Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0029463 (
osteosarcoma
)
16,637
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Proteins that promote cell migration, attachment and spreading are considered to play an important role in the regulation of cell function. Recently, a 44 kilodalton bone phosphoprotein (44K
BPP
) was shown to enhance the attachment of gingival fibroblasts and osteoblasts in vitro. The potential importance of this attachment protein in the regulation of mineralized tissue homeostasis prompted us to evaluate its ability to promote the attachment and migration of several other cell types. All the fibroblast cell lines and non-transformed calvaria cell lines assayed exhibited enhanced attachment and spreading in response to 44K
BPP
. Rat
osteosarcoma
cells (ROS 17/2.8) expressing osteoblast-like features, exhibited enhanced attachment in response to 44K
BPP
, while non-osteoblast-like cells (ROS 25/1) obtained from the same
osteosarcoma
did not. Two epithelial cell lines, CCL4 and A431, demonstrated enhanced attachment when exposed to fibronectin or laminin, but not 44K
BPP
. Another epithelial-like cell line, HT 1080, derived from a fibrosarcoma, showed enhanced attachment in the presence of all three attachment proteins. Fibronectin, but not 44K
BPP
, promoted the chemotactic migration of fibroblasts. These studies indicate that the role of 44K
BPP
attachment protein in the regulation of cell behavior is not restricted to bone cells.
...
PMID:Cell attachment activity of the 44 kilodalton bone phosphoprotein is not restricted to bone cells. 271 32
Osteosarcoma
(OS) is the most common primary pediatric bone tumor lethal to children and adolescents. Chemotherapeutic agents such as cisplatin are not effective for OS because of their poor accessibility to this cancer and severe systemic toxicity. In this study, a lipophilic platinum(II) complex bearing a bisphosphonate bone-targeting moiety, cis-[PtL(NH
3
)
2
Cl]NO
3
{BPP; L = tetraethyl [2-(pyridin-2-yl)ethane-1,1-diyl]bisphosphonate}, was prepared and characterized by NMR, electrospray ionization mass spectrometry, and single-crystal X-ray crystallography. The cytotoxicity of
BPP
toward OS cell lines U2OS and MG-63 was tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.
BPP
exhibits moderate inhibition against U2OS cells through a mechanism involving both DNA binding and a mevalonate pathway. The acute toxicity of
BPP
to mice is 7-fold lower than that of cisplatin. The relative low systemic toxicity may result from the steric hindrance of the ligand, which blocks
BPP
approaching the bases of DNA. The results suggest that incorporating bisphosphonates into a platinum complex not only enhances its bone-targeting property but also minimizes its reactivity toward DNA and thereby lowers the systematic toxicity of the complex. The diminished cytotoxicity of
BPP
could be compensated for by increasing the therapeutic dose with marginal harm. This strategy provides a new possibility for overcoming the ineffectiveness and systemic toxicity of platinum drugs in the treatment of OS.
...
PMID:A Potential Bone-Targeting Hypotoxic Platinum(II) Complex with an Unusual Cytostatic Mechanism toward Osteosarcoma Cells. 2951 7
