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Researchers have performed numerous studies on immunotherapy because of the high death rate associated with gastric cancer (GC). GC immunotherapy research has made tremendous progress, and we wanted to provide an update on this topic. On the basis of this update, we suggest performing a new medical evaluation before initiating immunotherapy in patients with GC to increase the success rate of immunotherapies. We propose that before patients start GC immunotherapy, they should be evaluated and given a score of one to two points for the following factors: immunopathological features, molecular and genomic features, potential consequences for bacterial pathogens, potential immunotherapeutic resistance and hyperprogressive illness, and the potential to use biomarkers to gauge their prognosis and immunotherapy responses to optimize immunotherapy following surgery. The proposed scoring system could also help in the diagnosis of GC. With all the advances in genetics, immunology, and microbiology, the diagnosis of GC could be improved, not changed. Currently, patients diagnosed with GC undergo surgical resection as the only permanent solution. Patients who meet the maximum score from the presented proposal could be eligible immediately after diagnosis for immunotherapy. Therefore, immunotherapy could be a first-line option for clinicians. [ABSTRACT FROM AUTHOR]

Small Heterodimer Partner (SHP; NR0B2) is an orphan receptor that acts as a transcriptional regulator, controlling various metabolic processes, and is a potential therapeutic target for cancer. Examining the correlation between the expression of NR0B2 and the risk of gastric diseases could open a new path for treatment and drug development. The Gene Expression Omnibus (GEO) database was utilized to explore NR0B2 gene expression profiles in gastric diseases. Co-expressed genes were identified through Weighted Correlation Network Analysis (WGCNA), and GO enrichment was performed to identify potential pathways. The Xcell method was employed to analyze immune infiltration relationships. To determine the potential causal relationship between NR0B2 expression and gastric diseases, we identified six single-nucleotide polymorphisms (SNPs) as a proxy for NR0B2 expression located within 100 kilobases of NR0B2 and which are associated with triglyceride homeostasis and performed drug-target Mendelian randomization (MR). Bioinformatics analysis revealed that NR0B2 expression levels were reduced in gastric cancer and increased in gastritis. GO analysis and Gene Set Enrichment Analysis (GSEA) showed that NR0B2 is widely involved in oxidation-related processes. Immune infiltration analyses found that NR0B2 was associated with Treg. Prognostic analyses showed that a low expression of NR0B2 is a risk factor for the poor prognoses of gastric cancer. MR analyses revealed that NR0B2 expression is associated with a risk of gastric diseases (NR0B2 vs. gastric cancer, p = 0.006, OR: 0.073, 95%CI: 0.011–0.478; NR0B2 vs. gastric ulcer, p = 0.03, OR: 0.991, 95%CI: 0.984–0.999; NR0B2 vs. other gastritis, p = 0.006, OR:3.82, 95%CI: 1.468–9.942). Our study confirms the causal relationship between the expression of NR0B2 and the risk of gastric diseases, and highlights its role in the progression of gastric cancer. The present study opens new avenues for exploring the potential of drugs that either activate or inhibit the NR0B2 receptor in the treatment of gastric diseases. [ABSTRACT FROM AUTHOR]

Helicobacter pylori is a human pathogen bacterium associated with gastritis, peptic ulcer, and gastric cancer. It can be identified through the 16S rRNA gene and characterized through cagA and vacA virulence genes. Clinical cultures of H. pylori were isolated and identified from human stomach biopsies. The isolates were characterized according to their colonial and microscopic morphology, and molecular genotyping was conducted to determine the bacterial virulence. A phylogenetic analysis of the 16S rRNA gene sequencing was performed. In addition, multilocus sequence typing analysis was performed to determine the phylogeographic nature of the isolated strains. Three bacterial isolates were selected from 22 gastric biopsies, identified as H. pylori through colonial morphology, Gram staining, urease, catalase, and oxidase tests and identification of the ureC gene through end-point PCR. Amplification of 16S rRNA, urea, and tonB genes was performed, as well. Differences between the cagA and vacA genotypes were determined among the isolates. The phylogenetic analysis confirmed the identity of the three isolates as the specie Helicobacter pylori. Different genotypes were obtained for each H. pylori strain, and all the clinical isolates showed the vacA s2/m2 genotype, indicating an absence of the VacA cytotoxin. Only HCGDL-MR01 is a cagA gene carrier with a greater risk to develop a serious disease, such as stomach cancer and peptic ulcer. The multilocus sequence typing placed all the strains within the hpEurope population structure. [ABSTRACT FROM AUTHOR]

Introduction: The purpose of this research was to determine how the P53/microRNA‐34a (miR‐34a)/survivin pathway contributes to oxaliplatin‐induced (L‐OHP) cell inhibition in gastric cancer. Methods: The BGC‐823 gastric cancer cells were selected, and we examined their viability following treatment with L‐OHP at different concentrations and time periods. The expression levels of miR‐34a, P53, and survivin in the cells were determined. Results: In the 12‐ and 24‐h groups, drug concentration of 15 μg/cm² (p <.005 in both) significantly lowered cell viability. In comparison to the control group, miR‐34a mRNA expression, P53 mRNA expression, and protein expression were all significantly greater in the 24‐h group (p =.0324, p =.0069, p =.0260, respectively), but survivin mRNA and protein expressions were significantly lower than those in the control group (p =.0338, p =.0032, respectively). There was a significant decrease in gastric cancer cells in the miR‐34a overexpression group (p =.0020), a significant increase in P53 mRNA and protein expression compared to the control group (p =.0080, p =.0121, respectively), and a significant decrease in survivin mRNA and protein expression compared to the control group. (p =.0213, p =.0069, respectively). Conclusion: Oxaliplatin inhibits tumor growth, invasion, and metastasis by upregulating miR‐34a, activating the expression of the upstream P53 gene, and driving the downregulation of survivin (P53/miR‐34a/survivin axis) in BGC‐823 gastric cancer cells. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relationship between serum microribonucleic acid (miR)-191-5p, miR-101-3p and clinicopathological features, phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) signaling pathway and prognosis in gastric cancer patients. Methods: 182 gastric cancer patients (gastric cancer group) admitted to our hospital from January 2019 to January 2021 and 90 healthy subjects (control group) who underwent physical examination in the physical examination center during the same period were selected. The expressions of serum miR-191-5p, miR-101-3p, PI3K mRNA and Akt mRNA were detected in two groups. The correlation between serum miR-191-5p, miR-101-3p and PI3K mRNA, Akt mRNA was analyzed by Pearson. The relationship between serum miR-191-5p, miR-101-3p and clinicopathological features of gastric cancer patients was analyzed. The 3-year overall survival (OS) rate of gastric cancer patients with different miR-191-5p and miR-101-3p expression was analyzed by Kaplan-Meier curve. Results: The expression of serum miR-191-5p and miR-101-3p in gastric cancer group was lower than that in control group (P<0.05), and the expression of PI3K mRNA and Akt mRNA was higher than that in control group (P<0.05). The expression of serum miR-191-5p and miR-101-3p in gastric cancer patients was negatively correlated with PI3K mRNA and Akt mRNA (P<0.05). The expression of serum miR-191-5p and miR-101-3p was related to TNM stage, lymph node metastasis, depth of invasion and differentiation of gastric cancer (P<0.05). The 3-year OS rate of gastric cancer patients with low expression of miR-191-5p was lower than that of gastric cancer patients with high expression of miR-191-5p, and the 3-year OS rate of gastric cancer patients with low expression of miR-101-3p was lower than that of gastric cancer patients with high expression of miR-101-3p (P<0.05). Conclusion: The expression of serum miR-191-5p and miR-101-3p in gastric cancer patients are significantly down-regulate, which are relate to TNM stage, lymph node metastasis, depth of invasion and degree of differentiation, may lead to poor prognosis by activating PI3K/Akt signaling pathway. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) ranks fifth in cancer incidence and fourth in cancer-related mortality worldwide. Reactive oxygen species (ROS) are highly oxidative oxygen-derived products that have crucial roles in cell signaling regulation and maintaining internal balance. ROS are closely associated with the occurrence, development, and treatment of GC. This review summarizes recent findings on the sources of ROS and the bidirectional regulatory effects on GC and discusses various treatment modalities for GC that are related to ROS induction. In addition, the regulation of ROS by natural small molecule compounds with the highest potential for development and applications in anti-GC research is summarized. The aim of the review is to accelerate the clinical application of modulating ROS levels as a therapeutic strategy for GC. [ABSTRACT FROM AUTHOR]

TRIM37 expression has been shown to be dysregulated in various types of cancers. This study was aimed to assess the clinical significance and potential utility of TRIM37 expression level as an indicator of prognosis in gastric cancer (GC) patients. The potential correlation between TRIM37 and the levels of β-catenin, Cyclin D and BCL2 was also investigated. qRT-PCR was used to determine the expression levels of TRIM37 in 40 fresh GC and their adjacent noncancerous tissues. Statistical analyses were conducted to evaluate the relationship between TRIM37 expression levels, overall survival (OS), various clinicopathological features, and the expression levels of β-catenin, Cyclin D, and Bcl-2. TRIM37 expression was significantly higher in the cancerous tissue samples compared to noncancerous tissues (Fold change=1.92, P=0.007). Moreover, Kaplan-Meier analysis indicated that high TRIM37 group exhibited shorter OS (P=0.003). TRIM37 overexpression was strongly associated with poor prognosis and predicts unfavorable outcomes in GC patients (HR=1.85, 95%CI: 1.28-2.66, P=0.001). A direct correlation was also observed between TRIM37 and elevated levels of β-catenin, a gene known for its role in cell proliferation among GC patients. TRIM37 overexpression is strongly linked with a poor prognosis in GC patients, highlighting its potential as an independent prognostic factor in GC and providing insight into its possible involvement in cancer development through Wnt/β-catenin signaling pathway. However, additional research is required to validate the potential prognostic value of TRIM37 in gastric cancer. [ABSTRACT FROM AUTHOR]

Lopezia racemosa is known as a "mosquito flower or perlilla." It is commonly found in corn crops. In traditional Mexican medicine, this plant is used to treat stomach cancer and urinary tract infections. Likewise, compounds and extracts isolated from plants have shown cytotoxic and anti‐inflammatory effects. The objective of this study was to evaluate the photochemoprotective effect of topical treatment with the methanolic extract of L. racemosa (MELR) as a photochemoprotective agent against the harmful effects of UV irradiation (UVR) on a bacterial model and hairless mice. The MELR components were separated and analyzed via HPLC‐UV‐ESI‐MS. Antioxidant activity was evaluated by the ability of MERL to scavenge DPPH and ABTS free radicals and by its FRAP capacity. The toxicity of MELR was evaluated in keratinocyte cultures. The photoprotective capacity of MELR was assessed through challenge experiments using models with bacteria and hairless CD1 et/et mice; cytokines related to the damage caused by UVR were also measured. In the methanolic extract of L. racemosa, five metabolites were detected and identified: two isomers of quercetin 6‐C glycoside, orientin, quercetin 3‐(6″‐acetylglycoside) and quercetin 3‐(6″‐galloylglycoside) 7‐(2,3‐dihydroxytetrahydro‐2H‐pyran‐4‐yl acetate). MELR exhibited DPPH and ABTS radical scavenging properties, in addition to Fe ion reducing activity. MELR showed a photoprotective effect against UVB radiation‐induced death in Escherichia coli bacteria. At the histological level, topical treatment of CD‐1 et/et mice with MERL reduced the damage caused by UVR. Quantification of interleukins in the blood of mice revealed that the expression of IL‐12 was greater in the control group treated with ultraviolet radiation than in the group protected with MELR. The methanolic extract of L. racemosa has photochemoprotective properties. [ABSTRACT FROM AUTHOR]

Objective: Gastric cancer (GC) is believed to be one of the most common digestive tract malignant tumors. However, mounting evidence indicates a link between the glycolysis and tumorigenesis, including gastric cancer. Methods: Our research identified 5508 differently expressed mRNAs in gastric cancer. Then, the genes highly associated with tumorigenesis were identified through weighted correlation network analysis (WGCNA). Bioinformatics analysis observed that these hub genes were significantly linked to the regulation of cell cycle, drug metabolism, and glycolysis. Among these hub genes, there is a critical gene involved in glycolysis regulation, namely fructose-bisphosphate B (ALDOB). Results: Analysis based on The Cancer Genome Atlas (TCGA) and three Gene Expression Omnibus (GEO) datasets revealed that ALDOB was significantly downregulated in GC compared with normal tissues. In addition, cell viability assay confirmed that ALDOB acted as a tumor suppressor. Finally, drug sensitivity analysis revealed that ALDOB increased the sensitivity of gastric cancer cells to most antitumor drugs, especially talazoparib, XAV939, and FTI-277. Our results showed that the expression of ALDOB was significantly lower in GC tissues than in normal tissues. And ALDOB significantly inhibited proliferation and migration, delayed glycolysis in GC cells. Consequently, our study suggests that ALDOB may be a potential target for the clinical treatment of gastric cancer. [ABSTRACT FROM AUTHOR]

Objective: NK cells play a vital role in tumor immune resistance. Various factors affect NK cell activity. While NK cell dysfunction has been observed in numerous malignancies, the underlying mechanisms in gastric cancer remain unclear. Method: Flow cytometry was used to identify the phenotypic distribution and expression of activated receptors on NK cells. ELISA was used to determine the expression of cytokines. We examined the expression of NK cell-related genes and explored their association with survival and prognosis. Additionally, we conducted PCR detection of miR-552-5p expression levels in plasma exosomes of patients and investigated its correlation with phenotypic distribution and activated receptors. We used flow cytometry and ELISA to verify the role of miR-552-5p in NK cell dysfunction. Furthermore, we investigated the potential role of PD-1/PD-L1 in regulating NK cell dysfunction in patients' cells. Results: We observed a significant decrease in the percentage of NKG2D and NKp30 and IFN-γ and TNF-α in patients than in healthy volunteers. Patients with low levels of CD56, CD16, NKG2D, and NKP46 exhibited poorer survival prognoses. Moreover, increased expression levels of plasma exosomal miR-552-5p in patients were negatively associated with NK cell phenotypic distribution and activated receptor expression. MiR-552-5p downregulated the secretion of perforin, granzyme, and IFN-γ as well as the expression of NKp30, NKp46, and NKG2D. Additionally, it suppressed the cytotoxicity of NK cells. The inhibitory effect of miR-552-5p, on NK cell function was reversed when anti-PD-L1 antibodies were used. Conclusion: Exosomal miR-552-5p targets the PD-1/PD-L1 axis, leading to impaired NK cell function. [ABSTRACT FROM AUTHOR]

Background: N-acetyltransferase 10 (NAT10), the only RNA cytosine acetyltransferase known in humans, contributes to cancer tumorigenesis and progression. This study aims to investigate the effect of NAT10 on the malignant biological properties of gastric cancer (GC) and its underlying mechanism. Methods: The expression and prognostic significance of NAT10 in GC were analyzed using The Cancer Genome Atlas (TCGA) and Sun Yat-sen University (SYSU) cohorts. The influence of NAT10 on the malignant biological behaviors of GC was detected by Cell Counting Kit-8 (CCK-8) assay, plate colony formation assay, 5-ethynyl-2′-deoxyuridine (EdU), Transwell migration and invasion assays, scratch wound assay, flow cytometric analysis, and animal studies. The overall level of N4 acetylcytidine (ac4C) in GC was detected by liquid chromatography with tandem mass spectrometry (LC–MS/MS). The downstream signal pathways of NAT10 were analyzed by Gene Set Enrichment Analysis (GSEA) and verified by Western blot (WB) and immunofluorescence (IF). Results: The significant upregulation of NAT10 expression in GC was associated with a poor prognosis. The knockdown of NAT10 markedly suppressed GC cell proliferation, migration, invasion, and cell cycle progression. Downregulating NAT10 reduced ac4C levels and inhibited AKT phosphorylation and epithelial–mesenchymal transition (EMT) in GC. Conclusions: NAT10 functions as an oncogene and may provide a new therapeutic target in GC. [ABSTRACT FROM AUTHOR]

Objective: To investigate the role and function of eIF6 in gastric cancer (GC). Methods: The expression level of eIF6 in GC tissues and normal tissues was detected in different high-throughput sequencing cohorts. Survival analysis, gene differential analysis, and enrichment analysis were performed in the TCGA cohort. Biological networks centered on eIF6 were constructed through two different databases. Immunohistochemistry (IHC) and Western blot were used to detect protein expression of eIF6, and qRT-PCR was used to detect eIF6 mRNA expression. The correlation between the expression of eIF6 in GC tissues and clinicopathological parameters of GC was analyzed. siRNA knockout of eIF6 was used to study the proliferation, migration, and invasion. The effects of eIF6 on cell cycle and Cyclin B1 were detected by flow cytometry and Western blot. Results: eIF6 was significantly overexpressed in GC tissues and predicted poor prognosis. In addition, 113 differentially expressed genes were detected in cancer-related biological pathways and functions by differential analysis. Biological networks revealed interactions of genes and proteins with eIF6. The expression intensity of eIF6 in cancer tissues was higher than that in adjacent tissues (P = 0.0001), confirming the up-regulation of eIF6 expression in GC tissues. The expression level of eIF6 was statistically significant with pTNM stage (P = 0.006). siRNA knockout of eIF6 significantly reduced the proliferation, colony formation, migration, and invasion ability of GC cells. Silencing of eIF6 also inhibited the cell cycle of GC cells in G2/M phase and decreased the expression level of CyclinB1. Conclusion: Our study suggests that eIF6 is up-regulated in GC and may promote the proliferation, migration, and invasion of GC by regulating cell cycle. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer is the third most common type of cancer worldwide. Gastric cancer has a 15% to 20% 5-year overall survival rate, even if the disease just affects the stomach wall. The prognosis is favorable if tumors and their precursors are discovered early on. The current study intended to enhance the prognosis of patients suffering from early-stage stomach cancer. Methods: In this study, 24 patients with stomach cancer who attended to Zagazig University Hospitals' outpatient clinic were included. Every patient underwent a complete medical history, a general examination, and an abdominal examination that included PR and PV. Laboratory tests were performed. Along with gastroscopy and biopsies, all patients also underwent CT, ultrasonography, and CXR scans. Results: There were six women and eighteen men in the study. The distal portion of the stomach was the site of malignancy in all 100 cancer patients under study. A statistically significant correlation was not observed between the sex of the cancer cases under study and either the age distribution or the tumor site. Conclusions: Laparoscopic distal gastrectomy is a safe and effective treatment that offers advantages over open conventional gastrectomy for treating stomach cancer. These advantages include a lower risk of intraoperative blood loss and overall consequences. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is the fifth most common cause of cancer-related death worldwide. Early detection is crucial for improving survival rates and treatment outcomes. However, accurate GC-specific biomarkers remain unknown. This study aimed to identify the metabolic differences between intestinal metaplasia (IM) and GC to determine the pathways involved in GC. A metabolic analysis of IM and tissue samples from 37 patients with GC was conducted using ultra-performance liquid chromatography with tandem mass spectrometry. Overall, 665 and 278 significant features were identified in the aqueous and 278 organic phases, respectively, using false discovery rate analysis, which controls the expected proportion of false positives among the significant results. sPLS-DA revealed a clear separation between IM and GC samples. Steroid hormone biosynthesis, tryptophan metabolism, purine metabolism, and arginine and proline metabolism were the most significantly altered pathways. The intensity of 11 metabolites, including N1, N2-diacetylspermine, creatine riboside, and N-formylkynurenine, showed significant elevation in more advanced GC. Based on pathway enrichment analysis and cancer stage-specific alterations, we identified six potential candidates as diagnostic biomarkers: aldosterone, N-formylkynurenine, guanosine triphosphate, arginine, S-adenosylmethioninamine, and creatine riboside. These metabolic differences between IM and GC provide valuable insights into gastric carcinogenesis. Further validation is needed to develop noninvasive diagnostic tools and targeted therapies to improve the outcomes of patients with GC. [ABSTRACT FROM AUTHOR]

Introduction: Toll-like receptors (TLRs) play a vital role in the innate immune response, recognizing pathogens and initiating the inflammatory response. Research suggests that TLRs may also have a significant impact on the development and progression of cancers, including gastric cancer (GC). Understanding the role of individual TLRs in the immunopathogenesis of gastric cancer may provide new information necessary to develop more effective diagnostic and therapeutic methods. Aim of the study: This study aimed to determine the role of selected TLR-2, -3, -4, and -9 in the immunopathogenesis of patients with newly diagnosed and untreated gastric cancer. Materials and methods: The study included 60 newly diagnosed, untreated GC patients and 25 healthy volunteers. The research included analyses assessing the percentage of the tested TLRs on T and B lymphocyte subpopulations using multicolor flow cytometry and assessing their concentration in the serum of the examined patients using ELISA tests. The statistical analyses performed included a comparison of patients in individual stages of gastric cancer, an analysis of the most common clinical subtypes of gastric cancer, and a comparative analysis of differences in the gender of recruited patients. Results: Our studies showed different expression levels of TLR-2, -3, -4, and -9 on T and B lymphocyte subpopulations, as well as their different concentrations in patients' serum. Significant differences in the expression of these receptors were observed depending on the stage of gastric cancer and its clinical subtypes. These differences were also visible in the context of patient gender. Summary: The results of our studies suggest that TLR-2, -3, -4, and -9 may play an important role in the immunopathogenesis of gastric cancer. The differential expression of these receptors depending on the stage of the disease, clinical subtype, and gender of patients may have potential diagnostic and therapeutic significance. Further research is necessary to understand better the mechanisms of action of TLRs in gastric cancer and to apply this knowledge in clinical practice. [ABSTRACT FROM AUTHOR]

Gastric cancer is one of the most common cancers worldwide, and new therapeutic strategies are urgently needed. Ferroptosis is an intracellular iron-dependent cell death induced by the accumulation of lipid peroxidation, a mechanism different from conventional apoptosis and necrosis. Therefore, induction of ferroptosis is expected to be a new therapeutic strategy. Glutathione peroxidase 4 (GPX4) and ferroptosis suppressor protein 1 (FSP1) have been identified as the major inhibitors of ferroptosis. Herein, we performed immunohistochemistry for GPX4, FSP1, and 4-HNE using tissues from patients with gastric cancer and investigated the relationship between these factors and prognosis. Patients with high GPX4 expression or high GPX4 expression and low 4-HNE accumulation tended to have a poor prognosis (p = 0.036, 0.023), whereas those with low FSP1 expression and high 4-HNE accumulation had a good prognosis (p = 0.033). The synergistic induction of cell death by inhibiting GPX4 and FSP1 in vitro was also observed, indicating that the cell death was non-apoptotic. Our results indicate that the expression and accumulation of lipid peroxidation-related factors play an important role in the clinicopathological significance of gastric cancer and that novel therapeutic strategies targeting GPX4 and FSP1 may be effective in treating patients with gastric cancer who have poor prognosis. [ABSTRACT FROM AUTHOR]

Couroupita guianensis, a medicinal plant autochthonal to South America and South India, is widely used in the ethnomedicine of the indigenous peoples of these regions thanks to its alleged antimicrobial, anti-inflammatory, antioxidant and wound-healing properties. The majority of studies have mainly analyzed organic extracts of the Indian plant's flowers and leaves, with limited research on its bark decoction, traditionally used in Amazonian shamanic medicine. In this study, we investigated the anticancer effects of the bark decoction and its main fractions obtained through chromatographic separation, as well as the underlying molecular mechanisms in AGS gastric cancer cells. Viability, cell proliferation, cell cycle, apoptosis and protein expression related to these processes were evaluated. Both the bark decoction and fraction III significantly inhibited cell viability, and the cytotoxic effect was linked to cell cycle blockade and the induction of apoptosis also through an engulfment of the autophagic flux. Increased expression or activation of the key proteins (p53, p21, cdk2, Bak, caspases, pAMPK, pAkt, beclin, p62 and LC3BII) involved in these processes was observed. The results obtained confirmed an important anticancer effect of C. guianensis bark decoction, providing scientific validation for its use in traditional medicine and highlighting its potential as a therapeutic agent against gastric cancer. [ABSTRACT FROM AUTHOR]

Activating enhancer-binding protein 2 (AP-2) is a family of transcription factors (TFs) that play crucial roles in regulating embryonic and oncogenic development. In addition to splice isoforms, five major family members encoded by the TFAP2A/B/C/D/E genes have been identified in humans, i.e., AP-2α/β/γ/δ/ε. In general, the first three TFs have been studied more thoroughly than AP-2δ or AP-2ε. Currently, there is a relatively limited body of literature focusing on the AP-2 family in the context of gastroenterological research, and a comprehensive overview of the existing knowledge and recommendations for further research directions is lacking. Herein, we have collected available gastroenterological data on AP-2 TFs, discussed the latest medical applications of each family member, and proposed potential future directions. Research on AP-2 in gastrointestinal tumors has predominantly been focused on the two best-described family members, AP-2α and AP-2γ. Surprisingly, research in the past decade has highlighted the importance of AP-2ε in the drug resistance of gastric cancer (GC) and colorectal cancer (CRC). While numerous questions about gastroenterological disorders await elucidation, the available data undoubtedly open avenues for anti-cancer targeted therapy and overcoming chemotherapy resistance. In addition to gastrointestinal cancers, AP-2 family members (primarily AP-2β and marginally AP-2γ) have been associated with other health issues such as obesity, type 2 diabetes, liver dysfunction, and pseudo-obstruction. On the other hand, AP-2δ has been poorly investigated in gastroenterological disorders, necessitating further research to delineate its role. In conclusion, despite the limited attention given to AP-2 in gastroenterology research, pivotal functions of these transcription factors have started to emerge and warrant further exploration in the future. [ABSTRACT FROM AUTHOR]

Helicobacter pylori is a prevalent, global infectious disease that causes dyspepsia, peptic ulcer disease, and gastric cancer. The American College of Gastroenterology commissioned this clinical practice guideline (CPG) to inform the evidence-based management of patients with H. pylori infection in North America. This CPG used Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology to systematically analyze 11 Population, Intervention, Comparison, and Outcome questions and generate recommendations. Where evidence was insufficient or the topic did not lend itself to GRADE, expert consensus was used to create 6 key concepts. For treatment-naive patients with H. pylori infection, bismuth quadruple therapy (BQT) for 14 days is the preferred regimen when antibiotic susceptibility is unknown. Rifabutin triple therapy or potassium-competitive acid blocker dual therapy for 14 days is a suitable empiric alternative in patients without penicillin allergy. In treatment-experienced patients with persistent H. pylori infection, "optimized" BQT for 14 days is preferred for those who have not been treated with optimized BQT previously and for whom antibiotic susceptibility is unknown. In patients previously treated with optimized BQT, rifabutin triple therapy for 14 days is a suitable empiric alternative. Salvage regimens containing clarithromycin or levofloxacin should only be used if antibiotic susceptibility is confirmed. The CPG also addresses who to test, the need for universal post-treatment test-of-cure, and the current evidence regarding antibiotic susceptibility testing and its role in guiding the choice of initial and salvage treatment. The CPG concludes with a discussion of proposed research priorities to address knowledge gaps and inform future management recommendations in patients with H. pylori infection from North America. [ABSTRACT FROM AUTHOR]

The integration of artificial intelligence (AI) in medical diagnostics represents a significant advancement in managing upper gastrointestinal (GI) cancer, which is a major cause of global cancer mortality. Specifically for gastric cancer (GC), chronic inflammation causes changes in the mucosa such as atrophy, intestinal metaplasia (IM), dysplasia, and ultimately cancer. Early detection through endoscopic regular surveillance is essential for better outcomes. Foundation models (FMs), which are machine or deep learning models trained on diverse data and applicable to broad use cases, offer a promising solution to enhance the accuracy of endoscopy and its subsequent pathology image analysis. This review explores the recent advancements, applications, and challenges associated with FMs in endoscopy and pathology imaging. We started by elucidating the core principles and architectures underlying these models, including their training methodologies and the pivotal role of large-scale data in developing their predictive capabilities. Moreover, this work discusses emerging trends and future research directions, emphasizing the integration of multimodal data, the development of more robust and equitable models, and the potential for real-time diagnostic support. This review aims to provide a roadmap for researchers and practitioners in navigating the complexities of incorporating FMs into clinical practice for the prevention/management of GC cases, thereby improving patient outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Stomach cancer is one of the most common causes of cancer worldwide, especially in the population over 65 years. The survival rate of the elderly is lower in comparison with young people, and they are underrepresented in clinical trials and research in general. The evaluation of Multidimensional Geriatric Assessment (MGA) would be key for assessing the prognosis of these patients and therefore having a more informed decision-making process when considering one of the most vulnerable populations. Methods: A search was performed in the OVID, Embase, and PubBMed databases. There was no restriction on publication time, language, or study design. Eligible studies were those that included geriatric patients with a diagnosis of nonmetastatic stomach cancer who receive oncospecific and surgical management, used Multidimensional/Comprehensive Geriatric Assessment (MGA), and which outcomes included at least overall survival, morbidity, and mortality. Results: Four studies were included, and the MGA battery was not implemented, but rather easily measurable scales such as nutritional status, functional status, cognitive and behavioral disorders, comorbidities, and polypharmacy. Some authors proposed that the assessment of overall survival is not explicit among the included studies; patients with gastric cancer and mild, moderate, severe, and total dependence had higher mortality than independent patients (39% [HR 1.39; 95% CI: 1.09–1.7], 68% [95% CI: 1.46–1.93], 187% [HR 2.87 95% CI: 2.47–3.34], and 234% [95% CI: 2.81–3.97]), respectively. The Zhou study showed an association between sarcopenia, assessed by imaging studies, and a longer hospital stay in days (16 [9] vs. 13 [6], p 0.004). The study by Pujara found that polypharmacy (OR 2.36 CI: 1.08–5.17) and weight loss greater than 10% in the past 6 months were associated with greater postoperative morbidity at 90 days (OR 2.36 CI: 1.08–5.17, OR 11.21 CI: 2.16–58.24). Conclusion: MGA was not broadly implemented. Geriatric assessment dependency appears to be a prognostic marker of survival in patients with gastric cancer. Sarcopenia appears to be an important prognostic marker for short- and long-term outcomes. Higher quality studies in this specific population are required to support the systematic use of this assessment for the choice of appropriate therapy according to the patient. [ABSTRACT FROM AUTHOR]

Background/Aims: Lymphoepithelioma-like carcinoma (LELC) is a rare subtype of gastric cancer. We aimed to identify the clinicopathological features and rate of lymph node metastasis (LNM) to investigate the feasibility of endoscopic submucosal dissection for early gastric LELC confined to the mucosa or submucosa. Methods: We compared the clinicopathological characteristics of 116 early gastric LELC patients and 5,753 early gastric well- or moderately differentiated (WD or MD) tubular adenocarcinoma patients treated by gastrectomy. Results: Compared to WD or MD early gastric cancer (EGC) patients, early LELC patients were younger and had a higher prevalence of proximally located tumors. Despite more frequent deep submucosal invasion (86.2% vs 29.8%), lymphatic invasion was less frequent (6.0% vs 16.2%) in early LELC patients than in WD or MD EGC patients. Among tumors with deep submucosal invasion, the tumor size was smaller, lymphatic invasion was less frequent (6.0% vs 40.2%) and the rate of LNM was lower (10.0% vs 19.4%) in patients with LELC than in those with WD or MD EGC. The overall rate of LNM in early LELC patients was 8.6% (10/116). The risk of LNM in patients with mucosal, shallow submucosal invasive, or deep submucosal invasive LELC was 0% (0/6), 0% (0/10), and 10% (10/100), respectively. Conclusions: Early LELC is a distinct subtype of EGC with more frequent deep submucosal invasion but less lymphatic invasion and LNM than WD or MD EGCs. Endoscopic submucosal dissection may be considered curative for patients with early LELC confined to the mucosa or shallow submucosa, given its negligible rate of LNM. [ABSTRACT FROM AUTHOR]

Endoscopic resection (ER)–a minimal invasive procedure, compared to surgical gastrectomy, with the advantage of preserving the entire stomach and maintaining the patient’s quality of life–is a widely used curative treatment for early gastric cancers (EGCs). Despite its advantages, such as the preservation of the whole stomach, a large area of the gastric mucosa with histologic changes such as atrophy and intestinal metaplasia remains after ER, and so does the risk of metachronous gastric cancers (MGCs). Therefore, regular surveillance endoscopy after curative ER of EGCs is important so that MGCs are detected early and so minimally invasive ER remains a treatment option. To date, the optimal interval for surveillance endoscopy after curative ER of EGCs has not been established. Therefore, this review summarizes the results of the published studies on this topic with the aim of establishing the optimal surveillance interval for early identification of MGCs. Based on my review, the median timing of MGC occurrence is within 3 years, and reports suggest biannual endoscopy during the first 3 years; however, the evidence suggests that individual patient characteristics may influence the risk of MGCs. Therefore, stratified endoscopic strategies for surveillance based on patient characteristics, such as age, family history of gastric cancer, synchronous gastric lesions, and corpus intestinal metaplasia, should be applied. [ABSTRACT FROM AUTHOR]

Gastric cancer is a prevalent malignant tumor worldwide, posing challenges due to its poor prognosis and limited treatment options. Cancer stem cells (CSCs) were demonstrated as a subset of cancer cells responsible for tumor initiation and progression, and their inherent resistance to conventional chemotherapy and radiotherapy critically contributes to tumor recurrence and metastasis. Promoting the eradication of cancer stem cells is crucial for enhancing the efficacy of cancer treatments. This study introduces a novel therapeutic strategy utilizing polyhedral magnetic nanoparticles (PMNPs) functionalized with CD44 antibodies and cell-penetrating peptides (CPPs) to improve uptake by gastric cancer stem cells (MCSCs). PMNPs, synthesized via thermal decomposition, exhibited a diameter of 90 nm ± 9 nm and a saturation magnetization of 79.9 emu/g. Functionalization enhanced their uptake capabilities. Under a rotating magnetic field (RMF) of 15 Hz, PMNPs disrupted cellular structure, leading to apoptosis and ferroptosis in MCSCs. The in vitro studies showed significant reduction in MCSCs viability, while in vivo studies demonstrated tumor growth suppression with minimal side effects and high biocompatibility. This work presents a novel strategy for designing magnetic nanoparticles to mechanically destroy cancer stem cells, offering a more efficient and safety treatment option for gastric cancer. [Display omitted] • Gastric cancer stem cells (MCSCs) serves as a linchpin in the genesis and progression of gastric cancer. • This dual functionalization enhances the uptake of polygonal magnetic nanoparticles (PMNPs) by gastric cancer stem cells. • Under a rotating magnetic field of 15 Hz, PMNPs induced apoptosis and ferroptosis in MCSCs by disrupting cellular structures. • The PMNPs system showed remarkable efficacy in inhibiting tumor growth in vivo and has significant biocompatibility. [ABSTRACT FROM AUTHOR]

Purpose: To compare performance of whole-body [68Ga]Ga-FAPI-04 and [18F]FDG PET imaging in the detection of Krukenberg tumors (KTs), primary site and extra-ovarian metastases of gastric signet-ring-cell carcinoma (GSRCC), and evaluate the value of [68Ga]Ga-FAPI-04 PET/MR imaging strategy and its potential impact on the management of KTs from GSRCC. Methods: Twelve patients with twenty-three KTs from GSRCC, who underwent both [68Ga]Ga-FAPI-04 pelvic PET/MR and whole-body [68Ga]Ga-FAPI-04 and [18F]FDG PET imaging were retrospectively analyzed. [68Ga]Ga-FAPI-04 and [18F]FDG uptakes were compared by using Wilcoxon signed-rank test or paired t test. McNemar's test was used to compare lesion detectability between two modalities. Two-tailed P<0.05 was considered statistically significant. Immunohistochemistry staining was utilized to analyze the fibroblast activation protein (FAP) expression in KTs. Results: A total of 12 patients with 23 KTs from GSRCC (8 synchronous and 4 metachronous) were evaluated. [68Ga]Ga-FAPI-04 was superior to [18F]FDG PET in detecting primary sites of GSRCC (100% [11/11] vs. 18.2% [2/11], p = 0.002), involved lymph nodes (90.9% [10/11] vs. 54.5% [6/11], p = 0.046) and peritoneal metastases (100% [12/12] vs. 41.7% [5/12], p = 0.008), with higher SUVmax and TBR (all p < 0.005). Both tracers had limited value in identifying KTs, with 100% false negative rate on [68Ga]Ga-FAPI-04 PET and a low detection rate of 8.7% on [18F]FDG PET. Fap immunohistochemistry showed negative or slight FAP expression in neoplastic signet ring cells and ovarian stroma. [68Ga]Ga-FAPI-04 PET/MR imaging strategy greatly improved the detection rate of Krukenberg tumors (87%, 20/23). After adding diffusion-weighted imaging (DWI), the detection rate was further improved (87.5% vs. 100%, p = 0.083). [68Ga]Ga-FAPI-04 PET/MR imaging strategy either upgraded TNM staging or changed treatment management in twelve patients. Conclusions: [68Ga]Ga-FAPI-04 PET outperformed [18F]FDG PET in detecting primary site and most extra-ovarian metastases of GSRCC, but both tracers had limited value in identifying Krukenberg tumors. Pelvis MRI should be applied to compensate the limitation of [68Ga]Ga-FAPI-04 PET imaging to identify Krukenberg tumours. The [68Ga]Ga-FAPI-04 PET/MR imaging strategy has the potential to impact treatment decisions for GSRCC patients with KTs. [ABSTRACT FROM AUTHOR]

Purpose: In recent years, clinicians have focused on the importance of preventing hypoglycemia. We evaluated the impact of different reconstruction procedures after proximal gastrectomy on glycemic variability in non-diabetic patients with gastric cancer. Methods: This prospective observational study was conducted between April 2020 and March 2023. Flash continuous glucose-monitoring, a novel method for assessing glycemic control, was used to evaluate the glycemic profiles after gastrectomy. A flash continuous glucose-monitoring sensor was placed subcutaneously at the time of discharge, and glucose trends were evaluated for 2 weeks. Results: The anastomotic methods for proximal gastrectomy were esophagogastrostomy in 10 patients and double-tract reconstruction in 10 patients. The time below this range (glucose levels < 70 mg/dL) was significantly higher in the double-tract reconstruction group than in the esophagogastrostomy group (p = 0.049). A higher nocturnal time below this range was significantly correlated with an older age and double-tract reconstruction (p = 0.025 and p = 0.025, respectively). Conclusion: These findings provide new insights into reconstruction methods after proximal gastrectomy by assessing postoperative hypoglycemia in non-diabetic patients with gastric cancer. [ABSTRACT FROM AUTHOR]

Purposes: The present study evaluated the impact of clinical guidelines for gastric cancer surgery on surgeons' choice of procedure in real-world practice. We focused on the 2014 guideline revision recommending laparoscopic surgery and the evidence concerning splenectomy for prophylactic lymphadenectomy reported in 2015 using the National Clinical Database, which is the most comprehensive database in Japan. Methods: We investigated the monthly percentages of laparoscopic distal gastrectomies performed for stage I gastric cancer (LDG%) and splenectomies performed during total gastrectomy for advanced cancer (TGS%) between 2014 and 2017. We evaluated the descriptive statistics of the time-series changes in the LDG%, TGS%, and annual trends of outcomes. Results: In total, 124,787 patients were enrolled. The mean LDG% and TGS% were 69.8% and 9.2%, respectively. The LDG% and TGS% were 66.4% and 16.7%, respectively, in January 2014 and 73.1% and 5.9%, respectively, in December 2017. LDG% consistently increased, and TGS% showed a consistent downward trend throughout the observation period. There was no significant change in this trend after the publication of the guideline recommendations or clinical trial results. Conclusion: No significant changes in surgical procedures were observed after publication of the guidelines or results of clinical trials. [ABSTRACT FROM AUTHOR]

Background: Robot-assisted minimally invasive gastrectomy (RAMIG) is increasingly used as a surgical approach for gastric cancer. This study assessed the effectiveness of RAMIG and studied which stages of the IDEAL-framework (1 = Idea, 2A = Development, 2B = Exploration, 3 = Assessment, 4 = Long-term follow-up) were followed. Methods: The Cochrane Library, Embase, Pubmed, and Web of Science were searched for studies on RAMIG up to January 2023. Data collection included the IDEAL-stage, demographics, number of participants, and study design. For randomized controlled trials (RCTs) and long-term studies, data on intra-, postoperative, and oncologic outcomes, survival, and costs of RAMIG were collected and summarized. Results: Of the 114 included studies, none reported the IDEAL-stage. After full-text reading, 18 (16%) studies were considered IDEAL-2A, 75 (66%) IDEAL-2B, 4 (4%) IDEAL-3, and 17 (15%) IDEAL-4. The IDEAL-stages were followed sequentially (2A-4), with IDEAL-2A studies still ongoing. IDEAL-3 RCTs showed lower overall complications (8.5–9.2% RAMIG versus 17.6–19.3% laparoscopic total/subtotal gastrectomy), equal 30-day mortality (0%), and equal length of hospital stay for RAMIG (mean 5.7–8.5 days RAMIG versus 6.4–8.2 days open/laparoscopic total/subtotal gastrectomy). Lymph node yield was similar across techniques, but RAMIG incurred significantly higher costs than laparoscopic total/subtotal gastrectomy ($13,423–15,262 versus $10,165–10,945). IDEAL-4 studies showed similar or improved overall/disease-free survival for RAMIG. Conclusion: During worldwide RAMIG implementation, the IDEAL-framework was followed in sequential order. IDEAL-3 and 4 long-term studies showed that RAMIG is similar or even better to conventional surgery in terms of hospital stay, lymph node yield, and overall/disease-free survival. In addition, RAMIG showed reduced postoperative complication rates, despite higher costs. [ABSTRACT FROM AUTHOR]

Antibody–drug conjugates (ADCs) represent a crucial component of targeted therapies in gastric cancer, potentially altering traditional treatment paradigms. Many ADCs have entered rigorous clinical trials based on biological theories and preclinical experiments. Modality trials have also been conducted in combination with monoclonal antibody therapies, chemotherapies, immunotherapies, and other treatments to enhance the efficacy of drug coordination effects. However, ADCs exhibit limitations in treating gastric cancer, including resistance triggered by their structure or other factors. Ongoing intensive researches and preclinical experiments are yielding improvements, while enhancements in drug development processes and concomitant diagnostics during the therapeutic period actively boost ADC efficacy. The optimal treatment strategy for gastric cancer patients is continually evolving. This review summarizes the clinical progress of ADCs in treating gastric cancer, analyzes the mechanisms of ADC combination therapies, discusses resistance patterns, and offers a promising outlook for future applications in ADC drug development and companion diagnostics. [ABSTRACT FROM AUTHOR]

Background: In 2019, the Gastrectomy Complications Consensus Group (GCCG) published a standardized set of complications aiming toward uniform reporting of post-gastrectomy complications. This study aimed to report outcomes after gastrectomy in the Netherlands according to GCCG definitions and compare them to previously reported national results and the European database reported by the GCCG. Methods: This nationwide, population-based cohort study included all patients undergoing gastrectomy for gastric cancer registered in the DUCA in 2020–2021. Postoperative morbidity and 30-day/in-hospital mortality were analyzed according to the GCCG definitions. For all patients, baseline characteristics and outcomes were compared with the GCCG cohort consisting of 27 European expert centers (GASTRODATA; 2017–2018). Results: In 2020–2021, 782 patients underwent gastrectomy in the Netherlands. Variation was seen in baseline characteristics between the Dutch and the GCCG cohort (N = 1349), most notably in minimally invasive surgery (80.6% vs 19.6%, p < 0.001). In the Netherlands, 223 (28.5%) patients developed a total of 407 complications, the most frequent being non-surgical infections (28.5%) and anastomotic leakage (13.4%). The overall complication and 30-day mortality rates were similar between the Dutch and GCCG cohort (28.5% vs 29.8%, p = 0.563; 3.7% vs 3.6%, p = 0.953). Higher surgical and endoscopic/radiologic reintervention rates were observed in the Netherlands compared to the GCCG cohort (10.7% vs 7.8%, p = 0.025; 10.9% vs 2.9%, p < 0.001). Conclusion: Reporting outcomes according to the standardized GCCG definitions allows for international benchmarking. Postoperative outcomes were comparable between Dutch and GCCG cohorts, but both exceed the international benchmark for expert gastrectomy care, highlighting targets for national and international quality improvement. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is a common malignancy that presents challenges in patient care worldwide. The mismatch repair (MMR) system is a highly conserved DNA repair mechanism that protects genome integrity during replication. Deficient MMR (dMMR) results in an increased accumulation of genetic errors in microsatellite sequences, leading to the development of a microsatellite instability-high (MSI-H) phenotype. Most MSI-H/dMMR GCs arise sporadically, mainly due to MutL homolog 1 (MLH1) epigenetic silencing. Unlike microsatellite-stable (MSS)/proficient MMR (pMMR) GCs, MSI-H/dMMR GCs are relatively rare and represent a distinct subtype with genomic instability, a high somatic mutational burden, favorable immunogenicity, different responses to treatment, and prognosis. dMMR/MSI-H status is a robust predictive biomarker for treatment with immune checkpoint inhibitors (ICIs) due to high neoantigen load, prominent tumor-infiltrating lymphocytes, and programmed cell death ligand 1 (PD-L1) overexpression. However, a subset of MSI-H/dMMR GC patients does not benefit from immunotherapy, highlighting the need for further research into predictive biomarkers and resistance mechanisms. This review provides a comprehensive overview of the clinical, molecular, immunogenic, and therapeutic aspects of MSI-H/dMMR GC, with a focus on the impact of ICIs in immunotherapy and their potential as neoadjuvant therapies. Understanding the complexity and diversity of the molecular and immunological profiles of MSI-H/dMMR GC will drive the development of more effective therapeutic strategies and molecular targets for future precision medicine. [ABSTRACT FROM AUTHOR]

Background: Accurate prediction of pathologic results for early gastric cancer (EGC) based on endoscopic findings is essential in deciding between endoscopic and surgical resection. This study aimed to develop an artificial intelligence (AI) model to assess comprehensive pathologic characteristics of EGC using white-light endoscopic images and videos. Methods: To train the model, we retrospectively collected 4,336 images and prospectively included 153 videos from patients with EGC who underwent endoscopic or surgical resection. The performance of the model was tested and compared to that of 16 endoscopists (nine experts and seven novices) using a mutually exclusive set of 260 images and 10 videos. Finally, we conducted external validation using 436 images and 89 videos from another institution. Results: After training, the model achieved predictive accuracies of 89.7% for undifferentiated histology, 88.0% for submucosal invasion, 87.9% for lymphovascular invasion (LVI), and 92.7% for lymph node metastasis (LNM), using endoscopic videos. The area under the curve values of the model were 0.992 for undifferentiated histology, 0.902 for submucosal invasion, 0.706 for LVI, and 0.680 for LNM in the test. In addition, the model showed significantly higher accuracy than the experts in predicting undifferentiated histology (92.7% vs. 71.6%), submucosal invasion (87.3% vs. 72.6%), and LNM (87.7% vs. 72.3%). The external validation showed accuracies of 75.6% and 71.9% for undifferentiated histology and submucosal invasion, respectively. Conclusions: AI may assist endoscopists with high predictive performance for differentiation status and invasion depth of EGC. Further research is needed to improve the detection of LVI and LNM. [ABSTRACT FROM AUTHOR]

Background: For the elderly patients with gastric cancer, it may be more challenging to tolerate complete neoadjuvant therapy (NAT). The impact of discontinued NAT on the surgical safety and pathological outcomes of elderly patients with poor tolerance remains poorly understood. Methods: Gastric cancer patients received gastrectomy with curative intent from the Dutch upper GI cancer audit (DUCA) database were included in this study. The independent association of age with not initiating and discontinuation of NAT was assessed with restricted cubic splines (RCS). According to the RCS results, age ≥ 70 years was defined as elderly. Short-term postoperative outcomes and pathological results were compared between elderly patients who completed and discontinued NAT. Results: Between 2011- 2021, total of 3049 patients were included. The risk of not initiating NAT increased from 70 years. In 1954 (64%) patients receiving NAT, the risk of discontinuation increased from 55 years, reaching the peak around 74 years. In the elderly, discontinued NAT was not independently associated with worse 30-day mortality, overall complications, anastomotic leakage, re-intervention, and pathologic complete response, but was associated with a higher risk of R1/2 resection (p-value = 0.001), higher ypT stage (p-value = 0.004), ypN + (p-value = 0.008), and non-response (p-value = 0.012). Conclusion: A decreased utilization of NAT has been observed in Dutch gastric cancer patients from 70 years due to old age considerations, possibly because of their high risk of discontinuation. Increasing the utilization of NAT may not adversely impact the surgical safety of gastric cancer population ≥ 70 years and may contribute to better pathological results. [ABSTRACT FROM AUTHOR]

Cisplatin (DDP) is a basic chemotherapy drug for gastric cancer (GC). With the increase of DDP drug concentration in clinical treatment, cancer cells gradually became resistant. Therefore, it is necessary to find effective therapeutic targets to enhance the sensitivity of GC to DDP. Studies have shown that Transmembrane protein 205 (TMEM205) is overexpressed in DDP-resistant human epidermoid carcinoma cells and correlates with drug resistance, and database analyses show that TMEM 205 is also overexpressed in GC, but its role in cisplatin-resistant gastric cancer remains unclear. In this study, we chose a variety of experiments in vivo and vitro, aiming to investigate the role of TMEM 205 in cisplatin resistance in gastric cancer. The results showed that TMEM 205 promoted proliferation, stemness, epithelial–mesenchymal transition (EMT), migration and angiogenesis of gastric cancer cells through activation of the Wnt/β-catenin signaling pathway. In addition, TMEM205 promotes GC progression by inducing M2 polarization of tumor-associated macrophages (TAMs). These results suggest that TMEM205 may be an effective target to regulate the sensitivity of GC to DDP, providing a new therapeutic direction for clinical treatment. [ABSTRACT FROM AUTHOR]

Background: Limited data exist for global prevalence of claudin 18 isoform 2 (CLDN18.2) positivity and association of CLDN18.2 status with clinical and tumor characteristics in patients with locally advanced (LA) unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma. We report prevalence of CLDN18.2 positivity (phase 3; SPOTLIGHT, NCT03504397; GLOW, NCT03653507) and concordance of CLDN18.2 status between a subset of pair-matched tumor samples (phase 2, ILUSTRO, NCT03505320; phase 1, NCT03528629) from clinical studies of zolbetuximab. Methods: Tumor samples from patients with LA unresectable or mG/GEJ adenocarcinoma were tested for CLDN18.2 status by immunohistochemistry. Human epidermal growth factor receptor 2 (HER2) expression was tested per central or local assessment. Results: Across SPOTLIGHT and GLOW, the prevalence of CLDN18.2 positivity (≥ 75% of tumor cells demonstrating moderate-to-strong membranous CLDN18 staining) was 38.4%. Prevalence was similar in gastric versus GEJ adenocarcinoma samples and regardless of collection method (biopsy versus resection) or collection site (primary versus metastatic). CLDN18.2 positivity was most prevalent in patients with diffuse-type tumors. In ILUSTRO and the phase 1 study, concordance of CLDN18.2 positivity was 61.1% between archival (i.e., any time before treatment) and baseline (i.e., ≤ 3 months before first treatment) samples, and concordance of any CLDN18 staining (≥ 1% of tumor cells demonstrating moderate-to-strong membranous CLDN18 staining) was 88.9%. Conclusions: CLDN18.2 was a highly prevalent biomarker in patients with HER2-negative, LA unresectable or mG/GEJ adenocarcinoma. CLDN18.2 positivity remained relatively stable over time in many patients. Biomarker testing for CLDN18.2 should be considered in standard clinical practice in these patients. [ABSTRACT FROM AUTHOR]

Background: Adjuvant chemotherapy following curative surgery for locally advanced gastric cancer (AGC) significantly improves long-term patient prognosis. However, delayed chemotherapy (DC), in which patients are unable to receive timely treatment, is a common phenomenon in clinical practice for various reasons. This study aimed to investigate the impact of DC on the prognosis of patients with stage II–III locally AGC and explore the associated risk factors. Methods: Data from four prospective studies were included in the pooled analysis. The planned chemotherapy (PC) group was defined as the time interval between surgery and the first chemotherapy ≤ 49 d, while the DC group was defined as the time interval between surgery and chemotherapy > 49 d. The prognosis, recurrence, and risk factors were compared, and a nomogram for predicting DC was established. Results: In total, 596 patients were included, of whom 531 (89.1%) had PC and 65 (10.9%) had DC. Survival analysis revealed that the 5-year overall survival (OS) and disease-free survival (DFS) were significantly lower in the DC group than those in the PC group (log-rank P < 0.001). Cox univariable and multivariable analyses showed that DC was an independent risk factor for OS and DFS in stage II–III patients (P < 0.05). Based on the significant factors for DC, a prediction model was established that had a good fit, high accuracy (AUC = 0.780), and clinical applicability in both the training and validation sets. Conclusion: Delayed chemotherapy after gastrectomy is associated with poor long-term prognosis in patients with locally advanced stage II–III GC disease. But standardized, full-cycle adjuvant chemotherapy after surgery may play a remedial role, and can to a certain extent compensate the poor effects caused by delayed chemotherapy. [ABSTRACT FROM AUTHOR]

Background: The CDKN2A gene is frequently affected by somatic copy number variations (SCNVs, including deletions and amplifications [SCNdel and SCNamp]) in the cancer genome. Using surgical gastric margin tissue samples (SMs) as the diploid reference in SCNV analysis via CDKN2A/P16-specific real-time PCR (P16-Light), we previously reported that the CDKN2A SCNdel was associated with a high risk of metastasis of gastric carcinoma (GC). However, the status of CDKN2A SCNVs in SMs and their clinical significance have not been reported. Methods: Peripheral white blood cell (WBC) and frozen GC and SM tissue samples were collected from patients (n = 80). Droplet digital PCR (ddPCR) was used to determine the copy number (CN) of the CDKN2A gene in tissue samples using paired WBCs as the diploid reference. Results: A novel P16-ddPCR system was initially established with a minimal proportion (or limit, 10%) of the detection of CDKN2A CN alterations. While CDKN2A SCNamp events were detected in both SMs and GCs, fewer CDKN2A SCNdel events were detected in SMs than in GCs (15.0% vs. 41.3%, P = 4.77E-04). Notably, significantly more SCNamp and fewer SCNdel of the CDKN2A gene were detected in SMs from GC patients without metastasis than in those from patients with lymph node metastasis by P16-ddPCR (P = 0.023). The status of CDKN2A SCNVs in SM samples was significantly associated with overall survival (P = 0.032). No cancer deaths were observed among the 11 patients with CDKN2A SCNamp. Conclusion: CDKN2A SCNVs in SMs identified by P16-ddPCR are prevalent and significantly associated with GC metastasis and overall survival. [ABSTRACT FROM AUTHOR]

Undifferentiated gastric carcinoma, characterized by anaplastic cells lacking distinct features of cytological or architectural differentiation, poses diagnostic and therapeutic challenges. Recent studies have suggested an association between this carcinoma and deficiencies in the SWI/SNF complex, particularly mutations in subunits such as SMARCA4. We herein report six cases of SMARCA4-deficient undifferentiated gastric carcinoma with molecular findings, highlighting the rarity and diagnostic pitfalls of this malignancy. Predominantly occurring in males over 50 years, these cases presented with nonspecific symptoms and were often diagnosed at an advanced stage. Histologically, the tumors exhibited a sheet-like growth pattern, reduced or absent epithelial markers, and loss of BRG-1 expression, with molecular analysis confirming SMARCA4 gene mutations. The response to conventional chemotherapy was poor, underscoring the importance of complete surgical resection and the development of alternative treatment modalities. [ABSTRACT FROM AUTHOR]

Introduction: The incidence of local recurrence following gastric endoscopic submucosal dissection (ESD) remains a clinical concern. We aimed to evaluate the impact of narrow safety margin (< 1 mm) on the recurrence rate. Methods: A retrospective cohort study was conducted across two centers. Cases of R0-ESD with subsequent recurrence were compared to matched controls in a 1:2 ratio in a case-cohort analysis. Results: Over a median period of 25 months (IQR 14-43), a recurrence rate of 3% (95%CI 1.7-4.3) was observed, predominantly (13/21) following R0 resections with favourable histology. Endoscopic retreatment was feasible in 18 of 21 recurrences. The proportion of R0-cases where the safety margin in both horizontal (HM) and vertical (VM) margin exceeded 1 mm was similarly distributed in the recurrence and non-recurrence group, representing nearly 20% of cases. However, cases with HM less than 1 mm, despite VM greater than 1 mm, nearly doubled in the recurrence group (7.7% vs. 3.9%), and tripled when both margins were under 1 mm (23.1% vs. 7.7%). Despite this trend, statistical significance was not achieved (p = 0.05). In the overall cohort, the only independent risk factor significantly associated with local recurrence was the presence of residual tumor at the HM (HM1) or not assessable HM (HMx) (OR 16.5 (95%CI 4.4-61.7), and OR 11.7 (95%CI 1.1-124.1), respectively). Conclusions: While not common or typically challenging to manage, recurrence post-ESD warrants attention and justifies rigorous post-procedural surveillance, especially in patients with HM1, HMx, and probably also in those with R0 resections but narrow safety margin. [ABSTRACT FROM AUTHOR]

• Fibroblasts can be activated as cancer-associated fibroblasts in the tumourmicroenvironment. • Cancer-associated fibroblasts help promote gastric cancer metastasis. • Cancer-Associated Fibroblasts Form Signalling Network with Gastric Cancer Cells. • Multiple drugs targeting cancer-associated fibroblasts have been found to inhibit gastric cancer progression. Despite advances in surgery, radiotherapy and immunotherapy, the mortality rate for gastric cancer remains one of the highest in the world. A large body of evidence has demonstrated that cancer-associated fibroblasts (CAFs), as core members of the stroma, can secrete cytokines, proteins and exosomes to create a tumour microenvironment that is conducive to cancer cell survival. CAFs can also interact with cancer cells to form a complex signalling network, enabling cancer cells to more easily metastasise to other organs and tissues in the body and develop metastatic foci. In this review, we provide an overview of the CAFs concept and activators. We focus on elucidating their effects on immune cells, intratumoural vasculature, extracellular matrix, as well as cancer cell activity, metastatic power and metabolism, and on enhancing the metastatic ability of cancer cells through activation of JAK/STAT, NF/κB and CXCL12/CXCR4. Various therapeutic agents targeting CAFs are also under development and are expected to improve the prognosis of gastric cancer in combination with existing treatment options. [ABSTRACT FROM AUTHOR]

Purpose: To explore the diagnostic value of dual-source computed tomography (DSCT) and neutrophil to lymphocyte ratio (NLR) for differentiating gastric signet ring cell carcinoma (SRC) from mixed SRC (mSRC) and non-SRC (nSRC). Methods: This retrospective study included patients with gastric adenocarcinoma who underwent DSCT between August 2019 and June 2021 at our Hospital. The iodine concentration in the venous phase (ICvp), standardized iodine concentration (NICVP), and the slope of the energy spectrum curve (kVP) were extracted from DSCT data. NLR was determined from laboratory results. DSCT (including ICVP, NICVP, and kVP) and combination (including DSCT model and NLR) models were established based on the multinomial logistic regression analysis. The receiver operator characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the diagnostic value. Results: A total of 155 patients (SRC [n = 45, aged 61.22 ± 11.4 years], mSRC [n = 60, aged 61.09 ± 12.7 years], and nSRC [n = 50, aged 67.66 ± 8.76 years]) were included. There were significant differences in NLR, ICVP, NICVP, and kVP among the SRC, mSRC, and nSRC groups (all P < 0.001). The AUC of the combination model for SRC vs. mSRC + nSRC was 0.964 (95% CI: 0.923-1.000), with a sensitivity of 98.3% and a specificity of 86.7%, higher than with DSCT (AUC: 0.959, 95% CI: 0.919–0.998, sensitivity: 90.0%, specificity: 89.9%) or NLR (AUC: 0.670, 95% CI: 0.577–0.768, sensitivity: 62.2%, specificity: 61.8%). Conclusion: DSCT combined with NLR showed high diagnostic efficacy in differentiating SRC from mSRC and nSRC. [ABSTRACT FROM AUTHOR]

Cancers have emerged as a significant concern due to their impact on public health and society. The examination and interpretation of tissue sections stained with Hematoxylin and Eosin (H&E) play a crucial role in disease assessment, particularly in cases like gastric cancer. Microsatellite instability (MSI) is suggested to contribute to the carcinogenesis of specific gastrointestinal tumors. However, due to the nonspecific morphology observed in H&E-stained tissue sections, MSI determination often requires costly evaluations through various molecular studies and immunohistochemistry methods in specialized molecular pathology laboratories. Despite the high cost, international guidelines recommend MSI testing for gastrointestinal cancers. Thus, there is a pressing need for a new diagnostic modality with lower costs and widespread applicability for MSI detection. This study aims to detect MSI directly from H&E histology slides in gastric cancer, providing a cost-effective alternative. The performance of well-known deep convolutional neural networks (DCNNs) and a proposed architecture are compared. Medical image datasets are typically smaller than benchmark datasets like ImageNet, necessitating the use of off-the-shelf DCNN architectures developed for large datasets through techniques such as transfer learning. Designing an architecture proportional to a custom dataset can be tedious and may not yield desirable results. In this work, we propose an automatic method to extract a lightweight and efficient architecture from a given heavy architecture (e.g., well-known off-the-shelf DCNNs) proportional to a specific dataset. To predict MSI instability, we extracted the MicroNet architecture from the Xception network using the proposed method and compared its performance with other well-known architectures. The models were trained using tiles extracted from whole-slide images, and two evaluation strategies, tile-based and whole-slide image (WSI)-based, were employed and compared. Additionally, a visual explanation of the best convolutional neural network model is presented to validate numerical results. The MicroNet architecture achieved the best accuracy (0.85) and area under the curve-receiver operating characteristic curve (0.93), outperforming previous works for the study dataset. The proposed method can be utilized by developers to design lightweight and efficient problem-based neural network architectures, such as MicroNet, for MSI prediction. [ABSTRACT FROM AUTHOR]

Human epidermal growth factor receptor 2 has been a pivotal biomarker for gastric cancer treatment strategies for many years. However, more than a decade after the ToGA trial demonstrated the efficacy of trastuzumab in improving survival, the development of treatments targeting human epidermal growth factor receptor 2 remains challenging. Several large-scale clinical trials of tyrosine kinase inhibitors, non-trastuzumab anti-human epidermal growth factor receptor 2 antibodies, and antibody–drug conjugates have failed to meet the primary endpoints. The concept of trastuzumab beyond progression and the complexity of resistance mechanisms to anti-human epidermal growth factor receptor 2 therapy after trastuzumab treatment presented significant obstacles, leading to trastuzumab being the sole therapy for human epidermal growth factor receptor 2-positive gastric cancer for some time. Nevertheless, the landscape has shifted in recent years, especially since the introduction of the antibody–drug conjugate trastuzumab deruxtecan in 2020. This has rekindled the interest in developing treatments targeting human epidermal growth factor receptor 2 in gastric cancer. [ABSTRACT FROM AUTHOR]

After immune checkpoint inhibitor (ICI) comes into third-line treatment of advanced gastric cancer, the therapeutic strategy has been dramatically changed. Recent first-line regimen, which consists of ICI and chemotherapeutic agents, prolonged progression-free survival, and subsequent treatment options enabled continuous treatment beyond second-line therapy. Moreover, the advent of vascular endothelial growth factor (VEGF)-targeted agents including angiogenesis inhibitors and TKIs provides an opportunity of considering the interaction between ICI and anti-VEGF agents, and facilitating novel treatment proposal. Although clinical benefit of prolonged VEGF blockade after disease progression has not been confirmed in gastric cancer, combination therapy of cytotoxic agents and anti-VEGF agent, such as irinotecan plus ramucirumab demonstrated favorable objective response rate and progression-free survival in third- or later-line setting. In this review, we discuss recent progress and future directions of later-line treatments of HER2-negative advancer gastric cancer. [ABSTRACT FROM AUTHOR]

Benign and malignant diseases of the upper gastrointestinal tract show gender-specific differences. The frequent gastroesophageal reflux disease is a prime example: men have an erosive reflux disease more often than women and are also younger at the time of onset. The rate of progression to a metaplastic Barrett's esophagus is also higher in men. In the case of achalasia, there are indications that surgical treatment by laparoscopic Heller's myotomy and semifundoplication 180° according to Dor leads to a markedly better improvement in the symptoms in women compared to men, although they showed a more pronounced dilation of the tubular esophagus. The female hormone status influences the localization and histopathology of adenocarcinoma of the esophagogastric junction and gastric carcinoma. Premenopausal and postmenopausal carcinomas differ significantly in women. In addition, high microsatellite instability (MSI high) is more frequent in women and is associated with a generally significantly better prognosis. The MSI high gastric carcinomas of women show better survival than MSI high carcinomas of men. The future inclusion of gender-specific aspects in studies of the upper gastrointestinal tract is desirable in order to generate adequate data and to enable differentiated treatment stratification in the future. [ABSTRACT FROM AUTHOR]

Dermatomyositis (DM) is associated with interstitial lung disease (ILD) and malignancy. However, the coexistence of ILD and malignancy (DM–ILD–malignancy) is rare, and limited information exists regarding its management. Herein, we report the case of a 70-year-old man who developed DM with rapidly progressive ILD and advanced gastric cancer and provide a literature review of managing DM–ILD–malignancy. The patient presented with typical DM skin rashes and shortness of breath, which worsened within 1 month, without muscular symptoms. Additionally, the patient tested negative for myositis-specific autoantibodies (MSAs). Computed tomography revealed ILD and advanced gastric cancer, which was confirmed on endoscopic examination to be a poorly differentiated adenocarcinoma. Although the patient's ILD progressed rapidly, surgical treatment of the cancer was prioritized. Prednisolone (PSL) 0.5 mg/kg was initiated 3 days before surgery and increased to 1 mg/kg at 7 days postoperative. Remarkable improvement in the skin rash and ILD was observed, and the PSL dose was tapered without immunosuppressants. A literature review revealed that anti-melanoma differentiation-associated gene 5 and anti-aminoacyl transfer RNA synthetase antibodies are the predominant MSAs in DM–ILD–malignancy, and the optimal treatment should be determined based on several factors, including ILD patterns, and malignancy type and stage. In particular, lung cancer may be a risk factor for the acute exacerbation of ILD, and preceding immunosuppression would be useful. Furthermore, prioritizing surgery for gastric cancer is effective because of its paraneoplastic nature. [ABSTRACT FROM AUTHOR]

Background/Aim: Despite the remarkable developments in chemotherapy for gastric cancer (GC), rapid tumor growth is sometimes experienced during chemotherapy. This study investigated the association of tumor growth rate (TGR) during second-line chemotherapy with the prognosis of patients with GC. Patients and Methods: We retrospectively reviewed 29 patients with GC treated with nab-paclitaxel plus ramucirumab as second-line chemotherapy between 2017 and 2019 at Osaka Metropolitan University. Of them, 13 cases with target lesions were classified into two groups according to TGR using a cutoff value of 0.25. Clinicopathological factors and survival outcomes were compared between the high TGR (n=5) and low TGR (n=8) groups. Results: The median duration of first-line chemotherapy was significantly longer in the high TGR group than in the low TGR group [median 298 days vs. 72.5 days, p=0.030]. Progressive disease (PD) was observed in 60% of patients with high TGR, whereas stable disease (SD) was observed in 75% patients with low TGR. The median survival time (MST) after starting chemotherapy was 488 days in the low TGR group but was not reached in the high TGR group (log rank p=0.215). The MST after PD was 145 days in the low TGR group but was not estimated in the high TGR group (log rank p=0.345). Conclusion: Based on the absence of significant differences in survival outcomes between the high and low TGR groups, sequential late-line chemotherapy might be considered important, even for patients with high TGR. [ABSTRACT FROM AUTHOR]

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Background: Gastrointestinal tumors represent a significant component of the cancer burden in Asia. This study aims to evaluate the burden of gastrointestinal tumors in Asia from 1990 to 2021 using data from the Global Burden of Disease Study 2021 (GBD 2021). Methods: The absolute incidence, mortality, and disability adjusted life years (DALYs) number and rate of six gastrointestinal tumors(colon and rectum cancer (CRC), stomach cancer (SC), pancreatic cancer (PC), esophageal cancer (EC), liver cancer (LC) and gallbladder and biliary tract cancer (GBTC)) in 48 Asian countries were extracted from GBD 2021. Differences were analyzed based on gender, age, year, location and socio-demographic index (SDI). Results: In 2021, SC accounted for the highest disease burden in Asia (DALYs=16.41million [95% UI: 13.70, 19.62]). From 1990 to 2021, the age-standardized incidence rates of EC, LC, and SC in Asia declined, while the incidence rates of CRC and PC increased significantly, with CRC showing the largest rise (AAPC=1.08 [95% CI: 1.02 to 1.12]). Gastrointestinal tumors DALY rates peaked at age 70 and above, with males generally exhibiting higher rates than females. Furthermore, East Asia bears a higher burden compared to other Asian subregions. A higher SDI correlates with increased DALY rates for PC, but no linear relationship was observed for other gastrointestinal tumors. Conclusion: The burden of gastrointestinal tumors in Asia remains high and may continue to increase. Therefore, effective prevention and treatment measures are essential to address the challenge posed by gastrointestinal tumors. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) treatment regimens are still unsatisfactory. Recently, Urolithin A (UroA) has gained tremendous momentum due to its anti-tumor properties. However, the therapeutic effect and underlying mechanisms of UroA in GC are unclear. We explored the effects and related mechanisms of UroA on GC both in vivo and in vitro. A Cell Counting Kit-8 was used to determine the influence of UroA on the proliferation of GC cell lines. The Autophagy inhibitor 3‐methyladenine (3MA) was employed to clarify the role of autophagy in the anti-tumor effect of UroA. Simultaneously, we detected the core-component proteins involved in autophagy and its downstream pathways. Subsequently, the in vivo anti-tumor effect of UroA was determined using a xenograft mouse model. Western blotting was used to detect the core protein components of the anti-tumor pathways, and 16S rDNA sequencing was used to detect the effect of UroA on the gut microbiota. We found that UroA suppressed tumor progression. The use of 3MA undermined the majority of the inhibitory effect of UroA on tumor cell proliferation, further confirming the importance of autophagy in the anti-tumor effect of UroA. Invigorating of autophagy activated the downstream Hippo pathway, thereby inhibiting the Warburg effect and promoting cell apoptosis. In addition, UroA modulated the composition of the gut microbiota, as indicated by the increase of probiotics and the decrease of pathogenic bacteria. Our research revealed new anti-tumor mechanisms of UroA, which may be a promising candidate for GC treatment. [ABSTRACT FROM AUTHOR]