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Search Results (568)

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Keywords = gastric malignancy

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34 pages, 1707 KiB  
Review
Mimicking Gastric Cancer Collagen Reorganization with Decellularized ECM-Based Scaffolds
by Néstor Corro, Sebastián Alarcón, Ángel Astroza, Roxana González-Stegmaier and Carolina Añazco
Biology 2025, 14(8), 1067; https://doi.org/10.3390/biology14081067 (registering DOI) - 16 Aug 2025
Abstract
The tumor microenvironment (TME) has a substantial impact on the progression of gastric cancer. Collagen, the most abundant protein in the extracellular matrix (ECM), forms a dense physical barrier that regulates anti-tumor immunity in the TME. It is a significant regulator of the [...] Read more.
The tumor microenvironment (TME) has a substantial impact on the progression of gastric cancer. Collagen, the most abundant protein in the extracellular matrix (ECM), forms a dense physical barrier that regulates anti-tumor immunity in the TME. It is a significant regulator of the signaling pathways of cancer cells, which are responsible for migration, proliferation, and metabolism. ECM proteins, particularly remodeling enzymes and collagens, can be modified to increase stiffness and alter the mechanical properties of the stroma. This, in turn, increases the invasive potential of tumor cells and resistance to immunotherapy. Given the dynamic nature of collagen, novel therapeutic strategies have emerged that target both collagen biosynthesis and degradation, processes that are essential for addressing ECM stiffening. This review delineates the upregulation of the expression and deposition of collagen, as well as the biological functions, assembly, and reorganization that contribute to the dissemination of this aggressive malignancy. Furthermore, the review emphasizes the importance of creating 3D in vitro models that incorporate innovative biomaterials that avoid the difficulties of traditional 2D culture in accurately simulating real-world conditions that effectively replicate the distinctive collagen microenvironment. Ultimately, it investigates the use of decellularized ECM-derived biomaterials as tumor models that are designed to precisely replicate the mechanisms associated with the progression of stomach cancer. Full article
(This article belongs to the Special Issue Tumor Biomechanics and Mechanobiology)
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66 pages, 2939 KiB  
Review
Mechanistic Insights and Clinical Implications of ELK1 in Solid Tumors: A Narrative Review
by Georgios Kalampounias, Theodosia Androutsopoulou and Panagiotis Katsoris
Cells 2025, 14(16), 1257; https://doi.org/10.3390/cells14161257 - 14 Aug 2025
Abstract
ELK1 is a Transcription factor (TF) belonging to the ETS-domain TF family, mainly activated via RAS-RAF-MEK-ERK signaling. As a nethermost pathway molecule, ELK1 binds to Serum-response elements (SREs) and directly regulates the transcription of Immediate early genes (IEGs) including FOS and EGR1. [...] Read more.
ELK1 is a Transcription factor (TF) belonging to the ETS-domain TF family, mainly activated via RAS-RAF-MEK-ERK signaling. As a nethermost pathway molecule, ELK1 binds to Serum-response elements (SREs) and directly regulates the transcription of Immediate early genes (IEGs) including FOS and EGR1. Due to ELK1’s influence on key cellular processes such as proliferation, migration, apoptosis evasion, and Epithelial-to-mesenchymal transition (EMT), its role as a key contributor to tumorigenesis is emerging. In recent years, elevated expression and/or activation of ELK1 has been reported in various malignancies, including lung, breast, prostate, colorectal, blood, gastric, liver, cervical, thyroid and ovarian cancer. ELK1 acts primarily through direct DNA binding but also through interaction with other oncogenes, noncoding RNA molecules, TFs, and upstream kinases (other than ERK1/2), thus participating in diverse axes of transcriptional regulation. Its crucial role in IEG expression has been particularly implicated in cancer progression, metastasis, and drug resistance. Owing to its role in multiple cellular functions and its subsequent oncogenic potential, further elucidation of intracellular ELK1 interactions is of paramount importance. This review aims to summarize current evidence on ELK1’s involvement in solid tumors, dissect reported mechanistic roles, and highlight recent insights that could fuel future ventures of high translational interest. Full article
(This article belongs to the Special Issue Cell Migration and Invasion)
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25 pages, 1677 KiB  
Review
The Multifaceted Role of Growth Differentiation Factor 15 (GDF15): A Narrative Review from Cancer Cachexia to Target Therapy
by Daria Maria Filippini, Donatella Romaniello, Francesca Carosi, Laura Fabbri, Andrea Carlini, Raffaele Giusti, Massimo Di Maio, Salvatore Alfieri, Mattia Lauriola, Maria Abbondanza Pantaleo, Lorena Arribas, Marc Oliva, Paolo Bossi and Laura Deborah Locati
Biomedicines 2025, 13(8), 1931; https://doi.org/10.3390/biomedicines13081931 - 8 Aug 2025
Viewed by 479
Abstract
Background: Growth Differentiation Factor 15 (GDF15) has emerged as a key biomarker and therapeutic target in oncology, with roles extending beyond cancer cachexia. Elevated GDF15 levels correlate with poor prognosis across several solid tumors, including colorectal, gastric, pancreatic, breast, lung, prostate, and head [...] Read more.
Background: Growth Differentiation Factor 15 (GDF15) has emerged as a key biomarker and therapeutic target in oncology, with roles extending beyond cancer cachexia. Elevated GDF15 levels correlate with poor prognosis across several solid tumors, including colorectal, gastric, pancreatic, breast, lung, prostate, and head and neck cancers. GDF15 modulates tumor progression through PI3K/AKT, MAPK/ERK, and SMAD2/3 signaling, thereby promoting epithelial-to-mesenchymal transition, metastasis, immune evasion, and chemoresistance via Nrf2 stabilization and oxidative stress regulation. Methods: We performed a narrative review of the literature focusing on the role of GDF15 in solid tumors, with a particular emphasis on head and neck cancers. Results: In head and neck squamous cell carcinoma (HNSCC), GDF15 overexpression is linked to aggressive phenotypes, radioresistance, poor response to induction chemotherapy, and failure of immune checkpoint inhibitors (ICIs). Similar associations are observed in colorectal, pancreatic, and prostate cancer, where GDF15 contributes to metastasis and therapy resistance. Targeting the GDF15-GFRAL axis appears therapeutically promising: the monoclonal antibody ponsegromab improved cachexia-related outcomes in the PROACC-1 trial, while visugromab combined with nivolumab enhanced immune response in ICI-refractory tumors. Conclusions: Further investigation is warranted to delineate the role of GDF15 across malignancies, refine patient selection, and evaluate combinatorial approaches with existing treatments. Full article
(This article belongs to the Special Issue Head and Neck Tumors, 4th Edition)
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21 pages, 3401 KiB  
Article
Allelic Variation of Helicobacter pylori vacA Gene and Its Association with Gastric Pathologies in Clinical Samples Collected in Jordan
by Mamoon M. Al-Hyassat, Hala I. Al-Daghistani, Lubna F. Abu-Niaaj, Sima Zein and Talal Al-Qaisi
Microorganisms 2025, 13(8), 1841; https://doi.org/10.3390/microorganisms13081841 - 7 Aug 2025
Viewed by 506
Abstract
Helicobacter pylori is a well-established causative agent of gastritis, peptic ulcers, gastric adenocarcinoma, and primary gastric lymphoma. It colonizes the human stomach and expresses numerous virulent factors that influence disease progression. Among these factors is the cytotoxin vacA gene, which encodes the vacuolating [...] Read more.
Helicobacter pylori is a well-established causative agent of gastritis, peptic ulcers, gastric adenocarcinoma, and primary gastric lymphoma. It colonizes the human stomach and expresses numerous virulent factors that influence disease progression. Among these factors is the cytotoxin vacA gene, which encodes the vacuolating capacity of the cytotoxin and plays a key role in the bacterium’s pathogenic potential. This study investigated the allelic diversity of the vacA among H. pylori strains infecting patients in Jordan with various gastric conditions and examined potential associations between vacA s-and m- genotypes, histopathological and endoscopic findings, and the development of gastric diseases. Gastric biopsies were collected from 106 patients at two hospitals in Jordan who underwent endoscopic examination. The collected biopsies for each patient were subjected to histopathological assessment, urease detection using the Rapid Urease Test (RUT), a diagnostic test for H. pylori, and molecular detection of the vacA gene and its s and m alleles. The histopathology reports indicated that 83 of 106 patients exhibited gastric disorders, of which 81 samples showed features associated with H. pylori infection. The RUT was positive in 76 of 106 with an accuracy of 93.8%. Real-time polymerase chain reaction (RT-PCR) targeting the 16S rRNA gene confirmed the presence of H. pylori in 79 of 81 histologically diagnosed cases as infected (97.5%), while the vacA gene was detected only in 75 samples (~95%). To explore genetic diversity, PCR-amplified fragments underwent sequence analysis of the vacA gene. The m-allele was detected in 58 samples (73%), the s-allele was detected in 45 (57%), while both alleles were not detected in 13% of samples. The predominant genotype combination among Jordanians was vacA s2/m2 (50%), significantly linked to mild chronic gastritis, followed by s1/m2 (35%) and s1/m1 (11.8%) which are linked to severe gastric conditions including malignancies. Age-and gender-related differences in vacA genotype were observed with less virulent s2m2 and s1m2 genotypes predominating in younger adults specially males, while the more virulent m1 genotypes were found exclusively in females and middle-aged patients. Genomic sequencing revealed extensive diversity within H. pylori, likely reflecting its long-standing co-evolution with human hosts in Jordan. This genetic variability plays a key role in modulating virulence and influencing clinical outcomes. Comprehensive characterization of vacA genotypic variations through whole-genome sequencing is essential to enhance diagnostic precision, strengthen epidemiological surveillance, and inform targeted therapeutic strategies. While this study highlights the significance of the vacA m and s alleles, future research is recommended in order to investigate the other vacA allelic variations, such as the i, d, and c alleles, to achieve a more comprehensive understanding of H. pylori pathogenicity and associated disease severity across different strains. These investigations will be crucial for improving diagnostic accuracy and guiding the development of targeted therapeutic strategies. Full article
(This article belongs to the Special Issue Helicobacter pylori Infection: Detection and Novel Treatment)
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12 pages, 441 KiB  
Article
Cytokine Regulation and Oxidative Stress in Helicobacter Pylori-Associated Gastric Adenocarcinoma at Different Stages: Insights from a Cross-Sectional Study
by Olga Smirnova, Aleksander Sinyakov and Eduard Kasparov
Int. J. Mol. Sci. 2025, 26(15), 7609; https://doi.org/10.3390/ijms26157609 - 6 Aug 2025
Viewed by 195
Abstract
Gastric adenocarcinoma is a malignant tumor that develops from the glandular cells of the inner wall of the stomach. The prevalence of this type of disease varies from 90 to 95% of all types of gastric cancer. The aim of our study was [...] Read more.
Gastric adenocarcinoma is a malignant tumor that develops from the glandular cells of the inner wall of the stomach. The prevalence of this type of disease varies from 90 to 95% of all types of gastric cancer. The aim of our study was to investigate the differences in the content of cytokines and oxidative stress markers in patients with gastric adenocarcinoma associated with H. pylori infection depending on the stage. The study included 281 patients with gastric cancer. At stage I of the disease—75 people, stage II—70 people, stage III—69 people, and stage IV of the disease—67 people. The levels of TNF-α, IL-2, IL-8, IFNγ, TNF-β, IL-17A, IL-6, IL-10, and IL-4 in the blood serum of patients and healthy individuals were determined by enzyme immunoassay and plasma oxidative stress scores (MDA, SOD, CAT, GST, GPO, CP). The present study revealed that H. pylori-infected gastric adenocarcinoma at different stages is associated with different plasma levels of cytokines, lipid peroxidation products, and antioxidant defense factors. Further studies are needed to evaluate the effectiveness of therapeutic strategies combining cytokine regulation and oxidative stress to improve clinical outcomes in gastric cancer. Full article
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23 pages, 406 KiB  
Systematic Review
Advances in Bidirectional Therapy for Peritoneal Metastases: A Systematic Review of Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) Combined with Systemic Chemotherapy
by Manuela Robella, Marco Vitturini, Andrea Di Giorgio, Matteo Aulicino, Martin Hubner, Emanuele Koumantakis, Felice Borghi, Paolo Catania, Armando Cinquegrana and Paola Berchialla
Cancers 2025, 17(15), 2580; https://doi.org/10.3390/cancers17152580 - 6 Aug 2025
Viewed by 479
Abstract
Background: Peritoneal metastases (PM) represent a common and challenging manifestation of several gastrointestinal and gynecologic malignancies. Bidirectional treatment—combining Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) with systemic chemotherapy—has emerged as a strategy to enhance locoregional control while maintaining systemic coverage. Objective: This systematic [...] Read more.
Background: Peritoneal metastases (PM) represent a common and challenging manifestation of several gastrointestinal and gynecologic malignancies. Bidirectional treatment—combining Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) with systemic chemotherapy—has emerged as a strategy to enhance locoregional control while maintaining systemic coverage. Objective: This systematic review aimed to analyze the study design, characteristics, and timing of the treatments administered—including the type of systemic chemotherapy, intraperitoneal agents used in PIPAC, and interval between administrations—as well as the clinical outcomes, safety profile, and overall methodological quality of the available literature on bidirectional treatment for peritoneal metastases. Methods: A systematic literature search was conducted across the PubMed, Embase, and Cochrane Library databases up to April 2025. Studies were included if they reported clinical outcomes of patients undergoing bidirectional treatment. Data extraction focused on survival, response assessment (PRGS, PCI), adverse events, systemic and intraperitoneal regimens, treatment interval, and study methodology. Results: A total of 22 studies involving 1015 patients (742 treated with bidirectional therapy) were included. Median overall survival ranged from 2.8 to 19.6 months, with the most favorable outcomes observed in gastric and colorectal cancer cohorts. PRGS improvement after multiple PIPAC cycles was reported in >80% of evaluable cases. High-grade adverse events (CTCAE ≥ 3) occurred in up to 17% of patients in most studies, with only one study reporting treatment-related mortality. However, methodological quality was generally moderate, with considerable heterogeneity in treatment protocols, response criteria, systemic regimens, and toxicity attribution. Conclusions: Bidirectional therapy with PIPAC and systemic chemotherapy appears to be a feasible and potentially effective strategy for selected patients with peritoneal metastases. Despite encouraging outcomes, definitive conclusions are limited by the retrospective nature and heterogeneity of available studies. Prospective standardized trials are needed to confirm efficacy, clarify patient selection, and optimize treatment protocols. Full article
(This article belongs to the Section Cancer Therapy)
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18 pages, 914 KiB  
Review
Advances in Surgical Management of Malignant Gastric Outlet Obstruction
by Sang-Ho Jeong, Miyeong Park, Kyung Won Seo and Jae-Seok Min
Cancers 2025, 17(15), 2567; https://doi.org/10.3390/cancers17152567 - 4 Aug 2025
Viewed by 620
Abstract
Malignant gastric outlet obstruction (MGOO) is a serious complication arising from advanced gastric or pancreatic head cancer, significantly impairing patients’ quality of life by disrupting oral intake and inducing severe gastrointestinal symptoms. With benign causes such as peptic ulcer disease on the decline, [...] Read more.
Malignant gastric outlet obstruction (MGOO) is a serious complication arising from advanced gastric or pancreatic head cancer, significantly impairing patients’ quality of life by disrupting oral intake and inducing severe gastrointestinal symptoms. With benign causes such as peptic ulcer disease on the decline, malignancies now account for 50–80% of gastric outlet obstruction (GOO) cases globally. This review outlines the pathophysiology, evolving epidemiology, and treatment modalities for MGOO. Therapeutic approaches include conservative management, endoscopic stenting, surgical gastrojejunostomy (GJ), stomach partitioning gastrojejunostomy (SPGJ), and endoscopic ultrasound-guided gastroenterostomy (EUS-GE). While endoscopic stenting offers rapid symptom relief with minimal invasiveness, it has higher rates of re-obstruction. Surgical options like GJ and SPGJ provide more durable palliation, especially for patients with longer expected survival. SPGJ, a modified surgical technique, demonstrates reduced incidence of delayed gastric emptying and may improve postoperative oral intake and survival compared to conventional GJ. EUS-GE represents a promising, minimally invasive alternative that combines surgical durability with endoscopic efficiency, although long-term data remain limited. Treatment selection should consider patient performance status, tumor characteristics, prognosis, and institutional resources. This comprehensive review underscores the need for individualized, multidisciplinary decision-making to optimize symptom relief, nutritional status, and overall outcomes in patients with MGOO. Full article
(This article belongs to the Special Issue Advances in the Treatment of Upper Gastrointestinal Cancer)
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37 pages, 1856 KiB  
Review
Current and Future Directions in Immunotherapy for Gastrointestinal Malignancies
by Catherine R. Lewis, Yazan Samhouri, Christopher Sherry, Neda Dadgar, Moses S. Raj and Patrick L. Wagner
Int. J. Transl. Med. 2025, 5(3), 33; https://doi.org/10.3390/ijtm5030033 - 31 Jul 2025
Viewed by 643
Abstract
Gastrointestinal (GI) malignancies are diverse and particularly challenging in terms of current immunotherapy but hold great opportunity for impact given that they constitute the highest cancer incidence and mortality rates worldwide. Traditional treatment options for solid GI malignancies include surgical intervention, chemotherapy, radiation, [...] Read more.
Gastrointestinal (GI) malignancies are diverse and particularly challenging in terms of current immunotherapy but hold great opportunity for impact given that they constitute the highest cancer incidence and mortality rates worldwide. Traditional treatment options for solid GI malignancies include surgical intervention, chemotherapy, radiation, or a combination of these treatments. Emerging modalities within immunotherapy are anticipated to extend the results with conventional therapy by stimulating the patient’s own intrinsic potential for tumor-specific immunologic rejection. Combination regimens of chemotherapy and tumor-infiltrating lymphocyte (TIL) therapy in advanced colorectal cancer and pancreatic cancer, autologous monocyte therapy in advanced gastric cancer, and CAR-T therapy trained against GI-selective tumor antigens such as carcinoembryonic antigen are currently being studied. Clinical trials are underway to study the combination of various chemotherapeutic agents along with immunotherapy in the management of cholangiocarcinoma, hepatocellular carcinoma, and esophageal cancer. Alternative therapies are needed based on the tumor immune microenvironment, which can lead to a personalized approach to treatment. In this review, we discuss the current status of various modalities of immunotherapy in common GI malignancies, along with their mechanisms of immune activation and cancer suppression. We will also discuss the use of immunotherapy in less common solid GI malignancies and touch on recent advancements and clinical trials. Full article
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18 pages, 1100 KiB  
Review
The Role of Prophylactic HIPEC in High-Risk Gastric Cancer Patients: Where Do We Stand?
by Alexandros Diamantis, Athina A. Samara, Anastasios Lafioniatis, Michel B. Janho, Theodoros Floros and Konstantinos Tepetes
Cancers 2025, 17(15), 2492; https://doi.org/10.3390/cancers17152492 - 28 Jul 2025
Viewed by 347
Abstract
For patients diagnosed with a malignancy at high risk of developing peritoneal metastases, the concept of prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) has emerged. The aim of the present study is to assess the role of prophylactic HIPEC in gastric cancer patients at high [...] Read more.
For patients diagnosed with a malignancy at high risk of developing peritoneal metastases, the concept of prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) has emerged. The aim of the present study is to assess the role of prophylactic HIPEC in gastric cancer patients at high risk of PC, based on the currently available data in the literature. In total, 14 RCTs and 16 non-RCTs were identified and included in the present review, with 1383 patients included in the RCTs (627 of whom underwent HIPEC) and 1647 patients included in the non-RCTs (with 609 undergoing HIPEC). Prophylactic HIPEC appears to be useful and effective in treating patients with high-risk gastric cancer, improving both overall and disease-free survival. The heterogeneity of data regarding treatment protocols and complication rates suggests that further research is necessary to develop optimal therapeutic approaches and personalized treatment options; in particular, large-scale randomized control trials are needed in order to elucidate the potential benefits associated with the use of prophylactic HIPEC. Full article
(This article belongs to the Special Issue Surgical Treatment of Abdominal Tumors)
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17 pages, 4161 KiB  
Article
Targeting CEACAM5: Biomarker Characterization and Fluorescent Probe Labeling for Image-Guided Gastric Cancer Surgery
by Serena Martinelli, Sara Peri, Cecilia Anceschi, Anna Laurenzana, Laura Fortuna, Tommaso Mello, Laura Naldi, Giada Marroncini, Jacopo Tricomi, Alessio Biagioni, Amedeo Amedei and Fabio Cianchi
Biomedicines 2025, 13(8), 1812; https://doi.org/10.3390/biomedicines13081812 - 24 Jul 2025
Viewed by 397
Abstract
Background: Gastric cancer (GC) is a malignant tumor of the gastrointestinal tract, characterized by high mortality rates and responsible for about one million new cases each year globally. Surgery is the main treatment, but achieving radical resection remains a relevant intraoperative challenge. [...] Read more.
Background: Gastric cancer (GC) is a malignant tumor of the gastrointestinal tract, characterized by high mortality rates and responsible for about one million new cases each year globally. Surgery is the main treatment, but achieving radical resection remains a relevant intraoperative challenge. Fluorescence-guided surgery offers clinicians greater capabilities for real-time detection of tumor nodules and visualization of tumor margins. In this field, the main challenge remains the development of fluorescent dyes that can selectively target tumor tissues. Methods: we examined the expression of the most suitable GC markers, including carcinoembryonic antigen cell adhesion molecule-5 (CEACAM5) and Claudin-4 (CLDN4), in GC cell lines. To further evaluate their expression, we performed immunohistochemistry (IHC) on tumor and healthy tissue samples from 30 GC patients who underwent partial gastrectomy at the Digestive System Surgery Unit, AOU Careggi, Florence. Additionally, we validated anti-CEACAM5 expression on patient-derived organoids. Furthermore, we developed a fluorescent molecule targeting CEACAM5 on the surface of GC cells and assessed its binding properties on patient tissue slices and fragments. Results: in this work, we first identified CEACAM5 as an optimal GC biomarker, and then we developed a fluorescent antibody specific for CEACAM5. We also evaluated its binding specificity for GC cell lines and patient-derived tumor tissue, achieving an optimal ability to discriminate tumor tissue from healthy mucosa. Conclusions: Overall, our results support the development of our fluorescent antibody as a promising tumor-specific imaging agent that, after further in vivo validation, could improve the accuracy of complete tumor resection. Full article
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18 pages, 3877 KiB  
Review
The Palliation of Unresectable Pancreatic Cancer: Evolution from Surgery to Minimally Invasive Modalities
by Muaaz Masood, Shayan Irani, Mehran Fotoohi, Lauren Wancata, Rajesh Krishnamoorthi and Richard A. Kozarek
J. Clin. Med. 2025, 14(14), 4997; https://doi.org/10.3390/jcm14144997 - 15 Jul 2025
Viewed by 529
Abstract
Pancreatic cancer is an aggressive malignancy, with a current 5-year survival rate in the United States of approximately 13.3%. Although the current standard for resectable pancreatic cancer most commonly includes neoadjuvant chemotherapy prior to a curative resection, surgery, in the majority of patients, [...] Read more.
Pancreatic cancer is an aggressive malignancy, with a current 5-year survival rate in the United States of approximately 13.3%. Although the current standard for resectable pancreatic cancer most commonly includes neoadjuvant chemotherapy prior to a curative resection, surgery, in the majority of patients, has historically been palliative. The latter interventions include open or laparoscopic bypass of the bile duct or stomach in cases of obstructive jaundice or gastric outlet obstruction, respectively. Non-surgical interventional therapies started with percutaneous transhepatic biliary drainage (PTBD), both as a palliative maneuver in unresectable patients with obstructive jaundice and to improve liver function in patients whose surgery was delayed. Likewise, interventional radiologic techniques included the placement of plastic and ultimately self-expandable metal stents (SEMSs) through PTBD tracts in patients with unresectable cancer as well as percutaneous cholecystostomy in patients who developed cholecystitis in the context of malignant obstructive jaundice. Endoscopic retrograde cholangiopancreatography (ERCP) and stent placement (plastic/SEMS) were subsequently used both preoperatively and palliatively, and this was followed by, or undertaken in conjunction with, endoscopic gastro-duodenal SEMS placement for gastric outlet obstruction. Although endoscopic ultrasound (EUS) was initially used to cytologically diagnose and stage pancreatic cancer, early palliation included celiac block or ablation for intractable pain. However, it took the development of lumen-apposing metal stents (LAMSs) to facilitate a myriad of palliative procedures: cholecystoduodenal, choledochoduodenal, gastrohepatic, and gastroenteric anastomoses for cholecystitis, obstructive jaundice, and gastric outlet obstruction, respectively. In this review, we outline these procedures, which have variably supplanted surgery for the palliation of pancreatic cancer in this rapidly evolving field. Full article
(This article belongs to the Special Issue Pancreatic Cancer: Novel Strategies of Diagnosis and Treatment)
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16 pages, 990 KiB  
Review
Repurposing Rafoxanide: From Parasite Killer to Cancer Fighter
by Teresa Pacifico, Lorenzo Tomassini, Livia Biancone, Giovanni Monteleone, Carmine Stolfi and Federica Laudisi
Biomedicines 2025, 13(7), 1686; https://doi.org/10.3390/biomedicines13071686 - 9 Jul 2025
Viewed by 517
Abstract
Rafoxanide, originally developed as a veterinary anthelmintic for the treatment of parasitic infections in livestock, has recently emerged as a promising therapeutic prospect in oncology. This compound has demonstrated notable antineoplastic effects against a variety of cancers, including skin, gastric, colorectal, and lung [...] Read more.
Rafoxanide, originally developed as a veterinary anthelmintic for the treatment of parasitic infections in livestock, has recently emerged as a promising therapeutic prospect in oncology. This compound has demonstrated notable antineoplastic effects against a variety of cancers, including skin, gastric, colorectal, and lung cancers, as well as hematological malignancies such as multiple myeloma. Rafoxanide exerts its anticancer activity through multiple complementary mechanisms, including the induction of endoplasmic reticulum stress, cell cycle arrest, apoptosis, and immunogenic cell death. Furthermore, the drug has been reported to inhibit key oncogenic signaling pathways (e.g., STAT3, NF-κB, c-FLIP, survivin) that contribute to tumor growth and metastasis. Preclinical studies in murine models have demonstrated significant reductions in tumor volume of up to 50% and a tumor-free rate exceeding 80%, with effective doses ranging from 7.5 to 40 mg/kg. This multitargeted mode of action distinguishes rafoxanide from conventional therapies and may help overcome resistance mechanisms that often limit the efficacy of cancer treatments. In this review, we summarize and discuss the growing body of evidence supporting rafoxanide’s therapeutic potential in oncology, as well as its possible applications in cancer treatment. Full article
(This article belongs to the Section Cancer Biology and Oncology)
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16 pages, 1146 KiB  
Review
Wnt Signaling and Circular RNAs in Esophageal and Gastric Cancers: Opportunities for Early Detection and Targeted Therapy
by Piotr Paweł Chmielewski, Bartłomiej Strzelec and Julia Rudno-Rudzińska
J. Clin. Med. 2025, 14(13), 4805; https://doi.org/10.3390/jcm14134805 - 7 Jul 2025
Viewed by 507
Abstract
Aberrant activation of Wnt/β-catenin signaling, frequently caused by oncogenic mutations, plays a crucial role in the development, progression, and therapy resistance of gastric, esophageal, hepatic, pancreatic, and colorectal cancers. Concurrently, circular RNAs (circRNAs), produced by back-splicing of precursor mRNAs (pre-mRNAs), have emerged as [...] Read more.
Aberrant activation of Wnt/β-catenin signaling, frequently caused by oncogenic mutations, plays a crucial role in the development, progression, and therapy resistance of gastric, esophageal, hepatic, pancreatic, and colorectal cancers. Concurrently, circular RNAs (circRNAs), produced by back-splicing of precursor mRNAs (pre-mRNAs), have emerged as critical modulators of this pathway. Accumulating evidence indicates that specific circRNAs regulate Wnt/β-catenin signaling by sponging microRNAs, interacting with RNA-binding proteins, modulating protein function, and altering the expression of pathway components. Some circRNAs are also subject to feedback regulation by Wnt signaling itself. Clinically, tumor-associated circRNAs are present in body fluids and correlate with disease stage, metastatic burden, and patient survival, underscoring their potential as early and minimally invasive biomarkers. Moreover, targeting oncogenic circRNAs has shown promise in preclinical models of Wnt-driven gastrointestinal malignancies. In this review, we summarize the current understanding of the interplay between circRNAs and Wnt/β-catenin signaling in gastric and esophageal cancers. We discuss the translational challenges and emerging opportunities for biomarker development and targeted therapy. Full article
(This article belongs to the Special Issue Gastroesophageal Cancer: Outcomes and Therapeutic Management)
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26 pages, 2069 KiB  
Review
Unraveling Helicobacter pylori: Insights into Pathogenesis, Immune Evasion, and Progress Toward Effective Vaccination
by Ayman Elbehiry, Eman Marzouk and Adil Abalkhail
Vaccines 2025, 13(7), 725; https://doi.org/10.3390/vaccines13070725 - 3 Jul 2025
Viewed by 903
Abstract
Helicobacter pylori (H. pylori) is one of the most prevalent chronic bacterial infections globally, significantly contributing to gastritis, peptic ulcers, and gastric malignancies. Its pathogenesis involves a complex array of virulence factors—including cagA, vacA, and urease—which facilitate mucosal colonization, [...] Read more.
Helicobacter pylori (H. pylori) is one of the most prevalent chronic bacterial infections globally, significantly contributing to gastritis, peptic ulcers, and gastric malignancies. Its pathogenesis involves a complex array of virulence factors—including cagA, vacA, and urease—which facilitate mucosal colonization, immune evasion, and persistent inflammation. A major challenge in vaccine development is the bacterium’s ability to manipulate both innate and adaptive immune responses, resulting in limited natural clearance and long-term persistence. This review synthesizes H. pylori pathogenesis and host immune dynamics, highlighting their implications for vaccine design. By elucidating the molecular and cellular mechanisms underlying host–pathogen interactions, we explore how these insights inform antigen selection, adjuvant optimization, and delivery strategies. By integrating basic science with translational objectives, this review aims to support the development of an effective H. pylori vaccine, addressing global health needs, particularly in regions with a high infection burden and limited access to treatment. Full article
(This article belongs to the Section Vaccines and Public Health)
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32 pages, 6839 KiB  
Article
Identification of Novel Molecular Panel as Potential Biomarkers of PAN-Gastrointestinal Cancer Screening: Bioinformatics and Experimental Analysis
by Fatemeh Hajibabaie, Parisa Mohamadynejad, Laleh Shariati, Kamran Safavi and Navid Abedpoor
Biology 2025, 14(7), 803; https://doi.org/10.3390/biology14070803 - 2 Jul 2025
Viewed by 571
Abstract
PAN-gastrointestinal cancers (PAN-GI cancers), including the oral, esophageal, gastric, hepatocellular, pancreatic=, and colorectal cancers, are the leading cause of cancer-related mortality. Despite recent advances in identifying the molecular mechanisms driving these malignancies, the high incidence and recurrence of the PAN-gastrointestinal cancers and the [...] Read more.
PAN-gastrointestinal cancers (PAN-GI cancers), including the oral, esophageal, gastric, hepatocellular, pancreatic=, and colorectal cancers, are the leading cause of cancer-related mortality. Despite recent advances in identifying the molecular mechanisms driving these malignancies, the high incidence and recurrence of the PAN-gastrointestinal cancers and the low survival rates of patients indicate the need to introduce biomarkers for early diagnosis to improve diagnostic and therapeutic approaches. In the present study, using integrated transcriptomics, RNA-Seq and microarray data, from the TCGA and GEO databases, respectively, were combined to discover and validate a global biomarker panel for PAN-gastrointestinal cancers. In order to validate the bioinformatics data, the expression levels of genes in the molecular panel were evaluated using real-time quantitative polymerase chain reaction (qPCR) in tumor tissues of 21 patients with early diagnosis of gastric cancer and colorectal cancer (Stage I and II). By examining the transcriptomic profiles of six types of PAN-gastrointestinal cancers, a network of closely related hub genes (n = 167) with biomarker potential (p value < 0.05) was identified. Also, using ROC curve analysis and the Youden index, a molecular panel consisting of AURKA, CEP55, DTL, and TTK was presented (95% confidence interval and p value < 0.05), which showed exceptional sensitivity and specificity in differentiating malignant tissue from normal tissue (AUC > 80%). The diagnostic efficacy of these markers was confirmed by further validation using qPCR in colorectal and gastric tumor samples (p value < 0.05). In conclusion, a novel molecular signature panel including the AURKA, CEP55, DTL, and TTK genes could improve early cancer detection and diagnostic accuracy, and it may contribute to the treatment outcomes of PAN-gastrointestinal cancer patients. Full article
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