Background Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with poor prognosis, and gemcitabine-based chemotherapy remains an effective option for the majority of PDAC patients. Hepatocyte nuclear factor 1α (HNF1A) is a tumor-suppressor in PDAC, but its role in gemcitabine chemoresistance of PDAC has not been clarified. Methods The function of HNF1A in gemcitabine was detected by overexpression and knockdown of HNF1A in vitro and in vitro . The regulatory network between HNF1A and ABCB1 was further demonstrated by luciferase assays, deletion/mutation reporter construct assays and CHIP assays. Findings Here, we found that HNF1A expression is significantly associated with gemcitabine sensitivity in PDAC cell lines. Moreover, we identified that HNF1A overexpression enhanced gemcitabine sensitivity of PDAC both in vitro and in vitro , while inhibition of HNF1A had the opposite effect. Furthermore, by inhibiting and overexpressing HNF1A, we revealed that HNF1A regulates the expression of MDR genes (ABCB1 and ABCC1) in PDAC cells. Mechanistically, we demonstrated that HNF1A regulates ABCB1 expression through binding to its specific promoter region and suppressing its transcription levels. Finally, the survival analyses revealed the clinical value of HNF1A in stratification of gemcitabine sensitive pancreatic cancer patients. Interpretation Our study paved the road for finding novel treatment combinations using conventional cytotoxic agents with functional restoration of the HNF1A protein, individualized treatment through HNF1A staining and improvement of the prognosis of PDAC patients. Fund National Natural Science Foundations of China and National Natural Science Foundation of Guangdong Province.
Background: Postmenopausal osteoporosis, a common yet chronic systemic metabolic disease, has become a major public health problem due to life expectancy increasing around the world. The differentiation of mesenchymal stem cells (MSCs) into osteoblasts, and the differentiation of circulating monocyte cells into osteoclasts, play an important role in the balance of bone metabolism. However, when both undergo pathological changes, it can lead to abnormalities, resulting in osteoporosis. This study aims to explore a new biomarker for postmenopausal osteoporosis, thereby providing a new entry point for bioinformatic research into the clinical diagnosis and treatment of the disease.Methods: Using the Gene Expression Omnibus (GEO) database, microarray analysis was conducted to identify differentially expressed genes in MSCs and monocytes in both postmenopausal osteoporosis patients and a healthy control group. The Database for Annotation, Visualization and Integrated Discovery (DAVID) database was used to analyze the function and enrichment of the selected genes, and a protein-protein interaction (PPI) network was constructed from the Search Tool for the Retrieval of Interacting Genes/ Proteins (STRING) website and displayed in Cytoscape. To achieve the final results, module analysis of the PPI network was performed by using Molecular Complex Detection (MCODE).Results: We identified 45 high-expression and 26 low-expression genes through the study, all of which underwent pathway enrichment analysis. This enrichment was observed in the cell cycle regulation, osteoclast differentiation, tumor necrosis factor (TNF) signaling pathway, and RNA transport. The top 10 hub genes of the PPI network were SF3B1,
Background: Pancreatic ductal adenocarcinoma (PDAC) is one of malignant tumors with the worst prognosis. Surgery and adjuvant chemotherapy are the main treatments for resectable pancreatic cancer. For borderline resectable PDAC, neoadjuvant chemotherapy has been advised. For clearly resectable PDAC, neoadjuvant chemotherapy also might be considered for the patients with high-risk features, but with no precise quantitative criteria to define these features. So, this study aimed to re-evaluate the relationship between high-risk features and prognosis of clearly resectable pancreatic cancer, and to define the precise criteria for these high-risk features.Methods: Data from 211 patients with clearly resectable pancreatic cancer were reviewed to assess the relationship between overall survival (OS) after surgery and high-risk features, and cut-off values were determined for high-risk features that were associated with poor prognosis of clearly resectable pancreatic cancer.Results: Lymph node metastasis (LNM), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and primary tumor size ≥6 cm were significant variables related to OS. CA19-9 ≥1,000 U/mL was statistically related to prognosis, as was CA19-9 ≥500 U/mL without obstructive jaundice. There was no significant relationship between abdominal and/or back pain and OS, but patients with moderate or severe pain accompanied by tumor size ≥4 cm or 10 times higher CA19-9 levels had worse prognosis.Conclusions: For clearly resectable pancreatic cancer with R0 resection, the high-risk features were clarified. Abdominal and/or back pain may not be used as a prognostic indicator alone, though combined with CA19-9 or tumor size it may be more valuable for predicting prognosis.
Background: Breast cancer is currently the leading cause of women's death. It is crucial to further improve the approach to treatment and the long-term survival rate of breast cancer patients, and to reduce the rates of recurrence and metastasis. It has been reported that the possibility of tumor metastasis depends on the metastatic potential of the tumor and the host defense against tumor metastasis, in which cellular immunity and the function of natural killer (NK) cells are critical to maintaining this balance. Surgical stress response and postoperative pain inhibit perioperative immune function in patients and increase the likelihood of dissemination and metastasis of cancer cells after cancer surgery. The study aims to investigate the effect of anesthetic factors and pain treatment on the long-term prognosis of patients with early stage lymph node negative breast preservation surgery.Methods: A total of 337 patients with early-stage lymph node negative breast cancer (ASA I-II) who had undergone successful breast-conserving surgery in our hospital were included in this retrospective analysis.Cases were divided into general anesthesia with postoperative analgesia group (GA + PCA), general anesthesia without postoperative analgesia group (GA), epidural anesthesia with postoperative analgesia group (EA + PCA), and epidural anesthesia without postoperative analgesia group (EA). The 5-year survival rate and 5-year disease-free survival were recorded in the 4 groups.Results: The general condition and length of hospital stay of the patients were not statistically different between the 4 groups. However, the 5-year survival rate and 5-year disease-free survival rate of the 4 groups were statistically different. The 5-year survival rate and 5-year disease-free survival rate were the lowest in the GA group, while the EA + PCA group had the highest 5-year disease-free survival rate. The 5-year survival rate and 5-year disease-free survival rate in the GA + PCA group were significantly higher than those in the GA group. The 5-year disease-free survival rate in EA group was significantly higher than GA group.Conclusions: Epidural anesthesia and postoperative pain treatment maybe beneficial to the long-term prognosis of patients with early-stage lymph node-negative breast cancer.
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