Journal of gastrointestinal oncology最新文献

{"title":"Efficacy of liquid biopsy in colorectal cancer.","authors":"Masahiro Yan, Nozomi Funatsu, Megumu Watanabe, Hiroyuki Uetake","doi":"10.21037/jgo-2025-268","DOIUrl":"10.21037/jgo-2025-268","url":null,"abstract":"","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 4","pages":"1785-1788"},"PeriodicalIF":2.0,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064490","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":"Establishment of a prognostic nomogram for intrahepatic cholangiocarcinoma patients receiving chemotherapy: a SEER-based study.","authors":"Qiuhan Heng, Mingxing Hou, Ying Leng, Hua Yu","doi":"10.21037/jgo-2025-143","DOIUrl":"10.21037/jgo-2025-143","url":null,"abstract":"<p><strong>Background: </strong>Chemotherapy is an important treatment for intrahepatic cholangiocarcinoma (ICC) patients, but there is a lack of survival prediction models. This study aims to develop a nomogram to predict cancer-specific survival (CSS) in ICC patients receiving chemotherapy.</p><p><strong>Methods: </strong>A retrospective analysis was performed using data from the Surveillance, Epidemiology, and End Results (SEER) database involving 1,363 ICC patients who receiving chemotherapy between 2010 and 2019. The patients were randomly allocated in a 7:3 ratio to the training cohort and validation cohort. Cox proportional hazards regression analysis was employed to identify prognostic factors for nomogram construction. The accuracy of the model was assessed using the concordance index (C-index), area under the curve (AUC) value, and calibration curve. Additionally, decision curve analysis (DCA), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were utilized to evaluate the clinical value of the nomogram and to compare it with tumor staging based on American Joint Committee on Cancer (AJCC) criteria.</p><p><strong>Results: </strong>Multivariate Cox regression analysis selected seven variables to establish the nomogram. The C-index and AUC value indicate that the nomogram has high accuracy. The calibration curve shows good consistency between the actual observed values and the nomogram-predicted CSS. Meanwhile, DCA, NRI, and IDI demonstrate that the nomogram has significant clinical applicability compared to tumor staging based on AJCC criteria. Furthermore, a risk classification system with satisfactory ability to identify different-risk patients was established.</p><p><strong>Conclusions: </strong>We have developed a nomogram for predicting the prognosis of ICC patients receiving chemotherapy, which can effectively assess the prognosis of this patient population.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 4","pages":"1562-1572"},"PeriodicalIF":2.0,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432954/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064597","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":"Prognostic nomogram for overall survival in rectal cancer with synchronous lung metastases using Surveillance, Epidemiology, and End Results data and a single-center external validation cohort.","authors":"Liyu Cao, Liting Lyu, Bin Wang, Xiaofang Dong","doi":"10.21037/jgo-2025-178","DOIUrl":"10.21037/jgo-2025-178","url":null,"abstract":"<p><strong>Background: </strong>Rectal cancer with synchronous lung metastases has a poor prognosis and high mortality. Despite treatment advancements, effective prognostic tools for early diagnosis and personalized treatment remain limited. This study develops and validates a survival nomogram to improve prognosis prediction and guide treatment strategies.</p><p><strong>Methods: </strong>A total of 1,257 patients with rectal cancer and synchronous lung metastasis were identified from the Surveillance, Epidemiology, and End Results (SEER) database. They were divided into a training cohort (n=880) and an internal validation cohort (n=377). An external validation cohort of 132 patients was retrospectively collected from Affiliated Dongyang Hospital of Wenzhou Medical University. A survival nomogram was developed using variables identified through univariate and multivariate Cox regression analyses and assessed using the concordance index (C-index), time-dependent receiver operating characteristic (ROC) curves, and calibration curves. Kaplan-Meier analysis and log-rank tests were used to compare overall survival (OS) outcomes.</p><p><strong>Results: </strong>Six key risk factors were identified: carcinoembryonic antigen (CEA) level, chemotherapy, tumor stage 2, tumor grade I, radiation therapy, and tumor size (5-100 mm). The nomogram demonstrated strong predictive accuracy for 1-, 3-, and 5-year OS, with area under the curve (AUC) ranging from 0.65 to 0.94. High-risk patients (score ≥104) had significantly worse OS than low-risk patients (P<0.001). Subgroup analysis confirmed that chemotherapy and radiotherapy significantly influenced survival (P<0.05).</p><p><strong>Conclusions: </strong>This validated survival nomogram provides a reliable tool for prognosis prediction and treatment planning in rectal cancer with synchronous lung metastasis, assisting in clinical decision-making.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 4","pages":"1483-1497"},"PeriodicalIF":2.0,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064822","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":"Andrographolide potentiates anti-tumor immunity in colorectal cancer (CRC) by targeting voltage-dependent anion channel (VDAC) and activating the cGAS-STING axis.","authors":"Jiaming Wu, Ben Li, Yutong Chen, Mili Zhang, Jin Li, Guangjian Dou, Yuping Peng, Liyong Huang, Yan Zhou, Zhiheng Chen","doi":"10.21037/jgo-2025-592","DOIUrl":"10.21037/jgo-2025-592","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is a global health burden characterized by significant morbidity and mortality rates. While current therapeutic strategies, including surgical intervention and adjuvant chemotherapy, have shown moderate success, patients with advanced-stage CRC frequently encounter substantial therapeutic obstacles, primarily stemming from acquired drug resistance and tumor immune evasion. Emerging research suggests that phytochemicals are promising therapeutic candidates due to their pleiotropic regulatory capacities, particularly their capability to modulate immune checkpoint inhibitor (ICI) resistance pathways. These bioactive compounds could be used to develop novel therapeutic approaches based on the epigenetic reprogramming of tumor cells and the remodeling of the metabolism-immune crosstalk axis in the tumor microenvironment (TME). This study aimed to investigate the effects and underlying mechanisms of andrographolide in targeting mitochondrial function and remodeling the tumor immune microenvironment in CRC.</p><p><strong>Methods: </strong>This study used Cell Counting Kit-8, live and dead cell staining, immunofluorescence, western blotting, enzyme-linked immunosorbent assay, flow analysis (using CT26 cells), and mouse xenografts to explore the anti-tumor effect and mechanism of andrographolide, a natural product, in CRC.</p><p><strong>Results: </strong>By targeting the voltage-dependent anion channel (VDAC) protein, andrographolide affects the mitochondrial membrane potential of CRC cells, activates the natural immune pathway of cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) during tumor proliferation, and reshapes the TME of CRC by recruiting dendric cells, CD4⁺ T cells, and CD8⁺ T cells, and reducing immunosuppressive regulatory T cells.</p><p><strong>Conclusions: </strong>This study revealed the anti-tumor effect of andrographolide in CRC and the mechanism of immune metabolism regulation. Our findings provide a theoretical basis for the application of natural products in CRC immunotherapy.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 4","pages":"1550-1561"},"PeriodicalIF":2.0,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064805","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":"A novel lactylation-related signature for predicting esophageal cancer prognosis and immune infiltration.","authors":"Liming Xie, Qiuxing Yang, Wenjing Zhao, Guangzhi Lan, Guomei Tai","doi":"10.21037/jgo-2024-1006","DOIUrl":"10.21037/jgo-2024-1006","url":null,"abstract":"<p><strong>Background: </strong>Esophageal cancer (ESCA) is a prevalent malignancy with high morbidity and mortality. It has been demonstrated that lactylation, a novel post-translational modification, is linked to tumor progression and immunity. The objective of this study was to look into the potential role of lactylation-related genes in the prognosis and immune microenvironment of ESCA.</p><p><strong>Methods: </strong>Lactylation-related prognostic genes (LRGs) in ESCA were screened using The Cancer Genome Atlas (TCGA) data. A consensus clustering analysis was conducted on the LRGs, and functional enrichment and immunoassays were performed for different clusters. We utilized least absolute shrinkage and selection operator (LASSO) and multivariate stepwise regression to develop a novel LRG prognostic signature. Subsequently, we assessed the performance of the signature through validation sets. Furthermore, we investigated the immune-related phenotypes of the signature and its response to treatment, as well as its sensitivity to drugs. Finally, experimental verification was performed through immunohistochemical (IHC) staining.</p><p><strong>Results: </strong>We identified 29 LRGs associated with ESCA, and we classified ESCA patients into two lactylation clusters with different prognostic and immune infiltration patterns based on gene expression differences. A new prognostic signature consisting of three prognostic genes (<i>NONO</i>, <i>H2BC18</i>, <i>POLDIP3</i>) was constructed, demonstrating exceptional prediction accuracy in both internal and external datasets. Riskscores derived from this signature were independent prognostic factors for ESCA. Significant differences regarding clinical features, underlying functions, immune infiltration, reactions to immune therapy, and susceptibility to drugs were observed in the two riskscore groups. Finally, IHC staining confirmed the roles of these three genes in ESCA.</p><p><strong>Conclusions: </strong>This study established a new ESCA prognostic signature composed of three lactylation-related genes, which can contribute to predicting prognosis and guiding clinical treatment.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 4","pages":"1711-1735"},"PeriodicalIF":2.0,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064863","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":"Retrospective analysis of Claudin18.2 expression in ethnically diverse patients with gastroesophageal adenocarcinoma.","authors":"Sara Wallam, Jimyung Park, Lawrence W Wu, Ryan H Moy","doi":"10.21037/jgo-2025-111","DOIUrl":"10.21037/jgo-2025-111","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Claudin18.2 (CLDN18.2), a tight junction molecule, is a novel therapeutic target for patients with advanced gastroesophageal adenocarcinoma. Recent phase III trials demonstrated improved survival with the addition of an anti-CLDN18.2 antibody (zolbetuximab) to first-line chemotherapy. However, expression of CLDN18.2 and its association with other biomarkers, especially in racial and ethnic minorities, remains poorly defined. We evaluated CLDN18.2 expression, its association with demographic and clinicopathologic characteristics, and its prognostic potential in a cohort of ethnically diverse patients.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We conducted a single-center retrospective cohort study among patients with gastric, gastroesophageal, and esophageal adenocarcinoma in whom CLDN18.2 immunohistochemistry had been performed. Positivity was defined as moderate-to-strong expression in ≥75% of tumor cells. We extracted demographic and clinicopathologic data from the electronic medical record. Associations with CLDN18.2 were investigated using the &lt;i&gt;t&lt;/i&gt;-test and Chi-squared test. Survival curves were calculated using the Kaplan-Meier method and compared using the log-rank test.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Among 75 evaluable patients, 32 (42.7%) were CLDN18.2 positive. Mean age was 66.2 years [standard deviation (SD), 13.2 years], 34.7% were female, and 62.7%, 18.7%, and 18.7%, had primary gastric, gastroesophageal junction, and esophageal tumors, respectively. At diagnosis, 32% were metastatic. The cohort was 49.3% White, 12% Black, 8% Asian, 21.3% other, and 9.3% unknown, and 20% identified as Hispanic. By ethnicity, 53.3% of Hispanic patients were CLDN18.2 positive compared to 38.2% of non-Hispanic patients. By race, 37.8% of White, 44.4% of Black, and 50% of Asian patients were CLDN18.2 positive. In univariate analyses, CLDN18.2 positivity was significantly associated with female sex (P=0.002) and human epidermal growth factor receptor 2 (HER2) negativity (P=0.03). &lt;i&gt;TP53&lt;/i&gt; mutations were found in 65.2% of patients with available next-generation sequencing data, but there was no association with CLDN18.2 positivity. CLDN18.2 positivity was also not associated with disease-free survival in patients with localized or locally advanced disease, progression-free survival on first-line therapy in metastatic patients, or overall survival in the total population.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;This study provides new information on CLDN18.2 expression in an ethnically diverse population and suggests that Hispanic patients may have higher rates of CLDN18.2 positivity than non-Hispanic patients. We also demonstrate the association between CLDN18.2 and female sex and HER2 negativity and lack of association with survival, consistent with published data. Future research should further investigate differences in CLDN18.2 expression and identify subpopulations of patients who may benefit from CLDN18.2-targeted therapies.&lt;","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 4","pages":"1420-1433"},"PeriodicalIF":2.0,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064929","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":"Sarcopenia following concurrent chemoradiotherapy for locally advanced esophageal squamous cell carcinoma.","authors":"Thiranai Vongcharoenpol, Wongsakorn Chaochankit, Sakchai Ruangsin, Supparerk Laohawiriyakamol, Siriporn Leelakiatpaiboon, Natee Ina, Rungarun Kittichet, Patrapim Sunpaweravong, Somkiat Sunpaweravong","doi":"10.21037/jgo-2025-87","DOIUrl":"10.21037/jgo-2025-87","url":null,"abstract":"<p><strong>Background: </strong>Multimodality treatment using chemotherapy, radiotherapy and surgery is standard practice for locally advanced esophageal squamous cell carcinoma (ESCC). Sarcopenia commonly occurs in patients with esophageal cancer. The effect of concurrent chemoradiotherapy (CCRT) on sarcopenia in patients with locally advanced ESCC remains unclear. We aimed to evaluate the effect of CCRT on sarcopenia in locally advanced ESCC.</p><p><strong>Methods: </strong>This study included patients with locally advanced ESCC who received CCRT without surgery between 2011-2020. Sarcopenia was assessed using the skeletal muscle index (SMI) at the third lumbar vertebra (L3), which includes the psoas, paraspinal, and abdominal wall muscles, based on cross-sectional computed tomography (CT) scans before and after CCRT.</p><p><strong>Results: </strong>In total, 213 patients with locally advanced ESCC who did not undergo esophagectomy after CCRT were included. Before CCRT, 178 patients (83.6%) had sarcopenia, while 35 patients (16.4%) did not. Moreover, 17 patients (48.6%) in the non-sarcopenia group developed sarcopenia after CCRT. The SMI significantly decreased after CCRT in both the sarcopenia and non-sarcopenia groups. The median overall survival (OS) was 12.6-15.7 months in all groups. The incidence of baseline sarcopenia showed no significant association with survival or CCRT-related toxicity. Male, high N-stage and decreasing body mass index (BMI) after CCRT were associated with poor survival prognosis.</p><p><strong>Conclusions: </strong>Most patients with locally advanced ESCC had sarcopenia. Moreover, CCRT was associated with sarcopenia. Therefore, assessing sarcopenia before treatment and initiating interventions for prevention or treatment of sarcopenia may improve sarcopenia status.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 4","pages":"1358-1365"},"PeriodicalIF":2.0,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432935/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064953","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 significance of transjugular intrahepatic portosystemic shunting for hepatocellular carcinoma complicated with portal hypertension.","authors":"Feng Dai, Chunhan Pan, Chunyang Xu, Yu Yao, Mu Su, Jianwu Ren, Zhiyuan Qiu, Mario Capasso, Xiuming Zhang","doi":"10.21037/jgo-2025-365","DOIUrl":"10.21037/jgo-2025-365","url":null,"abstract":"<p><strong>Background: </strong>Portal hypertension (PHT) and hepatocellular carcinoma (HCC) often appear concurrently in clinic, and PHT variceal bleeding arising due to systemic treatment of HCC remains a clinical issue that urgently requires a solution. This study aimed to examine the therapeutic effects and clinical significance of transjugular intrahepatic portosystemic shunting (TIPS) in patients with HCC complicated with PHT.</p><p><strong>Methods: </strong>In this retrospective study, 21 patients with HCC complicated with PHT who were admitted to The Second Hospital of Nanjing between June 2018 and June 2023 were included. TIPS was performed, and liver and kidney function, blood routine, and biochemical indicators such as ammonia were examined preoperatively, at 1 week postoperatively, and at 1 month postoperatively. To determine the improvements in stent blood flow, ascites, and esophageal and gastric varices, ultrasound and/or enhanced computed tomography were performed. Treatment was evaluated based on the Modified Solid Tumor Efficacy Evaluation Criteria. Parameters such as portal vein pressure and portal blood flow before and after TIPS were analyzed using paired-sample <i>t</i>-tests.</p><p><strong>Results: </strong>Postoperatively, the direct pressure of the portal vein of patients decreased significantly from 28.33±7.15 to 19.27±3.10 mmHg (P<0.05). The amount of ascites also significantly decreased, whereas esophageal and gastric varicose veins significantly improved. Meanwhile, no significant differences were observed in liver or kidney function indicators, including bilirubin, transaminase, and creatinine, from the preoperative to the postoperative period.</p><p><strong>Conclusions: </strong>TIPS can effectively improve the various symptoms of PHT without increasing the incidence of liver function damage or other complications in patients with HCC complicated with PHT.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 4","pages":"1648-1657"},"PeriodicalIF":2.0,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064390","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":"Mechanistic insights into the anti-tumor effects of neochlorogenic acid in hepatocellular carcinoma: <i>in vitro</i> and <i>in vivo</i> studies.","authors":"Menglong Xu, Yongchao Li, Wenqiang Sun, Haocheng Guan, Ruijun Shi, Shuwei Li","doi":"10.21037/jgo-2025-185","DOIUrl":"10.21037/jgo-2025-185","url":null,"abstract":"<p><strong>Background: </strong>Neochlorogenic acid (NCA), a naturally occurring polyphenolic compound, exhibits diverse biological activities. This study aimed to investigate the inhibitory effects of NCA on hepatocellular carcinoma (HCC) cells and elucidate its underlying molecular mechanisms.</p><p><strong>Methods: </strong>The anti-proliferative activity of NCA on human HCC cell lines HepG2 and Huh-7 was assessed using the Cell Counting Kit-8 (CCK-8) assay. Flow cytometry was employed to analyze apoptosis and cell cycle distribution. Wound-healing assays were conducted to evaluate the effects of NCA on cell migration. Transcriptome sequencing was performed on NCA-treated and untreated Huh-7 cells to identify differentially expressed genes (DEGs) and signaling pathways. Western blot was used to validate the expression of key apoptosis-related proteins. <i>In vivo</i> experiments were carried out using a nude mouse xenograft model to assess the anti-tumor effects of NCA.</p><p><strong>Results: </strong>NCA significantly inhibited the proliferation of HepG2 and Huh-7 cells, with half maximal inhibitory concentration (IC₅₀) values of 345.5 and 231.8 µM at 24 hours, and 244.0 and 199.2 µM at 48 hours, respectively. Flow cytometry revealed that NCA induced apoptosis and G1 phase cell cycle arrest. Wound-healing assays demonstrated that NCA effectively suppressed HCC cell migration. Transcriptome analysis revealed 2,297 DEGs in NCA-treated Huh-7 cells (Padj<0.01), with 1,162 upregulated and 1,135 downregulated. Pathway enrichment analysis indicated significant enrichments in pathways related to \"Alcoholism\", \"MicroRNAs in cancer\", \"Hepatocellular carcinoma\", and \"TGF-beta signaling pathway\". Western blot confirmed the upregulation of pro-apoptotic proteins [BCL2-associated X protein (BAX); cysteinyl aspartate specific proteinase 3 (CASP3), BH3 interacting domain death agonist (BID), and cytochrome C (CYCS)] and downregulation of the anti-apoptotic protein B-cell lymphoma 2 (BCL2). <i>In vivo</i>, NCA treatment significantly inhibited tumor growth.</p><p><strong>Conclusions: </strong>This study provides compelling evidence that NCA inhibits HCC cell growth and migration both <i>in vitro</i> and <i>in vivo</i> through the induction of apoptosis and cell cycle arrest. Transcriptomic analysis reveals that NCA induces widespread changes in transcriptional networks and metabolic pathways within HCC cells, highlighting its potential as a promising therapeutic strategy for HCC.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 4","pages":"1699-1710"},"PeriodicalIF":2.0,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064672","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":"Stereotactic body radiation therapy in oligometastatic pancreatic cancer: overall survival improvement and <i>SMAD4</i> as a predictor of progression-free survival.","authors":"Ahmed Elhariri, Jaydeepbhai Patel, Himil Mahadevia, Karnav Modi, Douaa Albelal, Umair Majeed, Jeremy C Jones, Mitesh J Borad, Nguyen H Tran, Michael S Rutenberg, Hani Babiker","doi":"10.21037/jgo-2025-100","DOIUrl":"10.21037/jgo-2025-100","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The 5-year overall survival (OS) for stage IV pancreatic cancer is dismal despite aggressive systemic therapy. Stereotactic body radiation therapy (SBRT) involves delivering precise, highly conformal, and biologically effective doses of radiation via a linear accelerator to the tumor region. Clinical trials have shown improvement in OS and progression-free survival (PFS) with SBRT plus standard chemotherapy in oligometastatic (&lt;5 metastatic lesions) solid tumors such as breast, lung, colorectal, and prostate cancers, when compared to chemotherapy alone. Factors predicting response to SBRT need to be further explored in oligometastatic pancreatic cancer (oPC). The study aims to assess the role of SBRT in the management of patients with oPC.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We conducted a retrospective cohort study of oPC patients treated at the Mayo Clinic during the period from January 2012 to January 2022, who underwent SBRT to at least one site, including the primary site and/or sites of metastases, received at least 4 months of chemotherapy, and had a minimum of 1-year follow-up. Pertinent data were collected from the electronic health records after institutional review board (IRB) approval. The response rates (RRs) were assessed using the RECIST v1.1 criteria, and the PFS and OS were calculated using the Kaplan-Meier method. Multivariate Cox regression was used to determine a statistically significant correlation between treatment and genomic characteristics with OS and PFS.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Sixty-one patients with oPC were identified, among whom 38% were female. Eighty-seven percent were Caucasian, and 13% were other ethnicities (African American, Hispanic, and Asian). The median age was 66 years. Patients received gemcitabine (gem) or 5-fluorouracil (5-FU) based chemotherapy. Eight-five percent of patients received chemotherapy within 3 months of SBRT and the median follow-up time of 16 months. The RR was 25% in the primary lesion and 17% in metastatic lesions. SBRT to primary pancreas lesion correlated with higher OS [hazard ratio (HR): 0.27, 95% confidence interval (CI): 0.082-0.89, P=0.03] but showed no difference in PFS (HR: 0.97, P=0.95) when compared to SBRT to any other metastatic site. SBRT to liver metastases had no improvement in OS (P=0.92) or PFS (P=0.70) versus SBRT to other metastatic sites. The type of chemotherapy (gem &lt;i&gt;vs&lt;/i&gt;. 5-FU based) alongside SBRT within 3 months did not influence OS (P=0.47) or PFS (P=0.62) in these patients. Among 30 patients who underwent circulating tumor deoxyribonucleic acid (ctDNA) testing, &lt;i&gt;SMAD4&lt;/i&gt; gene alteration correlated with significantly higher PFS (HR: 0.23, 95% CI: 0.065-0.87, P=0.03) but had no relation with OS (HR: 0.60, 95% CI: 0.18-2.03, P=0.41) compared to patients with undetectable &lt;i&gt;SMAD4&lt;/i&gt; alteration.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;SBRT plus chemotherapy may have benefits in some patients with oPC. SBRT to primary panc","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 4","pages":"1658-1666"},"PeriodicalIF":2.0,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064898","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}