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)

Convenient synthesis of 1-[[3-(2-hydroxyethylhetero)-1-alkoxy]alkyl]-5-fluorouracils 3-8 was accomplished via the use of tin (IV) chloride, capable of a 1,4-chelation on alkoxy-1,4-diheteroepanes. Increasing the reaction time led to 5-FU seven-membered nucleoside analogues which could be considered as upper isosteres of the effective antitumour agent Ftorafur. Using 1-[[3-(2-hydroxyethoxy)-1-alkoxy]propyl]-5-fluorouracil as a parent drug, several chemical modifications on the acyclic moiety were made with the aim of obtaining new compounds showing significant antiproliferative activity in rhabdomyosarcoma (RD) cells. 14 treatment in vitro caused time- and dose-dependent growth inhibition on RD cells. Interestingly, when they were treated with doses of 35 microM and 140 microM of 14 for 6 days, they showed morphological and phetotypic differentiation with increased expression of desmin, alpha-actinin and tropomyosin. We suggest a potential role for differentiation therapy as a therapeutic approach to the treatment of rhabdomyosarcoma.
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PMID:Diheterocyclanes as synthons for the preparation of novel series of nucleoside and acyclonucleoside analogues. 927 96

Three new antitumour drugs containing two 5-fluorouracil moieties at both ends of the structure and a two amide bond linker were synthesized. Appropriated bis-acetal were reacted with two equivalents of 5-FU to afford the desired compounds. These drugs were evaluated for their ability to induce myogenic maturation in vitro on human rhabdomyosarcoma cells in an experimental model. Compounds 5 and 6 induced morphological and phenotypical differentiation in rhabdomyosarcoma cells at 4.5 and 3.5 microM, respectively. These new cell differentiating agents could be used as an alternative to selective destruction of undifferentiated cells. A potential role of the differentiation therapy as an alternative approach to the treatment of rhabdomyosarcomas is suggested.
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PMID:Synthesis and evaluation of new 5-fluorouracil antitumor cell differentiating derivatives. 1251 27

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