RESUMEN
Gastric cancer (GC) is one of the leading causes of cancer-related deaths worldwide because of its high morbidity and the absence of effective therapies. Even though paclitaxel is a powerful anticancer chemotherapy drug, recent studies have indicated its ineffectiveness against GC cells. Long non-coding RNA (lncRNA) PVT1 has a high expression in GC cells and increases the progression of tumors via inducing drug resistance. In the present study, the effects of the siRNA-mediated lncRNA PVT1 gene silencing along with paclitaxel treatment on the rate of apoptosis, growth, and migration of AGS GC cells were investigated. AGS cells were cultured and then transfected with siRNA PVT1 using electroporation. The MTT test was used to examine the effect of treatments on the viability of cultured cells. Furthermore, the flow cytometry method was used to evaluate the impact of treatments on the cell cycle process and apoptosis induction in GC cells. Finally, the mRNA expression of target genes was assessed using the qRT-PCR method. The results showed that lncRNA PVT1 gene suppression, along with paclitaxel treatment, reduces the viability of cancer cells and significantly increases the apoptosis rate of cancer cells and the number of cells arrested in the G2/M phase compared to the control group. Based on the results of qRT-PCR, combined treatment significantly decreased the expression of MMP3, MMP9, MDR1, MRP1, Bcl-2, k-Ras, and c-Myc genes and increased the expression of the Bax gene compared to the control group. The results of our study showed that lncRNA PVT1 gene targeting, together with paclitaxel treatment, induces apoptosis, inhibits growth, alleviates drug resistance, and reduces the migratory capability of GC cells. Therefore, there is a need for further investigations to evaluate the feasibility and effectiveness of this approach in vivo in animal models.
Asunto(s)
Apoptosis , Resistencia a Antineoplásicos , Silenciador del Gen , Paclitaxel , ARN Largo no Codificante , Neoplasias Gástricas , ARN Largo no Codificante/genética , Paclitaxel/farmacología , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Línea Celular Tumoral , Apoptosis/efectos de los fármacos , Apoptosis/genética , Resistencia a Antineoplásicos/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Antineoplásicos Fitogénicos/farmacología , ARN Interferente Pequeño/genéticaRESUMEN
N6-Methyladenosine (m6A) modification and its regulators play critical roles in human cancers, but their functions and regulatory mechanisms in adenocarcinoma of the esophagogastric junction (AEG) remain unclear. Here, we identified that IGF2BP3 is the most significantly up-regulated m6A regulator in AEG tumors versus paired normal adjacent tissues from the expression profile of m6A regulators in a large cohort of AEG patients. Silencing IGF2BP3 inhibits AEG progression in vitro and in vivo. By profiling transcriptome-wide targets of IGF2BP3 and the m6A methylome in AEG, we found that IGF2BP3-mediated stabilization and enhanced expression of m6A-modified targets, including targets of the cell cycle pathway, such as CDC25A, CDK4, and E2F1, are critical for AEG progression. Mechanistically, the increased m6A modification of CDC25A accelerates the G1-S transition. Clinically, up-regulated IGF2BP3, METTL3, and CDC25A show a strong positive correlation in TCGA pan-cancer, including AEG. In conclusion, our study highlights the role of post-transcriptional regulation in modulating AEG tumor progression and elucidates the functional importance of the m6A/IGF2BP3/CDC25A axis in AEG cells.
Asunto(s)
Adenocarcinoma , Adenosina , Ciclo Celular , Neoplasias Esofágicas , Proteínas de Unión al ARN , Fosfatasas cdc25 , Humanos , Fosfatasas cdc25/metabolismo , Fosfatasas cdc25/genética , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Adenosina/análogos & derivados , Adenosina/metabolismo , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patología , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Animales , Unión Esofagogástrica/metabolismo , Unión Esofagogástrica/patología , Línea Celular Tumoral , Ratones , Regulación Neoplásica de la Expresión Génica , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Ratones Desnudos , Metiltransferasas/metabolismo , Metiltransferasas/genéticaRESUMEN
OBJECTIVE: Precancerous lesions of gastric cancer (PLGC) are key pathological stages in the transformation of gastric "inflammation-cancer", and timely and effective intervention at this stage is of great importance in the prevention and treatment of gastric cancer. Zhiwei Fuwei Pills (ZWFW), as a traditional Chinese medicine formulation, has been proven to have good clinical efficacy in the treatment of PLGC, but its specific mechanism of action has not been fully explained. Thus, this study validated the efficacy and explored the potential mechanisms of ZWFW in treating PLGC by integrating network pharmacology analyses and experimental verification. METHODS: The TCMSP database was used to obtain the active ingredients of ZWFW and their corresponding targets, and the GeneCards database was used to retrieve PLGC-related targets. The intersecting targets between ZWFW and PLGC were obtained through mapping, and protein-protein interaction (PPI) networks and "drug-active ingredient-target" networks were constructed by using Cytoscape software. The DAVID database was used for GO functional enrichment analysis and KEGG pathway enrichment analysis. AutoDockTools software was used for molecular docking of key active ingredients and key targets. In order to verify the analysis results of network pharmacology, TEM and H&E were used to observe the effects of different dosage groups of ZWFW on gastric mucosal microvasculature in PLGC rats. Subsequently, the ELISA, IF, IHC, RT-PCR and western blot were used to detected the expression levels of relevant targets in the tissues, so as to verify the potential mechanism of ZWFW in intervening PLGC. RESULTS: After the screening, 258 effective active ingredients and 325 targets were obtained, and 1294 disease-related targets were determined, resulting in 139 intersection targets through mapping. The KEGG enrichment results showed that PI3K/Akt and HIF-1 signaling pathway might play important roles in the treatment mechanism of PLGC. The molecular docking results showed that active ingredients of ZWFW all had a strong affinity and stable structure with key targets, including AKT1 and VEGF. In vivo experiments confirmed that ZWFW could improve gastric mucosal microvascular abnormalities in PLGC, effectively intervene in gastric mucosal pathological grading. Meanwhile, compared with the model group, this formulation could reduce the expression levels of PI3K, Akt, mTOR, HIF-1α, and VEGF in gastric mucosa, showing a dose-effect relationship. CONCLUSION: ZWFW can intervene in the neovascularization and pathological evolution of PLGC, and this mechanism of action may be achieved by inhibiting abnormal activation of the PI3K/Akt/mTOR/HIF-1α/VEGF signaling pathway.
Asunto(s)
Medicamentos Herbarios Chinos , Neovascularización Patológica , Farmacología en Red , Lesiones Precancerosas , Neoplasias Gástricas , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Animales , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Neovascularización Patológica/tratamiento farmacológico , Masculino , Lesiones Precancerosas/tratamiento farmacológico , Lesiones Precancerosas/patología , Mapas de Interacción de Proteínas , Factor A de Crecimiento Endotelial Vascular/metabolismo , Ratas Sprague-Dawley , Ratas , Simulación del Acoplamiento Molecular , AngiogénesisRESUMEN
Robotic surgery has been widely used in surgical gastric cancer treatments, including proximal gastrectomy. Single-port robotic system is gaining more popularity in robotic surgery, but there has been no report on its application in robotic proximal gastrectomy with right-sided overlap and single-flap valvuloplasty (RPG-ROSF). Here, we report an RPG-ROSF using a novel single-port robotic system in a 51-year-old male patient with an early-stage gastroesophageal cancer detected by gastroscopy. It took 90 min for robotic setup, 143 min for dissection, and 161 min for digestive tract reconstruction. There was no complication during and after the surgery. The patient was discharged in 8 days postsurgery. The pathological staging of the adenocarcinoma was pT1aN0M0. This preliminary study demonstrated the feasibility and safety of a novel single-port robot in RPG-ROSF.
Asunto(s)
Adenocarcinoma , Gastrectomía , Procedimientos Quirúrgicos Robotizados , Neoplasias Gástricas , Humanos , Masculino , Gastrectomía/métodos , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Persona de Mediana Edad , Adenocarcinoma/cirugía , Adenocarcinoma/patología , Neoplasias Esofágicas/cirugía , Neoplasias Esofágicas/patología , Colgajos QuirúrgicosRESUMEN
BACKGROUND: The use of robotic surgery (RS) for gastric cancer (GC) has been rapidly increasing. However, the utility of RS for advanced GC (AGC), especially T3 or more AGC, is unclear. METHODS: Ninety patients who underwent curative upfront minimally invasive surgery (MIS) (D2 lymph node dissection) for fStage II or III GC were enrolled in this study. Among these patients, 68 underwent MIS for T3 or more AGC. Thirty-six patients underwent RS, and 32 patients underwent laparoscopic surgery (LS). The short-term and long-term surgical outcomes were compared between the two groups. RESULTS: In the T3 or more AGC cohort, there were no significant intergroup differences in the operative time or blood loss volume. The number of retrieved lymph nodes tended to be higher in the RS than LS group (38.5 vs. 33.0, p = .11). The drain amylase content on postoperative day 1 was significantly lower in the RS than LS group (243.5 vs. 521.0 IU/L, p < .01). The morbidity rate (Clavien-Dindo grade ≥2) was similar between the groups. There were no significant differences between the LS and RS groups in the 3-year overall survival rate (80.7% vs. 74.5%, respectively; p = .95) or 3-year disease-free survival rate (75.0% vs. 69.7%, respectively; p = .95). CONCLUSIONS: RS for primary T3 or more AGC was safe and contributed to similar short-term and long-term outcomes compared with LS.
Asunto(s)
Gastrectomía , Procedimientos Quirúrgicos Robotizados , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Neoplasias Gástricas/mortalidad , Masculino , Femenino , Gastrectomía/métodos , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Resultado del Tratamiento , Laparoscopía , Estadificación de Neoplasias , Escisión del Ganglio Linfático , Adulto , Tempo Operativo , Tasa de SupervivenciaRESUMEN
BACKGROUND: The effect of omentum preservation (OP) on locally advanced gastric cancer (LAGC) remains controversial. This study aimed to investigate the long-term prognosis of LAGC patients with OP versus omentum resection (OR). METHODS: A comprehensive search of databases including PubMed, Web of Science, Embase, and Cochrane Library was conducted up until February 2024. Statistical analysis was performed using Stata 12.0 software. The primary outcome was to assess the impact of OP on the long-term prognosis of patients with LAGC, including overall survival (OS) and recurrence-free survival (RFS). RESULTS: A total of six case-control studies were included, encompassing a cohort of 1897 patients. The OP group consisted of 844 patients, while the OR group comprised 1053 patients. The study results showed that the OS (HR = 0.72, 95% CI: 0.58-0.90, P = 0.003) and 5-year RFS (HR = 0.79, 95% CI: 0.63-0.99, P = 0.038) in the OP group were superior to those observed in the OR group. Subgroup analysis indicated that 5-year OS (HR = 0.64, P = 0.003) and 5-year RFS (HR = 0.69, P = 0.005) in the OP group were also better than those in the OR group in Korea. However, the subgroup analysis conducted on stage T3-T4 tumors revealed no statistically significant differences in OS (P = 0.083) and 5-year RFS (P = 0.173) between the two groups. CONCLUSION: Compared with OR, OP shows non-inferiority in patients with LAGC and can be considered a potential treatment option for radical gastrectomy.
Asunto(s)
Gastrectomía , Epiplón , Neoplasias Gástricas , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Neoplasias Gástricas/mortalidad , Humanos , Epiplón/cirugía , Epiplón/patología , Pronóstico , Gastrectomía/métodos , Tasa de Supervivencia , Estudios de Casos y Controles , Tratamientos Conservadores del Órgano/métodosRESUMEN
BACKGROUND: The combination of laparoscopic and endoscopic approaches to neoplasia with a non-exposure technique (CLEAN-NET) is a laparoscopic and endoscopic cooperative surgery (LECS). It combines laparoscopic gastric resection and endoscopic techniques for local resection of gastric tumors, such as gastrointestinal stromal tumors (GIST), with minimal surgical margins. A conventional CLEAN-NET surgical procedure is complex, requiring careful techniques to preserve the cardia, particularly in case of nearby lesions. We describe the case of a patient who underwent a modified CLEAN-NET approach with a semi-circular seromuscular layer incision surrounding the base of the tumor, different from a circular shape seromuscular layer in the conventional CLEAN-NET: around the tumor to preserve mucosal continuity, which acts as a barrier to avoid intraoperative tumor dissemination. CASE PRESENTATION: A 43-year-old woman was referred to our hospital because of a gastric submucosal tumor near the cardia, detected on medical examination. The patient was diagnosed with gastric GIST based on the results of endoscopic ultrasound-guided fine-needle aspiration. Modified CLEAN-NET was performed with a semicircular incision of the seromuscular layer on the opposite side of the cardia, making the surgical procedure simple and minimizing partial resection of the gastric wall, including the tumor, while preserving the cardia. The operative time was 147 min, preoperative blood loss volume was 3 mL, and postoperative hospital stay was 9 days. The resected specimen revealed a minimal resection of the gastric wall, including the tumor. The cardia and gastric nerves were preserved, and the postoperative food intake was good. CONCLUSIONS: The modified CLEAN-NET with semicircular seromuscular layer dissection is a simple and reliable surgical procedure for GIST near the cardia.
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Cardias , Gastrectomía , Tumores del Estroma Gastrointestinal , Laparoscopía , Neoplasias Gástricas , Humanos , Tumores del Estroma Gastrointestinal/cirugía , Tumores del Estroma Gastrointestinal/patología , Femenino , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Cardias/cirugía , Cardias/patología , Adulto , Gastrectomía/métodos , Laparoscopía/métodos , Pronóstico , Gastroscopía/métodos , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico/métodosRESUMEN
INTRODUCTION: Mutated human epidermal growth factor receptor 2 (HER2) is an oncogene with critical pathogenic roles in breast cancer. HER2-low-positive breast cancer is a recently described subtype. We aimed to explore the clinical and molecular characteristics of gastric cancer with low HER2 expression, drawing on recent developments in breast cancer subtypes. MATERIALS AND METHODS: This retrospective study involved 129 patients with HER2-non-amplified gastric cancer treated in Iwate prefectural Iwai Hospital from 2013 to 2019. Tumors were classified as HER2-null or low-positive based on immunohistochemistry score 0 or 1 + or 2 + with HER2 negativity in situ hybridization, respectively. Statistical analyses, including Kaplan-Meier analyses and Cox proportional hazards model were conducted. RESULTS: Low HER2 expression was present in 26% (33/129) of the patients. Clinicopathological characteristics were not significantly different between the HER2-low and null groups. Kaplan-Meier analysis of overall survival was significantly longer in the HER2-low group than in the HER2-null group (P = 0.01). In multivariate Cox regression analysis, HER2-null status was associated with worse survival (hazard ratio 3.01; 95% confidence interval 1.18-7.65; and P = 0.02). CONCLUSION: This study highlights the prognostic importance of low HER2 expression in gastric cancer, similar to that observed in HER2-low-positive breast cancer, and suggests reclassification of gastric cancer to improve personalized treatment. Future studies should elucidate the molecular underpinnings of low HER2 expression in gastric cancer to guide novel therapeutic strategies and improve outcomes.
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Receptor ErbB-2 , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patología , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Receptor ErbB-2/metabolismo , Receptor ErbB-2/genética , Femenino , Estudios Retrospectivos , Pronóstico , Anciano , Persona de Mediana Edad , Masculino , Estimación de Kaplan-Meier , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Adulto , Anciano de 80 o más Años , Inmunohistoquímica , Modelos de Riesgos ProporcionalesRESUMEN
BACKGROUND: This study aims to evaluate the short-term efficacy for locally advanced gastric cancer (LAGC) who accepted laparoscopic gastrectomy (LG) after neoadjuvant SOX versus SOX plus immune checkpoint inhibitors (ICIs). METHODS: LAGC patients who accepted LG after neoadjuvant SOX (SOX-LG, n = 169) and SOX plus ICIs (SOX + ICIs-LG, n = 140) in three medical centers between Jan 2020 and Mar 2024 were analyzed. We compared the tumor regression, treatment-related adverse events (TRAEs), perioperative safety between two groups, and explored the risk factors of postoperative complications (POCs) for LG after neoadjuvant therapy. RESULTS: The baseline characteristics were comparable between two groups (P > 0.05). SOX + ICIs-LG group acquired a higher proportion of objective response (63.6% vs. 46.7%, P = 0.003), major pathological response (43.6% vs. 31.4%, P = 0.001), and pathological complete response (17.9% vs. 9.5%, P = 0.030). There were no significant differences in the TRAEs rates, operation time, R0 resection, retrieved lymph nodes, postoperative first flatus, and hospitalized days, overall and severe POCs between two groups (P > 0.05). Patients in the SOX-ICIs-LG group had lower estimated blood loss (EBL) compared with SOX-LG (P = 0.001). Multivariate analysis showed that more EBL (P = 0.003) and prognostic nutritional index (PNI) < 40 (P = 0.005) were independent risk factors of POCs for LG after neoadjuvant therapy. CONCLUSION: Neoadjuvant SOX plus ICIs brings better tumor regression and similar TRAEs compared with SOX alone for LAGC. SOX + ICIs-LG is safe and feasible to conduct with less EBL. Surgeons should focus on the perioperative management to control POCs for patients with PNI < 40 and more EBL.
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Gastrectomía , Inhibidores de Puntos de Control Inmunológico , Laparoscopía , Terapia Neoadyuvante , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Masculino , Femenino , Gastrectomía/métodos , Gastrectomía/efectos adversos , Estudios Retrospectivos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Terapia Neoadyuvante/métodos , Persona de Mediana Edad , China/epidemiología , Laparoscopía/métodos , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Resultado del Tratamiento , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , AdultoRESUMEN
BACKGROUND: Sitravatinib is a spectrum-selective tyrosine kinase inhibitor targeting TAM (TYRO3, AXL, MER), VEGFR-2, KIT, and MET. SAFFRON-104 (NCT03941873) was a multicohort phase Ib/II study investigating sitravatinib with/without tislelizumab, an anti-programmed cell death protein 1 (PD-1) antibody, in patients with advanced hepatocellular carcinoma (HCC) or gastric cancer/gastroesophageal junction cancer (GC/GEJC). METHODS: Eligible patients had histologically/cytologically confirmed advanced HCC or GC/GEJC. Phase I determined the recommended phase II dose (RP2D) of sitravatinib with/without tislelizumab. Phase II evaluated sitravatinib monotherapy in patients with pretreated HCC, and sitravatinib plus tislelizumab in anti-PD-(L)1-naïve or -treated HCC and anti-PD-(L)1-naïve GC/GEJC. Primary endpoints were safety/tolerability (phase I) and objective response rate (ORR) (phase II). RESULTS: At data cutoff (March 31, 2023), 111 patients were enrolled; 102 were efficacy-evaluable (median study follow-up 9.1 months [range: 0.7-36.9]). The RP2D of sitravatinib was determined as 120 mg orally once daily. In patients receiving sitravatinib monotherapy and sitravatinib in combination with tislelizumab, grade ≥ 3 treatment-related adverse events occurred in 14 (51.9%) and 42 (50.0%) patients, respectively. The ORR was 25% (95% confidence interval [CI]: 8.7-49.1) in patients with pretreated HCC receiving sitravatinib monotherapy. In patients receiving sitravatinib with tislelizumab, the ORR was 11.5% (95% CI 2.4-30.2) with anti-PD-(L)1-naïve HCC, 9.5% (95% CI 1.2-30.4) with anti-PD-(L)1-treated HCC, and 16.1% (95% CI 5.5-33.7) in patients with anti-PD-(L)1-naïve GC/GEJC. CONCLUSIONS: Sitravatinib with/without tislelizumab was generally well tolerated and showed preliminary antitumor activity in patients with advanced HCC and GC/GEJC.
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Anticuerpos Monoclonales Humanizados , Carcinoma Hepatocelular , Unión Esofagogástrica , Neoplasias Hepáticas , Neoplasias Gástricas , Humanos , Masculino , Femenino , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/farmacología , Anciano , Persona de Mediana Edad , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Unión Esofagogástrica/patología , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/patología , Anciano de 80 o más AñosRESUMEN
A bibliometric analysis of studies dedicated to autoimmune gastritis (AIG) recently published demonstrated a noteworthy surge in publications over the last three years. This can be explained by numerous publications from different regions of the world reporting the results of several studies that stimulated reassessment of our view of AIG as a precancerous condition. Follow-up studies and retrospective analyses showed that the risk of gastric cancer (GC) in AIG patients is much lower than expected if the patients ever being infected with Helicobacter pylori (H. pylori) were excluded. The low prevalence of precancerous lesions, such as the incomplete type of intestinal metaplasia, may explain the low risk of GC in AIG patients because the spasmolytic polypeptide-expressing metaplasia commonly observed in AIG does not involve clonal reprogramming of the gastric gland and can be considered as an adaptive change rather than a true precancerous lesion. However, changes in gastric secretion due to the progression of gastric atrophy during the course of AIG cause changes in the gastric mic-robiome, stimulating the growth of bacterial species such as streptococci, which may promote the development of precancerous lesions and GC. Thus, Streptococcus anginosus exhibited a robust proinflammatory response and induced the gastritis-atrophy-metaplasia-dysplasia sequence in mice, reproducing the well-established process for carcinogenesis associated with H. pylori. Prospective studies in H. pylori-naïve patients evaluating gastric microbiome changes during the long-term course of AIG might provide an explanation for the enigmatic increase in GC incidence in the last decades in younger cohorts, which has been reported in economically developed countries.
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Enfermedades Autoinmunes , Bibliometría , Mucosa Gástrica , Gastritis , Infecciones por Helicobacter , Helicobacter pylori , Lesiones Precancerosas , Neoplasias Gástricas , Neoplasias Gástricas/inmunología , Neoplasias Gástricas/patología , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/epidemiología , Humanos , Gastritis/inmunología , Gastritis/microbiología , Gastritis/epidemiología , Gastritis/patología , Infecciones por Helicobacter/epidemiología , Infecciones por Helicobacter/inmunología , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/patología , Helicobacter pylori/aislamiento & purificación , Helicobacter pylori/inmunología , Helicobacter pylori/patogenicidad , Lesiones Precancerosas/inmunología , Lesiones Precancerosas/microbiología , Lesiones Precancerosas/patología , Lesiones Precancerosas/epidemiología , Animales , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/epidemiología , Mucosa Gástrica/patología , Mucosa Gástrica/inmunología , Mucosa Gástrica/microbiología , Metaplasia , Factores de Riesgo , Estómago/patología , Estómago/inmunología , Estómago/microbiología , Microbioma Gastrointestinal/inmunología , RatonesRESUMEN
Upregulation of homeoprotein SIX1 in gastric cancer (GC) is related to tumour proliferation and invasion. MicroRNA-7160 (miR-7160) is a homeoprotein SIX1-targeting miRNA that downregulates miR-7160, leading to cancer development. Total gastric cancer samples were collected from six patients, and relative expression levels of SIX1 mRNA and miRNAs were analysed by qRT-PCR. To evaluate the regulation of SIX1 by miR-7160, pGL3-SIX1-mut, pGL3-SIX1, and miR-7160 mimics transfected into cells using lipofectamine 2000. After transfection, proliferation and apoptosis in cultured cells were assessed using the nuclear TUNEL staining and CCK8 reagent, respectively. We demonstrated that the downregulation of miR-7160 in human gastric cancer cells is related to the upregulation of SIX1 mRNA. In gastric cancer cell lines, miR-7160 overexpression could downregulate the expression and inhibit cancer cell proliferation and growth in vitro. However, overexpression of miR-7160 did not increase gastric cancer cell apoptosis. In vitro downregulation of SIX1 decreased vimentin, N-cadherin, and other EMT-related gene expression and increased E-cadherin expression. In brief, miR-7160, by targeting SIX1, inhibits gastric cancer proliferation and cell growth in vitro, which provides an idea for introducing a new treatment option for gastric cancer.
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Apoptosis , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Proteínas de Homeodominio , MicroARNs , Neoplasias Gástricas , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Proliferación Celular/genética , Línea Celular Tumoral , Apoptosis/genética , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Metástasis de la Neoplasia , Transición Epitelial-Mesenquimal/genética , Silenciador del Gen , Movimiento Celular/genéticaRESUMEN
A 7-year-old Korean shorthair cat was admitted to our hospital with chronic constipation. Abdominal ultrasonography incidentally revealed a focal asymmetric gastric mass. The mass was submucosal and hypoechoic without loss of wall layering. Histopathological examination revealed a gastric submucosal lipoma (GSL). Although there have been reports of gastric submucosal fat infiltration in cats, there have been no reports regarding GSL. To our knowledge, this is the first report describing the ultrasonographic characteristics of GSL in a cat. Gastric submucosal lipoma should be considered as a differential diagnosis when a focal hypoechoic submucosal mass without loss of wall layering in the stomach is observed on ultrasound images. Key clinical message: This case report describes the ultrasonographic characteristics of GSL in a cat and aims to provide useful information for the diagnosis of lipoma occurring in the feline gastrointestinal tract. The ultrasonographic features and histological results we describe should be helpful in diagnosing submucosal lipoma in cats with similar conditions.
Caractéristiques échographiques d'un lipome sous-muqueux gastrique chez un chat: une étude de casUn chat coréen à poil court âgé de 7 ans a été admis à notre hôpital pour constipation chronique. L'échographie abdominale a révélé de manière fortuite une masse gastrique focale asymétrique. La masse était dans la sousmuqueuse et hypoéchogène sans perte de stratification murale. L'examen histopathologique a révélé un lipome sous-mucosal gastrique (GSL). Bien qu'il y ait eu des rapports d'infiltration de graisse dans la sous-muqueuse gastrique chez le chat, aucun rapport n'a été signalé concernant le GSL. À notre connaissance, il s'agit du premier rapport décrivant les caractéristiques échographiques du GSL chez un chat. Le lipome sous-muqueux gastrique doit être envisagé comme diagnostic différentiel lorsqu'une masse sous-muqueuse hypoéchogène focale sans perte de stratification de la paroi de l'estomac est observée sur les images échographiques.Message clinique clé:Ce rapport de cas décrit les caractéristiques échographiques du GSL chez un chat et vise à fournir des informations utiles pour le diagnostic des lipomes survenant dans le tractus gastro-intestinal félin. Les caractéristiques échographiques et les résultats histologiques que nous décrivons devraient être utiles pour diagnostiquer le lipome sous-muqueux chez les chats présentant des conditions similaires.(Traduit par Dr Serge Messier).
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Enfermedades de los Gatos , Lipoma , Neoplasias Gástricas , Ultrasonografía , Animales , Gatos , Lipoma/veterinaria , Lipoma/diagnóstico por imagen , Lipoma/cirugía , Lipoma/patología , Enfermedades de los Gatos/diagnóstico por imagen , Enfermedades de los Gatos/cirugía , Enfermedades de los Gatos/patología , Ultrasonografía/veterinaria , Neoplasias Gástricas/veterinaria , Neoplasias Gástricas/diagnóstico por imagen , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Masculino , FemeninoRESUMEN
Gastric cancer is one of the most malignant digestive tract tumors worldwide and its progression is associated with gene expression and metabolic alteration. We revealed that the gastric cancer patients with lower expression level of TOB1 exhibited poorer overall survivals according to the data in Kaplan-Meier Plotter. The unphosphorylated TOB1 protein which is effective expressed lower in gastric cancer cells. The gastric cancer cells with TOB1 gene depletion performed higher abilities of proliferation, migration and invasion and lower ability of apoptosis in vitro. The TOB1 gene depletion also promoted the tumorigenesis of gastric cancer cells in vivo. The gastric cancer cells with TOB1 gene overexpression had the converse behaviors. The transcriptional and metabolic sequencing was performed. The analyzation results showed that genes correlate-expressed with TOB1 gene were enriched in the pathways related to ERK pathway, including focal adhesion pathway, which was verified using real-time quantitative PCR. After inhibiting ERK pathway, the proliferation, colony formation and migration abilities were reduced in gastric cancer cells with low phosphorylated TOB1 protein expression level. Moreover, Pearson correlation analysis was adopted to further analyze the correlation of enriched metabolic products and differentially expressed genes. The expression of Choline, UDP-N-acetylglucosamine, Adenosine and GMP were related to the function of TOB1. This study demonstrates the genes and metabolites related to focal adhesion pathway and ERK pathway are the potential diagnosis and therapeutic targets to gastric cancer with TOB1 depletion.
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Movimiento Celular , Proliferación Celular , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Sistema de Señalización de MAP Quinasas , Neoplasias Gástricas , Proteínas Supresoras de Tumor , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidad , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismo , Movimiento Celular/genética , Línea Celular Tumoral , Animales , Ratones , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Adhesiones Focales/genética , Adhesiones Focales/metabolismo , Apoptosis/genéticaRESUMEN
Tumor cells remodel the phenotype and function of tumor microenvironment (TME) cells to favor tumor progression. Previous studies have shown that neutrophils in TME are polarized to N2 tumor-associated neutrophils (TANs) by tumor derived factors, thus promoting tumor growth and metastasis, angiogenesis, therapy resistance, and immunosuppression. Exosomes act as critical intercellular messengers in human health and diseases including cancer. So far, the biological roles of exosomes from N2 TANs in gastric cancer have not been well characterized. Herein, we represented the first report that exosomes from N2 TANs promoted gastric cancer metastasis in vitro and in vivo. We found that exosomes from N2 TANs transferred miR-4745-5p/3911 to gastric cancer cells to downregulate SLIT2 (slit guidance ligand 2) gene expression. Adenovirus-mediated overexpression of SLIT2 reversed the promotion of gastric cancer metastasis by N2 TANs derived exosomes. We further revealed that gastric cancer cells induced glucose metabolic reprogramming in neutrophils through exosomal HMGB1 (high mobility group protein B1)/NF-κB pathway, which mediated neutrophil N2 polarization and miR-4745-5p/3911 upregulation. We further employed ddPCR (droplet digital PCR) to detect the expression of miR-4745-5p/3911 in N2 TANs exosomes from human serum samples and found their increased levels in gastric cancer patients compared to healthy controls and benign gastric disease patients. Conclusively, our results indicate that N2 TANs facilitate cancer metastasis via regulation of SLIT2 in gastric cancer cells by exosomal miR-4745-5p/3911, which provides a new insight into the roles of TME cells derived exosomes in gastric cancer metastasis and offers a potential biomarker for gastric cancer diagnosis.
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Exosomas , Regulación Neoplásica de la Expresión Génica , Péptidos y Proteínas de Señalización Intercelular , MicroARNs , Proteínas del Tejido Nervioso , Neutrófilos , Neoplasias Gástricas , Microambiente Tumoral , Neoplasias Gástricas/patología , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Exosomas/metabolismo , Exosomas/genética , Humanos , Neutrófilos/metabolismo , Neutrófilos/patología , MicroARNs/genética , Animales , Ratones , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Línea Celular Tumoral , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Péptidos y Proteínas de Señalización Intercelular/genética , Microambiente Tumoral/genética , Metástasis de la Neoplasia , Proteína HMGB1/metabolismo , Proteína HMGB1/genética , MasculinoRESUMEN
BACKGROUND: Potentially curative therapy for locally advanced gastric cancer consists of gastrectomy, usually in combination with perioperative chemotherapy. An oncological resection includes a radical (R0) gastrectomy and modified D2 lymphadenectomy; generally, a total omentectomy is also performed, to ensure the removal of possible microscopic disease. However, the omentum functions as a regulator of regional immune responses to prevent infections and prevents adhesions which could lead to bowel obstructions. Evidence supporting a survival benefit of routine complete omentectomy during gastrectomy is lacking. METHODS: OMEGA is a randomized controlled, open, parallel, non-inferiority, multicenter trial. Eligible patients are operable (ASA < 4) and have resectable (⦠cT4aN3bM0) primary gastric cancer. Patients will be 1:1 randomized between (sub)total gastrectomy with omentum preservation distal of the gastroepiploic vessels versus complete omentectomy. For a power of 80%, the target sample size is 654 patients. The primary objective is to investigate whether omentum preservation in gastrectomy for cancer is non-inferior to complete omentectomy in terms of 3-year overall survival. Secondary endpoints include intra- and postoperative outcomes, such as blood loss, operative time, hospital stay, readmission rate, quality of life, disease-free survival, and cost-effectiveness. DISCUSSION: The OMEGA trial investigates if omentum preservation during gastrectomy for gastric cancer is non-inferior to complete omentectomy in terms of 3-year overall survival, with non-inferiority being determined based on results from both the intention-to-treat and the per-protocol analyses. The OMEGA trial will elucidate whether routine complete omentectomy could be omitted, potentially reducing overtreatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT05180864. Registered on 6th January 2022.
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Estudios de Equivalencia como Asunto , Gastrectomía , Estudios Multicéntricos como Asunto , Epiplón , Neoplasias Gástricas , Humanos , Epiplón/cirugía , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Gastrectomía/efectos adversos , Gastrectomía/métodos , Resultado del Tratamiento , Factores de Tiempo , Calidad de Vida , Adulto , Ensayos Clínicos Controlados Aleatorios como Asunto , Masculino , Persona de Mediana Edad , Femenino , Anciano , Escisión del Ganglio Linfático/efectos adversos , Tratamientos Conservadores del Órgano/métodos , Tratamientos Conservadores del Órgano/efectos adversos , Supervivencia sin EnfermedadRESUMEN
BACKGROUD: According to the 2020 statistics from the World Health Organization's International Agency for Research on Cancer (IARC), it is projected that there will be over 1 million new cases of gastric cancer (GC) patients worldwide in 2020, resulting in approximately 770 000 deaths. Gastric cancer ranks fifth in terms of incidence rate and forth in death rate among malignant tumors. Despite advancements in early diagnostic techniques, the incidence of GC has exhibited a marginal decline; nevertheless, the mortality rate remains elevated for advanced inoperable patients with no currently available efficacious treatment options. RECENT FINDING: Chinese medicine (CM) has emerged as an efficacious treatment for GC, gradually gaining acceptance and widespread usage in China. It exhibits distinctive advantages in the prevention and treatment of metastasis. CM and natural medicine possess the ability to elicit antitumor effects by augmenting immune cell population, enhancing immune cell activity, and improving the tumor immune microenvironment. CMs and natural remedies encompass a diverse range of types, characterized by multiple targets, pathways, and extensive pharmacological effects. Consequently, they have become a prominent research area among oncologists worldwide. Numerous studies have demonstrated that CM and natural medicine can directly or indirectly enhance innate immune system components (including macrophages, natural killer cells, and myeloid suppressor cells), adaptive immune system elements (such as T lymphocytes and regulatory T cells), relevant cytokines (e.g., IL-2, IL-4, IL-10, TNF-α), and PD-1/PD-L1 axis regulation, thereby bolstering the cytotoxicity of immune cells against tumor cells. CONCLUSIONS: This ultimately leads to an improved tumor immune microenvironment facilitating superior antitumor efficacy. This paper critically examines the role of CM and natural medicine in regulating immunotherapy for GC, aiming to establish a new theoretical framework for the clinical treatment and prevention of gastric cancer within the realm of CM.
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Medicamentos Herbarios Chinos , Inmunoterapia , Medicina Tradicional China , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/inmunología , Neoplasias Gástricas/terapia , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Medicamentos Herbarios Chinos/uso terapéutico , Inmunoterapia/métodos , Medicina Tradicional China/métodos , Microambiente Tumoral/inmunología , Microambiente Tumoral/efectos de los fármacosRESUMEN
Long non-coding RNAs (lncRNAs) play an important role in the progression of gastric cancer (GC), but its specific regulatory mechanism remains to be further studied. We previously identified that lncRNA B3GALT5-AS1 was upregulated in GC serum. Here, we investigated the functions and molecular mechanisms of B3GALT5-AS1 in GC tumorigenesis. qRT-PCR was used to detect B3GALT5-AS1 expression in GC. EdU, CCK-8, and colony assays were utilized to assess the proliferation ability of B3GAL5-AS1, and transwell, tube formation assay were used to assess the invasion and metastasis ability. Mechanically, FISH and nuclear plasmolysis PCR identified the subcellular localization of B3GALT5-AS1. RIP and CHIP assays were used to analyse the regulation of B3GALT5-AS1 and B3GALT5. We observed that B3GALT5-AS1 was highly expressed in GC, and silencing B3GALT5-AS1 could inhibit the proliferation, invasion, and migratory capacities of GC. Additionally, B3GALT5-AS1 was bound to WDR5 and modulated the expression of B3GALT5 via regulating the ZEB1/ß-catenin pathway. High-expressed B3AGLT5-AS1 promoted GC tumorigenesis and regulated B3GALT5 expression via recruiting WDR5. Our study is expected to provide a new idea for clinical diagnosis and treatment.
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Movimiento Celular , Proliferación Celular , Progresión de la Enfermedad , Galactosiltransferasas , Regulación Neoplásica de la Expresión Génica , ARN Largo no Codificante , Neoplasias Gástricas , Homeobox 1 de Unión a la E-Box con Dedos de Zinc , beta Catenina , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Neoplasias Gástricas/metabolismo , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , beta Catenina/metabolismo , beta Catenina/genética , Proliferación Celular/genética , Línea Celular Tumoral , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/metabolismo , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/genética , Movimiento Celular/genética , Galactosiltransferasas/genética , Galactosiltransferasas/metabolismo , Animales , Ratones , Ratones Desnudos , Transducción de Señal , Carcinogénesis/genética , Carcinogénesis/patología , MasculinoRESUMEN
Paired immunoglobin-like type 2 receptor beta (PILRB) mainly plays a crucial role in regulating innate immunity, but whether PILRB is involved in cancer is poorly understood. Here, we report that PILRB potentiates the PI3K/AKT pathway to drive gastric tumorigenesis by binding and stabilizing IRS4, which could hyperactivate the PI3K/AKT pathway. Firstly, the levels of PILRB are upregulated in human gastric cancer (GC) specimens and associated with poor prognosis in patients with GC. In addition, our data show that PILRB promotes cell proliferation, colony formation, cell migration and invasion in GC cells in vitro and in vivo. Mechanistically, PILRB recruits the deubiquitination enzymes OTUB1 to IRS4 and relieves K48-linked ubiquitination of IRS4, protecting IRS4 protein from proteasomal-mediated degradation and subsequent activation of the PI3K/AKT pathway. Importantly, the levels of PILRB are positively correlated with IRS4 in GC specimens. Meanwhile, we also found that PILRB reprogrammed cholesterol metabolism by altering ABCA1 and SCARB1 expression levels, and PILRB-expression confers GC cell resistance to statin treatment. Taken together, our findings illustrate that the oncogenic role of PILRB in gastric tumorigenesis, providing new insights into the regulation of PI3K/AKT signaling in GC and establishing PILRB as a biomarker for simvastatin therapy resistance in GC.
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Carcinogénesis , Colesterol , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patología , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Animales , Colesterol/metabolismo , Carcinogénesis/metabolismo , Carcinogénesis/patología , Carcinogénesis/genética , Línea Celular Tumoral , Ratones , Ratones Desnudos , Proliferación Celular , Metástasis de la Neoplasia , Movimiento Celular , Masculino , Ratones Endogámicos BALB CRESUMEN
BACKGROUND: Myeloid-derived suppressor cells (MDSCs) are the major factor in gastric cancer (GC) immune evasion. Nevertheless, the molecular process underlying the expansion of MDSCs induced by tumor-derived exosomes (TDEs) remains elusive. METHODS: The levels of exosomal and soluble PD-L1 in ninety GC patients were examined via enzyme-linked immunosorbent assay (ELISA) to determine their prognostic value. To investigate the correlation between exosomal PD-L1 and MDSCs, the percentage of MDSCs in the peripheral blood of 57 GC patients was assessed via flow cytometry. Through ultracentrifugation, the exosomes were separated from the GC cell supernatant and detected via Western blotting, nanoparticle tracking analysis (NTA), and transmission electron microscopy (TEM). The function of exosomal PD-L1 in MDSCs was evaluated via immunofluorescence, Western blotting and flow cytometry in a GC cell-derived xenograft (CDX) model. RESULTS: The overall survival (OS) of GC patients in the high exosomal PD-L1 group was significantly lower than that of patients in the low exosomal PD-L1 group (P = 0.0042); however, there was no significant correlation between soluble PD-L1 and OS in GC patients (P = 0.0501). Furthermore, we found that the expression of exosomal PD-L1 was positively correlated with the proportions of polymorphonuclear MDSCs (PMN-MDSCs, r = 0.4944, P < 0.001) and monocytic MDSCs (M-MDSCs, r = 0.3663, P = 0.005) in GC patients, indicating that exosomal PD-L1 might induce immune suppression by promoting the aggregation of MDSCs. In addition, we found that exosomal PD-L1 might stimulate MDSC proliferation by triggering the IL-6/STAT3 signaling pathway in vitro. The CDX model confirmed that exosomal PD-L1 could stimulate tumor development and MDSC amplification. CONCLUSIONS: Exosomal PD-L1 has the potential to become a prognostic and diagnostic biomarker for GC patients. Mechanistically, MDSCs can be activated by exosomal PD-L1 through IL-6/STAT3 signaling and provide a new strategy against GC through the use of exosomal PD-L1 as a treatment target.