Colorectal cancer stem cell (CSC) has been regarded to be the root of colorectal cancer progression. However, there is still no effective therapeutic method targeting colorectal CSC in clinical application. Here, we investigated the effects of dichloroacetate (DCA) on colorectal cancer cell stemness. We showed that DCA could reduce colorectal cancer cell stemness in a dose‐dependent manner, which is evident by the decreased expression of stemness markers, tumor cell sphere‐formation and cell migration ability. In addition, it was found that DCA trigerred the ferroptosis of colorectal CSC, which is characterized as the upregulation of iron concentration, lipid peroxides, and glutathione level, and decreased cell viability. Mechanistic studies demonstrated that DCA could sequester iron in lysosome and thus trigger ferroptosis, which is necessary for DCA‐mediated attenuation on colorectal cancer cell stemness. Taken together, this work suggests that DCA might be a colorectal CSC‐killer.
Hepatocellular carcinoma (HCC) is a common malignancy with a poor prognosis worldwide. However, the pathogenesis of HCC remains poorly understood. In this study, we found that NOL12 was significantly overexpressed in independent HCC datasets from TCGA database. We confirmed that the expression level of NOL12 was upregulated in human HCC tissues and cell lines by RT-qPCR. High expression of NOL12 is associated with worse reduced overall survival (OS), high pathological grade, node metastasis, and advanced clinical stage in patients with HCC. Moreover, knockdown of NOL12 dramatically inhibits the proliferation and metastasis of HCC cells in vitro and in vivo. CIBERSORTx analysis revealed that twelve types of tumor-infiltrating immune cells (TICs) are correlated with NOL12 expression. The risk signature based on 8 NOL12-related genes is an independent prognostic factor for patients with HCC. The OS rate of patients in the low-risk score group was better than that in the high-risk score group. In addition, the total tumor mutation burden (TMB) in the high-risk score group increased significantly, and the risk scores could be used as an alternative indicator of immune checkpoint inhibitor (ICI) response. In conclusion, our findings indicated that NOL12 might be involved in the progression of HCC and can be used as a potential therapeutic target. Moreover, the NOL12-related risk signature may have predictive relevance with regard to ICI therapy.
Pancreatic adenosquamous carcinoma (ASPC) is a rare subtype of pancreatic cancer with lethal malignancy, and few studies have focused on the heterogeneity of ASPC. Here, we performed a single-cell sequencing procedure on pancreatic tumor tissue from an ASPC patient and a patient with high-grade intraductal papillary mucinous neoplasm (IPMN). Through the combined analysis of single-cell sequencing data from five pancreatic ductal adenocarcinoma (PDAC) patients, one IPMN patient, and one ASPC patient in a public database, we identified 11 main types of cells, including macrophages, B cells, cancer stem cells, ductal cells, fibroblasts, endo/stellate cells, neutrophils, acinar cells, T cells, natural killer (NK) cells, dendritic cells, and mast cells. Then, the different characteristics and differentiation paths of the immune microenvironment among IPMN, ASPC, and PDAC in macrophages, T cells, and cancer-associated fibroblasts (CAFs) were identified through multiple bioinformatics analyses. Two novel special cancer-associated fibroblasts were identified as nCAFs and imCAFs. Then, cancer cells in duct cells were identified using the infercnv software. Two ASPC-specific subgroups of cancer cells with squamous cell features were identified. Finally, the identified specific CAFs and cancer cells were mapped to TCGA-PAAD cohort through the cibersoftx software. All of these identified subgroups were calculated to have a significant prognostic value in pancreatic cancer patients. These findings will promote the clinical application of single-cell sequencing data of pancreatic cancer and deepen our understanding of ASPC.
BACKGROUND Solid pseudopapillary neoplasm (SPN) of the pancreas is a rare neoplasm that mainly affects young women. AIM To evaluate the impact of parenchyma-preserving surgical methods (PPMs, including enucleation and central pancreatectomy) in the treatment of SPN patients. METHODS From 2013 to 2019, patients who underwent pancreatectomy for SPNs were retrospectively reviewed. The baseline characteristics, intraoperative index, pathological outcomes, short-term complications and long-term follow-up data were compared between the PPM group and the conventional method (CM) group. RESULTS In total, 166 patients were included in this study. Of them, 33 patients (19.9%) underwent PPM. Most of the tumors (104/166, 62.7%) were found accidentally. Comparing the parameters between groups, the hospital stay d (12.35 vs 13.5 d, P = 0.49), total expense (44213 vs 54084 yuan, P = 0.21), operation duration (135 vs 120 min, P = 0.71), and intraoperative bleeding volume (200 vs 100 mL, P = 0.49) did not differ between groups. Regarding pathological outcomes, tumor size (45 vs 32 mm, P = 0.07), Ki67 index ( P = 0.53), peripheral tissue invasion (11.3% vs 9.1%, P = 0.43) and positive margin status (7.5% vs 6%, P = 0.28) also did not differ between groups. Moreover, PPM did not increase the risk of severe postoperative pancreatic fistula (3.8% vs 3.0%, P = 0.85) or tumor recurrence (3.0% vs 6.0%, P = 0.39). However, the number of patients who had exocrine insufficiency during follow-up was significantly lower in the PPM group (21.8% vs 3%, P = 0.024). CM was identified as an independent risk factor for pancreatic exocrine insufficiency (odds ratio = 8.195, 95% confident interval: 1.067-62.93). CONCLUSION PPM for SPN appears to be feasible and safe for preserving the exocrine function of the pancreas.
Worldwide, the incidence rate of gastric cancer ranks fifth, and the mortality rate of gastric cancer ranks third among all malignant tumors. However, the pathogenesis of gastric cancer remains poorly understood. In this study, we demonstrated that the expression level of NELFE is higher in human gastric cancer tissues than in adjacent nontumor tissues. A high level of NELFE is associated with worse postoperative overall survival (OS) and relapse-free survival (RFS) rates in patients with gastric cancer. Moreover, the expression of NELFE is correlated with high tumor grade and lymph node metastasis in gastric cancer patients. Knockdown of NELFE dramatically inhibits the cell proliferation and metastasis of gastric cancer xenografts in vivo. Furthermore, we found that NELFE binding to the 3’UTR of E2F2 affects the mRNA stability of E2F2 to regulate the expression level of E2F2. In gastric cancer, E2F2 also acts as an oncogene to inhibit the proliferation and migration of gastric cancer cells by knocking down the expression level of E2F2. However, overexpressing E2F2 in cells with NELFE knockdown significantly reverses the inhibition of cell proliferation and migration induced by NELFE knockdown. Therefore, NELFE at least partially functions as an oncogene through E2F2. Moreover, CIBERSORTx analysis of the proportion of tumor-infiltrating immune cells (TICs) revealed that immune cells are correlated with NELFE and E2F2 expression, suggesting that NELFE and E2F2 might be responsible for the preservation of the immunodominant status for gastric cancer. In conclusion, NELFE acts as an oncogene in gastric cancer and can be used as a potential therapeutic target.
BackgroundAlthough various pancreaticojejunal duct-to-mucosa anastomosis methods have been developed to reduce the postoperative risks of pancreaticoduodenectomy, pancreatic fistula remains the most serious complication with a high incident rate. The aim of this study is to compare the safety and effectiveness of one-layer and two-layer duct-to-mucosa pancreaticojejunostomy in patients undergoing pancreaticoduodenectomy.Methods/designIn this study, adult patients who sign consent forms will be recruited and scheduled for elective pancreaticoduodenectomy. One hundred and fourteen patients will be included and randomized before pancreaticojejunal reconstruction and after resection of the lesion from the pancreatic or periampullary region. The primary efficacy endpoint is the incident rate of postoperative pancreatic fistula. Statistical analysis will be based on the intention-to-treat population. Patients will be followed up for 3 months by monitoring for complications and other adverse events.DiscussionThis prospective, single-center, randomized, single-blinded, two-group parallel trial is designed to compare one-layer with two-layer duct-to-mucosa anastomosis for pancreaticojejunal anastomosis during elective pancreaticoduodenectomy.Trial registrationClinical Trials.gov: NCT02511951. Registered on 29 July 2015.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-016-1517-8) contains supplementary material, which is available to authorized users.
Background and aimsEndoscopic ultrasound (EUS) is playing a more and more important role in the management of pancreatic cystic lesion (PCLs). The aim of our study was to evaluate the clinical impact of EUS and EUS guided fine needle aspiration (FNA) on patients with low-risk PCLs.Materials and methodsLow-risk PCL patients who underwent EUS-FNA in 2 edoscopic centers were retrospectively collected and analyzed. The clinical impact of EUS-FNA on these patients was analyzed and the predictors for significance EUS-FNA (defined by diagnosis and treatment method change, new high-risk feature identified after imaging scans) were analyzed by logistic regression analyses.ResultsFrom July 2004 to February 2017, 186 patients with low-risk PCLs were included. The study cohort had a mean age of 52.4 ± 15.9 years (range: 19-86 years) with 89 (47.8%) male patients included. The clinical significance of EUS-FNAs was observed in 74 patients (39.8%). The presumed diagnoses of PCLs by imaging were changed in 51 (51/74, 68.9%) patients. Nineteen (19/74, 25.7%) new high-risk features were identified by EUS-FNA, and four patients (4/74, 5.4%) underwent surgery due to suspicious or malignant cytology. Based on multivariate analysis, large cyst size [odds ratio (OR): 1.12, 95% confidence interval (CI): 1.02–1.19, P = 0.033], young age (OR: 0.94, 95% CI: 0.91–0.99, P = 0.041) and BMI over 25 (OR: 3.15, 95% CI: 1.29–7.86, P = 0.013) were independent predictors of clinical significance for EUS-FNA. The optimal age and cyst size to predict significance EUS-FNA was 46.0 years and 2.3cm.ConclusionsOn the basis of a 2-center retrospective study, EUS-FNA was clinically significant in about 40% of low-risk PCLs, especially in young, large cyst size, and overweight patients.
BackgroundColorectal cancer (CRC) incidence has increased among patients aged <50 years. Exploring high‐risk factors and screening high‐risk populations may help lower early‐onset CRC (EO‐CRC) incidence. We developed noninvasive predictive models for EO‐CRC and investigated its risk factors.MethodsThis retrospective multicenter study collected information on 1756 patients (811 patients with EO‐CRC and 945 healthy controls) from two medical centers in China. Sociodemographic features, clinical symptoms, medical and family history, lifestyle, and dietary factors were measured. Patients from one cohort were randomly assigned (8:2) to two groups for model establishment and internal validation, and another independent cohort was used for external validation. Multivariable logistic regression, random forest, and eXtreme Gradient Boosting (XGBoost) were performed to establish noninvasive predictive models for EO‐CRC. Some variables in the model influenced EO‐CRC occurrence and were further analyzed. Multivariable logistic regression analysis yielded adjusted odd ratios (ORs) and 95% confidence intervals (CIs).ResultsAll three models showed good performance, with areas under the receiver operator characteristic curves (AUCs) of 0.82, 0.84, and 0.82 in the internal and 0.78, 0.79, and 0.78 in the external validation cohorts, respectively. Consumption of sweet (OR 2.70, 95% CI 1.89–3.86, P < 0.001) and fried (OR 2.16, 95% CI 1.29–3.62, P < 0.001) foods ≥3 times per week was significantly associated with EO‐CRC occurrence.ConclusionWe established noninvasive predictive models for EO‐CRC and identified multiple nongenetic risk factors, especially sweet and fried foods. The model has good performance and can help predict the occurrence of EO‐CRC in the Chinese population.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.