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SleepyHollow02
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Untersuchte Arbeit:
Seite: 76, Zeilen: 17 ff.
Quelle: Gu et al 2009
Seite(n): 0, Zeilen: 0
Recent studies using mouse xenografts have shown that a testosterone–albumin conjugate (testosterone-BSA) induced potent apoptotic regression of prostate tumors in vivo [Hatzoglou A, et al. 2005]. In addition, testosterone-BSA was also reported to potentiate the paclitaxel-mediated cytotoxicity both in vitro and in vivo [Kampa M, et al. 2006]. These reports are supported by in vivo experimental findings presented in this work. Indeed, when Balb/c mice were treated with testosterone-HSA and the 12-week tumor incidence of colon tumors was assessed the chemically induced tumors were reduced by 65% in the testosterone-HSA-treated animals. Most probably this effect was due to the apoptotic regression of tumor cells as indicated by the Tunel assay. These results point out clearly that activation of mAR by testosterone-HSA significantly affects the incidence of colon tumors in vivo and they are in line with the previously reported prostate tumor regression in mice [Hatzoglou A, et al. 2005, Kampa M, et al. 2006]. Interestingly, mAR is strongly expressed in tissues derived from p53-deficient xenograft tumors. Since p53 is a frequently inactivated gene in tumors, it is interesting to hypothesize that mAR activation [may result in eradication of p53 tumors in vivo.]

Hatzoglou A, Kampa M, Kogia C, Charalampopoulos I, Theodoropoulos PA, Anezinis P, Dambaki C, Papakonstanti EA, Stathopoulos EN, Stournaras C, et al. (2005). Membrane androgen receptor activation induces apoptotic regression of human prostate cancer cells in vitro and in vivo. J Clin Endocrinol Metab, 90: 893-903.

Kampa M, Kogia C, Theodoropoulos PA, Anezinis P, Charalampopoulos I, Papakonstanti EA, Stathopoulos EN, Hatzoglou A, Stournaras C, Gravanis A, Castanas E. (2006) Activation of membrane androgen receptors potentiates the antiproliferative effects of paclitaxel on human prostate cancer cells. Mol Cancer Ther, 5:1342-1351.

Recent studies using mouse xenografts have shown that a testosterone-albumin conjugate (testosterone-BSA) induced potent apoptotic regression of prostate tumors in vivo [7]. In addition, testosterone-BSA was also reported to potentiate the paclitaxel-mediated cytotoxicity both in vitro and in vivo [19] [...]

Interestingly, the chemically-induced colon tumors were reduced by 65% in the testosterone-HSA-treated animals. Most probably this effect was due to the apoptotic regression of tumor cells as indicated by the TUNEL assay (Fig. 7D, middle panel). These results point out clearly that activation of mAR by testosterone-HSA significantly affects the incidence of colon tumors in vivo. Interestingly, mAR is strongly expressed in tissues derived from p53- deficient xenograft tumors (Fig. 1d, d'). Since p53 is a frequently inactivated gene in tumors, it is interesting to hypothesize that mAR activation may result in eradication of p53 tumors in vivo.


17. Papadopoulou N, Papakonstanti EA, Kallergi G, Alevizopoulos K, Stournaras C: Membrane androgen receptor activation in prostate and breast tumor cells: Molecular signaling and clinical impact. IUBMB Life 2009, 61(1):56-61.

19. Kampa M, Kogia C, Theodoropoulos PA, Anezinis P, Charalampopoulos I, Papakonstanti EA, Stathopoulos EN, Hatzoglou A, Stournaras C, Gravanis A, Castanas E: Activation of membrane androgen receptors potentiates the antiproliferative effects of paclitaxel on human prostate cancer cells. Mol Cancer Ther 2006, 5:1342-1351.

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