Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hexabrachions are extracellular proteins expressed in certain tissues and at specific points in development. cDNA sequencing has revealed that they contain a region of repeats that are similar to the type III homology units of fibronectin. The corresponding region of fibronectin contains heparin- and DNA-binding domains. We have compared the heparin and DNA binding of hexabrachion secreted by the human glioblastoma cell line U87MG to that of fibronectin. Both proteins bound to heparin-agarose in low salt (0.05 M NaCl) buffers. Using linear salt gradients, hexabrachion was eluted from heparin prior to fibronectin. The addition of 5 mM CaCl2 decreased the affinity of both proteins for heparin, but it had a greater effect upon the binding of fibronectin. Free heparin but not chondroitin sulfate inhibited the binding of both proteins to heparin-agarose. In addition, hexabrachion bound to DNA as fibronectin does, and this binding could be inhibited by heparin but not by chondroitin sulfate. Unlike fibronectin, hexabrachion did not bind to gelatin when samples containing both proteins were passed over gelatin-agarose, also indicating that there was no interaction between hexabrachion and fibronectin. In contrast to hexabrachion isolated from brain, the protein secreted by the human glioblastoma cell line U87MG does not bear the HNK-1 epitope which is on a carbohydrate that can mediate interactions between cells.
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PMID:Binding of hexabrachions to heparin and DNA. 247 87

In vitro, when using low concentrations of ferritin (ng/ml) or CaCl2 (micrograms/ml), multiplication of a human, 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU)-resistant glioblastoma cell line (U251) is enhanced 1.5 to 2 times more actively than multiplication of a normal astrocyte line (CRL 1656). Ferritin and Ca2+ ions exhibit a marked effect on DNA isolated from these cells: glioblastoma DNA relaxation is strongly increased (as evidenced by increased 260 nm ultraviolet absorbance), being from 5 to 6 times that of astrocyte DNA, which remains only slightly affected. Under identical experimental conditions, Zn2+ and gallium ions selectively inhibit glioblastoma cell multiplication but at the same concentrations do not inhibit astrocyte multiplication. Ultraviolet absorbance measurements demonstrate that both of these agents condense relaxed glioblastoma DNA in vitro. Zn2+ or gallium ions added to culture medium containing stimulatory concentrations of ferritin or Ca2+ ions selectively and strongly inhibit enhancement of glioblastoma cell multiplication by these mitogens while not affecting normal multiplication of astrocytes.
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PMID:Differential effects of ferritin, calcium, zinc, and gallic acid on in vitro proliferation of human glioblastoma cells and normal astrocytes. 814 3

Major drawbacks to present-day cancer chemotherapy are its intrinsic lack of selectivity for tumour cells, resulting in severe damage to normal rapidly dividing cells, and the widespread emergence of drug resistance. Here experimental evidence is presented demonstrating that PB-100, a beta-carboline alkaloid, selectively inhibits in vitro multiplication of human BCNU-resistant glioblastoma cells (U251), but has no effect on normal astrocyte (CRL 1656) multiplication. PB-100 activity is dose-dependent. In the presence of ferritin or CaCl2, which are highly mitogenic for glioblastoma cells, higher doses of the alkaloid are required to inhibit multiplication completely. PB-100 is one of several compounds which were selected for their specific action on cancer DNA and cells, together with lack of activity on normal DNA and cells. Both the selectivity of PB-100 and its ability to overcome drug resistance stem from its effect on cancer DNA secondary structure. This activity is described and discussed, and therapeutic applications are mentioned.
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PMID:PB-100: a potent and selective inhibitor of human BCNU resistant glioblastoma cell multiplication. 829 50