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  The mixture was rotated end to overend for 4 h at room temperature

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jk123
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Počet príspevkov : 90
Registration date : 14.04.2015

 The mixture was rotated end to overend for 4 h at room temperature Empty
OdoslaťPredmet: The mixture was rotated end to overend for 4 h at room temperature    The mixture was rotated end to overend for 4 h at room temperature Icon_minitimeŠt november 19, 2015 5:25 am

We have showed that FW 04 806 is a Hsp90 inhibitor that directly JNJ-7706621 binds to the N terminus of Hsp90 and at tenuates Hsp90Cdc37 chaperoneco chaperone interac tions, leading to the degradation of multiple Hsp90 client proteins via the proteasome pathway, which may be the primary mechanism mediating the anticancer ac tivities of FW 04 806. The antagonistic efficacy of FW 04 806 against human breast cancer lines has been in vestigated at both the molecular and cellular levels. It has been demonstrated that FW 04 806 inhibits the HER2 overexpressed and HER2 underexpressed breast cancer cell lines SKBR3 and MCF 7 in a dose and time dependent manner with IC50 values of 12. 11 and 39. 44 uM, respect ively. Moreover, it was shown that FW 04 806 arrests cell cycle progression and induces programmed cell death.<br><br> It has further been shown that FW 04 806 displays an titumor effects in an in vivo LDN193189 animal model as well as in the in vitro settings previously described. Studies were conducted to investigate the effect of FW 04 806 on tu mors derived from cancer cell lines SKBR3 and MCF 7. High dose administration of FW 04 806 displayed an in hibitory effect on SKBR3 derived tumors was more pref erable in both the antitumor activity and mouse body weight than that of ADM, one of the most widely used chemotherapy drugs. Importantly, we found that FW 04 806 displays a better antitumor effect in SKBR3 tumor xenograft model than in MCF 7. The result is consistent with cell proliferation assay and in vitro apoptosis assay applied for SKBR3 and MCF 7.<br><br> As these cell lines are HER2 overexpressed and HER2 underexpressed respect ively, and HER2 is among the most sensitive Hsp90 clients, we assume that FW 04 806 has a preferential inhibi tory effect on HER2 overexpressed cancer cells. This as sumption is now being tested on other cancer cell lines. Moreover, mice survived at the dose of 900 mgkg in the acute toxicity test, and all LY2157299 溶解度 xenografts mice had no appre ciable adverse effects during the treatment. No histological abnormalities was found in lung, liver, heart, and kidneys of mice, suggested that FW 04 806 had a favorable toxicity profile. Conclusion In conclusion, as a novel Hsp90 inhibitor, FW 04 806 binds to the N terminal of Hsp90 and inhibits Hsp90 Cdc37 interaction, resulting in the disassociation of Hsp90Cdc37client complexes and the degradation of Hsp90 client proteins.<br><br> FW 04 806 displays promising antitumor activity against breast cancer cells both in vitro and in vivo, especially for HER2 overexpressed breast can cer cells. Our observations provide a basis for the further development of Hsp90 or HER2 targeted therapy for pa tients with breast cancer. Introduction Breast cancer is the most commonly diagnosed cancer and a leading cause of cancer death among women in both developed and developing nations. Furthermore, breast cancer has a low cure rate and easy recurrence, and always been treated with surgery. The most effective way is to search for drugs that could both induce apoptosis in cancer cell lines and delay tumor growth. Fatty acid synthase is the key enzyme required for de novo synthesis of fatty acids.
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