VDR promotes pancreatic cancer progression in vivo by activating CCL20-mediated M2 polarization of tumor associated macrophage.

BACKGROUND: Activation of VDR pathway was a promising anti-tumor therapy strategy. However, numerous clinical studies have demonstrated the effect of activating VDR is limited, which indicates that VDR plays a complex role in vivos. METHODS: We analyzed the TCGA database to examine the association between VDR expression and immune cell infiltration in pancreatic adenocarcinoma (PAAD). Western blot, ELISA, ChIP, and dual-luciferase reporter assays were performed to determine the mechanism of VDR regulating CCL20. Migration assay and immunofluorescence were used to investigate the role of CCL20 in M2 macrophage polarization and recruitment. We employed multiplexed immunohistochemical staining and mouse models to validate the correlation of VDR on macrophages infiltration in PAAD. Flow cytometry analysis of M2/M1 ratio in subcutaneous graft tumors. RESULTS: VDR is extensively expressed in PAAD, and patients with elevated VDR levels exhibited a significantly reduced overall survival. VDR expression in PAAD tissues was associated with increased M2 macrophages infiltration. PAAD cells overexpressing VDR promote macrophages polarization towards M2 phenotype and recruitment in vitro and vivo. Mechanistically, VDR binds to the CCL20 promoter and up-regulates its transcription. The effects of polarization and recruitment on macrophages can be rescued by blocking CCL20. Finally, the relationship between VDR and M2 macrophages infiltration was evaluated using clinical cohort and subcutaneous graft tumors. A positive correlation was demonstrated between VDR/CCL20/CD163 in PAAD tissues and mouse models. CONCLUSION: High expression of VDR in PAAD promotes M2 macrophage polarization and recruitment through the secretion of CCL20, which activates tumor progression. This finding suggests that the combination of anti-macrophage therapy may improve the efficacy of VDR activation therapy in PAAD.

Effects of magnetic resonance imaging (MRI)-detected extramural vascular invasion (mrEMVI) and tumor deposits (TDs) on distant metastasis and long-term survival after surgery for stage III rectal cancer: a retrospective study grouped based on the relationship between the bottom of the tumor and peritoneal reflection.

Background: To evaluate the effect of magnetic resonance imaging (MRI)-detected extramural vascular invasion (mrEMVI) and tumor deposits (TDs) on distant metastasis and long-term survival after surgery for stage III rectal cancer based on the relationship between the bottom of the tumor and peritoneal reflection. Methods: A retrospective study was performed on 694 patients who underwent radical resection for rectal cancer at the Harbin Medical University Tumor Hospital from October 2016 to October 2021. According to the surgical records, a new group was established based on the relationship between the lower end of the tumor and peritoneal reflection. On the peritoneal reflection group: the tumors are all located on the peritoneal reflection. Across the peritoneal reflection group: the tumors recurred across the peritoneal reflection. Under the peritoneal reflection group: the tumors are all located under the peritoneal reflection. We evaluated the effects of mrEMVI and TDs on postoperative distant metastasis and long-term survival of stage III rectal cancer by combining mrEMVI with TDs. Results: In the whole study population, neoadjuvant therapy (P=0.003) was negatively correlated with distant metastasis after rectal cancer surgery. Also, mesorectal fascia (MRF) (P=0.024), postoperative distant metastasis (P<0.001), and TDs (P<0.001) were independent risk factors for long-term survival after rectal cancer surgery. Lymph node metastasis (P<0.001) and neoadjuvant therapy (P=0.023) were independent risk factors for the presence or absence of TDs of rectal cancer. In the non-neoassisted subgroup, postoperative distant metastasis (P<0.001) was considered to be an independent risk factor for long-term survival after rectal cancer surgery. Conclusions: In the under the peritoneal reflection group, the combination of mrEMVI and TDs seems to play a certain guiding role in predicting distant metastasis and long-term survival after rectal cancer surgery.

Prediction scores of postoperative liver metastasis and long-term survival of pancreatic head cancer based on the distance between the mesenteric vessels and tumor, preoperative serum carbohydrate antigen 19-9 level, and lymph node metastasis rate.

BACKGROUND: The shortest distance between the superior mesenteric artery (SMA) or superior mesenteric vein (SMV) and the tumor margin was combined with preoperative serum carbohydrate antigen (CA) 19-9 and lymph node ratio (LNR) to evaluate joint effects on long-term survival and liver metastasis in patients with pancreatic head cancer after radical surgery. METHODS: This retrospective study included 149 patients who underwent pancreaticoduodenectomy for pancreatic head cancer at Harbin Medical University Tumor Hospital from May 2011 to March 2021. The preoperative serum CA 19-9 level and LNR were combined with the SMA or SMV distance. The joint association between long-term survival and postoperative liver metastasis was evaluated. RESULTS: Based on the receiver operating characteristic curve of postoperative liver metastasis or long-term survival, the optimal cut-off values of SMV distance were 3.1 and 0.7 mm, respectively, whereas the optimal cut-off value of SMA distance was 10.25 mm. The univariate model identified the liver metastasis score (p < 0.001) as a negative factor for postoperative liver metastasis of pancreatic head carcinoma. The SMV distance (p = 0.003), SMA distance (p < 0.001), LNR score (p < 0.001), and survival score (p < 0.001) were negatively correlated with long-term survival after pancreatic head cancer. The multivariate model highlighted SMA distance (p < 0.001), survival score (p = 0.001), and LNR score (p < 0.001) as independent risk factors for long-term survival in pancreatic head cancer. CONCLUSION: Liver metastasis score may be an independent predictor of postoperative liver metastasis in patients with pancreatic head cancer. Survival and LNR scores may be independent predictors of long-term postoperative survival in patients with pancreatic head cancer. However, the LNR score appears to improve long-term survival.

Value of 4D CT Angiography Combined with Whole Brain CT Perfusion Imaging Feature Analysis under Deep Learning in Imaging Examination of Acute Ischemic Stroke.

This study was aimed at investigating the application of deep learning 4D computed tomography angiography (CTA) combined with whole brain CT perfusion (CTP) imaging in acute ischemic stroke (AIS). A total of 46 patients with ischemic stroke were selected from the hospital as the research objects. Image quality was analyzed after the 4D CTA images were obtained by perfusion imaging. The results showed that whole brain perfusion imaging based on FCN can achieve automatic segmentation. FCN segmentation results took a short time, an average of 2-3 seconds, and the Dice similarity coefficient (DSC) and mean absolute distance (MAD) were lower than those of other algorithms. FCN segmentation distance was 17.87. The parameters of the central area, the peripheral area, and the mirror area of the perfusion map were compared, and the mean transit time (MTT) and time to peak (TTP) of the lesion were prolonged compared with the mirror area. Moreover, the peripheral CBV was increased, and the differences between the parameters were significant (P < 0.05). In conclusion, using the deep learning FCN network, 4D CTA combined with whole brain CTP imaging technology can effectively analyze the perfusion state and achieve clinically personalized treatment.