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 studying the bioenergetics of living cells, the microfluorometric analysis of coenzyme (NAD(P)H) responses to microinjected respiratory and glycolytic substrates enables, in principle, a search for qualitative/quantitative differences in normal versus carcinogen-treated (short-term, long-term) and malignant cells. Responses are compared in L-cells, same adapted to hypertonic media (i.e. L255, L355) and highly malignant rhabdomyosarcoma (CCL 136) cells. The largest responses to respiratory substrate (malate, isocitrate) and the lowest responses to glycolytic substrate (glucose-6-P) are in the L255, 355 cells which exhibit structural rearrangement and dense packing of mitochondria possibly due to high energy requirement for ion pumping. The converse is observed in the CCl 136 where there is no lack of these organelles, but they could be functionally deficient, as suggested by a predominant response to glucose-6-P compared to malate. In the control L-cell, the malate and glucose-6-P responses are relatively well balanced. Upon addition of dimethylnitrosamine to L-cells, there is an initial acceleration in the rate of glucose-6-P-induced NAD(P) reduction (? NADPH requirement for dimethylnitrosamine metabolization), followed by an upsurge of the malate response. In L355 cells, addition of the carcinogens dimethylnitrosamine or ethionine is followed by a strong reductive response to malate, and minimal response to glucose-6-P. The dramatic intensification of the NAD(P)H response to malate in L355 cells pretreated with an ATP trap (ethionine) or an uncoupler (dinitrophenol) strongly points to a requirement for ATP depletion. Weaker enhancement of NAD(P)H response (preferentially after glucose-6-P) is observed in the CCL 136 upon treatment with ethionine. The findings indicate the need for further study on differences in respiratory/glycolytic pathways and efficiency of ATP cycle in malignant cells exhibiting graded differences of structural/functional specialization.
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PMID:The differential effects of dimethylnitrosamine and ethionine on mitochondrial and extramitochondrial dehydrogenases in single intact cells. 669 53

We have isolated cDNAs and completed for the first time the primary structure for a novel collagenous chain that was partially characterized earlier and named alpha 1(Y) chain [Yoshioka, H. et al. (1992) Genomics 13, 884-886]. The size of the coding region was unexpectedly small compared with the length of the mRNA (> 10 kb), owing to the presence of a long 3' untranslated region (> 5 kb). The predicted polypeptide contained 1,142 amino acid residues with a 23-residue signal peptide consisting of 5 collagenous domains of 70-224 residues in length, interspersed and flanked with 6 noncollagenous (NC) domains. The primary structure is distinct from those of the 32 known collagen alpha-chains of types I through XVIII. Therefore, we designate this newly discovered collagen chain the alpha 1 chain of type XIX collagen. Sequence analysis suggested that this chain belongs to the recently discovered group of collagens known as FACITs (fibril associated collagens with interrupted triple-helices). Northern blotting analysis demonstrated hybridization of the cDNA to a large mRNA species (> 10 kb) extracted from a rhabdomyosarcoma cell line (CCL 136). We also isolated numerous truncated cDNA clones of which the 3' parts were different from the "proto" type of the mRNA of > 10-kb size. Sequence comparison between cDNAs and corresponding genomic DNA fragments indicated that unusual splicing events occurred through insufficient recognition at acceptor sites. Expression of the gene was extremely infrequent in the rhabdomyosarcoma cell line; it could be restricted to certain animal tissues both temporally and spatially during early development.
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PMID:The mRNA for alpha 1(XIX) collagen chain, a new member of FACITs, contains a long unusual 3' untranslated region and displays many unique splicing variants. 777 80

In vitro aggregation and fibrillization of synthetic amyloid beta-protein Abeta 1-40 was assessed in the conditioned media from rhabdomyosarcoma (CRL 1598, HTB 82, HTB 153, CCL 136), adenocarcinoma (CCL 218), neuroblastoma (SY5Y), and COS cells cultured in the absence and presence of 10% heat-inactivated fetal bovine serum (FBS). The aggregation and formation of cross beta-pleated sheet structures in Abeta was quantitated by Thioflavin T (ThT) fluorescence spectroscopy, while the morphology of Abeta fibrils was examined in negative staining in the electronmicroscope (EM). In cultures supplemented with 10% FBS, the conditioned media from CRL 1598, HTB 82, CCL 218, and SY5Y cell cultures stimulated Abeta aggregation in a time-dependent manner as compared to that of control (serum-containing medium that had not been exposed to cells). The order of stimulation was SY5Y > CRL 1598 > or = HTB 82 > CCL 218, and the stimulation was higher in 2 week cultures than in 1 week cultures. Similar studies using media from HTB 153, CCL 136 and COS cell cultures showed no effect on Abeta 1-40 aggregation. In serum-free cell cultures, only media from SY5Y and CRL 1598 could promote significant aggregation of Abeta 1-40. Negative staining in EM revealed Abeta fibril formation only with conditioned media from SY5Y and CRL 1598 cultured under serum free conditions; no Abeta fibrils were noticed in media from cell cultures supplemented with 10% FBS. We propose that both the SY5Y neuroblastoma cell line and the CRL 1598 rhabdomyosarcoma cell line may serve as experimental models for in vitro studies of extracellular aggregation and fibrillization of Abeta-protein in cell cultures, while rhabdomyosarcoma HTB 82 and adenocarcinoma CCL 218 may be models for study of Abeta aggregation only.
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PMID:Media from rhabdomyosarcoma and neuroblastoma cell cultures stimulate in vitro aggregation and fibrillization of amyloid beta-protein. 901 50

Namitecan (ST1968), a novel hydrophilic camptothecin analog of the 7-oxyiminomethyl series, was selected for clinical development on the basis of its promising preclinical efficacy. Since there is clinical evidence of efficacy of camptothecins against pediatric tumors, this study was performed to explore the antitumor and antiangiogenic activity of the camptothecin derivative in pediatric sarcoma models. With the exception of an undifferentiated rhabdomyosarcoma (A204), namitecan exhibited curative efficacy even at well-tolerated suboptimal doses in a panel of five models. The good therapeutic index of namitecan likely reflected a high and persistent drug accumulation at tumor site. The four responsive tumors were characterized by high topoisomerase I expression. In the RD/TE-671 rhabdomyosarcoma model the drug activity was associated with a marked antiangiogenic effect, which was consistent with the downregulation of proangiogenic factors, including VEGF, bFGF and the multifunctional chemokines CCL-2 and CXCL16. In agreement with this modulation, the combination of low doses of namitecan with other antiangiogenic agents, such as bevacizumab (a humanized anti-VEGF antibody) and sunitinib (a multitarget tyrosine kinase inhibitor effective against receptors implicated in the angiogenesis process), enhanced the antitumor effects. In conclusion, this preclinical study provides evidence of curative efficacy of namitecan at well-tolerated doses against pediatric sarcoma models, likely reflecting a contribution of antiangiogenic effects. Based on the promising therapeutic profile, namitecan is a good candidate for clinical evaluation in pediatric sarcomas.
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PMID:The curative efficacy of namitecan (ST1968) in preclinical models of pediatric sarcoma is associated with antiangiogenic effects. 2252 22

Rhabdomyosarcoma (RMS) is a devastating tumor of young people that is difficult to cure. To determine if oncolytic virus therapy can improve outcomes in individuals with RMS, myxoma virus expressing a red fluorescent protein (MYXV-red) was evaluated for antitumoral effects using a murine model of RMS. Fluorescent protein was expressed in four RMS cell lines inoculated with MYXV-red, indicating that these cells were semipermissive to MYXV infection. MYXV-red replication and cytopathic effects were further evaluated using human embryonal RMS (CCL-136) cells. Logarithmic growth of MYXV-red and significant cell death were observed 72 hours after inoculation with MYXV. The oncolytic effects of MYXV-red were then studied in nude mice that were injected subcutaneously with CCL-136 cells to establish RMS xenografts. Once tumors measured 5 mm in diameter, mice were treated with multiple intratumoral injections of MXYV-red or saline. The average final tumor volume and rate of tumor growth were significantly decreased, and median survival time was significantly increased in MYXV-red-treated mice (P-values =0.0416, 0.0037, and 0.0004, respectively). Histologic sections of MYXV-red-treated tumors showed increased inflammation compared to saline-treated tumors (P-value =0.0002). In conclusion, MXYV-red treatment of RMS tumors was successful in individual mice as it resulted in decreased tumor burden in eight of eleven mice with nearly complete tumor remission in five of eleven mice. These data hold promise that MYXV-red treatment may be beneficial for people suffering from RMS. To our knowledge, this is the first report of successful treatment of RMS tumors using an oncolytic poxvirus.
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PMID:Myxoma virus therapy for human embryonal rhabdomyosarcoma in a nude mouse model. 2757 97