0.05).CONCLUSION:Ketoconazole may play its role in treating OHSS by reducing the expression of VEGF.

Objective:To evaluate the therapeutic effects and prognostic factors of neoadjuvant chemoradiotherapy for locally advanced esophageal squamous cell carcinoma.Methods:The clinical data of a total of 148 patients with locally advanced esophageal squamous cell carcinoma enrolled in the Affiliated Cancer Hospital of Zhengzhou University from 2007 to 2017 were retrospectively analyzed. The patients received 5-Fu/Cisplatin or Paclitaxel/Cisplatin for chemotherapies. The total treatment dose for the radiotherapy was delivered at 36-40Gy under conventional fractionation. Kaplan-Meier method was used to calculate survival rates, and Log-rank test and Cox model were performed for univariate analysis and multivariate analysis, respectively.Results:The overall survival (OS) rates of 1-, 3-and 5-year were 74%, 51% and 51%, respectively, with a median survival time (MST) of 72.4 months. The carcinoma/disease-free survival (DFS) rates for 1, 3, 5 years were 60%, 51%, 45%, respectively, with a median time of 60.1 months. The 1-, 3-and 5-year OS rates of the pCR group were 86%, 70%, 70%, the ones of which in the non-pCR group were 70%, 44%, 43%, respectively ( P=0.002). The 1-, 3-and 5-year DFS rates were 76%, 71%, 68% for the pCR group, and 53%, 43%, 37% for the non-pCR group, respectively ( P=0.002). In pN(-) group and pN(+ ) group, the 1-, 3-and 5-year OS rates were 83%, 56%, 55% and 50%, 38%, 38%( P=0.004), respectively. Further, the 1-, 3-and 5-year DFS rates were 66%, 56%, 51% for the pN(-) group, and 43%, 38%, 31% for the pN(+ ) group ( P=0.006), respectively. Multivariate analysis revealed that pCR and pN status were independent prognostic factors for OS and DFS ( P=0.012, 0.011 and P=0.025, 0.033). Conclusion:Neoadjuvant chemoradiotherapy demonstrated significant therapeutic effects in the treatment of locally advanced esophageal squamous cell carcinoma, while pCR and pN status served as independent prognostic factors.

Evasion of apoptosis is a hallmark of cancer, attributed in part to overexpression of the anti-apoptotic protein B-cell lymphoma 2 (Bcl-2). In a variety of cancer types, including lymphoma, Bcl-2 is overexpressed. Therapeutic targeting of Bcl-2 has demonstrated efficacy in the clinic and is the subject of extensive clinical testing in combination with chemotherapy. Therefore, the development of co-delivery systems for Bcl-2 targeting agents, such as small interfering RNA (siRNA), and chemotherapeutics, such as doxorubicin (DOX), holds promise for enabling combination cancer therapies. Lipid nanoparticles (LNPs) are a clinically advanced nucleic acid delivery system with a compact structure suitable for siRNA encapsulation and delivery. Inspired by ongoing clinical trials of albumin-hitchhiking doxorubicin prodrugs, here we developed a DOX-siRNA co-delivery strategy via conjugation of doxorubicin to the surface of siRNA-loaded LNPs. Our optimized LNPs enabled potent knockdown of Bcl-2 and efficient delivery of DOX into the nucleus of Burkitts' lymphoma (Raji) cells, leading to effective inhibition of tumor growth in a mouse model of lymphoma. Based on these results, our LNPs may provide a platform for the co-delivery of various nucleic acids and DOX for the development of new combination cancer therapies.