USF1 Transcriptionally Regulates UGT1A3 and Promotes Lung Adenocarcinoma Progression by Regulating Neurotrophin Signaling Pathway.

Background: Lung cancer remains the leading cause of oncological death. There is an urgent need to discover new molecular targets and to develop new treatments. Our previous study showed that one of the UDP-glucuronosyltransferases (UGTs) family, UGT1A3, is an important prognostic factor for lung adenocarcinoma (LUAD), inhibiting UGT1A3 could significantly improve the efficacy of anti-tumor drugs. In this study, we aimed to explore the upstream transcriptional factor (USF1) of UGT1A3 and its way of playing a role in LUAD. Methods: The UGT1A3 promoter region was analyzed and dual-luciferase assay was involved to explore whether USF1 could bind to this region, and the possible regulation effects of USF1 to UGT1A3 was indicated by siRNA and recovery experiment. Then, the Cancer Genome Atlas database was used to analyze USF1 clinical features. The expression level of USF1 was detected by immunohistochemical assay and Western blotting. Cellular viability, proliferation, migration and invasion potential were also investigated. Meanwhile, the effect of USF1 in LUAD progression was detected in a mouse model. The downstream signaling pathway was analyzed by bioinformatic analysis and the expression of all related proteins was detected. Results: UGT1A3 was transcriptionally regulated by USF1, which was highly expressed in all investigated samples including patients' tissues, studied cells lines, and mouse models. The knockdown of USF1 inhibited cells viability, proliferation, migration and invasion, and reduced the tumor volume. Moreover, USF1 promoted the progress of LUAD by regulating the neurotrophin signaling pathway. Conclusion: As an important transcriptional regulator of UGT1A3, USF1 was highly expressed in LUAD and promoted LUAD progression by regulating the neurotrophin signaling pathway. These findings provide a new theoretical data that could serve as a good foundation for the treatment of LUAD.

Prognostic impact of tumor length in esophageal Cancer: a systematic review and Meta-analysis.

BACKGROUND: In clinical studies, it has been observed that esophageal cancer (EC) patient prognosis can be very different even for those patients with tumors of the same TNM stage. Tumor length has been analysed as a possible independent prognostic factor in many studies, but no unanimous conclusion has been reached. Therefore, this review used a meta-analysis to evaluate the association between tumor length and prognosis in EC patients. METHODS: A systematic search for relevant articles was performed in PubMed, Web of Science, and Embase. Hazard ratios (HRs) and 95% confidence intervals (CIs) were used as effective measures to estimate the correlation between tumor length and prognosis, including overall survival, disease-free survival, progression-free survival, disease-specific survival, and cancer-specific survival. STATA 15.0 software was used to perform the meta-analysis and the data synthesis. RESULTS: Finally, 41 articles with 28,973 patients were included in our study. The comprehensive statistical results showed that long tumors are an independent prognostic parameter associated with poor overall survival (OS) (HR = 1.30; 95% CI: 1.21-1.40, p < .001) and disease-free survival (DFS) (HR = 1.38; 95% CI: 1.18-1.61, p < .001) in EC patients. Subgroup analyses also suggested a significant correlation between long tumors and poor OS. Sensitivity analysis and publication bias evaluation confirmed the reliability and stability of the results. Similar results were obtained in the analyses of progression-free survival (PFS), disease-specific survival (DSS), and cancer-specific survival (CSS). CONCLUSION: The results of this meta-analysis showed that long tumors were related to poor OS, DFS, PFS, DSS and CSS in EC patients. Tumor length might be an important predictor of prognosis in EC patients, and it can be used as an independent staging index. Further well-designed and large-scale prospective clinical studies are needed to confirm these findings.

HN1L promotes invasion and metastasis of the esophagogastric junction adenocarcinoma.

BACKGROUND: Adenocarcinoma of the esophagogastric junction (AEG) refers to cancer that crosses the line of the gastroesophageal junction and includes distal esophageal cancer and proximal gastric cancer. It is characterized by early metastasis and a poor prognosis and has few treatment options. Here, we report a novel potential therapeutic target, hematological and neurological expressed 1-like (HN1L), in AEG. METHODS: A total of 38 patients who underwent surgical resection of AEG at the Department of Thoracic Surgery of Shandong Provincial Hospital from September 2018 to June 2019 were enrolled into the study. We detected the expression of HN1L in AEG and adjacent nontumor tissues by IHC staining. The clinicopathological characteristics of HN1L were statistically analyzed. Then, the expression of HN1L in different cell lines was detected by RT-q PCR. Finally, AGS and HGC-27 cell lines were performed to inhibit HN1L by shRNA in order to explore its role in the development of AEG. RESULTS: Immunohistochemical staining showed that the expression of HN1L in cancer tissues was higher than that in nontumor tissue (p < 0.001). High expression of HN1L was significantly correlated with TNM stage (p = 0.013) and lymph node metastasis (p = 0.03). The expression of HN1L was upregulated in tumor cell lines compared with normal cell line. Additionally, Cell function studies demonstrated that lentivirus-mediated shRNA silencing of HN1L expression could effectively reduce the proliferation, invasion, and metastasis of tumor cell lines and promote their apoptosis (p < 0.05). CONCLUSIONS: HN1L expression might contribute to the invasion and metastasis of AEG and is a promising therapeutic target.

[Progress of Chinese medicinal study on collateral circulation of coronary artery].

Effects of Chinese medicine on collateral circulation of coronary artery were reviewed, especially its regulatory effect through vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF).

[Effect of tongguan capsule on coagulant and fibrinolysis system in patients with coronary heart disease after percutaneous coronary intervention].

OBJECTIVE: To explore the effect and mechanism of Tongguan capsule (TGC) on coagulant and fibrinolysis system in patients with coronary heart disease (CHD) after percutaneous coronary intervention (PCI). METHODS: Adopting the prospective, randomized controlled method to observe the coagulant-fibrinolysis related indexes, including tissue plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), von Willebrand factor (vWF), antithrombin II (AT-III) and fibrinogen (FIB), in CHD patients after PCI, there were 26 patients in the treated group treated by TGC with Western medicine and 26 in the control group treated by Western medicine alone. RESULTS: After treatment, all the indexes were improved in both groups (P < 0.05). As comparison between the two groups, AT-III and t-PA were higher in the treated group than those in the control group; PAI-1 levels showed insignificant difference at 1 month after treatment, but at 3 months after treatment, it was significantly lower in the treated group (P < 0.05); vWF showed no significant difference either at 1 or at 3 months after treatment; and FIB was lower in the treated group both at 1 and 3 months after treatment (P < 0.01). CONCLUSION: TGC could improve the hypercoagulant status and adjust the balance between coagulant-fibrinolysis system of CHD patients after PCI by increasing AT-III and t-PA levels, and lowering FIB and PAI-1 levels in the body.