Background
Endoscopic submucosal dissection (ESD) is an endoscopic alternative to surgical resection of early gastric cancer (EGC). Besides offering both diagnostic and therapeutic capability, it has ...the benefits of reducing post-operative complications and provides fast recovery and better quality of life compared to surgical resection of neoplastic lesions. However, due to limitations of the procedure, its long-term outcomes are rather controversial.
Methods
This study has been carried out to investigate the long-term outcomes of ESD which includes the overall survival (OS), disease-free survival (DFS), and recurrence rate. The following databases were used to search for articles published until February 2018: Medline, Cochrane Library, PubMed, Web of Science, and EBSCO.
Results
A total of 13 eligible studies covering 4986 patients were selected for a meta-analysis based on specified inclusion and exclusion criteria. The difference of OS and disease-specific survival (DSS) between ESD and surgical treatment was not statistically significant (RR = 0.90, 95% CI = 0.68–1.19,
p
= 0.46; RR = 0.40, 95% CI = 0.15–1.03,
p
= 0.06, respectively). However, DFS in the ESD group was much lower than that in the surgery group (RR = 3.40, 95% CI = 2.39–4.84,
p
< 0.001). In terms of the treatment after recurrence, the proportion of patients who could receive radical treatment was significantly higher in the ESD than that in the gastrectomy (OR = 5.27, 95% CI = 2.35–11.79,
p
< 0.001).
Conclusions
This meta-analysis showed that ESD might be an alternative treatment option to surgery for patients with EGC in Asian countries. But a close surveillance program after ESD is of necessity, considering the higher possibility of tumor recurrence after ESD.
Gastric cancer is one of the most common cancers and is the second leading cause of cancer mortality worldwide. Therefore, it is urgent to explore new molecular biomarkers for early diagnosis, early ...treatment and prognosis for gastric cancer patients. Recently, increasing evidence has shown that epigenetic changes, such as aberrant DNA methylation, histone modifications, and noncoding RNAs (ncRNAs) expression, play substantial roles in the development and progression of malignancies. Among these changes, long non-coding RNAs (lncRNAs), a novel class of ncRNAs, are emerging as highly versatile actors in a variety of cellular processes by regulating gene expression at the epigenetic level as well as at the transcriptional and post-transcriptional levels. Hundreds of lncRNAs become dysregulated in the various pathological processes of gastric cancer, and multiple lncRNAs have been reported to function as tumor-suppressors or oncogenes, although the underlying mechanisms are still under investigation. Here, we provide an overview of the epigenetic regulation of chromatin and the molecular functions of lncRNAs; we focus on lncRNA-mediated epigenetic regulation of cancer-related gene expression in gastric cancer, as well as discuss the clinical implications of lncRNAs on epigenetic-related cancer treatments, which may contribute helpful approaches for the development of new potential strategies for future diagnosis and therapeutic intervention in human cancers.
•Upregulation USP3 or inhibitor miR-224-5p restored GC cells proliferation and migration.•Upregulation of USP3 restored GC cells proliferation and migration.•Hsa_circ_0017639 expression promotes ...gastric cancer proliferation and metastasis.
Gastric cancer (GC) is a common malignant tumor having poor prognosis globally. Circular RNA (circRNA) is a circular endogenous RNA generated by special selective splicing that occurs in various traits. Studies show that hsa_circ_0017639 is abnormally expressed and involved in tumorigenesis. Nevertheless, the hsa_circ_0017639 role in GC is unknown. This study detected hsa_circ_0017639 expression in a GC cell line using RT-qPCR. Subcellular localization of hsa_circ_0017639 was verified via FISH. We assessed correlations amongst miRNA, hsa_circ_0017639 and relative protein levels using luciferase reporter assays and RNA pulldown assays. The data illustrated that in hsa_circ_assays, expression was enhanced in GC cell. Downregulation of hsa_circ_0017639 decreased GC cell proliferation and migration in in vitro and in vivo experiments. RNA pulldown and RT-qPCR analysis verified that hsa_circ_0017639 sponged miR-224-5p. Bioinformatic and luciferase reporter assays validated that miR-224-5p and USP3 were downstream targets of hsa_circ_0017639. Upregulation of USP3 or downregulation of miR-224-5p restored proliferation and migration by MKN-28 and MGC-803 cells after hsa_circ_0017639 silencing. Upregulation of USP3 restored MKN-28 and MGC-803 cell proliferation and migration after overexpression of miR-224-5p. Our collective findings advised that hsa_circ_0017639 takes part in GC progression through regulating the miR-224-5p/USP3 axis, highlighting its potential as an effective GC therapeutic target.
In the phase III KEYNOTE-061 trial (NCT02370498), pembrolizumab did not significantly improve overall survival versus paclitaxel as second-line therapy for gastric/gastroesophageal junction (GEJ) ...adenocarcinoma with programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥1 tumors. The association of tissue tumor mutational burden (tTMB) status and clinical outcomes was determined, including the relationship with CPS and microsatellite instability-high (MSI-H) status.
In patients with whole exome sequencing (WES) data 420/592 (71%); pembrolizumab, 218; paclitaxel, 202, the association of tTMB with objective response rate (ORR; logistic regression), progression-free survival (PFS; Cox proportional hazards regression), and overall survival (OS; Cox proportional hazards regression) were measured using one-sided (pembrolizumab) and two-sided paclitaxel P values. tTMB was also evaluated using FoundationOne®CDx 205/592 (35%). Prespecified equivalent cut-offs of 175 mut/exome for WES and 10 mut/Mb for FoundationOne®CDx were used.
WES-tTMB was significantly associated with ORR, PFS, and OS in pembrolizumab-treated (all P < 0.001) but not paclitaxel-treated patients (all P > 0.6) in univariate analysis. The area under the receiver operating characteristics curve for WES-tTMB and response was 0.68 95% confidence interval (CI) 0.56-0.81 for pembrolizumab and 0.51 (95% CI 0.39-0.63) for paclitaxel in univariate analysis. There was low correlation between WES-tTMB and CPS in both treatment groups (r ≤ 0.16). WES-tTMB remained significantly associated with all clinical endpoints with pembrolizumab after adjusting for CPS and with PFS and OS after excluding known MSI-H tumors (n = 26). FoundationOne®CDx-tTMB demonstrated a positive association with ORR, PFS, and OS in pembrolizumab-treated patients (all P ≤ 0.003) but not PFS or OS in paclitaxel-treated patients (P > 0.1).
This exploratory analysis from KEYNOTE-061 is the first to demonstrate a strong association between tTMB and efficacy with pembrolizumab but not paclitaxel in patients with gastric/GEJ adenocarcinoma in a randomized setting. Data further suggest tTMB is a significant and independent predictor beyond PD-L1 status.
•Second-line pembrolizumab showed a strong association between tTMB and efficacy in gastric and gastroesophageal cancer.•There was low correlation between WES-tTMB and PD-L1 CPS.•WES-tTMB was associated significantly with pembrolizumab PFS and OS after excluding known MSI-H tumors.•Findings with FoundationOne®CDx-tTMB were similar to those with WES-tTMB.
Previous studies have indicated that vitamin D deficiency correlates with cancer risk and vitamin D potentiates antitumor effects in a variety of cancers. The antitumor effect of vitamin D on gastric ...cancer was rarely studied. We aimed to investigate the antitumor effect of vitamin D on gastric cancer and underlying mechanisms.
We investigated the antitumor activity of the active form of vitamin D, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) on gastric cancer cells (TMK1) and immortalized normal gastric cells (HFE145) by using MTT, colony formation and Flow cytometry assays. We demonstrated the important role of vitamin D receptor (VDR) and mutant p53 (mutp53) in mediating the antitumor action of 1,25(OH)2D3 by using siRNA, western-blot, immunofluorescent staining and immunoprecipitation assays.
1,25(OH)2D3 could significantly inhibit proliferation and induce cell cycle arrest in TMK1 but not in HFE145. Furthermore, 1,25(OH)2D3 stimulated p21 expression and suppressed cyclin-dependent kinase 2 (CDK2) expression in TMK1 in a VDR-dependent manner. High levels of VDR in human gastric cancer tissues and cancer cell lines implicated that vitamin D could display more potent pharmacological action against malignant cells. Besides, mutp53 but not wild type p53 was essential for 1,25(OH)2D3-stimulated upregulation of p21 in gastric cancer cells. Indeed, mutp53 could stabilize nuclear VDR level through interaction with VDR.
Our results suggest that 1,25(OH)2D3 inhibits gastric cancer cell growth through VDR and mutp53 interaction followed by the modulation of p21/CDK2. We propose that vitamin D might be used for the prophylactic treatment for malignant diseases in the stomach.
With the expectation to find out new anti-gastric cancer agents with high efficacy and selectivity, a series of novel tertiary sulfonamide derivatives were synthesized and the anti-cancer activity ...was studied in three selected cancer cell lines (MGC-803, PC-3, MCF-7) in vitro. Some of the synthesized compounds could significantly inhibit the proliferation of these tested cancer cells and were more potent than the positive control (5-Fu). The structure-activity relationship of tertiary sulfonamide derivatives was explored in this report. Among the tested compounds, compound 13g containing benzimidazole moiety showed the best anti-proliferation activities against MGC-803 cells (IC50 = 1.02 μM), HGC-27 cells (IC50 = 1.61 μM), SGC-7901 (IC50 = 2.30 μM) cells as well as the good selectivity between the cancer and normal cells. Cellular mechanism studies elucidated compound 13g inhibited the colony formation of gastric cancer cell lines. Meanwhile, compound 13g arrested cell cycle at G2/M phase and induced cell apoptosis. Mechanistically, compound 13g markedly decreased p-Akt and p-c-Raf expression, which revealed that compound 13g targeted gastric cancer cell lines via interfering with AKT/mTOR and RAS/Raf/MEK/ERK pathways. All the findings suggest that compound 13g might be a valuable lead compound for the anti-gastric cancer agents.
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•Novel sulfonamide derivatives containing benzimidazole moiety were designed and prepared.•Compound 13g displayed excellent anti-proliferative activity and lower toxicity against the non-cancer cells.•Structure-activity relationship of sulfonamide derivatives was depicted.•Compound 13g caused cell cycle arrest at G2/M phase and induced cell apoptosis.•Compound 13g could down-regulate the p-Akt and p-c-Raf expression.
To evaluate mortality reduction from gastric cancer by endoscopic screening, we undertook a population‐based cohort study in which both radiographic and endoscopic screenings for gastric cancer have ...been carried out. The subjects were selected from the participants of gastric cancer screening in two cities in Japan, Tottori and Yonago, from 2007 to 2008. The subjects were defined as participants aged 40–79 years who had no gastric cancer screening in the previous year. Follow‐up of mortality was continued from the date of the first screening to the date of death or up to December 31, 2013. A Cox proportional hazards model was used to estimate the relative risk (RR) of gastric cancer incidence, gastric cancer death, all cancer deaths except gastric cancer death, and all‐causes death except gastric cancer death. The number of subjects selected for endoscopic screening was 9950 and that for radiographic screening was 4324. The subjects screened by endoscopy showed a 67% reduction of gastric cancer compared with the subjects screened by radiography (adjusted RR by sex, age group, and resident city = 0.327; 95% confidence interval CI, 0.118–0.908). The adjusted RR of endoscopic screening was 0.968 (95%CI, 0.675–1.387) for all cancer deaths except gastric cancer death, and 0.929 (95%CI, 0.740–1.168) for all‐causes death except gastric cancer death. This study indicates that endoscopic screening can reduce gastric cancer mortality by 67% compared with radiographic screening. This is consistent with previous studies showing that endoscopic screening reduces gastric cancer mortality.
This study indicates that endoscopic screening can reduce gastric cancer mortality by 67% compared with radiographic screening. This is consistent with previous studies showing that endoscopic screening reduces gastric cancer mortality.
Background
A growing number of studies that differ in design, quality, and results report an association between the use of proton pump inhibitors (PPIs) and the risk of gastric cancer (GC). We ...conducted a systematic review and meta-analysis, when possible, of observational and interventional studies examining PPI use and risk of GC.
Methods
We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We identified studies fully published in English through January 2023 using MeSH and non-MeSH keywords. We used random effects models to calculate pooled risk estimates with 95% confidence interval (CI) between PPI use and overall GC, cardia GC, and non-cardia GC. We estimated heterogeneity (I
2
) among studies. We examined the effect of study design and quality, GC site,
H. pylori
infection, and PPI duration. We assessed quality using the Newcastle–Ottawa Quality Assessment Scale and Risk Of Bias In Non-randomized Studies of Interventions.
Results
We identified 15 observational studies, of which 13 were included in the meta-analysis (six cohort and seven case–control). There was a modest 1.67-fold increase in overall GC risk (95% CI 1.39, 2.00) and no increase in cardia GC risk odds ratio (OR) 1.12; 95% CI 0.80, 1.56 with PPI use. However, there was high heterogeneity (I
2
= 61.3%, p = 0.004) among studies. All but one study had at least moderate risk of bias. In the six studies accounting for
H. pylori
, GC risk associated with PPI use increased slightly (OR 1.78; 95% CI 1.25, 2.52). Duration response was not reported consistently to allow pooled estimates. We identified only one interventional randomized controlled study that included GC as an outcome of interest, and it did not show increased GC risk.
Conclusions
The overall available evidence is not supportive of a meaningful change in GC risk, either cardia or non-cardia, with PPI use.
•MicroRNAs (miRNAs) have critical roles in regulation of several aspects of gastric carcinogenesis.•MiRNAs can modulate sensitivity to chemotherapeutic agents via regulation of autophagy or efflux of ...these agents.•Serum or tissue levels of miRNAs can discriminate cancer patients from healthy subjects.•MiRNAs alter the function of several cancer-associated pathways such as PTEN/PI3K/AKT.
MicroRNAs (miRNAs) are a group of non-coding RNAs that have critical roles in regulation of expression of genes. They can inhibit or decrease expression of target genes mostly via interaction with 3′ untranslated region of their targets. Their crucial roles in the regulation of expression of tumor suppressor genes and oncogenes have potentiated them as contributors in tumorigenesis. Moreover, their stability in body fluids has enhanced their potential as cancer biomarkers. In the present review article, we describe the role of miRNAs in the pathogenesis of gastric cancer and advances in application of miRNAs as biomarkers and therapeutic targets in this kind of malignancy.
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