Are Phosphodiesterase-5 Inhibitors a New Frontier for Prevention of Colorectal Cancer?

Jovani, Manol; Chan, Andrew T.

doi:10.1053/j.gastro.2019.07.017

Cited by 3 publications

(2 citation statements)

References 19 publications

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“…Moreover, they suggest the correlative therapeutic hypothesis that reconstituting GUCY2C signaling, by oral ligand replacement, by reactivating endogenous hormone generation, or by receptorindependent elevation of cGMP, may be a novel strategy for colorectal chemoprevention. 4,5,27,28 Hormones regulating the GUCY2C axis are central to the pathophysiology of intestinal tumorigenesis. However, mechanisms regulating GUCA2A and GUCA2B levels in health and disease remain undefined.…”

Section: Methodsmentioning

confidence: 99%

A β-Catenin-TCF-Sensitive Locus Control Region Mediates GUCY2C Ligand Loss in Colorectal Cancer

Rappaport

Entezari

Caspi

et al. 2022

Cellular and Molecular Gastroenterology and Hepatology

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Section: Methodsmentioning

confidence: 99%

A β-Catenin-TCF-Sensitive Locus Control Region Mediates GUCY2C Ligand Loss in Colorectal Cancer

Rappaport

Entezari

Caspi

et al. 2022

Cellular and Molecular Gastroenterology and Hepatology

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“…Furthermore, phosphodiesterase five inhibitors have been associated with a lower risk of developing colorectal cancer. [60,61] Protooncogene tyrosine-protein kinase ROS (ROS1), an enzyme synthesized by a gene ROS1, that is involved in sending signals in cells and cell growth, so its inhibition can counteract tumoral development. [62] Others ITCs predicted targets are dihydrofolate reductase, coagulation factor X, serine/threonine-protein kinase pknB, and serine-protein kinase ATM.…”

Section: Target Profiling and Prediction Of Activity Type Of Isothiocyanatesmentioning

confidence: 99%

Chemoinformatic Analysis of Isothiocyanates: Their Impact in Nature and Medicine

Guerrero-Alonso

Antúnez-Mojica

Medina-Franco

2021

Molecular Informatics

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Isothiocyanates (ITCs) have a significant impact on food and natural product chemistry. Several dietary components and food chemicals contain the isothiocyanate moiety. In addition, many ITCs interact with macromolecules of biological relevance, making these compounds relevant for potential therapeutic applications and disease prevention. However, there is a lack of systematic analysis of ITCs in chemical and biological databases. Herein, we conducted a comprehensive analysis of ITCs present in public domain databases, including natural products, food chemicals, macromolecular targets of drugs, and the Protein Data Bank. A total of 154 ITCs were found, which can be classified into seven categories: acyclic, cyclic, polycyclic, aromatic, polyaromatic, indolic, and glycosylated. 24 ITCs were reported in 18 vegetable sources, mainly in cruciferous vegetables (Brassica oleracea L.). Calculated properties of pharmaceutical relevance indicated that 11 % of the 154 ITCs would be suitable to be orally absorbed and 48 % permeate the blood-brain-barrier. It was also found that seven molecular targets have been co-crystallized with ITCs and the most frequent is the macrophage migration inhibitory factor. It is expected that this work will contribute to the sub-disciplines of natural products and food informatics.

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No association between use of phosphodiesterase 5 inhibitors and colorectal cancer in men with erectile dysfunction

Soriano

Rodrı́guez

2020

Pharmacoepidemiology and Drug

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PurposeThere is an increase interest on the potential chemoprotective effect of selective phosphodiesterase 5 (PDE5) inhibitors. Several authors have shown in vivo the immune‐mediated anti‐tumor effect of these inhibitors on tumors arising from the digestive tract.ObjectivesTo test the potential effect of selective PDE5 inhibitors against colorectal cancer (CRC) onset previously observed.MethodsWe used data from The Health Improvement Network database and identified an established cohort of 200 000 new users of low‐dose aspirin and a matched comparison cohort aged 40‐84 years between 1 January 2000 and 31 December 2011. A follow‐up to identify CRC cases was performed within an extensive validation exercise. Nested case‐control analyses compared PDE5 inhibitors vs non‐use on CRC risk were performed.ResultsRestricting to males (59.3% controls and 59.5% cases), no association was observed among current users of PDE5 inhibitors (1.05 [95% CI: 0.69‐1.60]) and neither among recent (1.36 [95% CI: 0.81‐2.28]) or past users (1.06 [95% CI: 0.72‐1.58]). No duration response effect was found.ConclusionsOur results do not support an increased risk of CRC associated with the use of PDE5 inhibitors among men with erectile dysfunction.

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Are Phosphodiesterase-5 Inhibitors a New Frontier for Prevention of Colorectal Cancer?

Cited by 3 publications

References 19 publications

A β-Catenin-TCF-Sensitive Locus Control Region Mediates GUCY2C Ligand Loss in Colorectal Cancer

A β-Catenin-TCF-Sensitive Locus Control Region Mediates GUCY2C Ligand Loss in Colorectal Cancer

Chemoinformatic Analysis of Isothiocyanates: Their Impact in Nature and Medicine

No association between use of phosphodiesterase 5 inhibitors and colorectal cancer in men with erectile dysfunction

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