Top

Published in:

01-03-2007 | Original Paper

Circulating Ghrelin in Patients with Gastric or Colorectal Cancer

Authors: Qi Huang, Yue-Zu Fan, Bu-Jun Ge, Qin Zhu, Zhi-Yuan Tu

Published in: Digestive Diseases and Sciences | Issue 3/2007

Abstract

The purpose of this study was to investigate the pathophysiologic change of ghrelin in gastric and colorectal cancer patients, especially in those with cachexia. Fifty-eight gastric cancer patients, 20 colorectal cancer patients, and 24 healthy control individuals were included in this study. Thirty-one patients were defined as cachectic, based on the percentage of weight loss versus the previous normal weight. The remaining 47 patients were defined as noncachectic. Peripheral hormones, including ghrelin, insulin, leptin, growth hormone, glucagon, and cortisol, and body composition parameters were measured. Plasma ghrelin levels did not increase significantly in cachectic gastric (p=0.352) or colorectal (p=0.871) cancer patients as compared with controls and were not correlated with nutrition status and other hormones. The location of gastric cancer (proximal vs. distal) had no influence on ghrelin levels (p=0.966). These findings suggest that gastric and colorectal cancers may have their special effects on the production of ghrelin. Gastric or colorectal cancer cachexia may be partly due to the lack of increase in ghrelin, which makes exogenous ghrelin therapy feasible in this setting.

Dunlop R (1996) Clinical epidemiology of cancer cachexia. In: Cachexia-Anorexia in Cancer Patients. Oxford: Oxford University Press, pp 76–82

Ma G, Alexandar HR (1998) Prevalence and pathophysiology of cancer cachexia. In: Bruera E, Portenoy RK (eds). Topics in Palliative Care, Vol. 2. New York: Oxford University Press, pp 91–129

Fearon KCH, Moses AGW (2002) Cancer cachexia. Int J Cardiol 32:73–81CrossRef

Yoshikawa T, Yoshikazu N, Chiharu D (2001) Insulin resistance in patients with cancer: Relationships with tumor site, tumor stage, body-weight loss, acute-phase response, and energy expenditure. Nutrition 17:590–593PubMedCrossRef

Huang Q, Nai YJ, Jiang ZW, Li JS (2005) Change of the growth hormone-insulin-like growth factor-I axis in patients with gastrointestinal cancer: related to tumor type and nutritional status. Br J Nutr 93:853–858PubMedCrossRef

Aleman MR, Santolaria F, Batista N, de La Vega M, Gonzalez-Reimers E, Milena A, Llanos M, Gomez-Sirvent JL (2002) Leptin role in advanced lung cancer. A mediator of the acute phase response or a marker of the status of nutrition? Cytokine 19:21–26PubMedCrossRef

Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K (1999) Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402:656–660PubMedCrossRef

Nakazato M, Murakami N, Date Y, Kojima M, Matsuo H, Kangawa K, Matsukura S (2001) A role for ghrelin in the central regulation of feeding. Nature 409:194–198PubMedCrossRef

Tschop M, Smiley DL, Heiman ML (2000) Ghrelin induces adiposity in rodents. Nature 407:908–913PubMedCrossRef

10.

Wren AM, Seal LJ, Cohen MA, Brynes AE, Frost GS, Murphy KG, Dhillo WS, Ghatei MA, Bloom SR (2001) Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab 86:5992–5995PubMedCrossRef

11.

Druce MR, Neary NM, Small CJ, Milton J, Monteiro M, Patterson M, Ghatei MA, Bloom SR (2006) Subcutaneous administration of ghrelin stimulates energy intake in healthy lean human volunteers. Int J Obes (Lond) 30:293–296CrossRef

12.

Wisse BE, Frayo RS, Schwartz MW, Cummings DE (2001) Reversal of cancer anorexia by blockade of central melanocortin receptors in rats. Endocrinology 142:3292–3301PubMedCrossRef

13.

Shimizu Y, Nagaya N, Isobe T, Imazu M, Okumura H, Hosoda H, Kojima M, Kangawa K, Kohno N (2003) Increased plasma ghrelin level in lung cancer cachexia. Clin Cancer Res 9:774–778PubMed

14.

Nitenberg G, Raynard B (2000) Nutritional support of the cancer patient: issues and dilemmas. Crit Rev Oncol Hematol 34:137–168PubMed

15.

Hosada H, Kojima M, Matsuo H, Kangawa K (2000) Ghrelin and des-acyl ghrelin: two major forms of rat ghrelin peptide in gastrointestinal tissue. Biochem Biophys Res Commun 279:909–913CrossRef

16.

Aguilar-Parada E, Eisentraut AM, Linger RH (1969) Pancreatic glucagon secretion in normal and diabetic subjects. Am J Med Sci 257:415–419PubMedCrossRef

17.

Wide L, Porath J (1966) Radioimmunoassay of proteins with the use of Sephadex-coupled antibodies. Biochim Biophys Acta 139:257–260

18.

Date Y, Kojima M, Hosoda H, Sawaguchi A, Mondal MS, Suganuma T, Matsukura S, Kangawa K, Nakazato M (2000) Ghrelin, a novel growth hormone-releasing acylated peptide, is synthesized in a distinct endocrine cell type in the gastrointestinal tracts of rats and humans. Endocrinology 141:4255–4261PubMedCrossRef

19.

Shiiya T, Nakazato M, Mizuta M, Date Y, Mondal MS, Tanaka M, Nozoe S, Hosoda H, Kangawa K, Matsukura S (2002) Plasma ghrelin levels in lean and obese humans and the effect of glucose on ghrelin secretion. J Clin Endocrinol Metab 87:240–244PubMedCrossRef

20.

Hansen TK, Dall R, Hosoda H, Kojima M, Kangawa K, Christiansen JS, Jorgensen JO (2002) Weight loss increases circulating levels of ghrelin in human obesity. Clin Endocrinol 56:203–206CrossRef

21.

Tolle V, Kadem M, Bluet-Pajot MT, Frere D, Foulon C, Bossu C, Dardennes R, Mounier C, Zizzari P, Lang F, Epelbaum J, Estour B (2003) Balance in ghrelin and leptin plasma levels in anorexia nervosa patients and constitutionally thin women. J Clin Endocrinol Metab 88:109–116PubMedCrossRef

22.

Nagaya N, Kojima M, Uematsu M, Yamagishi M, Hosoda H, Oya H, Hayashi Y, Kangawa K (2001) Hemodynamic and hormonal effects of human ghrelin in healthy volunteers. Am J Physiol Regul Integr Comp Physiol 280:R1483–R1487PubMed

23.

Horvath TL, Diano S, Sotonyi P, Keiman M, Tschop M (2001) Ghrelin and the regulation of energy balance: a hypothalamic perspective. Endocrinology 142:4163–4169PubMedCrossRef

24.

Neary NM, Small CJ, Wren AM, Lee JL, Druce MR, Palmieri C, Frost GS, Ghatei MA, Coombes RC, Bloom SR (2004) Ghrelin increases energy intake in cancer patients with impaired appetite: acute, randomized, placebo-controlled trial. J Clin Endocrinol Metab 89:2832–2836PubMedCrossRef

25.

Hanada T, Toshinai K, Date Y, Kajimura N, Tsukada T, Hayashi Y, Kangawa K, Nakazato M (2004) Upregulation of ghrelin expression in cachectic nude mice bearing human melanoma cells. Metabolism 53:84–88PubMedCrossRef

26.

Garcia JM, Garcia-Touza M, Hijazi RA, Taffet G, Epner D, Mann D, Smith RG, Cunningham GR, Marcelli M (2005) Active ghrelin levels and active/total ghrelin ratio in cancer-induced cachexia. J Clin Endocrinol Metab 90:2920–2926PubMedCrossRef

27.

Luo FM, Liu XJ, Li SQ, Wang ZL, Liu CT, Yuan YM (2005) Circulating ghrelin in patients with chronic obstructive pulmonary disease. Nutrition 21:793–798PubMedCrossRef

28.

Palik E, Birkas KD, Faludi G, Karadi I, Cseh K (2005) Correlation of serum ghrelin levels with body mass index and carbohydrate metabolism in patients treated with atypical antipsychotics. Diabetes Res Clin Pract 68:S60–S64PubMedCrossRef

29.

Saad MF, Bernaba B, Hwu CM, Jinagouda S, Fahmi S, Kogosov E, Boyadjian R (2002) Insulin regulates plasma ghrelin concentration. J Clin Endocrinol Metab 87:3997–4000PubMedCrossRef

30.

Murdolo G, Lucidi P, Di Loreto C, Parlanti N, De Cicco A, Fanelli C, Perriello G, Mughetti D, Pippi R, Brozzetti A, Santeusanio F, De Feo P (2003) Circulating ghrelin levels of visceral obese men are not modified by a short-term treatment with very low doses of GH replacement. J Endocrinol Invest 26:244–249PubMed

31.

Cappiello V, Ronchi C, Morpurgo PS, Epaminonda P, Arosio M, Beck-Peccoz P, Spada A (2002) Circulating ghrelin levels in basal conditions and during glucose tolerance test in acromegalic patients. Eur J Endocrinol 147:189–194PubMedCrossRef

32.

Kishimoto M, Okimura Y, Nakata H, Kudo T, Iguchi G, Takahashi Y, Kaji H, Chihara K (2003) Cloning and characterization of the 5-flanking region of the human ghrelin gene. Biochem Biophys Res Commun 305:186–192PubMedCrossRef

33.

Sugino T, Yamaura J, Yamagishi M, Kurose Y, Kojima M, Kangawa K, Hasegawa Y, Terashima Y (2003) Involvement of cholinergic neurons in the regulation of the ghrelin secretory response to feeding in sheep. Biochem Biophys Res Commun 304:308–312PubMedCrossRef

34.

Lely AJ, Tschop M, Heiman ML, Ghigo E (2004) Biological, physiological, pathophysiological, and pharmacological aspects of ghrelin. Endocrine Rev 25:426–457CrossRef

35.

Dornonville de la Cour C, Bjorkqvist M, Sandvik AK, Bakke I, Zhao CM, Chen D, Hakanson R (2001) A-like cells in the rat stomach contain ghrelin and do not operate under gastrin control. Regul Pept 99:141–150PubMedCrossRef

36.

Aydin S, Ozercan IH, Dagli F, Aydin S, Dogru O, Celebi S, Akin O, Guzel SP (2005) Ghrelin immunohistochemistry of gastric adenocarcinoma and mucoepidermoid carcinoma of salivary gland. Biotech Histochem 80:163–168PubMedCrossRef

37.

Isomoto H, Ueno H, Nishi Y, Yasutake T, Tanaka K, Kawano N, Ohnita K, Mizuta Y, Inoue K, Nakazato M, Kohno S (2005) Circulating ghrelin levels in patients with various upper gastrointestinal diseases. Dig Dis Sci 50:833–838PubMedCrossRef

38.

Gale SM, Castracane VD, Mantzoros CS (2004) Energy homeostasis, obesity and eating disorders: recent advances in endocrinology. J Nutr 134:295–298PubMed

39.

Schwartz MW, Woods SC, Porte D Jr, Seeley RJ, Baskin DG (2000) Central nervous system control of food intake. Nature 404:661–665PubMed

40.

Huang Q, Zhang X, Jiang ZW, Liu BZ, Li N, Li JS (2005) Hypoleptinemia in gastric cancer patients: relation to body fat mass, insulin, and growth hormone. J Parenter Enteral Nutr 29:229–235CrossRef

41.

Tolle V, Bassant MH, Zizzari P, Poindessous-Jazat F, Tomasetto C, Epelbaum J, Bluet-Pajot MT (2002) Ultradian rhythmicity of ghrelin secretion in relation with GH, feeding behavior, and sleep-wake patterns in rats. Endocrinology 143:1353–1361PubMedCrossRef

42.

Cummings DE, Weigle DS, Frayo RS, Breen PA, Ma MK, Dellinger EP, Purnell JQ (2002) Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N Engl J Med 346:1623–1630PubMedCrossRef

43.

Barkan AL, Dimaraki EV, Jessup SK, Symons KV, Ermolenko M, Jaffe CA (2003) Ghrelin secretion in humans is sexually dimorphic, suppressed by somatostatin, and not affected by the ambient growth hormone levels. J Clin Endocrinol Metab 88:2180–2184PubMedCrossRef

44.

Gokcel A, Gumurdulu Y, Kayaselcuk F, Serin E, Ozer B, Ozsahin AK, Guvener N (2003) Helicobacter pylori has no effect on plasma ghrelin levels. Eur J Endocrinol 148:423–426PubMedCrossRef

45.

Shiotani A, Miyanishi T, Uedo N, Iishi H (2005) Helicobacter pylori infection is associated with reduced circulating ghrelin levels independent of body mass index. Helicobacter 10:373–378PubMedCrossRef

46.

Isomoto H, Ueno H, Saenko VA, Mondal MS, Nishi Y, Kawano N, Ohnita K, Mizuta Y, Ohtsuru A, Yamashita S, Nakazato M, Kohno S (2005) Impact of Helicobacter pylori infection on gastric and plasma ghrelin dynamics in humans. Am J Gastroenterol 100:1711–1720PubMedCrossRef

Title: Circulating Ghrelin in Patients with Gastric or Colorectal Cancer
Authors: Qi Huang
Yue-Zu Fan
Bu-Jun Ge
Qin Zhu
Zhi-Yuan Tu
Publication date: 01-03-2007
Publisher: Kluwer Academic Publishers-Plenum Publishers
Published in: Digestive Diseases and Sciences / Issue 3/2007
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI: https://doi.org/10.1007/s10620-006-9508-3

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2007

Endoscopic Removal of Large Sessile Colorectal Adenomas: Is It Safe and Effective?

Diagnosis of Malignant Hemangioendothelioma of the Small Intestine with Capsule Endoscopy

Dermatitis Herpetiformis: No Evidence of Bone Disease Despite Evidence of Enteropathy

Continuous Versus Cyclic Mesalazine Therapy for Patients Affected by Recurrent Symptomatic Uncomplicated Diverticular Disease of the Colon

Octreotide/Midodrine Therapy Significantly Improves Renal Function and 30-Day Survival in Patients with Type 1 Hepatorenal Syndrome

Early Decision for Precut Sphincterotomy: Is It a Risky Preference?

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials