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)

Analysis of mortality rates for all childhood (age less than 20 years) leukemias in upstate New York showed declines between 1969-1971 and 1978-1980 for ages 0-4 and 5-9 years, while data from a population-based cancer registry for a population of about 10.5 million indicated no decline in incidence rates. Survival rates were examined for 552 children diagnosed with acute lymphocytic leukemia (ALL) in 1973-1980 at less than 15 years of age. There was some evidence for improvement in survival rates over these years of diagnosis, especially among children diagnosed at ages 1-4 and 10-14 years. Hazard rates increased among cases (especially males) diagnosed in 1979 and 1980, however, and this finding requires confirmation from other studies; the possible effect of influenza epidemics also should be explored. Only one confirmed second primary cancer, a rhabdomyosarcoma of the eye, was ascertained (as of the end of 1983), but longer follow-up is needed on children with ALL.
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PMID:Recent trends in incidence and mortality rates for leukemias, and in survival rates for childhood acute lymphocytic leukemia, in Upstate New York. 345 21

The combination of dacarbazine and doxorubicin was given to 26 children with untreated rhabdomyosarcoma to determine its efficacy as front-line chemotherapy. A treatment course consisted of 250 mg/m2 of dacarbazine given iv on Days 1-5 and 60 mg/m2 of doxorubicin given iv on Day 1. After three courses of therapy, 17 patients (65%) achieved partial response and nine failed to respond. The side effects of treatment consisted of nausea, vomiting, flu-like symptoms, neutropenia associated with fever, mucositis, and thrombocytopenia (rarely). Although the response rate is comparable to other drug combinations, the lack of complete responses to the combination indicates that it is less effective as front-line therapy.
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PMID:Combination of dacarbazine and doxorubicin in the treatment of childhood rhabdomyosarcoma. 402 41

Carboxylesterases are a ubiquitous class of enzymes thought to be involved in xenobiotic metabolism and detoxification. Primary amino acid sequence data suggest that these proteins localize to the endoplasmic reticulum. However, since this family of proteins is highly homologous, the generation of specific reagents to monitor expression and subcellular localization has been unsuccessful. To accomplish in situ detection of a human alveolar macrophage carboxylesterase and a rabbit liver carboxylesterase, we constructed plasmids that expressed recombinant proteins containing an 11 amino acid influenza hemagglutinin tag near the C-terminus. These proteins retained carboxylesterase activity as determined by the conversion of o-nitrophenol acetate to o-nitrophenol. Following transfection of plasmids encoding these proteins into mammalian cells, cells were analyzed by both fluorescence and electron microscopy. The tagged enzymes were localized to the endoplasmic reticulum of both Cos7 monkey kidney cells and Rh30 human rhabdomyosarcoma cells. No tagged protein was detectable in the culture media. Hence, epitope tagging allowed the analysis of expression and localization of specific carboxylesterases. The methods described in this paper are, therefore, applicable to any protein, including those that are highly homologous to other candidate molecules.
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PMID:In situ subcellular localization of epitope-tagged human and rabbit carboxylesterases. 966 12

DNA vaccines have been shown to be an effective means of inducing cytotoxic T-lymphocyte (CTL) responses in both young and aged mice. Better understanding of the pathways by which antigens encoded by DNA vaccines are processed and presented to CTL may allow for improvements in CTL responses in older animals. Since CTL recognize short peptides presented by MHC class I molecules, and since ubiquitin-dependent proteolysis is widely believed to be responsible for degradation of endogenously synthesized antigens and generation of these peptide ligands, we sought to use ubiquitin (Ub) conjugation to target influenza virus nucleoprotein (NP) antigen into the Ub-proteasome degradation pathway for MHC class I-restricted antigen processing and presentation. However, the addition of the Ub moiety did not affect the half-life of Ub-NP protein in transiently transfected human rhabdomyosarcoma (RD) cells. Moreover, the modifications of NP DNA vaccine with Ub conjugation did not affect their ability to induce a CTL response specific for the H-2Kd-restricted NP147-155 epitope, as assessed by both percent cytolysis in bulk CTL culture and by CTL precursor (CTLp) frequency in limiting dilution analysis (LDA). In contrast, the anti-NP antibody (Ab) responses were dramatically reduced in mice immunized with low doses (1 microgram) of Ub-NP constructs, compared with mice immunized with wild-type NP DNA. These results demonstrate that Ub conjugation alone does not guarantee targeting of endogenously synthesized antigens for rapid degradation by proteasomes. Furthermore, the ability of ubiquintination to reduce Ab responses to NP without affecting CTL responses suggests that the Ub modifications result in a lower availability of full-length NP from transfected cells in vivo. The implications of these data on antigen presentation and cross-priming are discussed.
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PMID:Induction of MHC class I-restricted CTL response by DNA immunization with ubiquitin-influenza virus nucleoprotein fusion antigens. 977 46

Skeletal muscle differentiation and the activation of muscle-specific gene expression are dependent on the concerted action of the MyoD family and the MADS protein, MEF2, which function in a cooperative manner. The steroid receptor coactivator SRC-2/GRIP-1/TIF-2, is necessary for skeletal muscle differentiation, and functions as a cofactor for the transcription factor, MEF2. SRC-2 belongs to the SRC family of transcriptional coactivators/cofactors that also includes SRC-1 and SRC-3/RAC-3/ACTR/AIB-1. In this study we demonstrate that SRC-2 is essentially localized in the nucleus of proliferating myoblasts; however, weak (but notable) expression is observed in the cytoplasm. Differentiation induces a predominant localization of SRC-2 to the nucleus; furthermore, the nuclear staining is progressively more localized to dot-like structures or nuclear bodies. MEF2 is primarily expressed in the nucleus, although we observed a mosaic or variegated expression pattern in myoblasts; however, in myotubes all nuclei express MEF2. GRIP-1 and MEF2 are coexpressed in the nucleus during skeletal muscle differentiation, consistent with the direct interaction of these proteins. Rhabdomyosarcoma (RMS) cells derived from malignant skeletal muscle tumors have been proposed to be deficient in cofactors. Alveolar RMS cells very weakly express the steroid receptor coactivator, SRC-2, in a diffuse nucleocytoplasmic staining pattern. MEF2 and the cofactors, SRC-1 and SRC-3 are abundantly expressed in alveolar and embryonal RMS cells; however, the staining is not localized to the nucleus. Furthermore, the subcellular localization and transcriptional activity of MEF2C and a MEF2-dependent reporter are compromised in alveolar RMS cells. In contrast, embryonal RMS cells express SRC-2 in the nucleus, and MEF2 shuttles from the cytoplasm to the nucleus after serum withdrawal. In conclusion, this study suggests that the steroid receptor coactivator SRC-2 and MEF2 are localized to the nucleus during the differentiation process. In contrast, RMS cells display aberrant transcription factor SRC localization and expression, which may underlie certain features of the RMS phenotype.
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PMID:Subcellular localization of the steroid receptor coactivators (SRCs) and MEF2 in muscle and rhabdomyosarcoma cells. 1132 58