Immunohistochemical and quantitative mRNA assessment of ghrelin expression in gastric and oesophageal adenocarcinoma

Mottershead, Marcus; Karteris, Emmanuel; Barclay, Jill; Suortamo, Saira; Newbold, Mark; Randeva, Harpal S.; Nwokolo, Chuka U.

doi:10.1136/jcp.2006.038356

Cited by 34 publications

(17 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Interestingly, several studies revealed that ghrelin expression in cancer cells is decreased in comparison to healthy tissue. This was observed in thyroid, stomach, esophagus, pancreas and renal cell carcinoma [28,[34][35][36]. Therefore, if pro-proliferative properties of ghrelin should be considered, it could be discussed if its absence or poor expression in cancer tissue provides protection from further growth.…”

Section: Discussionmentioning

confidence: 99%

Ghrelin and obestatin in thyroid gland — immunohistochemical expression in nodular goiter, papillary and medullary cancer

Gurgul

Kasprzak

Błaszczyk

et al. 2015

Folia Histochem Cytobiol.

View full text Add to dashboard Cite

Introduction. Previous studies analyzing ghrelin and obestatin expression in thyroid gland tissue are not unanimous and are mostly related to ghrelin. The role of ghrelin and obestatin in the thyroid gland appears very interesting due to their probable involvement in cell proliferation. Furthermore, since the thyroid gland is associated with the maintenance of energy balance, the relationship between ghrelin, obestatin and thyroid function is worthy of consideration. The aim of the study was to assess ghrelin and obestatin immunocytochemical expression in nodular goiter (NG), papillary cancer (PTC) and medullary cancer (MTC). Material and methods. Analyzed samples included 9 cases of NG, 8 cases of PTC and 11 cases of MTC. The analysis of ghrelin and obestatin expression was performed by use of the immunohistochemical (IHC) EnVision system and evaluated with filter HSV software (quantitative morphometric analysis). Results. Quantitative ghrelin expression in MTC cells was higher than in NG (p = 0.013) and correlated negatively with the size of the tumor (r= -0.829, p < 0.05). We did not observe any differences in ghrelin expression neither between MTC and PTC nor between NG and PTC. Obestatin immunoexpression pattern in all analyzed specimens was irregular and poorly accented. The strongest immunoreactivity for obestatin was demonstrated in NG. In MTC obestatin expression was significantly weaker than in NG and PTC (p < 0.05 in both cases). In NG the intensity of obestatin immunostaining was significantly higher than that of ghrelin (p = 0.03). Conversely, ghrelin expression in MTC was definitely more evident than obestatin immunoreactivity (p < 0.01). There was no statistically significant difference between ghrelin and obestatin expression in PTC. No correlations were detected between reciprocal tissue expressions of ghrelin and obestatin in the analyzed specimens of NG, PTC or MTC. Conclusions. The differences between ghrelin expression in NG and MTC suggest that ghrelin may be involved in thyroid cell proliferation. The differences between ghrelin and obestatin immunoreactivity in benign and malignant thyroid tumors could support the theory of alternative transcription of the preproghrelin gene and independent production of ghrelin and obestatin.

show abstract

Section: Discussionmentioning

confidence: 99%

Ghrelin and obestatin in thyroid gland — immunohistochemical expression in nodular goiter, papillary and medullary cancer

Gurgul

Kasprzak

Błaszczyk

et al. 2015

Folia Histochem Cytobiol.

View full text Add to dashboard Cite

show abstract

“…In vitro studies suggest that ghrelin may enhance the proliferation of prostate and pancreatic (Duxbury et al, 2003) cancer cells, but not of a lung cancer cell line, where it induced dose-dependent inhibition of cell proliferation and increased apoptosis (Cassoni et al, 2006). Some tumours from archival samples express ghrelin , whereas others do not (Cassoni et al, 2006;Mottershead et al, 2007). Tumour incidence is not increased in patients with anorexia nervosa (Mellemkjaer et al, 2001) despite elevated ghrelin levels.…”

Section: Intravenous Ghrelin For Cancer Anorexia/cachexia F Strasser mentioning

confidence: 99%

Safety, tolerability and pharmacokinetics of intravenous ghrelin for cancer-related anorexia/cachexia: a randomised, placebo-controlled, double-blind, double-crossover study

Strasser¹,

et al. 2008

View full text Add to dashboard Cite

Twenty-one adult patients were randomised to receive ghrelin on days 1 and 8 and placebo on days 4 and 11 or vice versa, given intravenously over a 60-min period before lunch: 10 received 2 mg kg À1 (lower-dose) ghrelin; 11 received 8 mg kg À1 (upper-dose) ghrelin. Active and total ghrelin, growth hormone (GH), and insulin-like growth factor 1 levels were monitored at baseline (4 -5 days before day 1), during treatment days, and at end of study (day 17/18). Drug-related adverse events (assessed by NCI-CTC-toxicity criteria and cardiac examination) did not differ between ghrelin and placebo. No grade 3/4 toxicity or stimulation of tumour growth was observed. The peak increase of GH, a biological marker of ghrelin action, was 25 ng ml À1 with lower-dose and 42 ng ml À1 with upper-dose ghrelin. Morning fasting total ghrelin levels were higher (Po0.05) for upper-dose patients at end of study (3580 pg ml À1 ) than at baseline (990 pg ml À1 ). Insulin-like growth factor 1 levels did not change. At day 8, 81% of patients preferred ghrelin to placebo as against 63% at the end of study. Nutritional intake and eating-related symptoms, measured to explore preliminary efficacy, did not differ between ghrelin and placebo. Ghrelin is well tolerated and safe in patients with advanced cancer. For safety, tolerance, and patients' preference for treatment, no difference was observed between the lower-and upper-dose group.

show abstract

“…In vitro studies suggest that ghrelin may enhance the proliferation of prostate [50] and pancreatic [51] cancer cells, but not of a lung cancer cell line, where it induced dose-dependent inhibition of cell proliferation and increased apoptosis [52]. Some tumors from archival samples express ghrelin [53], whereas others (gastric cancer and esophageal cancer) do not [54]. According to a review that analyzed ghrelin administration studies, there was no report of anyone suffering from new cancer as an adverse event among 1,850 participants who were registered to 121 studies.…”

Section: Effects Of Ghrelin Administration After Total Gastrectomymentioning

confidence: 99%

Clinical application of ghrelin administration for gastric cancer patients undergoing gastrectomy

et al. 2013

View full text Add to dashboard Cite

Loss of body weight is a common (and the most serious) sequela after gastrectomy. It impairs quality of life, increases various diseases including infection, and may affect long-term survival. Ghrelin, an intrinsic ligand of the growth hormone secretagogue receptor, was discovered in the stomach in 1999. In addition to growth hormone secretion, ghrelin has pleiotropic functions including appetite stimulation, increasing bowel movement and absorption, and anti-inflammatory reactions. In consequence, ghrelin comprehensively leads positive energy balance and weight gain. The fundic gland of the stomach produces the majority of ghrelin, and plasma ghrelin declines to 10-30 % of the preoperative level after total gastrectomy and 50-70 % after distal gastrectomy. Although plasma ghrelin is never restored after total gastrectomy, it gradually recovers to the preoperative level within a few years after distal gastrectomy. Chronic gastritis due to Helicobacter pylori infection and vagotomy are additional factors that perturb the ghrelin secretion of gastric cancer patients after gastrectomy. A randomized clinical trial that revealed that recombinant ghrelin administration successfully increased both food intake and appetite, and ameliorated weight loss after total gastrectomy. Ghrelin administration could thus be a promising strategy to transiently improve the nutritional status of patients who who have undergone gastrectomy, but its effect in the long term remains unclear. Further studies are warranted to elucidate the mechanism of ghrelin and to create and evaluate the analogs that could be administered orally or subcutaneously.

show abstract

Immunohistochemical and quantitative mRNA assessment of ghrelin expression in gastric and oesophageal adenocarcinoma

Cited by 34 publications

References 45 publications

Ghrelin and obestatin in thyroid gland — immunohistochemical expression in nodular goiter, papillary and medullary cancer

Ghrelin and obestatin in thyroid gland — immunohistochemical expression in nodular goiter, papillary and medullary cancer

Safety, tolerability and pharmacokinetics of intravenous ghrelin for cancer-related anorexia/cachexia: a randomised, placebo-controlled, double-blind, double-crossover study

Clinical application of ghrelin administration for gastric cancer patients undergoing gastrectomy

Contact Info

Product

Resources

About