Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0035412 (rhabdomyosarcoma)
 6,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In cytosols from human rhabdomyosarcoma xenografts, the formation of vincristine (VCR)-tubulin complex and its stability were increased by GTP (Bowman et al.: Biochem. Biophys. Res. Commun., 135:695-700, 1986). We have further examined this modulation to determine whether a) GTP was protecting the VCR binding site from denaturation, b) the enhancement of complex formation was guanosine specific, and c) whether this influence was a direct interaction between GTP, VCR, and tubulin, or was mediated through another factor. In GTP-depleted cytosols from tumor xenografts HxRH18 and HxRh12, VCR binding activity was stable for at least 2 hours at 37 degrees C, indicating that the enhancement of complex formation and stability was not due to protection of tubulin integrity as measured by VCR binding; 10 nM GTP increased complex formation slightly, with complex formation increasing as GTP concentrations were increased to 5 microM, where maximum effect was observed. GTP and GDP (0.1 mM) both increased complex formation three-fold, while GMP, GMP-PNP, and ITP increased formation 1.5-fold. IMP, CTP, and ATP had no significant effect. Therefore, the modulation of VCR binding was relatively specific for the guanine nucleotides GDP and GTP. Microtubule protein, purified from Rh18 and Rh12 tumors by cycles of polymerization-depolymerization, bound VCR rapidly and binding was not influenced by GTP. This suggested that GTP modulation of VCR binding in cytosols was through a soluble factor lost in tubulin purification. In experiments with cytosol fractionated by molecular weight, there was inhibition of VCR binding activity by fractions with an mw range 20-50 kD. This inhibition was decreased by 25% by the addition of GTP. These data suggest that in tumor cytosols there may be competition between VCR and a natural ligand that is modulated by GTP. Two potential models for VCR binding are proposed.
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PMID:Influence of guanine nucleotides on vincristine binding in tumor cytosols and purified tubulin: evidence for an inhibitor of vincristine binding. 239 73

The influence of GTP on the formation and stability of [3H] vincristine (VCR)-tubulin complexes in cytosols from two human rhabdomyosarcoma xenografts which have different sensitivities to VCR has been evaluated. After removal of endogenous GTP the initial rate of [3H]VCR binding and the maximal level of bound drug were 2- to 3-fold higher in the presence of 0.1 mM GTP than in its absence. Similarly, the stability of complexes was GTP-dependent. Complex formed from Rh18 tumors, only moderately sensitive to VCR, dissociated at 37 degrees in the absence of GTP with a half-time of 67 min; complex from Rh12 tumors (exquisitely sensitive to VCR) was more stable. Neither complex dissociated in the presence of 0.1 mM GTP over 2 hr examined.
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PMID:GTP influences the binding of vincristine in human tumor cytosols. 396 72

beta-Adrenergic receptors were demonstrated in membrane preparations from 6 human Ewing's sarcomas and compared to those from 46 other pediatric cancers with the use of the beta-adrenergic antagonist (-)-(3H)dihydroalprenolol [(-)[3H]DHA]. In contrast to the high numbers of receptor sites found in Ewing's sarcomas (55-640 fmol x mg-1 protein; dissociation constant Kd, 1-2 nM), other childhood cancers (neuroblastoma, rhabdomyosarcoma, brain tumors, lymphoma, osteosarcoma, hepatoblastoma, yolk sac, and Wilms' tumor) contained in general fewer beta-adrenergic receptor sites. Characteristics of (-)-[3H]DHA binding were therefore more fully characterized in the Ewing's tumors. Competition of (-)-[3H]DHA binding by classical catecholamine agonists, as well as by subtype selective agents metoprolol and zinterol, demonstrated the presence of a homogeneous population of beta 1-adrenergic sites in several Ewing's tumors. Adenylate cyclase activity in all Ewing's sarcomas was enhanced by GTP and NaF. However, in spite of high numbers of beta-adrenergic receptors, (-)-isoproterenol was not very effective in the activation of adenylate cyclase activity in several of the Ewing's tumors tested. Neither guanyl-5'-yl-imidophosphate nor GTP altered agonist potency for the receptor site in these catecholamine-insensitive tumors. Hill coefficients obtained from the competition experiments with (-)-isoproterenol (in the presence or absence of guanine nucleotide) were approximately 1.0. These uncoupled receptors were resistant to N-ethylmaleimide denaturation and were densensitized only 50% during culture in the presence of (-)-isoproterenol. Thus Ewing's sarcomas are relatively rich in beta-adrenergic sites, and several tumors appear to have a coupling lesion involving guanine nucleotide-dependent regulatory protein interaction with beta-adrenergic receptors and adenylate cyclase, similar in phenotype to that described in the (unc) variant of S49 mouse lymphoma.
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PMID:beta-Adrenergic receptors in pediatric tumors: uncoupled beta 1-adrenergic receptor in Ewing's sarcoma. 631 52

BA-Han-1C rat rhabdomyosarcoma cells grow with a transformed phenotype and do not differentiate efficiently. Here, we report that these cells can be induced with pertussis toxin (PTX) to rapidly express the myogenin gene and form terminally differentiated myotubes. Potential targets for the effect mediated by PTX are G alpha i-2 and G alpha i-3 proteins, the only inhibitor GTP-binding proteins expressed in these cells. While G alpha i-2 is found at the plasma membrane, G alpha i-3 is predominantly associated with Golgi vesicles and endoplasmic reticulum, suggesting that it may regulate protein trafficking. Differentiation of BA-Han-1C cells can also be induced by suramin, heparin, and other polyanions. As these compounds bind certain peptide growth factors, we assume that differentiation of BA-Han-1C cells is blocked by pathways involving autocrine or paracrine acting growth stimulating peptides. We present evidence that bFGF and cAMP inhibit induced differentiation in BA-Han-1C cells similar to normal myogenic cell lines, suggesting that signaling pathways mediated by these compounds are unaltered.
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PMID:Differentiation of BA-HAN-1C rhabdomyosarcoma cells is controlled by a pertussis toxin sensitive signaling pathway. 829 37