RARE DISEASE
Zollinger-Ellison syndrome
Zollinger-Ellison syndrome
Zollinger-Ellison syndrome
Synonyms: Gastrinoma
Synonyms: Gastrinoma
Synonyms: Gastrinoma
Drug discovery
3
drugs
With orphan designations
Overview
Zollinger-Ellison syndrome (ZES) is caused by gastrin-secreting neuroendocrine tumors (gastrinomas), leading to gastric acid hypersecretion, refractory peptic ulcers, and chronic diarrhea [1][6][8]. Approximately 20-30% of cases occur in multiple endocrine neoplasia type 1 (MEN1) patients [4][6]. Diagnosis is confirmed by elevated fasting gastrin levels and secretin stimulation testing [10].
Burden
Complications: GI bleeding (25%), perforation, and metastatic spread (60–90% pancreatic gastrinomas) [6][7][9]
Survival: 10-year survival >90% with controlled acid secretion and localized disease; 30% with liver metastases [9][11]
Diagnosis requires vigilance in patients with refractory ulcers, chronic diarrhea, or MEN1 features [6][8].
Therapies
Acid suppression: High-dose proton pump inhibitors (PPIs) lifelong [6][10]
Surgery: Curative resection for localized sporadic tumors [9][10]; not recommended for MEN1-associated multifocal gastrinomas [9]
Advanced disease: Targeted therapy (everolimus/sunitinib), chemotherapy, or peptide receptor radionuclide therapy (PRRT) for metastases [1][9]
Categories: rare endocrine diseases, rare gastroenterological diseases, rare neoplastic diseases, rare transplant-related disorders
Research Papers
906 drug discovery papers about Zollinger-Ellison syndrome, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
906 drug discovery papers about Zollinger-Ellison syndrome, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
antibodies
2024-09-09 | Expression profiles of cadherin 17 and claudin 18.2 in comparison with peptide hormonal expression in pancreatic neuroendocrine tumours: Implications for targeted immunotherapy.
Cadherin 17 (CDH17) and claudin 18.2 (CLDN18.2) are highly selective markers of intestinal and gastric lineages and are expressed in adenocarcinomas of various organs. They have also been identified as potential targets for immunotherapy. Expression of CDH17 and CLDN18.2 has been observed in a subset of pancreatic neuroendocrine tumours (PanNETs). This study investigates the immunohistochemical expression of CDH17 and CLDN18 in PanNETs in comparison with hormonal expression profiles to provide baseline data for determining candidate indications for targeted therapy with CDH17 and CLDN18.2 in PanNETs, including insulinomas (n = 22), glucagonomas (n = 13), gastrinomas (n = 3), serotoninomas (n = 2) and PanNETs not otherwise specified (NOS) (n = 17). In the normal pancreas, CDH17 was expressed in the lateral membrane of ducts and some islet cells, whereas CLDN18 was occasionally expressed in the intercalated ducts and centroacinar cells. In PanNETs, CDH17 and CLDN18 was detected by membranous staining. CDH17 expression was observed in 10 to 17 (58.8 %) PanNETs NOS, 3 of 13 (23.1 %) glucagonomas, 1 of 3 (33.3 %,) gastrinomas, 1 of 2 (50 %) serotoninomas, and none of the insulinomas. According to predefined criteria, 7 of 17 (41.2 %) PanNETs NOS, 1 of 3 (33.3 %) gastrinomas, and 1 of 2 (50 %) serotoninomas were classified as CDH17-positive. There were no significant differences in clinicopathological features between CDH17-positive and CDH17-negative PanNETs, except for a higher tumour grade in the former (p<0.05). For CLDN18, expression was noted in 2 out of 3 (66.7 %) gastrinomas, one with focal staining and the other with diffuse staining. One of three (33.3 %) gastrinomas was classified as CLDN18-positive using predefined criteria. These findings suggest that a particular subset of PanNETs, including PanNET NOS, gastrinoma, and serotoninoma, may be potential candidates for CDH17-targeted immunotherapy. Additionally, gastrinoma may be a potential candidate for immunotherapy targeting CLDN18.2.
2014-01-27 | Gastrin: from pathophysiology to cancer prevention and treatment.
Gastrin has been identified as the principal effector of gastric secretion, but several studies have demonstrated its role as a biomarker of cancer risk and as a growth factor for colorectal, stomach, liver, and pancreatic cancer. Hypergastrinemia characterizes autoimmune gastritis, with body and fundic gland atrophy and increased risk for both gastric adenocarcinoma and neuroendocrine tumors. Gastric type I carcinoids develop in the context of autoimmune gastritis because of the stimulus exerted by gastrin on enterochromaffin-like cells and remain gastrin-sensitive for long durations because the removal of hypergastrinemia leads to tumor regression. The treatment of gastric carcinoid is still open to debate, but when the disease frequently relapses, or is multicentric or infiltrating, surgery is advocated or, in the alternative, a costly and long-lasting treatment with long-acting somatostatin analogues is prescribed. A technology allowing the preparation of an immunogen eliciting an immune system response with generation of antibodies against G17 has been developed. This vaccine has been tested in patients with colorectal, pancreatic or advanced gastric cancer. The vaccine has also been used in the treatment of gastric type I carcinoids, and the administration of G17DT in patients harboring these lesions leads to carcinoid regression. Antigastrin vaccination in the treatment of gastrointestinal cancer obviously needs validation, but this immunotherapy may well represent a simple, inexpensive, and active 'adjuvant' treatment.
2013-01-08 | Extracellular Drug Conjugate (EDC1) Technology for Targeted Neuroendocrine Cancer Therapy
Surgery is the only curative treatment for patients with neuroendocrine (NE) cancers. This study was designed to investigate the effect of a novel drug system using extracellular drug conjugate (EDC1) technology on the growth of NE cancer cells. The EDC1 system is comprised of an antibody that specifically targets diseased cells over-expressing dysadherin, an anti-cancer drug binding to the Na+, K+ -ATPase alpha subunit (NKA), and a linker made with CarboConnect technology connecting the antibody to the drug. Dysadherin is a cancer-associated cell membrane glycoprotein that promotes metastasis by down-regulating E-cadherin, a protein required for cell adhesion. Therefore, our study evaluated the effect of EDC1 on gastrointestinal (BON) and pulmonary (H727) carcinoid cells to determine the therapeutic potential for NE cancers.
2008-12-31 | Importance of gastrin in the pathogenesis and treatment of gastric tumors
In addition to regulating acid secretion, the gastric antral hormone gastrin regulates several important cellular processes in the gastric epithelium including proliferation, apoptosis, migration, invasion, tissue remodelling and angiogenesis.Elevated serum concentrations of this hormone are caused by many conditions, particularly hypochlorhydria (as a result of autoimmune or Helicobacter pylori (H pylori )-induced chronic atrophic gastritis or acid suppressing drugs) and gastrin producing tumors (gastrinomas).There is now accumulating evidence that altered local and plasma concentrations of gastrin may play a role during the development of various gastric tumors.In the absence of H pylori infection, marked hypergastrinemia frequently results in the development of gastric enterochromaffin cell-like neuroendocrine tumors and surgery to remove the cause of hypergastrinemia may lead to tumor resolution in this condition.In animal models such as transgenic INS-GAS mice, hypergastrinemia has also been shown to act as a cofactor with Helicobacter infection during gastric adenocarcinoma development.However, it is currently unclear as to what extent gastrin also modulates h u m a n g a s t r i c a d e n o c a r c i n o m a d e ve l o p m e n t .Therapeutic approaches targeting hypergastrinemia, s u c h a s i m m u n i z a t i o n w i t h G 1 7 DT, h ave b e e n evaluated for the treatment of gastric adenocarcinoma, with some promising results.Although the mild hypergastrinemia associated with proton pump inhibitor drug use has been shown to cause ECL-cell hyperplasia and to increase H pylori -induced gastric atrophy, there is currently no convincing evidence that this class of agents contributes towards the development of gastric neuroendocrine tumors or gastric adenocarcinomas in human subjects.
2005-05-01 | Increased Expression of Insulin-Like Growth Factor I and/or Its Receptor in Gastrinomas Is Associated with Low Curability, Increased Growth, and Development of Metastases
Abstract Purpose: Growth factors, particularly insulin-like growth factor I (IGF-I) and IGF-I receptor (IGF-IR) in some nonendocrine and a few endocrine tumors, are thought important in recurrence, growth, and aggressiveness. Whether this is true of neuroendocrine tumors such as gastrinomas is unclear. The aim of this study was to address this question in gastrinomas. Experimental Design: IGF-I and IGF-IR expression in gastrinomas from 54 patients with Zollinger-Ellison syndrome were analyzed and correlated with clinical/tumor characteristics. IGF-I and IGF-IR mRNA levels were determined by competitive reverse transcription-PCR. IGF-IR expression, assessed by immunohistochemistry, was done on a subset. Results: IGF-IR mRNA was found in 100% and IGF-I in 89%. IGF-I mRNA expression varied by >254-fold, IGF-IR by 2,670-fold, and the levels correlated in a given tumor. The IGF-IR level was lower in gastrinomas of patients who were rendered disease free and increased levels correlated with tumor growth, aggressiveness, extent, and with liver metastases. Increased IGF-I levels correlated with increased growth, tumor extent, and aggressiveness. Neither IGF-IR nor IGF-I levels correlated with tumor location, size, or its clinical/functional features. The IGF-IR correlated with disease-free survival. IGF-IRβ was found in 31 of 32 tumors (97%) by immunohistochemistry. Conclusions: These results indicate that IGF-I and IGF-IR are expressed in almost all gastrinomas. Furthermore, assessment of IGF-I/IGF-IR expression in gastrinomas may be clinically useful in identifying those patients with more aggressive tumors who might benefit from more aggressive treatment.
proteins
2025-06-12 | Last decade of advances in gastric neuroendocrine tumors: Innovations, challenges, and future directions.
Gastric neuroendocrine tumors (G-NETs) are rare tumors originating from enterochromaffin-like cells, with an incidence of 0.4 per 100000 annually. There are three main types: (1) Type I, linked to chronic atrophic gastritis and hypergastrinemia, makes up 75%-80% of G-NETs; (2) Type II, associated with Zollinger-Ellison syndrome (ZES) and multiple endocrine neoplasia, comprises 5%; and (3) Type III, sporadic tumors with a higher metastatic potential, accounting for 15%-25%. Diagnosis involves endoscopy, biopsy, and histological examination. Additional methods include serum gastrin testing, immunohistochemistry, and imaging techniques such as computer tomography or magnetic resonance imaging for detecting metastasis. Type I treatment usually involves endoscopic resection (ER), with surgical resection for recurrence. Somatostatin analogs (SSAs) can reduce tumor size, and the prognosis is generally excellent. Type II treatment centers on surgical removal of the gastrinoma, with ER for smaller lesions and SSAs for symptom management. Type III requires surgical resection (partial or total gastrectomy) with lymph node dissection, and possibly chemotherapy. This type has a worse prognosis due to its aggressive nature. Emerging treatments like Peptide Receptor Radionuclide Therapy are promising for advanced cases, and ongoing research into immunotherapies is expanding future treatment options. Regular endoscopic follow-up is crucial to monitor for recurrence or metastasis across all types. Our literature review explores the current perspectives on G-NETs and highlights the importance of further research to improve diagnostic precision and treatment, particularly for those associated with less favorable cases. To improve diagnostic precision and treatment, particularly for those associated with less favorable cases. A systematic search was conducted in PubMed, Scopus, and Web of Science until September 2024. Two independent reviewers screened titles, abstracts, and full texts for eligibility based on G-NET treatment in adults. Eligible studies included cohort studies, clinical trials, case series, and case reports, while in vitro, pediatric, and non-English studies were excluded. Relevant data were extracted independently, and disagreements were resolved through discussion. Study quality was assessed using appropriate tools. G-NETs are rare, classified into three types: (1) Type I; (2) Type II; and (3) Type III. Type I G-NETs, often associated with chronic atrophic gastritis, are typically slow-growing and low-grade, with favorable outcomes following surgical resection. Type II G-NETs arise in hypergastrinemia conditions like multiple endocrine neoplasia and ZES, showing moderate malignancy risk. Type III G-NETs, the most aggressive and least common, present with distant metastases and poor prognosis. Diagnosis relies on endoscopy, imaging, and biomarkers like chromogranin A. Treatment varies by type, ranging from ER to aggressive surgery and chemotherapy for advanced cases. Regular follow-up is essential to monitor recurrence, particularly for type III G-NETs. G-NETs require tailored diagnosis and treatment based on type and stage. Types I and II generally have better prognosis, while types III and IV are linked to poorer outcomes due to invasion and metastasis. Treatment strategies vary from ER for type I to extensive surgery for type III. Emerging therapies, like somatostatin analogs and peptide-receptor radionuclide therapies, show promise in advanced cases. Further research is essential to improve early diagnosis and treatment, particularly for high-risk lesions.
2023-09-07 | Recurrent Neuroendocrine Tumor of the Pancreas Presenting with Hypertension in the Setting of Hyperreninemia: A Case Report
Background: Pancreatic neuroendocrine tumors are a diverse group of neoplasms which coexist with gastrointestinal carcinoids as the main histiotypes of gastrointestinal neuroendocrine tumors.Pancreatic neuroendocrine tumors are found primarily in the pancreas and upper small intestine.Although pancreatic neuroendocrine tumors share many features with gastrointestinal carcinoids, they are generally considered separately because of their different clinical syndromes (carcinoid syndrome vs. pancreatic neuroendocrine tumor syndromes) molecular pathogenesis, biological behaviors, and difference in response to antineoplastic treatments.Common pancreatic neuroendocrine tumors include gastrinomas, insulinomas, glucagonomas, VIPomas, GRFomas, ACTHomas, somatostatinomas, pancreatic neuroendocrine tumors causing carcinoid syndrome and those causing hypercalcemia (PTHrPomas).A pancreatic neuroendocrine tumor secreting renin resulting in hypertension is exceptionally rare and has not been previously reported. Case Presentation:We present a 43-year-old female with a grade 2 neuroendocrine tumor diagnosed four years earlier, initially treated with distal pancreatectomy and splenectomy, who presented to her internist for routine follow up with a blood pressure of 150/100 mmHg.An MRI three months earlier showed no recurrent disease with stable Chromogranin A levels.A workup for secondary hypertension was pursued which discovered an elevation in renin and aldosterone levels without evidence of hypercoagulability or compromised vascular supply to the kidneys.Four months later, an MRI showed a new metastatic lesion in the liver and the Chromogranin A levels increased from her baseline.With two microwave ablations and Lanreotide, her blood pressure normalized as did her renin and aldosterone levels. Conclusion:Newly diagnosed hypertension in a patient with a history of a pancreatic neuroendocrine tumor should prompt a workup for secondary hypertension as this may be a sign of tumor recurrence.Hyperreninemia in the setting of a neoplasm has mostly been described with juxtaglomerular cell tumors of the kidney and has never been described with a pancreatic neuroendocrine tumor.Treating the underlying tumor can eliminate the overproduction of renin and normalize the blood pressure.
2023-07-02 | Spatial profiling of neuro-immune interactions in gastroenteropancreatic NETs
Abstract Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are heterogeneous malignancies that arise from complex cellular interactions within the tissue microenvironment. Here, we sought to decipher tumor-derived signals from the surrounding microenvironment by applying Nanostring Digital Spatial Profiling (DSP) to hormone-secreting and non-functional GEP-NETs. DSP was used to evaluate the expression of 40 neural and immune-related proteins in surgically resected duodenal and pancreatic NETs (n=20) primarily comprised of gastrinomas (18/20). A total of 279 regions of interest were examined between tumors, adjacent normal and abnormal-appearing epithelium, and the surrounding stroma. The results were stratified by tissue type and Multiple Endocrine Neoplasia I (MEN1) status and protein expression was validated by immunohistochemical (IHC) staining. A tumor immune cell autonomous inflammatory signature was further evaluated by IHC and RNAscope, while functional pro-inflammatory signaling was confirmed using patient-derived duodenal organoids. Gastrin-secreting and non-functional pancreatic NETs showed a higher abundance of immune cell markers and immune infiltrate compared to duodenal gastrinomas. Tumors displayed strong intra-tissue variation in the expression of neural- and immune-related proteins. Compared to non- MEN1 tumors, MEN1 gastrinomas showed reduced expression of immune cell markers and upregulated expression of neuropathological proteins. Duodenal gastrinomas showed strong expression of the pro- inflammatory and pro-neural factor IL-17B. Treatment of human duodenal organoids with IL- 17B activated NF-kB and STAT3 signaling and induced the expression of neuroendocrine markers. In conclusion, multiplexed spatial protein analysis identified tissue-specific neuro- immune signatures in GEP-NETs. Moreover, duodenal gastrinomas cell autonomously express immune and pro-inflammatory factors, including tumor-derived IL-17B, that stimulate the neuroendocrine phenotype.
2022-07-08 | Targeted treatment with somatostatin analogues: widening horizons of clinical practice
Targeted treatment with somatostatin analogues (SA) in acromegaly and neuroendocrine neoplasms may have some benefits compared to curative treatments, because these agents decrease excessive hormone secretion and exert a tumor-suppressive effect. Monotherapy and combination therapy with SA is well tolerated and bears no risk of debilitating iatrogenic complications. In acromegaly caused by somatotropin producing pituitary tumor, first generation SA are treatment of choice after non-radical adenomectomy, as well as in the cases when patients reject surgery. Treatment efficacy depends on the pathomorphological types of somatotropic tumors, which are different in their receptor phenotype, clinical scenario and proliferative activity. The first generation SA are successfully used for medical treatment of other pituitary tumors (thyrotropic, corticotropic, gonadotropic, lactotropic with resistance to dopamine agonists), as well as for adjuvant therapy of neuroendocrine and non-endocrine neoplasms and elimination of various gastrointestinal disorders. The anti-secretory and anti-tumor effects of SA have been proven for gastroenteropancreatic tumors (carcinoid syndrome, vipomas, gastrinomas, insulinomas, glucagonomas, somatostatinomas). Targeted selection of patients for treatment with first generation SA based on the receptor phenotypes of malignant cells would facilitate more rapid achievement of biochemical remission, improvement of quality of life and survival.
2021-06-03 | Somatostatin Analogs in Patients with Zollinger Ellison Syndrome (ZES): An Observational Study
Abstract PURPOSE : Zollinger Ellison syndrome (ZES) is a rare syndrome caused by gastrin hypersecretion from a gastrinoma. Gastrinoma treatment has two goals: the control of the gastrin-excess state and the control of tumor growth. While therapy for the syndrome is univocally based on proton pump inhibitors, the one for disease control is still debated. We here aimed at evaluating the role of SSAs in the control of tumor progression in a series of ZES patients.METHODS: A retrospective analysis of a prospectively collected database of ZES patients, followed and managed from 1990 to 2019, was performed. The patients' clinical, pathological, treatment, and follow-up data were analyzed. Data regarding SSAs therapy start, dosage, duration, and side effects were collected.RESULTS: 33 patients with ZES were diagnosed. Fourteen patients (42%) had a G1 NEN, five had G2 (15%), none had G3. Fifteen patients (45%) had metastatic disease. Overall, 12 (36%) underwent SSAs therapy. The median treatment duration was 36 months. Eight patients (67%) had a sustained response to SSA, four (33%) showed an early progression, with a significant difference in terms of PFS between the two groups (84 vs 2 months, p=0.004). No differences in terms of OS and PFS were observed between the two groups, despite the proportion of metastatic patients was greater in the SSA-treated group (75% vs 29% in the non-treated group, p=0.01). CONCLUSION: Present data support the use of SSAs in ZES, considering that gastrinoma is mainly a well-differentiated low-grade tumor (G1 or G2), with a high expression of somatostatin receptors.
small molecules
2026-08-01 | DEVELOPMENT AND EVALUATION OF ENTERIC-COATED PANTOPRAZOLE TABLETS FOR ENHANCED GASTRIC PROTECTION
Pantoprazole is a proton pump inhibitor widely used in the management of acid-related gastrointestinal disorders, including gastroesophageal reflux disease, peptic ulcer disease, and Zollinger–Ellison syndrome. Because Pantoprazole is highly unstable in acidic conditions, an enteric coating is essential to protect the drug from degradation in the stomach and ensure its release in the intestinal environment. The present study aimed to formulate and evaluate enteric-coated Pantoprazole tablets with improved stability and effective drug delivery. Preformulation studies were carried out to evaluate the physicochemical properties and compatibility of the drug with selected excipients. Six formulations (F1–F6) were prepared and subjected to pre-compression evaluation, including angle of repose, bulk density, tapped density, Carr's index, and Hausner's ratio, which demonstrated satisfactory flow and compressibility. The core tablets were evaluated for physical appearance, thickness, diameter, weight variation, hardness, friability, drug content, and disintegration time, followed by enteric coating and in vitro dissolution studies. Among the developed formulations, F6 exhibited the most desirable characteristics, including excellent mechanical strength, acceptable friability, uniform drug content, effective resistance to acidic medium, and maximum drug release in phosphate buffer after the enteric coating dissolved. The results confirmed that the optimized enteric-coated formulation successfully protected Pantoprazole from gastric degradation and provided efficient drug release in the intestinal environment. Therefore, formulation F6 was identified as the optimized formulation with suitable pharmaceutical properties and potential for effective oral therapy.
2026-08-01 | EP947 - ECE_1770 - Severe hypergastrinemia with mild clinical expression: the modulating role of autoimmune atrophic gastritis in metastatic gastrinoma
Abstract Background Gastrinomas are rare functioning neuroendocrine tumors characterized by inappropriate gastrin secretion leading to gastric acid hypersecretion and Zollinger–Ellison syndrome. Diagnosis usually requires the demonstration of hypergastrinemia in the setting of low gastric pH. In clinical practice, however, gastric pH assessment may be unavailable, and coexisting gastric disorders may confound symptomatic and biochemical interpretation,, and delay the diagnosis. Case Presentation We report the case of a 78-year-old woman with a well-differentiated pancreatic neuroendocrine tumorand extensive hepatic and lymph node metastases. The tumor was identified during evaluation of abdominal and pelvic discomfort. Cross-sectional imaging revealed a 61mm exophytic mass in the pancreatic body with diffuse liver metastases.Liver biopsy histopathology confirmed a metastatic pancreatic neuroendocrine tumor, with a Ki-67 proliferation index <3% and strong expression of neuroendocrine markers. Functional imaging with 68Ga-DOTATOC PET demonstrated very intense somatostatin receptor expression throughout the entire tumor burden. Biochemical evaluation revealed extreme fasting hypergastrinemia (99007 pg/mL). Clinically, the patient reported chronic abdominal pain and recurrent diarrhea but lacked other hallmark features of Zollinger–Ellison syndrome, such as peptic ulcer disease, severe gastroesophageal reflux, or significant weight loss. Gastric pH measurement was not available, limiting physiological confirmation of acid hypersecretion. Upper gastrointestinal endoscopy revealed body-predominant atrophic gastritis with focal intestinal metaplasia, active Helicobacter pylori infection and no ulcerations. In this context, autoimmune atrophic gastritis was suspected, which would explain the mild clinical expression of such high gastrin levels. Further tests showed positive anti-parietal cell antibodies and vitamine B12 deficiency, supporting this diagnosis. Germline genetic testing for MEN1 and CDKN1B revealed no pathogenic variants. LAR octreotide was initiated leading to diarrhea improvement, a dramatic fall in the gastrin levels (460 pg/mL in the last evaluation) and structural stable disease during the last three years. Conclusions This case represents a pathophysiological challenge. On one hand, an autoimmune atrophic gastritis could explain the clinical picture and be seen here as protective factor by reducing parietal cell mass and attenuating acid secretion, thereby limiting ulcerative complications despite extreme gastrin. On the other hand, atrophic gastritis itself can cause secondary hypergatrinemia, which may be a confounding effect.Awareness of such interplay is essential to avoid misinterpretation of isolated hypergastrinemia and to ensure timely diagnosis.
2026-07-21 | pH-Sensitive Enteric-Coated Omeprazole Pellet Systems for Sequential Gastrointestinal Drug Delivery: Formulation Strategies, Release Mechanisms, and Recent Advances
Oral drug delivery remains the most preferred route of administration because of its convenience, non-invasive nature, cost-effectiveness, and high patient compliance. However, the successful delivery of acid-labile drugs continues to present significant formulation challenges. Omeprazole, a proton pump inhibitor widely prescribed for the treatment of gastroesophageal reflux disease (GERD), peptic ulcer disease, and Zollinger–Ellison syndrome, is highly unstable in acidic environments and undergoes rapid degradation in the stomach before reaching its primary absorption site in the small intestine. Consequently, specialized formulation approaches are required to protect the drug during gastric transit while ensuring efficient intestinal release. Among various oral delivery systems, pH-sensitive enteric-coated pellets have emerged as one of the most successful strategies for improving the stability and bioavailability of omeprazole. Multiparticulate pellet systems provide uniform distribution throughout the gastrointestinal tract, reduce variability in gastric emptying, and offer greater flexibility in controlling drug release compared with conventional single-unit dosage forms. The incorporation of pH-responsive polymers such as Eudragit® L100 and Eudragit® S100 enables site-specific release by exploiting physiological pH variations within the gastrointestinal tract. Recent developments in pelletization technology, enteric coating systems, and Quality by Design (QbD) methodologies have significantly improved the performance and reproducibility of omeprazole formulations. This review critically examines gastrointestinal physiology, pH-dependent drug delivery principles, the physicochemical characteristics of omeprazole, and the evolution of enteric-coated pellet systems. Particular emphasis is placed on sequential drug release strategies, polymer selection, formulation challenges, and emerging advances in pH-sensitive oral drug delivery. The review highlights the pote
2026-05-20 | From SSTR to FAPI: Exploring a New Theranostic Pathway in Metastatic Grade 2 Gastrinoma with Loss of SSTR Expression
Somatostatin receptor (SSTR) PET/CT remains the cornerstone of imaging in neuroendocrine tumours (NETs), guiding both diagnosis and peptide receptor radionuclide therapy. However, dedifferentiated NETs may lose SSTR expression, limiting conventional theranostic approaches. In such cases, 18 F-fluorodeoxyglucose PET/CT can reveal metabolic heterogeneity; however, therapeutic options remain limited. Here, we present the imaging evidence of fibroblast activation protein inhibitor (FAPI) uptake in metastatic Grade 2 gastrinoma with loss of SSTR expression, providing FAPI as a potential alternative theranostic target in advanced NETs.
2026-05-06 | Formulation and Characterization of Enteric Coated Tablet Made by Combination of Pantoprazole and Omeprazole
Pantoprazole and omeprazole are proton pump inhibitors (PPIs) widely used in the treatment of acid-related gastrointestinal disorders such as peptic ulcer, GERD, and Zollinger–Ellison syndrome. Both drugs are highly unstable in acidic environments and undergo rapid degradation in the stomach. Therefore, the present study focuses on the formulation and characterization of enteric-coated tablets containing a combination of pantoprazole and omeprazole to protect them from gastric degradation and ensure targeted intestinal release. The tablets were prepared using direct compression/wet granulation techniques followed by enteric coating using polymers such as cellulose acetate phthalate and Eudragit L100. Preformulation studies including compatibility (FTIR), flow properties, and physicochemical parameters were evaluated. Post-compression parameters such as hardness, friability, weight variation, and drug content were assessed. In vitro dissolution studies showed minimal drug release in acidic pH (1.2) and maximum release in phosphate buffer (pH 6.8). Stability studies indicated that the formulation remained stable under accelerated conditions. The study concludes that enteric-coated combination tablets provide effective protection and improved bioavailability of both drugs.
antibodies
2024-09-09 | Expression profiles of cadherin 17 and claudin 18.2 in comparison with peptide hormonal expression in pancreatic neuroendocrine tumours: Implications for targeted immunotherapy.
Cadherin 17 (CDH17) and claudin 18.2 (CLDN18.2) are highly selective markers of intestinal and gastric lineages and are expressed in adenocarcinomas of various organs. They have also been identified as potential targets for immunotherapy. Expression of CDH17 and CLDN18.2 has been observed in a subset of pancreatic neuroendocrine tumours (PanNETs). This study investigates the immunohistochemical expression of CDH17 and CLDN18 in PanNETs in comparison with hormonal expression profiles to provide baseline data for determining candidate indications for targeted therapy with CDH17 and CLDN18.2 in PanNETs, including insulinomas (n = 22), glucagonomas (n = 13), gastrinomas (n = 3), serotoninomas (n = 2) and PanNETs not otherwise specified (NOS) (n = 17). In the normal pancreas, CDH17 was expressed in the lateral membrane of ducts and some islet cells, whereas CLDN18 was occasionally expressed in the intercalated ducts and centroacinar cells. In PanNETs, CDH17 and CLDN18 was detected by membranous staining. CDH17 expression was observed in 10 to 17 (58.8 %) PanNETs NOS, 3 of 13 (23.1 %) glucagonomas, 1 of 3 (33.3 %,) gastrinomas, 1 of 2 (50 %) serotoninomas, and none of the insulinomas. According to predefined criteria, 7 of 17 (41.2 %) PanNETs NOS, 1 of 3 (33.3 %) gastrinomas, and 1 of 2 (50 %) serotoninomas were classified as CDH17-positive. There were no significant differences in clinicopathological features between CDH17-positive and CDH17-negative PanNETs, except for a higher tumour grade in the former (p<0.05). For CLDN18, expression was noted in 2 out of 3 (66.7 %) gastrinomas, one with focal staining and the other with diffuse staining. One of three (33.3 %) gastrinomas was classified as CLDN18-positive using predefined criteria. These findings suggest that a particular subset of PanNETs, including PanNET NOS, gastrinoma, and serotoninoma, may be potential candidates for CDH17-targeted immunotherapy. Additionally, gastrinoma may be a potential candidate for immunotherapy targeting CLDN18.2.
2014-01-27 | Gastrin: from pathophysiology to cancer prevention and treatment.
Gastrin has been identified as the principal effector of gastric secretion, but several studies have demonstrated its role as a biomarker of cancer risk and as a growth factor for colorectal, stomach, liver, and pancreatic cancer. Hypergastrinemia characterizes autoimmune gastritis, with body and fundic gland atrophy and increased risk for both gastric adenocarcinoma and neuroendocrine tumors. Gastric type I carcinoids develop in the context of autoimmune gastritis because of the stimulus exerted by gastrin on enterochromaffin-like cells and remain gastrin-sensitive for long durations because the removal of hypergastrinemia leads to tumor regression. The treatment of gastric carcinoid is still open to debate, but when the disease frequently relapses, or is multicentric or infiltrating, surgery is advocated or, in the alternative, a costly and long-lasting treatment with long-acting somatostatin analogues is prescribed. A technology allowing the preparation of an immunogen eliciting an immune system response with generation of antibodies against G17 has been developed. This vaccine has been tested in patients with colorectal, pancreatic or advanced gastric cancer. The vaccine has also been used in the treatment of gastric type I carcinoids, and the administration of G17DT in patients harboring these lesions leads to carcinoid regression. Antigastrin vaccination in the treatment of gastrointestinal cancer obviously needs validation, but this immunotherapy may well represent a simple, inexpensive, and active 'adjuvant' treatment.
2013-01-08 | Extracellular Drug Conjugate (EDC1) Technology for Targeted Neuroendocrine Cancer Therapy
Surgery is the only curative treatment for patients with neuroendocrine (NE) cancers. This study was designed to investigate the effect of a novel drug system using extracellular drug conjugate (EDC1) technology on the growth of NE cancer cells. The EDC1 system is comprised of an antibody that specifically targets diseased cells over-expressing dysadherin, an anti-cancer drug binding to the Na+, K+ -ATPase alpha subunit (NKA), and a linker made with CarboConnect technology connecting the antibody to the drug. Dysadherin is a cancer-associated cell membrane glycoprotein that promotes metastasis by down-regulating E-cadherin, a protein required for cell adhesion. Therefore, our study evaluated the effect of EDC1 on gastrointestinal (BON) and pulmonary (H727) carcinoid cells to determine the therapeutic potential for NE cancers.
2008-12-31 | Importance of gastrin in the pathogenesis and treatment of gastric tumors
In addition to regulating acid secretion, the gastric antral hormone gastrin regulates several important cellular processes in the gastric epithelium including proliferation, apoptosis, migration, invasion, tissue remodelling and angiogenesis.Elevated serum concentrations of this hormone are caused by many conditions, particularly hypochlorhydria (as a result of autoimmune or Helicobacter pylori (H pylori )-induced chronic atrophic gastritis or acid suppressing drugs) and gastrin producing tumors (gastrinomas).There is now accumulating evidence that altered local and plasma concentrations of gastrin may play a role during the development of various gastric tumors.In the absence of H pylori infection, marked hypergastrinemia frequently results in the development of gastric enterochromaffin cell-like neuroendocrine tumors and surgery to remove the cause of hypergastrinemia may lead to tumor resolution in this condition.In animal models such as transgenic INS-GAS mice, hypergastrinemia has also been shown to act as a cofactor with Helicobacter infection during gastric adenocarcinoma development.However, it is currently unclear as to what extent gastrin also modulates h u m a n g a s t r i c a d e n o c a r c i n o m a d e ve l o p m e n t .Therapeutic approaches targeting hypergastrinemia, s u c h a s i m m u n i z a t i o n w i t h G 1 7 DT, h ave b e e n evaluated for the treatment of gastric adenocarcinoma, with some promising results.Although the mild hypergastrinemia associated with proton pump inhibitor drug use has been shown to cause ECL-cell hyperplasia and to increase H pylori -induced gastric atrophy, there is currently no convincing evidence that this class of agents contributes towards the development of gastric neuroendocrine tumors or gastric adenocarcinomas in human subjects.
2005-05-01 | Increased Expression of Insulin-Like Growth Factor I and/or Its Receptor in Gastrinomas Is Associated with Low Curability, Increased Growth, and Development of Metastases
Abstract Purpose: Growth factors, particularly insulin-like growth factor I (IGF-I) and IGF-I receptor (IGF-IR) in some nonendocrine and a few endocrine tumors, are thought important in recurrence, growth, and aggressiveness. Whether this is true of neuroendocrine tumors such as gastrinomas is unclear. The aim of this study was to address this question in gastrinomas. Experimental Design: IGF-I and IGF-IR expression in gastrinomas from 54 patients with Zollinger-Ellison syndrome were analyzed and correlated with clinical/tumor characteristics. IGF-I and IGF-IR mRNA levels were determined by competitive reverse transcription-PCR. IGF-IR expression, assessed by immunohistochemistry, was done on a subset. Results: IGF-IR mRNA was found in 100% and IGF-I in 89%. IGF-I mRNA expression varied by >254-fold, IGF-IR by 2,670-fold, and the levels correlated in a given tumor. The IGF-IR level was lower in gastrinomas of patients who were rendered disease free and increased levels correlated with tumor growth, aggressiveness, extent, and with liver metastases. Increased IGF-I levels correlated with increased growth, tumor extent, and aggressiveness. Neither IGF-IR nor IGF-I levels correlated with tumor location, size, or its clinical/functional features. The IGF-IR correlated with disease-free survival. IGF-IRβ was found in 31 of 32 tumors (97%) by immunohistochemistry. Conclusions: These results indicate that IGF-I and IGF-IR are expressed in almost all gastrinomas. Furthermore, assessment of IGF-I/IGF-IR expression in gastrinomas may be clinically useful in identifying those patients with more aggressive tumors who might benefit from more aggressive treatment.
proteins
2025-06-12 | Last decade of advances in gastric neuroendocrine tumors: Innovations, challenges, and future directions.
Gastric neuroendocrine tumors (G-NETs) are rare tumors originating from enterochromaffin-like cells, with an incidence of 0.4 per 100000 annually. There are three main types: (1) Type I, linked to chronic atrophic gastritis and hypergastrinemia, makes up 75%-80% of G-NETs; (2) Type II, associated with Zollinger-Ellison syndrome (ZES) and multiple endocrine neoplasia, comprises 5%; and (3) Type III, sporadic tumors with a higher metastatic potential, accounting for 15%-25%. Diagnosis involves endoscopy, biopsy, and histological examination. Additional methods include serum gastrin testing, immunohistochemistry, and imaging techniques such as computer tomography or magnetic resonance imaging for detecting metastasis. Type I treatment usually involves endoscopic resection (ER), with surgical resection for recurrence. Somatostatin analogs (SSAs) can reduce tumor size, and the prognosis is generally excellent. Type II treatment centers on surgical removal of the gastrinoma, with ER for smaller lesions and SSAs for symptom management. Type III requires surgical resection (partial or total gastrectomy) with lymph node dissection, and possibly chemotherapy. This type has a worse prognosis due to its aggressive nature. Emerging treatments like Peptide Receptor Radionuclide Therapy are promising for advanced cases, and ongoing research into immunotherapies is expanding future treatment options. Regular endoscopic follow-up is crucial to monitor for recurrence or metastasis across all types. Our literature review explores the current perspectives on G-NETs and highlights the importance of further research to improve diagnostic precision and treatment, particularly for those associated with less favorable cases. To improve diagnostic precision and treatment, particularly for those associated with less favorable cases. A systematic search was conducted in PubMed, Scopus, and Web of Science until September 2024. Two independent reviewers screened titles, abstracts, and full texts for eligibility based on G-NET treatment in adults. Eligible studies included cohort studies, clinical trials, case series, and case reports, while in vitro, pediatric, and non-English studies were excluded. Relevant data were extracted independently, and disagreements were resolved through discussion. Study quality was assessed using appropriate tools. G-NETs are rare, classified into three types: (1) Type I; (2) Type II; and (3) Type III. Type I G-NETs, often associated with chronic atrophic gastritis, are typically slow-growing and low-grade, with favorable outcomes following surgical resection. Type II G-NETs arise in hypergastrinemia conditions like multiple endocrine neoplasia and ZES, showing moderate malignancy risk. Type III G-NETs, the most aggressive and least common, present with distant metastases and poor prognosis. Diagnosis relies on endoscopy, imaging, and biomarkers like chromogranin A. Treatment varies by type, ranging from ER to aggressive surgery and chemotherapy for advanced cases. Regular follow-up is essential to monitor recurrence, particularly for type III G-NETs. G-NETs require tailored diagnosis and treatment based on type and stage. Types I and II generally have better prognosis, while types III and IV are linked to poorer outcomes due to invasion and metastasis. Treatment strategies vary from ER for type I to extensive surgery for type III. Emerging therapies, like somatostatin analogs and peptide-receptor radionuclide therapies, show promise in advanced cases. Further research is essential to improve early diagnosis and treatment, particularly for high-risk lesions.
2023-09-07 | Recurrent Neuroendocrine Tumor of the Pancreas Presenting with Hypertension in the Setting of Hyperreninemia: A Case Report
Background: Pancreatic neuroendocrine tumors are a diverse group of neoplasms which coexist with gastrointestinal carcinoids as the main histiotypes of gastrointestinal neuroendocrine tumors.Pancreatic neuroendocrine tumors are found primarily in the pancreas and upper small intestine.Although pancreatic neuroendocrine tumors share many features with gastrointestinal carcinoids, they are generally considered separately because of their different clinical syndromes (carcinoid syndrome vs. pancreatic neuroendocrine tumor syndromes) molecular pathogenesis, biological behaviors, and difference in response to antineoplastic treatments.Common pancreatic neuroendocrine tumors include gastrinomas, insulinomas, glucagonomas, VIPomas, GRFomas, ACTHomas, somatostatinomas, pancreatic neuroendocrine tumors causing carcinoid syndrome and those causing hypercalcemia (PTHrPomas).A pancreatic neuroendocrine tumor secreting renin resulting in hypertension is exceptionally rare and has not been previously reported. Case Presentation:We present a 43-year-old female with a grade 2 neuroendocrine tumor diagnosed four years earlier, initially treated with distal pancreatectomy and splenectomy, who presented to her internist for routine follow up with a blood pressure of 150/100 mmHg.An MRI three months earlier showed no recurrent disease with stable Chromogranin A levels.A workup for secondary hypertension was pursued which discovered an elevation in renin and aldosterone levels without evidence of hypercoagulability or compromised vascular supply to the kidneys.Four months later, an MRI showed a new metastatic lesion in the liver and the Chromogranin A levels increased from her baseline.With two microwave ablations and Lanreotide, her blood pressure normalized as did her renin and aldosterone levels. Conclusion:Newly diagnosed hypertension in a patient with a history of a pancreatic neuroendocrine tumor should prompt a workup for secondary hypertension as this may be a sign of tumor recurrence.Hyperreninemia in the setting of a neoplasm has mostly been described with juxtaglomerular cell tumors of the kidney and has never been described with a pancreatic neuroendocrine tumor.Treating the underlying tumor can eliminate the overproduction of renin and normalize the blood pressure.
2023-07-02 | Spatial profiling of neuro-immune interactions in gastroenteropancreatic NETs
Abstract Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are heterogeneous malignancies that arise from complex cellular interactions within the tissue microenvironment. Here, we sought to decipher tumor-derived signals from the surrounding microenvironment by applying Nanostring Digital Spatial Profiling (DSP) to hormone-secreting and non-functional GEP-NETs. DSP was used to evaluate the expression of 40 neural and immune-related proteins in surgically resected duodenal and pancreatic NETs (n=20) primarily comprised of gastrinomas (18/20). A total of 279 regions of interest were examined between tumors, adjacent normal and abnormal-appearing epithelium, and the surrounding stroma. The results were stratified by tissue type and Multiple Endocrine Neoplasia I (MEN1) status and protein expression was validated by immunohistochemical (IHC) staining. A tumor immune cell autonomous inflammatory signature was further evaluated by IHC and RNAscope, while functional pro-inflammatory signaling was confirmed using patient-derived duodenal organoids. Gastrin-secreting and non-functional pancreatic NETs showed a higher abundance of immune cell markers and immune infiltrate compared to duodenal gastrinomas. Tumors displayed strong intra-tissue variation in the expression of neural- and immune-related proteins. Compared to non- MEN1 tumors, MEN1 gastrinomas showed reduced expression of immune cell markers and upregulated expression of neuropathological proteins. Duodenal gastrinomas showed strong expression of the pro- inflammatory and pro-neural factor IL-17B. Treatment of human duodenal organoids with IL- 17B activated NF-kB and STAT3 signaling and induced the expression of neuroendocrine markers. In conclusion, multiplexed spatial protein analysis identified tissue-specific neuro- immune signatures in GEP-NETs. Moreover, duodenal gastrinomas cell autonomously express immune and pro-inflammatory factors, including tumor-derived IL-17B, that stimulate the neuroendocrine phenotype.
2022-07-08 | Targeted treatment with somatostatin analogues: widening horizons of clinical practice
Targeted treatment with somatostatin analogues (SA) in acromegaly and neuroendocrine neoplasms may have some benefits compared to curative treatments, because these agents decrease excessive hormone secretion and exert a tumor-suppressive effect. Monotherapy and combination therapy with SA is well tolerated and bears no risk of debilitating iatrogenic complications. In acromegaly caused by somatotropin producing pituitary tumor, first generation SA are treatment of choice after non-radical adenomectomy, as well as in the cases when patients reject surgery. Treatment efficacy depends on the pathomorphological types of somatotropic tumors, which are different in their receptor phenotype, clinical scenario and proliferative activity. The first generation SA are successfully used for medical treatment of other pituitary tumors (thyrotropic, corticotropic, gonadotropic, lactotropic with resistance to dopamine agonists), as well as for adjuvant therapy of neuroendocrine and non-endocrine neoplasms and elimination of various gastrointestinal disorders. The anti-secretory and anti-tumor effects of SA have been proven for gastroenteropancreatic tumors (carcinoid syndrome, vipomas, gastrinomas, insulinomas, glucagonomas, somatostatinomas). Targeted selection of patients for treatment with first generation SA based on the receptor phenotypes of malignant cells would facilitate more rapid achievement of biochemical remission, improvement of quality of life and survival.
2021-06-03 | Somatostatin Analogs in Patients with Zollinger Ellison Syndrome (ZES): An Observational Study
Abstract PURPOSE : Zollinger Ellison syndrome (ZES) is a rare syndrome caused by gastrin hypersecretion from a gastrinoma. Gastrinoma treatment has two goals: the control of the gastrin-excess state and the control of tumor growth. While therapy for the syndrome is univocally based on proton pump inhibitors, the one for disease control is still debated. We here aimed at evaluating the role of SSAs in the control of tumor progression in a series of ZES patients.METHODS: A retrospective analysis of a prospectively collected database of ZES patients, followed and managed from 1990 to 2019, was performed. The patients' clinical, pathological, treatment, and follow-up data were analyzed. Data regarding SSAs therapy start, dosage, duration, and side effects were collected.RESULTS: 33 patients with ZES were diagnosed. Fourteen patients (42%) had a G1 NEN, five had G2 (15%), none had G3. Fifteen patients (45%) had metastatic disease. Overall, 12 (36%) underwent SSAs therapy. The median treatment duration was 36 months. Eight patients (67%) had a sustained response to SSA, four (33%) showed an early progression, with a significant difference in terms of PFS between the two groups (84 vs 2 months, p=0.004). No differences in terms of OS and PFS were observed between the two groups, despite the proportion of metastatic patients was greater in the SSA-treated group (75% vs 29% in the non-treated group, p=0.01). CONCLUSION: Present data support the use of SSAs in ZES, considering that gastrinoma is mainly a well-differentiated low-grade tumor (G1 or G2), with a high expression of somatostatin receptors.
small molecules
2026-08-01 | DEVELOPMENT AND EVALUATION OF ENTERIC-COATED PANTOPRAZOLE TABLETS FOR ENHANCED GASTRIC PROTECTION
Pantoprazole is a proton pump inhibitor widely used in the management of acid-related gastrointestinal disorders, including gastroesophageal reflux disease, peptic ulcer disease, and Zollinger–Ellison syndrome. Because Pantoprazole is highly unstable in acidic conditions, an enteric coating is essential to protect the drug from degradation in the stomach and ensure its release in the intestinal environment. The present study aimed to formulate and evaluate enteric-coated Pantoprazole tablets with improved stability and effective drug delivery. Preformulation studies were carried out to evaluate the physicochemical properties and compatibility of the drug with selected excipients. Six formulations (F1–F6) were prepared and subjected to pre-compression evaluation, including angle of repose, bulk density, tapped density, Carr's index, and Hausner's ratio, which demonstrated satisfactory flow and compressibility. The core tablets were evaluated for physical appearance, thickness, diameter, weight variation, hardness, friability, drug content, and disintegration time, followed by enteric coating and in vitro dissolution studies. Among the developed formulations, F6 exhibited the most desirable characteristics, including excellent mechanical strength, acceptable friability, uniform drug content, effective resistance to acidic medium, and maximum drug release in phosphate buffer after the enteric coating dissolved. The results confirmed that the optimized enteric-coated formulation successfully protected Pantoprazole from gastric degradation and provided efficient drug release in the intestinal environment. Therefore, formulation F6 was identified as the optimized formulation with suitable pharmaceutical properties and potential for effective oral therapy.
2026-08-01 | EP947 - ECE_1770 - Severe hypergastrinemia with mild clinical expression: the modulating role of autoimmune atrophic gastritis in metastatic gastrinoma
Abstract Background Gastrinomas are rare functioning neuroendocrine tumors characterized by inappropriate gastrin secretion leading to gastric acid hypersecretion and Zollinger–Ellison syndrome. Diagnosis usually requires the demonstration of hypergastrinemia in the setting of low gastric pH. In clinical practice, however, gastric pH assessment may be unavailable, and coexisting gastric disorders may confound symptomatic and biochemical interpretation,, and delay the diagnosis. Case Presentation We report the case of a 78-year-old woman with a well-differentiated pancreatic neuroendocrine tumorand extensive hepatic and lymph node metastases. The tumor was identified during evaluation of abdominal and pelvic discomfort. Cross-sectional imaging revealed a 61mm exophytic mass in the pancreatic body with diffuse liver metastases.Liver biopsy histopathology confirmed a metastatic pancreatic neuroendocrine tumor, with a Ki-67 proliferation index <3% and strong expression of neuroendocrine markers. Functional imaging with 68Ga-DOTATOC PET demonstrated very intense somatostatin receptor expression throughout the entire tumor burden. Biochemical evaluation revealed extreme fasting hypergastrinemia (99007 pg/mL). Clinically, the patient reported chronic abdominal pain and recurrent diarrhea but lacked other hallmark features of Zollinger–Ellison syndrome, such as peptic ulcer disease, severe gastroesophageal reflux, or significant weight loss. Gastric pH measurement was not available, limiting physiological confirmation of acid hypersecretion. Upper gastrointestinal endoscopy revealed body-predominant atrophic gastritis with focal intestinal metaplasia, active Helicobacter pylori infection and no ulcerations. In this context, autoimmune atrophic gastritis was suspected, which would explain the mild clinical expression of such high gastrin levels. Further tests showed positive anti-parietal cell antibodies and vitamine B12 deficiency, supporting this diagnosis. Germline genetic testing for MEN1 and CDKN1B revealed no pathogenic variants. LAR octreotide was initiated leading to diarrhea improvement, a dramatic fall in the gastrin levels (460 pg/mL in the last evaluation) and structural stable disease during the last three years. Conclusions This case represents a pathophysiological challenge. On one hand, an autoimmune atrophic gastritis could explain the clinical picture and be seen here as protective factor by reducing parietal cell mass and attenuating acid secretion, thereby limiting ulcerative complications despite extreme gastrin. On the other hand, atrophic gastritis itself can cause secondary hypergatrinemia, which may be a confounding effect.Awareness of such interplay is essential to avoid misinterpretation of isolated hypergastrinemia and to ensure timely diagnosis.
2026-07-21 | pH-Sensitive Enteric-Coated Omeprazole Pellet Systems for Sequential Gastrointestinal Drug Delivery: Formulation Strategies, Release Mechanisms, and Recent Advances
Oral drug delivery remains the most preferred route of administration because of its convenience, non-invasive nature, cost-effectiveness, and high patient compliance. However, the successful delivery of acid-labile drugs continues to present significant formulation challenges. Omeprazole, a proton pump inhibitor widely prescribed for the treatment of gastroesophageal reflux disease (GERD), peptic ulcer disease, and Zollinger–Ellison syndrome, is highly unstable in acidic environments and undergoes rapid degradation in the stomach before reaching its primary absorption site in the small intestine. Consequently, specialized formulation approaches are required to protect the drug during gastric transit while ensuring efficient intestinal release. Among various oral delivery systems, pH-sensitive enteric-coated pellets have emerged as one of the most successful strategies for improving the stability and bioavailability of omeprazole. Multiparticulate pellet systems provide uniform distribution throughout the gastrointestinal tract, reduce variability in gastric emptying, and offer greater flexibility in controlling drug release compared with conventional single-unit dosage forms. The incorporation of pH-responsive polymers such as Eudragit® L100 and Eudragit® S100 enables site-specific release by exploiting physiological pH variations within the gastrointestinal tract. Recent developments in pelletization technology, enteric coating systems, and Quality by Design (QbD) methodologies have significantly improved the performance and reproducibility of omeprazole formulations. This review critically examines gastrointestinal physiology, pH-dependent drug delivery principles, the physicochemical characteristics of omeprazole, and the evolution of enteric-coated pellet systems. Particular emphasis is placed on sequential drug release strategies, polymer selection, formulation challenges, and emerging advances in pH-sensitive oral drug delivery. The review highlights the pote
2026-05-20 | From SSTR to FAPI: Exploring a New Theranostic Pathway in Metastatic Grade 2 Gastrinoma with Loss of SSTR Expression
Somatostatin receptor (SSTR) PET/CT remains the cornerstone of imaging in neuroendocrine tumours (NETs), guiding both diagnosis and peptide receptor radionuclide therapy. However, dedifferentiated NETs may lose SSTR expression, limiting conventional theranostic approaches. In such cases, 18 F-fluorodeoxyglucose PET/CT can reveal metabolic heterogeneity; however, therapeutic options remain limited. Here, we present the imaging evidence of fibroblast activation protein inhibitor (FAPI) uptake in metastatic Grade 2 gastrinoma with loss of SSTR expression, providing FAPI as a potential alternative theranostic target in advanced NETs.
2026-05-06 | Formulation and Characterization of Enteric Coated Tablet Made by Combination of Pantoprazole and Omeprazole
Pantoprazole and omeprazole are proton pump inhibitors (PPIs) widely used in the treatment of acid-related gastrointestinal disorders such as peptic ulcer, GERD, and Zollinger–Ellison syndrome. Both drugs are highly unstable in acidic environments and undergo rapid degradation in the stomach. Therefore, the present study focuses on the formulation and characterization of enteric-coated tablets containing a combination of pantoprazole and omeprazole to protect them from gastric degradation and ensure targeted intestinal release. The tablets were prepared using direct compression/wet granulation techniques followed by enteric coating using polymers such as cellulose acetate phthalate and Eudragit L100. Preformulation studies including compatibility (FTIR), flow properties, and physicochemical parameters were evaluated. Post-compression parameters such as hardness, friability, weight variation, and drug content were assessed. In vitro dissolution studies showed minimal drug release in acidic pH (1.2) and maximum release in phosphate buffer (pH 6.8). Stability studies indicated that the formulation remained stable under accelerated conditions. The study concludes that enteric-coated combination tablets provide effective protection and improved bioavailability of both drugs.
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Drug Discovery Landscape
3 orphan drug designations for Zollinger-Ellison syndrome, including 2 approved therapies.
3 orphan drug designations for Zollinger-Ellison syndrome, including 2 approved therapies.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
omeprazole-lansoprazole with buffer | small molecules | FDA | — | Effexus Pharmaceuticals, LLC |
Synthetic porcine secretin [Secreflo] | peptides | FDA | Approved | ChiRhoClin, Inc. |
Synthetic human secretin [Chirostim] | peptides | FDA | Approved | ChiRhoClin, Inc. |
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