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Nature Reviews Gastroenterology &Hepatology最新文献

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CAR T cell therapies in gastrointestinal cancers: current clinical trials and strategies to overcome challenges
IF 65.1 1区 医学
Nature Reviews Gastroenterology &Hepatology Pub Date : 2025-04-14 DOI: 10.1038/s41575-025-01062-y
Hinrich Abken
{"title":"CAR T cell therapies in gastrointestinal cancers: current clinical trials and strategies to overcome challenges","authors":"Hinrich Abken","doi":"10.1038/s41575-025-01062-y","DOIUrl":"https://doi.org/10.1038/s41575-025-01062-y","url":null,"abstract":"<p>Despite multimodal treatment options, most gastrointestinal cancers are still associated with high mortality rates and poor responsiveness to immunotherapy. The unprecedented efficacy of chimeric antigen receptor (CAR)-engineered T cells in the treatment of haematological malignancies raised interest in translating CAR T cell therapies to the treatment of gastrointestinal cancers. Treatment of solid cancers with canonical CAR T cells faces substantial challenges, including the dense architecture of the tumour tissue, the tolerogenic environment with low tumour-intrinsic immunogenicity, the rareness of targetable tumour-selective antigens, the antigenic heterogeneity of cancer cells, and the profound metabolic and immune cell disbalances. This Review provides an overview of CAR T cell trials in the treatment of gastrointestinal cancers, discussing considerations relating to safety, efficacy, potential reasons for failure and options for improving CAR T cells for the future. In addition, lessons regarding how to improve efficacy are drawn from CAR T cells armed with adjuvants that sustain their activation within the hostile environment and activate resident immune cells. As the field is rapidly evolving, current treatment modalities and editing CAR T cell functionalities are being refined towards a potentially more successful CAR T cell therapy for gastrointestinal cancers.</p>","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"16 1","pages":""},"PeriodicalIF":65.1,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Diet-driven microbiome restoration associated with cardiometabolic benefits
IF 65.1 1区 医学
Nature Reviews Gastroenterology &Hepatology Pub Date : 2025-04-10 DOI: 10.1038/s41575-025-01067-7
Jordan Hindson
{"title":"Diet-driven microbiome restoration associated with cardiometabolic benefits","authors":"Jordan Hindson","doi":"10.1038/s41575-025-01067-7","DOIUrl":"https://doi.org/10.1038/s41575-025-01067-7","url":null,"abstract":"<p>The effects of industrialization on the human gut microbiome have been associated with an increased risk of non-communicable diseases. In a new study published in <i>Cell</i>, researchers have investigated the effect of a non-industrialized-type diet on the gut microbiome and on the risk of chronic diseases.</p><p>The researchers conducted a randomized controlled feeding trial in 30 healthy Canadian adults. Participants were randomized to consume either a non-industrialized-type diet or their normal diet, and to receive a dose of either <i>Limosilactobacillus reuteri</i> or placebo. The high-fibre, mostly plant-based diet, termed the non-industrialized microbiome restore (NiMe) diet, was designed based on foods consumed in rural Papau New Guinea. <i>L. reuteri</i> is a bacterium not commonly observed in industrialized gut microbiomes.</p>","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"27 6 1","pages":""},"PeriodicalIF":65.1,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143813404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Metabolic diseases in the East Asian populations
IF 65.1 1区 医学
Nature Reviews Gastroenterology &Hepatology Pub Date : 2025-04-08 DOI: 10.1038/s41575-025-01058-8
Zhonghan Sun, Yan Zheng
{"title":"Metabolic diseases in the East Asian populations","authors":"Zhonghan Sun, Yan Zheng","doi":"10.1038/s41575-025-01058-8","DOIUrl":"https://doi.org/10.1038/s41575-025-01058-8","url":null,"abstract":"<p>East Asian populations, which account for approximately 20% of the global population, have become central to the worldwide rise of metabolic diseases over the past few decades. The prevalence of metabolic disorders, including type 2 diabetes mellitus, hypertension and metabolic dysfunction-associated steatotic liver disease, has escalated sharply, contributing to a substantial burden of complications such as cardiovascular disease, chronic kidney disease, cancer and increased mortality. This concerning trend is primarily driven by a combination of genetic predisposition, unique fat distribution patterns and rapidly changing lifestyle factors, including urbanization and the adoption of Westernized dietary habits. Current advances in genomics, proteomics, metabolomics and microbiome research have provided new insights into the biological mechanisms that might contribute to the heightened susceptibility of East Asian populations to metabolic diseases. This Review synthesizes epidemiological data, risk factors and biomarkers to provide an overview of how metabolic diseases are reshaping public health in East Asia and offers insights into biological and societal drivers to guide effective, region-specific strategies.</p>","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"34 1","pages":""},"PeriodicalIF":65.1,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143797750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A sensory neuron–gastric cancer circuit 感觉神经元-胃癌回路
IF 65.1 1区 医学
Nature Reviews Gastroenterology &Hepatology Pub Date : 2025-04-04 DOI: 10.1038/s41575-025-01066-8
Eleni Kotsiliti
{"title":"A sensory neuron–gastric cancer circuit","authors":"Eleni Kotsiliti","doi":"10.1038/s41575-025-01066-8","DOIUrl":"https://doi.org/10.1038/s41575-025-01066-8","url":null,"abstract":"<p>A new study published in <i>Nature</i> explored the role of sensory nerves in gastric cancer. “Cancer cells in extra-cranial solid tumours create an electrical circuit with the sensory nervous system,” says Timothy Wang, corresponding author of the study.</p><p>Using multiple mouse models of gastric cancer, the researchers showed that sensory nerves expressing calcitonin gene-related peptide (CGRP) created a neural network around tumour cells in the stomach. Knockout in vivo and in vitro experiments demonstrated that CGRP<sup>+</sup> neural expansion was dependent on NGF–TRK signalling and that gastric cells preferentially attracted CGRP<sup>+</sup> peptidergic nociceptive neurons.</p>","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"33 1","pages":""},"PeriodicalIF":65.1,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143775646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
International collaborative research to improve gallbladder cancer prevention
IF 65.1 1区 医学
Nature Reviews Gastroenterology &Hepatology Pub Date : 2025-04-04 DOI: 10.1038/s41575-025-01061-z
Dominique Scherer, Rajiv Kumar, Justo Lorenzo Bermejo
{"title":"International collaborative research to improve gallbladder cancer prevention","authors":"Dominique Scherer, Rajiv Kumar, Justo Lorenzo Bermejo","doi":"10.1038/s41575-025-01061-z","DOIUrl":"https://doi.org/10.1038/s41575-025-01061-z","url":null,"abstract":"The European–Latin American Research Consortium towards Eradication of Preventable Gallbladder Cancer (EULAT Eradicate GBC) is identifying geographical, environmental, lifestyle, genetic and molecular risk factors for gallbladder cancer. Collaborative research is essential to improve prevention of this aggressive tumour, especially in high-incidence, low-income and middle-income regions.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"37 1","pages":""},"PeriodicalIF":65.1,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143775568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Behavioural interventions increase uptake of CRC screening
IF 65.1 1区 医学
Nature Reviews Gastroenterology &Hepatology Pub Date : 2025-04-04 DOI: 10.1038/s41575-025-01064-w
Katrina Ray
{"title":"Behavioural interventions increase uptake of CRC screening","authors":"Katrina Ray","doi":"10.1038/s41575-025-01064-w","DOIUrl":"https://doi.org/10.1038/s41575-025-01064-w","url":null,"abstract":"<p>A new trial, published in <i>The Lancet</i>, has shown that adding a single sentence with a suggested deadline for return of a faecal immunochemical test (FIT) in the invitation letter reduced the need to issue reminder letters and led to a more timely FIT return as part of a national colorectal cancer (CRC) screening programme.</p><p>The TEMPO trial was a 2 × 4 factorial, eight-arm, randomized controlled trial in the nationwide Scottish Bowel Screening Programme in which 40,000 adults (aged 50–74 years) eligible for CRC screening were allocated randomly to one of eight groups that included either a standard invitation, a suggested FIT return deadline (1, 2 or 4 weeks) or use of a planning tool (with or without a FIT return deadline of 1, 2 or 4 weeks). “The intention–behaviour gap is well-recognized within behavioural science and we wanted to develop an intervention which supported people who were motivated and valued bowel screening to complete the FIT,” says author Kathryn Robb.</p>","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"36 1","pages":""},"PeriodicalIF":65.1,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143775647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Incorporating genetic variations in alcohol-associated liver disease trials for East Asian populations
IF 65.1 1区 医学
Nature Reviews Gastroenterology &Hepatology Pub Date : 2025-03-24 DOI: 10.1038/s41575-025-01060-0
Bossng Kang
{"title":"Incorporating genetic variations in alcohol-associated liver disease trials for East Asian populations","authors":"Bossng Kang","doi":"10.1038/s41575-025-01060-0","DOIUrl":"https://doi.org/10.1038/s41575-025-01060-0","url":null,"abstract":"<p>I read with great interest the article by Lee et al. (Lee, B. P. et al. Designing clinical trials to address alcohol use and alcohol-associated liver disease: an expert panel Consensus Statement. <i>Nat. Rev. Gastroenterol. Hepatol</i>. <b>21</b>, 626–645 (2024))<sup>1</sup>. In their Consensus Statement<sup>1</sup>, the authors are to be commended for their comprehensive framework, which integrates methodologies from alcohol use disorder and alcohol-associated liver disease (ALD) research to enhance the quality and efficacy of clinical trials. This effort represents a major step towards addressing the dual challenges of alcohol use and liver disease. However, further refinement is warranted regarding the application of heavy drinking thresholds, particularly in populations with unique genetic predispositions such as East Asian individuals, a population in which aldehyde dehydrogenase 2 (<i>ALDH2</i>) polymorphisms are highly prevalent<sup>2,3</sup>.</p>","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"3 1","pages":""},"PeriodicalIF":65.1,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143695501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Reply to ‘Incorporating genetic variations in alcohol-associated liver disease trials for East Asian populations’
IF 65.1 1区 医学
Nature Reviews Gastroenterology &Hepatology Pub Date : 2025-03-24 DOI: 10.1038/s41575-025-01059-7
Mack C. Mitchell, Brian P. Lee, Jessica Mellinger, Laura E. Nagy
{"title":"Reply to ‘Incorporating genetic variations in alcohol-associated liver disease trials for East Asian populations’","authors":"Mack C. Mitchell, Brian P. Lee, Jessica Mellinger, Laura E. Nagy","doi":"10.1038/s41575-025-01059-7","DOIUrl":"https://doi.org/10.1038/s41575-025-01059-7","url":null,"abstract":"<p>We thank Kang for their comments on our recent Consensus Statement (Lee, B. P. et al. Designing clinical trials to address alcohol use and alcohol-associated liver disease: an expert panel Consensus Statement. <i>Nat. Rev. Gastroenterol. Hepatol</i>. <b>21</b>, 626–645 (2024))<sup>1</sup> to incorporate genetic variations into consideration (Kang, B. Incorporating genetic variations in alcohol-associated liver disease trials for East Asian populations. <i>Nat. Rev. Gastroenterol. Hepatol</i>. https://doi.org/10.1038/s41575-025-01060-0 (2025))<sup>2</sup>. We agree that people who are deficient in ALDH2 and drink alcohol might be at increased risk of cancer of the upper digestive tract, oesophagus and liver. The increased risk of cancer in those who are ALDH2-deficient noted by Kang was not the focus of our initiative, but we appreciate the acknowledgement of the increased risk for this population.</p>","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"33 1","pages":""},"PeriodicalIF":65.1,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143695504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cell therapy for liver disorders: past, present and future
IF 65.1 1区 医学
Nature Reviews Gastroenterology &Hepatology Pub Date : 2025-03-18 DOI: 10.1038/s41575-025-01050-2
M. Carmen Ortuño-Costela, Massimo Pinzani, Ludovic Vallier
{"title":"Cell therapy for liver disorders: past, present and future","authors":"M. Carmen Ortuño-Costela, Massimo Pinzani, Ludovic Vallier","doi":"10.1038/s41575-025-01050-2","DOIUrl":"https://doi.org/10.1038/s41575-025-01050-2","url":null,"abstract":"<p>The liver fulfils a plethora of vital functions and, due to their importance, liver dysfunction has life-threatening consequences. Liver disorders currently account for more than two million deaths annually worldwide and can be classified broadly into three groups, considering their onset and aetiology, as acute liver diseases, inherited metabolic disorders and chronic liver diseases. In the most advanced and severe forms leading to liver failure, liver transplantation is the only treatment available, which has many associated drawbacks, including a shortage of organ donors. Cell therapy via fully mature cell transplantation is an advantageous alternative that may be able to restore a damaged organ’s functionality or serve as a bridge until regeneration can occur. Pioneering work has shown that transplanting adult hepatocytes can support liver recovery. However, primary hepatocytes cannot be grown extensively in vitro as they rapidly lose their metabolic activity. Therefore, different cell sources are currently being tested as alternatives to primary cells. Human pluripotent stem cell-derived cells, chemically induced liver progenitors, or ‘liver’ organoids, hold great promise for developing new cell therapies for acute and chronic liver diseases. This Review focuses on the advantages and drawbacks of distinct cell sources and the relative strategies to address different therapeutic needs in distinct liver diseases.</p>","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"7 1","pages":""},"PeriodicalIF":65.1,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
EASL Liver Cancer Summit 2025
IF 45.9 1区 医学
Nature Reviews Gastroenterology &Hepatology Pub Date : 2025-03-12 DOI: 10.1038/s41575-025-01057-9
Jordan Hindson
{"title":"EASL Liver Cancer Summit 2025","authors":"Jordan Hindson","doi":"10.1038/s41575-025-01057-9","DOIUrl":"10.1038/s41575-025-01057-9","url":null,"abstract":"","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"22 4","pages":"225-225"},"PeriodicalIF":45.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143598777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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