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)

The binding sites for human interferon-alpha (IFN-alpha) have been characterized on human lymphoblastoid, melanoma, rhabdomyosarcoma, and cervical carcinoma cells. Crosslinking of iodinated-recombinant DNA-derived IFN-alpha-Con1, an analog of the known IFN-alpha subtypes, to the cell surface with disuccinimidyl suberate yielded four IFN-receptor complexes of 118, 138, 159, and 260 kD on all cell lines that specifically bind IFN-alpha. Since IFN-alpha exists in solution as monomers, dimers, and trimers, and the three lower molecular weight IFN-alpha-receptor complexes differ by the molecular weight of IFN-alpha (20 kD), this suggests that the human IFN-alpha receptor of 100 kD binds more than one molecule of IFN-alpha. The higher molecular weight complex of 260 kD may result from dimerization of the receptor. None of these complexes was observed in a rhabdomyosarcoma subclone that does not specifically bind IFN-alpha. Pretreatment of cells with trypsin abolished the formation of these complexes. Pretreatment of cells with neuraminidase did not reduce IFN-alpha binding, but increased the electrophoretic mobility of all four IFN-alpha-receptor complexes. Other glycosidases (i.e., mannosidase, beta-galactosidase, and endoglycosidase F) had no effects on IFN-alpha binding or mobility of complexes. Thus, although the IFN-alpha receptor is a glycoprotein, the glycosylated portion is apparently not part of the IFN-alpha-binding domain. The formation of IFN-alpha-receptor complexes is independent of the duration of incubation with IFN (from 5 min to 1 h at 15 degrees C).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of interferon-alpha binding sites on human cell lines. 246 92

The cell uptake of the different forms (I and II) of [57Co]bleomycin A2 and B2 was studied in a Rhabdomyosarcoma cell culture. The results show that the uptake of form I appears to be significantly higher than the uptake of form II. The evidence presented indicates that form I is formed in vivo as well as in vitro from form II by biotransformation. Transferrin stimulates the uptake of Co-bleomycin B2 form I only. As a result of trypsin treatment, it is suggested that form II binds only on the outer cell membrane and is not able to pass this membrane.
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PMID:Labeled bleomycin as a tumor localizing agent III. Selectivity of tumor tissue uptake of the different forms of [57Co] bleomycin A2 and B2. 619 35

The rat R-1 rhabdomyosarcoma with a capacity for colony growth in vitro after excision of the tumour and dissociation by a trypsin method has been used to investigate the effectiveness of radio-chemotherapy. Growth delay data were compared with data on survival of cells derived from tumours treated in situ. An excess in growth delay was observed when vinblastine (1.5 mg/kg) was given at intervals of 0.3 to 2 d after or 4 d before a dose of 20 Gy of X-rays. Cell survival data indicate that the maximum effectiveness of the drug treatment and the combined treatment (vinblastine and a dose of 10 Gy) can be assessed 2 to 3 d after treatment. The fractions of surviving cells determined after combined therapy at 0, 1 and 2 d intervals were not significantly different from the fractions expected on the basis of simple multiplication of the fractions surviving individual treatments. The data suggest that the excess in tumour growth delay observed cannot be accounted for by co-operative interaction of the doses of radiation and drug.
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PMID:Cell survival and growth delay in rat R-1 tumours after radiation and vinblastine treatment. 693 37

The processing of human collagen type-V chains was studied using anti-peptide polyclonal antibodies raised against peptide sequences at the N-terminal non-triple-helical region of pro-alpha 1(V) and pro-alpha 2(V) chains. The anti-peptide polyclonal antibody raised against positions 48-57 of the N-terminal alpha 2(V) sequence recognized the mature form of the human alpha 2(V) chain extracted without any proteolytic treatment from several tissues in the presence of a mixture of protease inhibitors. It also recognized the pro-alpha 2(V) and pN-alpha 2(V) collagen chains secreted in the cell-culture media of the rhabdomyosarcoma A204 cell line. The pN-alpha 2(V) collagen chain from this cell line migrated during electrophoresis with the alpha 2(V) chain obtained from tissues. This demonstrates that the alpha 2(V) chain in tissues is incompletely processed and is present as the pN-alpha 2(V) collagen chain which lacks the C-propeptide. In comparison, an anti-peptide polyclonal antibody raised against residues at positions 284-299 of the N-terminal alpha 1(V) human sequence failed to recognize the mature form of the alpha 1(V) chain while it reacted with the pN-alpha 1(V) collagen chain form. These results suggest that the alpha 1(V) chain undergoes a processing event in the N-terminal region that involves the removal of at least the first 284 residues. Amino acid sequence analysis was performed on cyanogen-bromide-generated or trypsin-generated peptides of the two electrophoretic bands obtained for the tissue form of collagen V. The slower-migrating band corresponding to the intact alpha 1(V) chain gave, as expected, only sequences corresponding to the alpha 1(V) chain. However, the band previously considered to be the intact alpha 2(V) chain also gave sequences for the alpha 1(V) chain in addition to the alpha 2(V) chain. This result indicates the presence in tissue extracts of a further processed form of alpha 1(V) chain which migrates with the intact alpha 2(V) chain. On further analysis, we observed that the two bands of the tissue form of collagen V occurred in a 1:1 ratio whereas, after the pepsin digestion to remove non-collagenous regions, two bands were observed with an alpha 1(V)/alpha 2(V) chain ratio of 3:1. These results indicate that the alpha 1(V) chain exists in an additional stoichiometry, different from [alpha 1(V)]2 alpha 2(V).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Diversity in the processing events at the N-terminus of type-V collagen. 818 82

Previously we showed for coxsackievirus A9 (CAV-9) that specific interactions between the RGD motif of capsid protein VP1 and the alpha v beta 3 integrin are involved in virus binding and entry into green monkey kidney cells (GMK) and some other cell lines. The RGD-recognizing alpha v beta 3 integrin is known as the vitronectin receptor (VNR). During replication in the gut, CAV-9 like all other enteroviruses are exposed to host proteolytic enzymes, and we showed previously that the RGD-containing 15 amino acids long carboxy terminal extension of VP1 is cleaved off by trypsin. The trypsin-treated CAV-9 was still infectious, although at an apparently reduced level as assessed in GMK cells. This indicated that the virus was able to bypass the RGD-dependent entry and possibly use an alternative receptor. We have now found that in RD cells, a human rhabdomyosarcoma cell line, neither RGD-containing oligopeptides nor polyclonal antiserum to VNR are able to protect the cells from CAV-9 infection suggesting that the RGD motif is not involved in binding or entry of the virus into these cells. This result was further confirmed by demonstrating that, in RD cells, the trypsin-treated CAV-9 lacking the RGD-containing insert appeared to be as infectious as the untreated virus. The most striking difference between the virus receptors in the RD and the GMK cells was seen when the rate of virus uncoating was studied. For virus particles bound to the RD cells, the uncoating step started already at 18-20 degrees C and the process went on rapidly at 36 degrees C resulting in complete disintegration of cell-bound virions. In contrast, alpha v beta 3-bound virus particles in the GMK cells appeared to uncoat slowly even at 36 degrees C and during the 90 min observation period only a small, hardly visible fraction was found to be disintegrated. Trypsin-cleaved CAV-9 showed the rapid disintegration kinetics in GMK cells as well suggesting that these cells contain both types of receptor specificity. These results indicate that CAV-9 is able to use two different entry routes into host cells depending on the target cells and on phenotypic properties of the virus regulated by host proteases.
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PMID:Efficient RGD-independent entry process of coxsackievirus A9. 892 Aug 24

HSP47 is a stress protein (heat shock protein) which resides in the endoplasmic reticulum, and is postulated to function as a collagen-specific molecular chaperone. To elucidate the role of HSP47 in procollagen biosynthesis, we have established human embryonic kidney 293 cell lines, which were stably transfected with alpha1(III) procollagen chains with or without HSP47. 293 cells do not produce any extracellular matrix proteins including collagens, and the level of HSP47 expression is almost undetectable in this cell line. Recombinant type III procollagens in 293 cells form trypsin-resistant homotrimers, which are secreted into the medium as trimers in the presence or absence of recombinant mouse HSP47. The secretion of procollagen III was delayed in 293 cells stably transfected with proalpha1(III) collagen chains [293+proalpha1(III) cells] in comparison with human rhabdomyosarcoma cell line RD, which normally produces type III procollagens. In this study, we examined the rate of type III procollagen secretion in detail. In cells cotransfected with mouse HSP47 [293+proalpha1(III)+HSP47 cells], the rate of type III procollagen secretion was slower than in 293+proalpha1(III) cells. The binding of HSP47 with proalpha1(III) collagen chains was confirmed by immunoprecipitation using the chemical cross-linker, DSP. The electrophoretic mobility of proalpha1(III) collagen chains in 293+proalpha1(III) cells was slightly slower than that in RD cells, whereas the recombinant proalpha1(III) chains of 293+proalpha1(III)+HSP47 cells showed almost the same electrophoretic mobility as those of RD cells. The melting temperature (Tm) of type III procollagen in 293+proalpha1(III)+HSP47 cells was almost the same as that in RD cells, and the Tm in 293+proalpha1(III) cells was slightly higher than that in RD cells. These data suggest that the recombinant proalpha1(III) collagen chain is overmodified in 293+proalpha1(III) cells, but not in 293+proalpha1(III)+HSP47 cells.
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PMID:HSP47, a collagen-specific molecular chaperone, delays the secretion of type III procollagen transfected in human embryonic kidney cell line 293: a possible role for HSP47 in collagen modification. 972 80

The WT1 gene encodes a transcription factor implicated in normal and neoplastic development. The purpose of this study was to evaluate the diagnostic utility of a commercial WT1 antibody on a variety of pediatric small round blue cell tumors (SRBCT). A mouse monoclonal antibody (clone: 6F-H2, DAKO) raised against the N-terminal amino acids 1-181 of the human WT1 protein was tested. Microscopic sections from 66 specimens were stained using an antigen retrieval protocol with trypsin. The tumors included peripheral neuroectodermal tumors (PNET/Ewing's), neuroblastomas, desmoplastic small round cell tumors (DSRCT), lymphomas, Wilms' tumors, and rhabdomyosarcomas (RMS). One RMS case was investigated by Western blot analysis and RT-PCR to confirm the antibody specificity. A strong cytoplasmic staining was demonstrated in all RMS (11/11). The Western blot analysis confirmed the WT1 protein in the tissue, and the RT-PCR confirmed the presence of WT1 mRNA in the peripheral blood and tissue of one RMS patient. The Wilms' tumors had a variable nuclear and/or cytoplasmic positivity in most (17/24) cases. All PNET/Ewing's were negative. The nuclei of two lymphoblastic lymphomas stained strongly. A weak nuclear or cytoplasmic staining was reported in a few DSRCT (3/5), lymphomas (2/10), and neuroblastomas (2/8). This is a useful antibody in the differentiation of RMS from other SRBCTs. A strong cytoplasmic staining favors an RMS, and a strong nuclear staining is suggestive of a Wilms' tumor. A role for WT1 in the pathogenesis of rhabdomyosarcomas is raised. The limited sampling precludes any conclusions regarding the value of tissue or peripheral blood analysis for WT1 mRNA in patients with rhabdomyosarcoma.
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PMID:The expression of WT1 in the differentiation of rhabdomyosarcoma from other pediatric small round blue cell tumors. 1461 59