived synthetic peptides against osteosarcoma growth and metastasis. 2270