The most commonly occurring sarcoma of the soft tissue is gastrointestinal stromal tumor (GIST). Treatment and prevention of the disease necessitate an understanding of the molecular mechanisms involved. However, the role of BRD4 in the progression of GIST is still unclear. While it is known there are abundant infiltrating tumor-associated macrophages (TAMs) in the tumor microenvironment, the exact role of these cells has yet to be studied. This work showed an upregulation of BRD4 in GIST that was associated with GIST prognosis. Through gain and loss of function studies, it was found that BRD4 promotes GIST growth and angiogenesis in vitro and in vivo. Mechanistically, BRD4 enhances CCL2 expression by activating the NF-κB signaling pathway. Furthermore, this CCL2 upregulation causes recruitment of macrophages into the tumor leading to tumor growth. A likely mechanism for interactions in the GIST microenvironment has been outlined by this work to show the role and potential use of BRD4 as a treatment target in GIST.
Aim: To develop and validate a model to predict possibility of lymph node metastasis (LNM) in early gastric cancer. Materials & methods: An LNM prediction model was developed by logistic regression based on the demographics or characteristics of the tumor (N = 746) and then internally and externally validated (N = 126). Results: Four variables, lymphovascular invasion, differentiated types, diameter of tumor and T stage were screened into the model. The area under the receiver-operating characteristic curve of the model was 0.861 (95% CI: 0.851–0.864) in internal validation and 0.911 (95% CI: 0.848–0.974) in the validation set. Conclusion: The model shows excellent discrimination and calibration performance, and is potential to be a useful clinical model to predict the risk of LNM in early gastric cancer.
Background Radical gastrectomy with D2 lymphadenectomy is recognized as the standard treatment for resectable advanced gastric cancer. Preoperative fibrinogen and albumin measurements may bring clinical benefits in terms of providing advanced notice of a poor prognosis or recurrence in patients undergoing radical resection. The aim of this study was to identify markers that are predictive of a poor prognosis prior to surgery. Methods Eight hundred forty-two consecutive patients who underwent curative radical gastrectomy at our hospital between 2008 and 2012 were retrospectively reviewed. Based on plasma fibrinogen and serum albumin levels, preoperative fibrinogen and albumin scores (Fib-Alb scores) were investigated, and the prognostic significance was determined. Results The patients were classified according to a Fib-Alb score of 0 (n = 376), 1 (n = 327), or 2 (n = 139). When the correlation between the response rate and the change in the Fib-Alb score was investigated, the response rate was significantly lower in patients with an increased Fib-Alb score than in the other patients. In the survival analysis, patients in the Fib-Alb high-score group exhibited significantly worse recurrence-free survival (RFS) (P = 0.030) than patients in the other groups. A multivariate analysis using clinical stage and the change in the Fib-Alb score as covariates revealed that a change in the Fib-Alb score (Fib-Alb score 1, HR: 1.31, 95% CI: 1.03-1.66, P = 0.028; Fib-Alb score 2, HR: 1.61, 95% CI: 1.20-2.17, P = 0.001) was a significant independent predictive factor for RFS. Conclusions The prognosis of patients with high fibrinogen and low albumin levels is poor. The Fib-Alb score was shown to be an independent prognostic factor for postoperative recurrence in gastric cancer patients who underwent radical gastrectomy.
Postoperative adhesions are a common cause of adhesive small bowel obstruction (ASBO), and recognition of intestinal strangulation is important. The aim of this study is to analyze the clinical factors for strangulating obstruction and to identify the predictors for recurrence of ASBO.A retrospective study was conducted using the database in our department. Patients with ASBO from January 2013 to April 2016 were included in the study and were subject to follow-up. The clinical factors associated with strangulating obstruction and recurrence after treatment were analyzed by using univariate and multivariate logistic regression model.In total, 288 ASBO patients were included in the study. Of these, 37 (12.9%) patients had occurred strangulating obstructions, and 251 (87.1%) patients had simple obstructions. Four clinical parameters, including increasing heart rate (>100 bpm), increasing WBC count (>15 × 109/L), CT findings of thickening or swelling of the mesentery, and CT showing seroperitoneum were detected as independent clinical factors for intestinal strangulation. Eighty-four (29.2%) patients experienced recurrence of obstruction during the median 24 months of follow-up. Recurrence rates were reduced in patients who underwent surgical treatment compared with those who received conservative management [21.3% (26/122) vs 34.9% (58/166) (P = .010)]. Nevertheless, the recurrence rates were not significantly increased in patients with strangulating obstructions compared with those with simple ASBO [34.3% (12/35) vs 27.7% (72/253) (P = .186)].Four clinical parameters including tachycardia, leukocytosis, along with CT findings of thickening or swelling of the mesentery and CT showing seroperitoneum, associated with occurrence of intestinal strangulation in ASBO. ASBO patients who underwent surgical treatment had a reduced recurrence rate, but ASBO patients with strangulating obstructions had not increase the recurrence rates than those of patients with simple ASBO.
Curcumin and its chalcone derivatives have well‐known, explicit biological antitumor properties, such as instance antiproliferative and apoptotic effects via multiple molecular targets. In this study, we investigated the anticancer activity of curcumin derivative L6H4 (curcumin L6H4) on gastric cancer cells. Inhibitory effects of curcumin L6H4 on gastric cancer cells (BGC‐823) were studied by the diphenyltetrazolium (MTT) assay, and cell apoptosis was detected by Annexin‐V/propidium iodide (PI) staining and then analyzed by flow cytometry. A mouse xenotransplant gastric tumor model was established to detect the role of curcumin L6H4 in vivo. The apoptosis‐related proteins p53, p21, Bax, and Bcl‐2 in BGC‐823 cells and mouse xenotransplant models treated with curcumin L6H4 were determined by Western blot analysis. Curcumin L6H4 can significantly inhibit the proliferation and induce the apoptosis of BGC‐823 cells, thus enhancing the expression levels of p53, p21, Bax, and Bcl‐2 noticeably in vivo and in vitro. Meanwhile, curcumin L6H4 can remarkably suppress the growth of tumor cells in animal models. These results suggest that curcumin derivative L6H4 has potent of antitumor properties in vitro or in vivo.
Rationale:Neonatal appendicitis is extremely rare, and preoperative diagnosis is challenging. This study aimed to investigate the utility of ultrasound for the diagnosis of neonatal appendicitis.Patient concerns:Four cases of neonatal appendicitis were included in this case series. One was a female infant and the other 3 were male infants; they were aged from 10 to 17 days.Diagnoses:Neonatal appendicitis.Interventions:Four newborns in our hospital were diagnosed with neonatal appendicitis by abdominal ultrasound. Their sonographic features were summarized and compared with surgical and pathological findings.Outcomes:In these infants, abdominal ultrasound demonstrated ileocecal bowel dilatation, intestinal and bowel wall thickening, and localized encapsulated effusion in the right lower quadrant and the abscess area, which was assumed to surround the appendix.Lessons:Ultrasound is helpful for the diagnosis of neonatal appendicitis.
Gastrointestinal stromal tumors (GISTs) are primarily characterized by activating mutations of tyrosine kinase or platelet-derived growth factor receptor alpha. Although the revolutionary therapeutic outcomes of imatinib are well known, the long-term benefits of imatinib are still unclear. The effects of BRD9, a recently identified subunit of noncanonical BAF complex (ncBAF) chromatin remodeling complexes, in GISTs are not clear. In the current study, we evaluated the functional role of BRD9 in GIST progression. Our findings demonstrated that the expression of BRD9 was upregulated in GIST tissues. The downregulation or inhibition of BRD9 could significantly reduce cellular proliferation, and facilitates apoptosis in GISTs. BRD9 inhibition could promote PUMA-dependent apoptosis in GISTs and enhance imatinib activity in vitro and in vivo. BRD9 inhibition synergizes with imatinib in GISTs by inducing PUMA upregulation. Mechanism study revealed that BRD9 inhibition promotes PUMA induction via the TUFT1/AKT/GSK-3β/p65 axis. Furthermore, imatinib also upregulates PUMA by targeting AKT/GSK-3β/p65 axis. In conclusion, our results indicated that BRD9 plays a key role in the progression of GISTs. Inhibition of BRD9 is a novel therapeutic strategy in GISTs treated alone or in combination with imatinib.
In gastrointestinal stromal tumours (GISTs), the function of bromodomain‐containing 4 (BRD4) remains underexplored. BRD4 mRNA abundance was quantified in GISTs. In the current study, we investigated the role of BRD4 in GISTs. Our results show a significant enhancement in BRD4 mRNA and a shift from very low‐risk/low‐risk to high‐risk levels as per NCCN specifications. Overexpression of BRD4 correlated with unfavourable genotype, nongastric location, enhanced risk and decreased disease‐free survival, which were predicted independently. Knockout of BRD4 in vitro suppressed KIT expression, which led to inactivation of the KIT/PI3K/AKT/mTOR pathway, impeded migration and cell growth and made the resistant GIST cells sensitive to imatinib. The expression of KIT was repressed by a BRD4 inhibitor JQ1, which also induced myristoylated‐AKT‐suppressible caspases 3 and 9 activities, induced LC3‐II, exhibited dose‐dependent therapeutic synergy with imatinib and attenuated the activation of the PI3K/AKT/mTOR pathway. In comparison with their single therapy, the combination of JQ1/imatinib more efficiently suppressed the growth of xenografts and exhibited a reduction in KIT phosphorylation, a decrease in Ki‐67 and in the levels of phosphorylated PI3K/AKT/mTOR and enhanced TUNEL staining. Thus, we characterized the biological, prognostic and therapeutic implications of overexpressed BRD4 in GIST and observed that JQ1 suppresses KIT transactivation and nullifies the activation of PI3K/AKT/mTOR, providing a potential strategy for treating imatinib‐resistant GIST through dual blockade of KIT and BRD4.
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.