Gastroenterological Surgery
- Development of comprehensive supportive therapy with ghrelin in gastrointestinal cancer treatment
- Development of new multidisciplinary treatment strategies for advanced esophageal cancer
- Development of cancer vaccine therapy using cancer specific antigen NY-ESO-1
- Development of minimally invasive treatments using endoscopic surgery
- Intraoperative Fluorescence Navigation Diagnosis (ICG, 5-ALA) for improved surgery
Research and development of innovative ghrelin peptide formulation and drug safety for broad applicability in the gastrointestinal tract
Ghrelin is an important gastrointestinal hormone that is generally found in vertebrates and has an evolutionarily conserved amino acid sequence. Ghrelin is secreted as a 28 amino acid peptide and was first isolated from rat stomach in 1999. In addition to inducing the secretion of growth hormones, it also increases appetite, weight gain, gastric acid secretion, gastric emptying, cardiac activity, and renal protection.
(Figure 1: left panel, ghrelin peptide; right panel, immunostained images of ghrelin cells in gastric mucosa)
In humans, approximately 90% of ghrelin in the body is secreted from the stomach, meaning that in patients with gastric cancer who have a complete gastrectomy, ghrelin levels decline to about 10% after surgery and do not recover. When the stomach is removed, not only does food consumption decrease, but so too do appetite and weight. The same effect is seen with ghrelin deficiency. Therefore, the lab has conducted clinical trials to administer synthetic ghrelin to gastric cancer patients who had undergone complete stomach removal and examined its applicability. As a result, patients who received ghrelin had significantly increased food consumption, weight gain, and appetite [1].
Esophageal surgery causes appetite and weight loss, an inflammatory response, hypophagia due to anticancer drugs, and nausea and renal function decline. A synthetic ghrelin formulation was administered in randomized controlled clinical trials to treat cytokine inflammation. The lab demonstrated the effective use of ghrelin in several studies and was the first in the world to publish the findings [2-5].
By administering ghrelin to patients who received esophageal cancer surgery, inflammatory responses and complications associated with severe inflammation, such as pneumonia or atelectasis, were suppressed (Figure 2). Encouraged by these results, in 2017, the lab proceeded to manufacture ghrelin (OSK – 0028) as a drug for approval in the suppression of inflammatory reactions and pulmonary complications associated with esophageal cancer during the perioperative period. The lab has initiated clinical trials.
(Figure 2: left, suppression of inflammatory response after esophageal cancer surgery by ghrelin administration; right, chest X-ray image after esophageal cancer surgery with or without pulmonary complications)
Because ghrelin is a naturally secreted hormone in the human body, side effects due to its administration are rarely seen. Thus, ghrelin could be provided to patients quickly and effective in a broad range of diseases with no adverse effects, possibilities we are exploring with clinical trials.
References
1. Adachi et al. Gastroenterology 138 (4), 1312-1320, 2010.
2. Yamamoto et al. Surgery 148 (1), 31-38, 2010.
3. Hiura et al. Cancer 118 (19): 4785-94, 2012.
4. Yanagimoto et al. Br J Cancer 114 (12): 1318-25, 2016
5. Takata et al. Ann Surg 262 (2): 230-6, 2015.
