Human pancreatic ductal adenocarcinoma (PDAC) exhibits marginal responses to anti-PD-1/PD-L1 immunotherapy and its mechanism remains poorly understood. We have investigated the effect of anti-PD-L1 and c-Myc inhibition in PDAC. Using 87 patients with PDAC from our hospital database we found a significant correlation between the expression of PD-L1 and c-Myc. Moreover, the expression of both PD-L1 and c-Myc was associated with poor overall survival. In addition, we confirmed this finding with the PDAC patients in the TCGA database. Using several PDAC cell lines we demonstrated a significant correlation between the expression of PD-L1 and c-Myc. We also found that expression of PD-L1 correlated with high-grade histology. JQ1, an inhibitor of c-Myc inhibited PD-L1 expression and tumor growth. Using xenograft models, we demonstrated that the combination of JQ1 and anti-PD-L1 antibody exerted synergistic inhibition of PDAC growth. Our data demonstrated that the expression of PD-L1 and c-Myc may be helpful prognostic biomarkers, and their inhibition may potentially serve as an effective treatment for PDAC.
BACKGROUND: Sclerosing angiomatoid nodular transformation of the spleen is one kind of exceedingly rare benign lesions originated from spleen. The incidence and pathogen remain unclear partially due to its rarity and short history. Consequently, preoperative diagnosis become extremely perplex. Splenectomy is a predominated therapy approach as well as diagnosis method for sclerosing angiomatoid nodular transformation of the spleen. We reported a case underwent computed tomography scan, magnetic resonance imaging and ultrasonic scan preoperatively. Examinations conclusion highly suspected sclerosing angiomatoid nodular transformation of the spleen and was confirmed by pathology after laparoscopic splenectomy. We herein reviewed some literatures on imaging characters of to reveal the possibility of preoperative diagnosis when clinicians encounter and investigated whether laparoscopic splenectomy is an appropriate treatment.CASE PRESENTATION: A 50-year-old female was found with a low dense mass in the spleen by abdominal computed tomography incidentally without any positive symptom. Further enhanced computed tomography scan revealed the lesion with asynchronous enhancement and magnetic resonance imaging showed radio-like rift missing from central. Ultrasonic scan imaging presented hypoechoic gap in the center, pretty similar to magnetic resonance imaging. These radiology imaging features deduced to Sclerosing angiomatoid nodular transformation of the spleen. Laparoscopic splenectomy was performed successfully by our team and histopathological findings convinced the preoperative diagnosis. Gross inspection was coincident to the performance of magnetic resonance imaging.CONCLUSION: By comprehending imaging character profoundly, sclerosing angiomatoid nodular transformation of the spleen can be a differential diagnosis preoperatively when encounter lesion of spleen. We believe that laparoscopic splenectomy is a reliable and effective therapy option for such rare benign lesion of spleen without risk of recurrence.
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