Trial reportCancer prevention research (Philadelphia, Pa.)2017
Bioactivity of Oral Linaclotide in Human Colorectum for Cancer Chemoprevention.
Trial report in Cancer prevention research (Philadelphia, Pa.), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Guanylate cyclase-C Signaling Axis as a theragnostic target in colorectal cancer: a systematic review of literature.Frontiers in oncology · 2023Pooled it
- Targeting molecular and genetic pathways driving tumorigenesis for precision therapy in colorectal cancer.Cancer biology & therapy · 2026Review
- Was It Worth It? Response Data from >650 US and International Participants in Chemoprevention Trials.Cancer prevention research (Philadelphia, Pa.) · 2026Article
- Article
- Computational prognostic evaluation of Alzheimer's drugs from FDA-approved database through structural conformational dynamics and drug repositioning approaches.Scientific reports · 2023Article
- Guanylyl cyclase C ameliorates visceral pain: an unsuspected link.The Journal of clinical investigation · 2023Article
- Intestinal neuropod cell GUCY2C regulates visceral pain.The Journal of clinical investigation · 2023Article
- Decoding signaling mechanisms: unraveling the targets of guanylate cyclase agonists in cardiovascular and digestive diseases.Frontiers in pharmacology · 2023Review
- Guanylyl cyclase C as a diagnostic and therapeutic target in colorectal cancer.Personalized medicine · 2022Review
- A β-Catenin-TCF-Sensitive Locus Control Region Mediates GUCY2C Ligand Loss in Colorectal Cancer.Cellular and molecular gastroenterology and hepatology · 2022Article
- Receptor Guanylyl Cyclase C and Cyclic GMP in Health and Disease: Perspectives and Therapeutic Opportunities.Frontiers in endocrinology · 2022Review
- Phase I double-blind, placebo-controlled trial of dolcanatide (SP-333) 27 mg to explore colorectal bioactivity in healthy volunteers.Cancer biology & therapy · 2021Article
- Guanylyl cyclase C as a biomarker for immunotherapies for the treatment of gastrointestinal malignancies.Biomarkers in medicine · 2021Review
- An update on guanylyl cyclase C in the diagnosis, chemoprevention, and treatment of colorectal cancer.Expert review of clinical pharmacology · 2020Review
- APC-β-catenin-TCF signaling silences the intestinal guanylin-GUCY2C tumor suppressor axis.Cancer biology & therapy · 2020Article
- Two distinct GUCY2C circuits with PMV (hypothalamic) and SN/VTA (midbrain) origin.Brain structure & function · 2019Article
- Characterisation of proguanylin expressing cells in the intestine - evidence for constitutive luminal secretion.Scientific reports · 2019Article
- Blunted Evoked Prouroguanylin Endocrine Secretion in Chronic Constipation.Clinical and translational gastroenterology · 2019Article
- Silencing the GUCA2A-GUCY2C tumor suppressor axis in CIN, serrated, and MSI colorectal neoplasia.Human pathology · 2019Article
- The enduring promise of phosphodiesterase 5 inhibitors for colon cancer prevention.Translational gastroenterology and hepatology · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Guanylate cyclase C (GUCY2C) is a tumor-suppressing receptor silenced by loss of expression of its luminocrine hormones guanylin and uroguanylin early in colorectal carcinogenesis. This observation suggests oral replacement with a GUCY2C agonist may be an effective targeted chemoprevention agent. Linaclotide is an FDA-approved oral GUCY2C agonist formulated for gastric release, inducing fluid secretion into the small bowel to treat chronic idiopathic constipation. The ability of oral linaclotide to induce a pharmacodynamic response in epithelial cells of the colorectum in humans remains undefined. Here, we demonstrate that administration of 0.87 mg of oral linaclotide daily for 7 days to healthy volunteers, after oral colon preparation with polyethylene glycol solution (MoviPrep), activates GUCY2C, resulting in accumulation of its product cyclic (c)GMP in epithelial cells of the cecum, transverse colon, and distal rectum. GUCY2C activation by oral linaclotide was associated with homeostatic signaling, including phosphorylation of vasodilator-stimulated phosphoprotein and inhibition of proliferation quantified by reduced Ki67-positive epithelial cells. In the absence of the complete oral colonoscopy preparation, linaclotide did not alter cGMP production in epithelial cells of the colorectum, demonstrating that there was an effect related to the laxative preparation. These data show that the current FDA-approved formulation of oral linaclotide developed for small-bowel delivery to treat chronic idiopathic constipation is inadequate for reliably regulating GUCY2C in the colorectum to prevent tumorigenesis. The study results highlight the importance of developing a novel GUCY2C agonist formulated for release and activity targeted to the large intestine for colorectal cancer prevention.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.