Search Results (3,513)

Helicobacter pylori is a major causative agent of chronic gastritis, gastric and duodenal ulcers, gastric cancer, and mucosa-associated lymphoid tissue lymphoma. Transmission to humans may occur through the consumption of contaminated food. This study investigated the prevalence of H. pylori in fresh raw meat from different animal sources and assessed the efficiency of selective media for its recovery in Dhamar Governorate, Yemen. A total of 380 meat samples, including beef (n = 125), sheep (n = 135), and goat (n = 120), were collected from slaughterhouses (n = 127), retail markets (n = 124), and butcher shops (n = 129). Three selective media: Modified Campy-blood Agar (MCA), Belo Horizonte Agar (BHA), and Egg Yolk Emulsion (EYE) medium were evaluated for comparative recovery from each meat source. Overall, H. pylori was detected in 47 samples (12.4%), with a relatively high prevalence in beef (15.2%), followed by goat (12.5%) and sheep (9.6%). By source, butcher shop samples comparatively showed the highest prevalence (15.5%), especially in beef (19.1%), goat (14.3%), and sheep (13.3%), as compared to the slaughterhouses (11.8%) and retail markets (9.7%). Differences among meat types and sources were not statistically significant (p = 0.394 and p = 0.362). Overall, selective media comparison revealed that MCA showed a relatively high recovery rate (6.6%), followed by EYE (3.4%) and BHA (2.4%). A seasonal trend was observed, with peak prevalence in April (20%). These findings suggest that raw meat may represent a potential source of exposure to H. pylori, although its role in transmission to humans remains to be fully clarified. Regular monitoring, improved hygiene practices, and stricter control of environmental contamination are recommended to reduce associated public health risks. Full article

HER2 testing represents a cornerstone of the treatment algorithm in advanced gastric and gastroesophageal junction adenocarcinoma (GC), yet its evaluation remains complex due to tumor heterogeneity and methodological variability. Unlike breast cancer, HER2 expression in GC is often incomplete and heterogeneous, resulting in discordant results between biopsies, resections, and metastatic sites. Both spatial and temporal HER2 heterogeneity are key determinants of testing reproducibility, diagnostic accuracy, and treatment selection and response in GC. Optimizing sampling through multiple, well-targeted biopsies, standardizing IHC/ISH protocols, and reassessing HER2 status at progression may be crucial steps to ensure diagnostic accuracy. The recognition of HER2-low disease introduces a new pathological and clinical subgroup of GC with potential sensitivity to antibody–drug conjugates, while emerging techniques such as circulating tumor DNA analysis are increasingly applied to detect HER2 amplification and co-existing genetic alterations. Integrating molecular tools and standardized reassessment strategies can enhance HER2 testing reliability and enable more precise treatment strategies, with the potential to minimize HER2 resistance mechanisms. This review provides a practice-oriented guide on the interpretation and optimization of HER2 testing in gastric cancer, while providing insight into the underlying molecular mechanisms driving heterogeneity and resistance. Full article

Gastrointestinal (GI) cancers constitute an umbrella term for a wide variety of malignancies that are located in the digestive tract (esophageal, gastric, small and large intestine, anus, liver, gallbladder, and pancreas), with 25% of total cancers and 35% of cancer-related deaths being attributed to them. An alarming trend of rising GI malignancy diagnoses, especially in younger age groups, underscores the need for discoveries in liquid-based biomarkers that facilitate both early detection and optimal disease management. Extracellular vesicles (EVs) not only constitute promising nano-sized biomarkers, but also, via bioengineering, have shown a great therapeutic potential, with artificial intelligence (AI) revolutionizing their research via the selection of the best biomarkers from omics, the recognition of pathophysiological patterns, and facilitating a faster drug-development via AI-driven EV engineering, drug delivery modeling, and target identification. In this review, we will provide a clear insight into the implementation of AI methodologies in EV-based biomarker discovery and therapeutics for pancreatic and hepatobiliary cancer. Full article

Resistance to 5-fluorouracil (5-FU), a cornerstone chemotherapy for gastric cancer (GC), is a major clinical obstacle, often driven by the upregulation of its target enzyme, thymidylate synthase (TS). In this study, we investigated the potential of the pan-histone deacetylase inhibitor (HDACi) panobinostat to synergize with 5-FU. In GC cell lines, panobinostat treatment alone suppressed cell viability, clonogenicity, and migration, and this was associated with the induction of G1-phase cell cycle arrest and mitochondria-mediated apoptosis. Crucially, Panobinostat acted synergistically with 5-FU, leading to enhanced cytotoxicity. Mechanistically, 5-FU treatment alone induced a compensatory upregulation of TS protein, a known resistance mechanism. Panobinostat not only suppressed basal TS expression but, more importantly, abrogated this 5-FU-induced upregulation. Furthermore, panobinostat downregulated a network of oncogenes and cell cycle regulators, including c-Myc and key cyclins. These findings indicate that panobinostat can enhance 5-FU cytotoxicity by targeting TS expression and reprogramming oncogenic transcriptional networks, supporting its potential as a complementary strategy for overcoming fluoropyrimidine resistance in GC therapy. Full article

Background: Xanthohumol (XN), a prenylated chalcone flavonoid derived from hops (Humulus lupulus), is increasingly recognized as a highly pleiotropic natural compound. Objective: We aimed to structure XN’s mechanistic hierarchy with emerging translational relevance across disease areas. Methods: We performed a comprehensive and integrative literature review of XN for its biological and translational effects across cancer, metabolic, neurological, cardiovascular, hepatic, renal, and dermatological disorders. Results: Mechanistically, XN exerts diverse bioactivities by inhibiting major pro-oncogenic and pro-inflammatory pathways, such as NF-κB, PI3K/Akt/mTOR, STAT3, HIF-1α, and selective MAPK cascades, while activating cytoprotective signaling, such as the Nrf2/ARE and AMPK pathways. Through these coordinated actions, XN modulates redox homeostasis, mitochondrial integrity, apoptosis, autophagy, ferroptosis, and inflammatory responses. In oncology, XN demonstrates broad-spectrum anticancer activity in preclinical models by inhibiting proliferation; inducing cell cycle arrest and apoptosis; suppressing epithelial–mesenchymal transition, angiogenesis, and metastasis; and restoring chemosensitivity in resistant cancers, including breast, lung, gastric, liver, and head-and-neck carcinomas. Beyond cancer, XN exhibits multi-organ protective bioactivities through antioxidative, antimicrobial, antiviral, and anti-inflammatory activities; inhibition of ferroptosis and excitotoxicity; and preservation of mitochondrial integrity. It shows beneficial effects in preclinical models of Parkinson’s disease, Alzheimer’s disease, hepatic steatosis and fibrosis, renal ischemia–reperfusion injury, cardiovascular dysfunction, skin photoaging, and atopic dermatitis. Human subject studies demonstrate that XN is safe and well tolerated, with observed reductions in oxidative DNA damage and inflammatory cytokine release. Recent advances in micellar formulations have improved XN’s systemic bioavailability and thus its translational feasibility. Conclusions: In summary, XN is a safe, multifunctional natural compound with strong potential for modulating disease-relevant biological pathways associated with cancer, neurodegenerative diseases, metabolic disorders, and inflammatory skin conditions. Continued efforts to enhance its bioavailability and conduct rigorous clinical trials are essential to fully establish its clinical relevance in patient populations. Full article

Combination chemotherapy regimens are commonly employed to treat advanced gastric adenocarcinoma (GAC), yet median survival remains less than one year. Nab-paclitaxel has demonstrated significant antitumor activity in preclinical GAC models. Overexpression of growth factors and their receptors is prevalent in GAC and contributes to its pathophysiology, with aberrant activation of the HGF/c-Met pathway reported in up to 50% of patients. We hypothesized that merestinib, a small-molecule inhibitor of c-Met, Axl, and DDR1/2, would enhance the therapeutic response to nab-paclitaxel in GAC. In high c-Met–expressing MKN-45 peritoneal dissemination xenografts in female NOD/SCID mouse models, animal survival was 17 days in controls, 37 days with nab-paclitaxel (118% increase), 24 days with merestinib (41% increase), and 43 days with the combination (153% increase), demonstrating significantly enhanced survival compared with either monotherapy. In MKN-45 subcutaneous xenografts, tumor volumes in the control, nab-paclitaxel, merestinib, and combination groups were 503 mm³, 115 mm³, 91 mm³, and −9.7 mm³ (indicating tumor regression), respectively. In low c-Met-expressing SNU-1 xenografts, tumor volumes were 219 mm³, 105 mm³, 131 mm³, and 57 mm³, respectively. IHC analysis of tumor cell proliferation and microvessel density in MKN-45 tumors supported these findings. In vitro, nab-paclitaxel and merestinib each reduced cell proliferation in GAC-associated cells, with enhanced inhibitory effects when used in combination. In MKN-45 cells, merestinib increased the expression of pro-apoptotic proteins and decreased phosphorylation of c-Met, EGFR, IGF-1R, ERK, and AKT. These results indicate that combining merestinib with nab-paclitaxel may represent a promising therapeutic strategy to improve outcomes for patients with GAC. Full article

Background/Objectives: Recurrence after curative gastrectomy for gastric cancer remains common, and treatment options are limited. In selected patients with isolated locoregional relapse, salvage re-gastrectomy may provide durable disease control. This study compared outcomes of salvage re-gastrectomy and chemotherapy for isolated locoregional recurrence. Methods: We reviewed 500 consecutive gastrectomies performed between 2010 and 2024. In total, 66 patients (12.8%) developed isolated locoregional recurrence after previous R0 resection: 25 underwent salvage re-gastrectomy, and 41 received chemotherapy. Propensity-score matching (intended 1:2) was used to balance clinical and pathologic variables, yielding 42 patients (17 surgery, 25 chemotherapy). The primary endpoint was overall survival (OS) from recurrence diagnosis; secondary endpoints included perioperative outcomes and patterns of treatment failure. Results: There were no 30-, 60-, or 90-day deaths after salvage re-gastrectomy. Overall mortality was lower in the surgical group (41.2%) compared with chemotherapy (80.0%; p = 0.010). Salvage re-gastrectomy was independently associated with better OS (HR 0.15, 95% CI 0.02–0.87, and p = 0.035). A longer disease-free interval correlated strongly with survival (ρ = 0.80 and p < 0.001). Surgical patients experienced fewer local (0% vs. 52%) and peritoneal (0% vs. 20%) recurrences. Conclusions: For carefully selected patients with late, isolated locoregional recurrence, salvage re-gastrectomy is feasible and associated with longer survival and improved local control compared with chemotherapy alone. Larger prospective studies are warranted. Full article

Secretory Leukocyte Protease Inhibitor (SLPI) is a conserved serine protease inhibitor expressed on mucosal surfaces, which has multiple functions including anti-protease, anti-microbial and anti-inflammatory properties. SLPI plays critical roles in tissue homeostasis and pathology. Through its anti-protease ability, SLPI safeguards tissues from excessive damage caused by proteolytic enzymes released during inflammation and contributes to extracellular matrix remodeling, thereby influencing the cellular and tumor microenvironment. Furthermore, SLPI expression is implicated in shaping the immune landscape that facilitates tumor progression, and in driving epithelial–mesenchymal transition (EMT). Consequently, it is not surprising that SLPI plays a complex and context-dependent role across various malignancies. It is overexpressed in most cancers such as colorectal, gastric, pancreatic, and breast carcinomas, and this overexpression often correlates with a more advanced and aggressive disease. Conversely, its levels are reduced in head and neck squamous cell carcinoma and hepatocellular carcinoma, where elevated expression may be associated with a more favorable prognosis. This diverse behavior underscores that SLPI function in cancer is tissue-specific and dependent on the functional or pathological state. In prostate cancer, SLPI expression exhibits a bimodal behavior: levels are reduced in the early stages of the disease compared to normal tissues but become significantly upregulated in more advanced and aggressive stages of disease, with significantly higher levels observed in patients with castration-resistant prostate cancer. Elevated SLPI levels in prostate cancer correlate with a reduced prostate-specific antigen (PSA) progression-free survival. In this review, we outline the current evidence regarding the multifaceted functions of SLPI and its expanding role in cancer, focusing primarily on the recently described molecular mechanisms and clinical significance of SLPI in prostate carcinoma. Full article

Gastric cancer (GC), often diagnosed at advanced or metastatic stages, remains a significant clinical challenge requiring novel biomarkers for early detection, risk stratification, and effective, personalized treatment optimization. Emerging evidence underscores a strong association between gut microbiome dysbiosis and GC initiation, progression, and therapeutic outcomes. This review explores the potential of the advanced/metastatic gastric microbiome as a source of diagnostic and targetable biomarkers and its role in modulating responses to immunotherapy. Although Helicobacter pylori (H. pylori) is the most significant risk factor for GC, several other gastrointestinal taxa—including Fusobacterium nucleatum (F. nucleatum)—have been implicated in advanced GC (AGC). At its inception, microbial dysbiosis contributes to chronic inflammation and immune evasion, thereby influencing tumor behavior and treatment efficacy. Integrating microbiome-based biomarkers into risk stratification, GC staging, and targetable treatment frameworks may enhance early detection, inform immunotherapy strategies, and improve patient-specific treatment responses. Bifidobacterium and Lactobacillus rhamnosus GG have the potential to change the immunotherapy framework with their direct influence on dendritic cell (DC) and cytotoxic T cell (CTL) activity. However, clinical translation is impeded by methodological heterogeneity, causality limitations, and a lack of clinical trials. Nonetheless, the integration of microbiome profiling and the development of therapeutic microbiome modulation strategies, such as personalized probiotics regimens and fecal microbiota transplantation, hold substantial potential for improving clinical outcomes and reducing treatment-related toxicity in GC management. Full article

Endocervical adenocarcinoma is now classified within an etiologic framework based on the presence or absence of high-risk human papillomavirus (HPV) infection. Gastric-type endocervical adenocarcinoma (GAS) is the prototypical HPV-independent subtype, accounting for up to 25% of endocervical adenocarcinomas and showing a particularly high frequency in East Asia. GAS is typically diagnosed at a more advanced stage than usual-type HPV-associated endocervical adenocarcinoma (UEA); exhibits deep stromal and parametrial invasion, lymphovascular space invasion, and a strong propensity for ovarian and peritoneal metastasis; and is associated with markedly worse survival, even in stage I disease. Radiological evaluation is challenging because of diffuse infiltrative growth, prominent mucin production, and frequent underestimation of extra-cervical spread. Histologically, GAS shows gastric-type (pyloric) differentiation, ranging from minimal deviation adenocarcinoma to poorly differentiated forms, and often overlaps with precursor lesions such as atypical lobular endocervical glandular hyperplasia and gastric-type adenocarcinoma in situ. Immunophenotypically, GAS is typically p16-negative, ER/PR-negative, and frequently exhibits mutant-type p53 and expression of gastric markers including MUC6, HIK1083, and claudin 18.2. Recent next-generation sequencing and multi-omics studies have revealed recurrent alterations in TP53, CDKN2A, STK11, KRAS, ARID1A, KMT2D, and homologous recombination-related genes, together with the activation of PI3K/AKT, WNT/β-catenin, TGF-β, and EMT pathways and characteristic metabolic reprogramming. GAS is highly resistant to conventional chemotherapy and radiotherapy, and its current management follows guidelines for squamous and usual-type adenocarcinoma. Emerging data support precision-medicine approaches targeting HER2/HER3, PD-1/PD-L1, and claudin 18.2, and suggest a role for PARP inhibition and other genotype-directed therapies in selected subsets. Given its aggressive biology and rising relative incidence in the HPV-vaccination era, GAS represents a critical unmet need in gynecologic oncology. Future progress hinges on developing reliable diagnostic biomarkers, refining imaging protocols, and validating targeted therapies through international clinical trials. Full article

Epithelial-mesenchymal transition (EMT) is a key driver of invasion, metastasis, and treatment resistance in gastric cancer, yet its post-transcriptional regulation by microRNAs (miRNAs) is not fully delineated. We performed a structured literature search in PubMed, Web of Science, and Scopus for studies evaluating miRNAs in relation to EMT in gastric cancer and synthesised tumor-intrinsic, microenvironmental, and circulating EMT-related miRNA networks. Downregulated, predominantly tumor-suppressive miRNAs, including miR-34a, miR-200 family, miR-148a, miR-204, miR-30a, miR-101, miR-218, miR-26a, miR-375, miR-506, and others, converge on EMT transcription factors and pathways such as ZEB1/2, Snail, TGF-β/SMAD, Wnt/β-catenin, c-Met, and PI3K/AKT, and their restoration reverses EMT phenotypes in preclinical models. Upregulated oncomiRs, such as miR-21, miR-17-5p, miR-106b-5p, miR-23a, miR-130a-3p, miR-196a-5p, miR-181a, miR-616-3p, miR-301a-3p, miR-150, miR-27a-3p and miR-192/215, target tumor suppressors and reinforce these pathways. Cancer-associated fibroblast, macrophage, neutrophil, and natural killer cell-derived miRNAs, together with systemic indices such as the neutrophil-to-lymphocyte ratio and mediators like FAM3C, add microenvironmental layers of EMT regulation. Several EMT-related miRNAs show consistent associations with invasion, metastasis, peritoneal dissemination, prognosis, and chemoresistance, and many are detectable in circulation. Overall, EMT-related miRNAs orchestrate gastric cancer cell plasticity and tumor-microenvironment crosstalk and represent promising biomarker and therapeutic candidates that warrant validation in prospective, subtype-stratified, and translational studies. Full article

Background/Objectives: Peritoneal metastases (PMs) remain difficult to treat because the peritoneum–plasma barrier limits drug penetration from the systemic circulation. Intraperitoneal chemotherapy (IPC), particularly repeated intraperitoneal (IP) administration via implantable ports, can achieve high local drug exposure with prolonged retention. This review summarizes the pharmacological rationale, clinical evidence, and future directions of catheter-based IPC, with emphasis on combined IP and systemic chemotherapy for ovarian, gastric, and pancreatic cancers. Methods: We narratively reviewed prospective clinical trials and key retrospective studies evaluating IPC and compared repeated catheter-based IPC with hyperthermic intraperitoneal chemotherapy (HIPEC) and pressurized intraperitoneal aerosol chemotherapy (PIPAC). Efficacy, safety, practice considerations, and opportunities for ascites-based monitoring were examined. Results: In ovarian cancer, several randomized trials demonstrated improved progression-free survival (PFS), and in selected trials, improved overall survival (OS) was demonstrated using IP plus intravenous (IV) therapy, although in the latter trials, toxicity and catheter-related complications limited treatment completion. A phase III Intraperitoneal Therapy for Ovarian Cancer with Carboplatin (iPocc) trial further showed significantly prolonged PFS with IP carboplatin and weekly paclitaxel, with non-catheter-related toxicity comparable to that of IV therapy. In gastric and pancreatic cancer, phase II studies reported symptomatic control, cytologic conversion, and higher rates of conversion surgery in selected patients, although confirmatory phase III data are limited. Device complications, including infection, obstruction, and leakage, occurred, but were manageable. Conclusions: Repeated catheter-based IPC is a feasible approach that enhances intraperitoneal drug delivery and complements IV chemotherapy. Future priorities include randomized trials, pharmacokinetic optimization, and biomarker-guided patient selection, supported by serial ascites assessment to refine indications and improve outcomes. Full article

Chronic atrophic gastritis (CAG) is a key precursor in the Correa cascade leading to gastric cancer and is driven by long-standing Helicobacter pylori infection, autoimmune reactions, environmental exposures, and persistent inflammation. Emerging evidence indicates that mild to moderate atrophy and part of intestinal metaplasia exhibit a degree of reversibility when etiological eradication, microenvironmental optimization, and regenerative stimulation are achieved. This review summarizes recent advances in the pathological basis, evaluation systems, therapeutic mechanisms, and clinical management strategies of CAG. Reversibility is closely related to residual glandular reserve, stem-cell plasticity, and effective mitigation of chronic inflammation. Current assessment tools integrate OLGA/OLGIM histological staging, high-quality endoscopy with AI assistance, and serological biomarkers. Fundamental interventions include early H. pylori eradication, mucosal protective agents, micronutrients, and small-molecule drugs targeting inflammation, oxidative stress, and epithelial regeneration. Novel strategies such as mesenchymal stem cells, exosomes, and focal endoscopic therapies demonstrate regenerative potential in preclinical studies. Traditional Chinese medicine provides multi-target regulation of inflammation, apoptosis, microecology, and stem-cell-related pathways, contributing to histological improvement. Contemporary guidelines emphasize early eradication, risk-stratified surveillance, and comprehensive intervention. Future directions focus on unified evaluation criteria, long-term prospective studies, multimodal combination regimens, and integration of AI-based risk modeling to achieve precise, cancer-preventive CAG management. Full article

Background/Objectives: Patients who undergo gastrectomy for gastric adenocarcinoma and subsequently develop chronic intestinal failure requiring long-term home parenteral nutrition (HPN) represent a clinically vulnerable cohort in whom survival is shaped by profound nutritional depletion and systemic inflammation. Immuno-nutritional biomarkers may support improved risk stratification in this setting. Methods: This retrospective study included adults who underwent gastrectomy for gastric cancer and developed malignant chronic intestinal failure requiring HPN. Immuno-nutritional status at HPN qualification was evaluated using the Controlling Nutritional Status (CONUT) score and the lymphocyte-to-monocyte ratio (LMR). Overall survival was analysed using Cox proportional hazards models. LMR discrimination was assessed using receiver operating characteristic (ROC) analysis with a Youden-derived cut-off, and differences in AUC were tested using DeLong’s method. Results: Ninety-seven patients met the inclusion criteria. Median overall survival was 176 days. In multivariable analysis, CONUT and LMR were the only independent predictors of survival. Each one-point increase in CONUT was associated with an approximately 70% increase in mortality risk. LMR demonstrated good discriminative ability (AUC 0.795), and a cut-off of 2.083 differentiated survival trajectories. The combined CONUT–LMR model improved prognostic classification, and DeLong’s test confirmed a significant AUC difference compared with single-marker models. Kaplan–Meier curves showed clear separation across CONUT and LMR strata (log-rank p < 0.001). Conclusions: Among patients requiring long-term HPN after gastrectomy for gastric cancer, CONUT and LMR provide complementary prognostic information. Their combined use enhances survival stratification and may support earlier identification of patients with high-risk trajectories. Full article

Introduction: By leveraging dedicated datasets and predictive modeling, machine-learning (ML) algorithms can estimate the probability of both short- and long-term outcomes after surgery. The aim of this study was to evaluate the ability of ML-based models to predict postoperative complications in patients with gastric cancer (GC) undergoing multimodal therapy. In particular, we aimed to develop a free, publicly accessible online calculator based on preoperative variables. Materials and Methods: Patients with histologically confirmed locally advanced (cT2-4N0-3M0) GC who underwent multimodal treatment with curative intent between 2013 and 2023 were included in the study. ML models evaluation pipeline was used with Stratified 5-Fold Cross-Validation. Results: A total of 368 patients were included in the final analytic cohort. Among five algorithm classes under 5-fold cross-validation, Compute Area Under the Receiver Operating Characteristic Curve (ROC AUC) was 0.9719, 0.9652, 0.9796, 0.8339 and 0.7581 for XGBoost, Catboost, Random Forest, SVM and Logistic Regression, respectively. Macro F1 was 0.8714, 0.5094, 0.8820, 0.8714 and 0.4579 for XGBoost, SVM, Random Forest, CatBoost and Logistic Regression, respectively. Overall Accuracy was 0.8897, 0.5980, 0.8885, 0.8750 and 0.5466 for XGBoost, SVM, Random Forest, CatBoost and Logistic Regression models, respectively. Conclusions: In this Central and Eastern European cohort of patients with locally advanced GC, ML models using non-linear decision rules-particularly Random Forest and XGBoost- substantially outperformed conventional linear approaches in predicting the severity of postoperative complications. Prospective external validation is needed to clarify the model’s clinical utility and its potential role in perioperative decision support. Full article