ABSTRACT
BACKGROUND: The protein arginine methyltransferase family includes nine members, with PRMT5 being the major type II arginine methyltransferase. PRMT5 is upregulated in a variety of tumors and promotes tumorigenesis and tumor cell proliferation and metastasis, making it a potential tumor therapy target. Recently, PRMT5 inhibitor research and development have become hotspots in the tumor therapy field. METHODS: We classified and summarized PRMT5 inhibitors according to different binding mechanisms. We mainly analyzed the structure, biological activity, and binding interactions of PRMT5 inhibitors with the PRMT5 enzyme. RESULTS: At present, many PRMT5 inhibitors with various mechanisms of action have been reported, including substrate-competitive inhibitors, SAM-competitive inhibitors, dual substrate-/SAMcompetitive inhibitors, allosteric inhibitors, PRMT5 degraders, MTA-cooperative PRMT5 inhibitors and PPI inhibitors. CONCLUSION: These inhibitors are beneficial to the treatment of tumors. Some drugs are being used in clinical trials. PRMT5 inhibitors have broad application prospects in tumor therapy.
Subject(s)
Neoplasms , Protein-Arginine N-Methyltransferases , Humans , Protein-Arginine N-Methyltransferases/chemistry , Protein-Arginine N-Methyltransferases/metabolism , Neoplasms/drug therapy , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/chemistry , Cell Line, Tumor , Arginine/metabolismABSTRACT
Endoscopic submucosal dissection (ESD) is an accepted treatment for early esophageal cancer and precancerous lesions, but resection of a large mucosal area often leads to postoperative esophageal stricture. Biomaterials provide a new option for the treatment of post-ESD ulcers. In this study, we developed a well-defined ammonolysis-based tetra-armed poly (ethylene glycol) (Tetra-PEG) hydrogel and investigated its efficacy and related mechanisms for preventing esophageal ESD-induced stricture in a porcine model. In terms of material properties, Tetra-PEG hydrogel present great biocompatibilityï¼great capability to retain moisture, strong tissue adhesion and high mechanical strength. Then, six domestic female pigs were randomly divided into PEG (n = 3) and control groups (n = 3). A 3/4 of the esophageal circumference ESD was performed in all pigs. In PEG group, Tetra-PEG hydrogel was easily delivered via endoscopy and adhered to the ulcer bed tightly. Compared to control group, Tetra-PEG hydrogel accelerated esophageal ulcer healing at an early stage with enhanced epithelium regeneration, milder inflammation and lesser fibrosis by regulating TGF-ß/Smad2 signaling. Taken together, our findings reveal Tetra-PEG hydrogel is a promising and attractive candidate for preventing the formation of fibrotic stricture in the process of esophageal ESD-induced ulcer repair.
Subject(s)
Endoscopic Mucosal Resection , Esophageal Stenosis , Female , Swine , Animals , Esophageal Stenosis/etiology , Esophageal Stenosis/prevention & control , Esophageal Stenosis/pathology , Endoscopic Mucosal Resection/adverse effects , Constriction, Pathologic , Hydrogels/pharmacology , Ulcer/pathology , Ulcer/surgery , Biocompatible Materials , FibrosisABSTRACT
BACKGROUND: Previous studies have reported the effectiveness of narrow-band imaging (NBI) and linked-color imaging (LCI) in improving the detection of colorectal neoplasms. There has however been no direct comparison between LCI and NBI in the detection of colorectal sessile serrated lesions (SSLs). The present study aimed to compare the effectiveness of LCI and NBI in detecting colorectal SSLs. METHODS: A prospective, parallel, randomized controlled trial was conducted. The participants were randomly assigned to the LCI or NBI arms. The primary end point was the SSL detection rate (SDR). RESULTS: 406 patients were involved; 204 in the LCI arm and 202 in the NBI arm. The total polyp detection rate, adenoma detection rate, and SDR were 54.2â%, 38.7â%, and 10.8%, respectively. The SDR was not significantly different between the LCI and NBI arms (12.3â% vs. 9.4â%; Pâ=â0.36). The differences in the detection rate and the per-patient number of polyps, adenomas, diminutive lesions, and flat lesions between LCI and NBI also were not statistically significant. Multivariate analysis showed that LCI and NBI were not independent factors associated with SDR, whereas Boston Bowel Preparation Scale score (odds ratio [OR] 1.35, 95â%CI 1.03-1.76; Pâ=â0.03), withdrawal time (OR 1.13, 95â%CI 1.00-1.26; Pâ=â0.04), and operator experience (OR 3.73, 95â%CI 1.67-8.32; Pâ=â0.001) were independent factors associated with SDR. CONCLUSIONS: LCI and NBI are comparable for SSL detection, as well as for the detection of polyps and adenomas.
Subject(s)
Adenoma , Colonic Polyps , Colorectal Neoplasms , Humans , Colonic Polyps/diagnostic imaging , Colonic Polyps/pathology , Colonoscopy/methods , Prospective Studies , Colorectal Neoplasms/diagnostic imaging , Colorectal Neoplasms/pathology , Narrow Band Imaging/methods , Adenoma/diagnostic imaging , Adenoma/pathologyABSTRACT
BACKGROUND & AIMS: Linked color imaging (LCI) is a novel technology that improves the color differences between colorectal lesions and the surrounding mucosa. The present study aims to compare the detection of colorectal sessile serrated lesions (SSL) using LCI with white light imaging (WLI). METHOD: A large-scale, multicenter, parallel prospective randomized controlled trial was conducted in 4 hospitals in China. The participants were randomly assigned to the LCI group and WLI group. The primary endpoint was the SSL detection rate (SDR). RESULTS: A total of 884 patients were involved in the intention-to-treat analysis, with 441 patients in the LCI group and 443 patients in the WLI group. The total polyp detection rate, adenoma detection rate, and SDR were 51.8%, 35.7%, and 8.6%, respectively. The SDR was significantly higher in the LCI group than in the WLI group (11.3% vs 5.9%, P = .004). Furthermore, LCI significantly increased the number of polyps and adenomas detected per patient, when compared with WLI (P < .05). In addition, there was higher detection rate of diminutive and flat lesions in the LCI group (P < .05). Multivariate analysis revealed that LCI is an independent factor associated with SDR (hazard ratio, 1.990; 95% confidence interval, 1.203-3.293; P = .007), along with withdrawal time (hazard ratio, 1.157; 95% confidence interval, 1.060-1.263; P = .001) and operator experience (hazard ratio, 1.850; 95% confidence interval, 1.045-3.273; P = .035). CONCLUSIONS: LCI is significantly superior to WLI for SSL detection, and may improve polyp and adenoma detection. LCI can be recommended as an appropriate method for routine inspection during colonoscopy (http://www.chictr.org.cn number, ChiCTR2000035705).
Subject(s)
Adenoma , Colonic Polyps , Colorectal Neoplasms , Humans , Colonic Polyps/diagnostic imaging , Colonic Polyps/pathology , Colorectal Neoplasms/diagnostic imaging , Colorectal Neoplasms/pathology , Prospective Studies , Colonoscopy/methods , Adenoma/diagnostic imaging , Adenoma/pathologyABSTRACT
INTRODUCTION: Adequate exposure of the dissection site is very important for colorectal endoscopic submucosal dissection (ESD). We aimed to investigate the safety and efficacy of the preincision traction (PIT) method using an internal clip-with-spring device in comparison with the conventional on-demand traction (ODT) method in assisting colorectal ESD. METHODS: This was a prospective nested case-control study. A total of 26 patients for PIT-ESD and other 26 patients for ODT-ESD were involved. Data on clinical characteristics and therapeutic outcomes were collected and analyzed. RESULTS: The en bloc resection rate (both 100%) and curative resection rate (92.3% vs 96.2%) showed no significant difference between the 2 groups. Compared with ODT-ESD, PIT-ESD significantly reduced the procedure time (29.8 ± 18.4 vs 57.4 ± 33.7 minutes, P = 0.001) and submucosal injection volume (49.6 ± 32.3 vs 70.8 ± 37.6 mL, P = 0.034), decreased the rate of intraoperative bleeding (26.9% vs 57.7%, P = 0.025) and muscular injury (7.7% vs 34.6%, P = 0.038), and shortened the postoperative hospital stay (1.8 ± 0.8 vs 2.5 ± 1.2, P = 0.015). DISCUSSION: The PIT method could significantly improve the safety and efficacy of colorectal ESD.
Subject(s)
Colorectal Neoplasms , Endoscopic Mucosal Resection , Humans , Treatment Outcome , Endoscopic Mucosal Resection/adverse effects , Endoscopic Mucosal Resection/methods , Traction/adverse effects , Case-Control Studies , Prospective Studies , Colorectal Neoplasms/surgeryABSTRACT
BACKGROUND AND AIMS: Computer-aided diagnosis of EUS images was quite useful in differentiating pancreatic cancer from normal tissue and chronic pancreatitis. This study investigated the feasibility of using computer-aided diagnostic techniques to extract EUS image parameters to distinguish autoimmune pancreatitis from chronic pancreatitis. METHODS: A new descriptor, local ternary pattern variance, was introduced to improve the performance of the classification model. Patients with autoimmune pancreatitis (n = 81) or chronic pancreatitis (n = 100) were recruited for this study. Representative EUS images were selected, and 115 parameters from 10 categories were extracted from the region of interest. Distance-between-class and sequential forward selection algorithms were used for their ideal combination of features that allowed a support vector machine predictive model to be built, trained, and validated. The accuracy, sensitivity, specificity, positive predictive values (PPVs), and negative predictive values (NPVs) were used to evaluate the performance of experimental results. RESULTS: Fourteen parameters from 3 categories were selected as an ideal combination of features. The sample set was randomly divided into a training set and a testing set by using two different algorithms-the leave-one-out algorithm and the half-and-half method. The half-and-half method yielded an average (± standard deviation) accuracy of 89.3 ± 2.7%, sensitivity of 84.1 ± 6.4%, specificity of 92.5 ± 3.3%, PPV of 91.6 ± 3.7%, and NPV of autoimmune pancreatitis of 88.0 ± 4.1%. CONCLUSIONS: This study shows that, with the local ternary pattern variance textural feature, computer-aided diagnosis of EUS imaging may be valuable to differentiate autoimmune pancreatitis from chronic pancreatitis. Further refinement of such models could generate tools for the clinical diagnosis of autoimmune pancreatitis.
Subject(s)
Algorithms , Autoimmune Diseases/diagnosis , Diagnosis, Computer-Assisted/methods , Diagnostic Imaging , Pancreatitis/diagnosis , Diagnosis, Differential , Humans , Pancreatitis, Chronic/diagnosis , ROC Curve , Reproducibility of Results , Retrospective StudiesABSTRACT
BACKGROUND: The negative predictive value of endoscopic ultrasonography-guided fine needle aspiration for the diagnosis of solid pancreatic lesions remains low, and the biopsy specimens are sometimes inadequate for appropriate pathological diagnosis. AIMS: To evaluate the usefulness of a novel method of contrast-enhanced harmonic endoscopic ultrasonography-guided fine-needle aspiration for the differential diagnosis and adequate sampling of solid pancreatic lesions. METHODS: Patients with a diagnosis of solid pancreatic lesions who underwent fine-needle aspiration guided by contrast-enhanced harmonic endoscopic ultrasonography or by endoscopic ultrasonography from October 2010 to July 2013 were retrospectively identified and classified into the CH-EUS or EUS group, respectively. Surgical pathology and/or follow-up results were defined as the final diagnosis. Operating characteristics and adequacy of biopsy specimens by fine-needle aspiration were compared between the two groups. RESULTS: Operating characteristics for contrast-enhanced harmonic endoscopic ultrasonography-guided fine-needle aspiration in solid pancreatic lesions were as follows: area under the curve = 0.908, sensitivity = 81.6%, specificity = 100%, positive predictive value = 100%, negative predictive value = 74.1%, and accuracy = 87.9%. The percentage of adequate biopsy specimens in the CH-EUS group (96.6%) was greater than that in the EUS group (86.7%). CONCLUSION: Simultaneous contrast-enhanced harmonic endoscopic ultrasonography during fine-needle aspiration is useful for improving the diagnostic yield and adequate sampling of solid pancreatic lesions.