Clinical Cancer Research, Published OnlineFirst April 10, 2014, IF=8.193

1. Clinical Cancer Research, Published OnlineFirst April 10, 2014, IF=8.193 Autophagy inhibition augments the anticancer effects of epirubicin treatment in anthracycline-sensitive and -resistant triple-negative breast cancer 古春博 2014.12.15 IMI CONFIDENTIAL

2. Introduction • Triple-negative breast cancer (TNBC) was coined in 2005 for cancers lacking detectable expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2/NEU/ERBB2). • Patients with TNBC have poorer outcomes due to drug resistance and more aggressive recurrent disease compared with other subtypes. • Autophagy has a cytoprotective function that enables cancer cells to cope with cytotoxic or other stresses induced by treatment. Thus, anticancer therapies commonly lead to the upregulation of autophagy. IMI CONFIDENTIAL

3. FDA-approved chloroquine or hydroxychloroquine in combination with chemo- or radiotherapy for the treatment of different cancers, including breast, colon, brain, prostate, and non–small cell lung cancers, are currently under way. In this study, we show that epirubicin induced autophagic flux in TNBC cell lines.We developed anthracycline-resistant TNBC cell lines and demonstrate that in the absence of treatment , they exhibit relatively high levels of autophagic flux, compared with their parental cell lines. We provide evidence supporting the effective combination of epirubicin with pharmacologic (chloroquine and hydroxychloroquine) or genetic (siRNA) inhibition of autophagy, both in TNBC parental cell lines and their derivative anthracycline-resistant lines, in vitro and in xenograft mouse models.

4. Figure 1. Epirubicin treatment reduces cell viability and increases autophagic flux in TNBC cells

5. Figure 2 TNBC cells resistant to epirubicin have higher levels of autophagic flux relative to parent cells.

6. Figure 3. Combination treatment of autophagy inhibition and epirubicin enhances the loss in cell viability.

7. Figure 4. Autophagy inhibition reduces viability and augments cell death of TNBC lines resistant to epirubicin.

8. Figure 5. Assessment of in vivo autophagy-related protein levels in MDA-MB-231 xenograft tumors.

9. Figure 6. Combinatorial epirubicin (EPI) and hydroxychloroquine (HCQ) treatment reduces growth in MDA-MB-231 and MDA-MB-231-R8 tumor xenograft models.

10. Thank you!

11. 投稿案例分析 以前的稿件，只投一个杂志，经过1-3个月后，很多拒稿现象。之后由于忙于手头的工作，又在延迟了投稿过程，导致稿件堆积。 解决办法： ①、将所有SCI补充投稿杂志至3个； ②、每月给主管发送两次投稿记录，由主管监督。