World Journal of Gastrointestinal Oncology最新文献

{"title":"Bidirectional relationship between depression and the risk and prognosis of gastric cancer.","authors":"Zhe Chen, Ting-Jie Gong, Lu Zhao","doi":"10.4251/wjgo.v17.i12.113272","DOIUrl":"10.4251/wjgo.v17.i12.113272","url":null,"abstract":"<p><p>Gastric cancer (GC) is a highly prevalent and life-threatening malignant tumor worldwide, posing a serious threat to human health. Depression is also highly prevalent among patients with GC. A complex bidirectional relationship exists between the two. A total of 52 articles were included in this study to synthesize the evidence on the association between depression and the risk of GC as well as the prognosis of affected patients. The findings indicated that depression can activate the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis, promote the release of catecholamine neurotransmitters, and influence the proliferation, invasion, and metastasis of GC through signaling pathways such as the β2-adrenergic receptor. Furthermore, the severity of depression is positively correlated with indicators of GC progression. At the same time, GC can induce or aggravate depression through psychological and cognitive factors, social environment interactions, and diverse pathophysiological mechanisms, including tumor biological characteristics, treatment-related damage, and metabolic disorders. These interactions form a vicious cycle. This minireview summarizes the existing evidence and provides a theoretical basis for clinical interventions aimed at improving treatment outcomes and quality of life in patients with GC.</p>","PeriodicalId":23762,"journal":{"name":"World Journal of Gastrointestinal Oncology","volume":"17 12","pages":"113272"},"PeriodicalIF":2.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12754319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145890104","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":"Clinical characteristics of colorectal polyps in patients with non-alcoholic fatty liver disease in high altitude areas.","authors":"Chun-Yan Wang, Lin Ma, Ying Zhao, Xiao-Jiang Zhang, Shuang Li, Yong-Gang Liu, Hai-Ming Guo, Jun-Guo Qi, Jian-Quan Wang, Wei-Xin Ye, Jian-Zhou Li, Tao Zhang","doi":"10.4251/wjgo.v17.i12.112761","DOIUrl":"10.4251/wjgo.v17.i12.112761","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Colorectal cancer has high global incidence and mortality rates. Colorectal polyps are relatively common, with adenomatous polyps having a higher risk of malignant transformation. Non-alcoholic fatty liver disease (NAFLD) has been identified as a risk factor for the development of colorectal adenomas. Here, inpatients with NAFLD from the Second People's Hospital of Xining, in Qinghai Province, and the Second People's Hospital of Tianjin were investigated, comparing the biochemical indicators, colonoscopy findings, and pathological results of polyps between patients from low-altitude (Tianjin) and high-altitude (Qinghai Province) areas. Risk factors associated with the occurrence of adenomatous polyps in NAFLD patients from high-altitude areas were also explored.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Aim: &lt;/strong&gt;To investigate the clinical characteristics of colorectal polyps in NAFLD patients from high-altitude areas.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A total of 848 patients with NAFLD were enrolled. Of these, 118 underwent colonoscopy between January 2021 and January 2024 at the Second People's Hospital of Tianjin (low-altitude), while the remaining 730 patients were assessed during the same period at the Second People's Hospital of Xining, Qinghai (high-altitude). All enrolled patients met the diagnostic criteria for NAFLD, and the excised colorectal polyps were analyzed pathologically.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Colorectal polyps were found in 585 cases (80.1%) in the Qinghai cohort and 91 patients (77.1%) in the Tianjin group, indicating a slightly higher incidence in the Qinghai group, although the difference was non-significant (&lt;i&gt;P&lt;/i&gt; = 0.449, &lt;i&gt;P&lt;/i&gt; &gt; 0.05). The two groups showed no significant difference in sex (&lt;i&gt;P&lt;/i&gt; = 0.153, &lt;i&gt;P&lt;/i&gt; &gt; 0.05) but differed significantly in the proportion of younger patients (&lt;i&gt;P&lt;/i&gt; &lt; 0.01), although no differences were seen in terms of middle-aged and elderly patients (&lt;i&gt;P&lt;/i&gt; &gt; 0.05). No differences in polyp numbers were observed between the two regions (&lt;i&gt;P&lt;/i&gt; &gt; 0.05), while significant differences were found between the ≤ 0.5 cm and &gt; 1 cm and ≤ 2 cm proportions in both regions (&lt;i&gt;P&lt;/i&gt; &lt; 0.05), with no differences in other size categories (&lt;i&gt;P&lt;/i&gt; &gt; 0.05). Polyp locations (proximal colon, distal colon) also differed significantly (&lt;i&gt;P&lt;/i&gt; &lt; 0.05). Patients in Qinghai were more prone to adenomatous polyps, accounting for 89.2% of polyps, compared to those from Tianjin (&lt;i&gt;P&lt;/i&gt; &lt; 0.05). Patients in Qinghai had a higher incidence of tubular adenomas with low-grade dysplasia, while tubular adenomas with high-grade dysplasia predominated in patients from Tianjin (&lt;i&gt;P&lt;/i&gt; &lt; 0.05). Patients in Tianjin had a significantly higher proportion of mixed hyperplastic-adenomatous polyps (&lt;i&gt;P&lt;/i&gt; &lt; 0.05), as well as greater proportions of mixed hyperplastic-adenomas with low-grade dysplasia (&lt;i&gt;P&lt;/i&gt; &lt; 0.05). The incidence of hyperplastic polyps was markedly higher in Tianjin, accounti","PeriodicalId":23762,"journal":{"name":"World Journal of Gastrointestinal Oncology","volume":"17 12","pages":"112761"},"PeriodicalIF":2.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12754325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888863","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":"miR-136: A biomarker in the inflammation-cancer transformation of gastric cancer.","authors":"Hao Lyu, Jia-Si Chen, Jing-Feng Tang, Ce-Fan Zhou","doi":"10.4251/wjgo.v17.i12.114173","DOIUrl":"10.4251/wjgo.v17.i12.114173","url":null,"abstract":"<p><p>The study by Chen <i>et al</i> found that miR-136 plays an indispensable role in the inflammation-cancer transformation in gastric cancer (GC). The authors conducted <i>in vivo</i> and <i>in vitro</i> experiments and verified them in conjunction with functional and molecular mechanisms. Their key findings indicate that <i>Helicobacter pylori</i> (<i>H. pylori</i>) activated NF-κB/miR-136/PDCD11 axis to induce the growth of <i>H. pylori</i>-positive GC tumors. And miR-136 is markedly associated with characteristics related to the gastric mucosal histopathological, supporting its use as a diagnostic biomarker and a therapeutic target for early <i>H. pylori</i>-induced GC. Chronic inflammation is one of the important precancerous lesions. With the development of emerging technologies such as multi-omics technology, the pathways linking chronic inflammation to cancer have been extensively elucidated. In this letter, we focus on introducing the molecular mechanisms of chronic inflammation in the development of GC, which will provide new insights for early diagnosis, personalized treatment, and prognosis assessment of GC.</p>","PeriodicalId":23762,"journal":{"name":"World Journal of Gastrointestinal Oncology","volume":"17 12","pages":"114173"},"PeriodicalIF":2.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12754305/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145889991","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":"Pancreatic neuroendocrine microtumors in the elderly: A retrospective study using cadaveric pancreatic tissue.","authors":"Ting Yang, Ke Ren, Xiang-Quan Chen, Taku Toriumi, Yutaro Natsuyama, Jun Li, Aoi Sukeda, Toshitaka Nagao, Shuang-Qin Yi","doi":"10.4251/wjgo.v17.i12.113198","DOIUrl":"10.4251/wjgo.v17.i12.113198","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic neuroendocrine microtumors (PNEMTs) are small (< 5 mm), non-functioning, well-differentiated neuroendocrine neoplasms. Although they are rare, they are not invariably benign. PNEMTs are typically discovered incidentally during autopsy. However, data regarding the occurrence of PNEMTs in the elderly population, particularly those identified incidentally in cadaveric studies, remain limited.</p><p><strong>Aim: </strong>To investigate the prevalence and histopathological characteristics of PNEMTs in elderly individuals by analyzing cadaveric pancreatic tissues.</p><p><strong>Methods: </strong>We conducted a retrospective analysis of 85 pancreatic specimens (age range: 58-109 years) obtained from cadavers for anatomical education and research at the Department of Life Dentistry, Nippon Dental University. Paraffin sections of the pancreatic head, body, and tail were prepared for histological and immunohistochemical analysis.</p><p><strong>Results: </strong>Five cases with PNEMTs (5/85, 5.9%; male, <i>n</i> = 33; female, <i>n</i> = 52; mean age: 85.8 ± 12.1 years) were identified. The tumors were solitary, well circumscribed, and located within the pancreatic parenchyma (body: <i>n</i> = 4; tail: <i>n</i> = 1), and all were < 5 mm (range: 0.54-2.20 mm) in size. All tumors showed strong chromogranin A and synaptophysin positivity, and were predominantly glucagon (GLU)-positive. Ki-67 immunostaining indicated minimal proliferative activity; therefore, these tumors were considered non-functioning, GLU-producing, well-differentiated grade 1 PNEMTs.</p><p><strong>Conclusion: </strong>Small, predominantly low-grade, GLU-secreting PNEMTs were present in 5.9% of elderly individuals, highlighting the prevalence of subclinical PNEMTs and the need for careful follow-up.</p>","PeriodicalId":23762,"journal":{"name":"World Journal of Gastrointestinal Oncology","volume":"17 12","pages":"113198"},"PeriodicalIF":2.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12754284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145889957","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":"Molecular mechanism of non-coding RNAs-mediated radiosensitivity regulation in colorectal cancer.","authors":"Xiao Li, Xiu-Xia Hao, Rui-Qing Zhu, Hong-Wei Zhou","doi":"10.4251/wjgo.v17.i12.113636","DOIUrl":"10.4251/wjgo.v17.i12.113636","url":null,"abstract":"<p><p>Colorectal cancer (CRC) remains a formidable global health challenge and is associated with dismal survival outcomes and high mortality among patients diagnosed at advanced stages. Despite advancements in early screening and therapeutic interventions, the outcomes of patients with advanced-stage CRC remain suboptimal, as these patients continue to exhibit a persistently low 5-year survival rate. Palliative radiotherapy (RT) is crucial for advanced CRC patients, but radioresistance remains a significant clinical challenge. This resistance is attributed to multiple mechanisms, such as genetic heterogeneity, dysregulated DNA damage repair and tumor microenvironment metabolic disorders. Recent studies have shown that noncoding RNAs (ncRNAs), mainly microRNAs, long ncRNAs (lncRNAs) and circular RNAs, play pivotal roles in regulating CRC radiosensitivity through diverse mechanisms, such as epithelial-mesenchymal transition, epigenetic reprogramming, posttranscriptional regulation and oncogenic signaling pathway activation. For example, microRNAs such as miR-141-3p and miR-630 enhance CRC radiosensitivity by targeting oncogenic pathways. In addition, lncRNAs, including the lncRNAs HOTAIR and LINC00630, influence the radiosensitivity of CRC through interactions with the DNA damage repair machinery and epigenetic modulators, respectively. In addition, circ_0124554 acts as a competitive endogenous RNA to regulate oncogenic signaling. ncRNAs also serve as potential biomarkers for predicting radiosensitivity and prognosis. This review synthesizes the current evidence on the ncRNA-mediated regulatory networks that influence CRC radiosensitivity, emphasizing their potential as therapeutic targets to overcome RT resistance and improve outcomes in advanced CRC. By bridging mechanistic insights with clinical applications, this work aims to guide future research and the implementation of precision RT strategies.</p>","PeriodicalId":23762,"journal":{"name":"World Journal of Gastrointestinal Oncology","volume":"17 12","pages":"113636"},"PeriodicalIF":2.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12754332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145889959","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":"Combining irreversible electroporation and immunotherapy for hepatocellular carcinoma: Reflections and directions for advancement.","authors":"Arunkumar Krishnan, Diptasree Mukherjee","doi":"10.4251/wjgo.v17.i12.113598","DOIUrl":"10.4251/wjgo.v17.i12.113598","url":null,"abstract":"<p><p>We read with great interest the recent article by Xing <i>et al</i>, which describes the synergy between irreversible electroporation and anti-programmed death-1 therapy in a murine hepatocellular carcinoma model. The study offers valuable mechanistic insights into local ablation, enhancing the efficacy of immune checkpoint blockade. However, critical methodological limitations and an overstatement of mechanistic conclusions warrant cautious interpretation. We recommend clarifying experimental details, optimizing murine models, applying more robust statistical analyses, and tempering conclusions to reflect the correlative nature of the findings. Further work should investigate immune mechanisms, durability of response, and safety in clinically relevant models to maximize translational potential. These refinements will strengthen the study's impact in advancing ablation-immunotherapy strategies in hepatocellular carcinoma.</p>","PeriodicalId":23762,"journal":{"name":"World Journal of Gastrointestinal Oncology","volume":"17 12","pages":"113598"},"PeriodicalIF":2.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12754295/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145889670","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":"Exploring the improvement effect of intestinal network monitoring system on intestinal preparation quality of colonoscopy.","authors":"Mei-Juan Xi, Yan-Ping Gong, Jian Tao, Fang Li, Min-Yi Xu, Xing Gu, Han Bao, Sheng Jiang, Bing Xu","doi":"10.4251/wjgo.v17.i12.111101","DOIUrl":"10.4251/wjgo.v17.i12.111101","url":null,"abstract":"<p><strong>Background: </strong>Colonoscopy quality relies heavily on adequate bowel preparation, yet traditional methods often result in suboptimal compliance. Emerging network-based monitoring systems offer promise for improving both preparation quality and patient cooperation, potentially enhancing clinical outcomes.</p><p><strong>Aim: </strong>To evaluate the effectiveness of an intestinal network monitoring system in enhancing the quality of bowel preparation for colonoscopy and its impact on patient psychological and physiological responses, compliance, and adverse event rates.</p><p><strong>Methods: </strong>Between July 2019 and July 2020, 800 enteroscopy patients who met the inclusion criteria in the outpatient clinic of the gastroenterology department of our hospital were randomly divided into 400 cases each in the experimental group (network monitoring group) and the control group (verbal + written preaching group), and the psychological and physiological stress response situation, colon Boston Bowel Preparation Scale, enteroscopy to blindness, arrival time to blindness, and polyp detection rate of the patients were compared before and after the intervention, compliance and adverse reactions were compared.</p><p><strong>Results: </strong>There was no difference in anxiety and depression scores, heart rate and systolic blood pressure between the groups before the intervention (<i>P</i> > 0.05), and after the intervention, the patients' anxiety and depression scores were lower and lower in the study group (<i>P</i> < 0.05); heart rate and systolic blood pressure were elevated, but lower in the test group (<i>P</i> < 0.05). The left hemicolon, right hemicolon, transverse colon and total Boston Bowel Preparation Scale scores were lower in the test group than in the control group (<i>P</i> < 0.05), the colonoscopy arrival rate and polyp detection rate were higher than those in the control group, and the time to arrival and time to exit the scope were shorter than those in the control group (<i>P</i> < 0.05), and the dietary preparations, the preparations for taking medications and the total adherence scores were higher than those in the control group (<i>P</i> < 0.05). The incidence of adverse reactions in the experimental group was 11.00%, which was lower than that in the control group (<i>P</i> < 0.05).</p><p><strong>Conclusion: </strong>The Bowel Network Monitoring System has potential clinical promotion value in improving the quality of colonoscopic bowel preparation, which can effectively alleviate patient anxiety and depression, improve the quality of colonoscopic bowel preparation and patient compliance, and has a high degree of safety.</p>","PeriodicalId":23762,"journal":{"name":"World Journal of Gastrointestinal Oncology","volume":"17 12","pages":"111101"},"PeriodicalIF":2.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12754311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145889831","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":"Cost <i>vs</i> clinical utility on application of large language models in clinical practice: A double-edged sword.","authors":"Sunny Chi Lik Au","doi":"10.4251/wjgo.v17.i12.114341","DOIUrl":"10.4251/wjgo.v17.i12.114341","url":null,"abstract":"<p><p>As large language models increasingly permeate medical workflows, a recent study evaluating ChatGPT 4.0's performance in addressing patient queries about endoscopic submucosal dissection and endoscopic mucosal resection offers critical insights into three domains: Performance parity, cost democratization, and clinical readiness. The findings highlight ChatGPT's high accuracy, completeness, and comprehensibility, suggesting potential cost efficiency in patient education. Yet, cost-effectiveness alone does not ensure clinical utility. Notably, the study relied exclusively on text-based prompts, omitting multimodal data such as photographs or endoscopic scans. This is a significant limitation in a visually driven field like endoscopy, where large language model performance may drop precipitously without image context. Without multimodal integration, artificial intelligence tools risk failing to capture key diagnostic signals, underscoring the need for cautious adoption and robust validation in clinical practice.</p>","PeriodicalId":23762,"journal":{"name":"World Journal of Gastrointestinal Oncology","volume":"17 12","pages":"114341"},"PeriodicalIF":2.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12754347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145889717","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":"Involvement of bile acids in cholangiocarcinoma progression <i>via</i> the Hippo-yes-associated protein signaling pathway.","authors":"Jun Hu, Gan Zhang, Shuo Yang, Xian-Feng Shen, Meng Zhou, Lin-Sheng Huang, Hao-Ming Lan","doi":"10.4251/wjgo.v17.i12.112366","DOIUrl":"10.4251/wjgo.v17.i12.112366","url":null,"abstract":"<p><strong>Background: </strong>Cholangiocarcinoma (CCA) is a highly aggressive malignancy with limited therapeutic options. Dysregulation of the Hippo-yes-associated protein (YAP) signaling pathway plays a key role in tumor progression, but the effects of distinct bile acids on this pathway remain unclear.</p><p><strong>Aim: </strong>To investigate the roles of glycochenodeoxycholic acid (GDCA) and deoxycholic acid (DCA) in CCA progression through Hippo-YAP signaling and to evaluate the effects of YAP-targeted interventions.</p><p><strong>Methods: </strong>The <i>in vitro</i> experiments were performed using HuCCT1 CCA cells treated with GDCA, DCA, and combinations with a YAP inhibitor (verteporfin) or agonist (GA-017). Key molecular changes in the Hippo-YAP pathway were assessed by western blot, immunofluorescence, and reverse transcription quantitative real-time polymerase chain reaction. Functional assays, including Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine, Transwell, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-nick end labelling, were conducted to evaluate cell proliferation, migration, invasion, and apoptosis. <i>In vivo</i>, nude mice bearing subcutaneous HuCCT1 tumors were treated with GDCA, DCA, or combined YAP modulators. Tumor growth was monitored, and molecular analyses of tumor tissues were performed using western blot.</p><p><strong>Results: </strong>The GDCA significantly activated YAP by reducing mammalian STE20-like protein kinase 1 and large tumor suppressor 1 phosphorylation, promoting YAP nuclear translocation, and enhancing tumor cell proliferation, migration, and invasion. In contrast, DCA inhibited YAP activation, suppressed tumor cell functions, and increased apoptosis. GDCA combined with YAP inhibitors attenuated its tumor-promoting effects, while DCA combined with YAP agonists reversed its inhibitory effects. <i>In vivo</i>, GDCA accelerated tumor growth, while DCA reduced tumor size and weight, with molecular changes consistent with <i>in vitro</i> findings.</p><p><strong>Conclusion: </strong>The GDCA and DCA exert opposing effects on CCA progression through Hippo-YAP signaling. GDCA promotes tumor growth <i>via</i> YAP activation, while DCA inhibits these processes. YAP-targeted interventions demonstrate therapeutic potential, providing insights into new treatment strategies for CCA.</p>","PeriodicalId":23762,"journal":{"name":"World Journal of Gastrointestinal Oncology","volume":"17 12","pages":"112366"},"PeriodicalIF":2.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12754318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145889802","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":"Transient receptor potential melastatin 6 and transient receptor potential melastatin 6/7 antagonists suppress colon adenocarcinoma HT-29 cells.","authors":"Nattida Kampuang, Siriporn Chamniansawat, Pawin Pongkorpsakol, Supisara Treveeravoot, Narongrit Thongon","doi":"10.4251/wjgo.v17.i12.110736","DOIUrl":"10.4251/wjgo.v17.i12.110736","url":null,"abstract":"<p><strong>Background: </strong>Magnesium (Mg²⁺) plays a fundamental role in numerous cellular processes, including enzymatic reactions, DNA replication, oxidative stress response, and cytoskeletal dynamics. In fact, dysregulation of Mg²⁺ homeostasis has been increasingly associated with the development and progression of cancer, particularly colorectal cancer (CRC). Transient receptor potential melastatin (TRPM) channels, especially TRPM6 and TRPM7, are essential regulators of epithelial Mg²⁺ influx. While TRPM7 promotes CRC progression, the role of TRPM6 and TRPM6/7 channels remains unclear.</p><p><strong>Aim: </strong>To investigate the role of membrane-localized TRPM6 and TRPM6/7 channels in Mg²⁺ influx, spheroid (SP) formation, stemness, and migration.</p><p><strong>Methods: </strong>We used parental and SP-derived HT-29 cells at comparable passages as <i>in vitro</i> models. Mass spectrometry confirmed full-length sequences, phosphorylation, and methionine oxidation of TRPM6 and TRPM7. Mg²⁺ influx, total and free Mg²⁺ levels were measured by fluorescence imaging and biochemical assays. TRPM6 / TRPM7 expression and markers were analyzed by western blot. Functional assays, including secondary SP formation and wound healing, assessed stemness and migration. Cells were treated with Mg²⁺ transport inhibitors: Co(III)hexamine, 2-aminoethyl diphenylborinate (TRPM6/7 blocker), and Mesendogen (TRPM6 inhibitor).</p><p><strong>Results: </strong>The expression of membrane-bound TRPM6, TRPM7, and TRPM6/7 was significantly higher in SP cells than in parental cells. Mass spectrometric analysis confirmed the presence of full-length TRPM6 and TRPM7 with increased phosphorylation and oxidation in SP cells. Enhanced Mg²⁺ influx and total intracellular Mg²⁺ levels were observed in SP cells. Free ionized intracellular Mg²⁺ levels remained comparable across all experimental groups. Pharmacological inhibition of TRPM6 and TRPM6/7 significantly reduced Mg²⁺ influx, decreased total Mg²⁺ content, compromised CRC SP stability, abolished cancer stem-like properties, impaired cell migration, and downregulated pro-tumorigenic markers, including Nanog, cyclooxygenase-2, and matrix metalloproteinase-9.</p><p><strong>Conclusion: </strong>Membrane-localized TRPM6 and TRPM6/7 channels regulate Mg²⁺ influx and promote CRC stemness, SP stability, and migration, highlighting their potential as therapeutic targets to inhibit CRC progression and metastasis.</p>","PeriodicalId":23762,"journal":{"name":"World Journal of Gastrointestinal Oncology","volume":"17 12","pages":"110736"},"PeriodicalIF":2.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12754298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145889947","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}