laparoscopy-endoscopy-cooperative-surgery-for-treatment-gastric

Laparoscopy-endoscopy Cooperative Surgery for the Treatment of Gastric Gastrointestinal Stromal Tumors

In view of the shortcomings of endoscopic or laparoscopic surgeries alone in the treatment of gastric gastrointestinal stromal tumors (G-GISTs), this ...

Sun Yat-sen University

The T-cell surface molecule TIGIT is an immune checkpoint molecule that inhibits T-cell responses, but its roles in cancer are little understood. In this study, we evaluated the role TIGIT checkpoint plays in the development and progression of gastric cancer. We show that the percentage of CD8 T cells that are TIGIT was increased in gastric cancer patients compared with healthy individuals. These cells showed functional exhaustion with impaired activation, proliferation, cytokine production, and metabolism, all of which were rescued by glucose. In addition, gastric cancer tissue and cell lines expressed CD155, which bound TIGIT receptors and inactivated CD8 T cells. In a T cell-gastric cancer cell coculture system, gastric cancer cells deprived CD8 T cells of glucose and impaired CD8 T-cell effector functions; these effects were neutralized by the additional glucose or by TIGIT blockade. In gastric cancer tumor cells, CD155 silencing increased T-cell metabolism and IFNγ production, whereas CD155 overexpression inhibited T-cell metabolism and IFNγ production; this inhibition was neutralized by TIGIT blockade. Targeting CD155/TIGIT enhanced CD8 T-cell reaction and improved survival in tumor-bearing mice. Combined targeting of TIGIT and PD-1 further enhanced CD8 T-cell activation and improved survival in tumor-bearing mice. Our results suggest that gastric cancer cells inhibit CD8 T-cell metabolism through CD155/TIGIT signaling, which inhibits CD8 T-cell effector functions, resulting in hyporesponsive antitumor immunity. These findings support the candidacy of CD155/TIGIT as a potential therapeutic target in gastric cancer. .

CD155T/TIGIT Signaling Regulates CD8 T-cell Metabolism and Promotes Tumor Progression in Human Gastric Cancer.

The association between cellular senescence and Helicobacter pylori-induced atrophic gastritis is not clear. Here, we explore the role of cellular senescence in H pylori-induced atrophic gastritis and the underlying mechanism.

Inflammation-Associated Senescence Promotes Helicobacter pylori-Induced Atrophic Gastritis.

 Measuring postoperative carcinoembryonic antigen (CEA) is recommended by guidelines to help detecting recurrence of gastric cancer patients. However, the prognostic significance of elevated preoperative CEA is unclear. This study aims to investigate whether patients with elevated preoperative CEA have a higher risk of recurrence than patients with normal preoperative CEA.  We conducted a retrospective cohort study at a gastric cancer center in South China. Consecutive patients with stage I to III gastric adenocarcinoma who underwent curative resection at the center from January 2001 to February 2016 were identified. Patients were grouped into two cohorts: normal preoperative CEA (≤ 5 ng/ml), and elevated preoperative CEA (> 5 ng/ml). 3-year recurrence-free survival (RFS) and hazard function curves over time were estimated.  A total of 1,596 patients (1,063 {66.6%} male; median {Interquartile range, IQR} age, 59 {50-66} years) were identified. Patients with elevated preoperative CEA had 15.5% lower 3-year RFS (n=222 {70.4%}) than the cohorts with normal preoperative CEA (n=1,374 {85.9%}). The hazard function of recurrence for the two cohorts peaked at the similar time (around 10 months after surgery). Multivariate Cox analyses confirmed that elevated preoperative CEA was independently associated with shorter RFS (Hazard Ratio {HR}, 1.69; 95% confidence interval {CI}, 1.26-2.27;  = 0.001).  Patients with elevated preoperative CEA are at increased risk for recurrence, especially within the first 24 months after surgery.

Association of Preoperative Serum Carcinoembryonic Antigen and Gastric Cancer Recurrence: A Large Cohort Study.

 Tac2-N (TC2N) is a tandem C2 domain-containing protein, acting as a novel oncogene or suppressor in different kinds of cancers. However, the status of  expression and its significance in gastric cancer (GC) is still unclear. The present study is aimed to elucidate the clinicopathological significance and prognostic value of  level in GC.  We used sequencing data from the Cancer Genome Atlas (TCGA) database to analyze  expression in GC by UALCAN database and Gene Expression Profiling Interactive Analysis tools (GEPIA).  expression level in 12 pairs of fresh GC tissues and adjacent nontumorous tissues was detected by quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR) and Western blot (WB) assays. Immunohistochemical (IHC) staining was used to detect TC2N protein expression in Paraffin-embedded tissues in our center.  proliferation, migration and invasion assays were used to evaluate the effect of  on functional capability of gastric cancer cells. LinkedOmics was used to identify gene expressions associated with .  The mRNA and protein expression of  in gastric cancer were both significantly higher than normal gastric mucosa. It was also elevated in gastric cancer cells compared with normal gastric epithelium cell.  assays suggested that  facilitated proliferation, migration and invasion of gastric cancer cells. Bioinformatic analysis showed a widespread impact of  on the transcriptome and a strong interaction with tumor associated genes. We also found that  was an independent prognostic factor for long-term survival in GC patients and its high expression was evidently associated with poor overall survival and recurrence-free survival.  Our results show that high level of TC2N correlates with poor prognosis in patients with gastric cancer and promotes the development of gastric cancer. Thus, TC2N expression can serve as a prognostic biomarker for patients with gastric cancer.

Overexpression of TC2N is associated with poor prognosis in gastric cancer.

MAPK6-AKT signaling promotes tumor growth and resistance to mTOR kinase blockade.

Twin grasper-assisted endoscopic mucosa-inverting closure for large perforations after endoscopic full-thickness resection: a new endoscopic technique.

Long noncoding RNAs (lncRNAs) have been reported to regulate diverse tumorigenic processes. However, little is known about long intergenic non-protein coding RNA 00893 (LINC00893) and its role in gastric cancer (GC). Herein we investigated its biological functions and molecular mechanism in GC. LINC00893 was decreased in GC tissues but significantly elevated in AGS cells after treatment with Nutlin-3. In GC patients, it was found that low expression of LINC00893 was correlated with tumor growth, metastasis and poor survival. Functionally, overexpression of LINC00893 suppressed the proliferation, migration and invasion of GC cells. Mechanistically, LINC00893 regulated the expression of epithelial-mesenchymal transition (EMT)-related proteins by binding to RNA binding fox-1 homolog 2 (RBFOX2) and promoting its ubiquitin-mediated degradation, thus suppressing the EMT and related functions of GC. In addition, the transcription factor p53 can regulate the expression of LINC00893 in an indirect way. Taken together, these results suggested that LINC00893 regulated by p53 repressed GC proliferation, migration and invasion by functioning as a binding site for RBFOX2 to regulate its stability and the expression of EMT-related proteins. LINC00893 acts as a tumor-inhibiting lncRNA that is induced by p53 in GC and regulates EMT by binding to RBFOX2, thus providing a novel experimental basis for the clinical treatment of GC.

Article	Year
CD155T/TIGIT Signaling Regulates CD8 T-cell Metabolism and Promotes Tumor Progression in Human Gastric Cancer. Cancer research\| PubMed ID: 28883004	2017
Inflammation-Associated Senescence Promotes Helicobacter pylori-Induced Atrophic Gastritis. Cellular and molecular gastroenterology and hepatology\| PubMed ID: 33161156	2021
Association of Preoperative Serum Carcinoembryonic Antigen and Gastric Cancer Recurrence: A Large Cohort Study. Journal of Cancer\| PubMed ID: 33391436	2021
Overexpression of TC2N is associated with poor prognosis in gastric cancer. Journal of Cancer\| PubMed ID: 33403038	2021
MAPK6-AKT signaling promotes tumor growth and resistance to mTOR kinase blockade. Science advances\| PubMed ID: 34767444	2021
Twin grasper-assisted endoscopic mucosa-inverting closure for large perforations after endoscopic full-thickness resection: a new endoscopic technique. Endoscopy\| PubMed ID: 34933359	2021
p53-Induced LINC00893 Regulates RBFOX2 Stability to Suppress Gastric Cancer Progression. Frontiers in cell and developmental biology\| PubMed ID: 35127712	2021

Qinbo Cai

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