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Tytuł oryginału: Co-targeting HER2/ErbB2 and insulin-like growth factor-1 receptors causes synergistic inhibition of growth in HER2-overexpressing breast cancer cells.
Autorzy: Camirand Anne, Lu Yuhong, Pollak Michael
Źródło: Med. Sci. Monitor 2002: 8 (12) s.BR521-BR526, il., bibliogr. 32 poz.
Sygnatura GBL: 313,278

Hasła klasyfikacyjne GBL:
  • onkologia

    Typ dokumentu:
  • praca doświadczalna
  • tytuł obcojęzyczny

    Wskaźnik treści:
  • ludzie
  • in vitro

    Streszczenie angielskie: Background: The humanized anti-HER2 monoclonal antibody trastuzamab (Herceptin) is useful in the treatment of ErbB2-overexpressing breast cancers, but its efficiency is limited because development of resistance is common. In order to study the possibility of improving the efficacy of therapies directed against HER2/erbB2, we investigated the effects of co-targeting this receptor and the insulin-like growth factor 1 receptor (IGF-1R), a widely-expressed protein tyrosine kinase with important roles in suppression of apoptosis and stimulation of proliferation. Material/methods: The experimental strategy involved combining trastuzumab treatment and reduction of IGF-1R signaling through incremental heat-induced expression of the dominant-negative IGF-1 receptor 486/STOP under the control of the heat-sensitive Drosophila HSP70 promoter, in HER2/erbB2-overexpressing MCF7her 18 breast cancer cells. Results: Isobologram analysis of combinatorial treatment data revealed a strong synergistic interaction between trastuzumab treatment and the indication of the dominant-negative IGF-1R expression, resulting in potentiation of growth inhibition in transfected cancer cells. Conclusions: These observations support the concept that simultaneously co-targeting tyrosine kinase receptors may be therapeutically useful, and provide a specific rationale for combining IGF-1R and HER2/erbB2 targeting strategies in anti-neoplastic approaches.

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