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1.
Carbohydr Polym ; 336: 122125, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38670756

RESUMEN

In this study, we developed a tissue-adhesive and long-term antibacterial hydrogel consisting of protamine (PRTM) grafted carboxymethyl chitosan (CMC) (PCMC), catechol groups modified CMC (DCMC), and oxidized hyaluronic acid (OHA), named DCMC-OHA-PCMC. According to the antibacterial experiments, the PCMC-treated groups showed obvious and long-lasting inhibition zones against E. coli (and S. aureus), and the corresponding diameters varied from 10.1 mm (and 15.3 mm) on day 1 to 9.8 mm (and 15.3 mm) on day 7. The DCMC-OHA-PCMC hydrogel treated groups also exhibited durable antibacterial ability against E. coli (and S. aureus), and the antibacterial rates changed from 99.3 ± 0.21 % (and 99.6 ± 0.36 %) on day 1 to 76.2 ± 1.74 % (and 84.2 ± 1.11 %) on day 5. Apart from good mechanical and tissue adhesion properties, the hydrogel had excellent hemostatic ability mainly because of the grafted positive-charged PRTM. As the animal assay results showed, the hydrogel was conducive to promoting the deposition of new collagen (0.84 ± 0.03), the regeneration of epidermis (98.91 ± 6.99 µm) and wound closure in the process of wound repairing. In conclusion, the presented outcomes underline the prospective potential of the multifunctional CMC-based hydrogel for applications in wound dressings.


Asunto(s)
Antibacterianos , Quitosano , Quitosano/análogos & derivados , Escherichia coli , Hemostasis , Hidrogeles , Protaminas , Piel , Staphylococcus aureus , Cicatrización de Heridas , Quitosano/química , Quitosano/farmacología , Cicatrización de Heridas/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Hidrogeles/química , Hidrogeles/farmacología , Animales , Escherichia coli/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Protaminas/química , Protaminas/farmacología , Hemostasis/efectos de los fármacos , Piel/efectos de los fármacos , Ratones , Masculino , Ratas , Hemostáticos/farmacología , Hemostáticos/química , Adhesivos Tisulares/farmacología , Adhesivos Tisulares/química
2.
Lab Invest ; 104(5): 102042, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38431117

RESUMEN

Esophageal squamous cell carcinoma stands as a notably aggressive malignancy within the digestive system. In cases of early esophageal cancer without lymph node metastasis, endoscopic surgical resection offers a viable alternative, often resulting in improved patient quality of life. However, the paucity of methods to preoperatively ascertain lymph node involvement complicates surgical planning. SOX4 gene was previously found to be highly associated with invasive metastasis in our work through single-cell RNA sequencing on 5 paired tumor/peritumor tissues. This research included the collection of 124 tissue samples from 106 patients (106 tumor and 18 lymph node specimens). Samples were methodically arranged into a tissue microarray and treated with immunohistochemical staining. Statistical analysis was conducted to assess the relationship between them. In the univariate analysis, 3 factors were identified as statistically significant in relation to lymph node metastasis: T category (P = .014), vascular invasion (P < .001), and SOX4 intensity (P = .001). Additionally, when evaluating SOX4 intensity alongside other clinical indicators, SOX4 was shown to independently influence lymph node metastasis. Further, the multivariate analysis revealed that vascular invasion (P < .001) and SOX4 intensity (P = .003) were significantly associated with lymph node metastasis, exhibiting hazard ratios of 10.174 and 7.142, respectively. The results of our study indicate that both SOX4 expression and vascular invasion serve as predictors of lymph node metastasis in patients diagnosed with category T1 esophageal squamous cell carcinoma, underscoring the potential utility of SOX4 in prognostic evaluations.


Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Metástasis Linfática , Factores de Transcripción SOXC , Humanos , Masculino , Factores de Transcripción SOXC/metabolismo , Factores de Transcripción SOXC/genética , Femenino , Persona de Mediana Edad , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas de Esófago/metabolismo , Carcinoma de Células Escamosas de Esófago/patología , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/secundario , Carcinoma de Células Escamosas de Esófago/cirugía , Anciano , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Ganglios Linfáticos/patología , Ganglios Linfáticos/metabolismo , Adulto , Pronóstico
3.
Front Immunol ; 15: 1295305, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38481990

RESUMEN

Introduction: Ubiquitination is a crucial biological mechanism in humans, essential for regulating vital biological processes, and has been recognized as a promising focus for cancer therapy. Our objective in this research was to discover potential enzymes associated with ubiquitination that may serve as therapeutic targets for individuals with esophageal carcinoma (ESCA). Methods: To identify genes linked to the prognosis of ESCA, we examined mRNA sequencing data from patients with ESCA in the TCGA database. Further investigation into the role of the candidate gene in ESCA was conducted through bioinformatic analyses. Subsequently, we carried out biological assays to assess its impact on ESCA development. Results: Through univariate Cox regression analysis, we identified Ubiquitin Conjugating Enzyme E2 B (UBE2B) as a potential gene associated with the prognosis of ESCA. UBE2B exhibited significant upregulation and was found to be correlated with survival outcomes in ESCA as well as other cancer types. Additionally, UBE2B was observed to be involved in various biological pathways linked to the development of ESCA, including TNF-a signaling via NF-κB, epithelial-mesenchymal transition, inflammatory response, and hypoxia. Moreover, immune-related pathways like B cell activation (GO: 0042113), B cell receptor signaling pathway (GO: 0050853) and B cell mediated immunity (GO:0019724) were also involved. It was found that high expression of UBE2B was correlated with the increase of several kinds of T cells (CD8 T cells, Th1 cells) and macrophages, while effector memory T cell (Tem) and Th17 cells decreased. Furthermore, UBE2B showed potential as a prognostic biomarker for ESCA, displaying high sensitivity and specificity. Notably, proliferation and migration in ESCA cells were effectively suppressed when the expression of UBE2B was knocked down. Conclusions: To summarize, this study has made a discovery regarding the importance of gaining new insights into the role of UBE2B in ESCA. UBE2B might be an oncogene with good ability in predicting and diagnosing ESCA. Consequently, this discovery highlights the feasibility of targeting UBE2B as a viable approach for treating patients with ESCA.


Asunto(s)
Carcinoma , Neoplasias Esofágicas , Humanos , Pronóstico , Oncogenes , Linfocitos B , Neoplasias Esofágicas/genética , Biomarcadores , Enzimas Ubiquitina-Conjugadoras/genética
4.
Gastrointest Endosc ; 99(2): 186-192.e1, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37611811

RESUMEN

BACKGROUND AND AIMS: After endoscopic full-thickness resection (EFTR), reliable closure of the perforation is critical. However, it is technically difficult to close some defects by using metal clips alone or by purse-string suturing, which may lead to unreliable closure. Inspired by the process of pulling up the 2 ends of the incision in the surgical suture, we developed a new endoscopic closure technique, the "internal traction-assisted suspended closure" technique. This pilot study was performed as an initial evaluation of the feasibility and safety of this new endoscopic closure technique. METHODS: Data from patients in whom this suspended closure technique was used to close full-thickness defects after EFTR were retrospectively reviewed. The primary outcome was successful closure rate. Secondary outcomes were closure time, length of postprocedural hospital stay, and incidence of postprocedural adverse events. Defect size and tumor characteristics were also analyzed. RESULTS: Eight patients who underwent the suspended closure technique after EFTR were included. All patients were successfully treated with the suspended closure technique, and no patient developed serious adverse events. The median length of the defect was 3.25 cm (range, 2.5-9.0) and the median width was 2.8 cm (range, 1.8-6.0). The median closing time was 13 minutes (range, 6-24). CONCLUSIONS: The internal traction-assisted suspended closure technique is a simple, reliable, and easy-to-use technique for large full-thickness defects after endoscopic resection.


Asunto(s)
Resección Endoscópica de la Mucosa , Neoplasias Gástricas , Humanos , Gastroscopía/métodos , Proyectos Piloto , Neoplasias Gástricas/cirugía , Estudios Retrospectivos , Tracción , Resultado del Tratamiento
5.
Surg Endosc ; 37(8): 5883-5893, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37069428

RESUMEN

BACKGROUNDS: Esophageal gastrointestinal stromal tumors (E-GISTs) are extremely rare and surgical resection is the recommended approach. However, surgical resection usually causes severe trauma that may result in significant postoperative morbidity. Endoscopic resection (ER) has developed rapidly in recent years and has been widely used in gastrointestinal lesions. Nevertheless, the feasibility and efficacy of ER in the management of E-GISTs are unknown. METHODS: Retrospective data were collected from January 2011 to December 2020 in a large tertiary center of China. Twenty-eight patients with E-GISTs treated by ER were included in the study. RESULTS: Of the 28 patients, there were 21 males and 7 females, with a median age of 55 years (40-70 years). The median tumor size was 15 mm (5-80 mm). The technical success rate was 100% (28/28), while the en bloc resection rate was 96.4% (27/28). The median operation time was 35 min (10-410 min). Sixteen (57.2%) tumors were categorized into very low risk group, six (21.4%) into low risk group, and six (21.4%) into high risk group. Pathologists carefully examined margins of each lesion. There were 11 lesions (39.3%) determined as R0 resection and 17 lesions (60.7%) as R1 resection with positive margins. The median hospital stay was 2 days (range, 1-8 days). One patient suffered from hydrothorax and required drainage, leading to a major adverse event rate of 3.6% (1/28). There was no conversion to surgery, and no death occurred within 30 days after the procedure. Imatinib was given to two patients after ER under multidisciplinary team surveillance. During follow-up (median of 54 months, 9-122 months), no recurrences or metastasis were observed. CONCLUSION: ER is safe and effective for E-GISTs and might become an optional choice in the future. Multicenter, prospective, large samples with long-term follow-up studies are still needed.


Asunto(s)
Resección Endoscópica de la Mucosa , Neoplasias Esofágicas , Tumores del Estroma Gastrointestinal , Neoplasias Gástricas , Masculino , Femenino , Humanos , Persona de Mediana Edad , Tumores del Estroma Gastrointestinal/cirugía , Tumores del Estroma Gastrointestinal/patología , Resultado del Tratamiento , Estudios Prospectivos , Estudios Retrospectivos , Neoplasias Esofágicas/cirugía , China , Neoplasias Gástricas/cirugía , Resección Endoscópica de la Mucosa/métodos
6.
Clin Transl Med ; 13(3): e1203, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36855810

RESUMEN

BACKGROUND AND AIMS: The early diagnosis and intervention of oesophageal squamous cell carcinoma (ESCC) are particularly important because of the lack of effective therapies and poor prognosis. Comprehensive research on early ESCC at the single-cell level is rare due to the need for fresh and high-quality specimens obtained from ESD. This study aims to systematically describe the cellular atlas of human intramucosal ESCC. METHODS: Five paired samples of intramucosal ESCC, para-ESCC oesophageal tissues from endoscopically resected specimens and peripheral blood mononuclear cells were adopted for scRNA-seq analysis. Computational pipeline scMetabolism was applied to quantify the metabolic diversity of single cells. RESULTS: A total of 164 715 cells were profiled. Epithelial cells exhibited high intra-tumoural heterogeneity and two evolutionary trajectories during ESCC tumorigenesis initiated from proliferative cells, and then through an intermediate state, to two different terminal states of normally differentiated epithelial cells or malignant cells, respectively. The abundance of CD8+ TEX s, Tregs and PD1+ CD4+ T cells suggested an exhausted and suppressive immune microenvironment. Several genes in immune cells, such as CXCL13, CXCR5 and PADI4, were identified as new biomarkers for poor prognosis. A new subcluster of malignant cells associated with metastasis and angiogenesis that appeared at an early stage compared with progressive ESCC was also identified in this study. Intercellular interaction analysis based on ligand-receptor pairs revealed the subcluster of malignant cells interacting with CAFs via the MDK-NCL pathway, which was verified by cell proliferation assay and IHC. This indicates that the interaction may be an important hallmark in the early change of tumour microenvironment and serves as a sign of CAF activation to stimulate downstream pathways for facilitating tumour invasion. CONCLUSION: This study demonstrates the changes of cell subsets and transcriptional levels in human intramucosal ESCC, which may provide unique insights into the development of novel biomarkers and potential intervention strategies.


Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Carcinoma de Células Escamosas de Esófago/genética , Leucocitos Mononucleares , Transcriptoma/genética , Células Epiteliales , Neoplasias Esofágicas/genética , Microambiente Tumoral/genética
7.
Nat Commun ; 14(1): 1666, 2023 03 25.
Artículo en Inglés | MEDLINE | ID: mdl-36966136

RESUMEN

Esophageal squamous cell carcinoma (ESCC) is malignant while the carcinogenesis is still unclear. Here, we perform a comprehensive multi-omics analysis of 786 trace-tumor-samples from 154 ESCC patients, covering 9 histopathological stages and 3 phases. Proteogenomics elucidates cancer-driving waves in ESCC progression, and reveals the molecular characterization of alcohol drinking habit associated signatures. We discover chromosome 3q gain functions in the transmit from nontumor to intraepithelial neoplasia phases, and find TP53 mutation enhances DNA replication in intraepithelial neoplasia phase. The mutations of AKAP9 and MCAF1 upregulate glycolysis and Wnt signaling, respectively, in advanced-stage ESCC phase. Six major tracks related to different clinical features during ESCC progression are identified, which is validated by an independent cohort with another 256 samples. Hyperphosphorylated phosphoglycerate kinase 1 (PGK1, S203) is considered as a drug target in ESCC progression. This study provides insight into the understanding of ESCC molecular mechanism and the development of therapeutic targets.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Proteogenómica , Humanos , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas/genética , Mutación
8.
NPJ Digit Med ; 6(1): 41, 2023 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-36918730

RESUMEN

Optimal bowel preparation is a prerequisite for a successful colonoscopy; however, the rate of inadequate bowel preparation remains relatively high. In this study, we establish a smartphone app that assesses patient bowel preparation using an artificial intelligence (AI)-based prediction system trained on labeled photographs of feces in the toilet and evaluate its impact on bowel preparation quality in colonoscopy outpatients. We conduct a prospective, single-masked, multicenter randomized clinical trial, enrolling outpatients who own a smartphone and are scheduled for a colonoscopy. We screen 578 eligible patients and randomize 524 in a 1:1 ratio to the control or AI-driven app group for bowel preparation. The study endpoints are the percentage of patients with adequate bowel preparation and the total BBPS score, compliance with dietary restrictions and purgative instructions, polyp detection rate, and adenoma detection rate (secondary). The prediction system has an accuracy of 95.15%, a specificity of 97.25%, and an area under the curve of 0.98 in the test dataset. In the full analysis set (n = 500), adequate preparation is significantly higher in the AI-driven app group (88.54 vs. 65.59%; P < 0.001). The mean BBPS score is 6.74 ± 1.25 in the AI-driven app group and 5.97 ± 1.81 in the control group (P < 0.001). The rates of compliance with dietary restrictions (93.68 vs. 83.81%, P = 0.001) and purgative instructions (96.05 vs. 84.62%, P < 0.001) are significantly higher in the AI-driven app group, as is the rate of additional purgative intake (26.88 vs. 17.41%, P = 0.011). Thus, our AI-driven smartphone app significantly improves the quality of bowel preparation and patient compliance.

9.
Endosc Ultrasound ; 11(5): 393-400, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36255027

RESUMEN

Background and Objectives: Standard suction technique (SST), slow-pull technique (SPT), and wet suction technique (WEST) of EUS-FNA are designed to improve the diagnostic yields of solid and solid-cystic lesions. We conducted a multicenter, prospective, randomized crossover trial to compare SST, SPT, and WEST on specimen quality and diagnostic accuracy using a 22G needle. Methods: Patients with solid or solid-cystic lesions referred for EUS-FNA at four tertiary hospitals from December 2017 to August 2019 were considered eligible. All lesions were sampled using a 22G needle by the three techniques performed consecutively in a randomized order. The primary outcome was quality of the specimen acquired by each technique regarding blood contamination, tissue integrity and cellularity for diagnosis, graded on a predefined scale. The secondary outcomes were the diagnostic yield of EUS-FNA and the incidence of adverse events. ClinicalTrial. gov registration number: NCT03567863. Results: A total of 300 patients (mean age, 60.6 years, 188 men) were enrolled. WEST was superior (mean score 4.02 ± 1.51) over SST (3.67 ± 1.57, P = 0.018), but comparable to SPT (3.83 ± 1.55, P = 0.370) in overall specimen quality evaluation. WEST produced better tissue integrity (1.42 ± 0.74) and higher cellularity (1.32 ± 0.80) than SST and SPT. SPT (1.43 ± 0.69) was superior to SST (1.27 ± 0.72, P = 0.004) and WEST (1.28 ± 0.71, P = 0.006) in avoiding blood contamination. WEST achieved a diagnostic accuracy of 74.7%, higher than SST (64.4%, P = 0.007) and SPT (65.0%, P = 0.012). One bleeding event occurred with a pancreatic lesion. Conclusions: WEST was comparable to SPT and superior to SST in the overall quality of the specimen and achieved highest diagnostic yield.

10.
Nanomaterials (Basel) ; 12(16)2022 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-36014706

RESUMEN

The removal of contaminants of emerging concern (CECs) has become a hot research topic in the field of environmental engineering in recent years. In this work, a simple pyrolysis method was designed to prepare a high-performance biochar-loaded zero-valent copper (CuC) material for the catalytic degradation of antibiotics ENR by PMS. The results showed that 10 mg/L of ENR was completely removed within 30 min at an initial pH of 3, CuC 0.3 g/L, and PMS 2 mmol/L. Further studies confirmed that the reactive oxygen species (ROS) involved in ENR degradation are ·OH, SO4-·, 1O2, and O2-. Among them, 1O2 played a major role in degradation, whereas O2-· played a key role in the indirect generation of 1O2. On the one hand, CuC adsorbed and activated PMS to generate ·OH, SO4-· and O2-·. O2-· was unstable and reacted rapidly with H2O and ·OH to generate large amounts of 1O2. On the other hand, both the self-decomposition of PMS and direct activation of PMS by C=O on biochar also generated 1O2. Five byproducts were generated during degradation and eventually mineralized to CO2, H2O, NO3-, and F-. This study provides a facile strategy and new insights into the biochar-loaded zero-valent transition-metal-catalyzed PMS degradation of CECs.

12.
Gland Surg ; 11(2): 426-431, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35284304

RESUMEN

Background: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) allows for the analysis of diagnostic tissue specimens from various regions. For pancreatic tumors, especially un-resectable ones, how to obtain pathological confirmation is important for determining sub-sequent treatment. The purpose of this study is to investigate the clinical utility of EUS-FNA in patients who failed to obtain a pathological diagnosis in surgical exploration. Methods: Patients who underwent EUS-FNA due to unsuccessful biopsy in surgical exploration in our center were retrospectively reviewed. All of the patients were diagnosed with resectable disease before surgery but were found to be unresectable during surgery. The positive rate of pathological diagnosis of EUS-FNA was analyzed. Results: A total of 11 patients were included in this study, among which 8 were males and 3 were females. The median age of the patients was 55 years (range, 48 to 73 years). The median lesion size was 34 mm (range, 25 to 44 mm). The median number of needle passes was 3 (range, 1 to 3). Two patients underwent biliary stent implantation while 3 patients underwent gastrojejunostomy before EUS-FNA. The technical success rate of EUS-FNA was 100% (11/11); 10 (90.9%, 10/11) samples were positive and 1 was negative (being inadequate). Conclusions: Intraoperative biopsy is the first choice diagnostic modality for unresectable pancreatic neoplasms. However, for patients who fail to obtain a pathological diagnosis in surgical exploration, EUS-FNA is still worth an attempt.

13.
J Gastroenterol Hepatol ; 37(7): 1333-1341, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35332574

RESUMEN

BACKGROUND AND AIM: Developments of endoscopic techniques brought the possibility of endoscopic resection for gastrointestinal stromal tumors (GISTs) of larger sizes. We aim to compare safety and short-term outcomes between endoscopic and laparoscopic resections of gastric GISTs with a diameter of 2-5 cm. METHODS: This is a single-center, retrospective cohort study. The clinical data, perioperative conditions, and the adverse events of patients who underwent endoscopic or laparoscopic resection for gastric GIST of 2-5 cm in Zhongshan Hospital, Fudan University, from January 2016 to December 2020 were retrospectively reviewed. RESULTS: A total of 346 patients were reviewed; 12 patients who failed to accomplish the planned procedure were excluded; 182 underwent laparoscopic resection; and 152 underwent endoscopic resection. Significant differences exist in the tumor size between the laparoscopic group (3.43 ± 0.86 cm) and the endoscopic group (2.78 ± 0.73 cm) (P < 0.01). Compared with laparoscopic resection, endoscopic resection was associated with faster recovery (P < 0.01), shorter hospital stays (P < 0.01), and lower cost (P < 0.01). The incidence of Clavien-Dindo grade II-V adverse events in the endoscopic group (3/152) was significantly lower than that in the laparoscopic group (12/182) (P = 0.04). After a propensity score matching analysis, the endoscopic group showed similar incidences of complications with the laparoscopic group, while the advantages over laparoscopic resection in postoperative hospital stay, time to first oral intake, and hospitalization expenses remained significant (P < 0.01). CONCLUSIONS: Endoscopic resection is a safe and cost-effective method for 2-5 cm of gastric GISTs compared with laparoscopic resection.


Asunto(s)
Tumores del Estroma Gastrointestinal , Laparoscopía , Neoplasias Gástricas , Gastrectomía/efectos adversos , Gastrectomía/métodos , Tumores del Estroma Gastrointestinal/patología , Tumores del Estroma Gastrointestinal/cirugía , Humanos , Laparoscopía/efectos adversos , Laparoscopía/métodos , Tiempo de Internación , Estudios Retrospectivos , Neoplasias Gástricas/patología , Resultado del Tratamiento
14.
Surg Endosc ; 36(6): 4042-4049, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35137258

RESUMEN

BACKGROUND AND AIMS: Gastrointestinal stromal tumors (GIST) are mostly seen in the stomach. Clinical data on GISTs ≤ 2 cm with > 5 mitosis/50 HPFs are limited. This study aimed to analyze small GISTs with high histological grades to gain a more comprehensive understanding of their clinical characteristics with long-term follow-up. METHODS: This was a nested cohort study of patients with gastric GISTs ≤ 2 cm and > 5 mitosis/50 HPFs. Individuals with endoscopically resected gastric specimens diagnosed as GISTs between January 2008 and July 2019 were enrolled. We analyzed baseline clinicopathological characteristics, perioperative characteristics, risk of recurrence, and metastasis during follow-up. RESULTS: A total of 55 patients diagnosed with gastric GISTs ≤ 2 cm and > 5 mitosis/50 HPFs were enrolled. The mean tumor size was 1.6 ± 0.4 cm (median 1.7 cm, range 0.8-2.0 cm). ESD was performed in 33 patients (60.0%) and EFTR in 22 patients (40.0%). Mean mitotic figures were 8.9/50 HPFs. Postoperative bleeding in one patient (1.8%) was the only severe adverse event. The mean follow-up period was 61.2 ± 33.9 months (median 53 months, range 13-133 months). Five patients (5/55, 9.1%) received additional therapies, including partial gastrectomy and adjuvant Imatinib. Only two patients (2/55, 3.6%) showed signs of recurrence. We observed no significant difference regarding baseline clinical characteristics and recurrence among GISTs with mitosis < 10/50 HPF and ≥ 10/50 HPF. No patient had signs of metastasis during follow-up. CONCLUSION: Endoscopic resection of gastric GISTs ≤ 2 cm with > 5 mitosis/50 HPFs has a low risk of recurrence and metastasis in the long term. Endoscopic resection of GISTs is safe and feasible.


Asunto(s)
Tumores del Estroma Gastrointestinal , Neoplasias Gástricas , Estudios de Cohortes , Gastrectomía , Tumores del Estroma Gastrointestinal/patología , Tumores del Estroma Gastrointestinal/cirugía , Humanos , Pronóstico , Estudios Retrospectivos , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Resultado del Tratamiento
17.
Int J Biol Sci ; 17(1): 259-270, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33390848

RESUMEN

Esophageal squamous cell carcinoma (ESCC) causes aggressive and lethal malignancies with extremely poor prognoses, and accounts for about 90% of cases of esophageal cancer. Neuropilin and tolloid-like 2 (NETO2) protein coding genes have been associated with various human cancers. Nevertheless, little information is reported about the phenotypic expression and its clinical significance in ESCC progression. Here, our study found that NETO2 expression in ESCC patients was associated with tumor clinical stage and lymph node metastasis status. Gain-of-function and loss-of-function analyses showed that NETO2 stimulated ESCC cell proliferation while suppressing apoptosis in vitro and enhanced tumor growth in vivo. Moreover, knockdown of NETO2 significantly inhibited migration and invasion in combination with regulation of epithelial-mesenchymal transition (EMT) related markers. Mechanistically, overexpression of NETO2 increased the phosphorylation of ERK, PI3k/AKT, and Nuclear factor erythroid-2-related factor 2(Nrf2), whereas silencing NETO2 decreased the phosphorylation of these targets. Our data suggest that Nrf2 was a critical downstream event responsible for triggering the PI3K/AKT and ERK signaling pathways and plays a crucial role in NETO2-mediated tumorigenesis. Taken together, NETO2 acts as an oncogene and might serve as a novel therapeutic target or prognostic biomarker in ESCC patients.


Asunto(s)
Carcinoma de Células Escamosas/metabolismo , Neoplasias Esofágicas/metabolismo , Proteínas de la Membrana/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Transición Epitelial-Mesenquimal , Neoplasias Esofágicas/diagnóstico , Femenino , Humanos , Sistema de Señalización de MAP Quinasas , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Fosfatidilinositol 3-Quinasas/metabolismo , Pronóstico , Proteínas Proto-Oncogénicas c-akt/metabolismo
18.
Cancer Cell Int ; 20: 45, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32063746

RESUMEN

BACKGROUND: Aberrant expression of ubiquitin-specific peptide 22 (USP22) has been detected in various cancers. This study aimed to investigate the role of USP22 and the underlying mechanism in human gastric cancer. METHODS: The expression pattern of USP22 in human gastric cancer was detected in a tissue microarray containing 88 pairs of gastric cancer tissue and adjacent normal tissue samples from patients with primary gastric cancer using immunohistochemical staining. The correlation of USP22 expression with clinical characteristics of patients, as well as their prognostic values in the overall survival of patients, were evaluated. USP22-overexpressing SGC7901 and USP22-silencing AGS cells were used to explore the role of USP22 in gastric cancer cell behavior in vitro and in vivo. Chromatin immunoprecipitation was performed to identify differentially expressed genes induced by USP22 overexpression. Western blot analysis was conducted to detect the activation of RAS/ERK and PI3K/AKT signaling in USP22-overexpressing SGC7901 cells and xenograft tumor tissues. Knockdown of RAS activator son of sevenless 1 (SOS1) was performed to investigate the role of SOS1 in USP22-regulated gastric cancer cell behavior and RAS signaling both in vitro and in vivo. RESULTS: USP22 protein expression was significantly increased in human gastric cancer tissues, compared with adjacent normal tissues, and was positively correlated with local tumor stage. Gain- and loss-of-function assays showed that USP22 promoted gastric cancer cell growth and cell cycle transition while suppressing apoptosis in vitro. Consistent results were observed in a xenograft mouse model. Chromatin immunoprecipitation revealed that the overexpression of USP22 induced the upregulation of RAS activator son of sevenless 1 (SOS1) in SGC7901 cells. Western blot analysis showed that USP22 overexpression also induced activation of the RAS/ERK and PI3K/AKT pathways in SGC7901 cells and xenograft tumor tissues. Furthermore, SOS1 silencing could reverse the effects of USP22 on gastric cancer cell behavior and RAS signaling both in vitro and in vivo. CONCLUSIONS: Our results suggest that USP22 acts as an oncogene in gastric cancer in a SOS1-dependent manner, identifying the USP22/SOS1/RAS axis as a potential therapeutic target in gastric cancer.

19.
Surg Endosc ; 34(1): 159-169, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31139992

RESUMEN

BACKGROUND: The endoscopic resection of gastrointestinal mesenchymal tumors (GIMTs) is widely accepted because of its minimal invasiveness. However, one major concern is the high rate of positive microscopic margins remaining following endoscopic resection, which was thought to be related to a higher risk of recurrence. This study aimed to determine whether positive margins affect the recurrence rate of gastric GIMTs and the factors associated with positive margins. METHODS: Patients with gastric GIMTs were recruited retrospectively from January 2008 to December 2013. Clinical and pathological features, endoscopic procedure information, and follow-up data were collected and analyzed. RESULTS: The study included 777 patients. All tumors were removed along with the pseudocapsule without macroscopic residual (ER0), and the median tumor size was 15.2 mm (range 3-100 mm). Pathological evaluation revealed 371(47.7%) GISTs. The rate of microscopic R1 resection rate was 47.0% (443/777). In a stepwise multivariate analysis, a significantly increased incidence of R1 resection was recorded for the GISTs (OR 11.13, 95% CI 3.00-41.37). In a subgroup analysis of GISTs, a univariate analysis revealed that EFTR achieved a higher rate of R0 resection (OR 0.56, 95% CI 0.31-1.00), but it was proven insignificant in a stepwise multivariate analysis. Local recurrence occurred in two patients (0.3%) during a mean follow-up time of 34.2 months. Differences in the recurrence rates between the R0 and R1 groups were statistically insignificant (P = 0.841). CONCLUSIONS: R1 resection for gastric GIMTs is not related to a higher recurrence rate than R0 resection, and ER0 resection is sufficient for gastric GIMTs.


Asunto(s)
Resección Endoscópica de la Mucosa , Gastrectomía , Tumores del Estroma Gastrointestinal , Márgenes de Escisión , Neoplasias Gástricas , Resección Endoscópica de la Mucosa/efectos adversos , Resección Endoscópica de la Mucosa/métodos , Femenino , Gastrectomía/efectos adversos , Gastrectomía/métodos , Tumores del Estroma Gastrointestinal/patología , Tumores del Estroma Gastrointestinal/cirugía , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Evaluación de Procesos y Resultados en Atención de Salud , Estudios Retrospectivos , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía
20.
Ann Transl Med ; 7(14): 314, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31475184

RESUMEN

BACKGROUND: Unexplained common bile duct (CBD) dilatation may be caused by many etiologies, such as periampullary tumors, a pancreatic neoplasm, choledocholithiasis or an inflammatory stenosis. The aim of this study is to evaluate the diagnostic yield of endoscopic ultrasonography (EUS) in patients with unexplained CBD dilatation, in combination with tumor markers, liver chemistry, symptoms, surgical history and whether there is dilatation of the pancreatic duct (PD). METHODS: From January 2016 to July 2017, 115 patients were referred for EUS in our center for CBD dilatation of an unknown etiology. A treatment plan is made based on the EUS result combined with the other clinical information. The final diagnosis is determined by surgical histology or follow-up of at least 3 months. RESULTS: The sensitivity, specificity and accuracy of EUS for patients with choledocholithiasis were 100.0% (10/10), 100.0% (105/105) and 100.0% (115/115), respectively. The sensitivity, specificity and accuracy of EUS for patients with periampullary tumor were 86.5% (32/37), 89.7% (70/78) and 88.7% (102/115), respectively. The sensitivity, specificity and accuracy of EUS for patients with inflammatory stenosis were 88.2% (60/68), 89.4% (42/47) and 88.7% (102/115), respectively. The overall accuracy of EUS for diagnosing an undetermined etiology for CBD dilatation was 88.7% (102/115) and was higher than the accuracy of ultrasound (US) (64.1%), computed tomography (CT) (66.2%), magnetic resonance imaging (MRI) (67.0%) or PET-CT (66.0%). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of EUS combined with tumor markers for patients with malignant dilatation of CBD were 91.9% (34/37), 97.4% (76/78), 94.4% (34/36), 96.2% (76/79) and 95.7% (110/115), respectively. PD dilation (P=0.026) and weight loss (P=0.035) had significant predictive values of malignancy. CONCLUSIONS: EUS is an effective diagnostic tool for determining the etiology of a CBD dilatation, and offers meaningful information for guiding a treatment plan. EUS used in conjunction with tumor markers has high yield in differentiating benign and malignant CBD dilatation. More attention should be paid to patients with PD dilation or weight loss to prevent misdiagnosis of malignant CBD dilation.

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