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Integrated densities across fractions

Expression of CD24, phospho-Met, MDR-1 and MRP in cisplatin-treated EC xenogrft tumors

CD24 knocked down EC cells are more cisplatin-resistant

Figure legends of supplemental figure 1 - 5.

Endometrial cancer is the most prevalent gynecologic cancer in the Western world, and the number of advanced chemotherapy-resistant cancers is increasing with the absolute increase in patients. The development of resistance to chemotherapeutic drugs by cancer cells represents a major challenge in the clinical cure of advanced and metastatic cancers. CD24 has been reported to be a marker for a poor prognosis in several tumors, and we herein examined the functions of CD24 in human endometrioid adenocarcinoma cell lines and evaluated how it contributes to cancer drug resistance. We demonstrated that CD24 was responsible for the recruitment of phosphorylated Met to the lipid raft domain of the cell membrane, resulting in amplification of the Met signaling cascade, ultimately leading endometrial cancer cells to express higher levels of ATP-binding cassette (ABC) transporters. Our findings suggest that CD24-mediated amplification of the Met cascade may contribute to the drug resistance of endometrial cancer. Mol Cancer Ther; 14(10); 2353–63. ©2015 AACR.

Confirmation of CD24 overexpression in CD24 DNA construct transfected cells

Endometrial cancer is the most prevalent gynecologic cancer in the Western world, and the number of advanced chemotherapy-resistant cancers is increasing with the absolute increase in patients. The development of resistance to chemotherapeutic drugs by cancer cells represents a major challenge in the clinical cure of advanced and metastatic cancers. CD24 has been reported to be a marker for a poor prognosis in several tumors, and we herein examined the functions of CD24 in human endometrioid adenocarcinoma cell lines and evaluated how it contributes to cancer drug resistance. We demonstrated that CD24 was responsible for the recruitment of phosphorylated Met to the lipid raft domain of the cell membrane, resulting in amplification of the Met signaling cascade, ultimately leading endometrial cancer cells to express higher levels of ATP-binding cassette (ABC) transporters. Our findings suggest that CD24-mediated amplification of the Met cascade may contribute to the drug resistance of endometrial cancer. Mol Cancer Ther; 14(10); 2353–63. ©2015 AACR.

Purpose: Vascular endothelial growth factor (VEGF) plays a central role in tumor angiogenesis and is regarded as a promising therapeutic target. We hypothesized that treatment with bevacizumab, a humanized recombinant anti-VEGF monoclonal antibody, could enhance antitumor response to cisplatin and prolong survival in a murine ovarian cancer model.Experimental Design: We conducted an MTS assay to examine the effect of bevacizumab on proliferation of the VEGF producing human ovarian cancer cell lines in vitro. Next, the antiangiogenic activity of bevacizumab was investigated by in vivo angiogenesis and wound healing assays. We then determined the toxicity and antitumor response of bevacizumab and cisplatin as single agents or in combination in xenograft models of ovarian cancer. Finally, using the same xenograft model, we examined the effect of these regimens, as well as bevacizumab maintenance therapy, on survival.Results: Bevacizumab had no effect on the proliferation of ovarian cancer cells in vitro but significantly inhibited angiogenesis and delayed wound healing in vivo. Bevacizumab inhibited i.p. tumor growth and ascites production in the nu/nu mouse xenograft model and enhanced the therapeutic efficacy of cisplatin. Combination therapy with bevacizumab and cisplatin for 3 weeks was associated with complete disappearance of all macroscopic evidence of disease. Moreover, maintenance treatment with bevacizumab after 3 weeks of induction combination therapy inhibited recurrence and significantly prolonged survival.Conclusions: Bevacizumab has significant antitumor activity not only as a single agent or in combination with cisplatin but may also prolong survival when used as maintenance therapy after a complete response to cisplatin-based chemotherapy.