Journal of gastrointestinal oncology最新文献

{"title":"Efficacy and safety of camrelizumab in combination with S-1 plus oxaliplatin sequenced by camrelizumab-based maintenance therapy as a first-line treatment for advanced gastric or gastroesophageal junction adenocarcinoma: a retrospective cohort study.","authors":"Wan-Ren Peng, Fei Zhang, Wen-Wen Ma, Jie Da, Han-Qing Yu, Lu-Lu Fan, Zhen-Ya Jia, Jing Xu, Zi-Cong Gao, Chang-Chun Shao, Guo-Ping Sun","doi":"10.21037/jgo-2025-189","DOIUrl":"10.21037/jgo-2025-189","url":null,"abstract":"<p><strong>Background: </strong>S-1 plus oxaliplatin (SOX) is a first-line standard-of-care treatment for patients with advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. Programmed cell death protein 1 (PD-1) inhibitors plus chemotherapy, including SOX have also shown promising outcomes in such patients. This study was performed to evaluate the efficacy and safety of camrelizumab plus SOX sequenced by camrelizumab-based maintenance therapy as a first-line treatment for advanced G/GEJ adenocarcinoma.</p><p><strong>Methods: </strong>In total, 31 patients with an age of 18 years or older and newly diagnosed with human epidermal growth factor receptor 2 (HER2)-negative advanced G/GEJ adenocarcinoma who underwent camrelizumab in combination with SOX followed by camrelizumab plus S-1 from February 2020 to December 2023 were enrolled in the study. All patients were regularly followed up every 1-2 months. The primary endpoint of the study was progression-free survival (PFS). And the safety profiles were also assessed.</p><p><strong>Results: </strong>As of December 31, 2023, 25 male and 6 female patients were enrolled. The median follow-up time was 14.6 months. The median PFS time of the patients treated with the combination regimen was 7.3 months [95% confidence interval (CI): 3.0-11.6]. In addition, the median overall survival (OS) time was 13.3 months (95% CI: 10.3-16.4), and the median duration of response (DoR) was 5.0 months (95% CI: 2.0-8.1). Moreover, the objective response rate (ORR) and disease control rate (DCR) were 71.0% and 87.1%, respectively. Further, the most commonly observed grade ≥3 adverse events (AEs) were increased gamma-glutamyltransferase (GGT) (9.7%) and a decreased neutrophil count (6.5%). No treatment-related deaths occurred.</p><p><strong>Conclusions: </strong>First-line treatment with camrelizumab in combination with SOX sequenced by camrelizumab-based maintenance therapy demonstrated favorable outcomes for and was well tolerated by patients with advanced G/GEJ adenocarcinoma. Thus, it might serve as a first-line standard-of-care treatment for such patients. However, prospective randomized studies should be carried out to confirm the findings.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 2","pages":"342-353"},"PeriodicalIF":2.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The highly expressed <i>GOLPH3</i> in colorectal cancer cells activates smoothened to drive glycolysis and promote cancer cell growth and radiotherapy resistance.","authors":"Kunli Zhu, Jing Fan, Hongchao Cai, Changchun Zhou, Zhe Gong, Zhenxiang Li, Jinming Yu","doi":"10.21037/jgo-2025-193","DOIUrl":"10.21037/jgo-2025-193","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is a frequently diagnosed cancer across the world and has increased in prevalence over the last decade. This study aimed to assess the biological roles, influences on radiosensitivity, and possible molecular mechanism of Golgi phosphoprotein 3 (<i>GOLPH3</i>) in CRC.</p><p><strong>Methods: </strong>Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), and immunohistochemistry (IHC) were used to examine GOLPH3 expression. <i>In vivo</i> and <i>in vitro</i> assays were carried out to clarify the function of <i>GOLPH3</i> in CRC. The differentially expressed genes (DEGs) in CRC cells with knockdown of <i>GOLPH3</i> were identified through RNA sequencing (RNA-seq). Based on the DEGs associated with <i>GOLPH3</i> knockdown and the data from The Cancer Genome Atlas (TCGA) database, the pathways that could be regulated by <i>GOLPH3</i> were predicted via Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis.</p><p><strong>Results: </strong>In CRC, <i>GOLPH3</i> was upregulated, and <i>GOLPH3</i> upregulation was predictive of a poor prognosis. <i>GOLPH3</i> knockdown inhibited CRC cell proliferation, migration, and invasion but promoted apoptosis and reduced radiotherapy resistance. Conversely, in CRC cells with <i>GOLPH3</i> overexpression, malignant biological behavior and radiotherapy resistance were enhanced. <i>In vivo</i>, <i>GOLPH3</i> knockdown impeded tumor growth. Mechanistically, <i>GOLPH3</i> promoted the localization of smoothened (SMO) on the cell membrane, thereby activating AMP-activated protein kinase (AMPK)-mediated glycolysis. Additionally, the final product of glycolysis, lactate, induced H3 lysine 18 lactylation (H3K18), which could be enriched on the promoter of <i>GOLPH3</i> and stimulate the transcription of <i>GOLPH3</i>.</p><p><strong>Conclusions: </strong><i>GOLPH3</i> promoted CRC progression and enhanced radiotherapy resistance via glycolysis mediated by the SMO-AMPK axis.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 2","pages":"415-434"},"PeriodicalIF":2.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using an indocyanine green fluorescent imaging technique for laparoscopic rectal cancer surgery: a case report.","authors":"Youqiang Liu, Songjie Li, Zhenya Zhang, Chenhui Li, Pengwei Li, Hongqing Ma, Guiying Wang","doi":"10.21037/jgo-2025-245","DOIUrl":"10.21037/jgo-2025-245","url":null,"abstract":"<p><p>Colorectal cancer is a clinically common malignancy with high incidence and mortality rates. Surgery remains the preferred treatment option for colorectal cancer. Laparoscopic surgery is more widely used than open surgery due to its advantages of reduced surgical trauma and faster postoperative recovery. However, complications such as anastomotic leakage, bleeding, intestinal obstruction, and intra-abdominal infections can still occur, prolonging hospital stays and impairing patient recovery. In particular, anastomotic leakage is a severe complication that significantly affects the postoperative recovery of patients. Indocyanine green (ICG) fluorescence imaging (FI) combined with 4K laparoscopy has emerged as a promising approach for enhancing surgical quality. ICG is a water-soluble tricarbocyanine dye with low toxicity, a strong binding affinity to plasma proteins, and a short half-life, making it suitable for intraoperative use. It enables the real-time visualization of blood flow, which facilitates the detection of metastases, the assessment of anastomotic perfusion, and precise lymph node dissection. This technology has been shown to improve the detection of positive lymph nodes and reduce postoperative complications. We report the case of a 66-year-old male patient with rectal adenocarcinoma who underwent fluorescent laparoscopy-assisted radical resection of rectal cancer (Dixon procedure). The patient initiated ambulation on postoperative day (POD) 1, followed by successful flatus passage and bowel movement initiation on POD 2, and was discharged on POD 6 after the removal of the pelvic drain. This article highlights the application techniques and advantages of ICG-FI laparoscopic technology in rectal cancer surgery to provide a reference for its clinical application.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 2","pages":"766-777"},"PeriodicalIF":2.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential metastatic mechanisms and clinical aspects in patients with non-gastrointestinal tumor metastasis to the upper gastrointestinal tract.","authors":"Magnus Sundbom","doi":"10.21037/jgo-2025-102","DOIUrl":"10.21037/jgo-2025-102","url":null,"abstract":"","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 2","pages":"786-790"},"PeriodicalIF":2.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Bacillus velezensis</i> inhibits azoxymethane/dextran sulphate sodium induced colitis associated colorectal cancer via the small molecule <i>HeLM</i>.","authors":"Edward Horwell, Charlotte Freer-Smith, Huynh A Hong, Philip Bearn, Simon M Cutting","doi":"10.21037/jgo-24-610","DOIUrl":"10.21037/jgo-24-610","url":null,"abstract":"<p><strong>Background: </strong>Ulcerative colitis (UC) is a chronic inflammatory condition of the colon. There is a direct correlation between the severity and chronicity of colitis and subsequent risk of colitis associated colorectal cancer (CAC). We have recently shown that a strain of <i>Bacillus velezensis</i> (EHv5) can ameliorate colonic inflammation in the acute setting. This was found to be mediated via the secondary metabolite <i>HeLM</i> and its multifactorial interactions on Toll-like receptors. It is yet to be seen if sustained administration will alleviate colitis over a prolonged period and reduce the risk of CAC. This study will examine the therapeutic potential of EHv5 in ameliorating UC in the chronic setting and assess its ability to prevent CAC.</p><p><strong>Methods: </strong>CAC was induced in mice (BALB/c) by the administration of intraperitoneal azoxymethane (AOM) and chronic colitis by multiple cycles of dextran sulphate sodium (DSS). Mice were divided into four groups: (I) a negative control; (II) a positive control; (III) the treatment arm receiving <i>EHv5</i>; and (IV) an isogenic mutant of <i>EHv5</i> that does not produce HeLM, but is otherwise identical. Colitis was assessed throughout the experiment using clinical, biochemical, and endoscopic assessments. A novel scoring system was devised, the chronic colitis associated cancer activity index (CACI) and is compared to the established Disease Activity Index (DAI). Faecal blood and serum haematinics were assessed for iron deficiency anaemia. Tumorigenesis was measured at multiple time points endoscopically and histologically at the end of the experiment.</p><p><strong>Results: </strong>Compared to the positive control, there was a significant reduction in both the severity and chronicity of colitis in the group receiving <i>EHv5</i> as measured clinically, endoscopically and with faecal calprotectin. This translated to a significant reduction in both the number and grade of tumours-20% of the group receiving treatment developed tumours of any grade, compared to 80% in the positive control. The CACI score was more reflective to the severity of colitis as the experiment progressed than DAI.</p><p><strong>Conclusions: </strong><i>EHv5</i> provides sustained amelioration of chronic inflammation in a murine model of UC. Strikingly, the effect is such that it significantly reduces the risk of CAC tumour development. This protective effect was not seen in the isogenic mutant, confirming HeLM to be the mechanistic mediator of this beneficial effect.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 2","pages":"470-484"},"PeriodicalIF":2.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"D3 lymph node dissection improves perioperative outcomes and overall survival in patients with cT2N0 colorectal cancer.","authors":"Bolun Song, Liming Wang, Yinggang Chen, Yasumitsu Hirano","doi":"10.21037/jgo-2024-980","DOIUrl":"10.21037/jgo-2024-980","url":null,"abstract":"<p><strong>Background: </strong>The extent of lymphadenectomy undertaken in patients with cT2N0 colorectal cancer (CRC) remains controversial. The aim of our study was to compare survival in such patients by level of lymph node dissection (LND) performed.</p><p><strong>Methods: </strong>This retrospective cohort study was conducted at a high-volume cancer center in Japan. Eligible patients (n=524) submitted to radical resections for cT2N0 CRC between April 2007 and December 2020 were included. Subjects were subsequently stratified by nature of LND (D2 <i>vs.</i> D3) and propensity score matched at 1:2 ratio. We then analyzed group rates of overall survival (OS) and relapse-free survival (RFS) before and after matching.</p><p><strong>Results: </strong>Before matching, the D3 (<i>vs.</i> D2) LND group experienced a shorter mean operative time, less intraoperative blood loss, fewer postoperative complications, and a briefer average hospital stay, showing significantly better OS (P=0.001) as well. The estimated hazard ratio (HR) was 2.0 [95% confidence interval (CI): 1.0-3.9; P=0.04]. After matching, a significant difference in OS (P=0.007) was still observed, with an estimated HR of 2.3 (95% CI: 1.0-5.1; P=0.044).</p><p><strong>Conclusions: </strong>D3 LND improves perioperative outcomes and OS in patients with cT2N0 CRC. Accurate preoperative imaging diagnostics are critical for proper surgical management for cT2N0 CRC.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 2","pages":"517-527"},"PeriodicalIF":2.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-omics analyses develop and validate the optimal prognostic model on overall survival prediction for resectable hepatocellular carcinoma.","authors":"Ying Han, Ajuan Zeng, Xueying Liang, Yingying Jiang, Fenglin Wang, Lele Song","doi":"10.21037/jgo-24-710","DOIUrl":"10.21037/jgo-24-710","url":null,"abstract":"<p><strong>Background: </strong>Prediction of prognosis in patients with hepatocellular carcinoma (HCC) by single-omics profiling has been widely studied. However, the prognosis related to biomarkers of multiple omics has not been investigated. We aimed to establish and validate a prediction model for prognosis prediction of resectable HCC combining multi-omics and clinicopathological factors.</p><p><strong>Methods: </strong>The training cohort involved multi-omics data of 330 patients with resectable HCC (stage I-IIIA) at mutational, copy number variation (CNV), transcriptional, and methylation levels from The Cancer Genome Atlas (TCGA) database, along with clinicopathological information. The validation cohort involved samples from 40 HCC patients of Beijing Youan Hospital. Univariate and multivariate analyses were performed in single-omics with clinicopathological variables regarding patient prognosis, and independent risk factors were combined to establish the multi-omics model. The predictive accuracy was assessed by the receiver operating characteristic (ROC) method.</p><p><strong>Results: </strong>The mutational, copy number, transcriptional, and methylation alterations in HCC were characterized. <i>TP53</i>, <i>CTNNB1</i>, and <i>TTN</i> were among the genes with the top mutational frequency, and <i>FBN1</i> and <i>MAP1B</i> mutations were independent risk factors for patient overall survival (OS). 1q21.3 and 1q23.3 ranked the highest in copy number amplifications, and 8p12 and 8p23.3 ranked the highest in deletions, and <i>CSMD1</i>, <i>TP53</i>, and <i>RB1</i> were genes with the most frequent CNVs. <i>AFP</i>, <i>GPC3</i>, and <i>TERT</i> were among genes with the most significant aberrant transcription, and the transcription of <i>CCNJL</i>, <i>FRMD1</i>, and <i>GRPEL2</i> were independent risk factors for OS. Both hypermethylation and hypomethylation can be observed. The aberrant methylation of <i>CXorf15</i>, <i>DACT2</i>, <i>GP6</i>, <i>KIAA1522</i>, and <i>PDIA3</i> were independent risk factors. Single-omics models were established with independent risk factors, and were validated by internal and external datasets. A prognostic model for OS with multi-omics independent risk factors and clinicopathlogical information was established. Internal and external validation achieved an optimal maximal area under the curve (AUC) of 0.98 at 1 year and 0.88 at 2 years, respectively.</p><p><strong>Conclusions: </strong>A multi-omics model combining molecular aberrancies and clinicopathological information was established and proved to be optimal for prognosis prediction of resectable HCC. This model may be helpful for therapeutic strategy selection and survival assessment.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 2","pages":"628-649"},"PeriodicalIF":2.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Claudin 18 immunohistochemistry in cholangiocarcinoma.","authors":"Niyati Desai, Huaibin M Ko, Michael Lee, Ladan Fazlollahi, Ryan H Moy, Sam S Yoon, Helen Remotti, Brynn Levy, Andrew T Turk, Stephen M Lagana","doi":"10.21037/jgo-2024-925","DOIUrl":"10.21037/jgo-2024-925","url":null,"abstract":"<p><strong>Background: </strong>Monoclonal antibodies against claudin (CLDN) 18.2 (a component of tight junctions) in gastric epithelial cells are an emerging therapeutic option for patients with advanced gastric and esophageal adenocarcinoma. Phase 2 and 3 trials have shown clinical efficacy in patients whose tumors show high expression of CLDN18 by immunohistochemistry, and the US Food and Drug Administration has recently approved a drug for patients with advanced gastric and gastroesophageal adenocarcinoma and high CLDN18 expression. Adenocarcinoma of the bile ducts, a.k.a. cholangiocarcinoma (CCA), may share morphologic and immunophenotypic qualities with gastric adenocarcinoma, and are lethal tumors with limited therapeutic options. The purpose of this study was to determine if primary tumors of the bile ducts show expression of CLDN18 with the use of a monoclonal antibody to CLDN18, and if so, if the extent of expression is similar to that seen in the gastric and esophageal tumors of patients who responded to anti-CLDN18.2 therapeutics.</p><p><strong>Methods: </strong>Tissue microarrays containing 41 intrahepatic cholangiocarcinomas, 36 hilar cholangiocarcinomas, and 28 distal bile duct cholangiocarcinomas were stained with a monoclonal antibody which detects CLDN18 (Ventana 43-14A). The percentage of tumor cells staining and intensity was recorded for each case with tumors with 75% of cells showing moderate to strong intensity being considered high expressers.</p><p><strong>Results: </strong>High expression was seen in 14.63% of intrahepatic, 8.3% of hilar, and 17.8% of distal bile duct cholangiocarcinomas. Overall, 13.33% of CCAs expressed CLDN18 to an extent which would qualify for treatment in the gastric and esophageal trials.</p><p><strong>Conclusions: </strong>Given the poor prognosis and current lack of therapeutic options, trials of anti-CLDN18.2 inhibitors could be considered in patients with CCA and high expression of CLDN18 by immunohistochemistry.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 2","pages":"671-678"},"PeriodicalIF":2.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Lacticaseibacillus casei</i> 393 modulates KRAS and APC expression and cytokine levels in colitis-associated colon cancer.","authors":"Anne Santerre, María Del Rosario Huizar-López, Jaime Coronilla-Martínez, Pablo Cesar Ortiz-Lazareno, Josefina Casas-Solís","doi":"10.21037/jgo-24-667","DOIUrl":"10.21037/jgo-24-667","url":null,"abstract":"<p><strong>Background: </strong>Colitis-associated colon cancer (CAC) is a specific subset of colorectal cancer (CRC) affecting patients with inflammatory bowel diseases (IBDs). Chronic colon inflammation orchestrates immune surveillance or escape and may drive neoplastic initiation and progression. <i>Lacticaseibacillus casei</i> 393 (<i>L. casei</i> 393) is a lactic acid microorganism that, beyond its nutritional value, provides health benefits. To explore the therapeutic potential of this probiotic against CAC, we evaluated colon histopathology, circulating cytokines, and the expression of the Kristen rat viral sarcoma oncogene homolog (KRAS) and the adenomatosis polyposis coli (APC) tumor-suppressing gene in the murine model of CAC induced with azoxymethane (AOM) and dextran sodium sulfate (DSS).</p><p><strong>Methods: </strong>BALB/c mice (n=7/group) received two doses of AOM (10 mg/kg body weight) followed by three 5-day cycles of 2% DSS. <i>L. casei</i> 393 was administered orally [1×10⁶ colony forming units (CFU)/100 µL/mouse/twice a week/6 months] either alone, before AOM-DSS, or starting at the same time as AOM-DSS. Colon histopathology was assessed by hematoxylin-eosin staining, circulating cytokines by flow cytometry, and the expression of colonic KRAS and APC by quantitative reverse transcription polymerase chain reaction (RT-qPCR).</p><p><strong>Results: </strong>AOM-DSS induced CAC in BALB/c mice, which presented severe colon damage, high cytokine levels, and altered KRAS and APC expression. Conversely, <i>L. casei</i> 393 ingestions, starting at the same time as CAC induction, restored colon architecture and modulated cytokine levels and gene expression.</p><p><strong>Conclusions: </strong>The present experimental work supports the therapeutic potential of <i>L. casei</i> 393 against CAC, as it shows that its ingestion restored the damaging effect of AOM-DSS through its anti-inflammatory properties that helped modulate KRAS and APC mRNA expression.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 2","pages":"568-579"},"PeriodicalIF":2.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Primary gastric squamous cell carcinoma in a young adult with immunotherapy complications: a case report.","authors":"Yu-Han Chen, Bowon Joung, Dani Ran Castillo, Gagandeep Brar","doi":"10.21037/jgo-2024-884","DOIUrl":"10.21037/jgo-2024-884","url":null,"abstract":"<p><strong>Background: </strong>Primary gastric squamous cell carcinoma (GSCC) is a rare and aggressive malignancy, accounting for less than 0.1% of all gastric cancers. Its clinical presentation and management remain a challenge due to the lack of standardized treatment protocols and limited understanding of its molecular profile.</p><p><strong>Case description: </strong>We report the case of a 33-year-old male presented with significant weight loss, severe acid reflux, and progressive subcutaneous masses. Diagnostic imaging and biopsies confirmed stage IV GSCC, with no evidence of other potential metastatic origins. Genetic analysis revealed pathogenic variants in the phosphatase and tensin homolog gene (PTEN), ataxia telangiectasia mutated gene (ATM), and Fanconi anemia, complementation group M (FANCM), along with intermediate tumor mutational burden (TMB). The patient was treated with a combination of leucovorin calcium, fluorouracil, and oxaliplatin (FOLFOX) chemotherapy and nivolumab. Despite aggressive treatment, the patient experienced rapid disease progression and severe thrombocytopenia likely resulting from multifactorial causes, including severe sepsis, liver dysfunction, chemotherapy effects, tumor progression, and possible immune checkpoint inhibitor-related thrombocytopenia (irTCP). The severe complications led to death following palliative extubation.</p><p><strong>Conclusions: </strong>This case highlights the complexity of diagnosing and managing GSCC, especially in younger patients. Identifying genetic alterations provides valuable insights into the disease's molecular profile. Further research is needed to develop effective and standardized treatment strategies for this rare malignancy.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 2","pages":"743-749"},"PeriodicalIF":2.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}