ArticleDigestive diseases and sciences2020
A Cholecystokinin Receptor Antagonist Halts Nonalcoholic Steatohepatitis and Prevents Hepatocellular Carcinoma.
Article in Digestive diseases and sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04152473 (Phase 1 Study to Test Safety and Dose of Proglumide as an Anti-fibrotic Agent in Non-alcoholic Steatohepatitis), which is not on this map. Cited by 15 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Phase 1 Study to Test Safety and Dose of Proglumide as an Anti-fibrotic Agent in Non-alcoholic Steatohepatitis (NASH)
Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- Safety and Dosing Study of a Cholecystokinin Receptor Antagonist in Non-alcoholic Steatohepatitis.Clinical pharmacology and therapeutics · 2022Trial
- Interruption of cross-communication pathways alters the immune cell signature of pancreatic cancer and decreases tumor growth.Cell communication and signaling : CCS · 2026Article
- CCK-1R-selective and non-selective cholecystokinin antagonists, lorglumide, and proglumide increased toxicity of carboplatin to granulocyte-macrophage progenitor cells (CFU-GM) of bone marrow of rats.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Article
- Implicating the cholecystokinin B receptor in liver stem cell oncogenesis.American journal of physiology. Gastrointestinal and liver physiology · 2024Article
- Treatment with a Cholecystokinin Receptor Antagonist, Proglumide, Improves Efficacy of Immune Checkpoint Antibodies in Hepatocellular Carcinoma.International journal of molecular sciences · 2023Article
- An autocrine signaling circuit in hepatic stellate cells underlies advanced fibrosis in nonalcoholic steatohepatitis.Science translational medicine · 2023Article
- Hunger & satiety signals: another key mechanism involved in the NAFLD pathway.Frontiers in endocrinology · 2023Review
- Nutrient-Based Appetite Regulation.Journal of obesity & metabolic syndrome · 2022Review
- Safety and Pharmacokinetic Assessment of Oral Proglumide in Those with Hepatic Impairment.Pharmaceutics · 2022Article
- Proglumide Reverses Nonalcoholic Steatohepatitis by Interaction with the Farnesoid X Receptor and Altering the Microbiome.International journal of molecular sciences · 2022Article
- A Novel Purine and Uric Metabolism Signature Predicting the Prognosis of Hepatocellular Carcinoma.Frontiers in genetics · 2022Article
- Multi-organ Coordination of Lipoprotein Secretion by Hormones, Nutrients and Neural Networks.Endocrine reviews · 2021Review
- Vaccination with Polyclonal Antibody Stimulator (PAS) Prevents Pancreatic Carcinogenesis in the KRAS Mouse Model.Cancer prevention research (Philadelphia, Pa.) · 2021Article
- Targeting the Cholecystokinin Receptor: A Novel Approach for Treatment and Prevention of Hepatocellular Cancer.Cancer prevention research (Philadelphia, Pa.) · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
BACKGROUND AND
aimsNonalcoholic steatohepatitis (NASH) is a common inflammatory liver condition that may lead to cirrhosis and hepatocellular carcinoma (HCC). Risk factors for NASH include a saturated fat diet, altered lipid metabolism, and genetic and epigenetic factors, including microRNAs. Serum levels of cholecystokinin (CCK) are elevated in mice and humans that consume a high-saturated fat diet. CCK receptors (CCK-Rs) have been reported on fibroblasts which when activated can induce fibrosis; however, their role in hepatic fibrosis remains unknown. We hypothesized that elevated levels of CCK acting on the CCK-Rs play a role in the development of NASH and in NASH-associated HCC.
methodsWe performed a NASH Prevention study and Reversal study in mice fed a saturated fat 75% choline-deficient-ethionine-supplemented (CDE) diet for 12 or 18 weeks. In each study, half of the mice received untreated drinking water, while the other half received water supplemented with the CCK-R antagonist proglumide. CCK-R expression was evaluated in mouse liver and murine HCC cells.
resultsCCK receptor antagonist treatment not only prevented NASH but also reversed hepatic inflammation, fibrosis, and steatosis and normalized hepatic transaminases after NASH was established. Thirty-five percent of the mice on the CDE diet developed HCC compared with none in the proglumide-treated group. We found that CCK-BR expression was markedly upregulated in mouse CDE liver and HCC cells compared with normal hepatic parenchymal cells, and this expression was epigenetically regulated by microRNA-148a.
conclusionThese results support the novel role of CCK receptors in the pathogenesis of NASH and HCC.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.