Sung, E. Z. H., Arasaradnam, Ramesh P., Jarvie, E. M., James, Sean, Goodyear, S. J., Borman, R. A., Snead, David, Sanger, G. J. and Nwokolo, Chuka U.. (2012) Effects of neo-adjuvant chemotherapy for oesophago-gastric cancer on neuro-muscular gastric function. Molecular Biology Reports, Vol.39 (No.12). pp. 9989-9994. ISSN 0301-4851

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Abstract

Delayed gastric emptying symptoms are often reported after chemotherapy. This study aims to characterise the effects of chemotherapy on gastric neuro-muscular function. Patients undergoing elective surgery for oesophago-gastric cancer were recruited. Acetylcholinesterase, nNOS, ghrelin receptor and motilin expressions were studied in gastric sections from patients receiving no chemotherapy (n = 3) or oesophageal (n = 2) or gastric (n = 2) chemotherapy. A scoring system quantified staining intensity (0–3; no staining to strong). Stomach sections were separately suspended in tissue baths for electrical field stimulation (EFS) and exposure to erythromycin or carbachol; three patients had no chemotherapy; four completed cisplatin-based chemotherapy within 6 weeks prior to surgery. AChE expression was markedly decreased after chemotherapy (scores 2.3 ± 0.7, 0.5 ± 0.2 and 0 ± 0 in non-chemotherapy, oesophageal- and gastric-chemotherapy groups (p < 0.03 each) respectively. Ghrelin receptor and motilin expression tended to increase (ghrelin: 0.7 ± 0.4 vs 2.0 ± 0.4 and 1.2 ± 0.2 respectively; p = 0.04 and p = 0.2; motilin: 0.7 ± 0.5 vs 2.2 ± 0.5 and 2.0 ± 0.7; p = 0.06 and p = 0.16). Maximal contraction to carbachol was 3.7 ± 0.7 g and 1.9 ± 0.8 g (longitudinal muscle) and 3.4 ± 0.4 g and 1.6 ± 0.6 (circular) in non-chemotherapy and chemotherapy tissues respectively (p < 0.05 each). There were loss of AChE and reduction in contractility to carbachol. The tendency for ghrelin receptors to increase suggests an attempt to upregulate compensating systems. Our study offers a mechanism by which chemotherapy markedly alters neuro-muscular gastric function.

Item Type:	Journal Article
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) R Medicine > RM Therapeutics. Pharmacology
Divisions:	Faculty of Medicine > Warwick Medical School > Health Sciences
Library of Congress Subject Headings (LCSH):	Drugs -- Side effects, Esophagus -- Cancer -- Chemotherapy, Stomach -- Cancer -- Chemotherapy, Stomach -- Physiology
Journal or Publication Title:	Molecular Biology Reports
Publisher:	Springer
ISSN:	0301-4851
Date:	December 2012
Volume:	Vol.39
Number:	No.12
Page Range:	pp. 9989-9994
Identification Number:	10.1007/s11033-012-1866-7
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
Funder:	GlaxoSmithKline
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URI:	http://wrap.warwick.ac.uk/id/eprint/50138

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