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

Human coronaviruses have been associated with common colds, diarrhea and enterocolitis, and have been implicated in multiple sclerosis. HLA class I molecules may play a critical role as receptor for OC43 because monoclonal antibody (mAb)W6/32 to HLA-A, -B and -C specificities completely blocks infectivity in human rhabdomyosarcoma (RD) cells. The role of HLA class 1 antigen as the virus receptor was examined using HLA-A3.1 stably transfected human plasma cells and untransfected HMY.C1R cells which do not express HLA-A and -B molecules. When the cells (5 x 10(6)) were infected at a multiplicity of one, the HLA.A3 transfected cells produced 10(8) PFU of virus whereas no replication occurred in the HMY.C1R cells mAb W6/32 reduced the virus yield by 99.9%. Cell membranes from HMY.C1R, HMY.A3 cells and chicken erythrocytes were biotinylated as live cells. Immunoprecipitation with polyclonal antiviral antibody to detect binding of biotinylated cell membranes to virus revealed that biotinylated HMY.A3 membranes coprecipitated with virus-antibody complexes when the immunoprecipitates were electrophoresed on SDS-PAGE gel, electroblotted and stained with Avidin-horseradish peroxidase. The results provide direct evidence that OC43 virus can recognize HLA class I as receptor on the cell surface.
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PMID:Human coronavirus OC43 interacts with major histocompatibility complex class I molecules at the cell surface to establish infection. 795 63

MAGE, BAGE and GAGE genes encode tumor-associated antigens that are presented by HLA class I molecules and recognized by CD8(+) cytolytic T lymphocytes. These antigens are currently regarded as promising targets for active, specific tumor immunotherapy because MAGE, BAGE and GAGE genes are expressed in many human cancers of different histotype and are silent in normal tissues, with the exception of spermatogonia and placental cells. MAGE, BAGE and GAGE gene expression has been extensively studied in different tumors of adults but is largely unknown in many forms of pediatric solid cancer. Using RT-PCR, we analyzed MAGE-1, MAGE-2, MAGE-3, MAGE-4, MAGE-6, BAGE, GAGE-1,-2 or -8 and GAGE-3,-4,-5,-6 or -7b gene expression in 31 samples of pediatric rhabdomyosarcoma, the most frequent form of malignant soft tissue tumor in children. MAGE genes were expressed in a substantial proportion of patients (MAGE-1, 38%; MAGE-2, 51%; MAGE-3, 35%; MAGE-4, 22%; MAGE-6, 35%), while expression of BAGE (6%); GAGE-1, GAGE-2 and GAGE-8 (9%); and GAGE-3, GAGE-4, GAGE-5, GAGE-6 and GAGE-7B (16%) was less frequent. Overall, 58% of tumors expressed at least 1 gene, and 35% expressed 3 or more genes simultaneously. Our data suggest that a subset of rhabdomyosarcoma patients could be eligible for active, specific immunotherapy directed against MAGE, BAGE and GAGE antigens.
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PMID:MAGE, BAGE and GAGE gene expression in human rhabdomyosarcomas. 1139 26

An abnormal HLA expression has been detected in some tumors including rhabdomyosarcoma (RMS). Classical cytotoxic treatment of these tumors, the most common childhood soft tissue malignancy, may induce multidrug resistance (MDR) associated with the expression of a 170-kDa membrane-associated glycoprotein (P-glycoprotein). In order to analyse the connection between modulation of HLA expression and the development of the MDR phenotype mediated by P-glycoprotein in RMS, we used three resistant RMS cell lines; two of these resistant cell lines (TE.32.7.DAC and RD-DAC) were established by in vitro exposure to actinomycin D, a drug of choice in the treatment of RMS; the resistant RMS- GR cell line was established from an embryonal RMS tumor after polychemotherapy. Our results showed that all the resistant cell lines showed a significant increase in the expression of HLA class I surface antigens in comparison to drug-sensitive cells. Blockade of P-glycoprotein with verapamil led to a decrease in HLA class I expression in RMS resistant cell lines. However, no modulation of HLA class II expression was observed in any of the three analyzed cell lines. These findings support the hypothesis that the development of resistance mediated by mdr 1/P-glycoprotein, directly influences the expression of HLA class I in RMS cells, inducing to upregulation. This effect may be relevant to the application in RMS of immunotherapy against tumor-associated antigens presented by HLA class I molecules.
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PMID:Modulation of HLA class I expression in multidrug-resistant human rhabdomyosarcoma cells. 1274 Jun 41

Effectiveness of conventional cytotoxic treatment of rhabdomyosarcoma (RMS) may be limited by the development of multidrug resistance (MDR) mediated by mdr1 gene. This gene codes for P-glycoprotein (P-gp) which has been related to a immunoregulatory function. Modulation of HLA expression by P-gp has been described in different types of tumor cells including RMS. However, very little is known about biological implications of the P-gp expression in RMS patients treated with conventional chemotherapy. In order to study the problem, we used embryonal RMS tissue samples from treated patients. Our results indicated that positive RMS samples to mdr1 show higher HLA class I expression than those which were negative to mdr1 PCR, what indicates a significant correlation between the expression of both molecules. In addition, we developed two resistant RMS cell lines (A-204-1 and 2) using similar concentrations of actinomycin D as are plasma levels in clinical situation. Both resistant cell lines showed mdr1 expression and an increase of HLA class I expression which was dose-dependent. These results demonstrated that conventional chemotherapy of embryonal RMS is able to induce resistance which can modulate HLA class I expression and suggest that immunological studies of these tumors may be necessary to the design new specific therapeutic strategies.
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PMID:Induction of drug resistance in embryonal rhabdomyosarcoma treated with conventional chemotherapy is associated with HLA class I increase. 1665 92

Neoplastic cells exhibit defects in their ability to differentiate; therefore, differentiation therapy represents a viable option to control cancer growth and progression. Rhabdomyosarcomas (RMS), a malignant tumor of skeletal muscle, is the most common soft tissue sarcoma in children and is characterized by its poor response to cytotoxic treatment and significant morbidity. Since modulation of alpha-tubulin and human leukocyte antigen (HLA) class I expression has been detected during malignant transformation, we analyzed in this study the expression pattern of both kinds of proteins after the treatment with 5-FU derivatives in the human RMS RD cell line. Cytotoxic assays, scanning and transmission electron microscopy, flow cytometry and immunocytochemical analyses were used. The compounds analyzed belonged to the following three categories: (a) symmetrical bis(5-fluorouracil-1-yl) derivatives with a linker that connects the N(1) atoms of both pyrimidine moieties by means of two amide bonds; and (b) an ester with the 5-FU base. The whole structure corresponds to the terminal fragment of the molecules included in (a) and (c) 5-fluorouracil acyclonucleoside-like structures. 1-[[3-(3-Chloro-2-hydroxypropoxy)-1-methoxy]propoxy]propyl]-5-fluorouracil (2), that belongs to the class (a) produced the highest increment of tubulin and its intense capillary distribution throughout the cytoplasm. On the other hand, N,N-bis[3-(5-fluorouracil-1-yl)-3-methoxypropanoyl]-alpha,alpha;-diamino-m-xylene (5) and 2 that are included in the class (c) caused the major percentage of marked cells by the HLA class I proteins. In short, our results showed that the 5-FU derivatives increase HLA class I expression and showed greater microtubule stability with an important network of tubulin beams related with the degree of differentiation of RD cells. These results could mean a more favorable prognosis of the patients affected with these tumors.
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PMID:5-fluorouracil derivatives induce differentiation mediated by tubulin and HLA class I modulation. 1750 94

Several echoviruses use decay accelerating factor (DAF) as a cell surface receptor. However, most of them require additional cell surface coreceptors. We investigated the respective roles of DAF and class I human leukocyte antigen (HLA) molecules in the early steps of the echovirus 11 (EV11) lifecycle in rhabdomyosarcoma (RD) cells. EV11 infection was inhibited at an early stage by anti-beta2-microglobulin (beta2m) and anti-HLA monoclonal antibodies and by a soluble monochain HLA class I molecule. Expression of class I HLA molecules restored the early steps of the EV11 lifecycle, but its expression was not sufficient for EV11 replication and particle production. Expression of HLA class I molecules was associated with leukocyte cell line permissiveness to EV11 infection. In conclusion, HLA class I molecules are involved in the early steps of EV11 infection of RD cells and appear to participate in a complex interplay of surface molecules acting as coreceptors, including DAF.
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PMID:Role of class I human leukocyte antigen molecules in early steps of echovirus infection of rhabdomyosarcoma cells. 1882 25

MYCN is a well-known oncogene over-expressed in different human malignancies including neuroblastoma (NB), rhabdomyosarcoma, medulloblastoma, astrocytoma, Wilms' tumor, and small cell lung cancer. In the case of NB, MYCN amplification is an established biomarker of poor-prognosis. MYCN belongs to a family of transcription factors (the most important of which is C-MYC) that show a high degree of homology. Down-regulation of MYC protein expression leads to tumor regression in animal models, indicating that MYC proteins represent interesting therapeutic targets. Pre-requisites for a candidate tumor-associated antigen (TAA) to be targeted by immunotherapeutic approaches are the following, (i) expression should be tumor-restricted, (ii) the putative TAA should be up-regulated in cancer cells, and (iii) protein should be processed into immunogenic peptides capable of associating to major histocompatibility complex molecules with high affinity. Indeed, the MYCN protein is not expressed in human adult tissues and up-regulated variably in NB cells, and MYCN peptides capable of associating to HLA-A1 or HLA-A2 molecules with high affinity have been identified. Thus the MYCN protein qualifies as putative TAA in NB. Additional issues that determine the feasibility of targeting a putative TAA with cytotoxic T lymphocytes (CTLs) and will be here discussed are the following, (i) the inadequacy of tumor cells per se to act as antigen-presenting cells witnessed, in the case of NB cells, by the low to absent expression of HLA class I molecules, the lack of co-stimulatory molecules and multiple defects in the HLA class I related antigen processing machinery, and (ii) the immune evasion mechanisms operated by cancer cells to fool the host immune system, such as up-regulation of soluble immunosuppressive molecules (e.g., soluble MICA and HLA-G in the case of NB) or generation of immunosuppressive cells in the tumor microenvironment. A final issue that deserves consideration is the strategy used to generate CTL.
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PMID:MYCN: from oncoprotein to tumor-associated antigen. 2316 96