ABSTRACT
NDFIP1 has been previously reported as a tumor suppressor in multiple solid tumors, but the function of NDFIP1 in NSCLC and the underlying mechanism are still unknown. Besides, the WW domain containing proteins can be recognized by NDFIP1, resulted in the loading of the target proteins into exosomes. However, whether WW domain-containing transcription regulator 1 (WWTR1, also known as TAZ) can be packaged into exosomes by NDFIP1 and if so, whether the release of this oncogenic protein via exosomes has an effect on tumor development has not been investigated to any extent. Here, we first found that NDFIP1 was low expressed in NSCLC samples and cell lines, which is associated with shorter OS. Then, we confirmed the interaction between TAZ and NDFIP1, and the existence of TAZ in exosomes, which requires NDFIP1. Critically, knockout of NDFIP1 led to TAZ accumulation with no change in its mRNA level and degradation rate. And the cellular TAZ level could be altered by exosome secretion. Furthermore, NDFIP1 inhibited proliferation in vitro and in vivo, and silencing TAZ eliminated the increase of proliferation caused by NDFIP1 knockout. Moreover, TAZ was negatively correlated with NDFIP1 in subcutaneous xenograft model and clinical samples, and the serum exosomal TAZ level was lower in NSCLC patients. In summary, our data uncover a new tumor suppressor, NDFIP1 in NSCLC, and a new exosome-related regulatory mechanism of TAZ.
Subject(s)
Humans , Carcinoma, Non-Small-Cell Lung/metabolism , Carrier Proteins/metabolism , Cell Line , Cell Proliferation , Exosomes/metabolism , Lung Neoplasms/genetics , Membrane Proteins/metabolism , Transcriptional Coactivator with PDZ-Binding Motif Proteins/metabolismABSTRACT
Objective:To investigate the efficacy of double balloon enteroscopy (DBE) in the treatment of bleeding from small intestinal vascular lesion and risk factors of bleeding recurrence .Methods:From April 2013 to May 2020, at Air Force Medical Center, the clinical data of 65 patients with confirmed or suspected bleeding from small intestinal vascular lesion were retrospectively analyzed. The patients were divided into DBE treatment group (patients of Yano classification 1a and 1b received argon plasma coagulation, and patients of Yano classification 2 and 3 accepted combination of titanium clip and submucosal injection of lauromacrogol sclerosing agent) and non-DBE treatment group (traditional treatments such as stopping anticoagulant or antiplatelet drugs, blood transfusion, and iron supplementation). The bleeding recurrence of patients with single small intestinal vascular lesion between DBE treatment group and non-DBE treatment group, and patients with single or mulitiple vascular lesion of DBE treatment group were compared. Univariate analysis was used to analyze the clinical data of patients with or without recurrent bleeding. Multivariate logistic regression model was used to analyze the independent risk factors and protective factors of recurrent bleeding in small intestinal vascular lesion. Independent sample t test, chi-square test and Fisher exact probability method were used for statistical analysis. Results:Forty-four (25 of single vascular lesion and 19 of multiple vascular lesion) patients were diagnosed with small intestinal vascular lesions and received DBE treatment (DBE treatment group). Twenty-one patients with single vascular lesion accepted traditional treatment (non-DBE treatment group). The recurrent rate of bleeding in patients with single vascular lesion of DBE treatment group was lower than that in patients with single vascular lesion of non-DBE treatment group and patients with multiple vascular lesion of DBE treatment group (24.0%, 6/25 vs. 71.4%, 15/21 and 12/19), and the differences were statistically significant ( χ2=10.348 and 6.848, P=0.001 and 0.009). The results of univariate analysis showed that the proportion of blood transfusion, hypertension, complicated with valvular heart disease and DBE treatment in patients with rebleeding or not rebleeding from small intestinal vascular lesion was different with statistically significant (69.7%(23/33) vs. 37.5%(12/32), 51.5%(17/33) vs. 18.8%(6/32), 42.4%(14/33) vs. 12.5%(4/32) and 54.5%(18/33) vs. 81.2%(26/32), χ2=6.777, 7.628, 7.265, and 5.298, all P<0.05). The results of multivariate logistic regression analysis indicated that blood transfusion during the course of disease (odds ratien ( OR)=3.736, 95% confidence interval ( CI) 1.082 to 12.898, P=0.037) and complication with valvular heart disease ( OR=4.916, 95% CI 1.107 to 21.829, P=0.036) were independent risk factors of bleeding recurrence in patients with small intestinal vascular lesions. DBE treatment was the protective factor of bleeding recurrence in patients with small intestinal vascular lesion ( OR=0.214, 95% CI 0.057 to 0.808, P=0.023). Conclusions:DBE is effective in the treatment of small intestinal vascular lesion bleeding, especially for single vascular lesion. Blood transfusion during disease course and complication with valvular heart disease are independent risk factors for bleeding recurrence in patients with small intestinal vascular lesion.
ABSTRACT
Objective:To evaluate the value of blood urea nitrogen (BUN)/creatinine (Cr) ratio for guiding the access route of double balloon enteroscopy (DBE) for small intestinal bleeding.Methods:The clinical information was collected from 105 patients who underwent DBE for suspected small intestinal bleeding at Air Force Medical Center from January 2015 to October 2019. Patients were divided into the elevated BUN/Cr group ( n=52) and the normal BUN/Cr group ( n=53), with a cut-off value of 81. Comparison was made for the detection rate of lesions between the oral route and anal route separately in the two groups using Chi-square test. Results:Among the 105 patients with suspected small intestinal bleeding, definite causes of bleeding were identified in 79 patients by DBE, and the overall lesion detection rate was 75.24% (79/105). In the elevated BUN/Cr group, the overall lesion detection rate was 76.92% (40/52), among which 79.49% (31/39) was through oral and 47.37% (9/19) through anal enteroscopy. In the normal BUN/Cr group, the overall lesion detection rate was 73.58% (39/53), and 63.64% (21/33) was transoral and 51.43% (18/35) transanal. The lesion detection rate of transoral enteroscopy in the elevated group was significantly higher than that in the normal group ( χ2=6.576, P=0.010). There was no significant difference in the lesion detection rate of transanal enteroscopy between the two groups ( χ2=2.230, P=0.135). Conclusion:For patients with active small intestinal bleeding (active bleeding within 48 hours), the BUN/Cr ratio higher than 81 may indicate that DBE should be performed firstly via oral route.