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Helicobacter pylori, invades the gastric mucosa and is one of the causative agents of stomach cancer and peptic ulcers. Origanum vulgare, is a flavouring herb used worldwide. But little is known about the effects of extracts prepared by maceration in cold PBS. This study was aimed at determining the superoxide dismutase (SOD)- and peroxidase (Px)-like antioxidant activities as well as the immunomodulatory activity (anti-inflammatory/pro-inflammatory) of an aqueous extract of O. vulgare by evaluating the production of nitric oxide (NO) in macrophages stimulated with H. pylori derivatives. The cold extract presented SOD-like and Px-like activities with effective concentration 50 (EC50) values of Px = 489.7 ± 48 µg/ml and SOD= 384.7 ± 30 µg/ml. The extract was also capable of modulating the production of NO in macrophages stimulated by H. pylori derivatives by exerting a pro-inflammatory activity at high concentrations and an anti-inflammatory activity at low concentrations. [ABSTRACT FROM AUTHOR]

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Objective: To explore the effect of multimodal analgesia based on the concept of enhanced recovery after surgery (ERAS) in patients undergoing laparoscopic radical gastrectomy (LRG) for gastric cancer (GC). Methods: Clinical data of 128 patients undergoing LRG for GC, admitted to Sir Run Run Shaw Hospital, Zhejiang University School of Medicine from March 2021 to March 2022, were retrospectively analyzed. Among them, 66 patients received a multimodal analgesic management based on ERAS (ERAS group), and 62 patients were treated with conventional mode of analgesia (control group). Pain levels, rehabilitation status, as well as inflammatory factors and stress response indicators before and after surgery were compared between the two groups. Results: There was no significant difference in baseline data between the two groups (P>0.05). The postoperative pain and recovery in the ERAS group were better than those in the control group (P<0.05). After the surgery, serum levels of tumor necrosis factor-alpha (TNF-α), Interleukin 6 (IL-6), and C-reactive protein (CRP) in both groups increased compared to before the surgery, but were significantly lower in the ERAS group compared to the control group (P<0.05). After the surgery, serum malondialdehyde (MDA) and xanthine oxidase (XOD) levels in both groups increased, while superoxide dismutase (SOD) levels decreased compared to preoperative levels. The observed postoperative levels of serum MDA and XOD were significantly lower in the ERAS group, while the postoperative SOD levels were higher compared to the control group (P<0.05). Conclusions: Patients undergoing LRG for GC can benefit from a multimodal pain management plan based on ERAS to reduce postoperative pain, alleviate inflammation, stress responses, and shorten the postoperative recovery process. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of probiotics combined with enteral nutrition therapy on intestinal flora, digestive tract symptoms and endogenous environment in patients with gastric cancer undergoing chemotherapy. Methods: In this retrospective study, eighty patients with gastric cancer undergoing chemotherapy admitted to Affiliated Hospital of Hebei University from January 2021 to September 2023 were included and divided into two groups by random number table method: the enteral nutrition group and the probiotics combined enteral nutrition group (n=40 each group). The differences in the number of intestinal flora, nutritional indicators, immune function, endotoxin, D-lactic acid levels between the two groups, and the digestive tract symptoms of the two groups before and after treatment were compared and recorded. Results: The levels of serum total protein (TP), prealbumin (PAB), albumin (ALB) and transferrin (TF) in both groups were higher than those before treatment, and those in the probiotics combined with enteral nutrition group were higher than those in the enteral nutrition group (p< 0.05). The levels of immunoglobulin A (lgA), immunoglobulin M (lgM) and immunoglobulin G (lgG) in the two groups were lower than before treatment, and those in the probiotics combined with the enteral nutrition group were lower than those in the enteral nutrition group (p< 0.05). Conclusion: Probiotics combined with enteral nutrition results in various benefits in the treatment of patients with gastric cancer undergoing chemotherapy, improving immunity, and reducing gastrointestinal symptoms. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the clinical significance and stage migration effect of radiological diameter-to-thickness (DT) ratio in HER2-positive resectable advanced gastric cancer (HER2-p RAGC). Methods: 369 HER2-p RAGC patients were retrospectively enrolled and information on clinical pathological characteristics, radiological DT ratio, and outcomes [i.e., overall survival (OS) and progression-free survival (PFS)] was collected. Pearson's Chi-square and Student's t-test were employed to compare baseline characteristics. Clinical outcomes were estimated using Kaplan–Meier analysis and Log-rank test. Univariate and multivariate Cox regression models were utilized to analyze independent prognostic factors. Results: HER2-p RAGC patients were stratified into two groups using a DT ratio cutoff value of 4.0 (p < 0.05). Patients with a DT ratio < 4.0 exhibited significantly longer OS (58.0 vs. 31.0 months) and PFS (43.0 vs. 24.0 months) than those with a DT ratio ≥ 4.0. DT ratio significantly predicted prognosis for N0 and II stage patients (p < 0.05). Patients with gastric body and antrum cancers demonstrated longer OS and PFS in the DT ratio < 4.0 group (p = 0.046, 0.017, 0.036 and 0.028). Multivariate Cox proportional hazard model identified age, pathological T category, pathological N category, pathological TNM category and DT ratio as independent prognostic factors. Notably, pStage II patients with a DT ratio ≥ 4.0 exhibited a similar prognosis to pStage III patients with a DT ratio < 4.0 (p = 0.418 for OS, 0.867 for PFS). Conclusion: Radiological DT ratio could evaluate the prognosis and detect higher malignant cases in HER2-p RAGC patients. Moreover, DT ratio might guide clinicians make postoperative strategies. Trial registration: Retrospectively registered. [ABSTRACT FROM AUTHOR]

Background: Peritoneal metastasis of gastric cancer is closely associated with dismal prognosis. In previous preclinical proof-of-concept studies, an amido-bridged nucleic acid (AmNA)-modified antisense oligonucleotide (ASO), designated ASO-4733 that targets the gene encoding synaptotagmin XIII (SYT13), inhibited cellular functions required for the formation of peritoneal metastasis of gastric cancer cells. ASO-4733 achieved therapeutic effects when intra-abdominally administered to mouse xenograft models. Here, we conducted an analysis of Syt13-deficient mice to determine the pharmacokinetics and toxicity of intra-abdominal administration of ASO-4733. Methods: The effects of Syt13-deficiency in mice were determined. Good Laboratory Practice toxicity tests and the toxicokinetics of intra-abdominal administration of ASO-4733 were conducted in cynomolgus monkeys and rats. The pharmacokinetics of ASO-4733 administered intravenously or intra-abdominally to rats were investigated. Results: Syt13-deficient mice exhibited normal reproduction, organ functions, and motor functions. Weekly intra-abdominal administration of ASO-4733 (125 mg/kg), corresponding to a 50-fold increase of the estimated clinical dose for 4 weeks, was well tolerated by cynomolgus monkeys. In rats, off-target toxicity (not attributable to hybridization) was observed after weekly intra-abdominal administration of ASO-4733. Blood concentrations of ASO-4733 were lower and rose more slowly after intra-abdominal administration compared with intravenous administration. Conclusions: The preclinical profile of intra-abdominal administration of ASO-4733 demonstrated its suitability for entry into clinical trials of patients with peritoneal metastasis of gastric cancer. [ABSTRACT FROM AUTHOR]

Background: Large type 3 (diameter ≥ 8 cm) and type 4 gastric cancers have been arbitrarily combined in Japan as a single entity. However, whether these two types are oncologically similar remain unclear. This study aimed to clarify this issue. Methods: In this retrospective study, we analyzed a database of 3,575 patients from nine institutions who underwent gastrectomy between 2010 and 2014. Using propensity scores to balance significant variables, we compared prognoses and tumor recurrences. Results: Of patients with clinical T3/T4 who underwent R0 resection, 75 and 73 had large type 3 and 4 tumors, respectively. Patients with type 4 tumors had significantly lower overall survival rates than those of patients with large type 3 tumors (hazard ratio [HR] 1.77; 95% confidence interval [CI] 1.14–2.74). However, among the large type 3 tumors, a remarkable difference in prognosis was observed between the differentiated and undifferentiated histological types. A comparison was made between large type 3 with undifferentiated phenotype and type 4, each with 39 patients after propensity score matching. Outcomes in both groups were similar in terms of overall survival (HR 1.28; 95% CI 0.73–2.25) and relapse-free survival (HR 1.34; 95% CI 0.80–2.27). No statistically significant differences were observed in the incidence of peritoneal recurrence (35.9% vs. 46.1%, P = 0.36) and lymph node recurrence (25.6% vs. 12.8%, P = 0.15). Conclusions: Large type 3 tumors with undifferentiated phenotype and type 4 tumors were oncologically similar. This subgroup could be considered as a new entity for future clinical trials. [ABSTRACT FROM AUTHOR]

Background: Lipolysis-stimulated lipoprotein receptor (LSR), a lipid receptor, is associated with cancer progression. However, detailed effects on intracellular metabolism are unclear. We aimed to elucidate the mechanism of LSR-mediated lipid metabolism in gastric cancer. Methods: We investigated lipid metabolic changes induced by lipoprotein administration in gastric cancer cells and evaluated the significance of LSR expression and lipid droplets formation in gastric cancer patients. The efficacy of inhibiting β-oxidation in gastric cancer cells was also examined in vitro and vivo. Results: In gastric cancer cells, LSR promoted cellular uptake of lipoprotein and cell proliferation. Furthermore, the inhibition of LSR in gastric cancer cells expressing high levels of LSR counteracted both effects. Immunohistochemical analysis of human gastric cancer tissues showed that the increase in lipid droplets via LSR is a factor that influences prognosis. Lipidomics analysis of LSR-high-expressing gastric cancer cells revealed an increase in β-oxidation. Based on these results, we used etomoxir, a β-oxidation inhibitor, and found that it inhibited cell proliferation as well as the suppression of LSR. Similarly, in a mouse xenograft model of LSR-highly expressing gastric cancer cells, the tumor growth effect of high-fat diet feeding was counteracted by etomoxir, consistent with the Ki-67 labeling index. Conclusions: We demonstrated that lipids are taken up into gastric cancer cells via LSR and cause an increase in β-oxidation, resulting in the promotion of cancer progression. Controlling LSR-mediated lipid metabolism may be a novel therapeutic strategy for gastric cancer. [ABSTRACT FROM AUTHOR]

Background: The significance of reinforcement of the duodenal stump with seromuscular sutures and the effectiveness of reinforced staplers in preventing duodenal stump leakage remain unclear. We aimed to explore the importance of duodenal stump reinforcement and determine the optimal reinforcement method for preventing duodenal stump leakage. Methods: This retrospective cohort study was conducted between January 1, 2012 and December 31, 2021, with data analyzed between December 1, 2022 and September 30, 2023. This multicenter study across 57 institutes in Japan included 16,475 patients with gastric cancer who underwent radical gastrectomies. Elective open or minimally invasive (laparoscopic or robotic) gastrectomy was performed in patients with gastric cancer. Results: Duodenal stump leakage occurred in 153 (0.93%) of 16,475 patients. The proportions of males, patients aged ≥ 75 years, and ≥ pN1 were higher in patients with duodenal stump leakage than in those without duodenal stump leakage. The incidence of duodenal stump leakage was significantly lower in the group treated with reinforcement by seromuscular sutures or using reinforced stapler than in the group without reinforcement (0.72% vs. 1.19%, p = 0.002). Duodenal stump leakage incidence was also significantly lower in high-volume institutions than in low-volume institutions (0.70% vs. 1.65%, p = 0.047). The rate of duodenal stump leakage-related mortality was 7.8% (12/153). In the multivariate analysis, preoperative asthma and duodenal invasion were identified as independent preoperative risk factors for duodenal stump leakage-related mortality. Conclusions: The duodenal stump should be reinforced to prevent duodenal stump leakage after radical gastrectomy in patients with gastric cancer. [ABSTRACT FROM AUTHOR]

Background: Homologous recombination deficiency (HRD) is one of the crucial hallmarks of cancer. It is associated with a favorable response to platinum-based chemotherapy. We explored the distinctive clinicopathological features of gastric cancer (GC) with HRD and the clinical significance of HRD in platinum-based first-line chemotherapy for unresectable metastatic GC. Methods: We enrolled 160 patients with GC in this study. Their tumor samples were subjected to genomic profiling utilizing targeted tumor sequencing. HRD was defined as the presence of alterations in any of 16 HR genes (BARD1, BLM, BRCA1, BRCA2, BRIP1, MRE11A, NBN, PALB2, PARP1, POLD1, RAD50, RAD51, RAD51C, RAD51D, WRN, and XRCC2). The clinicopathological features and treatment outcomes of first-line chemotherapy for unresectable metastatic GC were compared between HRD and non-HRD groups. Results: Forty-seven patients (29.4%) were classified into the HRD group. This group had a significantly lower proportion of macroscopic type 3 or 4 tumors and higher TMB than the non-HRD group. Among patients who underwent platinum-based first-line chemotherapy, the HRD group had a greater response rate and longer progression-free survival after treatment (median 8.0 months vs. 3.0 months, P = 0.010), with an adjusted hazard ratio of 0.337 (95% confidence interval 0.151–0.753). HRD status was not associated with treatment outcomes in patients who did not undergo platinum-based chemotherapy. Conclusions: Low proportion of macroscopic type 3 or 4 tumors and a high TMB are distinctive features of GC with HRD. HRD status is a potential predictive marker in platinum-based first-line chemotherapy for unresectable metastatic GC. [ABSTRACT FROM AUTHOR]

Background: Clinical findings and postoperative follow-up data on remnant gastric cancer (RGC) are limited due to its rarity. Additionally, the preoperative staging, radical surgery, and managing recurrence in RGC present significant clinical challenges. Methods: We analyzed the clinicopathological findings, adjuvant chemotherapy, and patterns of postoperative recurrence of 313 consecutive patients who underwent curative surgery for RGC at 17 Japanese institutions. This study investigated the optimal management of RGC and the impact of adjuvant chemotherapy (AC) on recurrence-free survival (RFS). Results: Pathological stages I, II, and III were observed in 55.9% (N = 175), 24.9% (N = 78), and 19.2% (N = 60) of the patients, respectively. The overall concordance rate between clinical and pathological T staging was 58.3%, with a clinical T4 sensitivity of 41.4% for diagnosing pathological T4. During the median follow-up period of 4.6 years, disease recurrence occurred in 24.3% of patients. Most recurrences (over 80%) occurred within 2.5 years, and 96.1% within 5 years after RGC surgery. Peritoneal recurrence was the most common in patients with advanced RGC, accounting for 14.1% in stage II and 28.3% in stage III. Multivariable regression analysis showed that AC was significantly associated with a longer RFS, with a hazard ratio of 0.45 (95% confidence interval: 0.26–0.76). Conclusions: Our study underscores the importance of early detection, accurate preoperative staging, and postoperative surveillance in managing advanced RGC cases. Despite some limitations, our findings indicate that AC may provide survival benefits comparable to those seen in primary gastric cancer. [ABSTRACT FROM AUTHOR]

Background: Previous studies have investigated cardiovascular disease (CVD) risks in cancer patients, but there is limited knowledge concerning the CVD risk in adult and young adolescent (AYA) survivors of gastric cancer. Objectives: This study aims to investigate the incidence of CVD in AYA gastric cancer survivors, analyzing it by treatment type and identifying associated risk factors. Methods: We conducted a retrospective cohort study using Korean National Health Insurance Service data collected from 2006 to 2019. Propensity score matching (1:3, caliper < 0.1) was performed using the variables age, sex, income, residential area, and presence of comorbidities, and we classified participants into gastric cancer (n = 6562) and non-cancer control (n = 19,678) groups. Cox regression models were used to calculate hazard ratios (HRs) for CVD incidence. The study assessed CVD incidence by cancer treatment and identified risk factors through multivariable Cox regression. Results: During a median 6.5-year follow-up, AYA gastric cancer survivors consistently exhibited greater CVD incidence. Their risk of CVD was significantly elevated compared to that of controls (HR, 1.18; 95% confidence interval [CI] 1.05–1.33). In particular, deep vein thrombosis (HR, 3.93; 95% CI 3.06–14.67) and pulmonary embolism (HR, 6.58; 95% CI 3.06–14.67) risks were notably increased. Chemotherapy was associated with an increased risk of stroke, heart failure, atrial fibrillation, deep vein thrombosis, and pulmonary embolism. Hypertension (HR, 1.58; 95% CI 1.10–2.26) and dyslipidemia (HR, 1.46; 95% CI 1.06–2.20) emerged as risk factors for CVD development. Conclusion: This study reports elevated risks of CVD in AYA gastric cancer survivors and emphasizes the need for vigilant monitoring of CVD in this population. [ABSTRACT FROM AUTHOR]

Background: Gastric foveolar type neoplasia is a rare histological variant of gastric tumors. It is very difficult to differentiate between benign and malignant intraepithelial foveolar neoplasia (IFN). Although limited molecular alterations have been identified in IFNs, somatic copy number alterations (SCNAs), which are linked to tumor progression, have not been systematically evaluated in IFN. Methods: The aim of the present study was to comprehensively examine SCNAs using a SNP array in 37 cases of IFN, compared with intestinal type dysplasia, including 39 low grade (LGD) and 32 high grade dysplasia (HGD) cases. In addition, gene mutations were evaluated using a gene panel. Finally, we attempted to determine molecular profiles using a hierarchical clustering analysis. Results: Two patterns could be categorized according to the SCNAs in 108 tumors examined: high (subgroup 1) and low (subgroup 2) frequencies of SCNAs. Although IFN and LGD were associated with subgroup 2, HGD was found in both subgroups. The median numbers of total SCNAs and copy number gains were higher in IFN or HGD than in LGD. In addition, the IFN genotype was characterized by altered genes located at 4p13–4q35.2, including RAP1GDS1 and LEF1, which may be associated with IFN development. Finally, no significant mutations were found in IFNs using a gene panel. Conclusions: The current molecular profiles of IFN may help elucidate the mechanisms of IFN development. [ABSTRACT FROM AUTHOR]

Background: The impact of economic engagement on the health of cancer survivors is notable. Our study aims to explore the association between early loss of economic activity (EA) and the risk of all-cause mortality among gastric cancer survivors. Methods: This retrospective cohort study utilized data from Korea's National Health Insurance Service, focusing on 30–59-year-old gastric cancer patients who received either surgery or endoscopic procedures from January 2009 to December 2013. The primary outcome measure was all-cause mortality. Early loss of EA was identified when a patient's insurance status shifted to dependent within one year following treatment. Adjusted hazard ratios (HRs) and 95% confidence intervals (CI) for all-cause mortality were estimated using multivariable Cox proportional hazards models, conducting separate analyses for surgical and endoscopic groups. Results: Among 24,159 patients (median follow-up, 9.9 years), 2976 (12.3%) experienced all-cause mortality. Specifically, 2835 of these deaths occurred in patients who underwent surgery, while 141 were in the endoscopic procedure group. Early loss of EA was recorded in 14.4% of the surgery group and 7.7% of the endoscopic procedure group. Adjusted HRs (95% CI) for all-cause mortality associated with early loss of EA were 1.39 (1.27–1.54) for the surgery group and 2.27 (1.46–3.52) for the endoscopic procedure group. Conclusions: This study highlights a significant association between the early loss of EA and an increased risk of all-cause mortality in those who have undergone curative treatments for gastric cancer. It underscores the crucial role of sustaining EA in enhancing the health outcomes of these survivors. [ABSTRACT FROM AUTHOR]

Background: Nivolumab + chemotherapy is now a standard of care for HER2-negative, previously untreated, unresectable or recurrent gastric/gastroesophageal junction cancer (advanced gastric cancer), but long-term follow-up data of clinical trials are limited. Methods: ATTRACTON-4 was a phase 3, double-blind, placebo-controlled trial in Japan, South Korea, and Taiwan. Patients were randomized to either nivolumab or placebo, both combined with the physician's choice of SOX (oral S-1 [tegafur–gimeracil–oteracil potassium] + oxaliplatin) or CAPOX (capecitabine + oxaliplatin). We report the primary endpoints—centrally assessed progression-free survival (PFS) and overall survival (OS)—and landmark analyses of OS among patients alive using 3-year follow-up data. Results: At the cutoff date (May 10, 2021), 17/359 patients in the nivolumab + chemotherapy group and 6/358 in the placebo + chemotherapy group were continuing study treatment. PFS (centrally assessed) was longer in the nivolumab + chemotherapy group (median 10.94 vs. 8.48 months; hazard ratio [HR] 0.67, 95% confidence interval [CI] 0.55–0.82). Although OS did not differ between the two groups (median 17.45 vs. 17.15 months; HR 0.89, 95% CI 0.75–1.05), the landmark analysis of OS, calculating HRs at each landmark time point (every month), was getting numerically better in the nivolumab + chemotherapy group over time. Approximately 80% of patients who achieved complete response in the nivolumab + chemotherapy group were alive at 3 years. No new safety signals or major late-onset select treatment-related adverse events were observed for nivolumab + chemotherapy. Conclusion: This 3-year follow-up of ATTRACTION-4 confirmed the long-term clinical benefit and manageable safety of nivolumab + chemotherapy in patients with previously untreated advanced gastric cancer. Trial registration: NCT02746796 [ABSTRACT FROM AUTHOR]

Background: Integrating molecular-targeted agents into combination chemotherapy is transformative for enhancing treatment outcomes in cancer. However, realizing the full potential of this approach requires a clear comprehension of the genetic dependencies underlying drug synergy. While the interactions between conventional chemotherapeutics are well-explored, the interplay of molecular-targeted agents with conventional chemotherapeutics remains a frontier in cancer treatment. Hence, we leveraged a powerful functional genomics approach to decode genomic dependencies that drive synergy in molecular-targeted agent/chemotherapeutic combinations in gastric adenocarcinoma, addressing a critical need in gastric cancer therapy. Methods: We screened pharmacological interactions between fifteen molecular-targeted agent/conventional chemotherapeutic pairs in gastric adenocarcinoma cells, and examined the genome-scale genetic dependencies of synergy integrating genome-wide CRISPR screening with the shRNA-based signature assay. We validated the synergy in cell death using fluorescence-based and lysis-dependent inference of cell death kinetics assay, and validated the genetic dependencies by single-gene knockout experiments. Results: Our combination screen identified SN-38/erlotinib as the drug pair with the strongest synergism. Functional genomics assays unveiled a genetic dependency signature of SN-38/erlotinib identical to SN-38. Remarkably, the enhanced cell death with improved kinetics induced by SN-38/erlotinib was attributed to erlotinib's off-target effect, inhibiting ABCG2, rather than its on-target effect on EGFR. Conclusion: In the era of precision medicine, where emphasis on primary drug targets prevails, our research challenges this paradigm by showcasing a robust synergy underpinned by an off-target dependency. Further dissection of the intricate genetic dependencies that underlie synergy can pave the way to developing more effective combination strategies in gastric cancer therapy. [ABSTRACT FROM AUTHOR]

Background: The purpose of the study was to conduct a comprehensive genomic characterization of gene alterations, microsatellite instability (MSI), and tumor mutational burden (TMB) in submucosal-penetrating (Pen) early gastric cancers (EGCs) with varying prognoses. Methods: Samples from EGC patients undergoing surgery and with 10-year follow-up data available were collected. Tissue genomic alterations were characterized using Trusight Oncology panel (TSO500). Pathway instability (PI) scores for a selection of 218 GC-related pathways were calculated both for the present case series and EGCs from the TCGA cohort. Results: Higher age and tumor location in the upper-middle tract are significantly associated with an increased hazard of relapse or death from any cause (p = 0.006 and p = 0.032). Even if not reaching a statistical significance, Pen A tumors more frequently present higher TMB values, higher frequency of MSI-subtypes and an overall increase in PI scores, along with an enrichment in immune pathways. ARID1A gene was observed to be significantly more frequently mutated in Pen A tumors (p = 0.006), as well as in patients with high TMB (p = 0.027). Tumors harboring LRP1B alterations seem to have a higher hazard of relapse or death from any cause (p = 0.089), being mutated mainly in relapsed patients (p = 0.093). Conclusions: We found that the most aggressive subtype Pen A is characterized by a higher frequency of ARID1A mutations and a higher genetic instability, while LRP1B alterations seem to be related to a lower disease-free survival. Further investigations are needed to provide a rationale for the use of these markers to stratify prognosis in EGC patients. [ABSTRACT FROM AUTHOR]

Anastomotic leaks and stenoses remain critical complications in esophagectomy and are related to conduit perfusion. Surgical gastric preconditioning has been described but requires additional surgery and creates scar tissue, potentially hindering future operation. We sought to evaluate the feasibility and safety of percutaneous gastric preconditioning by angioembolization to improve perfusion of gastric conduits before esophagectomy in a high-risk patient cohort. Patients pending an esophagectomy for cancer and deemed to be high risk for anastomotic complications underwent preconditioning by image-guided angioembolization. Preconditioning was performed on an outpatient basis by means of superselective embolization of the left gastric and short gastric arteries. Intraoperative conduit perfusion evaluation with indocyanine green and postoperative surgical outcomes was reviewed. Seventeen patients underwent gastric preconditioning, with no complications observed. Thirteen of the 17 patients ultimately underwent esophagectomy; the remaining four patients were not candidates for an operation. Patients proceeded to surgery a median of 23 days (interquartile range, 21–27 days) after preconditioning. The intraoperative indocyanine green perfusion of all conduits was appropriate, with no tip demarcation and with a median time to dye uptake of 20s (interquartile range, 15–20s). There were no anastomotic stenoses or leaks noted within the series. Gastric conduit preconditioning by percutaneous angioembolization of the left gastric and short gastric arteries can be performed safely and without operative delay in high-risk patients. Further evaluation of preconditioning for conduit optimization is warranted to limit the critical complications of anastomotic leak and stenosis in esophagectomy. [ABSTRACT FROM AUTHOR]

Purpose: This study investigated the prognostic value of the geriatric nutritional risk index (GNRI) in patients undergoing curative gastrectomy for remnant gastric cancer (RGC). Methods: This multicenter retrospective study included 105 patients with RGC of ≥ 65 years of age who underwent curative gastrectomy at 10 institutions in Japan between January 2000 and December 2016. Postoperative complications, overall survival (OS), and disease-specific survival (DSS) were analyzed. Results: Receiver operating curve analyses indicated that the optimal cutoff value of the GNRI for OS was 95.4. Patients were categorized into high and low GNRI groups based on the optimal GNRI cutoff value. The GNRI was significantly correlated with body mass index (p < 0.001), amount of bleeding (p = 0.021), Clavien–Dindo grade 5 postoperative complications (p = 0.040), death caused by primary disease (p = 0.010), and death caused by other diseases (p = 0.002). The OS and DSS were significantly worse in the low GNRI group. A low GNRI and T3 or deeper tumor invasion were independent prognostic factors for OS and DSS. Conclusions: The GNRI is a promising predictor of both short- and long-term outcomes in older patients with RGC. [ABSTRACT FROM AUTHOR]

Background: Proximal gastrectomy (PG) is one of function-preserving gastrectomy (FPG). In this study, we compared the long-term results of proximal gastric cancer (PGC) patients undergoing proximal gastrectomy and total gastrectomy (TG). Method: Patients diagnosed with PGC and receiving PG or TG between 2004 and 2020 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was applied to minimize confounding factors. Kaplan-Meier analysis and log-rank test were used to compare overall survival (OS) and cancer-specific survival (CSS) between the PG and TG groups. Univariate and multivariate Cox regression analyses were performed to identify independent risk factors affecting OS. Result: A total of 3916 patients were recruited according to the inclusion and exclusion criteria, with 2614 undergoing PG and 1302 undergoing TG. After 1:1 PSM matching, 912 pairs of data were included for analysis. Before PSM matching, PG group tended to have better OS and CSS outcomes. However, after PSM matching, both surgical approaches showed similar long-term results. Conclusion: PG for PGC yields comparable long-term outcomes to TG and demonstrates safety in terms of oncologic outcomes. [ABSTRACT FROM AUTHOR]

Background: Pimitespib (TAS‐116), a first‐in‐class, oral, selective heat‐shock protein 90 inhibitor, is approved as fourth‐line treatment for gastrointestinal stromal tumors in Japan. This phase 1 study evaluated the cardiac safety of pimitespib. Methods: In this open‐label, nonrandomized, multicenter study, Japanese patients (aged ≥20 years) with refractory, advanced solid tumors received placebo on day −1, then pimitespib 160 mg daily on days 1–5 of the cardiac safety evaluation period. Electrocardiograms were conducted at baseline, and on days −2, −1, 1, and 5; and blood samples were collected on days 1 and 5. Patients then received once‐daily pimitespib for 5 days every 3 weeks. The primary end point was the time‐matched difference in QT interval corrected for heart rate using the Fridericia correction (QTcF) between pimitespib and placebo. Pharmacokinetics, safety, and preliminary efficacy were also assessed. Results: Of the 22 patients in the cardiac safety‐evaluable population, no clinically relevant QTc prolongation was observed; the upper bound of the one‐sided 95% confidence interval for the time‐matched difference in change from baseline in QTcF was <20 msec at all time points on days 1 and 5. Pimitespib pharmacokinetic parameters were consistent with previous data, and the time‐matched difference in change from baseline in QTcF showed no marked increase as plasma concentrations increased. The safety profile was acceptable; 40% of patients experienced grade 3 or greater adverse drug reactions, mostly diarrhea (20%). The median progression‐free survival was 3.1 months. Conclusions: In Japanese patients with refractory, advanced solid tumors, pimitespib was not associated with clinically relevant QTc prolongation, and there were no cardiovascular safety concerns. Plain Language Summary: Pimitespib is a new anticancer drug that is being used to treat cancer in the stomach or intestines (gastrointestinal stromal tumors).This study demonstrated that pimitespib had no marked effect on heart rhythm or negative effects on the heart or blood vessels and had promising anticancer effects in Japanese patients with advanced solid tumors who were unable to tolerate or benefit from standard treatment. [ABSTRACT FROM AUTHOR]

Accurate prediction of gastric cancer survival state is one of great significant tasks for clinical decision‐making. Many advanced machine learning classification techniques have been applied to predict the survival status of cancer patients in three or 5 years, however, many of them have a low sensitivity because of class imbalance. This is a non‐negligible problem due to the poor prognosis of gastric cancer patients. Furthermore, models in the medical domain require strong interpretability to increase their applicability. Due to the better performance and interpretability of the XGBoost model, we design a loss function taking into account cost sensitive and focal loss from the algorithm level for XGBoost to deal with the imbalance problem. We apply the improved model into the prediction of the survival status of gastric cancer patients and analyse the important related features. We use two types of indicators to evaluate the model, and we also design the confusion matrix of two models' predictive results to compare two models. The results show that the improved model has better performance. Furthermore, we calculate the importance of features related to survival with three different time periods and analyse their evolution, which are consistent with existing clinical research or further expand their research conclusions. These all support for clinically relevant decision‐making and has the potential to expand into survival prediction of other cancer patients. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) remains a global healthcare challenge because of its high incidence and poor prognosis. The efficacy of current chemotherapy regimens for advanced GC is limited. T cells, which have been implicated in the progression of GC, have a significant impact in the tumor microenvironment. With a more detailed understanding of the mechanisms underlying the cancer immunoediting process, immunotherapy may become a promising treatment option for patients with GC. Several clinical trials are currently investigating different mechanisms targeting the tumor immune response. The present review summarized T cell-involved immune responses and various immunotherapy strategies for GC. [ABSTRACT FROM AUTHOR]

The long survival of patients with primary cancer increases the chance of such patients developing second primary cancer (SPC). The development of SPC in cancer survivors exerts a large psychological, social and economic burden on patients and their families. The aim of the present study was to assess the risk of cancer survivors developing SPC. The study included patients who had been diagnosed with a first primary cancer in five organs (stomach, colorectum, lung, breast and thyroid), which are the five most common sites of cancer in patients from Korea, at the regional cancer center in Jeonbuk National University Hospital between January 2007 and December 2009. The standardized incidence ratio (SIR) of SPC according to sex and site was calculated from 5,209 patients who were followed up to September 2017. General incidence was acquired from the National Cancer Registry of Republic of Korea. SPC occurred in 6.2% (323/5,209) of patients, and the incidence of SPC among the five major types of cancer was in the order of breast (8.8%, 46/524), colorectum (8.6%, 86/1,003), gastric (6.6%, 89/1,358), thyroid (4.7%, 67/1,437) and lung cancer (3.9%, 35/887). When all SPC sites were included, the SIRs of SPC in patients with colorectal cancer and breast cancer were >1.0 (1.21 and 1.66, respectively). Breast cancer and thyroid cancer exhibited a high site relationship (P<0.05), and colorectal cancer had a high site relationship with gastric cancer (P<0.05). The present study analyzed the incidence and pattern of SPC in patients with cancer who were diagnosed with primary carcinoma in five organs. The results of the study may be useful for effective follow-up and early detection of SPC in patients with cancer. [ABSTRACT FROM AUTHOR]

The flexible ultrasonic scalpels are currently required for surgical treatment of deep-seated areas of the living body. One of the surgical treatments for early-stage gastric cancer is surgery to remove the superficial layers of the stomach. Endoscopic surgery is used for early-stage gastric cancer. Polypectomy, one of the endoscopic surgical methods, involves hooking a snare over the affected area, squeezing, and applying a high-frequency electric current to burn it off. On the other hand, ultrasonic scalpels are effective at lower temperatures than conventionally used electrocautery scalpels, and have the advantage of having less thermal effect on tissues other than the affected area. However, due to the challenges associated with the propagation of ultrasonic waves, the use of flexible wires for this purpose in current research is limited. In this study, we attempted to observe the characteristics of ultrasonic wave propagation to the wire in the snare, which is a part of the electrocautery used in the polypectomy. The development of flexible ultrasonic scalpels will be advanced when ultrasonic propagation with less energy loss to the strand wire can be realized. In addition, Finite Element Method analysis was performed to identify the heat sources generated when ultrasonic vibration is applied to a stranded wire and to investigate a solution. Additionally, to find conditions where ultrasonic energy propagation is strong and heat generation is minimal, the partial single lines model was examined. The analysis confirmed that heat was generated by friction between strands of stranded wire. [ABSTRACT FROM AUTHOR]

To determine the preoperative detection of signet ring cancer cells (SRC) on upper endoscopy (EGD) in patients with CDH1 pathogenic variant (PV) undergoing gastrectomy. To evaluate the development of advanced diffuse gastric cancer (DGC) in patients choosing surveillance. Guidelines recommend prophylactic total gastrectomy (pTG) in CDH1 PV carriers with family history of DGC between 18 and 40 years. Annual EGD with biopsies according to established protocols is recommended in carriers with no SRC and no family history of DGC, with consideration of pTG. Retrospective analysis of asymptomatic patients with CDH1 PVs with ≥ 1 surveillance EGD. Outcomes included pre-operative EGD detection of SRC, surgical stage, and progression to advanced DGC in those electing surveillance with EGD. 48 patients with CDH1 PVs who had ≥ 1 EGD were included. 24/ 48 (50%) underwent gastrectomy, including pTG in 7 patients. SRCC were detected on gastrectomy specimen in 21/24 (87.5%). SRCs were identified by EGD in 17/21 patients who had SRCC on gastrectomy specimens (sensitivity 81%, 17/21). All cancers were stage pT1a. The remaining 17 patients (50% with a family history of gastric cancer) continue in annual EGD surveillance with a median follow-up of 34.6 months. No SRCC or advanced DGC have been diagnosed. No CDH1 PV carriers without SRCC on random biopsies followed in an endoscopic program developed advanced DGC over a median follow up of 3 years. In the short term, EGD surveillance might be a safe alternative to immediate pTG in experienced hands in referral centers. [ABSTRACT FROM AUTHOR]

Background: The research on the associations between tissue inhibitors of metalloproteinase-1 (TIMP1) expression and the clinicopathological characteristics and prognosis of patients with gastric cancer (GC) have resulted in contradictory findings. Exploring the associations between TIMP1 and clinicopathological parameters and the prognosis of GC patients is essential. Methods: We searched the literature in the databases according to the inclusion and exclusion criteria. Hazard ratios (HRs), odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to evaluate the relationships between TIMP1 expression and the clinicopathological parameters and prognosis of GC patients. Results: Nine studies with 1,200 GC patients were included. Our results indicated that TIMP1 expression was not related to sex, age, TNM stage, depth of invasion, lymph node metastasis, or tumor size in GC patients. However, TIMP1 expression was associated with the differentiation of GC. Furthermore, TIMP1 expression was associated with poor prognosis in GC patients. Conclusion: TIMP1 expression was related to tumor differentiation and poor prognosis but not sex, age, TNM stage, depth of invasion, lymph node metastasis or tumor size. [ABSTRACT FROM AUTHOR]

Objective: This study employs integrated bioinformatics analysis and in vitro cellular experiments to elucidate the role of Synaptotagmin-12 (SYT12) in the progression of gastric cancer. Methods: We utilized databases and platforms such as Xiantao Academic Tools, UALCAN, Kaplan-Meier plotter analysis, and The Cancer Genome Atlas (TCGA) to extract datasets on SYT12 in gastric cancer. We analyzed the relationship between SYT12 expression and the clinicopathological features, prognosis, diagnosis, and immune infiltration of stomach adenocarcinoma (STAD) patients. Verification was conducted using samples from 31 gastric cancer patients. Additionally, in vitro cellular experiments were performed to determine the role and potential mechanisms of SYT12 in the malignant behavior of gastric cancer cells. Results: Comprehensive bioinformatics analysis indicated that SYT12 is highly expressed in most cancers and is associated with promoter DeoxyriboNucleic Acid (DNA) methylation levels. SYT12 expression correlated with clinicopathological features, immune cell infiltration, immune checkpoint gene expression, and poor prognosis in STAD patients. In vitro experiments suggest that SYT12 may promote the proliferation and migration of gastric cancer cells by inducing epithelial-mesenchymal transition (EMT). Conclusions: This study highlights the significant role of SYT12 in gastric cancer, suggesting its potential as a new target for early diagnosis, treatment, immunological, and prognostic evaluation in gastric cancer, offering new insights for precision medicine in this disease. [ABSTRACT FROM AUTHOR]

The success of immunotherapy for cancer treatment is limited by the presence of an immunosuppressive tumor microenvironment (TME); Therefore, identifying novel targets to that can reverse this immunosuppressive TME and enhance immunotherapy efficacy is essential. In this study, enrichment analysis based on publicly available single‐cell and bulk RNA sequencing data from gastric cancer patients are conducted, and found that tumor‐intrinsic interferon (IFN) plays a central role in TME regulation. The results shows that KDM3A over‐expression suppresses the tumor‐intrinsic IFN response and inhibits KDM3A, either genomically or pharmacologically, which effectively promotes IFN responses by activating endogenous retroviruses (ERVs). KDM3A ablation reconfigures the dsRNA‐MAVS‐IFN axis by modulating H3K4me2, enhancing the infiltration and function of CD8 T cells, and simultaneously reducing the presence of regulatory T cells, resulting in a reshaped TME in vivo. In addition, combining anti‐PD1 therapy with KDM3A inhibition effectively inhibited tumor growth. In conclusions, this study highlights KDM3A as a potential target for TME remodeling and the enhancement of antitumor immunity in gastric cancer through the regulation of the ERV‐MAVS‐IFN axis. [ABSTRACT FROM AUTHOR]

Objectives Methods Results Conclusions This study aims to investigate the independent and joint trajectories of resilience, anxiety, and depression symptoms and research the interaction between older gastric cancer survivors' resilience and anxiety–depression during the period of 1 year after surgery.The participants were 381 older gastric cancer survivors, with a mean age of 69 years. Resilience, anxiety, and depression symptoms were assessed immediately after surgery, and at 3, 6, and 12 months post‐surgery, respectively. A longitudinal design was employed to capture the dynamic changes in resilience, anxiety, and depression levels among older gastric cancer survivors post‐surgery. Latent growth mixture model and random intercept cross‐lagged panel model were used to analyse the trajectories of resilience and anxiety–depression and the interaction between them.Two latent trajectories were identified for the resilience, four latent trajectories were identified for the anxiety, and five latent trajectories were identified for the depression, respectively, with three joint trajectories identified: gradual‐increasing resilience, gradual‐decreasing anxiety, and depression group (10.0%); gradual‐decreasing resilience, gradual‐increasing anxiety, and depression group (21.2%); and rapid‐growth resilience, rapid‐decline anxiety, and depression group (68.8%). Resilience among older gastric cancer survivors exhibits significant bidirectional and negative predictive effects on anxiety and depression.Individual differences in resilience, anxiety, and depression trajectories exist among older gastric cancer survivors, with heterogeneous joint progression patterns, and the relationship between resilience and anxiety–depression appears bidirectional. More sophisticated intervention programmes tailored to the unique characteristics of the relevant trajectories are necessary to enhance resilience and mitigate the risk of anxiety and depression. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) presents a significant global health burden, with metastasis being the leading cause of treatment failure and mortality. NAT10, a regulatory protein involved in mRNA acetylation, has been implicated in various cancers. However, its role in GC, especially concerning metastasis and immune interactions, remains unclear. Utilizing multi‐omics data from gastric cancer samples, we conducted comprehensive analyses to investigate NAT10 expression, its correlation with clinical parameters and immune relevance. Bioinformatics analysis and digital image processing were employed for this purpose. Furthermore, in vitro and in vivo experiments were conducted to elucidate the functional role of NAT10 in gastric cancer progression, aiming to provide deeper biological insights. Our findings reveal a significant association between NAT10 expression and various aspects of transcriptional, protein, as well as tumor immunity in GC patients. Additionally, we demonstrated that NAT10 promotes gastric cancer cell proliferation and migration, both in cellular models and in animal studies, suggesting its involvement in early tumor microvascular metastasis. NAT10 emerges as a promising molecular target, offering potential avenues for further research into molecular mechanisms and therapeutic strategies for GC. [ABSTRACT FROM AUTHOR]

Background and Aim Methods Results Conclusion The implementation of computer‐aided detection (CAD) devices in esophagogastroduodenoscopy (EGD) could autonomously identify gastric precancerous lesions and neoplasms and reduce the miss rate of gastric neoplasms in prospective trials. However, there is still insufficient evidence of their use in real‐life clinical practice.A real‐world, two‐center study was conducted at Wenzhou Central Hospital (WCH) and Renmin Hospital of Wuhan University (RHWU). High biopsy rate and low biopsy rate strategies were adopted, and CAD devices were applied in 2019 and 2021 at WCH and RHWU, respectively. We compared differences in gastric precancerous and neoplasm detection of EGD before and after the use of CAD devices in the first half of the year.A total of 33 885 patients were included and 32 886 patients were ultimately analyzed. In WCH of which biopsy rate >95%, with the implementation of CAD, more the number of early gastric cancer divided by all gastric neoplasm (EGC/GN) (0.35% vs 0.59%, P = 0.028, OR [95% CI] = 1.65 [1.0–2.60]) was found, while gastric neoplasm detection rate (1.39% vs 1.36%, P = 0.897, OR [95% CI] = 0.98 [0.76–1.26]) remained stable. In RHWU of which biopsy rate <20%, the gastric neoplasm detection rate (1.78% vs 3.23%, P < 0.001, OR [95% CI] = 1.84 [1.33–2.54]) nearly doubled after the implementation of CAD, while there was no significant change in the EGC/GN.The application of CAD devices devoted to distinct increases in gastric neoplasm detection according to different biopsy strategies, which implied that CAD devices demonstrated assistance on gastric neoplasm detection while varied effectiveness according to different implementation scenarios. [ABSTRACT FROM AUTHOR]

AbstractBackgroundMethodsResultsConclusionsTalin-1 (TLN1) is crucial in cell migration, metastasis, and cancer development. This study evaluated Talin-1 expression and its clinical significance in gastric cancer (GC), along with human epidermal growth factor receptor-2 (HER-2) expression and its correlation with Talin-1.Bioinformatics analysis assessed the potential prognostic value of Talin-1 and HER-2 in GC patients. The study included 223 GC patients (Signet Ring Cells and Intestinal subtypes) and 29 non-malignant tissue samples. Immunohistochemistry (IHC) on tissue microarray slides evaluated Talin-1 and HER-2 expression and clinical significance. Receiver operating characteristic (ROC) curves assessed their diagnostic value.Bioinformatics identified Talin-1 as a potential prognostic factor and HER-2 as an oncogene in GC. Talin-1 and HER-2 expression increased in SRC-type GC samples compared to non-malignant tissues. High cytoplasmic Talin-1 expression inversely correlated with tumor expansion and invasion in SRC-type GC. Increased HER-2 expression positively correlated with metastasis. ROC curves showed significant diagnostic values for both proteins.Higher cytoplasmic Talin-1 expression is associated with less invasive tumor behavior, while increased membranous HER-2 expression is associated with metastasis in SRC-type GC. These findings suggest potential use in assessing diagnosis and screening high-risk cancer patients, particularly those with SRC-type GC. [ABSTRACT FROM AUTHOR]

The role of circadian rhythm genes (CRGs) in gastric cancer (GC) is poorly understood. This study aimed to develop a CRG signature to improve understanding of prognosis and immunotherapy responses in GC patients. We integrated the The Cancer Genome Atlas-Stomach adenocarcinoma (TCGA-STAD) dataset with CRGs to develop a prognostic signature for GC. The signature's predictive ability was validated using Kaplan-Meier and ROC curves. The CIBERSORT algorithm evaluated immune cell proportions, and tumor immune dysfunction and exclusion score, as well as immune phenotype score, determined the response to immunotherapy for STAD patients. Finally, we assessed signature genes expression using real-time quantitative polymerase chain reaction. We developed a 4-CRG signature for STAD, demonstrating accurate prognostic ability. The low-risk group showed increased B cell memory and CD8 + T cells, and decreased M2 Macrophages compared to the high-risk group. Patients in the low-risk group had a higher likelihood of benefiting from immunotherapy. Additionally, gastric cancer tissues exhibited elevated expression of OPN3 and decreased expression of TP53 compared to adjacent tissue. This study successfully established a prognostic signature for CRGs, accurately predicting prognosis and immunotherapeutic response among STAD patients, providing insights for the development of personalized therapeutic strategies for these patients. [ABSTRACT FROM AUTHOR]

Cardia gastric cancer (CGC) is prevalent in East Asia, and noninvasive, cost-effective screening methods are needed. This study investigated the diagnostic value of serum pepsinogen (PG), gastrin-17 (G-17), Helicobacter pylori (H. pylori) antibodies, and proteomic profiling for CGC and precancerous lesions. We conducted a case-control study involving biopsy-confirmed patients with CGC (n = 60), low-grade intraepithelial neoplasia (CLGD, n = 60), high-grade intraepithelial neoplasia (CHGD, n = 64), and healthy controls (n = 120) matched for age and sex from high-incidence areas in China. Serological markers including PGI, PGII, G-17, and H. pylori were measured using ELISA and Western blot, while plasma protein markers were assessed using Olink® technology. The VSOLassoBag algorithm and nine machine learning (ML) algorithms were employed to identify crucial features and construct predictive models. Various evaluation metrics, including the area under the receiver-operating-characteristic curve (AUC), were utilized to compare predictive performance. Elevated PGII levels, decreased PGR, and H. pylori infection were significantly associated with an increased risk of CGC and precancerous lesions (P for trend < 0.05). The eXtreme Gradient Boosting (XGBoost) model performed best in discriminative ability among the 9 ML models. Following feature reduction based on predictive performance, a final explainable XGBoost model was developed, incorporating five protein biomarkers (CDHR2, ICAM4, PTPRM, CDC27, and FLT1). This model exhibited excellent performance in distinguishing individuals with CGC and precancerous lesions from healthy controls (AUC = 0.931 for CGC, 0.867 for CHGD, and 0.763 for CLGD), surpassing the traditional serological marker-based model. This study underscores the diagnostic potential of serological markers and proteomic profiling in the detection of CGC. Further validation and exploration of combined biomarker approaches are warranted to enhance early diagnosis and improve outcomes in high-risk populations. [ABSTRACT FROM AUTHOR]

Context. Gastric and oesophageal cancers are common. They are also expected to increase in incidence in the next few years and are characterized by poor prognosis. Surprisingly, whereas the incidence of severe anxiety and depression is high in patients with gastric and oesophageal cancers, the influence of symptoms of depression and anxiety on postoperative complications has barely been explored. Methods. In a retrospective study based on a prospectively collected database, 629 cancer patients were enrolled. Symptoms of depression and anxiety (Hospital Anxiety and Depression Scale scores) and sociodemographic and medical information were collected immediately after diagnosis and before any treatment. The surgical approach (i.e. gastrectomy or oesophagectomy) and postoperative complications according to the Clavien–Dindo classification were collected after surgery. Results. After controlling for known medical predictors (i.e. surgical strategy, alcohol and tobacco consumption, American Society of Anaesthesiologists classification physical status score) of postoperative complications, no effect of symptoms of depression or anxiety was detected. Discussion. The observed results are surprising given the literature. However, several potential arguments can be put forwards regarding methods and measures, controlling variables, and conceptual distinctions. Despite the absence of significant results, this topic should be more deeply investigated by applying methodological and conceptual adjustments. [ABSTRACT FROM AUTHOR]

Objectives: To systematically evaluate the efficacy and safety of enteral nutrition with ω-3 polyunsaturated fatty acid preparations or standard enteral nutrition preparations used in patients with gastric cancer during perioperative period, and to provide reference for clinical rational drug use. Methods: Pubmed, EMbase, The Cochrane Library, CNKI and Wanfang Medical databases were searched by computer to collect relevant literature. The search period was from the establishment of the database to August 1, 2024. Meta-analysis was performed using Revman5.4 software after two researchers independently screened literature, extracted data, and evaluated the risk of bias in included studies. Results: A total of 20 randomized controlled studies were included. The Meta results showed that there was no statistical difference in mortality between the enteral nutrition with ω-3 polyunsaturated fatty acid group and the control group (RR = 0.46, P = 0.17). However, the IEN group demonstrated superior advantages in reducing infection complications (RR = 0.81, P = 0.05) and wound infection (RR = 0.61, P = 0.04) among gastric cancer patients, as well as improving immune-related indicators (including IgG, IgA, IgM, CD4, and CD4/CD8), inflammation-related markers (including CRP, IL-1β, and IL-6), and nutritional indicators (including Total protein, Albumin, and Transferrin). Conclusion: enteral nutrition with ω-3 polyunsaturated fatty acid preparation has advantages in the efficacy and safety of perioperative nutritional therapy in patients with gastric cancer, and can be used as a clinical choice. Due to the limited number and quality of included studies, the above conclusions need to be verified by more high-quality studies. [ABSTRACT FROM AUTHOR]

Purpose: To highlight the trends and frontiers of RNA methylation in cancer over the past 10 years. Methods: Research publications on RNA methylation in cancer were retrieved from the Web of Science Core Collection database. VOSviewer, CiteSpace, and Bibliometrix were used to conduct bibliometric and visualization analysis of countries, institutions, authors, journals, and keywords relevant to this field. Results: From 2014 to 2023, research on RNA methylation in cancer has developed rapidly, with an overall increase in the number of publications and citations. China (4320 papers, 115056citations), Sun Yat Sen University (274 papers, 15698 citations), and Zhang, Wei (48 papers, 893 citations) are respectively the countries, institutions, and authors with the highest number of published papers and citations. Frontiers in Oncology (182 papers, 2524 citations) and Molecular Cancer (69 papers, 9224 citations) are the journals with the highest number of published papers and citations in this field, respectively. Cooccurrence analysis of keywords indicates that the research topics can be divided into five clusters: Cluster one: The Role of RNA Methylation in Tumor Heterogeneity, Therapeutic Response, and Prognosis; Cluster two: The Role of Noncoding RNA in RNA Methylation and Tumors; Cluster three: Potential Therapeutic Targets of RNA Methylation in Tumors; Cluster four: The role of RNA methylation in tumor progression and metastasis: A case study of hepatocellular carcinoma and gastric cancer; Cluster five: Regulation mechanisms of m6A methylation in leukemia cell differentiation and tumorigenesis. Conclusion: This is the first comprehensive study using bibliometrics to analyze the trends and frontiers of RNA methylation in cancer over the past 10 years, pointing out promising research directions for the future and providing valuable references for researchers in this field. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer (GC) is one of the most common malignant tumors of the digestive tract worldwide. Both environmental and genetic factors contribute to the occurrence and development of GC. Surgery and chemotherapy are the main treatment modalities for gastric cancer; however, some patients show insensitivity to chemotherapeutic agents. Chemotherapy resistance is one of the primary reasons for poor treatment outcomes and the high likelihood of recurrence and metastasis in gastric cancer patients. Numerous studies have confirmed a correlation between the dysregulation of microRNA expression and the development of various malignant tumors, as well as their resistance to chemotherapeutic agents. However, the role of microRNA-582-3p in gastric cancer cells and its mechanism in the resistance of gastric cancer cells to oxaliplatin have not been studied. Methods: We first used q-PCR, CCK8, transwell, and scratch assays to validate the expression of microRNA-582-3p in gastric cancer tissues and cells, while also analyzing the relationship between its expression levels and the clinical pathological data of patients. Additionally, we further confirmed the impact of microRNA-582-3p on gastric cancer cell progression and oxaliplatin resistance through knockdown and overexpression experiments. Subsequently, to explore the specific mechanisms of microRNA-582-3p in gastric cancer, we verified the downstream target of microRNA-582-3p, ATG7, using dual-luciferase reporter assays and examined the effect of ATG7 on gastric cancer cell functions. Moreover, we conducted rescue experiments to further validate the interaction between microRNA-582-3p and ATG7. Results: Our experimental results confirmed that microRNA-582-3p is lowly expressed in gastric cancer tissues and cells, and the expression level of miR-582-5p is correlated with the T stage of patients, while showing no correlation with the patients' gender, age, tumor size, degree of differentiation, or N stage. Additionally, we found that microRNA-582-3p functions as a tumor suppressor in gastric cancer cells, as its overexpression inhibits the biological functions of gastric cancer cells and increases their sensitivity to oxaliplatin. Furthermore, we identified binding sites between microRNA-582-3p and the autophagy-related gene ATG7, observing that knockdown of microRNA-582-3p increases ATG7 expression, while its overexpression reduces ATG7 levels. Moreover, ATG7 is overexpressed in gastric cancer cells; knockdown of ATG7 inhibits the biological functions of gastric cancer cells and increases their sensitivity to oxaliplatin, whereas overexpression of ATG7 reverses the inhibitory effect of miR-582-5p on gastric cancer. Conclusion: Our study confirms that microRNA-582-3p acts as a tumor suppressor in gastric cancer cells, and its role may be mediated through the regulation of ATG7 expression levels. MicroRNA-582-3p may serve as a potential target for gastric cancer treatment and a predictive biomarker. [ABSTRACT FROM AUTHOR]

Although the efficacy of trastuzumab deruxtecan (T-DXd) against HER2-positive gastric cancers (GCs) has driven its clinical application, the precise mechanisms governing its immunomodulatory role remain unclear. In this study, we examined the immune-related mechanisms of action of T-DXd in GC cells. T-DXd exhibited potent antitumor effects in GC cells across diverse HER2 expression levels by inducing DNA damage and apoptosis. Activation of the DNA damage response by T-DXd led to increased PD-L1 expression. RNA-Seq analysis revealed that T-DXd modulated immune-related pathways, resulting in the upregulation of genes associated with inflammation and IFN signaling. Importantly, T-DXd activated the cGAS-STING pathway, inducing an IFN-I response in HER2-positive GC cells. Furthermore, T-DXd activated dendritic cells via the cancer cell-intrinsic cGAS-STING-IFN axis and enhanced PBMC-mediated tumor cell killing by activating CD8+ T cells. These findings provide valuable insights into the role of the cytosolic DNA sensing pathway in the action of T-DXd and offer a compelling rationale for combining T-DXd with immune checkpoint blockade therapies in GC treatment. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer (GC) is a leading malignant disease in numerous countries, including Taiwan with limited therapeutic options. Animal viruses including oncolytic avian reovirus (ARV) have the possibility to avoid pre-existing immunity in humans, while being safe and immunostimulatory. Here, we provide a novel insight into oncolytic ARV and UV-ARV-sensitized patient's peripheral blood mononuclear cells (P-PBMCs) and tumor infiltrating lymphocytes (TILs) killing primary GC (PGC) cells through the surface TLR3 and TRAIL/DR4/DR5 immunogenic apoptosis pathway. Methods: We conducted a comprehensive study to reveal whether ARV- or UV-inactivated ARV (UV-ARV)-modulated P-PBMCs or TILs killing ARV- and UV-ARV-sensitized AGS cells and PGC cells derived from clinical patients and to investigate the regulation of surface TLR3 receptor and upstream signaling pathways. Apoptosis analysis by flow cytometry and Western blot, suppression of signal pathway by specific inhibitors, in situ proximity ligation assay (PLA), time-resolved flurometry and lactate dehydrogenase (LDH) cytotoxicity assays, and an in vitro co-culture model were established to study the interplay between ARV- and UV-ARV-sensitized P-PBMCs and TILs to kill PGC cells and their upstream pathways. Results: Our results reveal that increased levels of DR4 and DR5 were observed in ARV and UV-ARV sensitized PGC cells through the TLR3/p38/p53 signaling pathway. Importantly, we found that the σC protein of ARV or UV-ARV interacted with surface TLR3 of CD8+ TILs, thereby triggering the TLR3/NF-κB/IFN-γ/TRAIL signaling pathway which induces immunogenic apoptosis of PGC cells. This study sheds further light on the molecular basis behind ARV oncolysis and facilitates the ARV or UV-ARV as a cancer therapeutic. Conclusions: The study provides novel insights into ARV- or UV-ARV-sensitized P-PBMCs and CD8+ TILs to kill PGC cells through the immunogenic apoptosis pathway. We conclude that P-PBMCs can easily be obtained from GC patients and provide a rich source as TILs to kill PGC cells. [ABSTRACT FROM AUTHOR]

AbstractAsbestos is a group of naturally occurring fibrous minerals that were commonly used in the construction of cement pipes for drinking water distribution systems. These pipes deteriorate and can release asbestos fibers into drinking water, raising concerns about potential risk to human health. The objective of this work was to synthesize human, animal, and in vitro evidence on potential health risks due to ingested asbestos in drinking water and evaluate the weight of evidence (WoE) of human health risk. A systematic review of epidemiological evidence was conducted, along with critical review of animal and in vitro evidence, followed by WoE evaluation that integrated human, animal, and in vitro evidence. The systematic review included 17 human studies with health outcomes mostly related to various cancer sites, with the majority focusing on the gastrointestinal system. The WoE evaluation resulted in very low levels of confidence or insufficient evidence of a health effect for cancers in 15 organ systems and for three non-cancer endpoints. While eight studies reported possible associations with stomach cancer in males, few high-quality studies were available to verify a causal relationship. Based on high-quality animal studies, an increased risk for cancer or non-cancer endpoints was not supported, aligning with findings from human studies. Overall, the currently available body of evidence is insufficient to establish a clear link between asbestos contamination in drinking water and adverse health effects. Due to the lack of both high-quality epidemiological studies and a validated kinetic model for ingested asbestos, additional research on this association is warranted. [ABSTRACT FROM AUTHOR]

Patients with gastric cancer (GC) are more susceptible to coronavirus disease 2019 (COVID-19), which further worsens their already challenging prognosis. However, there are no effective treatment options for these patients. Lentinan is a potent bioactive component with antiviral and antitumor effects. We hypothesized that lentinan might exert powerful pharmacological effects in patients with GC and COVID-19. In this study, a prognostic model of patients with GC/COVID-19 was constructed and used to apply a network pharmacology approach to reveal biological functions, drug targets, and molecular mechanisms of the action of lentinan against GC/COVID-19. Clinical analysis revealed key prognostic genes in patients with GC/COVID-19. The results of network pharmacology analysis suggested that the therapeutic effect of lentinan on GC/COVID-19 mainly involves the modulation of several neutrophil-related biological processes, as well as the nucleotide-binding and oligomerization domain-like receptor and interleukin-17 signaling pathways. In addition, C-X-C motif chemokine ligand 8, vascular endothelial growth factor A, ribonuclease 3, and F2 were identified as key genes of lentinan against GC/COVID-19. Key prognostic genes were identified in patients with GC/COVID-19 through the construction of a prognostic model. Pharmacological functions and signaling pathways of lentinan against GC/COVID-19 were revealed. These included the regulation of neutrophils and NOD-like receptor signaling pathways. The findings provide the first published evidence of the potential value of lentinan as a complementary therapy for GC/COVID-19. [ABSTRACT FROM AUTHOR]

Thioredoxin reductase 1 (TXNRD1) has been identified as one of the promising chemotherapeutic targets in cancer cells. Therefore, a novel TXNRD1 inhibitor could accelerate chemotherapy in clinical anticancer research. In this study, glaucocalyxin A (GlauA), a natural diterpene extracted from Rabdosia japonica var. glaucocalyx, was identified as a novel inhibitor of TXNRD1. We found that GlauA effectively inhibited recombinant TXNRD1 and reduced its activity in gastric cancer cells without affecting the enzyme's expression level. Mechanistically, the selenocysteine residue (U498) of TXNRD1 was irreversibly modified by GlauA through a Michael addition. Additionally, GlauA formed a covalent adduct with glutathione (GSH) and disrupted cellular redox balance by depleting cellular GSH. The inhibition of TXNRD1 and depletion of GSH by GlauA conferred its cytotoxic effects in spheroid culture and Transwell assays in AGS cells. The disulfide stress induced cytotoxicity of GlauA could be mitigated by adding reducing agents, such as DTT and β‐ME. Furthermore, the FDA‐approval drug auranofin, a TXNRD1 inhibitor, triggered oligomerization of the cytoskeletal protein Talin‐1 in AGS cells, indicating that inhibiting TXNRD1 triggered disulfide stress. In conclusion, this study uncovered GlauA as an efficient inhibitor of TXNRD1 and demonstrated the potential of TXNRD1 inhibition as an effective anticancer strategy by disrupting redox homeostasis and inducing disulfide stress. [ABSTRACT FROM AUTHOR]

Background: There were about 1,090,000 gastric cancer (GC) cases in 2020 in China. The incidence and mortality rates ranked the fifth and third among all kinds of cancers in China. Early diagnosis plays an important role in the treatment and prognosis of gastric cancer. In recent years, noninvasive diagnosis, especially plasma exosome lncRNAs, has become a promissing biomarkers with high specificity and sensitivity for early diagnosis of cancers. Methods: In this study, plasma exosomes of patients with early gastric cancer were extracted efficiently by affinity membrane separation technology, including affinity adsorption, elution, affinity membrane regeneration and other steps. After identified by electron microscopy observation, particle size analysis and Western blot verification, the lncRNAs in the exosomes were extracted and were analysized by high-throughput RNA sequencing (RNA-Seq). The differentially expressed lncRNAs were verified by RT-qPCR in 93 patients with early gastric cancer and 49 normal controls. Results: Electron microscopy, particle size analysis and Western blot showed that exosomes were successfully isolated from plasma. RNA-Seq results show that 76 lncRNAs were upregulated and 260 lncRNAs were downregulated in plasma exosomes of early gastric cancer patients compared with normal controls. RTqPCR analysis indicated that a total of 6 lncRNAs were significantly and differentially expressed in gastric cancer patients compared to normal controls, with 2 (lncmstrg. 1319590, Lncmstrg. 2312697) highly expressed and 4 lowly expressed (lncmstr-g.1004024.1, lncmstrg. 2441832.8, lncmstrg. 315376.1, lncmstrg.907985.2,) (p < 0.05). The survival curve analysis indicated that lncmstrg.2441832.8 and lncmstrg.2312697 had higher sensitivity and specificity for the diagnosis of gastric cancer, respectively and AUC curve areas were 0.6211 and 0.631, p < 0.05, respectively, which were greater than the traditional clinical detection indexes CEA (0.61) and AFP (0.57). When combined lncmstrg.2441832.8 and lncmstrg.2312697 in gastric cancer diagnosis, AUC curve area reached 0.73, which was greater than CA199 (0.71). Conclusion: Lncmstrg.2441832.8 and lncmstrg.2312697 may be a potential and promissing biomarkers for early diagnosis of gastric cancer. [ABSTRACT FROM AUTHOR]

Tumor immunotherapy has been widely used in clinical treatment of various cancers. However, some patients of these cancers do not respond to immunotherapy effectively. And H. pylori infection has been considered to be related to the efficacy of immunotherapy. This review aims to summarize the different effects and mechanisms of H. pylori infection on immunotherapy in different kinds of cancers. We searched the relevant literature on H. pylori and tumor immunotherapy, and summarized to form a review. Generally, H. pylori infection plays a role in affecting kinds of cancers' development, besides gastric cancer. Current evidence suggests that H. pylori infection may reduce the efficacy of immunotherapy for colorectal cancer, non-small cell lung cancer and melanoma, but due to the lack of sufficient evidence, more data is needed to prove that. While for gastric cancer, the effects remain controversial. The H. pylori regulation effects and metabolisms involved in systematic related cancers should be paid attention to. Whether H. pylori should be eradicated when immunotherapy performed may be a critical consideration for some kinds of tumors. [ABSTRACT FROM AUTHOR]

The three-stranded DNA-RNA triplex hybridization is involved in various biological processes, including gene expression regulation, DNA repair, and chromosomal stability. However, the DNA-RNA triplex mediating mechanisms underlying tumorigenesis remain to be fully elucidated. Here, we show that peptidylprolyl isomerase A (PPIA) serves as anchor to recruit GAU1 lncRNA by interacting with exon 4 of GAU1 and enhances the formation of SENP5/GAU1 DNA-lncRNA triplex. Intriguingly, TFR4 region of GAU1 exon 3 and TTS4 region of SENP5 promoter DNA constitute fragments forming the SENP5/GAU1 triplex. The SENP5/GAU1 triplex subsequently triggers the recruitment of the methyltransferase SET1A to exon 1 of GAU1, leading to the enrichment of H3K4 trimethylation and the activation of SENP5 transcription for driving the tumorigenesis of gastric cancer in vitro and in vivo. Our study reveals a mechanism of PPIA-guided SENP5/GAU1 DNA-lncRNA triplex formation in tumorigenesis and providing a concept in the dynamics of isomerase assisted DNA-RNA hybridization. This study investigates the regulatory mechanisms of DNA-lncRNA triplexes, specifically their role in gastric cancer through the stable formation and precise oncogenic activity of the SENP5/GAU1 triplex. It shows how PPIA orchestrates the SENP5/GAU1 DNA-lncRNA triplex. [ABSTRACT FROM AUTHOR]

Objective: The efficacy of lymph node ratio (LNR) as a prognostic indicator in locally advanced gastric cancer (LAGC) patients underwent radical resection after neoadjuvant immunochemotherapy (NICT) remains to be demonstrated. The objective of the current retrospective study is to investigate the relationship between LNR and survival in patients with LAGC who underwent radical resection after NICT. Methods: A retrospective analysis was performed on 121 cases of LAGC in patients underwent radical resection after NICT between July 2020 and October 2023. The LNR values of the patients were divided into two groups using X-tile software. The first group, designated the low LNR group, comprised patients with LNR values of ≤ 33%. The second group, designated the high LNR group, comprised patients with LNR values of > 33%. The correlation between patient survival rates and a range of clinical and pathological variables was examined. Results: Overall, 121 patients were enrolled: 108 with low-LNR (LNR ≤ 33%) and 13 with high-LNR (LNR > 33%). A better 2-year overall survival (OS) (88.5% vs. 32.6%; p < 0.001) and progression-free survival (PFS) (80.2% vs. 23.5%; p < 0.001) were observed in patients with low LNR. A similar result was also found in those with non-pathological complete response group (non-pCR), where the 2-year OS was 87.2% vs. 32.6% (p < 0.001), and the 2-year PFS was 77.7% vs. 23.5% (p < 0.001). Compared to the pathologic lymph nodes staging (ypN), LNR exhibited similar prognostic capabilities for OS and PFS. Multivariate analysis indicated that LNR was an independent prognostic factor for both OS (HR 6.258, 95% CI 1.798–21.778; p = 0.004) and PFS (HR 3.431, 95% CI 1.341–8.780; p = 0.010), but not ypN. Conclusions: LNR may serve as a viable indicator for prognostication in LAGC patients treated with NICT. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer is a significant global malignancy with poor prognosis. Although the emergence of immune checkpoint inhibitors (ICIs) prolonged the duration of survival, resistance and progression are inevitable. We aim to evaluate the effectiveness of programmed death-1 (PD-1) inhibitors in immunotherapy beyond progression (IBP). Method: We divided the advanced gastric cancer patients who received two lines immunotherapy into same regimen group (with same PD-1 inhibitor regime after IBP) and different regimen group (with different PD-1 inhibitor regime after IBP). Statistical analysis conducted to compare patient characteristics and evaluate survival differences between groups. Result: The clinical outcome analysis showed that the same PD-1 inhibitor regime seemed to exhibit a higher disease control rate (DCR) (51.8% vs. 29.2%, P = 0.062), significantly prolonged progression-free survival 2 (PFS2) (162 vs. 75 days, P = 0.001) and overall survival (OS) (312 vs. 166 days, P = 0.022) when compared with those of cross line. In the multivariate analysis, when using different regimen group as reference, the same regimen group was found to be independently associated with improved PFS2 [hazard ratio (HR) = 0.467, 95% confidence interval (CI): 0.267–0.816, P = 0.008] and OS (HR = 0.508, 95%CI: 0.278–0.927, P = 0.027). Conclusion: Continuation of the same type of PD-1 inhibitor regime in IBP shows clinical benefits and represents a promising therapeutic approach. [ABSTRACT FROM AUTHOR]

A 75‐year‐old female was diagnosed with a type 0‐I, moderately differentiated, early gastric carcinoma on the posterior wall of the middle gastric body during esophagogastroduodenoscopy (EGD). Several small whitish structures, referred to as white globe appearances (WGAs), were noted on the oral side outside the demarcation line of the cancerous protrusion. Although this area was flat without cancerous mucosal changes on the surface, subepithelial cancer extension was suspected. The histopathology of the resected specimen revealed that the carcinoma with submucosal invasion had significant lymphatic invasion with submucosal lateral extent along lymphatic vessels. In some areas, the carcinoma within the lymphatic vessels regressed from the submucosal layer towards the mucosal lamina propria, penetrating the muscularis mucosas. The intralymphatic carcinoma reaching just beneath the epithelium was considered to manifest WGA features during endoscopy. [ABSTRACT FROM AUTHOR]