von Dott. Raffaele La Montagna
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| [1.] Rlm/Fragment 005 05 - Diskussion Zuletzt bearbeitet: 2014-12-01 13:39:34 Singulus | Feldman and Feldman 2001, Fragment, Gesichtet, Rlm, SMWFragment, Schutzlevel sysop, Verschleierung |
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| Untersuchte Arbeit: Seite: 5, Zeilen: 5-20 |
Quelle: Feldman and Feldman 2001 Seite(n): 36, 37, Zeilen: 36: right col. 14-16, 21-25, 28-33; 37: left col. 1-7, 25-31 |
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| One possible mechanism by which a prostate cancer circumvents the effects of androgen ablation therapy is by increasing its sensitivity to very low levels of androgens. There are several potential mechanisms that would allow increased tumor-cell proliferation, despite low circulating androgens in the patient. One mechanism to accomplish this is by increasing the expression of the AR itself. Approximately 30% of tumors that become androgen independent after ablation therapy have amplified the AR gene (3). A second hypersensitive mechanism for tumor progression results in high-level expression of the AR, increased stability, and enhanced nuclear localization of AR in recurrent tumor cells. A third hypersensitive mechanism to circumvent androgen ablation therapy is by increasing the local production of androgens, to compensate for the overall decline in circulating testosterone. Prostate cells could increase the rate of conversion of testosterone to the more potent hormone DHT by increasing 5α-reductase activity.
3) Koivisto, P. et al. Androgen receptor gene amplification: a possible molecular mechanism for androgen deprivation therapy failure in prostate cancer. Cancer Res. 57, 314–319. |
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Type 1: the hypersensitive pathway One possible mechanism by which a prostate cancer circumvents the effects of androgen ablation therapy is by increasing its sensitivity to very low levels of androgens. [...] AR amplification. There are several potential mechanisms that would allow increased tumour-cell proliferation, despite low circulating androgens in the patient. One mechanism to accomplish this is by increasing the expression of the AR itself. [...] Approximately 30% of tumours that become androgen independent after ablation therapy have amplified the AR gene, resulting in increased AR expression, whereas none of the primary tumours from the same patients before androgen ablation had an AR gene amplification15,25. [Page 37] Increased AR sensitivity. A second hypersensitive mechanism for tumour progression was found in animal models of the transition from androgen-dependent prostate cancer to apparent AIPC27.This pathway results in high-level expression of the AR, increased stability, and enhanced nuclear localization of AR in recurrent tumour cells. [...] Increased androgen levels. A third hypersensitive mechanism to circumvent androgen ablation therapy is by increasing the local production of androgens, to compensate for the overall decline in circulating testosterone. Prostate cells could increase the rate of conversion of testosterone to the more potent hormone DHT by increasing 5α-reductase activity. 15. Koivisto, P. et al. Androgen receptor gene amplification: a possible molecular mechanism for androgen deprivation therapy failure in prostate cancer. Cancer Res. 57, 314–319. 25. Visakorpi, T. et al. In vivo amplification of the androgen receptor gene and progression of human prostate cancer. Nature Genet. 9, 401–406 (1995). This study defined the amplified AR as a mechanism for the hypersensitive pathway. 27. Gregory, C. W., Johnson, R. T. Jr, Mohler, J. L., French, F. S. & Wilson, E. M. Androgen receptor stabilization in recurrent prostate cancer is associated with hypersensitivity to low androgen. Cancer Res. 61, 2892–2898. |
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Letzte Bearbeitung dieser Seite: durch Benutzer:Singulus, Zeitstempel: 20141201134115