GR-891: a novel 5-fluorouracil acyclonucleoside prodrug for differentiation therapy in rhabdomyosarcoma cells

@article{Marchal1999GR891AN,
  title={GR-891: a novel 5-fluorouracil acyclonucleoside prodrug for differentiation therapy in rhabdomyosarcoma cells},
  author={Juan Antonio Marchal and Jos{\'e} C. Prados and Consolaci{\'o}n Melguizo and Jos{\'e} A. G{\'o}mez and J M Campos and Miguel Angel Gallo and Antonio Espinosa and N. Arena and A. Ar{\'a}nega},
  journal={British Journal of Cancer},
  year={1999},
  volume={79},
  pages={807 - 813}
}
SummaryDifferentiation therapy provides an alternative treatment of cancer that overcomes the undesirable effects of classical chemotherapy, i.e. cytotoxicity and resistance to drugs. This new approach to cancer therapy focuses on the development of specific agents designed to selectively engage the process of terminal differentiation, leading to the elimination of tumorigenic cells and recovery of normal cell homeostasis. A series of new anti-cancer pyrimidine acyclonucleoside-like compounds… 
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Toxin‐based selection of insulin‐producing cells with improved defense properties for islet cell transplantation
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Identifying the mechanisms through which cell defense properties act will help clarify the process responsible for β‐cell regeneration in type I diabetes patients, and possible involvement of different expression of cytoprotective genes in the selection of cell subpopulations, which demonstrate a broad spectrum of resistance.
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Immunocytochemical and scanning electron microscopy studies seemed to confirm that the association in which the differentiating agent followed the 5-FU treatment strongly impaired cellular integrity and function and that cytoskeletal elements, particularly microfilaments and surface structures could play an essential role in the mechanisms of cytotoxicity.
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The combined sequential cytotoxic-differentiation therapy resulting in synergistic cytotoxicity and differentiation may be the basis of a new approach to cancer therapy and may aid in reducing the amounts of chemotherapeutic agents required for effective treatment, while maintaining or even increasing their therapeutic effects.
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The in vitro and in vivo effectiveness of the two differentiation agents, in particular retinoic acid (RA) and hexamethylene bisacetamide (HMBA) are compared and the prospects for differentiation therapy as an effective strategy in the treatment and management of malignancy are evaluated.
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