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Jing Ni,1 Xianzhong Cheng,1 Jin Chen,1 Wenwen Guo,2 Zhiqin Dai1 1Department of Gynecologic Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu 210009, People’s Republic of China; 2Department of Pathology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210009, People’s Republic of ChinaCorrespondence: Zhiqin DaiDepartment of Gynecologic Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, 42# Baiziting Street, Nanjing, Jiangsu 210009, People’s Republic of ChinaTel +86-25-83284675Email zhiqind@163.comPurpose: Survival of platinum-resistant ovarian cancer (PROC) patients is significantly shortened to around 12 months. Anlotinib is a new multi-target tyrosine kinase inhibitor. The goal of this study is to evaluate the efficacy and safety of anlotinib in PROC patients.Patients and Methods: PROC patients treated with anlotinib in Jiangsu Cancer Hospital between June 2018 to September 2019 were recruited. Most patients received an initial bolus of 12mg orally once daily on days 1– 14 of a 21-day cycle (except one received a dose of 10mg and another one received a dose of 8mg orally once a day). The adverse events (AEs) and efficacy were analyzed by CTCAE 4.0 and RECIST 1.1.Results: Of all 15 enrolled patients, 12 patients received anlotinib as multi-line therapy and 3 patients received it as maintenance therapy. In the multi-line therapy group, eight patients received anlotinib monotherapy and four patients received anlotinib combined with chemotherapy. Ultimately, evaluation showed that one patient achieved partial response (PR), five patients achieved stable disease (SD) and one patient had progressive disease (PD) with monotherapy, yielding objective response rate (ORR) of 14.3% (95% CI=0.01– 0.58) and disease control rate (DCR) of 85.7% (95% CI=0.42– 0.99). One patient achieved PR, two patients achieved SD with combination therapy, yielding ORR of 33.3% (95% CI=0.02– 0.87) and DCR of 100% (95% CI=0.31– 1.00). Three patients with maintenance therapy were followed up for 5, 8, and 11 months, respectively. The most grade 1– 2 AEs were hand-foot syndrome, nausea, and hypertension. Serious AEs (SAEs) (Grade 3– 4) were observed in one patient with oral ulcer and another patient with hand-foot syndrome that were managed by dose reduction.Conclusion: Anlotinib was of promising efficacy and well tolerated in PROC patients. This is the first retrospective study about exploratory therapy for ovarian cancer patients with anlotinib.Keywords: platinum-resistant ovarian cancer, anlotinib, efficacy, safety

Minmin Yu,1,2,* Baozhen Xu3,*, Hui Yang4,*, Songlin Xue,2 Rong Zhang,2 Hongmei Zhang,5 Xiaoyan Ying,1 Zhiqin Dai61Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, People’s Republic of China; 2Department of Obstetrics and Gynecology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing 210003, People’s Republic of China; 3Department of Obstetrics and Gynecology, Nanjing Lishui People’s Hospital, Nanjing 211200, People’s Republic of China; 4Department of Obstetrics and Gynecology, Huaian Maternal and Child Health Care Hospital, Huaian 223002, People’s Republic of China; 5Department of Clinical Research Center, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing 210003, People’s Republic of China; 6Department of Gynecologic Oncology, Jiangsu Cancer Hospital, Nanjing 210009, People’s Republic of China*These authors contributed equally to this workBackground: Cervical cancer is one of the most lethal malignancies among women in the world. Every year about 311,365 women die because of cervical cancer. Chemo-resistance is the main reason of the lethal malignancies, and the mechanism of chemo-resistance in cervical cancer still remains largely elusive.Purpose: Previous studies reported that microRNAs played important biological roles in the chemo-resistance in many types of cancers, in the present study we tried to investigate the biological roles of microRNA-218 in chemo-resistance in cervical cancer cells.Results: Real-time PCR results indicated microRNA-218 was downregulated in cisplatin-resistant HeLa/DDP and SiHa/DDP cells compared with the mock HeLa and SiHa cells. CCK-8 assay results showed upregulation of microRNA-218 enhanced the cisplatin sensitivity of cervical cancer cells; while downregulation of microRNA-218 decreased the cisplatin sensitivity of cervical cancer cells. Dual-luciferase assay indicated survivin was a direct target of microRNA-218. Western blotting and PCR results indicated the expression of survivin in HeLa/DDP and SiHa/DDP cells was significantly increased compared with HeLa and SiHa cells. Further study indicated induction of microRNA-218 decreased the expression of survivin while inhibition of microRNA-218 increased the expression of survivin in cervical cancer cells. Cell apoptosis results indicated induction of microRNA-218 induced the cell apoptosis in cervical cancer cells.Conclusion: Our data revealed microRNA-218 enhanced the cisplatin sensitivity in cervical cancer cells through regulation of cell growth and cell apoptosis, which could potentially benefit to the cervical cancer treatment in the future.Keywords: miR-218, cervical cancer, cisplatin resistant, apoptosis, survivin