Pub Date : 2025-02-01Epub Date: 2024-07-24DOI: 10.1016/j.ajg.2024.06.003
Limin Zhang , Shanbing Yang , Kangmei Jia , Shuwen Du , Yan Jia , Xiaojuan Lu , Jiheng Wang
Background and study aims
Mucosal healing (MH) is a crucial indicator of therapeutic effectiveness and prognosis in Crohn’s disease (CD). Rapid achievement and long-term maintenance of MH can alleviate the financial and psychological burden on patients. This study aimed to investigate the factors associated with MH in CD patients and enhance clinicians’ understanding.
Patients and methods
Patients diagnosed with CD between January 2010 and December 2019 at our hospital were included and divided into two groups based on the attainment of MH during the follow-up period. Demographic data, symptoms, disease classification, laboratory examination results, and treatments were collected and compared between the two groups. Factors with a P-value <0.2 were subjected to multivariate logistic regression analysis to identify the related factors of MH.
Results
Multivariate logistic regression analysis of CD patients revealed that educational level [odds ratio (OR) = 8.167, 95 % confidence interval (CI) 1.440–46.303, P = 0.018] and biological therapy (OR = 15.291, 95 % CI 1.404–166.543, P = 0.025) were associated with MH.
Conclusion
Educational level and biological therapy are factors related to MH in CD patients. These findings suggest that the use of biological therapy and patients’ better understanding of the disease contribute to achieving MH.
背景和研究目的:黏膜愈合(MH)是衡量克罗恩病(CD)治疗效果和预后的重要指标。快速实现并长期保持黏膜愈合可减轻患者的经济和心理负担。本研究旨在调查与克罗恩病患者MH相关的因素,并加深临床医生对这些因素的理解:纳入 2010 年 1 月至 2019 年 12 月在我院确诊的 CD 患者,并根据随访期间的 MH 实现情况分为两组。收集两组患者的人口统计学数据、症状、疾病分类、实验室检查结果和治疗方法,并进行比较。P值结果的因素:对 CD 患者进行的多变量逻辑回归分析显示,教育水平[几率比(OR)= 8.167,95% 置信区间(CI)1.440-46.303,P = 0.018]和生物治疗(OR = 15.291,95% CI 1.404-166.543,P = 0.025)与 MH 相关:结论:教育水平和生物疗法是CD患者MH的相关因素。这些研究结果表明,使用生物疗法和患者更好地了解疾病有助于实现MH。
{"title":"Education level and biologic therapy are the related factors of mucosal healing in Patients with Crohn’s disease","authors":"Limin Zhang , Shanbing Yang , Kangmei Jia , Shuwen Du , Yan Jia , Xiaojuan Lu , Jiheng Wang","doi":"10.1016/j.ajg.2024.06.003","DOIUrl":"10.1016/j.ajg.2024.06.003","url":null,"abstract":"<div><h3>Background and study aims</h3><div>Mucosal healing (MH) is a crucial indicator of therapeutic effectiveness and prognosis in Crohn’s disease (CD). Rapid achievement and long-term maintenance of MH can alleviate the financial and psychological burden on patients. This study aimed to investigate the factors associated with MH in CD patients and enhance clinicians’ understanding.</div></div><div><h3>Patients and methods</h3><div>Patients diagnosed with CD between January 2010 and December 2019 at our hospital were included and divided into two groups based on the attainment of MH during the follow-up period. Demographic data, symptoms, disease classification, laboratory examination results, and treatments were collected and compared between the two groups. Factors with a <em>P</em>-value <0.2 were subjected to multivariate logistic regression analysis to identify the related factors of MH.</div></div><div><h3>Results</h3><div>Multivariate logistic regression analysis of CD patients revealed that educational level [odds ratio (OR) = 8.167, 95 % confidence interval (CI) 1.440–46.303, <em>P</em> = 0.018] and biological therapy (OR = 15.291, 95 % CI 1.404–166.543, <em>P</em> = 0.025) were associated with MH.</div></div><div><h3>Conclusion</h3><div>Educational level and biological therapy are factors related to MH in CD patients. These findings suggest that the use of biological therapy and patients’ better understanding of the disease contribute to achieving MH.</div></div>","PeriodicalId":48674,"journal":{"name":"Arab Journal of Gastroenterology","volume":"26 1","pages":"Pages 41-44"},"PeriodicalIF":1.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141761835","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}
Pub Date : 2025-02-01Epub Date: 2024-02-29DOI: 10.1016/j.ajg.2024.01.010
Zhizhi Wang, Wangdi Liao, Youxiang Chen, Shunhua Long
We report, for the first time, the safety and effectiveness of antituberculosis drugs after tuberculosis activation during ustekinumab treatment in Crohn’s disease.
我们首次报告了克罗恩病患者在接受乌司替库单抗治疗期间结核病激活后抗结核药物的安全性和有效性。
{"title":"Treatment with antituberculosis agents after tuberculosis activation during ustekinumab treatment: Safety and effectiveness","authors":"Zhizhi Wang, Wangdi Liao, Youxiang Chen, Shunhua Long","doi":"10.1016/j.ajg.2024.01.010","DOIUrl":"10.1016/j.ajg.2024.01.010","url":null,"abstract":"<div><div>We report, for the first time, the safety and effectiveness of antituberculosis drugs after tuberculosis activation during ustekinumab treatment in Crohn’s disease.</div></div>","PeriodicalId":48674,"journal":{"name":"Arab Journal of Gastroenterology","volume":"26 1","pages":"Pages 23-25"},"PeriodicalIF":1.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139997945","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}
Pub Date : 2025-02-01Epub Date: 2024-02-26DOI: 10.1016/j.ajg.2023.12.008
Raghda Marzaban , Rania Mohamed Samy , Mona Ahmed Kassem , Mira Atef
Background and study aims
The multidrug resistance 1 (MDR1) gene is a gene involved in the pathogenesis of inflammatory bowel disease (IBD).The aim of the study is to investigate the association of MDR-1 gene polymorphisms (C2345T and G2677T) and IBD incidence in Egyptian patients, and its relation with disease severity.
Patients and methods
This is a case-control study where genotyping of MDR-1 gene C3435T and G2677T single nucleotide polymorphisms (SNPs) were assayed.
Results
Forty naïve IBD patients, who were composed of 25 UC and 15CD, were compared to 60 healthy controls. They were young aged with significant female predominance, particularly in CD (P = 0.004). UC was mainly (48 %) presented in moderate severity while CD was mainly (53.3 %) presented with mild severity. MDR-1 gene C3435T SNP was not statistically related to IBD, whether in terms of genotypes or alleles, yet its T allele was significantly related to moderate cases of UC (P = 0.014). However, GG genotype of G2677T SNP was significantly low in IBD (P = 0.013), while TT genotype and T allele were significantly related to CD (P = 0.011, and 0.012 respectively). Moreover, G allele proved to be associated significantly with moderate cases of UC (P = 0.001) and mild cases of CD (P = 0.002).
Conclusions
MDR-I gene G2677T SNP GG genotype proved to be protective against IBD, thus may be considered in diagnostic workup of IBD including its severity.
研究背景与目的:本研究旨在调查埃及患者中MDR-1基因多态性(C2345T和G2677T)与IBD发病率的关系,以及与疾病严重程度的关系:这是一项病例对照研究,对MDR-1基因C3435T和G2677T单核苷酸多态性(SNPs)进行了基因分型:研究将 40 名天真的 IBD 患者与 60 名健康对照者进行了比较,其中包括 25 名 UC 患者和 15 名 CD 患者。这些患者年龄较轻,女性明显占多数,尤其是 CD 患者(P = 0.004)。UC 主要(48%)表现为中度严重,而 CD 主要(53.3%)表现为轻度严重。无论是基因型还是等位基因,MDR-1 基因 C3435T SNP 与 IBD 都没有统计学关系,但其 T 等位基因与 UC 中度病例有显著关系(P = 0.014)。然而,G2677T SNP 的 GG 基因型与 IBD 的相关性明显较低(P = 0.013),而 TT 基因型和 T 等位基因与 CD 的相关性明显较高(P = 0.011 和 0.012)。此外,G等位基因与中度UC病例(P = 0.001)和轻度CD病例(P = 0.002)明显相关:结论:MDR-I基因G2677T SNP GG基因型被证明对IBD具有保护作用,因此在诊断IBD(包括其严重程度)时可予以考虑。
{"title":"Multidrug resistance Gene-1 polymorphisms (C3435T and G2677T) and the risk of inflammatory bowel disease in Egyptian patients","authors":"Raghda Marzaban , Rania Mohamed Samy , Mona Ahmed Kassem , Mira Atef","doi":"10.1016/j.ajg.2023.12.008","DOIUrl":"10.1016/j.ajg.2023.12.008","url":null,"abstract":"<div><h3>Background and study aims</h3><div>The multidrug resistance 1 (MDR1) gene is a gene involved in the pathogenesis of inflammatory bowel disease (IBD).The aim of the study is to investigate the association of MDR-1 gene polymorphisms (C2345T and G2677T) and IBD incidence in Egyptian patients, and its relation with disease severity.</div></div><div><h3>Patients and methods</h3><div>This is a case-control study where genotyping of MDR-1 gene C3435T and G2677T single nucleotide polymorphisms (SNPs) were assayed.</div></div><div><h3>Results</h3><div>Forty naïve IBD patients, who were composed of 25 UC and 15CD, were compared to 60 healthy controls. They were young aged with significant female predominance, particularly in CD (P = 0.004). UC was mainly (48 %) presented in moderate severity while CD was mainly (53.3 %) presented with mild severity. MDR-1 gene C3435T SNP was not statistically related to IBD, whether in terms of genotypes or alleles, yet its T allele was significantly related to moderate cases of UC (P = 0.014). However, GG genotype of G2677T SNP was significantly low in IBD (P = 0.013), while TT genotype and T allele were significantly related to CD (P = 0.011, and 0.012 respectively). Moreover, G allele proved to be associated significantly with moderate cases of UC (P = 0.001) and mild cases of CD (P = 0.002).</div></div><div><h3>Conclusions</h3><div>MDR-I gene G2677T SNP GG genotype proved to be protective against IBD, thus may be considered in diagnostic workup of IBD including its severity.</div></div>","PeriodicalId":48674,"journal":{"name":"Arab Journal of Gastroenterology","volume":"26 1","pages":"Pages 3-8"},"PeriodicalIF":1.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139984182","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}
Crohn's disease (CD) is an inflammatory disease that can affect any part of the gastrointestinal tract and presents with myriad symptoms. Various treatments, including biological treatments, are available. The use of biologics increases the risk of opportunistic infections, with no association with serious infections (1). To the best of our knowledge, there are no established recommendations or case studies for patients with CD infected with Brucella being actively treated with biologics and immunomodulators to date. Herein, we report the first case of brucellosis diagnosed in a patient with CD treated with biologics and immunomodulators.
A 40-year-old man had been treated with anti-tumour necrosis factor (anti-TNF) drugs, namely, infliximab and azathioprine, for CD for the past eight years. During a follow-up visit, the patient complained of loss of appetite, fever, weight loss, and joint discomfort. The patient reported a history of raw milk consumption. Blood cultures indicated the growth of Brucella species. Infliximab and azathioprine were held, and brucellosis treatment was initiated, including rifampin 600 mg once daily, doxycycline 100 mg twice daily, and streptomycin 1 g intramuscularly daily. A multidisciplinary team comprising gastroenterologists and infectious disease specialists decided to initiate brucellosis treatment and resume biologics and immunomodulators 4 weeks after starting Brucella treatment.
克罗恩病(CD)是一种炎症性疾病,可影响胃肠道的任何部位,并表现出多种症状。目前有多种治疗方法,包括生物治疗。使用生物制剂会增加机会性感染的风险,但与严重感染无关(1)。据我们所知,迄今为止还没有针对感染布鲁氏菌的 CD 患者积极使用生物制剂和免疫调节剂治疗的既定建议或病例研究。在此,我们报告了第一例在接受生物制剂和免疫调节剂治疗的 CD 患者中确诊的布鲁氏菌病。一名 40 岁的男性患者在过去八年中一直使用抗肿瘤坏死因子(anti-TNF)药物(即英夫利昔单抗和硫唑嘌呤)治疗 CD。在一次随访中,患者主诉食欲不振、发热、体重减轻和关节不适。患者称曾饮用生牛奶。血液培养显示有布鲁氏菌生长。患者停用了英夫利昔单抗和硫唑嘌呤,并开始接受布鲁氏菌病治疗,包括利福平 600 毫克,每天一次;强力霉素 100 毫克,每天两次;链霉素 1 克,每天肌肉注射。由胃肠病专家和传染病专家组成的多学科团队决定开始布鲁氏菌病治疗,并在开始布鲁氏菌治疗4周后恢复生物制剂和免疫调节剂的使用。
{"title":"Brucellosis in a patient with Crohn's disease treated with infliximab: A case report","authors":"Mansour Altuwaijri , Nasser Alkhraiji , Mosaab Almasry , Saad Alkhowaiter , Nuha Al Amaar , Ammar Alotaibi","doi":"10.1016/j.ajg.2024.03.001","DOIUrl":"10.1016/j.ajg.2024.03.001","url":null,"abstract":"<div><div>Crohn's disease (CD) is an inflammatory disease that can affect any part of the gastrointestinal tract and presents with myriad symptoms. Various treatments, including biological treatments, are available. The use of biologics increases the risk of opportunistic infections, with no association with serious infections (1). To the best of our knowledge, there are no established recommendations or case studies for patients with CD infected with Brucella being actively treated with biologics and immunomodulators to date. Herein, we report the first case of brucellosis diagnosed in a patient with CD treated with biologics and immunomodulators.</div><div>A 40-year-old man had been treated with anti-tumour necrosis factor (anti-TNF) drugs, namely, infliximab and azathioprine, for CD for the past eight years. During a follow-up visit, the patient complained of loss of appetite, fever, weight loss, and joint discomfort. The patient reported a history of raw milk consumption. Blood cultures indicated the growth of Brucella species. Infliximab and azathioprine were held, and brucellosis treatment was initiated, including rifampin 600 mg once daily, doxycycline 100 mg twice daily, and streptomycin 1 g intramuscularly daily. A multidisciplinary team comprising gastroenterologists and infectious disease specialists decided to initiate brucellosis treatment and resume biologics and immunomodulators 4 weeks after starting Brucella treatment.</div></div>","PeriodicalId":48674,"journal":{"name":"Arab Journal of Gastroenterology","volume":"26 1","pages":"Pages 38-40"},"PeriodicalIF":1.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140186011","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}
Pub Date : 2025-02-01Epub Date: 2025-01-04DOI: 10.1016/j.ajg.2024.12.001
Chen Zeng , Hanjiang Zeng , Yehan Li , Bing Wu
Congenital extrahepatic portosystemic shunt, also known as Abernethy malformation, is a rare anatomic vascular malformation. Patients with Abernethy malformation may present with abdominal pain, abnormal liver function tests, hepatopulmonary syndrome, pulmonary hypertension, and/or portosystemic encephalopathy. Accurate identification of the shunt and portal vein and effective management of complications is vital in these patients. Routine imaging examinations are useful for the diagnosis and classification of Abernethy malformation. However, these examinations may miss some portal vein branches. Digital subtraction angiography is invaluable when routine imaging cannot precisely identify the hepatic portal vein in this situation.
{"title":"Case Report: Type Ib Abernethy malformation","authors":"Chen Zeng , Hanjiang Zeng , Yehan Li , Bing Wu","doi":"10.1016/j.ajg.2024.12.001","DOIUrl":"10.1016/j.ajg.2024.12.001","url":null,"abstract":"<div><div>Congenital extrahepatic portosystemic shunt, also known as Abernethy malformation, is a rare anatomic vascular malformation. Patients with Abernethy malformation may present with abdominal pain, abnormal liver function tests, hepatopulmonary syndrome, pulmonary hypertension, and/or portosystemic encephalopathy. Accurate identification of the shunt and portal vein and effective management of complications is vital in these patients. Routine imaging examinations are useful for the diagnosis and classification of Abernethy malformation. However, these examinations may miss some portal vein branches. Digital subtraction angiography is invaluable when routine imaging cannot precisely identify the hepatic portal vein in this situation.</div></div>","PeriodicalId":48674,"journal":{"name":"Arab Journal of Gastroenterology","volume":"26 1","pages":"Pages 129-131"},"PeriodicalIF":1.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142928439","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}
Pub Date : 2025-02-01Epub Date: 2024-05-06DOI: 10.1016/j.ajg.2024.01.009
Foroogh Alborzi Avanaki , Naser Ebrahimi Daryani , Najmeh Aletaha , Nazanin Hesabgar , Mohammad Saeid Rezaee-Zavareh , Reza Hadi
Background and study aims
Diet is an important underlying factor in ulcerative colitis (UC) disease. The present study aimed to investigate the effect of a gluten-free diet (GFD) on disease severity, quality of life, and inflammatory markers in patients with UC.
Patients and Methods
In this triple-blind randomized placebo-controlled clinical trial, we evaluated the effect of a GFD on the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), fecal calprotectin, disease severity, and quality of life in patients with mild to moderate UC. Patients’ quality of life and severity of symptoms were evaluated using the Inflammatory Bowel Disease Questionnaire (IBDQ) and Simple Clinical Colitis Activity Index (SCCAI), respectively. Patients received this regimen for six weeks and were evaluated before and after the intervention.
Results
The mean age of patients (n = 26) was 39.31 years (standard deviation = 9.34). In both study groups, the mean ESR, CRP, IBDQ, and SCCAI showed no statistically significant improvement with the dietary intervention. Fecal calprotectin was increased in both groups without statistical significance.
Conclusions
We could not find any significant effect of GFD on inflammatory markers, quality of life, and disease severity among patients with mild to moderate UC. It is too early to suggest the gluten-free diet as a safe and beneficial regimen for UC patients. There is a need for further investigations with larger sample sizes and longer follow-ups as clinical trials and cohort studies to obtain more reliable results.
{"title":"Short-term effect of gluten-free diet on disease severity, quality of life, and inflammatory markers among patients with mild to moderate ulcerative colitis: A triple-blind randomized placebo-controlled trial","authors":"Foroogh Alborzi Avanaki , Naser Ebrahimi Daryani , Najmeh Aletaha , Nazanin Hesabgar , Mohammad Saeid Rezaee-Zavareh , Reza Hadi","doi":"10.1016/j.ajg.2024.01.009","DOIUrl":"10.1016/j.ajg.2024.01.009","url":null,"abstract":"<div><h3>Background and study aims</h3><div>Diet is an important underlying factor in ulcerative colitis (UC) disease. The present study aimed to investigate the effect of a gluten-free diet (GFD) on disease severity, quality of life, and inflammatory markers in patients with UC.</div></div><div><h3>Patients and Methods</h3><div>In this triple-blind randomized placebo-controlled clinical trial, we evaluated the effect of a GFD on the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), fecal calprotectin, disease severity, and quality of life in patients with mild to moderate UC. Patients’ quality of life and severity of symptoms were evaluated using the Inflammatory Bowel Disease Questionnaire (IBDQ) and Simple Clinical Colitis Activity Index (SCCAI), respectively. Patients received this regimen for six weeks and were evaluated before and after the intervention.</div></div><div><h3>Results</h3><div>The mean age of patients (n = 26) was 39.31 years (standard deviation = 9.34). In both study groups, the mean ESR, CRP, IBDQ, and SCCAI showed no statistically significant improvement with the dietary intervention. Fecal calprotectin was increased in both groups without statistical significance.</div></div><div><h3>Conclusions</h3><div>We could not find any significant effect of GFD on inflammatory markers, quality of life, and disease severity among patients with mild to moderate UC. It is too early to suggest the gluten-free diet as a safe and beneficial regimen for UC patients. There is a need for further investigations with larger sample sizes and longer follow-ups as clinical trials and cohort studies to obtain more reliable results.</div></div>","PeriodicalId":48674,"journal":{"name":"Arab Journal of Gastroenterology","volume":"26 1","pages":"Pages 18-22"},"PeriodicalIF":1.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140877691","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}
Pub Date : 2025-02-01Epub Date: 2025-01-04DOI: 10.1016/j.ajg.2024.12.002
Mingxing Li , Tailin Chen , Rongshi Huang, Yanhui Cen, Feilan Zhao, Rong Fan, Guozhen He
Background and study aims
As a novel immunotherapy, chimeric antigen receptor T (CAR-T) cell technology is successful in treating hematologic malignancies, and exhibits potential benefits in partial solid tumors. Therapies targeting one antigen have some weaknesses, and dual-targeted CAR-T cells may be a better option. Alpha-fetoprotein (AFP) and glypican-3 (GPC3) are both highly expressed in hepatocellular carcinoma (HCC) and serve as important markers. Our study aimed to compare the cytotoxicity effect of AFP and GPC3 dual-targeted CAR-T cells on HCC cells in vitro and its therapeutic effects on a SCID xenograft model with those of single-targeted CAR-T cells.
Materials and methods
pLVX lentivirus vectors loaded with AFP CAR, GPC3 CAR, or AFP-GPC3 CAR constructs were transfected into human T lymphocytes. Control T, AFP CAR-T, GPC3 CAR-T, and AFP-GPC3 CAR-T cells were used as effector cells, and HLE (AFP-GPC3-), Sh-GPC3-Huh-7 (AFP+), Sh-AFP-Huh-7 (GPC3+), and Huh-7 (AFP+GPC3+) cells were used as target cells. After their co-culture for 6 h, the LDH cytotoxicity assay was employed to estimate the cell-killing effects of CAR-T cells on the target HCC cells. SCID mice bearing Huh-7 cell-derived neoplasms were injected with CAR-T cells, after which the pathological changes, CD3ζ expression, and IL-2 and IFN-γ levels in mouse tumor tissues were determined.
Results
AFP and GPC3 were highly expressed in Huh-7 cells. AFP-GPC3 CAR-T cells exerted significant cell-killing effects on the HCC cells that expressed specific targeting antigen molecules (AFP and GPC3). Besides, AFP-GPC3 CAR-T cells better promoted Th cytokine secretion by Huh-7 cells than AFP CAR-T and GPC3 CAR-T cells. In vivo results suggested that AFP-GPC3 CAR-T cells better inhibited the growth of Huh-7 cell (AFP+GPC3+)-derived neoplasms than AFP CAR-T and GPC3 CAR-T cells.
Conclusion
AFP and GPC3 dual-targeted CAR-T cells showed better anti-tumor effects in HCC than AFP or GPC3 single-targeted CAR-T cells.
{"title":"Chimeric antigen receptor-T cells targeting AFP-GPC3 mediate increased antitumor efficacy in hepatocellular carcinoma","authors":"Mingxing Li , Tailin Chen , Rongshi Huang, Yanhui Cen, Feilan Zhao, Rong Fan, Guozhen He","doi":"10.1016/j.ajg.2024.12.002","DOIUrl":"10.1016/j.ajg.2024.12.002","url":null,"abstract":"<div><h3>Background and study aims</h3><div>As a novel immunotherapy, chimeric antigen receptor T (CAR-T) cell technology is successful in treating hematologic malignancies, and exhibits potential benefits in partial solid tumors. Therapies targeting one antigen have some weaknesses, and dual-targeted CAR-T cells may be a better option. Alpha-fetoprotein (AFP) and glypican-3 (GPC3) are both highly expressed in hepatocellular carcinoma (HCC) and serve as important markers. Our study aimed to compare the cytotoxicity effect of AFP and GPC3 dual-targeted CAR-T cells on HCC cells <em>in vitro</em> and its therapeutic effects on a SCID xenograft model with those of single-targeted CAR-T cells.</div></div><div><h3>Materials and methods</h3><div>pLVX lentivirus vectors loaded with AFP CAR, GPC3 CAR, or AFP-GPC3 CAR constructs were transfected into human T lymphocytes. Control T, AFP CAR-T, GPC3 CAR-T, and AFP-GPC3 CAR-T cells were used as effector cells, and HLE (AFP<sup>-</sup>GPC3<sup>-</sup>), Sh-GPC3-Huh-7 (AFP<sup>+</sup>), Sh-AFP-Huh-7 (GPC3<sup>+</sup>), and Huh-7 (AFP<sup>+</sup>GPC3<sup>+</sup>) cells were used as target cells. After their co-culture for 6 h, the LDH cytotoxicity assay was employed to estimate the cell-killing effects of CAR-T cells on the target HCC cells. SCID mice bearing Huh-7 cell-derived neoplasms were injected with CAR-T cells, after which the pathological changes, CD3ζ expression, and IL-2 and IFN-γ levels in mouse tumor tissues were determined.</div></div><div><h3>Results</h3><div>AFP and GPC3 were highly expressed in Huh-7 cells. AFP-GPC3 CAR-T cells exerted significant cell-killing effects on the HCC cells that expressed specific targeting antigen molecules (AFP and GPC3). Besides, AFP-GPC3 CAR-T cells better promoted Th cytokine secretion by Huh-7 cells than AFP CAR-T and GPC3 CAR-T cells. <em>In vivo</em> results suggested that AFP-GPC3 CAR-T cells better inhibited the growth of Huh-7 cell (AFP<sup>+</sup>GPC3<sup>+</sup>)-derived neoplasms than AFP CAR-T and GPC3 CAR-T cells.</div></div><div><h3>Conclusion</h3><div>AFP and GPC3 dual-targeted CAR-T cells showed better anti-tumor effects in HCC than AFP or GPC3 single-targeted CAR-T cells.</div></div>","PeriodicalId":48674,"journal":{"name":"Arab Journal of Gastroenterology","volume":"26 1","pages":"Pages 84-93"},"PeriodicalIF":1.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933186","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}
Pub Date : 2025-02-01Epub Date: 2025-01-10DOI: 10.1016/j.ajg.2024.12.003
Hend Ibrahim Shousha , Eman M.F. Barakat , Eman Rewisha , Mohamed El-Kassas , Ehab Fawzy Moustafa , Mohamed Said , Ashraf Omar Abdelaziz , Safaa Ragab Askar , Eman Elkhateeb , Ahmed Tawheed , Mohamed Omar Abdelmalek , Ahmed Ramadan , Ahmed Hosni Abdelmaksoud , Mostafa Abd Alfattah Shamkh , Hamdy Sayed , Ahmed Radwan Riad , Anwar nassief , Mohamed Mahmoud Nabeel , Yasser Arafat Abdelrazek , Nermeen Abdeen , Mohamed Kohla
Background and study aims
Few studies have considered patients treated with trans-arterial chemoembolization (TACE) for non-viral-induced hepatocellular carcinoma (HCC), with some reporting that those patients may have larger tumors, emphasizing the need for determination of the factors affecting survival in such patients. This work aims to study the characteristics and survival of patients with non-viral related HCC treated with TACE.
Patients and methods
This is a multicenter observational study. Patients (166) with non-viral related HCC treated with TACE were recruited from six tertiary care centers (January 2008- June 2022). Follow-up continued until death or the end of the study (August 2023).
Results
The patients had a mean age of 60.2 ± 9.5 years, a male predominance of 79.5 %. The mean size of the lesions was 5.71 ± 3.02 cm, and 42.8 % of the patients had a single lesion. After a median follow-up period of 27.02 months (IQR 14.99–39.37), the median overall survival (OS) was 42.14 months. The Cox regression hazard model revealed that the independent factors affecting survival were: multiple focal lesions, exceeding five in number, have a substantially higher hazard of death (HR = 8.5, p-value = 0.001) compared to those with a single focal lesion. HAP score grade D exhibited a threefold increase in the hazard of death (HR = 3.8, p-value 0.007). Individuals who did not respond positively to treatment faced a significantly higher risk of death (HR = 10.76, p-value 0.001). Albumin-bilirubin score (ALBI), Easy ALBI, platelet albumin (PAL), platelet albumin bilirubin score (PALBI), The hepatoma arterial-embolisation (HAP) and Tumor burden score were found not to impact the survival of our patients.
Conclusion
Tumor burden is an important determinant of survival after TACE in patients with non-viral HCC. HAP score can be implemented in selecting patients who would benefit from TACE.
{"title":"Survival of patients with non-viral hepatocellular carcinoma treated with trans-arterial chemoembolization: A multicenter cohort study","authors":"Hend Ibrahim Shousha , Eman M.F. Barakat , Eman Rewisha , Mohamed El-Kassas , Ehab Fawzy Moustafa , Mohamed Said , Ashraf Omar Abdelaziz , Safaa Ragab Askar , Eman Elkhateeb , Ahmed Tawheed , Mohamed Omar Abdelmalek , Ahmed Ramadan , Ahmed Hosni Abdelmaksoud , Mostafa Abd Alfattah Shamkh , Hamdy Sayed , Ahmed Radwan Riad , Anwar nassief , Mohamed Mahmoud Nabeel , Yasser Arafat Abdelrazek , Nermeen Abdeen , Mohamed Kohla","doi":"10.1016/j.ajg.2024.12.003","DOIUrl":"10.1016/j.ajg.2024.12.003","url":null,"abstract":"<div><h3>Background and study aims</h3><div>Few studies have considered patients treated with <em>trans</em>-arterial chemoembolization (TACE) for non-viral-induced hepatocellular carcinoma (HCC), with some reporting that those patients may have larger tumors, emphasizing the need for determination of the factors affecting survival in such patients. This work aims to study the characteristics and survival of patients with non-viral related HCC treated with TACE.</div></div><div><h3>Patients and methods</h3><div>This is a multicenter observational study. Patients (166) with non-viral related HCC treated with TACE were recruited from six tertiary care centers (January 2008- June 2022). Follow-up continued until death or the end of the study (August 2023).</div></div><div><h3>Results</h3><div>The patients had a mean age of 60.2 ± 9.5 years, a male predominance of 79.5 %. The mean size of the lesions was 5.71 ± 3.02 cm, and 42.8 % of the patients had a single lesion. After a median follow-up period of 27.02 months (IQR 14.99–39.37), the median overall survival (OS) was 42.14 months. The Cox regression hazard model revealed that the independent factors affecting survival were: multiple focal lesions, exceeding five in number, have a substantially higher hazard of death (HR = 8.5, p-value = 0.001) compared to those with a single focal lesion. HAP score grade D exhibited a threefold increase in the hazard of death (HR = 3.8, p-value 0.007). Individuals who did not respond positively to treatment faced a significantly higher risk of death (HR = 10.76, p-value 0.001). Albumin-bilirubin score (ALBI), Easy ALBI, platelet albumin (PAL), platelet albumin bilirubin score (PALBI), The hepatoma arterial-embolisation (HAP) and Tumor burden score were found not to impact the survival of our patients.</div></div><div><h3>Conclusion</h3><div>Tumor burden is an important determinant of survival after TACE in patients with non-viral HCC. HAP score can be implemented in selecting patients who would benefit from TACE.</div></div>","PeriodicalId":48674,"journal":{"name":"Arab Journal of Gastroenterology","volume":"26 1","pages":"Pages 94-103"},"PeriodicalIF":1.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142966793","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}
Pub Date : 2025-02-01Epub Date: 2025-01-04DOI: 10.1016/j.ajg.2024.12.004
Bo Wang, Tao Wu
Background and study aims
Nicotinamide N-methyltransferase (NNMT) is aberrantly expressed in tumors and is implicated in the progression and chemoresistance of cancers. This project attempts to explore the specific molecular mechanism by which NNMT enhances 5-fluorouracil (5-FU) resistance in gastric cancer (GC).
Materials and methods
By bioinformatics analysis, the expression of NNMT in GC was analyzed and its relationship with patients’ prognoses was examined. The signaling pathway enriched by NNMT was analyzed by the Kyoto Encyclopedia of Genes and Genomes (KEGG). Western blot (WB) and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were employed to measure the mRNA and protein expression of NNMT in normal gastric epithelial cells and GC cells. CCK8 was employed to measure cell viability and the IC50 of 5-FU. The apoptosis rate was assessed by Flow cytometry. WB measured the protein expression of Ki67, epithelial-mesenchymal transition (EMT)-related proteins, PI3K, AKT, p-AKT, NNMT, and H3K9me3. We applied the Transwell assay to measure cell migration and invasion ability. The content of S-adenosylmethionine (SAM) and S-adenosyl-L-homocysteine (SAH) in cells was measured by enzyme-linked immunosorbent assay (ELISA).
Result
NNMT was greatly upregulated in GC tissues and cells, exhibiting a negative linkage with patients’ prognoses. Knocking down NNMT remarkably repressed the vitality, proliferation, anti-apoptotic ability, migration, and invasion of GC cells but elevated the sensitivity of cancer cells to 5-FU. However, overexpression of NNMT inhibited H3K9 methylation by reducing the universal methyl donor SAM, activated the PI3K/AKT pathway, facilitated GC malignant progression, and triggered resistance to 5-FU.
Conclusion
Upregulation of NNMT expression in GC cells can induce 5-FU resistance by repressing the activation of PI3K/AKT through the inhibition of histone methylation.
{"title":"NNMT suppresses H3K9me3 to facilitate malignant progression and drug resistance in gastric cancer","authors":"Bo Wang, Tao Wu","doi":"10.1016/j.ajg.2024.12.004","DOIUrl":"10.1016/j.ajg.2024.12.004","url":null,"abstract":"<div><h3>Background and study aims</h3><div>Nicotinamide N-methyltransferase (NNMT) is aberrantly expressed in tumors and is implicated in the progression and chemoresistance of cancers. This project attempts to explore the specific molecular mechanism by which NNMT enhances 5-fluorouracil (5-FU) resistance in gastric cancer (GC).</div></div><div><h3>Materials and methods</h3><div>By bioinformatics analysis, the expression of NNMT in GC was analyzed and its relationship with patients’ prognoses was examined. The signaling pathway enriched by NNMT was analyzed by the Kyoto Encyclopedia of Genes and Genomes (KEGG). Western blot (WB) and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were employed to measure the mRNA and protein expression of NNMT in normal gastric epithelial cells and GC cells. CCK8 was employed to measure cell viability and the IC<sub>50</sub> of 5-FU. The apoptosis rate was assessed by Flow cytometry. WB measured the protein expression of Ki67, epithelial-mesenchymal transition (EMT)-related proteins, PI3K, AKT, p-AKT, NNMT, and H3K9me3. We applied the Transwell assay to measure cell migration and invasion ability. The content of S-adenosylmethionine (SAM) and S-adenosyl-L-homocysteine (SAH) in cells was measured by enzyme-linked immunosorbent assay (ELISA).</div></div><div><h3>Result</h3><div>NNMT was greatly upregulated in GC tissues and cells, exhibiting a negative linkage with patients’ prognoses. Knocking down NNMT remarkably repressed the vitality, proliferation, anti-apoptotic ability, migration, and invasion of GC cells but elevated the sensitivity of cancer cells to 5-FU. However, overexpression of NNMT inhibited H3K9 methylation by reducing the universal methyl donor SAM, activated the PI3K/AKT pathway, facilitated GC malignant progression, and triggered resistance to 5-FU.</div></div><div><h3>Conclusion</h3><div>Upregulation of NNMT expression in GC cells can induce 5-FU resistance by repressing the activation of PI3K/AKT through the inhibition of histone methylation.</div></div>","PeriodicalId":48674,"journal":{"name":"Arab Journal of Gastroenterology","volume":"26 1","pages":"Pages 104-111"},"PeriodicalIF":1.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933190","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}
Pub Date : 2025-02-01Epub Date: 2025-01-28DOI: 10.1016/j.ajg.2025.01.007
Kai-Chiao Chuang , Jui-Yuan Chung
{"title":"Cholecystocutaneous fistula: A rare case in an elderly female with a massive abdominal mass","authors":"Kai-Chiao Chuang , Jui-Yuan Chung","doi":"10.1016/j.ajg.2025.01.007","DOIUrl":"10.1016/j.ajg.2025.01.007","url":null,"abstract":"","PeriodicalId":48674,"journal":{"name":"Arab Journal of Gastroenterology","volume":"26 1","pages":"Pages 132-136"},"PeriodicalIF":1.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061124","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}