Canadian Institutes of Health Research grant to JL

A Mantovani

AH Wiese

AK Mustafa

Angela Ianaro

AR Moser

B Gemici

BA Teicher

BN Chorley

Charlotte Cheadle

Fabio Cominelli

G Farrugia

G Yang

H Kimura

H Rechreche

Jane A. Mitchell

JL Wallace

John L. Wallace

K Kashfi

K Seyama

KL Flannigan

Kyle L. Flannigan

L Li

M Chattopadhyay

M Valladares-Ayerbes

M Whiteman

Mark Paul-Clark

Maxim Freydin

MC Jaramillo

Melissa Chan

MPG Barnett

Nicholas Kirkby

O Tetsu

Pallavi Devchand

PM Kearney

R Blackler

RC Macadam

RF Logan

RJ Fijneman

RS Sandler

S Fiorucci

SD Solomon

T Iwama

T Kudo

T Watanabe

Terence A. Agbor

W Elsheikh

Wagdi Elsheikh

Y Kishimoto

Y Narushima

Y Zhu

Z Pálinkás

PLoS ONE

PubMed

Paul-Clark, M

Elsheikh, W

Kirkby, N

Chan, M

Devchand, P

Agbor, TA

Flannigan, KL

Cheadle, C

Freydin, M

Ianaro, A

Mitchell, JA

Wallace, JL

Queen Mary Research Online

Profound Chemopreventative Effects of a Hydrogen Sulfide-Releasing NSAID in the APC(Min/+) Mouse Model of Intestinal Tumorigenesis

Nonsteroidal anti-inflammatory drugs have been shown to reduce the incidence of gastrointestinal
cancers, but the propensity of these drugs to cause ulcers and bleeding limits their
use. H2S has been shown to be a powerful cytoprotective and anti-inflammatory substance
in the digestive system. This study explored the possibility that a H2S-releasing nonsteroidal
anti-inflammatory drug (ATB-346) would be effective in a murine model of hereditary intestinal
cancer (APCMin+ mouse) and investigated potential mechanisms of action via transcriptomics
analysis. Daily treatment with ATB-346 was significantly more effective at preventing
intestinal polyp formation than naproxen. Significant beneficial effects were seen with a
treatment period of only 3–7 days, and reversal of existing polyps was observed in the
colon. ATB-346, but not naproxen, significantly decreased expression of intestinal cancerassociated
signaling molecules (cMyc, β-catenin). Transcriptomic analysis identified 20
genes that were up-regulated in APCMin+ mice, 18 of which were reduced to wild-type levels
by one week of treatment with ATB-346. ATB-346 is a novel, gastrointestinal-sparing antiinflammatory
drug that potently and rapidly prevents and reverses the development of precancerous
lesions in a mouse model of hereditary intestinal tumorigenesis. These effects
may be related to the combined effects of suppression of cyclooxygenase and release of
H2S, and correction of most of the APCMin+-associated alterations in the transcriptome.
ATB-346 may represent a promising agent for chemoprevention of tumorigenesis in the GI
tract and elsewhere

Spiral - Imperial College Digital Repository

Nonsteroidal anti-inflammatory drugs have been shown to reduce the incidence of gastrointestinal cancers, but the propensity of these drugs to cause ulcers and bleeding limits their use. H2S has been shown to be a powerful cytoprotective and anti-inflammatory substance in the digestive system. This study explored the possibility that a H2S-releasing nonsteroidal anti-inflammatory drug (ATB-346) would be effective in a murine model of hereditary intestinal cancer (APCMin+ mouse) and investigated potential mechanisms of action via transcriptomics analysis. Daily treatment with ATB-346 was significantly more effective at preventing intestinal polyp formation than naproxen. Significant beneficial effects were seen with a treatment period of only 3-7 days, and reversal of existing polyps was observed in the colon. ATB-346, but not naproxen, significantly decreased expression of intestinal cancer-associated signaling molecules (cMyc, β-catenin). Transcriptomic analysis identified 20 genes that were up-regulated in APCMin+ mice, 18 of which were reduced to wild-type levels by one week of treatment with ATB-346. ATB-346 is a novel, gastrointestinal-sparing anti-inflammatory drug that potently and rapidly prevents and reverses the development of pre-cancerous lesions in a mouse model of hereditary intestinal tumorigenesis. These effects may be related to the combined effects of suppression of cyclooxygenase and release of H2S, and correction of most of the APCMin+-associated alterations in the transcriptome. ATB-346 may represent a promising agent for chemoprevention of tumorigenesis in the GI tract and elsewhere

Terence A Agbor

Kyle L Flannigan

Jane A Mitchell

John L Wallace

Directory of Open Access Journals

Profound Chemopreventative Effects of a Hydrogen Sulfide-Releasing NSAID in the APCMin/+ Mouse Model of Intestinal Tumorigenesis.

Crossref

Profound Chemopreventative Effects of a Hydrogen Sulfide-Releasing NSAID in the APCMin/+ Mouse Model of Intestinal Tumorigenesis

Nonsteroidal anti-inflammatory drugs have been shown to reduce the incidence of gastrointestinal cancers, but the propensity of these drugs to cause ulcers and bleeding limits their use. H2S has been shown to be a powerful cytoprotective and anti-inflammatory substance in the digestive system. This study explored the possibility that a H2S-releasing nonsteroidal anti-inflammatory drug (ATB-346) would be effective in a murine model of hereditary intestinal cancer (APCMin+ mouse) and investigated potential mechanisms of action via transcriptomics analysis. Daily treatment with ATB-346 was significantly more effective at preventing intestinal polyp formation than naproxen. Significant beneficial effects were seen with a treatment period of only 3–7 days, and reversal of existing polyps was observed in the colon. ATB-346, but not naproxen, significantly decreased expression of intestinal cancer-associated signaling molecules (cMyc, β-catenin). Transcriptomic analysis identified 20 genes that were up-regulated in APCMin+ mice, 18 of which were reduced to wild-type levels by one week of treatment with ATB-346. ATB-346 is a novel, gastrointestinal-sparing anti-inflammatory drug that potently and rapidly prevents and reverses the development of pre-cancerous lesions in a mouse model of hereditary intestinal tumorigenesis. These effects may be related to the combined effects of suppression of cyclooxygenase and release of H2S, and correction of most of the APCMin+-associated alterations in the transcriptome. ATB-346 may represent a promising agent for chemoprevention of tumorigenesis in the GI tract and elsewhere

Paul Clark, Mark

Elsheikh, Wagdi

Kirkby, Nicholas

Chan, Melissa

Devchand, Pallavi

Agbor, Terence A.

Flannigan, Kyle L.

Cheadle, Charlotte

Freydin, Maxim

Mitchell, Jane A.

Wallace, John L.

IANARO, ANGELA

Archivio della ricerca - Università degli studi di Napoli Federico II

Profound chemopreventative effects of a hydrogen sulfide-releasing nsaid in the APCMin/+ mouse model of intestinal tumorigenesis

https://qmro.qmul.ac.uk/xmlui/bitstream/123456789/32293/1/Paul-Clark%20et%20al.%202016.%20Profound%20Chemopreventative%20Effects%20of%20a%20Hydrogen%20Sulfide-Releasing%20NSAID

Profound Chemopreventative Effects of a Hydrogen Sulfide-Releasing NSAID in the APC(Min/+) Mouse Model of Intestinal Tumorigenesis

Abstract

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Queen Mary Research Online

Spiral - Imperial College Digital Repository

Directory of Open Access Journals

Crossref

Archivio della ricerca - Università degli studi di Napoli Federico II