World Journal of Gastroenterology最新文献

{"title":"Dual cut-offs and beyond: Expanding the role of transient elastography in primary biliary cholangitis.","authors":"Vasily Isakov, Alexei Goncharov","doi":"10.3748/wjg.v32.i8.115416","DOIUrl":"https://doi.org/10.3748/wjg.v32.i8.115416","url":null,"abstract":"<p><p>Accurate fibrosis staging is pivotal in the management of primary biliary cholangitis (PBC). Although liver biopsy is considered the diagnostic gold standard, its invasiveness limits widespread use in disease monitoring. Chen <i>et al</i> provided strong evidence validating vibration-controlled transient elastography (VCTE) as a noninvasive alternative for identifying advanced fibrosis in Chinese patients with PBC. By establishing dual cut-offs (≤ 10.0 kPa and > 14.5 kPa) with high diagnostic performance, the authors offer a clinically applicable tool that could substantially reduce the need for biopsy. Nevertheless, challenges persist, including the management of intermediate \"grey zone\" results, technical variability, and the confounding effects of cholestasis and inflammation. The integration of elastography with biochemical and prognostic indices, such as the GLOBE and UK-PBC scores, is essential for individualized care. This editorial discusses the expanding role of VCTE in PBC, current limitations, and future research directions toward standardized, integrated, noninvasive fibrosis assessment, and individualized PBC care.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"32 8","pages":"115416"},"PeriodicalIF":5.4,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12968558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147436218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bridging innovation and clinical reality: Interpreting the comparative study of deep learning models for multi-class upper gastrointestinal disease segmentation.","authors":"Yu-Han Yang","doi":"10.3748/wjg.v32.i8.115297","DOIUrl":"https://doi.org/10.3748/wjg.v32.i8.115297","url":null,"abstract":"<p><p>In this editorial we comment on the article by Chan <i>et al</i>. The study presents the most comprehensive comparative evaluation to date of deep learning models for multi-class segmentation of upper gastrointestinal diseases, leveraging a novel 3313-image, nine-class clinical dataset alongside the public EDD2020 benchmark. Their results demonstrate that hierarchical, pre-trained encoders (notably Swin-UMamba-D) deliver the highest segmentation accuracy, while SegFormer balances accuracy with computational efficiency, an important consideration for clinical deployment. Beyond raw performance metrics, the work confronts core translational barriers: Limited and biased datasets, lighting and imaging variability, boundary ambiguity, and multi-label complexity. This Editorial argues that the manuscript marks a pivotal shift from isolated technical advances toward clinically-minded validation of segmentation systems, and proposes a concrete agenda for the field to accelerate safe, generalizable, and ethically responsible adoption of automated endoscopic assistance.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"32 8","pages":"115297"},"PeriodicalIF":5.4,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12968536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147436229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Xing-Pi-Qing-Gan decoction alleviates alcoholic liver disease by down-regulating <i>DDIT3</i> and restoring <i>Nrf2</i>/<i>HO-1</i> antioxidant signaling: Multi-omics and experimental evidence.","authors":"Na-Fei Huang, Ping Ling, Yu-Jie Xu, Xiao-Feng Feng, Yi Zheng, Tao Sun","doi":"10.3748/wjg.v32.i8.115077","DOIUrl":"https://doi.org/10.3748/wjg.v32.i8.115077","url":null,"abstract":"<p><strong>Background: </strong>Alcoholic liver disease (ALD) is driven by oxidative stress, lipid metabolism, inflammation, and apoptosis. Current therapies lack efficacy in targeting multi-pathway mechanisms. Xing-Pi-Qing-Gan decoction (XPQG) is an improved traditional Chinese medicine designed to alleviate ALD, but its molecular mechanism remains unknown.</p><p><strong>Aim: </strong>To illustrate the therapeutic targets and molecular pathways of XPQG for the treatment of ALD by integrating chemical profiling, network pharmacology, transcriptomics, and experimental verification <i>in vivo</i> and <i>in vitro</i>.</p><p><strong>Methods: </strong>The components of XPQG were analyzed using ultra-high performance liquid chromatography quadrupole-time-of-flight mass spectrometry. Then, the protective effect of XPQG on ethanol-induced liver injury, especially its regulatory effect on <i>DDIT3</i> expression and associated <i>Nrf2</i>/<i>HO-1</i> antioxidant signaling, was investigated through <i>in vivo</i> animal experiments and <i>in vitro</i> cell experiments. A mouse model of ALD was developed, and the mechanism of XPQG was validated through hematoxylin and eosin (H&E) staining, Western blot, and quantitative RT-PCR. In addition, the key role of <i>DDIT3</i> in XPQG-mediated protection was further verified by <i>siDDIT3</i> cell transfection technology. Animal experiments with the reactive oxygen species inhibitor N-acetylcysteine (NAC) further validated the mechanism of XPQG to alleviate liver injury by regulating oxidative stress.</p><p><strong>Results: </strong>In ethanol-treated HepG2 cells, XPQG dose-dependently reduced the formation of lipid droplets, inhibited the expression of tumor necrosis factor-α, interleukin-6, interleukin-1β, and alleviated oxidative stress. In mice, XPQG (15.2 g/kg) lowered the liver/body weight ratio, alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transferase; H&E and Oil Red O demonstrated a reduction in steatosis. Network pharmacology and RNA-seq converged on MAPK signaling, suggesting <i>DDIT3</i> as a likely key effector in XPQG-mediated protection. <i>DDIT3</i> knockdown in HepG2 cells attenuated the benefits of XPQG, supporting <i>DDIT3</i> as a critical effector mechanism in XPQG-mediated protection. The use of NAC further illustrates the correlation of drugs to oxidative stress in disease effects.</p><p><strong>Conclusion: </strong>In summary, the results of the study suggest that XPQG is effective in improving ethanol-induced acute liver injury (ALD). Its mechanism involves the suppression of <i>DDIT3</i> and the enhancement of <i>Nrf2</i>/<i>HO-1</i> pathway activity.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"32 8","pages":"115077"},"PeriodicalIF":5.4,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12968574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147435445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use of yttrium-90 radioembolization to control liver metastases in pancreatic acinar cell carcinoma and pancreatoblastoma: Two case reports.","authors":"Nebojsa Skorupan, David Sperling, Charles Nutting, Markku Miettinen, Allen Cohn, Christine Alewine","doi":"10.3748/wjg.v32.i8.113861","DOIUrl":"https://doi.org/10.3748/wjg.v32.i8.113861","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic acinar cell carcinoma (PACC) and pancreatoblastoma (Pb) are rare exocrine pancreatic malignancies with liver-dominant metastatic patterns and poor prognosis. Limited treatment options exist beyond the extrapolated pancreatic ductal adenocarcinoma regimens. Yttrium-90 (Y-90) radioembolization has demonstrated efficacy in various hepatic malignancies but remains understudied in these rare pancreatic tumors. These cases illustrate the potential role of Y-90 radioembolization in achieving durable hepatic disease control in PACC and Pb patients.</p><p><strong>Case summary: </strong>Case 1: A 62-year-old man with metastatic PACC underwent four Y-90 radioembolizations over 46 months, achieving partial responses after each treatment with sustained disease control exceeding one year without systemic therapy. Case 2: A 78-year-old woman with metastatic Pb following radical pancreaticoduodenectomy received four sequential Y-90 treatments targeting hepatic metastases, demonstrating partial responses to the treated metastases which established ongoing local disease control. Both patients tolerated multiple Y-90 sessions well with minimal complications. The treatments were successfully integrated with systemic therapies and provided meaningful symptom relief. These cases demonstrate the radiosensitivity of these rare malignancies and the feasibility of repeated Y-90 administrations over extended intervals in selected patients.</p><p><strong>Conclusion: </strong>Y-90 radioembolization achieves durable hepatic response in rare pancreatic exocrine malignancies with a favorable safety profile.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"32 8","pages":"113861"},"PeriodicalIF":5.4,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12968565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147435535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting <i>Dialister</i>-driven succinate accumulation: A novel strategy for Crohn's disease activity control and recurrence prevention.","authors":"Sheng Xu, Zheng Zhu, Hui-Ming Zhang, Yue-Ting Xu, Pei-Hong Shi, Yang Zheng, Yi-Tong Chen, Guang-Rong Lu, Bin-Jiao Zheng","doi":"10.3748/wjg.v32.i8.116173","DOIUrl":"10.3748/wjg.v32.i8.116173","url":null,"abstract":"<p><p>Crohn's disease (CD) activity and postoperative recurrence significantly affect patients' quality of life, highlighting the need for new treatment and prevention strategies. We read with interest Boronat-Toscano <i>et al</i>'s study on <i>Dialister</i>-driven succinate accumulation in CD. By analyzing the fecal microbiota, circulating succinate levels, and clinical indices using clinical samples, the researchers explored the roles of <i>Dialister</i> and succinate in CD, a previously unaddressed area. They revealed that active CD is characterized by high succinate levels, which are associated with disease severity and inflammatory indicators. The enrichment of <i>Dialister</i>, linked to impaired succinate clearance and postoperative recurrence, offers new insights. The study identified succinate and <i>Dialister</i> as potential therapeutic targets, advancing understanding of CD pathophysiology and paving the way for further investigations. Future studies should involve large, multicenter cohorts for validation, explore <i>Dialister</i>'s strain-specific metabolic mechanisms, and develop treatments targeting the \"succinate axis\", thus connecting fundamental research with clinical applications.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"32 8","pages":"116173"},"PeriodicalIF":5.4,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12968552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147436200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Primary melanoma of the gastrointestinal tract.","authors":"Paola De Nardi, Stefania Guida, Giuseppe Damiano, Nathalie Rizzo, Ana Maria Samanes Gajate, Silvia Teresa Riva, Giovanni Paolino, Michele Colombo, Roberta Tummineri, Franco Rongioletti, Santo Raffaele Mercuri, Arturo Chiti, Pierpaolo Sileri, Vincenzo Russo","doi":"10.3748/wjg.v32.i8.114571","DOIUrl":"https://doi.org/10.3748/wjg.v32.i8.114571","url":null,"abstract":"<p><p>Primary melanomas of the gastrointestinal tract are rare malignancies, representing less than 2% of all melanomas and 37% of mucosal melanomas. They arise <i>de novo</i> from the mucosal gastrointestinal epithelium, most frequently in the anorectum and esophagus. Their etiology is unclear: Unlike cutaneous melanomas, they are not associated with ultraviolet exposure while genetic predisposition, chronic inflammation, and immune deficiency are among suspected risk factors. They show a relatively low tumor mutational burden with <i>KIT</i> gene mutations being the most common alteration. Symptoms are based on tumor location and may include abdominal pain, bleeding, weight loss, nausea and vomiting, difficulty swallowing in esophageal melanomas, or bowel obstruction. The diagnosis relies on endoscopic studies and cross-sectional imaging. Surgery represents the mainstay of treatment in localized disease and may also provide palliation in more advanced stages. Due to their aggressive nature, adjunctive treatments such as immunotherapy and targeted therapy are often employed while chemotherapy is of limited value. Prognosis is poor, with median survival often below one year in more severe cases. Early detection and novel treatments, including cancer vaccines, immunotherapy combinations, and personalized medicine approaches, are promising to improve survival and quality of life.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"32 8","pages":"114571"},"PeriodicalIF":5.4,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12968566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147436145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peroxiredoxin 1 as a novel pyroptosis inducer in colorectal cancer: Insights and future directions.","authors":"Zi-Ke Chen, Jia-Wei Zhao, Wen-Ying Meng, Yu-Gang Wang","doi":"10.3748/wjg.v32.i8.116016","DOIUrl":"10.3748/wjg.v32.i8.116016","url":null,"abstract":"<p><p>This letter aims to comment on the paper by He <i>et al</i>, which investigated the role and mechanism of peroxiredoxin 1 (Prdx1) in colorectal cancer (CRC). In the original study, Prdx1 messenger RNA and protein levels were significantly increased in 60 clinical samples from CRC patients, <i>in vitro</i> cell experiments (RKO, SW480, HCT116 cells) and subcutaneous xenograft tumor mouse model. Recombinant Prdx1 (rPrdx1) inhibited the malignant behavior of RKO and SW480 cells, which was mechanistically shown to activate the NOD-like receptor thermal protein domain associated protein 3/caspase-1/gasdermin D (GSDMD) pathway to induce pyroptosis. Consequently, this pyroptosis-based anti-tumor activity effectively inhibited the growth of CRC xenografts in mice. We commend the study's scientific validity and innovation, the findings of which warrant further investigation into clinical translation, such as developing Prdx1/GSDMD co-expression markers and exploring rPrdx1-based combination therapies for advancing individualized CRC treatment.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"32 8","pages":"116016"},"PeriodicalIF":5.4,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12968526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147436136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endoscopic ultrasound-guided transhepatic antegrade stone removal for choledocholithiasis after pancreaticoduodenectomy: A case report and review of literature.","authors":"Yu-Ming Li, Aimaiti Yasen, Si-Fang Chen, Jian Fan, Xiao-Bing Huang, Guo-Hua Zuo, Lu Zheng","doi":"10.3748/wjg.v32.i8.116856","DOIUrl":"https://doi.org/10.3748/wjg.v32.i8.116856","url":null,"abstract":"<p><strong>Background: </strong>The special choledocholithiasis (common hepatic duct stone) proximal to hepaticojejunostomy anastomosis following pancreaticoduodenectomy (PD) presents significant therapeutic challenges because of surgically altered anatomy, which precludes the use of conventional endoscopic retrograde cholangiopancreatography. Endoscopic ultrasound (EUS) offers a minimally invasive alternative for antegrade stone extraction. Here, we report a rare case of EUS-guided transhepatic antegrade stone removal (EUS-TASR) in a patient with choledocholithiasis occurring eleven years after PD.</p><p><strong>Case summary: </strong>A 58-year-old male with a history of PD for a duodenal tumor eleven years prior presented with a three-month history of intermittent upper abdominal discomfort. Imaging revealed a nodular filling defect in the common hepatic duct and mild intrahepatic biliary dilatation, confirming choledocholithiasis. Given the altered anatomy, endoscopic retrograde cholangiopancreatography was deemed unfeasible; thus, EUS-TASR with endoscopic nasobiliary drainage was successfully performed. The endoscopic nasobiliary drainage tube was removed on postoperative day 7, and the patient was discharged in stable condition on postoperative day 8. At the ten-month follow-up, the patient remained asymptomatic without complications.</p><p><strong>Conclusion: </strong>EUS-TASR is a viable, minimally invasive approach for managing choledocholithiasis in post-PD patients with altered anatomy where conventional endoscopic access is restricted.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"32 8","pages":"116856"},"PeriodicalIF":5.4,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12968530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147436224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progression after endoscopic treatment for type I gastric neuroendocrine tumors: A single-center retrospective study.","authors":"Ze-Liang Yang, Hui-Ke Wang, Yong Liu, Li-Zhou Dou, Yue-Ming Zhang, Hoi-Ioi Ng, Shun He, Yihe-Bali Chi, Gui-Qi Wang","doi":"10.3748/wjg.v32.i8.114268","DOIUrl":"https://doi.org/10.3748/wjg.v32.i8.114268","url":null,"abstract":"<p><strong>Background: </strong>Endoscopic treatment is the primary therapy for type I gastric neuroendocrine tumors (G-NETs), but it may not address the underlying pathogenesis, increasing the risk of progression.</p><p><strong>Aim: </strong>To investigate the effectiveness of endoscopic treatment and identify progression risk factors.</p><p><strong>Methods: </strong>This retrospective study involved 128 patients with type I G-NETs treated between January 2009 and May 2024. The patients were categorized into non-progressive (<i>n</i> = 87) and progressive (<i>n</i> = 41) groups. Baseline characteristics, treatment details, and follow-up data were analyzed using univariate and multivariate Cox regression analyses to identify prognostic variables.</p><p><strong>Results: </strong>The baseline characteristics analysis showed no significant differences between the groups. The median follow-up time was 25.5 months (14.00-58.50 months). The univariate and multivariate analyses confirmed that endoscopic treatment combined with adjuvant somatostatin analogs (SSAs) was associated with a lower risk of progression (hazard ratio = 0.38, 95% confidence interval: 0.17-0.90, <i>P</i> = 0.027), whereas a neutrophil-to-lymphocyte ratio (NLR) of ≥ 2 indicated a higher risk (hazard ratio = 2.14, 95% confidence interval: 1.08-4.26, <i>P</i> = 0.030). Kaplan-Meier analysis confirmed NLR ≥ 2 and adjuvant SSA use as independent prognostic variables.</p><p><strong>Conclusion: </strong>Combining endoscopic treatment with SSAs is effective for managing type I G-NETs. SSAs and NLR were identified as independent prognostic factors, highlighting their potential to reduce recurrence risk and improve outcomes.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"32 8","pages":"114268"},"PeriodicalIF":5.4,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12968573/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147436227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Wogonin derivative V8 enhances bortezomib efficacy in gastric carcinoma by disrupting lysosome-mediated drug resistance.","authors":"Si-Chan Li, Shun-Zi Shao, Yu-Hang Zhang, Yu Zhou, Wen-Tao Shang, Yuan Gao, Qi-Bin He, Qing-Long Guo, Chuan-Yong Guo, Xiao-Bo Zhang","doi":"10.3748/wjg.v32.i8.113299","DOIUrl":"https://doi.org/10.3748/wjg.v32.i8.113299","url":null,"abstract":"<p><strong>Background: </strong>Bortezomib (BTZ) is ineffective in gastric carcinoma (GC) due to lysosome-mediated resistance. Wogonin derivative V8 targets lysosomes.</p><p><strong>Aim: </strong>To address the limited efficacy of BTZ in GC and explore whether wogonin derivative V8 enhances anti-GC effects by overcoming lysosome-mediated resistance.</p><p><strong>Methods: </strong><i>In vitro</i> experiments used four human GC cell lines (MGC-803, BGC-823, AGS, and HGC-27) to assess cell viability (cell counting kit-8), lysosomal function (LysoSensor staining), autophagy (western blotting for light chain 3/p62), and drug synergy [combination index (CI)]. Liquid chromatography/mass spectrometry measured intracellular BTZ concentration. Transcription factor EB (TFEB), a master regulator of lysosomal and autophagy genes, was investigated using small interfering RNA silencing and plasmid overexpression. <i>In vivo</i> efficacy/safety was tested in MGC-803 xenograft nude mice, and patient-derived tumor organoids (PDOs) validated clinical relevance.</p><p><strong>Results: </strong>BTZ was trapped in GC cell lysosomes, reducing its proteasome accessibility and inducing resistance; lysosome number correlated positively with the half-maximal inhibitory concentration of BTZ. V8 induced lysosomal damage/deacidification, increasing intracellular BTZ availability. V8 + BTZ synergistically inhibited GC cell growth (CI < 1), upregulated proteotoxic stress markers (<i>ATF4</i>, immunoglobulin heavy chain binding protein) and apoptotic mediators (cleaved caspase-3). TFEB knockdown enhanced V8 + BTZ cytotoxicity, whereas its overexpression reduced cell death, indicating a protective role of TFEB in gastric cancer cells. In xenografts, V8 + BTZ significantly reduced tumor volume/weight (<i>P</i> < 0.01) without organ toxicity. PDOs showed enhanced sensitivity to V8 + BTZ <i>vs</i> monotherapy.</p><p><strong>Conclusion: </strong>Lysosomes mediate BTZ resistance in GC; V8 overcomes this by disrupting lysosomes, enabling BTZ to target proteasomes. V8 + BTZ is a safe, effective strategy against GC.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"32 8","pages":"113299"},"PeriodicalIF":5.4,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12968567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147435484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}