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OBJECTIVE: Gastric cancer (GC) stands as a prevalent and deadly global malignancy. Despite its role as a preoperative neoadjuvant therapy, Apatinib's effectiveness is curtailed among GC patients exhibiting elevated YY1 expression. YY1's connection to adverse prognosis, drug resistance, and GC metastasis is established, yet the precise underlying mechanisms remain elusive. This study aims to unravel potential pathogenic pathways attributed to YY1. DESIGN: Utilizing bioinformatics analysis, we conducted differentially expressed genes, functional annotation, and pathway enrichment analyses, and further validation through cellular and animal experiments. RESULTS: Higher YY1 expression correlated with diminished postoperative progression-free survival (PFS) and disease-specific survival (DSS) rates in TCGA analysis, identifying YY1 as an independent DSS indicator in gastric cancer (GC) patients. Notably, YY1 exhibited significantly elevated expression in tumor tissues compared to adjacent normal tissues. Bioinformatics analysis revealed noteworthy differentially expressed genes (DEGs), transcriptional targets, factors, and co-expressed genes associated with YY1. LASSO Cox analysis unveiled Transferrin as a prospective pivotal protein regulated by YY1, with heightened expression linked to adverse DSS and PFS outcomes. YY1's role in governing the p53 signaling pathway and ferroptosis in GC cells was further elucidated. Moreover, YY1 overexpression dampened immune cell infiltration within GC tumors. Additionally, YY1 overexpression hindered GC cell ferroptosis and mediated Apatinib resistance via the p53 pathway. Remarkably, IFN-a demonstrated efficacy in reversing Apatinib resistance and immune suppression in GC tissues. CONCLUSIONS: Our findings underscore the pivotal role of YY1 in driving GC progression and influencing prognosis, thus pinpointing it as a promising therapeutic target to enhance patient outcomes.
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BACKGROUND AND AIM: Endoscopic resection has been successfully used for the removal of digestive submucosal tumors (SMTs). However, the cardia has been considered a challenging location for endoscopic resection due to its narrow lumen and sharp angle. The objective of this study was to establish a clinical scoring model to grade the technical difficulty of endoscopic resection for cardial SMTs. METHODS: A total of 246 patients who suffered cardial SMTs and received endoscopic resection were included in this retrospective study. All of them were randomized into the training cohort (n = 123) or internal validation cohort (n = 123). Potential predictors were analyzed using univariate analysis. Then, covariates with P < 0.05 were selected for the multivariate logistic regression model. The ß coefficients from the logistic regression model were used to create a scoring system for technical difficulty prediction by rounding the score to the nearest integer of the absolute ß coefficient value. RESULTS: The clinical score consisted of the following factors: male gender (2 points), extraluminal growth (3 points), and maximum diameter ≥3 cm (3 points). The scoring model demonstrated good discriminatory power, with an area under the receiver operating characteristic curve of 0.860 and a 95% confidence interval of 0.763-0.958. The model also showed a good goodness of fit in the Hosmer-Lemeshow test (P = 0.979). In the training cohort, the probability of encountering technical difficulty in the easy (score = 0), intermediate (score = 1-3), difficult (score = 4-6), and very difficult (score >6) categories was 0, 6.8%, 33.3%, and 100.0%, respectively; similarly, in the validation cohort, it was 0, 5.6%, 22.2%, and 50.0%, respectively. CONCLUSIONS: This scoring system could serve as a valuable tool for clinicians in predicting the technical difficulty of endoscopic resection for cardial SMTs.
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Cardias , Neoplasias Gástricas , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Cardias/cirugía , Anciano , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Modelos Logísticos , Resección Endoscópica de la Mucosa/métodos , Factores Sexuales , Adulto , Valor Predictivo de las PruebasRESUMEN
BACKGROUND AND AIMS: Stenosis after esophageal endoscopic submucosal dissection (ESD) has a high incidence, and muscular injury is an important risk factor for esophageal stenosis. Hence, this study aimed to classify muscular injury degrees and investigate their association with postoperative stenosis. METHODS: This retrospective study included 1033 patients with esophageal mucosal lesions treated with ESD between August 2015 and March 2021. Demographic and clinical parameters were analyzed, and stenosis risk factors were identified using multivariate logistic regression. A novel muscular injury classification system was proposed and used to investigate the association between different muscular injury degrees and postoperative stenosis. Finally, a scoring system was established to predict muscular injury. RESULTS: Of 1033 patients, 118 (11.4%) had esophageal stenosis. The multivariate analysis demonstrated that the history of endoscopic esophageal treatment, circumferential range, and muscular injury were significant risk factors for esophageal stenosis. Patients with type II muscular injuries tended to develop complex stenosis (n = 13 [36.1%], P < .05), and type II muscular injuries were more likely to predispose patients to severe stenosis than type I (73.3% and 92.3%, respectively). The scoring system showed that patients with high scores (3-6) were more likely to have muscular injury. The score model presented good discriminatory power in the internal validation (area under the receiver-operating characteristic curve, .706; 95% confidence interval, .645-.767) and goodness-of-fit in the Hosmer-Lemeshow test (P = .865). CONCLUSIONS: Muscular injury was an independent risk factor for esophageal stenosis. The scoring system demonstrated good performance in predicting muscular injury during ESD.
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Carcinoma de Células Escamosas , Resección Endoscópica de la Mucosa , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Estenosis Esofágica , Humanos , Estenosis Esofágica/epidemiología , Estenosis Esofágica/etiología , Constricción Patológica , Resección Endoscópica de la Mucosa/efectos adversos , Estudios Retrospectivos , Neoplasias Esofágicas/cirugía , Factores de RiesgoRESUMEN
BACKGROUND AND AIM: Endoscopic resection (ER) has been used to remove submucosal tumors (SMTs) in recent years; however, duodenal ER is associated with high rates of immediate or delayed bleeding and perforation. Whether ER can be recommended for the treatment of duodenal SMTs remains controversial. Therefore, we aimed to investigate the clinical outcomes associated with the ER of duodenal SMTs and to assess possible predictive factors for complications and incomplete resection. METHODS: This retrospective study included 141 patients with duodenal SMTs. The therapeutic outcomes from ER and procedure-related complications were analyzed. RESULTS: Of the 141 patients, 78.7% achieved complete resection and nine (6.4%) developed complications. The multivariate analysis suggested that location near the duodenal papilla (P = 0.010) and diameter exceeding 15 mm (P = 0.091) of duodenal SMTs were independent risk factors for complications in ER. Besides, submucosal fibrosis (P = 0.042), location near the duodenal papilla (P = 0.049), and irregular morphology (P = 0.067) were independent risk factors for incomplete resection. CONCLUSIONS: ER can be recommended as an effective and minimally invasive treatment for duodenal SMTs.
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Resección Endoscópica de la Mucosa , Neoplasias Gástricas , Humanos , Estudios Retrospectivos , Endoscopía , Factores de Riesgo , Resección Endoscópica de la Mucosa/efectos adversos , Resultado del Tratamiento , Neoplasias Gástricas/cirugíaRESUMEN
OBJECTIVE: To evaluate the effectiveness and safety of endoscopic resection and various suturing methods to treat non-ampullary duodenal submucosal tumors (NAD-SMTs). DESIGN: We performed a retrospective observational study of patients with NAD-SMTs who underwent endoscopic resection at Zhongshan Hospital, Fudan University, China, between June 2017 and December 2020. Data on patient characteristics, treatments and follow-up results were collected. The association between clinicopathologic characteristics and different suturing methods or adverse events were analyzed. RESULTS: Of 128 patients analyzed, 26 underwent endoscopic mucosal resection (EMR), 64 underwent endoscopic submucosal excavation (ESE), and 38 underwent endoscopic full-thickness resection (EFTR). EMR and ESR are both appropriate for non-full-thickness lesions, whereas ESE is more appropriate for tumors located in the bulb or descending duodenum. Gastric tube drainage is more strongly recommended after ESE. Satisfactory suturing is also vital endoscopic resection of NAD-SMTs. Metallic clips are often used in EMR or ESE of non-full-thickness lesions. The pathological findings revealed that the full-thickness lesions were predominantly gastrointestinal stromal tumors (GIST), Brunner's tumor or lipoma, and the surgeons usually used purse-string sutures to close the wounds. The operation time was longer for purse-string suture closure than metallic clip closure. Eleven patients had complications. Risk factors for adverse events included large-diameter tumor (≥ 2 cm), location in the descending part of the duodenum, involvement of the fourth layer of the duodenal wall, EFTR, and GIST. CONCLUSIONS: Endoscopic resection of NAD-SMTs is effective but is associated with a high incidence of complications due to their anatomical peculiarities. Preoperative diagnosis is quite important. Careful selection of treatment and suturing methods are necessary to reduce the risk of adverse effects. Given the increased frequency of severe complications during or following duodenal endoscopic resection, this procedure should be performed by experienced endoscopists.
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Resección Endoscópica de la Mucosa , Tumores del Estroma Gastrointestinal , Neoplasias Gástricas , Humanos , Tumores del Estroma Gastrointestinal/cirugía , Tumores del Estroma Gastrointestinal/patología , Neoplasias Gástricas/cirugía , NAD , Resultado del Tratamiento , Endoscopía , Resección Endoscópica de la Mucosa/métodos , Estudios RetrospectivosRESUMEN
BACKGROUND & AIMS: Although the treatment of hepatocellular carcinoma (HCC) has been revolutionized by the advent of effective systemic therapies, the prognosis of patients with HCC remains dismal. Herein, we examined the pathophysiological role of PARG and assessed the utility of targeting dePARylation for HCC therapy. METHODS: The oncogenic function of PARG was evaluated in 2 orthotopic xenograft models and a Pargflox/flox mice model. The therapeutic efficacy of PARG inhibitors in combination with an anti-PD-1 antibody were assessed in murine orthotopic models. Microarray analysis was used to evaluate the pathological relevance of the PARG/DDB1/c-Myc/MMR axis. RESULTS: High PARG expression was strongly associated with poor HCC prognosis. Hepatocyte-specific PARG deletion significantly impaired liver tumorigenesis. PARG promoted HCC growth and metastasis through DDB1-dependent modulation of c-Myc. Specifically, PARG dePARylated DDB1 and consequently promoted DDB1 autoubiquitination, thus stabilizing the c-Myc protein in HCC cells. PARG downregulation attenuated c-Myc-induced MMR expression and PARG deficiency was correlated with a favorable prognosis in patients with HCC treated with anti-PD-1-based immunotherapy. In addition, PARG inhibitors could act in synergy with anti-PD-1 antibodies in orthotopic mouse models. CONCLUSIONS: PARG can act as an oncogene in HCC by modulating PARG/DDB1/c-Myc signaling and could be used as a biomarker to identify patients with HCC who may benefit from anti-PD-1 treatment. Our findings suggest that co-inhibition of PARG and PD-1 is an effective novel combination strategy for patients with HCC. LAY SUMMARY: The increase in deaths due to hepatocellular carcinoma (HCC) is a growing concern, with the mechanisms responsible for HCC development still incompletely understood. Herein, we identify a novel mechanism by which the protein PARG contributes to HCC development. Inhibition of PARG increased the efficacy of anti-PD-1 therapy (a type of immunotherapy) in HCC. These findings support the future clinical development of PARG inhibitors, potentially in combination with anti-PD-1 inhibitors.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Animales , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Humanos , Inmunoterapia , Neoplasias Hepáticas/patología , Ratones , Proteínas Proto-Oncogénicas c-myc/genética , Proteínas Proto-Oncogénicas c-myc/metabolismo , Transducción de SeñalRESUMEN
BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is a fatal disease characterized by vast molecular heterogeneity. Although major advances in tumour genetics has led to the identification of new biomarkers, the prognosis of patients with HCC remains dismal. METHODS: Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and western blot (WB) were used to evaluate meiosis-specific nuclear structural 1 (MNS1) expression in HCC cells. Immunohistochemistry staining was used to evaluate MNS1 expression in HCC tissues. Clinical significance of MNS1 was evaluated by Cox regression analysis. Transwell assays were conducted to assess cells migration ability. Cell counting kit-8 and colony formation assays were performed to detect cells proliferation ability. NOD/SCID/γc(null) (NOG) mice model was adopted to investigate functions of MNS1 in vivo. RESULTS: The expression of MNS1, which is elevated in most HCC tissues, correlated with poor survival in HCC patients. Functional experiments revealed the oncogenic role of MNS1, which promotes HCC growth and metastasis through AKT-dependent modulation of ß-catenin. ß-Catenin expression was crucial for MNS1's oncogenic effects. MNS1 indirectly translocated ß-catenin from the cytoplasm to the nucleus via the MNS1-GSK3ß axis. CONCLUSIONS: MNS1 promotes HCC growth and metastasis via activating PI3K/AKT signalling and may serve as an important prognostic biomarker as well as potential novel therapeutic target for HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Animales , Carcinoma Hepatocelular/genética , Proteínas de Ciclo Celular , Línea Celular Tumoral , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Hepáticas/genética , Ratones , Ratones Endogámicos NOD , Ratones SCID , Fosfatidilinositol 3-Quinasas/metabolismo , Pronóstico , Proteínas Proto-Oncogénicas c-akt/genética , beta Catenina/metabolismoRESUMEN
Previous research suggests that far upstream element-binding protein 1 (FUBP1) plays an important role in various tumors including epatocellular carcinoma (HCC). However, the role of FUBP1 in liver cancer remains controversial, and the regulatory pathway by FUBP1 awaits to be determined. This study aims to identify the role of FUBP1 in HCC progression. Our result shows that the high level of FUBP1 expression in HCC predicts poor prognosis after surgery. Overexpression of FUBP1 promotes HCC proliferation, invasion, and metastasis by activating transforming growth factor-ß (TGF-ß)/Smad pathway and enhancing epithelial-mesenchymal transition (EMT) in vitro and in vivo. Inhibitor of Thrombospondin-1 (LSKL) could inhibit HCC proliferation and invasion in vitro and in vivo by blocking the activation of TGF-ß/Smad pathway mediated by thrombospondin-1 (THBS1). Our study identified the critical role of FUBP1-THBS1-TGF-ß signaling axis in HCC and provides potentially new therapeutic modalities in HCC.
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Carcinoma Hepatocelular/genética , Proteínas de Unión al ADN/genética , Neoplasias Hepáticas/genética , Proteínas de Unión al ARN/genética , Trombospondina 1/genética , Factor de Crecimiento Transformador beta1/genética , Animales , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Xenoinjertos , Humanos , Neoplasias Hepáticas/patología , Masculino , Ratones , Invasividad Neoplásica/genética , Invasividad Neoplásica/patología , Metástasis de la Neoplasia , Péptidos/farmacología , Transducción de Señal/efectos de los fármacos , Proteínas Smad/genética , Trombospondina 1/antagonistas & inhibidores , Análisis de Matrices TisularesRESUMEN
BACKGROUND: Prognosis of hepatocellular carcinoma (HCC) remains poor due to high recurrence rate and ineffective treatment options, highlighting the need to better understand the mechanism of recurrence and metastasis in HCC. METHODS: We first collected messenger RNA (mRNA) expression data from 442 cases of HCC patients from The Cancer Genome Atlas (TCGA) database as well as 251 HCC patients from Zhongshan Hospital during 2009 and 2010 to analyze the expression pattern from tissue microarray (TMA) of baculoviral IAP repeat containing 3 (BIRC3). Then, we used BIRC3 gain-of-function (overexpression) and loss-of-function (knockdown) studies to examine the effect of BIRC3 on HCC cell proliferation and invasion. In addition, we also investigated the undying mechanism by which BIRC3 contributes to HCC tumor progression. Functionally, we also used a BIRC3-specific inhibitor AT-406 in HCC xenograft model to explore the potential therapeutic benefit of targeting BIRC3 in liver cancer. RESULTS: BIRC3 serves as a novel prognostic indicator for HCC patients undergoing curative resection. BIRC3 promotes HCC epithelial-mesenchymal transition (EMT), cell migration, and metastasis via upregulating MAP3K7, therefore, inducing ERK1/2 phosphorylation. The specific BIRC3 inhibitor AT-406 can inhibit HCC cell proliferation and reduce pulmonary metastases. CONCLUSION: BIRC3 induces tumor proliferation and metastasis in vitro and in vivo. BIRC3 may serve as a novel therapeutic target for liver cancer.
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Proteína 3 que Contiene Repeticiones IAP de Baculovirus/metabolismo , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Animales , Proteína 3 que Contiene Repeticiones IAP de Baculovirus/genética , Biomarcadores de Tumor/metabolismo , Western Blotting , Línea Celular Tumoral , Movimiento Celular/genética , Movimiento Celular/fisiología , Proliferación Celular/genética , Proliferación Celular/fisiología , Transición Epitelial-Mesenquimal/genética , Transición Epitelial-Mesenquimal/fisiología , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Regulación Neoplásica de la Expresión Génica/fisiología , Humanos , Inmunohistoquímica , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Reacción en Cadena en Tiempo Real de la Polimerasa , Análisis de Matrices TisularesRESUMEN
Aim: To elucidate the integrative combinational gene regulatory network landscape of hepatocellular carcinoma (HCC) molecular carcinogenesis from diverse background. Materials & methods: Modified gene regulatory network analysis was used to prioritize differentially regulated genes and links. Integrative comparisons using bioinformatics methods were applied to identify potential critical molecules and pathways in HCC with different backgrounds. Results: E2F1 with its surrounding regulatory links were identified to play different key roles in the HCC risk factor dysregulation mechanisms. Hsa-mir-19a was identified as showed different effects in the three HCC differential regulation networks, and showed vital regulatory role in HBV-related HCC. Conclusion: We describe in detail the regulatory networks involved in HCC with different backgrounds. E2F1 may serve as a universal target for HCC treatment.
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Carcinoma Hepatocelular/genética , Factor de Transcripción E2F1/metabolismo , Redes Reguladoras de Genes , Neoplasias Hepáticas/genética , MicroARNs/genética , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/virología , Biología Computacional , Conjuntos de Datos como Asunto , Supervivencia sin Enfermedad , Factor de Transcripción E2F1/antagonistas & inhibidores , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Hepacivirus/aislamiento & purificación , Hepacivirus/patogenicidad , Virus de la Hepatitis B/aislamiento & purificación , Virus de la Hepatitis B/patogenicidad , Humanos , Estimación de Kaplan-Meier , Hígado/patología , Hígado/virología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/virología , MicroARNs/metabolismo , PronósticoRESUMEN
Accumulating evidence suggests that long non-coding RNA (lncRNA) plays important roles in some malignant tumors. However, the mechanism underlying how lncRNA regulates hepatocellular carcinoma (HCC) process remains largely unknown. In this study, we explored the potential role of lncRNA 00607 as a novel tumor suppressor in HCC. In this study, we examined the regulation of lncRNA 00607 by the important inflammatory cytokine tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). We also determined the expression of LINC000607 in 159 HCC tumors and paired adjacent tissues. Effects of LINC000607 in HCC proliferation and apoptosis were examined in vitro in HCC cell lines and in vivo tumor xenografts. Furthermore, we also examine underlying mechanism by which lncRNA 00607 regulates NF-κB p65 and how LIN00607 exerts its tumor suppressor role in HCC. We found that lncRNA 00607 expression level is lower in HCC tumors compared with matched normal liver tissue, and its low expression predicts worse prognosis in HCC. Functionally, lncRNA 00607 overexpression leads to decreased HCC cell proliferation in vitro and in vivo, enhanced apoptosis and chemotherapeutic drug sensitivity. Mechanistically, lncRNA 00607 inhibits the p65 transcription by binding to the p65 promoter region, therefore contributing to increased p53 levels in HCC. Taken together, the findings of this study show that the TNF-α/IL-6-lncRNA 00607-NF-κB p65/p53 signaling axis represents a novel therapeutic avenue in cancer chemotherapy.
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Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , ARN Largo no Codificante/genética , Transducción de Señal/genética , Factor de Transcripción ReIA/genética , Proteína p53 Supresora de Tumor/genética , Animales , Apoptosis/genética , Línea Celular Tumoral , Proliferación Celular/genética , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Células Hep G2 , Humanos , Masculino , Ratones , Ratones Desnudos , Persona de Mediana Edad , Regiones Promotoras Genéticas/genética , Transcripción Genética/genéticaRESUMEN
BACKGROUND AND AIMS: Accurate recognition of endoscopic instruments facilitates quantitative evaluation and quality control of endoscopic procedures. However, no relevant research has been reported. In this study, we aimed to develop a computer-assisted system, EndoAdd, for automated endoscopic surgical video analysis based on our dataset of endoscopic instrument images. METHODS: Large training and validation datasets containing 45,143 images of 10 different endoscopic instruments and a test dataset of 18,375 images collected from several medical centers were used in this research. Annotated image frames were used to train the state-of-the-art object detection model, YOLO-v5, to identify the instruments. Based on the frame-level prediction results, we further developed a hidden Markov model to perform video analysis and generate heatmaps to summarize the videos. RESULTS: EndoAdd achieved high accuracy (>97%) on the test dataset for all 10 endoscopic instrument types. The mean average accuracy, precision, recall, and F1-score were 99.1%, 92.0%, 88.8%, and 89.3%, respectively. The area under the curve values exceeded 0.94 for all instrument types. Heatmaps of endoscopic procedures were generated for both retrospective and real-time analyses. CONCLUSIONS: We successfully developed an automated endoscopic video analysis system, EndoAdd, which supports retrospective assessment and real-time monitoring. It can be used for data analysis and quality control of endoscopic procedures in clinical practice.
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BACKGROUND: Gastric cystica profunda (GCP) represents a rare condition characterized by cystic dilation of gastric glands within the mucosal and/or submucosal layers. GCP is often linked to, or may progress into, early gastric cancer (EGC). AIM: To provide a comprehensive evaluation of the endoscopic features of GCP while assessing the efficacy of endoscopic treatment, thereby offering guidance for diagnosis and treatment. METHODS: This retrospective study involved 104 patients with GCP who underwent endoscopic resection. Alongside demographic and clinical data, regular patient follow-ups were conducted to assess local recurrence. RESULTS: Among the 104 patients diagnosed with GCP who underwent endoscopic resection, 12.5% had a history of previous gastric procedures. The primary site predominantly affected was the cardia (38.5%, n = 40). GCP commonly exhibited intraluminal growth (99%), regular presentation (74.0%), and ulcerative mucosa (61.5%). The leading endoscopic feature was the mucosal lesion type (59.6%, n = 62). The average maximum diameter was 20.9 ± 15.3 mm, with mucosal involvement in 60.6% (n = 63). Procedures lasted 73.9 ± 57.5 min, achieving complete resection in 91.3% (n = 95). Recurrence (4.8%) was managed via either surgical intervention (n = 1) or through endoscopic resection (n = 4). Final pathology confirmed that 59.6% of GCP cases were associated with EGC. Univariate analysis indicated that elderly males were more susceptible to GCP associated with EGC. Conversely, multivariate analysis identified lesion morphology and endoscopic features as significant risk factors. Survival analysis demonstrated no statistically significant difference in recurrence between GCP with and without EGC (P = 0.72). CONCLUSION: The findings suggested that endoscopic resection might serve as an effective and minimally invasive treatment for GCP with or without EGC.
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Resección Endoscópica de la Mucosa , Neoplasias Gástricas , Masculino , Humanos , Anciano , Estudios Retrospectivos , Endoscopía , Neoplasias Gástricas/diagnóstico por imagen , Neoplasias Gástricas/cirugía , Mucosa Gástrica/diagnóstico por imagen , Mucosa Gástrica/cirugía , Mucosa Gástrica/patología , Resección Endoscópica de la Mucosa/métodos , Gastroscopía/métodosRESUMEN
BACKGROUND: Calcifying fibrous tumors (CFTs) are rare mesenchymal lesions that can occur in various sites throughout the body, including the tubular gastrointestinal (GI) tract. AIM: To analyze the clinical findings of 36 patients with GI tract CFTs to provide guidance for diagnosis and treatment. METHODS: This retrospective study included 36 patients diagnosed with CFTs of the GI tract. We collected demographic and clinical information and conducted regular follow-ups to assess for local recurrence. RESULTS: The stomach was the most commonly involved site, accounting for 72.2% of the 36 CFTs. Endoscopic mucosal resection (n = 1, 2.8%), endoscopic submucosal dissection (n = 14, 38.9%), endoscopic full-thickness resection (n = 16, 44.4%), and submucosal tunneling endoscopic resection (n = 5, 13.9%) were used to resect calcifying fibrous tumors. Overall, 34 (94.4%) CFTs underwent complete endoscopic resections with a mean procedure time of 39.8 ± 29.8 min. The average maximum diameter of the tumors was 10.6 ± 4.3 cm. No complications, such as bleeding or perforation, occurred during an average hospital stay of 2.9 ± 1.2 d. In addition, two patients developed new growth of CFTs near the primary tumor sites, and none of the patients developed distant metastases during the follow-up period. CONCLUSION: GI tract CFTs are rare and typically benign tumors that can be effectively managed with endoscopic procedures.
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OBJECTIVE: The gut microbiota plays a critical role in the appropriate development and maintenance of the enteric nervous system (ENS). Esophageal achalasia (EA) is a rare motility disorder characterized by the selective degeneration of inhibitory neurons in the esophageal myenteric plexus. This study aimed to evaluate the composition of the esophageal microbiota in achalasia and explore the potential microbial mechanisms involved in its pathogenesis. DESIGN: The lower esophageal mucosal microbiota was analyzed in patients with achalasia and control participants using 16 S rRNA sequencing. The association between the esophageal microbiota and achalasia was validated by inducing esophageal dysbiosis in C57BL/10 J and C57BL/10ScNJ (TLR4KO) mice via chronic exposure to ampicillin sodium in their drinking water. RESULTS: The esophageal microbiota in EA patients had lower diversity and a predominance of Gram-negative bacteria (Type II microbiota) compared to that in the healthy controls. Additionally, the relative abundance of Rhodobacter decreased significantly in patients with achalasia, which correlated with an enrichment of lipopolysaccharide (LPS) biosynthesis based on the COG database. Antibiotic-treated mice showed an esophageal microbiota characterized by increased abundance of Gram-negative bacteria (Type II microbiome), decreased abundance of Rhodobacter, and enriched LPS biosynthesis. Compared to the control and TLR4KO mice, the antibiotic-treated wild-type mice had higher LES resting pressure, increased LES contraction rate after carbachol stimulation, and decreased relaxation response to L-arginine. Moreover, the number of myenteric neurons decreased, while the number of lamina propria macrophages (LpMs) increased after antibiotic exposure. Furthermore, the TLR4-MYD88-NF-κB pathway was up-regulated, and the production of TNF-α, IL-1ß, and IL-6 increased in the antibiotic-treated mice. CONCLUSIONS: Patients with achalasia exhibit esophageal dysbiosis, which may induce aberrant esophageal motility.
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Acalasia del Esófago , Microbioma Gastrointestinal , Ratones , Animales , Acalasia del Esófago/patología , Lipopolisacáridos , Disbiosis , Ratones Endogámicos C57BL , Neuronas/patología , Antibacterianos/farmacologíaRESUMEN
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.
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The overall response rate for anti-PD-1 therapy remains modest in hepatocellular carcinoma (HCC). We found that a combination of IFNα and anti-PD-1-based immunotherapy resulted in enhanced antitumor activity in patients with unresectable HCC. In both immunocompetent orthotopic and spontaneous HCC models, IFNα therapy synergized with anti-PD-1 and the combination treatment led to significant enrichment of cytotoxic CD27+CD8+ T cells. Mechanistically, IFNα suppressed HIF1α signaling by inhibiting FosB transcription in HCC cells, resulting in reduced glucose consumption capacity and consequentially establishing a high-glucose microenvironment that fostered transcription of the T-cell costimulatory molecule Cd27 via mTOR-FOXM1 signaling in infiltrating CD8+ T cells. Together, these data reveal that IFNα reprograms glucose metabolism within the HCC tumor microenvironment, thereby liberating T-cell cytotoxic capacities and potentiating the PD-1 blockade-induced immune response. Our findings suggest that IFNα and anti-PD-1 cotreatment is an effective novel combination strategy for patients with HCC. SIGNIFICANCE: Our study supports a role of tumor glucose metabolism in IFNα-mediated antitumor immunity in HCC, and tumor-infiltrating CD27+CD8+ T cells may be a promising biomarker for stratifying patients for anti-PD-1 therapy. See related commentary by Kao et al., p. 1615. This article is highlighted in the In This Issue feature, p. 1599.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Linfocitos T CD8-positivos , Carcinoma Hepatocelular/metabolismo , Glucosa/metabolismo , Glucosa/farmacología , Humanos , Interferón-alfa/metabolismo , Interferón-alfa/farmacología , Interferón-alfa/uso terapéutico , Neoplasias Hepáticas/metabolismo , Microambiente TumoralRESUMEN
The aim of this study was to identify novel prognostic mRNA and microRNA (miRNA) biomarkers for hepatocellular carcinoma (HCC) using methods in systems biology. Differentially expressed mRNAs, miRNAs, and long non-coding RNAs (lncRNAs) were compared between HCC tumor tissues and normal liver tissues in The Cancer Genome Atlas (TCGA) database. Subsequently, a prognosis-associated mRNA co-expression network, an mRNA-miRNA regulatory network, and an mRNA-miRNA-lncRNA regulatory network were constructed to identify prognostic biomarkers for HCC through Cox survival analysis. Seven prognosis-associated mRNA co-expression modules were obtained by analyzing these differentially expressed mRNAs. An expression module including 120 mRNAs was significantly correlated with HCC patient survival. Combined with patient survival data, several mRNAs and miRNAs, including CHST4, SLC22A8, STC2, hsa-miR-326, and hsa-miR-21 were identified from the network to predict HCC patient prognosis. Clinical significance was investigated using tissue microarray analysis of samples from 258 patients with HCC. Functional annotation of hsa-miR-326 and hsa-miR-21-5p indicated specific associations with several cancer-related pathways. The present study provides a bioinformatics method for biomarker screening, leading to the identification of an integrated mRNA-miRNA-lncRNA regulatory network and their co-expression patterns in relation to predicting HCC patient survival.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroARNs , ARN Largo no Codificante , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes , Humanos , Neoplasias Hepáticas/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
Various epidemiology studies showed the correlation between Alzheimer's disease (AD) and low incidence of cancer. However, the etiology underlying etiology of AD-related carcinogenesis remains largely elusive. Our study focused on characterizing the role of TM2D1 (TM2 domain containing 1) in hepatocellular carcinoma. TM2D1 is also known as ß-amyloid peptide binding protein and is critical to the pathogenesis of AD. We found that TM2D1 is increasingly expressed in HCC tumors relative to the peritumoral tissues of the matched tumors and high TM2D1 expression predicts unfavorable clinical outcomes. TM2D1 overexpression induced HCC cell proliferation, migration and invasion, which was related to the epithelial-mesenchymal transition (EMT) observed in these cells. Conversely, TM2D1 depletion led to opposite phenotype in HCC. Mechanistically, we found that TM2D1 promoted Akt and ß-catenin hyper-activation, which corresponded with molecular marker change in EMT signaling pathway. Taken together, our results indicated that TM2D1 played an important role in the EMT process in HCC cells by activating AKT and ß-catenin signaling and may become a promising therapeutic target in HCC.