Despite the accumulating knowledge of alterations in pancreatic cancer molecular pathways, no substantial improvements in the clinical prognosis have been made and this malignancy continues to be a leading cause of cancer death in the Western World. The orphan nuclear receptor COUP-TFII is a regulator of a wide range of biological processes and it may exert a prooncogenic role in cancer cells; interestingly, indirect evidences suggest that the receptor could be involved in pancreatic cancer. The aim of this study was to evaluate the expression of COUP-TFII in human pancreatic tumors and to unveil its role in the regulation of pancreatic tumor growth. We evaluated COUP-TFII expression by immunohistochemistry on primary samples. We analyzed the effect of the nuclear receptor silencing in human pancreatic cancer cells by means of shRNA expressing cell lines. We finally confirmed the in vitro results by in vivo experiments on nude mice. COUP-TFII is expressed in 69% of tested primary samples and correlates with the N1 and M1 status and clinical stage; Kaplan-Meier and Cox regression analysis show that it may be an independent prognostic factor of worst outcome. In vitro silencing of COUP-TFII reduces the cell growth and invasiveness and it strongly inhibits angiogenesis, an effect mediated by the regulation of VEGF-C. In nude mice, COUP-TFII silencing reduces tumor growth by 40%. Our results suggest that COUP-TFII might be an important regulator of the behavior of pancreatic adenocarcinoma, thus representing a possible new target for pancreatic cancer therapy.Pancreatic ductal adenocarcinoma (PDAC) is a devastating cancer characterized by a dismal prognosis even for early stage disease. Worldwide it is one of the leading causes of cancer death with mortality rate overlapping the incidence in the general population.1 PDAC natural history denotes its aggressive behavior with a high frequency of distant metastasis and tendency to recurrence. Treatment of PDAC is primarily a combination of adjuvant chemotherapy with modestly effective drugs and curative surgery.2 Unfortunately, at the time of diagnosis, most patients present a locally advanced or metastatic disease that precludes a successful surgical resection; in addition, PDAC patients frequently develop or possess innate resistance to chemotherapy drugs. 3The combined lack of efficient drugs and the aggressive nature of pancreatic cancer determines a catastrophic combination of events that reduces the 5 years survival to less than 5%.1 Therefore, the development of new therapeutic interventions is urgently needed, given the fact that the anticancer therapies in place lack target selectivity and, in most cases, cause severe adverse effects and overall systemic toxicity. 4,5

Introduction: For a long time, accelerated partial breast irradiation (APBI) effectiveness for ductal carcinoma in situ (DCIS) has been debated, due to conflicting published results. Recent encouraging data from phase 3 trials reopened new perspectives for this radiation approach. The aim of the present study was to analyze the long-term efficacy and safety results of the series of patients with DCIS enrolled in the APBI arm of the APBI-IMRT-Florence phase 3 trial (NCT02104895). Methods: Patients were treated in a phase 3 randomized trial comparing whole breast irradiation (50 Gy in 25 fractions to the whole breast, plus 10 Gy in 5 fractions to the tumor bed) to APBI (30 Gy in 5 nonconsecutive fractions) using the intensity-modulated radiotherapy technique. Results: Overall, 22 patients were treated in the APBI arm. Median age was 62 years (mean 59; range 42–75 years). At a median follow-up of 9.2 years (mean 8.8; range 3.8–12.1 years), no contralateral invasive/DCIS occurrence, distant metastasis, or breast cancer–related death were recorded. The 5- and 10-year local recurrence, distant metastasis–free survival, and breast cancer–specific survival were 100%. The 10-year overall survival rate was 90.9%. No late toxicity at 5 and 10 years was recorded. Conclusions: Waiting for pending studies and mature follow-up, we confirmed the efficacy and safety of APBI for low-risk DCIS.

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