Delving into the Latest Updates on Netazepide with Synapse

BACKGROUNDAmong bariatric techniques, sleeve gastrectomy (SG) stands out owing to its efficiency. The role of the stomach as a secretory organ of many substances, such as gastrin, related to insulin secretion is well known. Gastrin induces insulin release in isolated pancreatic islets, limiting somatostatin-14 intraislet release, and has been associated with blood glucose level improvement in diabetic models after SG. SG involves gastric resection along the greater curvature. This study aimed to determine the role of gastrin in glucose metabolism improvement after SG with the aid of the gastrin antagonist netazepide.METHODSIn 12 sham-operated, 12 SG-operated, and 12 SG-operated/netazepide-treated Wistar rats, we compared medium- and long-term plasma insulin, oral glucose tolerance test (OGTT) results, and plasma gastrin levels. In addition, gastrin expression was assessed in the gastric remnant, and the beta-cell mass was measured.RESULTSSG induced a medium-term elevation of the insulin response and plasma gastrin levels without modification of the OGTT results. However, long-term depletion of the insulin response with elevated OGTT areas under the curve and plasma gastrin levels appeared after SG. Netazepide prevented the SG effect on these parameters. Gastrin tissue expression was greater in SG animals than in SG/netazepide-treated or control animals. The beta-cell mass was lower in the SG group than in the control or SG/netazepide group.CONCLUSIONGastrin plays a central role in glucose improvement after SG. It stimulates a medium-term strong insulin response but also causes long-term beta-cell mass depletion and a loss of insulin response. These effects are prevented by gastrin antagonists such as netazepide.

01 Feb 2023·Journal of Gastroenterology

Risk of gastric and oesophageal adenocarcinomas following discontinuation of long-term proton-pump inhibitor therapy

Letter

Author: Waldum, Helge

A review.Holmberg et al. described reduction of gastric and oesophageal adenocarcinomas following discontinuation of proton-pump inhibitor therapy .While PPIs have for long been suspected to cause gastric adenocarcinomas originating from the enterochromaffin-like (ECL) cell via hypergastrinemia , a role by PPIs in oesophageal adeno-carcinogenesis has not been accepted. Gastrin, a peptide hormone, affects cell function only via the CCK- 2 (gastrin) receptor, which is localized on the ECL cell, and possibly on some cells in Barrett's mucosa .The CCK-2 receptor in Barrett's mucosa was postulated to mediate the oesophageal adeno-carcinogenic effect .However, previous studies have indicated that PPI treatment reduces the risk of oesophageal carcinomas, and the gastrin antagonist netazepide failed to affect Barrett's oesophagus .Furthermore, in just published AGA guidelines on Barrett's oesophagus PPI treatment was still advocated.Therefore, the role of PPIs in oesophageal adeno-carcinogenesis is not clear, and future studies are required.

26 Sep 2021·World Journal of Clinical CasesQ4 · MEDICINE

Gastric neuroendocrine neoplasms: A review

Q4 · MEDICINE

Review

Author: Sezikli, Mesut ; Köseoğlu, Hüseyin ; Duzenli, Tolga

Gastric neuroendocrine neoplasms (g-NENs) or neuroendocrine tumors are generally slow-growing tumors with increasing incidence. They arise from enterochromaffin like cells and are divided into four types according to clinical characteristic features. Type 1 and 2 are gastrin dependent, whereas type 3 and 4 are sporadic. The reason for hypergastrinemia is atrophic gastritis in type 1, and gastrin releasing tumor (gastrinoma) in type 2 g-NEN. The diagnosis of g-NENs needs histopathological investigation taken by upper gastrointestinal endoscopy. g-NENs are positively stained with chomogranin A and synaptophysin. Grading is made with mitotic index and ki-67 proliferation index on histopathological analysis. It is crucial to discriminate between types of g-NENs, because the management, treatment and prognosis differ significantly between subtypes. Treatment options for g-NENs include endoscopic resection, surgical resection with or without antrectomy, medical treatment with somatostatin analogues, netazepide or chemotherapy regimens. Follow-up without excision is another option in appropriate cases. The prognosis of type 1 and 2 g-NENs are good, whereas the prognosis of type 3 and 4 g-NENs are close to the prognosis of gastric adenocancer.

100 Deals associated with Netazepide

Login to view more data

External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB12355

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Gastric Neuroendocrine Tumor G1	Phase 2	GB	Trio Medicines Ltd.	04 Jan 2011
Gastritis, Atrophic	Phase 2	GB	Trio Medicines Ltd.	04 Jan 2011
Barretts esophagus with high grade dysplasia	Phase 2	GB	Trio Medicines Ltd.	01 Jun 2010
Barretts esophagus with high grade dysplasia	Phase 2	US	Trio Medicines Ltd.	01 Jun 2010
Barrett Esophagus	Phase 2	-	Ferring BV	-
Zollinger-Ellison Syndrome	Phase 2	-	Ferring BV	-
Carcinoid Tumor	Discovery	GB	Trio Medicines Ltd.	04 Jan 2011
Carcinoid Tumor	Discovery	GB	Trio Medicines Ltd.	04 Jan 2011
Gastric Neuroendocrine Tumor G1	Discovery	GB	Trio Medicines Ltd.	04 Jan 2011
Gastritis, Atrophic	Discovery	GB	Trio Medicines Ltd.	04 Jan 2011

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01298999 (CTgov)	Phase 2	Barrett Esophagus \| Barretts esophagus with high grade dysplasia	27	YF476 (YF476)	bcixjgymfh(fkbzmlvynl) = bnykceiqqc tsunvtxrqj (pspqxsbbxf, dqfcbueljf - hypfpaflcm) View more	-	23 Nov 2021
				Placebo (Placebo)	bcixjgymfh(fkbzmlvynl) = hoqaurwfgr tsunvtxrqj (pspqxsbbxf, zygpabduie - nuzobzeizl) View more
NCT02597712 (CTgov)	Phase 2	Barrett Esophagus	27	YF476 (Treatment)	uikbswkmya(bpjrqhwhly) = dfekobeqwv jcbpveqhov (zwcrqrnjwi, lgaoqexzac - thdwkgqpvu) View more	-	12 Apr 2021
				YF476 placebo (YF476 Placebo)	uikbswkmya(bpjrqhwhly) = djdvnudmrp jcbpveqhov (zwcrqrnjwi, huhlamrrng - hvpcctcnbu) View more
NCT01298999 (Pubmed \| Cancer Prev Res (Phila))	Phase 2	Barrett Esophagus	20	Netazepide	lyswhuaize(mzannannrj) = uzqvytllwf bcqanycfoz (zfmjouecpe, 620.7)	-	29 Mar 2021
				Placebo	lyswhuaize(mzannannrj) = txkudaleuw bcqanycfoz (zfmjouecpe, 640.3)
NCT02454075 (CTgov)	Phase 2	Zollinger-Ellison Syndrome \| Gastric Neuroendocrine Tumor G1	3	YF476	uosouskgky(ucpjsjjvhy) = zhfgttnhva dimcvipdtq (safklqcgbv, wkytpzoduw - uqltvfbzcu) View more	-	29 Jan 2021