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Education level and biologic therapy are the related factors of mucosal healing in Patients with Crohn’s disease 教育水平和生物疗法是克罗恩病患者粘膜愈合的相关因素。
IF 1.1 4区 医学 Q4 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-02-01 Epub Date: 2024-07-24 DOI: 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。
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引用次数: 0
Treatment with antituberculosis agents after tuberculosis activation during ustekinumab treatment: Safety and effectiveness 在乌司替单抗治疗期间,结核病激活后的抗结核药物治疗:安全性和有效性。
IF 1.1 4区 医学 Q4 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-02-01 Epub Date: 2024-02-29 DOI: 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。
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引用次数: 0
Multidrug resistance Gene-1 polymorphisms (C3435T and G2677T) and the risk of inflammatory bowel disease in Egyptian patients 埃及患者的多耐药基因-1 多态性(C3435T 和 G2677T)与炎症性肠病的风险。
IF 1.1 4区 医学 Q4 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-02-01 Epub Date: 2024-02-26 DOI: 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。
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引用次数: 0
Brucellosis in a patient with Crohn's disease treated with infliximab: A case report 一名接受英夫利昔单抗治疗的克罗恩病患者感染布鲁氏菌病:病例报告。
IF 1.1 4区 医学 Q4 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-02-01 Epub Date: 2024-03-21 DOI: 10.1016/j.ajg.2024.03.001
Mansour Altuwaijri , Nasser Alkhraiji , Mosaab Almasry , Saad Alkhowaiter , Nuha Al Amaar , Ammar Alotaibi
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。
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引用次数: 0
Case Report: Type Ib Abernethy malformation 1例报告:b型畸形。
IF 1.1 4区 医学 Q4 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-02-01 Epub Date: 2025-01-04 DOI: 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.
先天性肝外门系统分流,又称阿伯内蒂畸形,是一种罕见的解剖性血管畸形。Abernethy畸形患者可能表现为腹痛、肝功能异常、肝肺综合征、肺动脉高压和/或门系统性脑病。准确识别分流和门静脉并有效处理并发症对这些患者至关重要。常规影像学检查对Abernethy畸形的诊断和分类是有用的。然而,这些检查可能会遗漏一些门静脉分支。在这种情况下,当常规成像不能准确识别肝门静脉时,数字减影血管造影是非常宝贵的。
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引用次数: 0
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 无麸质饮食对轻度至中度溃疡性结肠炎患者的疾病严重程度、生活质量和炎症指标的短期影响:三盲随机安慰剂对照试验。
IF 1.1 4区 医学 Q4 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-02-01 Epub Date: 2024-05-06 DOI: 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.
背景和研究目的:饮食是溃疡性结肠炎(UC)疾病的一个重要潜在因素。本研究旨在探讨无麸质饮食(GFD)对溃疡性结肠炎患者的疾病严重程度、生活质量和炎症指标的影响:在这项三盲随机安慰剂对照临床试验中,我们评估了无麸质饮食对轻度至中度 UC 患者的红细胞沉降率(ESR)、C 反应蛋白(CRP)、粪便钙蛋白、疾病严重程度和生活质量的影响。患者的生活质量和症状严重程度分别通过炎症性肠病问卷(IBDQ)和简易临床结肠炎活动指数(SCCAI)进行评估。患者接受了为期六周的治疗,并在干预前后接受了评估:患者(26 人)的平均年龄为 39.31 岁(标准差为 9.34)。在两个研究组中,ESR、CRP、IBDQ 和 SCCAI 的平均值在饮食干预后均无显着改善。两组的粪便钙蛋白均有所增加,但无统计学意义:我们没有发现麸质饮食对轻度至中度 UC 患者的炎症指标、生活质量和疾病严重程度有任何明显影响。现在就建议将无麸质饮食作为对 UC 患者安全有益的方案还为时尚早。有必要进一步开展样本量更大、随访时间更长的临床试验和队列研究,以获得更可靠的结果。
{"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 ,&nbsp;Naser Ebrahimi Daryani ,&nbsp;Najmeh Aletaha ,&nbsp;Nazanin Hesabgar ,&nbsp;Mohammad Saeid Rezaee-Zavareh ,&nbsp;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}
引用次数: 0
Chimeric antigen receptor-T cells targeting AFP-GPC3 mediate increased antitumor efficacy in hepatocellular carcinoma 靶向AFP-GPC3的嵌合抗原受体- t细胞介导肝细胞癌抗肿瘤疗效的增强。
IF 1.1 4区 医学 Q4 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-02-01 Epub Date: 2025-01-04 DOI: 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.
背景与研究目的:CAR-T细胞技术作为一种新型的免疫疗法,在血液系统恶性肿瘤的治疗中取得了成功,并在部分实体肿瘤中显示出潜在的疗效。靶向一种抗原的疗法有一些弱点,双靶向CAR-T细胞可能是更好的选择。甲胎蛋白(AFP)和胰甘聚糖-3 (GPC3)在肝细胞癌(HCC)中均高表达,是重要的标志物。我们的研究旨在比较AFP和GPC3双靶向CAR-T细胞对体外肝癌细胞的细胞毒性作用,以及其对SCID异种移植模型的治疗效果。材料和方法:将携带AFP CAR、GPC3 CAR或AFP-GPC3 CAR构建体的pLVX慢病毒载体转染人T淋巴细胞。以对照T细胞、AFP CAR-T细胞、GPC3 CAR-T细胞和AFP-GPC3 CAR-T细胞为效应细胞,以HLE (AFP-GPC3-)、Sh-GPC3-Huh-7 (AFP+)、Sh-AFP-Huh-7 (AFP+GPC3+)细胞为靶细胞。共培养6小时后,采用LDH细胞毒性试验评估CAR-T细胞对靶HCC细胞的杀伤作用。给患有Huh-7细胞源性肿瘤的SCID小鼠注射CAR-T细胞,然后检测小鼠肿瘤组织的病理变化、CD3ζ的表达以及IL-2和IFN-γ的水平。结果:AFP和GPC3在Huh-7细胞中高表达。AFP-GPC3 CAR-T细胞对表达特异性靶向抗原分子(AFP和GPC3)的HCC细胞具有显著的细胞杀伤作用。此外,AFP-GPC3 CAR-T细胞比AFP- CAR-T和GPC3 CAR-T细胞更能促进Huh-7细胞分泌Th细胞因子。体内实验结果表明,AFP-GPC3 CAR-T细胞比AFP- CAR-T和GPC3 CAR-T细胞更能抑制Huh-7细胞(AFP+GPC3+)衍生肿瘤的生长。结论:AFP和GPC3双靶向CAR-T细胞在HCC中的抗肿瘤作用优于AFP或GPC3单靶向CAR-T细胞。
{"title":"Chimeric antigen receptor-T cells targeting AFP-GPC3 mediate increased antitumor efficacy in hepatocellular carcinoma","authors":"Mingxing Li ,&nbsp;Tailin Chen ,&nbsp;Rongshi Huang,&nbsp;Yanhui Cen,&nbsp;Feilan Zhao,&nbsp;Rong Fan,&nbsp;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}
引用次数: 0
Survival of patients with non-viral hepatocellular carcinoma treated with trans-arterial chemoembolization: A multicenter cohort study 经动脉化疗栓塞治疗的非病毒性肝细胞癌患者的生存率:一项多中心队列研究
IF 1.1 4区 医学 Q4 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-02-01 Epub Date: 2025-01-10 DOI: 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.
背景和研究目的:很少有研究考虑经动脉化疗栓塞(TACE)治疗非病毒诱导的肝细胞癌(HCC)的患者,一些研究报道这些患者可能有较大的肿瘤,强调需要确定影响此类患者生存的因素。本研究旨在研究TACE治疗非病毒相关性HCC患者的特点和生存率。患者和方法:这是一项多中心观察性研究。从六个三级医疗中心(2008年1月至2022年6月)招募了接受TACE治疗的非病毒性相关性HCC患者(166例)。随访一直持续到死亡或研究结束(2023年8月)。结果:患者平均年龄60.2±9.5岁,男性占79.5%。病灶的平均大小为5.71±3.02 cm, 42.8%的患者为单发病灶。中位随访期为27.02个月(IQR 14.99 ~ 39.37),中位总生存期(OS)为42.14个月。Cox回归风险模型显示,影响生存的独立因素为:多灶性病变数量超过5个,死亡风险显著高于单灶性病变(HR = 8.5, p值= 0.001)。HAP评分D级患者死亡风险增加3倍(HR = 3.8, p值0.007)。对治疗无积极反应的个体面临着显著更高的死亡风险(HR = 10.76, p值0.001)。白蛋白-胆红素评分(ALBI)、Easy ALBI、血小板白蛋白(PAL)、血小板白蛋白-胆红素评分(PALBI)、肝癌动脉栓塞(HAP)和肿瘤负荷评分均不影响患者的生存。结论:肿瘤负荷是非病毒性HCC患者TACE术后生存的重要决定因素。HAP评分可用于选择从TACE获益的患者。
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引用次数: 0
NNMT suppresses H3K9me3 to facilitate malignant progression and drug resistance in gastric cancer NNMT抑制H3K9me3促进胃癌的恶性进展和耐药。
IF 1.1 4区 医学 Q4 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-02-01 Epub Date: 2025-01-04 DOI: 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.
背景和研究目的:烟酰胺n -甲基转移酶(Nicotinamide N-methyltransferase, NNMT)在肿瘤中异常表达,与肿瘤的进展和化疗耐药有关。本项目旨在探讨NNMT增强胃癌(GC) 5-氟尿嘧啶(5-FU)耐药的具体分子机制。材料与方法:采用生物信息学分析方法,分析NNMT在GC中的表达,并探讨其与患者预后的关系。通过京都基因与基因组百科全书(KEGG)分析了NNMT富集的信号通路。采用Western blot (WB)和定量逆转录聚合酶链反应(qRT-PCR)检测正常胃上皮细胞和胃癌细胞中NNMT mRNA和蛋白的表达。CCK8检测细胞活力和5-FU的IC50。流式细胞术检测细胞凋亡率。WB检测Ki67、上皮-间质转化(epithelial-mesenchymal transition, EMT)相关蛋白、PI3K、AKT、p-AKT、NNMT和H3K9me3的蛋白表达。我们采用Transwell法测定细胞迁移和侵袭能力。采用酶联免疫吸附法(ELISA)测定细胞中s -腺苷蛋氨酸(SAM)和s -腺苷-l -同型半胱氨酸(SAH)的含量。结果:NNMT在胃癌组织和细胞中显著上调,与患者预后呈负相关。抑制NNMT显著抑制胃癌细胞的活力、增殖、抗凋亡能力、迁移和侵袭能力,但提高癌细胞对5-FU的敏感性。然而,过表达NNMT通过降低通用甲基供体SAM抑制H3K9甲基化,激活PI3K/AKT通路,促进GC恶性进展,并引发对5-FU的耐药。结论:GC细胞中上调NNMT表达可通过抑制组蛋白甲基化抑制PI3K/AKT的激活,从而诱导5-FU耐药。
{"title":"NNMT suppresses H3K9me3 to facilitate malignant progression and drug resistance in gastric cancer","authors":"Bo Wang,&nbsp;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}
引用次数: 0
Cholecystocutaneous fistula: A rare case in an elderly female with a massive abdominal mass 胆囊皮瘘:一例罕见的老年女性腹部肿块。
IF 1.1 4区 医学 Q4 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-02-01 Epub Date: 2025-01-28 DOI: 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 ,&nbsp;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}
引用次数: 0
期刊
Arab Journal of Gastroenterology
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