Search Results (1,307)

Background: Gastric cancer is a major global health concern. Although sex- and gender-based differences have been described, they are not yet well established, and the available evidence is often inconsistent. This systematic review aims to explore these differences in the incidence, clinicopathological characteristics, risk factors, treatment, and survival of gastric cancer, thereby contributing to healthcare equity. Methods: A systematic search was conducted in the main medical bibliographic databases (PubMed, Embase and Web of Science) in February 2026 following the PRISMA 2020 guidelines. Studies on gastric cancer were selected based on predefined inclusion and exclusion criteria. The results were synthesized qualitatively according to incidence, clinicopathological characteristics, risk factors, treatment outcomes, and survival. Due to the heterogeneity and predominantly observational design of the included studies, no meta-analysis or formal risk-of-bias assessment was conducted. Results: A total of 38 studies, involving more than 500,000 participants, were included. Most reported a higher incidence of gastric cancer in men, with a predominance of intestinal and well-differentiated tumors, while diffuse and poorly differentiated tumors were more common in women. Men showed higher rates of smoking, alcohol consumption, and postoperative complications. Overall survival tended to be higher in women, especially in early stages, although some studies described worse outcomes among young women. Conclusions: This review highlights relevant sex- and gender-related differences in gastric cancer and underscores the need to systematically incorporate these variables into future research to advance towards more personalized medicine. The available evidence was limited by the predominance of retrospective observational studies and heterogeneity across study designs and reported outcomes. Full article

This study evaluated the effects of adding zinc oxide nanoparticles (ZnNP), L-arginine (L-Arg), or a combination of both to the diets of growing rabbits to mitigate the physiological and productive consequences of heat stress. Two hundred and eighty 35-day-old New Zealand White rabbits were randomly assigned to four experimental treatments, with 70 rabbits per treatment and seven replicates (10 rabbits/replicate). The control group (Ctr) received the base diet without additives, while the diets of the other groups were fortified with arginine (L-Arg; 3 g/kg), zinc oxide nanoparticles (ZnNP; 40 mg/kg), or a combination of both (Arg-Zn). The results showed that the combined Arg-Zn significantly improved weight gain rate, feed conversion rate, carcass weight, and nutrient digestibility compared to the control group (p < 0.05). At the physiological level, we observed increased serum levels of total antioxidant capacity (T-AOC), glutathione peroxidase (GPx), superoxide dismutase (SOD), immunoglobulin G (IgG), immunoglobulin A (IgA), and triiodothyronine (T3), along with decreased levels of malondialdehyde (MDA), alanine aminotransferase (ALT), and aspartate aminotransferase (AST, p < 0.05) in Arg-Zn-fed rabbits. However, adding the Arg-Zn mixture contributed to a reduction in pathogenic bacteria counts and increased the volatile fatty acid (VFA) levels. At the molecular level, the gene expression of the inflammatory cytokines IL-6 and tumor necrosis factor alpha (TNF-α) decreased; however, the gene expression of claudins-1 (CLDN-1), cationic amino acid transporter-1 (CAT-1), mucin-2 (MUC-2), sodium-glucose co-transporter-1 (SGLT-1), and interferon gamma (IFNγ) increased (p < 0.05) in Arg-Zn-fed rabbits. These results suggest that dietary supplementation with ZnNP and L-Arg may serve as an effective nutritional strategy for improving growth performance, antioxidant status, immune function, and intestinal integrity in rabbits exposed to high ambient temperatures. Full article

Colorectal cancer (CRC) is intricately linked to gut microbiota dysbiosis and tryptophan (Trp) metabolic dysregulation. This study aimed to clarify the role and mechanisms of 20(S/R)-ginsenoside Rh1 in suppressing colorectal cancer through the regulation of gut microbiota and Trp metabolism. Azoxymethane/dextran sulfate sodium (AOM/DSS)was employed to induce a CRC mouse model, followed by treatment with 20(S/R)-ginsenoside Rh1 at 100 mg·kg⁻¹·day⁻¹ for 6 weeks. 20(S/R)-ginsenoside Rh1 significantly reduced the disease activity index (DAI) score, restored colon length, and decreased tumor count. 20(S/R)-Ginsenoside Rh1 ameliorated gut dysbiosis by increasing gut microbial diversity and elevating the prevalence of beneficial bacteria, including Lactobacillus, and stimulated the production of indole derivatives, including indole-3-propionic acid (IPA), indole-3-acetic acid (IAA), and indole-3-lactic acid (ILA) by enriching Trp -metabolizing bacteria such as Lactobacillus reuteri. These changes further activated the AhR/CYP1A1/IL-22 and PXR/TLR4 pathways, upregulated the expression of intestinal tight junction proteins, suppressed the secretion of proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IFN-γ, and elevated the levels of the anti-inflammatory cytokine IL-10. Furthermore, 20(S/R)-ginsenoside Rh1 reduces the serum kynurenine (Kyn)/Trp ratio, downregulates the expression of forkhead box P3 (FoxP3), a marker of regulatory T (Treg) cells, and increases the number of CD8⁺ T cells by inhibiting the expression of indoleamine 2,3-dioxygenase 1 (IDO1) in colonic tissue. In conclusion, 20(S/R)-ginsenoside Rh1 showed potential anti-CRC activity, with our study observing links between its action and gut microbiota structure regulation, Trp metabolism modulation, AhR/PXR-mediated intestinal barrier activation, and IDO1-related immune suppression reversal. Full article

Gastric adenomas are epithelial premalignant neoplasms which may appear similar on endoscopic examination; however, histologically, they are classified into four distinct subtypes according to the World Health Organization (WHO) Classification of Tumors of the Digestive System: intestinal adenoma, foveolar-type adenoma, oxyntic gland adenoma, and pyloric gland adenoma. Each subtype has characteristic histologic features that are essential for accurate diagnosis, although distinction can be challenging due to overlapping morphologic patterns. Moreover, these entities differ in their potential for malignant transformation and in their associations with hereditary or syndromic conditions. The objective of this review is to provide a practical guide for the histopathologic diagnosis of gastric adenomas, summarize the evidence regarding their risk of associated malignancy or malignant transformation, and review current recommendations for clinical follow-up and management. Given that various lesions may present endoscopically as gastric polyps, this manuscript also reviews both epithelial and non-epithelial mimickers of gastric adenomas. Full article

Obesity is a major risk factor for colorectal cancer (CRC) and is increasingly recognized as a contributor to cancer-related cognitive impairment; however, the mechanistic pathways linking metabolic dysfunction, tumor progression, and brain dysfunction remain incompletely defined. Emerging evidence indicates that obesity-induced gut microbial dysbiosis and intestinal barrier disruption may serve as a biologically plausible mechanism connecting these processes via the gut–brain axis although direct clinical causality remains to be firmly established. In obesity, alterations in gut microbiota composition characterized by depletion of barrier-protective taxa and enrichment of pro-inflammatory and genotoxic pathobionts compromise epithelial tight-junction integrity and promote metabolic endotoxemia. The translocation of microbial products, including lipopolysaccharide, sustains chronic systemic inflammation, accelerates CRC progression, and remodels the tumor microenvironment. Notably, these peripheral inflammatory signals extend beyond the intestine and tumor, disrupting blood–brain barrier integrity, activating microglia and astrocytes, and impairing synaptic plasticity within hippocampal and frontal networks. Clinically, these processes manifest as cancer-related cognitive impairment (CRCI), with predominant deficits in attention, processing speed, and working memory, which are often detectable around the time of diagnosis and independent of chemotherapy exposure. This review synthesizes in vivo, in vitro, and human evidence into a proposed theoretical “two-barrier failure” model of obesity-associated CRC and cognitive dysfunction. In addition to mechanistic synthesis, we discuss barrier-centered therapeutic strategies, including targeted probiotics, postbiotics, SCFA supplementation, obesity management through dietary and weight-loss interventions, and potential pharmacological approaches to epithelial and neurovascular barrier protection. We also outline testable clinical trial designs for evaluating these interventions in obesity-associated CRC. Full article

Radiation-induced intestinal injury (RIII) is a common complication of tumor radiotherapy, significantly impacting patients’ quality of life and posing challenges for developing effective medical countermeasures. This study investigated the reparative effects of the traditional Chinese medicine Pyrrosia petiolosa (Christ) Ching on radiation damage through in vivo and in vitro models. By integrating gut microbiota and untargeted metabolomics analyses, it elucidated the multidimensional mechanisms through which P. petiolosa regulates the microbiome as well as metabolic homeostasis. In vitro experiments demonstrated that P. petiolosa effectively suppressed radiation-induced inflammatory factors (IL-6, TNF-α, and IL-1β) and alleviated radiation-induced oxidative stress (MDA, GSH, and SOD). In vivo models further confirmed that P. petiolosa significantly alleviated radiation-induced intestinal inflammation and leukopenia, while protecting the structural and functional integrity of mouse small intestinal crypt villi. Mechanistic studies revealed P. petiolosa reshaped the gut microbiota by promoting enrichment of beneficial bacteria such as Bacteroides, concurrently restoring the homeostasis of key metabolic pathways, including glutathione, glycerophospholipids, and the tricarboxylic acid cycle. Analysis of the microbiome–metabolome interaction network revealed that treatment with P. petiolosa altered the correlation patterns between gut microbiota and fecal metabolites, including potentially beneficial bacteria and metabolites associated with inflammatory and oxidative stress responses. These findings suggest that microbiome–metabolome remodeling may contribute to the protective effects of P. petiolosa against radiation-induced intestinal damage. Overall, this study provides preliminary evidence that P. petiolosa may alleviate acute radiation-induced intestinal damage through anti-inflammatory and antioxidant effects accompanied by changes in gut microbiota and metabolic homeostasis, while identifying candidate targets for future functional validation. Full article

Plant polysaccharides, such as Astragalus polysaccharide (APS) and Glycyrrhiza polysaccharide (GPS), have potential as functional feed additives. This study investigated the effects of dietary APS and GPS on growth-related traits, serum biochemical and immune indices, antioxidant capacity, intestinal health, and microbial diversity in early-weaned squabs. A total of 192 15-day-old Silver King squabs were randomly divided into four groups: the control group (CK), the 800 mg/kg APS group, the 450 mg/kg GPS group, and the APS + GPS combination group (AG group), with 12 replicates per group and 4 squabs per replicate. The experiment lasted for 28 days. The results showed that final body weight tended to be higher in the APS, GPS, and AG groups, whereas breast width and breast depth were significantly increased in the GPS and AG groups (p < 0.01). The GPS and AG groups exhibited increased serum immunoglobulin A (IgA; p < 0.05) and immunoglobulin G (IgG; p < 0.01) levels, as well as reduced levels of pro-inflammatory cytokines, including interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α; p < 0.01). All treatments increased serum total antioxidant capacity (T-AOC; p < 0.01), while the AG group reduced malondialdehyde (MDA) levels and increased total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) activities (p < 0.01). Duodenal and jejunal T-AOC increased in all treatment groups (p < 0.01), and APS and AG increased ileal T-AOC (p < 0.01). However, intestinal MDA concentrations increased in several segments, indicating a complex and segment-specific oxidative response. The AG group also increased jejunal lipase activities (p < 0.05). Microbiome analysis suggested that Helicobacter was correlated with immune-related indicators, while Lactobacillus was identified as an important core genus in the microbial co-occurrence network. These findings suggest that dietary APS and GPS may regulate immune function, oxidative–antioxidant responses, intestinal function, and gut microbial composition, thereby supporting physiological adaptation in early-weaned squabs. Full article

The reduction of antibiotic use in livestock production necessitates the development of reliable in vitro models for evaluating alternative immunomodulatory compounds. In this study, porcine hepatocyte–non-parenchymal (NP) cell co-cultures and small intestinal explants exposed to pathogen-associated molecular patterns (PAMPs), including lipopolysaccharide (LPS), lipoteichoic acid (LTA), flagellin and polyinosinic–polycytidylic acid (poly I:C), were established as inflammatory models. Hepatic co-cultures exhibited pronounced inflammatory responses, with LPS and LTA increasing hepatocellular interleukin (IL)-4, IL-6, IL-8 and tumor necrosis factor (TNF)-α release, alongside elevated extracellular lactate dehydrogenase activity and maintained metabolic activity, indicating membrane perturbation without marked cytotoxicity. Poly I:C was found to be cytotoxic, accompanied by an altered cytokine profile. All PAMPs enhanced reactive oxygen species production without remarkable lipid peroxidation in most cases. In contrast, intestinal explants showed high resilience with unchanged viability and limited cytokine responses. Only IL-6 and IL-8 were detectable, with LPS elevating IL-8, while poly I:C and flagellin increased IL-6 levels. These findings demonstrate marked tissue-specific differences in inflammatory responsiveness. The hepatic co-culture model provides a sensitive system for studying robust inflammatory reactions, whereas intestinal explants are suitable for investigating moderate, gut-specific immune responses. In conclusion, these complementary models offer valuable tools for evaluating antibiotic alternatives in swine. Full article

We evaluated the effects of different levels of DON (LD 441 and HD 1223 μg DON/kg in diet) on the growth performance, immunity, reproductive hormones, and intestinal health of immature gilts. No significant differences were observed in average daily gain, average daily feed intake, or feed to gain ratio between the LD group and the HD group (p > 0.05). The red blood cell count and hematocrit were higher in the LD group compared with the HD group on d 21 (p < 0.05). The gamma-glutamyl transferase activity in the LD group on d 1, 21, 28, 35, and 42 was higher (p < 0.05) compared with the HD group. The aspartate aminotransferase, total antioxidant capacity, and lactic dehydrogenase levels on d 35 were higher in the LD group than those in the HD group (p < 0.05). On d 35, the levels of interleukin 1β, interleukin-4, interleukin-10, tumor necrosis factor-α, and interferon-γ in LD were higher than those in the HD group (p < 0.05). The levels of immunoglobulin A, immunoglobulin M, immunoglobulin G, and complement 4 on d 35 were higher in the LD group compared with those in the HD group (p < 0.05). The gonadotrophin-releasing hormone, luteotrophic hormone, follicle-stimulating hormone, or estradiol did not differ between LD and HD groups throughout the experiment (p > 0.05). For fecal microbiota, Streptococcus in the HD group was reduced compared with the LD group (p < 0.05). In summary, feeding diets contaminated with 1223 μg DON/kg exerted adverse effects on serum profiles of gilts but did not affect their growth performance or reproductive hormones in the present study. Full article

Background/Objectives: Natural macromolecule-based drug delivery carriers have gained extensive attention for biomedical applications. This study aimed to construct an efficient oral delivery system for the widely used antitumor drug docetaxel (DTX) by utilizing natural nanoparticles derived from Ganoderma (LZ-Nnps). Methods: LZ-Nnps loaded with DTX (LZ-Nnps-DTX) were fabricated via an optimized heat-induced self-assembly approach and characterized for morphology, particle size, zeta potential, stability, drug loading, encapsulation efficiency, and molecular interactions with DTX. Intestinal absorption, pharmacokinetics, and tissue distribution were respectively assessed, while antitumor efficacy, macrophage internalization mechanisms, and immunomodulatory activation were further investigated. Results: The optimized formulation showed a particle size of 361.3 ± 5.3 nm, zeta potential of −39.55 ± 1.31 mV, drug loading of 1.51 ± 0.08%, and near-complete encapsulation efficiency (99.97 ± 0.02%), with favorable stability in gastrointestinal fluids. Hydrogen bonding and hydrophobic interactions effectively kept DTX in a stable amorphous state. LZ-Nnps-DTX markedly improved DTX aqueous solubility, dissolution, and intestinal absorption. In vivo assays showed oral LZ-Nnps-DTX achieved 34-fold higher C_max and 7.8-fold larger plasma AUC_0-t than free DTX, and mainly accumulated in the liver and lung. The nanoparticles entered Caco-2 cells via macropinocytosis and mainly accumulated in the liver. LZ-Nnps-DTX exerted strong cytotoxicity against HepG2, A549, and HCT116 cells, was internalized by RAW264.7 macrophages through caveolae-mediated endocytosis and phagocytosis, and stimulated TNF-α and NO production to suppress tumor growth. Conclusions: These findings demonstrate that LZ-Nnps-DTX effectively enhances oral bioavailability, exerts potent antitumor effects, and activates macrophage-mediated immunity, supporting its promise as an oral DTX delivery system. Full article

Fever of unknown origin (FUO) remains a persistent diagnostic challenge in clinical medicine despite significant advances in laboratory testing and imaging techniques. The definition of FUO has evolved since the original criteria proposed in 1961 and currently refers to persistent fever exceeding approximately 38.2–38.3 °C without a definitive diagnosis after an adequate diagnostic evaluation. Gastrointestinal diseases represent an important but often underrecognized group of conditions associated with FUO. The aim of this review is to synthesize current evidence on the gastroenterological causes of FUO, with particular emphasis on pathophysiological mechanisms, diagnostic strategies, and therapeutic management. The analysis highlights the role of inflammatory, infectious, and neoplastic gastrointestinal disorders in the etiology of prolonged fever. Key mechanisms involve systemic inflammatory responses mediated by cytokines such as interleukin-1, interleukin-6, and tumor necrosis factor, as well as immune processes associated with the gut-associated lymphoid tissue (GALT) and interactions between intestinal microbiota and host immunity. Among the most frequently reported gastroenterological causes of FUO are inflammatory bowel diseases, intra-abdominal infections and abscesses, hepatobiliary disorders, pancreatitis, and gastrointestinal malignancies. Diagnostic evaluation requires a stepwise approach integrating laboratory testing, microbiological studies, imaging modalities, and endoscopic procedures, with advanced techniques such as computed tomography and fluorodeoxyglucose positron emission tomography improving detection of occult inflammatory or neoplastic processes. Therapeutic management is primarily guided by the identification of the underlying cause, while empirical treatment should be carefully considered to avoid masking diagnostic clues. A better understanding of the gastrointestinal mechanisms underlying FUO and the development of more efficient diagnostic algorithms may improve clinical outcomes and reduce the number of undiagnosed cases. Full article

Dietary supplementation with sodium butyrate or bovine colostrum modulates the gut–liver axis in weaned piglets. Sodium butyrate exerted beneficial effects on liver function and lipid parameters, while also inhibiting inflammation and promoting the maintenance of the intestinal barrier. A particularly pronounced effect was observed with bovine colostrum supplementation, which significantly increased average daily weight gain (p < 0.001). In addition, piglets receiving colostrum consumed more feed and exhibited a significantly lower feed conversion ratio (p = 0.002). Metabolic changes induced by sodium butyrate and bovine colostrum supplementation resulted in alterations in the hepatic fatty acid profile, including a reduction in n-3 polyunsaturated fatty acids and a decrease in collagen fiber content in the liver (p = 0.03). The nutritional interventions did not significantly affect microbial diversity indices; however, marked changes in volatile fatty acid concentrations were observed in the large intestine. These changes indicate enhanced microbial fermentation and increased nutrient absorption in the experimental groups. Significant increases were detected in acetic acid (p = 0.003) as well as in butyric, isobutyric, and valeric acids (p = 0.014, p = 0.024, and p = 0.038, respectively). Supplementation with sodium butyrate and dried bovine colostrum also led to increased hepatic concentrations of macro- and microelements in piglets from the experimental groups. Genomic analyses suggest that sodium butyrate modulates hepatic metabolic and inflammatory pathways by downregulating PPAR (peroxisome proliferator-activated receptor) and SIRT3 (sirtuin 3) expression and reducing TNF (tumor necrosis factor) gene expression, highlighting its potential role in regulating lipid metabolism, oxidative stress, and inflammation in a porcine model. Overall, the results indicate that both supplements may contribute to the modulation of gut microbial activity and liver metabolism in weaned piglets. Full article

Under intensive farming conditions, a decline in feed intake after weaning in suckling piglets often results in reduced body weight or diarrhea. We hypothesized that a sow–piglet co-feeding strategy during the suckling period—in which piglets participate in the sow’s feeding process and consume both lactating sow feed and creep feed—could alleviate certain aspects of weaning stress. To test this hypothesis, 102 newborn piglets (Large White × Duroc × Min Pig) were selected and divided into a co-feeding group (CF) and a non-co-feeding group (NCF), based on whether they had access to the sow’s feed during lactation. The study investigated the effects of the two feeding strategies on piglet growth performance, diarrhea incidence, behavior, and post-weaning immune status, intestinal morphology, and antioxidant capacity. The results showed that the CF group had significantly higher body weight at the end of the nursery period (p < 0.05) and a significantly lower post-weaning observed fecal staining rate (p < 0.05). At 16–17 days post-weaning, piglets in the CF group exhibited a significant increase in feeding behavior (p < 0.05). Compared with the NCF group, the CF group showed highly significant reductions in serum levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ) (p < 0.01), as well as significantly increased intestinal superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities (p < 0.05) and significantly reduced malondialdehyde (MDA) content (p < 0.05). In terms of intestinal morphology, the CF group had a highly significant increase in the villus-to-crypt ratio in the jejunum (p < 0.01) and a highly significant reduction in crypt depth (p < 0.05), while villus length did not differ significantly between groups (p > 0.05). Overall, in the present study, sow–piglet co-feeding during the suckling period effectively alleviated weaning stress and reduced the incidence of diarrhea. These beneficial effects appear to be associated with reduced inflammatory responses, enhanced antioxidant capacity, and improved intestinal morphology. It should be noted that the relatively late weaning age used in this study likely facilitated the piglets’ ability to efficiently utilize solid feed and derive benefits from the co-feeding strategy. Therefore, caution should be exercised when extrapolating these findings to earlier weaning ages, at which the digestive tract is less mature. Full article

Background/Objectives: Sleep deprivation (SD) induces the accumulation of reactive oxygen species (ROS) in the intestine, causing inflammation in the intestine, thereby damaging the intestinal epithelial barrier function. As a traditional Chinese medicine, Dendrobium huoshanense (DHS) modulates intestinal flora, maintains the intestinal mucosal barrier, and promotes gastrointestinal motility and digestive secretion. However, the role and mechanism of DHS in improving SD-induced intestinal injury have not been fully studied. Methods: The SD model was established by subjecting rats to complete SD using a specialised SD instrument. Hematoxylin and eosin (HE) staining was performed to evaluate pathological injury in ileal tissues. Enzyme-linked immunosorbent assay (ELISA) and biochemical methods were used to quantify the main inflammatory cytokines, oxidative stress markers, and hypothalamic–pituitary–adrenal (HPA) axis activity. The expression levels of E-cadherin and Occludin proteins in the ileum tissue were analyzed by Western blotting. Additionally, the pH value of ileal mucus, unit secretion, water content, and dry matter weight were measured. Differential metabolites in rat ileum mucus were profiled using ultra-high-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). Results: DHS alleviated the pathological injury of the ileum induced by SD. DHS reduced the levels of serotonin (5-HT), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), while increasing interleukin-10 (IL-10) levels, thereby attenuating systemic inflammatory responses. Furthermore, DHS decreased malondialdehyde (MDA) content and elevated glutathione (GSH) and superoxide dismutase (SOD) levels in ileal tissues. DHS also upregulated the protein expression of E-cadherin and Occludin in intestinal tissues. In addition, DHS decreased the pH of ileal mucus, promoted intestinal mucus secretion, and increased dry matter content, facilitating the restoration of the mucus barrier. DHS may alleviate SD-induced ileal injury by modulating steroid hormone biosynthesis. DHS decreased the levels of adrenocorticotropic hormone (ACTH), cortisol (CORT), and corticotropin-releasing hormone (CRH), indicating that DHS suppresses the abnormal activation of the hypothalamic–pituitary–adrenal (HPA) axis. Conclusions: In this study, a comprehensive multi-index evaluation showed that DHS could significantly improve the ileal injury caused by SD in rats. The mechanism involved regulating the balance of serum neurotransmitters and inflammatory factors, reducing oxidative stress in tissues, and improving the physicochemical properties of intestinal mucus. Metabolomic analysis further revealed that these protective effects may be mediated via the regulation of steroid hormone biosynthesis pathways and are associated with the inhibition of abnormal HPA axis activation. Full article

Neuroendocrine tumors (NETs) constitute a heterogeneous and predominantly malignant group of neuroendocrine neoplasms that arise from endocrine cells dispersed throughout the body. Their clinical presentation, biological behavior, prognosis, and therapeutic management vary considerably depending on the primary tumor location and hormonal activity. Despite substantial progress in understanding the biology of NETs, identifying reliable molecular biomarkers for diagnosis, prognosis, and prediction of treatment response remains a major challenge. Increasing attention has therefore been devoted to the molecular characterization of NETs, with particular focus on recurrent genetic alterations that may contribute to tumor initiation and progression. In this review, we summarize current knowledge and recent findings referring to certain genes involved in the tumorigenesis of pancreatic and intestinal neuroendocrine tumors. We chose the genes based on data from the COSMIC (Catalogue of Somatic Mutations in Cancer) database, which compiles somatic mutations identified across numerous human cancers. We outline the biological functions of these changes and discuss their potential prognostic and predictive role as molecular markers. We also discuss their clinical relevance in both sporadic and familial forms of NETs, alongside their implications for future research and personalized management strategies. Full article