World Journal of Gastrointestinal Oncology最新文献

{"title":"Network pharmacology: Changes the treatment mode of \"one disease-one target\" in cancer treatment.","authors":"Shuai Liu, Yong-Wei Yu","doi":"10.4251/wjgo.v17.i1.101581","DOIUrl":"https://doi.org/10.4251/wjgo.v17.i1.101581","url":null,"abstract":"<p><p>The article concluded that network pharmacology provides new ideas and insights into the molecular mechanism of traditional Chinese medicine (TCM) treatment of cancer. TCM is a new choice and hot spot in the field of cancer treatment. We have also previously published studies on TCM and network pharmacology. In this letter, we summarize the new paradigm of network pharmacology in cancer treatment mechanisms.</p>","PeriodicalId":23762,"journal":{"name":"World Journal of Gastrointestinal Oncology","volume":"17 1","pages":"101581"},"PeriodicalIF":2.5,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012551","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":"Interleukin-17A facilitates tumor progression <i>via</i> upregulating programmed death ligand-1 expression in hepatocellular carcinoma.","authors":"Zhong-Xia Yang, Li-Ting Zhang, Xiao-Jun Liu, Xue-Bin Peng, Xiao-Rong Mao","doi":"10.4251/wjgo.v17.i1.97831","DOIUrl":"https://doi.org/10.4251/wjgo.v17.i1.97831","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is an inflammation-associated tumor with a dismal prognosis. Immunotherapy has become an important treatment strategy for HCC, as immunity is closely related to inflammation in the tumor microenvironment. Inflammation regulates the expression of programmed death ligand-1 (PD-L1) in the immunosuppressive tumor microenvironment and affects immunotherapy efficacy. Interleukin-17A (IL-17A) is involved in the remodeling of the tumor microenvironment and plays a protumor or antitumor role in different tumors. We hypothesized that IL-17A participates in tumor progression by affecting the level of immune checkpoint molecules in HCC.</p><p><strong>Aim: </strong>To investigate the effect and mechanism of action of IL-17A on PD-L1 expression and to identify attractive candidates for the treatment of HCC.</p><p><strong>Methods: </strong>The upregulation of PD-L1 expression in HCC cells by IL-17A was assessed by reverse transcription PCR, western blotting, and flow cytometry. Mechanistic studies were conducted with gene knockout models and pathway inhibitors. The function of IL-17A in immune evasion was explored through coculture of T cells and HCC cells. The effects of IL-17A on the malignant biological behaviors of HCC cells were evaluated <i>in vitro</i>, and the antitumor effects of an IL-17A inhibitor and its synergistic effects with a PD-L1 inhibitor were studied <i>in vivo</i>.</p><p><strong>Results: </strong>IL-17A upregulated PD-L1 expression in HCC cells in a dose-dependent manner, whereas IL-17A receptor knockout or treatment with a small mothers against decapentaplegic 2 inhibitor diminished the PD-L1 expression induced by IL-17A. IL-17A enhanced the survival of HCC cells in the coculture system. IL-17A increased the viability, G2/M ratio, and migration of HCC cells and decreased the apoptotic index. Cyclin D1, <i>VEGF</i>, <i>MMP9</i>, and <i>Bcl-1</i> expression increased after IL-17A treatment, whereas <i>BAX</i> expression decreased. The combination of IL-17A and PD-L1 inhibitors showed synergistic antitumor efficacy and increased cluster of differentiation 8 + T lymphocyte infiltration in an HCC mouse model.</p><p><strong>Conclusion: </strong>IL-17A upregulates PD-L1 expression <i>via</i> the IL-17A receptor/phosphorylation-small mothers against decapentaplegic 2 signaling pathway in HCC cells. Blocking IL-17A enhances the therapeutic efficacy of PD-L1 antibodies in HCC <i>in vivo</i>.</p>","PeriodicalId":23762,"journal":{"name":"World Journal of Gastrointestinal Oncology","volume":"17 1","pages":"97831"},"PeriodicalIF":2.5,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012619","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 pathological types and imaging features in pancreatic cancer: A comprehensive study.","authors":"Yang-Gang Luo, Mei Wu, Hong-Guang Chen","doi":"10.4251/wjgo.v17.i1.99153","DOIUrl":"https://doi.org/10.4251/wjgo.v17.i1.99153","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic cancer remains one of the most lethal malignancies worldwide, with a poor prognosis often attributed to late diagnosis. Understanding the correlation between pathological type and imaging features is crucial for early detection and appropriate treatment planning.</p><p><strong>Aim: </strong>To retrospectively analyze the relationship between different pathological types of pancreatic cancer and their corresponding imaging features.</p><p><strong>Methods: </strong>We retrospectively analyzed the data of 500 patients diagnosed with pancreatic cancer between January 2010 and December 2020 at our institution. Pathological types were determined by histopathological examination of the surgical specimens or biopsy samples. The imaging features were assessed using computed tomography, magnetic resonance imaging, and endoscopic ultrasound. Statistical analyses were performed to identify significant associations between pathological types and specific imaging characteristics.</p><p><strong>Results: </strong>There were 320 (64%) cases of pancreatic ductal adenocarcinoma, 75 (15%) of intraductal papillary mucinous neoplasms, 50 (10%) of neuroendocrine tumors, and 55 (11%) of other rare types. Distinct imaging features were identified in each pathological type. Pancreatic ductal adenocarcinoma typically presents as a hypodense mass with poorly defined borders on computed tomography, whereas intraductal papillary mucinous neoplasms present as characteristic cystic lesions with mural nodules. Neuroendocrine tumors often appear as hypervascular lesions in contrast-enhanced imaging. Statistical analysis revealed significant correlations between specific imaging features and pathological types (<i>P</i> < 0.001).</p><p><strong>Conclusion: </strong>This study demonstrated a strong association between the pathological types of pancreatic cancer and imaging features. These findings can enhance the accuracy of noninvasive diagnosis and guide personalized treatment approaches.</p>","PeriodicalId":23762,"journal":{"name":"World Journal of Gastrointestinal Oncology","volume":"17 1","pages":"99153"},"PeriodicalIF":2.5,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012714","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":"Transarterial chemoembolization combined with lenvatinib and sintilimab <i>vs</i> lenvatinib alone in intermediate-advanced hepatocellular carcinoma.","authors":"Fei-Da Wu, Hai-Feng Zhou, Wei Yang, Di Zhu, Bi-Fei Wu, Hai-Bin Shi, Sheng Liu, Wei-Zhong Zhou","doi":"10.4251/wjgo.v17.i1.96267","DOIUrl":"https://doi.org/10.4251/wjgo.v17.i1.96267","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is the most common form of liver cancer that has limited treatment options and a poor prognosis. Transarterial chemoembolization (TACE) is the first-line treatment for intermediate-stage HCC but can induce tumour hypoxia, thereby promoting angiogenesis. Recent studies suggested that combining TACE with anti-angiogenic therapies and immunotherapy might improve efficacy. Lenvatinib, a tyrosine kinase inhibitor, has demonstrated superior outcomes compared to sorafenib, while immune checkpoint inhibitors such as sintilimab show potential when combined with TACE. However, the efficacy and safety of TACE combined with lenvatinib and sintilimab (TACE + SL) compared to TACE with lenvatinib alone (TACE + L) in patients with intermediate-advanced HCC has not yet been investigated.</p><p><strong>Aim: </strong>To evaluate the efficacy and safety of TACE + SL therapy in comparison to TACE + L therapy in patients with intermediate-advanced HCC.</p><p><strong>Methods: </strong>A retrospective analysis was performed on patients with intermediate-advanced HCC who received TACE plus lenvatinib with or without sintilimab between September 2019 and September 2022. Baseline characteristics were compared, and propensity score matching was applied. Overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) were evaluated between the two groups, and adverse events were analyzed.</p><p><strong>Results: </strong>The study included 57 patients, with 30 in the TACE + SL group and 27 in the TACE + L group. The TACE + SL group demonstrated significantly improved median PFS and OS compared to the TACE + L group (PFS: 14.1 months <i>vs</i> 9.6 months, <i>P</i> = 0.016; OS: 22.4 months <i>vs</i> 14.1 months, <i>P</i> = 0.039), along with a higher ORR (70.0% <i>vs</i> 55.6%). After propensity score matching, 30 patients were included, with the TACE + SL group again showing longer median PFS and a trend toward improved OS (PFS: 14.6 months <i>vs</i> 9.2 months, <i>P</i> = 0.012; OS: 23.9 months <i>vs</i> 16.3 months, <i>P</i> = 0.063), and a higher ORR (73.3% <i>vs</i> 53.3%). No severe adverse events were reported.</p><p><strong>Conclusion: </strong>TACE + SL demonstrated superior outcomes in terms of OS and PFS, compared to TACE + L. These findings suggest that the addition of sintilimab might enhance the therapeutic response in patients with intermediate-advanced HCC.</p>","PeriodicalId":23762,"journal":{"name":"World Journal of Gastrointestinal Oncology","volume":"17 1","pages":"96267"},"PeriodicalIF":2.5,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012721","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":"Correlations of the expression of Cx43, SCF^FBXW7, p-cyclin E1 (Ser73), p-cyclin E1 (Thr77) and p-cyclin E1 (Thr395) in colon cancer tissues.","authors":"Rong-Gang Luan, Ming-Da Liu, Zi-Feng Deng, Cong-Lan Lu, Mei-Ling Yu, Ming-Yu Zhang, Rong Liu, Ran An, You-Liang Yao, Dong-Bei Guo, Yong-Xing Zhang, Lei Zhao","doi":"10.4251/wjgo.v17.i1.98410","DOIUrl":"https://doi.org/10.4251/wjgo.v17.i1.98410","url":null,"abstract":"<p><strong>Background: </strong>Previous cellular studies have demonstrated that elevated expression of Cx43 promotes the degradation of cyclin E1 and inhibits cell proliferation through ubiquitination. Conversely, reduced expression results in a loss of this capacity to facilitate cyclin E degradation. The ubiquitination and degradation of cyclin E1 may be associated with phosphorylation at specific sites on the protein, with Cx43 potentially enhancing this process by facilitating the phosphorylation of these critical residues<b>.</b></p><p><strong>Aim: </strong>To investigate the correlation between expression of Cx43, SKP1/Cullin1/F-box (SCF)^FBXW7, p-cyclin E1 (ser73, thr77, thr395) and clinicopathological indexes in colon cancer.</p><p><strong>Methods: </strong>Expression levels of Cx43, SCF^FBXW7, p-cyclin E1 (ser73, thr77, thr395) in 38 clinical colon cancer samples were detected by immunohistochemistry and were analyzed by statistical methods to discuss their correlations.</p><p><strong>Results: </strong>Positive rate of Cx43, SCF^FBXW7, p-cyclin E1(Ser73), p-cyclin E1 (Thr77) and p-cyclin E1 (Thr395) in detected samples were 76.32%, 76.32%, 65.79%, 5.26% and 55.26% respectively. Positive expressions of these proteins were not related to the tissue type, degree of tissue differentiation or lymph node metastasis. Cx43 and SCF^FBXW7(<i>r</i> = 0.749), p-cyclin E1 (Ser73) (<i>r</i> = 0.667) and p-cyclin E1 (Thr395) (<i>r</i> = 0.457), SCF^FBXW7 and p-cyclin E1 (Ser73) (<i>r</i> = 0.703) and p-cyclin E1 (Thr395) (0.415) were correlated in colon cancer (<i>P</i> < 0.05), and expressions of the above proteins were positively correlated in colon cancer.</p><p><strong>Conclusion: </strong>Cx43 may facilitate the phosphorylation of cyclin E1 at the Ser73 and Thr195 sites through its interaction with SCF^FBXW7, thereby influencing the ubiquitination and degradation of cyclin E1.</p>","PeriodicalId":23762,"journal":{"name":"World Journal of Gastrointestinal Oncology","volume":"17 1","pages":"98410"},"PeriodicalIF":2.5,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012517","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":"Characteristics of gut microbiota dysbiosis in patients with colorectal polyps.","authors":"Xian-Rong Wu, Xiao-Hong He, Yong-Fang Xie","doi":"10.4251/wjgo.v17.i1.98872","DOIUrl":"https://doi.org/10.4251/wjgo.v17.i1.98872","url":null,"abstract":"<p><p>This editorial, inspired by a recent study published in the <i>World Journal of Gastrointestinal Oncology</i>, covers the research findings on microbiota changes in various diseases. In recurrent colorectal polyps, the abundances of <i>Klebsiella</i>, <i>Parvimonas</i>, and <i>Clostridium</i> increase, while those of <i>Bifidobacterium</i> and <i>Lactobacillus</i> decrease. This dysbiosis may promote the formation and recurrence of polyps. Similar microbial changes have also been observed in colorectal cancer, inflammatory bowel disease, autism spectrum disorder, and metabolic syndrome, indicating the role of increased pathogens and decreased probiotics in these conditions. Regulating the gut microbiota, particularly by increasing probiotic levels, may help prevent polyp recurrence and promote gut health. This microbial intervention strategy holds promise as an adjunctive treatment for patients with colorectal polyps.</p>","PeriodicalId":23762,"journal":{"name":"World Journal of Gastrointestinal Oncology","volume":"17 1","pages":"98872"},"PeriodicalIF":2.5,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012143","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":"Development of a nomogram for overall survival in patients with esophageal carcinoma: A prospective cohort study in China.","authors":"Shi-Shi Yu, Xi Zheng, Xiao-Sheng Li, Qian-Jie Xu, Wei Zhang, Zhong-Li Liao, Hai-Ke Lei","doi":"10.4251/wjgo.v17.i1.96686","DOIUrl":"https://doi.org/10.4251/wjgo.v17.i1.96686","url":null,"abstract":"<p><strong>Background: </strong>Esophageal carcinoma (EC) presents a significant public health issue in China, with its prognosis impacted by myriad factors. The creation of a reliable prognostic model for the overall survival (OS) of EC patients promises to greatly advance the customization of treatment approaches.</p><p><strong>Aim: </strong>To create a more systematic and practical model that incorporates clinically significant indicators to support decision-making in clinical settings.</p><p><strong>Methods: </strong>This study utilized data from a prospective longitudinal cohort of 3127 EC patients treated at Chongqing University Cancer Hospital between January 1, 2018, and December 12, 2020. Utilizing the least absolute shrinkage and selection operator regression alongside multivariate Cox regression analyses helped pinpoint pertinent variables for constructing the model. Its efficacy was assessed by concordance index (C-index), area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis (DCA).</p><p><strong>Results: </strong>Nine variables were determined to be significant predictors of OS in EC patients: Body mass index (BMI), Karnofsky performance status, TNM stage, surgery, radiotherapy, chemotherapy, immunotherapy, platelet-to-lymphocyte ratio, and albumin-to-globulin ratio (ALB/GLB). The model demonstrated a C-index of 0.715 (95%CI: 0.701-0.729) in the training cohort and 0.711 (95%CI: 0.689-0.732) in the validation cohort. In the training cohort, AUCs for 1-year, 3-year, and 5-year OS predictions were 0.773, 0.787, and 0.750, respectively; in the validation cohort, they were 0.772, 0.768, and 0.723, respectively, illustrating the model's precision. Calibration curves and DCA verified the model's predictive accuracy and net benefit.</p><p><strong>Conclusion: </strong>A novel prognostic model for determining the OS of EC patients was successfully developed and validated to help clinicians in devising individualized treatment schemes for EC patients.</p>","PeriodicalId":23762,"journal":{"name":"World Journal of Gastrointestinal Oncology","volume":"17 1","pages":"96686"},"PeriodicalIF":2.5,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012521","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":"Pretreatment red blood cell distribution width as a predictive marker for postoperative complications after laparoscopic pancreatoduodenectomy.","authors":"Xian-Rang Cao, Yin-Long Xu, Jia-Wei Chai, Kai Zheng, Jun-Jie Kong, Jun Liu, Shun-Zhen Zheng","doi":"10.4251/wjgo.v17.i1.98168","DOIUrl":"https://doi.org/10.4251/wjgo.v17.i1.98168","url":null,"abstract":"<p><strong>Background: </strong>Red blood cell distribution width (RDW) is associated with the development and progression of various diseases.</p><p><strong>Aim: </strong>To explore the association between pretreatment RDW and short-term outcomes after laparoscopic pancreatoduodenectomy (LPD).</p><p><strong>Methods: </strong>A total of 804 consecutive patients who underwent LPD at our hospital between March 2017 and November 2021 were retrospectively analyzed. Correlations between pretreatment RDW and clinicopathological characteristics and short-term outcomes were investigated.</p><p><strong>Results: </strong>Patients with higher pretreatment RDW were older, had higher Eastern Cooperative Oncology Group scores and were associated with poorer short-term outcomes than those with normal RDW. High pretreatment RDW was an independent risk factor for postoperative complications (POCs) (hazard ratio = 2.973, 95% confidence interval: 2.032-4.350, <i>P</i> < 0.001) and severe POCs of grade IIIa or higher (hazard ratio = 3.138, 95% confidence interval: 2.042-4.824, <i>P</i> < 0.001) based on the Clavien-Dino classification system. Subgroup analysis showed that high pretreatment RDW was an independent risk factor for Clavien-Dino classification grade IIIb or higher POCs, a comprehensive complication index score ≥ 26.2, severe postoperative pancreatic fistula, severe bile leakage and severe hemorrhage. High pretreatment RDW was positively associated with the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio and was negatively associated with albumin and the prognostic nutritional index.</p><p><strong>Conclusion: </strong>Pretreatment RDW was a special parameter for patients who underwent LPD. It was associated with malnutrition, severe inflammatory status and poorer short-term outcomes. RDW could be a surrogate marker for nutritional and inflammatory status in identifying patients who were at high risk of developing POCs after LPD.</p>","PeriodicalId":23762,"journal":{"name":"World Journal of Gastrointestinal Oncology","volume":"17 1","pages":"98168"},"PeriodicalIF":2.5,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664621/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012711","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":"Dihydropyrimidine dehydrogenase polymorphisms in patients with gastrointestinal malignancies and their impact on fluoropyrimidine tolerability: Experience from a single Italian institution.","authors":"Mariarosaria D'Amato, Gennaro Iengo, Nicola Massa, Chiara Carlomagno","doi":"10.4251/wjgo.v17.i1.96822","DOIUrl":"https://doi.org/10.4251/wjgo.v17.i1.96822","url":null,"abstract":"<p><strong>Background: </strong>Fluoropyrimidines are metabolized in the liver by the enzyme dihydropyrimidine dehydrogenase (DPD), encoded by the <i>DPYD</i> gene. About 7% of the European population is a carrier of <i>DPYD</i> gene polymorphisms associated with reduced DPD enzyme activity.</p><p><strong>Aim: </strong>To assess the prevalence of <i>DPYD</i> polymorphisms and their impact on fluoropyrimidine tolerability in Italian patients with gastrointestinal malignancies.</p><p><strong>Methods: </strong>A total of 300 consecutive patients with a diagnosis of gastrointestinal malignancy and treated with a fluoropyrimidine-based regimen were included in the analysis and divided into two cohorts: (1) 149 patients who started fluoropyrimidines after <i>DPYD</i> testing; and (2) 151 patients treated without <i>DPYD</i> testing. Among the patients in cohort A, 15% tested only the <i>DPYD2A</i> polymorphism, 19% tested four polymorphisms (<i>DPYD</i>2A, HapB3, c.2846A>T, and <i>DPYD</i>13), and 66% tested five polymorphisms including <i>DPYD</i>6.</p><p><strong>Results: </strong>Overall, 14.8% of patients were found to be carriers of a <i>DPYD</i> variant, the most common being <i>DPYD</i>6 (12.1%). Patients in cohort A reported ≥ G3 toxicities (<i>P</i> = 0.00098), particularly fewer nonhematological toxicities (<i>P</i> = 0.0028) compared with cohort B, whereas there was no statistically significant difference between the two cohorts in hematological toxicities (<i>P</i> = 0.6944). Significantly fewer chemotherapy dose reductions (<i>P</i> = 0.00002) were observed in cohort A compared to cohort B, whereas there was no statistically significant differences in chemotherapy delay.</p><p><strong>Conclusion: </strong>Although this study had a limited sample size, it provides additional information on the prevalence of <i>DPYD</i> polymorphisms in the Italian population and highlights the role of pharmacogenetic testing to prevent severe toxicity.</p>","PeriodicalId":23762,"journal":{"name":"World Journal of Gastrointestinal Oncology","volume":"17 1","pages":"96822"},"PeriodicalIF":2.5,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012525","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":"BIBR1532 inhibits proliferation and metastasis of esophageal squamous cancer cells by inducing telomere dysregulation.","authors":"Qin Wang, Qing-Rong Li, Lei Xu, Zi-Chun Yuan, Xiao Liu, Mao-Ju Tang, Man Luo, Xiao-Wu Zhong, Qiang Ma, Xiao-Lan Guo","doi":"10.4251/wjgo.v17.i1.99376","DOIUrl":"https://doi.org/10.4251/wjgo.v17.i1.99376","url":null,"abstract":"<p><strong>Background: </strong>Esophageal squamous cell carcinoma (ESCC) is a malignant tumor with high morbidity and mortality, and easy to develop resistance to chemotherapeutic agents. Telomeres are DNA-protein complexes located at the termini of chromosomes in eukaryotic cells, which are unreplaceable in maintaining the stability and integrity of genome. Telomerase, an RNA-dependent DNA polymerase, play vital role in telomere length maintain, targeting telomerase is a promising therapeutic strategy for cancer.</p><p><strong>Aim: </strong>To investigate the efficacy and underlying mechanisms of BIBR1532, a telomerase inhibitor, in ESCC.</p><p><strong>Methods: </strong>KYSE150 and KYSE410 cells were cultured and exposed to various concentrations of BIBR1532. Cell viability was assessed at 48 hours and 72 hours to determine the IC₅₀ values. The effects of BIBR1532 on ESCC cell proliferation, migration, and cellular senescence were evaluated using the cell counting kit-8 assay, plate colony formation assay, scratch assay, transwell assay, and β-galactosidase staining, respectively. Western blotting was performed to detect the expression of proteins in BIBR1532-treated ESCC cells, such as human telomerase reverse transcriptase (hTERT), key molecules involved in DNA damage response (DDR) or cellular senescence, as well as telomere-binding proteins. Additionally, a tumor-bearing nude mouse model was established to evaluate the anti-cancer effect of BIBR1532 <i>in vivo</i>.</p><p><strong>Results: </strong>The IC₅₀ values for KYSE150 and KYSE410 cells after 48 hours of BIBR1532 exposure were 48.53 μM and 39.59 μM, respectively. These values decreased to 37.22 μM and 22.71 μM, respectively, following a longer exposure of 72 hours. BIBR1532 exhibited dose-dependent effects on KYSE150 and KYSE410 cells, including decreased hTERT expression, inhibition of proliferation and metastasis, and induction of cellular senescence. Mechanistically, BIBR1532 upregulated the expression of the DDR protein, γ-H2AX, and activated the ataxia telangiectasia and Rad3-related protein (ATR)/ check point kinase 1 (CHK-1) and ataxia-telangiectasia mutated gene (ATM)/CHK2 pathways. BIBR1532 downregulated the expression of telomere-binding proteins, including telomeric-repeat binding factor 1 (TRF1), TRF2, protection of telomeres 1, and TIN2-interacting protein 1. In a nude mouse xenograft model, BIBR1532 significantly suppressed tumor growth, reduced hTERT expression, and increased γ-H2AX protein levels. Hematoxylin and eosin staining of various organs, including the heart, liver, spleen, lungs, and kidneys, revealed no apparent adverse effects.</p><p><strong>Conclusion: </strong>BIBR1532 exerts anti-cancer effects on ESCC by inducing DDR through the ATR/CHK1 and ATM/CHK2 pathways and downregulating the expression of telomere-binding proteins.</p>","PeriodicalId":23762,"journal":{"name":"World Journal of Gastrointestinal Oncology","volume":"17 1","pages":"99376"},"PeriodicalIF":2.5,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012065","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}