Effectiveness of serological markers of gastric mucosal atrophy in the gastric precancer screening and in cancer prevention.

BACKGROUND: New markers are needed to improve the effectiveness of serological screening for atrophic gastritis. AIM: To develop a cost-effective method for serological screening of atrophic gastritis with a high level of sensitivity. METHODS: Of the 169 patients with atrophic gastritis, selected by the visual endoscopic Kimura-Takemoto method, 165 showed histological mucosal atrophy using the updated Kimura-Takemoto method. All 169 patients were examined for postprandial levels of gastrin-17 (G17) and pepsinogen-1 (PG1) using GastroPanel® (Biohit Plc, Helsinki, Finland). RESULTS: We used the histological standard of five biopsies of the gastric mucosa, in accordance with the Kimura-Takemoto classification system to assess the sensitivity of G17 in detecting gastric mucosal atrophy. We also compared the morpho-functional relationships between the detected histological degree of gastric mucosal atrophy and the serological levels of G17 and PG1, as the markers of atrophic gastritis. The sensitivity of postprandial G17 was 62.2% for serological levels of G17 (range: 0-4 pmol/L) and 100% for serological G17 (range: 0-10 pmol/L) for the detection of monofocal severe atrophic gastritis. No strong correlation was found between the levels of PG1 and degree of histological atrophy determined by the Kimura-Takemoto classification system to identify the severity of mucosal atrophy of the gastric corpus. In the presented clinical case of a 63-year-old man with multifocal atrophic gastritis, there is a pronounced positive long-term dynamics of the serological marker of atrophy - postprandial G17, after five months of rennet replacement therapy. CONCLUSION: Serological screening of multifocal atrophic gastritis by assessment of postprandial G17 is a cost-effective method with high sensitivity. Postprandial G17 is an earlier marker of regression of atrophic gastritis than a morphological examination of a gastric biopsy in accordance with the Sydney system. Therefore, postprandial G17 is recommended for dynamic monitoring of atrophic gastritis after treatment.

Gastrin-releasing peptide receptor antagonist RC-3095 inhibits Porphyromonas gingivalis lipopolysaccharide-accelerated atherosclerosis by suppressing inflammatory responses in endothelial cells and macrophages.

OBJECTIVE: Porphyromonas gingivalis (P. gingivalis), one of the major periodontopathogens, is associated with the progression and exacerbation of atherosclerosis. In this study, we aimed to investigate whether the gastrin-releasing peptide receptor antagonist, RC-3095, could attenuate P. gingivalis LPS-induced inflammatory responses in endothelial cells and macrophages, as well as atherosclerosis in an ApoE-/- mouse model treated with P. gingivalis LPS. METHODS: The effect of RC-3095 on P. gingivalis LPS-induced endothelial inflammation was examined using HUVECs and rat aortic endothelium. THP-1 cells were polarized into M1 macrophages by exposure to P. gingivalis LPS, with or without RC-3095. The effect of RC-3095 on atherosclerosis progression was assessed in high-fat-fed male ApoE-/- mice through injections of P. gingivalis LPS, RC-3095, or a combination of both. RESULTS: RC-3095 significantly reduced P. gingivalis LPS-induced leukocyte adhesion to endothelial cells and aortic endothelium by suppressing NF-κB-dependent expressions of ICAM-1 and VCAM-1. In addition, RC-3095 inhibited the P. gingivalis LPS-induced polarization of M1 macrophages by blocking the MAPK and NF-κB signaling pathways. Moreover, RC-3095 decreased the area of atherosclerotic lesions in ApoE-/- mice, which was accelerated by P. gingivalis LPS injection, and lowered the expressions of ICAM-1 and VCAM-1 in the aortic tissue of mice with atherosclerosis. CONCLUSIONS: RC-3095 can alleviate P. gingivalis LPS-induced endothelial inflammation, macrophage polarization, and atherosclerosis progression, suggesting its potential as a therapeutic approach for periodontal pathogen-associated atherosclerosis.

Occurrence and characteristics of endoscopic gastric polyps in patients with autoimmune gastritis (AGAPE study): A multicentric cross-sectional study.

BACKGROUND: Autoimmune gastritis (AIG) leads to increased gastrin (G) levels due to hypo-achlorhydria, providing proliferative stimuli on the gastric mucosa. AIMS: To evaluate the incidence and characteristics of gastric polyps in AIG patients across six tertiary centers in Italy. METHODS: A multicentric, cross-sectional study enrolled patients with AIG diagnosed from January 2000 to June 2023, who underwent at least one endoscopy. Data on demographics, clinical history, biochemical profiles, and endoscopic and histopathological findings were systematically collected. RESULTS: Among 612 AIG patients followed for a median of 4 years, 222 (36.3 %) developed at least one gastric polyp. Of these, 214 were non-endocrine lesions detected in 162 patients, including 151 inflammatory (70.5 %), 29 adenomatous (13.6 %), 18 fundic gland polyps (8.4 %), 13 adenocarcinomas (6.1 %), and one MALT lymphoma. Additionally, 108 patients had gastric neuroendocrine neoplasms (gNENs), with 48 also having non-endocrine polyps. Older age and higher gastrin and chromogranin A levels were associated with polyp occurrence. No differences in OLGA/OLGIM stages or Helicobacter pylori status were noted among patients with and without lesions. CONCLUSION: This large multicentric study underscores the substantial occurrence of gastric polyps in AIG patients, including notable rates of gNENs and adenocarcinomas, emphasizing the importance of proactive endoscopic surveillance and histopathological examination for effective management.

Pleural pro-gastrin releasing peptide is a potential diagnostic marker for malignant pleural effusion induced by small-cell lung cancer.

Background: Serum pro-gastrin releasing peptide (proGRP) is a well-recognized diagnostic marker for small cell lung cancer (SCLC). Pleural effusion is common in patients with advanced SCLC. The diagnostic accuracy of pleural proGRP for malignant pleural effusion (MPE) has not yet been established. This study aimed to evaluate the diagnostic accuracy of pleural proGRP for MPE. Methods: We prospectively recruited patients with undiagnosed pleural effusions from two centers (Hohhot and Changshu). An electrochemiluminescence immunoassay was used to detect pleural fluid proGRP. The diagnostic accuracy of proGRP for MPE was evaluated using a receiver operating characteristic (ROC) curve. Results: In both the Hohhot (n=153) and Changshu (n=58) cohorts, pleural proGRP in MPE patients did not significantly differ from that in patients with benign pleural effusions (BPEs) (Hohhot, P=0.91; Changshu, P=0.12). In the Hohhot and Changshu cohorts, the areas under the curves (AUCs) of proGRP were 0.51 [95% confidence interval (CI): 0.41-0.60] and 0.62 (95% CI: 0.47-0.77), respectively. However, patients with SCLC-induced MPE had significantly higher proGRP levels than those with BPE and other types of MPE (P=0.001 for both). In the pooled cohort, the AUC of proGRP for SCLC-induced MPE was 0.90 (95% CI: 0.78-1.00, P=0.001). At a threshold of 40 pg/mL, proGRP had a sensitivity of 1.00 (95% CI: 0.61-1.00) and specificity of 0.59 (95% CI: 0.52-0.66). The positive likelihood ratio was 2.61 (95% CI: 1.99-3.41), and the negative likelihood ratio was 0. Conclusions: Pleural proGRP has no diagnostic value for MPE, but has high diagnostic accuracy for SCLC-induced MPE. In patients with proGRP levels <40 pg/mL, MPE secondary to SCLC can be excluded.

Influence of a diet meal plan on pepsinogen I and II, gastrin-17, and nutritional status in gastric ulcer patients.

BACKGROUND: Gastric ulcers (GUs) have a high risk of clinical morbidity and recurrence, and further exploration is needed for the prevention, diagnosis, and treatment of the disease. AIM: To investigated the effects of a diet plan on pepsinogen (PG) I, PG II, gastrin-17 (G-17) levels and nutritional status in patients with GUs. METHODS: A total of 100 patients with GUs treated between May 2022 and May 2023 were enrolled, with 47 patients in the control group receiving routine nursing and 53 patients in the experimental group receiving dietary nursing intervention based on a diet plan. The study compared the two groups in terms of nursing efficacy, adverse events (vomiting, acid reflux, and celialgia), time to symptom improvement (burning sensation, acid reflux, and celialgia), gastric function (PG I, PG II, and G-17 levels), and nutritional status [prealbumin (PA) and albumin (ALB) levels]. RESULTS: The experimental group showed a markedly higher total effective rate of nursing, a significantly lower incidence of adverse events, and a shorter time to symptom improvement than the control group. Additionally, the experimental group's post-intervention PG I, PG II, and G-17 levels were significantly lower than pre-intervention or control group levels, whereas PA and ALB levels were significantly higher. CONCLUSION: The diet plan significantly reduced PG I, PG II, and G-17 levels in patients with GUs and significantly improved their nutritional status.

Bimodal MRI/Fluorescence Nanoparticle Imaging Contrast Agent Targeting Prostate Cancer.

We developed a novel site-specific bimodal MRI/fluorescence nanoparticle contrast agent targeting gastrin-releasing peptide receptors (GRPrs), which are overexpressed in aggressive prostate cancers. Biocompatible ultra-small superparamagnetic iron oxide (USPIO) nanoparticles were synthesized using glucose and casein coatings, followed by conjugation with a Cy7.5-K-8AOC-BBN [7-14] peptide conjugate. The resulting USPIO(Cy7.5)-BBN nanoparticles were purified by 100 kDa membrane dialysis and fully characterized using transmission electron microscopy (TEM), dynamic light scattering (DLS), Fourier transform infrared (FTIR) spectroscopy, and magnetic resonance imaging (MRI) relaxivity, as well as evaluated for in vitro and in vivo binding specificity and imaging efficacy in PC-3 prostate cancer cells and xenografted tumor-bearing mice. The USPIO(Cy7.5)-BBN nanoparticles had a core diameter of 4.93 ± 0.31 nm and a hydrodynamic diameter of 35.56 ± 0.58 nm. The r2 relaxivity was measured to be 70.2 ± 2.5 s-1 mM-1 at 7T MRI. The Cy7.5-K-8AOC-BBN [7-14] peptide-to-nanoparticle ratio was determined to be 21:1. The in vitro GRPr inhibitory binding (IC50) value was 2.5 ± 0.7 nM, indicating a very high binding affinity of USPIO(Cy7.5)-BBN to the GRPr on PC-3 cells. In vivo MRI showed significant tumor-to-muscle contrast enhancement in the uptake group at 4 h (31.1 ± 3.4%) and 24 h (25.7 ± 2.1%) post-injection compared to the blocking group (4 h: 15.3 ± 2.0% and 24 h: -2.8 ± 6.8%; p < 0.005). In vivo and ex vivo near-infrared fluorescence (NIRF) imaging revealed significantly increased fluorescence in tumors in the uptake group compared to the blocking group. These findings demonstrate the high specificity of bimodal USPIO(Cy7.5)-BBN nanoparticles towards GRPr-expressing PC-3 cells, suggesting their potential for targeted imaging in aggressive prostate cancer.

A pathway for detection of gastric cancer biomarkers via using a layer-by-layer coated D-shaped grinding long-period fiber grating sensor.

Gastric cancer significantly contributes to global cancer mortality, often leading to inoperable stages and high recurrence rates post-surgery. Elevated levels of G-17 and G-gly have been identified as potential risk factors, particularly in patients with duodenal ulcers. This study introduces an innovative D-shaped grinding long-period fiber grating sensor (D-LLPFGs) designed for non-invasive detection of the gastrin G-17 antigen, employing a layer-by-layer chemical self-assembly to bond G-17 antibodies onto the fiber surface through hydrogen bonding. The D-LLPFGs sensor demonstrated significant spectral shifts within 1 min of antigen-antibody interaction, highlighting its rapid detection capability. At an optimized antibody concentration of 4 µg/ml, antigen testing across different concentrations (10, 12.5, 20, 50 µg/ml) showed peak changes at 12.5 µg/ml antigen, with a 1.186 nm shift and 0.503 dB loss. The sensor exhibited a wavelength sensitivity of 0.095 nm/µg/ml, indicating its high sensitivity and potential in gastric cancer classification, diagnosis, and treatment. This research concludes that the D-shaped fiber sensor is an effective and sensitive tool for detecting G-17 antigen levels, presenting a significant advancement in non-invasive gastric cancer diagnosis. Its quick response time and high sensitivity highlight its potential for broad biomedical applications, offering a new avenue for early cancer detection and improving patient prognosis. The success of this study opens the door to further exploration and implementation of fiber optic sensors in clinical settings, marking a significant step forward in the fight against gastric cancer.

Synthesis and Evaluation of the First 68Ga-Labeled C-Terminal Hydroxamate-Derived Gastrin-Releasing Peptide Receptor-Targeted Tracers for Cancer Imaging with Positron Emission Tomography.

Gastrin-releasing peptide receptor (GRPR), overexpressed in many solid tumors, is a promising imaging marker and therapeutic target. Most reported GRPR-targeted radioligands contain a C-terminal amide. Based on the reported potent antagonist D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-NHOH, we synthesized C-terminal hydroxamate-derived [68Ga]Ga-LW02075 ([68Ga]Ga-DOTA-pABzA-DIG-D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-NHOH) and [68Ga]Ga-LW02050 ([68Ga]Ga-DOTA-Pip-D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-NHOH), and compared them with the closely related and clinically validated [68Ga]Ga-SB3 ([68Ga]Ga-DOTA-pABzA-DIG-D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-NHEt). Binding affinities (Ki) of Ga-SB3, Ga-LW02075, and Ga-LW02050 were 1.20 ± 0.31, 1.39 ± 0.54, and 8.53 ± 1.52 nM, respectively. Both Ga-LW02075 and Ga-LW02050 were confirmed to be GRPR antagonists by calcium release assay. Imaging studies showed that PC-3 prostate cancer tumor xenografts were clearly visualized at 1 h post injection by [68Ga]Ga-SB3 and [68Ga]Ga-LW02050 in PET images, but not by [68Ga]Ga-LW02075. Ex vivo biodistribution studies conducted at 1 h post injection showed that the tumor uptake of [68Ga]Ga-LW02050 was comparable to that of [68Ga]Ga-SB3 (5.38 ± 1.00 vs. 6.98 ± 1.36 %ID/g), followed by [68Ga]Ga-LW02075 (3.97 ± 1.71 %ID/g). [68Ga]Ga-SB3 had the highest pancreas uptake (37.3 ± 6.90 %ID/g) followed by [68Ga]Ga-LW02075 (17.8 ± 5.24 %ID/g), while the pancreas uptake of [68Ga]Ga-LW02050 was only 0.53 ± 0.11 %ID/g. Our data suggest that [68Ga]Ga-LW02050 is a promising PET tracer for detecting GRPR-expressing cancer lesions.

Autoimmune Gastritis and Hypochlorhydria: Known Concepts from a New Perspective.

Autoimmune atrophic gastritis is an immune-mediated disease resulting in autoimmune destruction of the specialized acid-producing gastric parietal cells. As a consequence, in autoimmune atrophic gastritis, gastric acid secretion is irreversibly impaired, and the resulting hypochlorhydria leads to the main clinical manifestations and is linked, directly or indirectly, to the long-term neoplastic complications of this disease. In the last few years, autoimmune atrophic gastritis has gained growing interest leading to the acquisition of new knowledge on different aspects of this disorder. Although reliable serological biomarkers are available and gastrointestinal endoscopy techniques have substantially evolved, the diagnosis of autoimmune atrophic gastritis is still affected by a considerable delay and relies on histopathological assessment of gastric biopsies. One of the reasons for the diagnostic delay is that the clinical presentations of autoimmune atrophic gastritis giving rise to clinical suspicion are very different, ranging from hematological to neurological-psychiatric up to gastrointestinal and less commonly to gynecological-obstetric symptoms or signs. Therefore, patients with autoimmune atrophic gastritis often seek advice from physicians of other medical specialties than gastroenterologists, thus underlining the need for increased awareness of this disease in a broad medical and scientific community.

Predictive efficacy of combined tumor markers and gastrin for recurrence after endoscopic submucosal dissection in early gastric cancer patients.

OBJECTIVE: This study aims to evaluate the predictive value of tumor markers combined with gastrin for tumor recurrence after endoscopic submucosal dissection (ESD) in patients with early gastric cancer. METHODS: The clinicopathological data of 169 patients with early gastric cancer treated with ESD between March 2019 and January 2021 were retrospectively analyzed. The patients were divided into a relapse group (n=45) and a non-recurrence group (n=124). Clinical data such as carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA19-9), alpha-fetoprotein (AFP), gastrin 17, pepsinogen I and pepsinogen II, as well as tumor size and degree of infiltration were examined to construct a recurrence prediction model using lasso regression. RESULTS: The comprehensive model showed superior predictive power (AUC=0.958, C-index=0.966) over biomarker-only models (AUC=0.925), indicating a significant improvement in the prediction of recurrence risk. Decision curve analysis confirmed the clinical utility of the model with a maximum net benefit of 73.37%. Key indicators such as CEA, CA19-9, AFP, gastrin 17 and pepsinogens I and II were statistically significant in predicting recurrence with P values < 0.01. CONCLUSION: The comprehensive model combining tumor markers with clinical data provides a more accurate and clinically valuable tool for predicting recurrence in early gastric cancer patients after ESD. This approach facilitates personalized risk assessment and may significantly improve prognostic management, emphasizing the importance of a multifaceted strategy in the management of early gastric cancer.

Omeprazole taken once every other day can effectively prevent aspirin-induced gastrointestinal mucosal damage in rats.

BACKGROUND: Proton-pump inhibitors (PPIs) prevent aspirin-associated gastric and duodenal mucosal damage. However, long-term use of PPIs can lead to various adverse reactions, such as gastric polyps and enterochromaffin-like cell hyperplasia. Current research indicates that the abovementioned adverse reactions are mainly related to hypergastrinemia. We investigated whether low-frequency administration of omeprazole could effectively repair aspirin-induced mucosal damage and reduce the increase in gastrin levels associated with long-term use of PPIs. METHODS: Sprague‒Dawley rats were divided into four treatment groups: daily aspirin, daily aspirin and omeprazole once every day (qd), daily aspirin and omeprazole once every other day (qod), and daily aspirin and omeprazole once every three days (1/d3). After 15 days of feeding, blood samples were collected, and the stomachs of sacrificed rats were subjected to macroscopic, histological, and immunohistochemical studies. Moreover, in clinical practice, patients with peptic ulcers caused by aspirin took a standard dose of omeprazole (20 mg) every other day. Two months later, gastroscopy was performed to examine the healing of the ulcers. RESULTS: Both the omeprazole qd and omeprazole qod administrations effectively prevented aspirin-induced gastric peptic ulcers, with no significant difference between the two groups in the inhibition of parietal cell secretion of gastric acid and cell apoptosis. However, omeprazole 1/d3 failed to completely prevent aspirin-induced gastric mucosal injury. Notably, the gastrin levels, cell proliferation ability and cholecystokinin B receptor expression of the omeprazole qd group were significantly higher than those of the omeprazole qod group. In clinical work, patients with peptic ulcers caused by aspirin were given a standard dose of omeprazole every other day, and their ulcers healed after 2 months, as observed by gastroscopy. CONCLUSIONS: Omeprazole administration once every other day can effectively prevent aspirin-induced peptic ulcers and reduce hypergastrinemia, which may reduce the long-term adverse effects of PPI treatment.

Choledochoduodenostomy combined with Billroth II procedure for extrahepatic biliary obstruction and duodenal perforation in a cat.

Case summary: A 5-year-old neutered Somali cat presented with a 2-week history of icterus. Diagnostic imaging revealed extrahepatic biliary obstruction (EHBO) due to a common bile duct (CBD) mass. During exploratory laparotomy, a duodenal perforation was discovered incidentally. Choledochoduodenostomy combined with the Billroth II procedure was performed after resection of the CBD mass and the proximal duodenum to treat the EHBO and duodenal perforation. Based on histological and immunohistochemical findings, the CBD mass was diagnosed as a neuroendocrine carcinoma with gastrin-producing cell differentiation. The cat recovered almost uneventfully and was discharged 11 days after surgery. The cat survived for nearly 100 days without recurrence of EHBO or duodenal perforation; however, intermittent vomiting and weight loss persisted despite supportive medications. Relevance and novel information: To the best of our knowledge, there is no detailed report on the application of choledochoduodenostomy combined with the Billroth II procedure in cats, as we used to treat the EHBO and duodenal perforation in the present case. As serum gastrin concentrations were elevated on the first day of hospitalisation, the CBD mass was diagnosed as a neuroendocrine carcinoma with gastrin-producing cell differentiation, which seemed to have caused not only EHBO but also duodenal perforation (Zollinger-Ellison syndrome). The cat survived for almost 100 days without any perioperative complications. However, this combined procedure might be considered as only a salvage option and not as a definitive treatment option in cats requiring simultaneous biliary and gastrointestinal reconstruction because postoperative supportive care could not improve the cat's condition or maintain its quality of life.

Rebound Acid Hypersecretion after Withdrawal of Long-Term Proton Pump Inhibitor (PPI) Treatment-Are PPIs Addictive?

Proton pump inhibitors (PPIs) are widely used in the long-term treatment of gastroesophageal reflux disease (GERD) and other upper gastrointestinal disorders, such as the healing of peptic ulcers and/or prophylactic treatment of peptic ulcers. PPIs are also widely used as symptomatic treatment in patients with functional dyspepsia. One of the adverse effects of the long-term use of PPI is rebound acid hypersecretion (RAHS), which can occur after the withdrawal of PPI therapy due to a compensatory increase in gastric acid production. Mechanisms of the RAHS have been well established. Studies have shown that pentagastrin-stimulated acid secretion after the discontinuation of PPIs increased significantly compared to that before treatment. In healthy volunteers treated with PPIs, the latter induced gastrointestinal symptoms in 40-50% of subjects after the discontinuation of PPI therapy but after stopping the placebo. It is important for practicing physicians to be aware and understand the underlying mechanisms and inform patients about potential RAHS before discontinuing PPIs in order to avoid continuing unnecessary PPI therapy. This is important because RAHS may lead patients to reuptake PPIs as symptoms are incorrectly thought to originate from the recurrence of underlying conditions, such as GERD. Mechanisms of RAHS have been well established; however, clinical implications and the risk factors for RAHS are not fully understood. Further research is needed to facilitate appropriate management of RAHS in the future.

Synthesis and Evaluation of Novel 68Ga-Labeled [D-Phe6,Leu13ψThz14]bombesin(6-14) Analogs for Cancer Imaging with Positron Emission Tomography.

Gastrin-releasing peptide receptor (GRPR) is overexpressed in various cancers and is a promising target for cancer diagnosis and therapy. However, the high pancreas uptake and/or metabolic instability observed for most reported GRPR-targeted radioligands might limit their clinical applications. Our group recently reported a GRPR-targeted antagonist tracer, [68Ga]Ga-TacsBOMB2 ([68Ga]Ga-DOTA-Pip-D-Phe6-Gln7-Trp8-Ala9-Val10-Gly11-His12-Leu13ψThz14-NH2), which showed a minimal pancreas uptake in a preclinical mouse model. In this study, we synthesized four derivatives with unnatural amino acid substitutions (Tle10-derived Ga-LW01158, NMe-His12-derived Ga-LW01160, α-Me-Trp8- and Tle10-derived Ga-LW01186, and Tle10- and N-Me-Gly11-derived Ga-LW02002) and evaluated their potential for detecting GRPR-expressing tumors with positron emission tomography (PET). The binding affinities (Ki(GRPR)) of Ga-LW01158, Ga-LW01160, Ga-LW01186, and Ga-LW02002 were 5.11 ± 0.47, 187 ± 17.8, 6.94 ± 0.95, and 11.0 ± 0.39 nM, respectively. [68Ga]Ga-LW01158, [68Ga]Ga-LW01186, and [68Ga]Ga-LW02002 enabled clear visualization of subcutaneously implanted human prostate cancer PC-3 tumor xenografts in mice in PET images. Ex vivo biodistribution studies showed that [68Ga]Ga-LW01158 had the highest tumor uptake (11.2 ± 0.65 %ID/g) and good tumor-to-background uptake ratios at 1 h post-injection. Comparable in vivo stabilities were observed for [68Ga]Ga-LW01158, [68Ga]Ga-LW01186, and [68Ga]Ga-LW02002 (76.5-80.7% remaining intact in mouse plasma at 15 min post-injection). In summary, the Tle10 substitution, either alone or combined with α-Me-Trp8 or NMe-Gly11 substitution, in Ga-TacsBOMB2 generates derivatives that retained good GRPR binding affinity and in vivo stability. With good tumor uptake and tumor-to-background imaging contrast, [68Ga]Ga-LW01158 is promising for detecting GRPR-expressing lesions with PET.

Gastrin Releasing Peptide Receptors-targeted PET Diagnostics and Radionuclide Therapy for Prostate Cancer Management: Preclinical and Clinical Developments of the Past 5 Years.

Each tumor has its own distinctive molecular identity. Treatment, therefore, should be tailored to this unique cancer phenotype. Theragnostics uses the same compound for targeted imaging and treatment, radiolabeled to an appropriate radionuclide, respectively. Gastrin-releasing peptide receptors (GRPRs) are overexpressed in prostate cancer, and radiolabeled GRPR antagonists have shown high diagnostic performance at staging and biochemical recurrence. Several GRPR-targeting theragnostic compounds have been developed preclinically. Their translation into clinics is underway with 4 clinical trials recruiting participants with GRPR-expressing tumors.

Progastrin: An Overview of Its Crucial Role in the Tumorigenesis of Gastrointestinal Cancers.

Defining predictive biomarkers for targeted therapies and optimizing anti-tumor immune response is a main challenge in ongoing investigations. Progastrin has been studied as a potential biomarker for detecting and diagnosing various malignancies, and its secretion has been associated with cell proliferation in the gastrointestinal tract that may promote tumorigenesis. Progastrin is a precursor molecule of gastrin, synthesized as pre-progastrin, converted to progastrin after cleavage, and transformed into amidated gastrin via biosynthetic intermediates. In cancer, progastrin does not maturate in gastrin and becomes a circulating and detectable protein (hPG80). The development of cancer is thought to be dependent on the progressive dysregulation of normal signaling pathways involved in cell proliferation, thus conferring a growth advantage to the cells. Understanding the interaction between progastrin and the immune system is essential for developing future cancer strategies. To that end, the present review will approach the interlink between gastrointestinal cancers and progastrin by exploring the underlying molecular steps involved in the initiation, evolution, and progression of gastrointestinal cancers. Finally, this review will focus on the clinical applications of progastrin and investigate its possible use as a diagnostic and prognostic tumor circulating biomarker for disease progression and treatment effectiveness, as well as its potential role as an innovative cancer target.

Prospective Randomized Controlled Clinical Trial of the Long-Term Effects of Omeprazole on Healthy Dogs.

The use of omeprazole as a preventive treatment for gastrointestinal ulcers in veterinary medicine has been questioned during previous years. The aim of the present study is to assess the long-term effect of omeprazole on cobalamin and serum gastrin levels in healthy dogs. Eighteen healthy dogs were included: 10 in the control group and 8 in the omeprazole group. Three samples were collected: before starting the treatment (T0), 30 days after the start of treatment (T1), and at 60 days (T2). The mean cobalamin value (ng/L) in the control group was 481.4 (±293.70) at T0, 481.4 (±170.21) at T1, and 513.2 (±174.50) at T2. In the omeprazole group, the values were 424.62 (±161.57) at T0, 454.5 (±160.96) at T1, and 414.87 (±127.90) at T2. No statistically significant changes were detected in cobalamin levels between the three-time period in both study groups. These results agree with previous findings in felines but contrast with human medicine studies. The median gastrin values (pg/mL) in the control group were 62.45 [30.17-218.75] at T0, 76.06 [30.67-199.87] at T1, and 63.02 [35.81-176.06] at T2. The median gastrin value in the omeprazole group was 67.59 [55.96-101.60] at T0, 191.77 [75.31-1901.77] at T1, and 128.16 [43.62-1066.46] at T2. Statistically significant differences were detected (p = 0.008), indicating an increase in gastrin levels after initiating treatment with omeprazole. In conclusion, the increased levels of gastrin observed in this population underscore the importance of conducting a comprehensive clinical assessment to identify potential gastrointestinal disorders, particularly in consideration of the usage of omeprazole as a preventive treatment.

Evaluation of Gastric pH and Gastrin Concentrations in Horses Subjected to General Inhalation Anesthesia in Dorsal Recumbency.

The prevalence of gastric disorders in high-performance horses, especially gastric ulceration, ranges from 50 to 90%. These pathological conditions have negative impacts on athletic performance and health. This study was designed to evaluate changes in gastric pH during a 24 h period and to compare gastrin concentrations at different time points in horses undergoing general inhalation anesthesia and dorsal recumbency. Twenty-two mixed-breed mares weighing 400 ± 50 kg and aged 8 ± 2 years were used. Of these, eight were fasted for 8 h and submitted to 90 min of general inhalation anesthesia in dorsal recumbency. Gastric juice samples were collected prior to anesthesia (T0), and then at 15 min intervals during anesthesia (T15-T90). After recovery from anesthesia (45 ± 1 min), samples were collected every hour for 24 h (T1 to T24) for gastric juice pH measurement. During this period, mares had free access to Bermuda grass hay and water and were fed a commercial concentrate twice (T4 and T16). In a second group (control), four non-anesthetized mares were submitted to 8 h of fasting followed by nasogastric intubation. Gastric juice samples were then collected at T0, T15, T30, T45, T60, T75, and T90. During this period, mares did not receive food or water. After 45 min, mares had free access to Bermuda grass hay and water, and gastric juice samples were collected every hour for four hours (T1 to T4). In a third group comprising ten non-fasted, non-anesthetized mares with free access to Bermuda grass hay and water, gastric juice samples were collected 30 min after concentrate intake (T0). In anesthetized mares, blood gastrin levels were measured prior to anesthesia (8 h fasting; baseline), during recovery from anesthesia, and 4 months after the anesthetic procedure, 90 min after the morning meal. Mean values of gastric juice pH remained acidic during general anesthesia. Mean pH values were within the physiological range (4.52 ± 1.69) and did not differ significantly between time points (T15-T90; p > 0.05). After recovery from anesthesia, mean gastric pH values increased and remained in the alkaline range throughout the 24 h period of evaluation. Significant differences were observed between T0 (4.88 ± 2.38), T5 (7.08 ± 0.89), T8 (7.43 ± 0.22), T9 (7.28 ± 0.36), T11 (7.26 ± 0.71), T13 (6.74 ± 0.90), and T17 (6.94 ± 1.04) (p < 0.05). The mean gastric juice pH ranged from weakly acidic to neutral or weakly alkaline in all groups, regardless of food and water intake (i.e., in the fasted, non-fasted, and fed states). Mean gastric pH measured in the control group did not differ from values measured during the 24 h post-anesthesia period or in the non-fasted group. Gastrin concentrations increased significantly during the post-anesthetic period compared to baseline (20.15 ± 7.65 pg/mL and 15.15 ± 3.82 pg/mL respectively; p < 0.05). General inhalation anesthesia and dorsal recumbency did not affect gastric juice pH, which remained acidic and within the physiological range. Gastric juice pH was weakly alkaline after recovery from anesthesia and in the fasted and fed states. Serum gastrin levels increased in response to general inhalation anesthesia in dorsal recumbency and were not influenced by fasting. Preventive pharmacological measures are not required in horses submitted to general anesthesia and dorsal recumbency.

Proton Pump Inhibitor Associated Multiple Gastric Hyperplastic Polyps With Uncontrollable Bleeding: A Case Report.

BACKGROUND/AIM: The long-term use of proton pump inhibitors (PPIs) has been reported to be strongly associated with the development of fundic gland polyps (FGPs). Conversely, a few cases of gastric hyperplastic polyps (GHPs) associated with PPI use have been reported. We experienced a case of PPI-associated multiple GHPs with uncontrollable bleeding. CASE REPORT: A 64 year old man with a history of rheumatoid arthritis presented to the hospital with complaints of vertigo and black stools. Blood tests revealed anemia and hypoproteinemia. Esophagogastroduodenoscopy (EGD) showed blood and black residue accumulated in the stomach. The source of the bleeding was multiple hyperplastic polyps. Bleeding could be stopped even with fasting, and total blood transfusions amounted to 28 units of RBCs were required in 18 days. After the cessation of PPI, EGD showed that the polyps had almost disappeared. Pathological diagnosis of resected polyp was hyperplastic polyp, which was characterized by capillary hyperplasia and edema. Gastrin receptors were over-expressed in the foveolar epithelium and not in the capillaries. Methotrexate (MTX)-induced portal hypertensive gastroenteropathy was revealed during follow-up. We consider that the effect of portal hypertension may have caused the capillary hyperplasia. CONCLUSION: Although PPI-related polyps are usually fundic gland polyps and do not cause life-threatening adverse events, we experienced PPI-related GHPs in which hemostasis was difficult to control.

Gastrin: a new branch of the gastropancreatic axis that can explain the effect of sleeve gastrectomy on glucose metabolism.

BACKGROUND: Among 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. METHODS: In 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. RESULTS: SG 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. CONCLUSION: Gastrin 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.