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 vitro cultures and clonal derivatives have been established from rat rhabdomyosarcomas induced by Moloney-Murine Sarcoma Virus (MSV) or by nickel sulfide; differentiation ability has been studied as expression of desmin, embryonic and adult myosin isoforms, alpha-actin isoforms and cellular fusion. The two rhabdomyosarcoma models showed different levels of myogenic differentiation. Multinucleated myotube-like structures were frequently observed in cultures derived from nickel-induced tumours. Desmin was present in 50-80% of cells and embryonic myosin in up to 10%. In MSV-tumour-derived cultures and in their metastases or clonal derivatives two cell types are present in different ratios: spindle-shaped cells, adherent to plastic surfaces, and rounded cells, loosely attached or floating free in the medium. These cultures showed features of myogenic differentiation (10-80% desmin-positive cells), but embryonic myosin expression and production of multinucleated myotube-like structures were very rare events. Cultures from autochthonous lymph node and lung metastatic cells showed similar patterns of differentiation. Retinoic acid increased differentiated features (myotube formation and embryonic myosin expression) only in nickel-induced rhabdomyosarcoma cells. The two models described here mimic the heterogeneity in differentiation pattern found among human rhabdomyosarcomas. Myogenic differentiation ability was retained at a good level by nickel-induced tumours, whereas it was strongly impaired in MSV-induced tumours.
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PMID:In vitro differentiation of rhabdomyosarcomas induced by nickel or by Moloney murine sarcoma virus. 203 98

N-homocysteine thiolactonyl retinamide was synthesized from trans retinoic acid and the free base of homocysteine thiolactone. In doses of 90-1800 mg/kg given i.p. in mixed lipid vehicle over nine weeks, the compound decreased to 60% of controls the number of lung tumors which was induced in A/J mice by 20 mg of ethyl carbamate. The highest dose also decreased the mean volume of lung tumors to 50% of controls, resulting in a total tumor volume of 30% of controls. Retinoic acid itself at 450 mg/kg was toxic, and no chemopreventive activity was observed. The free base and the lipophilic perchlorate salt of homocysteine thiolactone both increased the number of lung tumors to 114-117% of controls, indicating a co-carcinogenic effect. In C57BL/6N mice with transplanted MUO4 rhabdomyosarcoma, N-homocysteine thiolactonyl retinamide in a dose of 1000 mg/kg given over 11-21 days decreased the weight of the tumors to 30-70% of controls. These results show that N-homocysteine thiolactonyl retinamide has chemopreventive activity against chemical carcinogenesis and antineoplastic activity against a transplanted neoplasm.
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PMID:Chemopreventive and antineoplastic activity of N-homocysteine thiolactonyl retinamide. 365 91

Rhabdomyosarcoma (RMS) is the most frequent soft tissue sarcoma in children. Despite multiple attempts at intensifying chemotherapeutic approaches to treatment, only moderate improvements in survival have been made for patients with advanced disease. Retinoic acid is a differentiation agent that has shown some antitumor efficacy in RMS cells in vitro; however, the effects are of low magnitude. E-3-(4'-hydroxyl-3'-adamantylbiphenyl-4-yl) acrylic acid (ST1926) is a novel orally available synthetic atypical retinoid, shown to have more potent activity than retinoic acid in several types of cancer cells. We used in vitro and in vivo models of RMS to explore the efficacy of ST1926 as a possible therapeutic agent in this sarcoma. We found that ST1926 reduced RMS cell viability in all tested alveolar (ARMS) and embryonal (ERMS) RMS cell lines, at readily achievable micromolar concentrations in mice. ST1926 induced an early DNA damage response (DDR), which led to increase in apoptosis, in addition to S-phase cell cycle arrest and a reduction in protein levels of the cell cycle kinase CDK1. Effects were irrespective of TP53 mutational status. Interestingly, in ARMS cells, ST1926 treatment decreased PAX3-FOXO1 fusion oncoprotein levels, and this suppression occurred at a post-transcriptional level. In vivo, ST1926 was effective in inhibiting growth of ARMS and ERMS xenografts, and induced a prominent DDR. We conclude that ST1926 has preclinical efficacy against RMS, and should be further developed in this disease in clinical trials.
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PMID:The synthetic retinoid ST1926 as a novel therapeutic agent in rhabdomyosarcoma. 2645 52