LSD1 inhibition suppresses the growth of clear cell renal cell carcinoma upregulating P21 signaling

Histone lysine-specific demethylase 1 (LSD1) has been implicated in the disease progression of several types of solid tumors. This study provides the first evidence showing that LSD1 overexpression occurred in 62.6% (224/358) of clear cell renal cell carcinomas (ccRCC). LSD1 expression was associated with the progression of ccRCC, as indicated by TNM stage (=0.006), especially tumor stage (=0.017) and lymph node metastasis (=0.030). High LSD1 expression proved to be an independent prognostic factor for poor overall survival (<0.001) and recurrence-free survival (<0.001) of ccRCC patients. We further show that LSD1 inhibition by siRNA knockdown or using the small molecule inhibitor SP2509 suppressed the growth of ccRCC and . Mechanistically, inhibition of LSD1 decreased the H3K4 demethylation at the gene promoter, which was associated with P21 upregulation and cell cycle arrest at G1/S in ccRCC cells. Our findings provide new mechanistic insights into the role of LSD1 in ccRCC and suggest the therapeutic potential of LSD1 inhibitors in ccRCC treatment.

Effect of Prophylactic Pancreatic Duct Stenting on Post-ERCP Pancreatitis in Patients With Risk Factors / 胃肠病学

Background:Pancreatitis is the main complication of ERCP,and a variety of risk factors will increase its risk. Studies showed that temporary pancreatic duct stent can reduce the incidence of post-ERCP pancreatitis (PEP). Aims:To study the efficacy and safety of prophylactic pancreatic duct stenting on preventing PEP in patients with risk factors. Methods:Patients undergone ERCP and accompanied with one or more PEP-associated risk factors from November 2013 to November 2016 at Huaibei People's Hospital were enrolled,and were divided randomly into pancreatic duct stenting group (observation group)and non-stenting group (control group). Serum levels of amylase at 4,24 and 48 hours after the procedure and incidence of PEP were compared between the two groups. Results:A total of 297 patients were enrolled, and 147 patients were in observation group,and 150 patients in control group. No significant differences in gender,age and ERCP disease spectrum were found between the two groups (P > 0. 05). Incidence of PEP was significantly decreased in observation group than in control group (6. 1％ vs. 16. 0％,P 0. 05). Conclusions:Prophylactic pancreatic duct stenting may decrease the incidence of PEP in patients accompanied with PEP-associated risk factors, especially could decrease the severity of PEP. However, the incidence of hyperamylasemia is not decreased.