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National Institute of Gastroenterology ... Publications | LitMetric

176 results match your criteria: "National Institute of Gastroenterology IRCCS "S. de Bellis"[Affiliation]"

The role of inflammasomes in hepatocellular carcinoma: Mechanisms and therapeutic insights.

Ann Hepatol

December 2024

Scientific Direction, National Institute of Gastroenterology, "S. de Bellis", IRCCS Research Hospital, Via Turi 27, Castellana Grotte, 70013 Bari, Italy. Electronic address:

Hepatocellular carcinoma is among the most frequent forms of primary liver cancer and develops within a context of chronic inflammation, frequently associated with a multitude of risk factors, including viral infections, metabolic dysfunction-associated fatty liver disease, metabolic dysfunction-associated steatohepatitis and liver fibrosis. The tumor microenvironment is crucial for the progression of HCC, as immune cells, tumor-associated fibroblasts and hepatic stellate cells interact to promote chronic inflammation and tumor spread. Inflammasomes, the multiprotein complexes that launch the innate immune response, emerge as important mediators in the pathogenesis of HCC.

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Inflammasomes in Intestinal Disease: Mechanisms of Activation and Therapeutic Strategies.

Int J Mol Sci

December 2024

National Institute of Gastroenterology S. De Bellis, IRCCS Research Hospital, Via Turi 27, 70013 Castellana Grotte, BA, Italy.

NOD-like receptors (NLRs) are a family of cytosolic pattern recognition receptors (PRRs) implicated in the innate immune sensing of pathogens and damage signals. NLRs act as sensors in multi-protein complexes called inflammasomes. Inflammasome activity is necessary for the maintenance of intestinal homeostasis, although their aberrant activation contributes to the pathogenesis of several gastrointestinal diseases.

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Very low-calorie ketogenic diets (VLCKD) are an effective weight-loss strategy for obese individuals, reducing risks of liver conditions such as non-alcoholic steatohepatitis and fibrosis. Small extracellular vesicles (sEVs) are implicated in liver fibrosis by influencing hepatic cell phenotypes and contributing to liver damage. This study investigates sEVs derived from serum of 60 obese adults categorized into low fibrosis risk (LR) and intermediate/high fibrosis risk (IHR) groups based on FibroScan elastography (FIB E scores, limit value 8 kPa) and all participants underwent an 8-week VLCKD intervention.

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Studies conducted in the last few years have suggested a connection between clinical outcomes and the time of immune checkpoint inhibitors (ICIs) infusion. However, few data are available regarding the differences between early and late time-of-day (ToD) administration in metastatic renal cell carcinoma (mRCC) patients receiving immunotherapy and immune-based combinations. In this meta-analysis, we aimed to fully investigate the influence of timing of administration on the efficacy of mRCC immunotherapy, by comparing early ToD versus late ToD dosing in this setting.

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Immunobiology of biliary tract cancer and recent clinical findings in approved and upcoming immune checkpoint inhibitors.

Expert Opin Biol Ther

December 2024

S.S.D. C.O.r.O. Bed Management Presa in Carico, TDM, IRCCS Istituto Tumori "Giovanni Paolo II", Bari, Italy.

Introduction: Recently, immunotherapy has offered new hope for treating biliary tract cancer (BTC). However, several issues are to be considered, including the lack of validated predictive biomarkers that could help to identify patient groups which are most likely to benefit from such therapeutic approaches.

Areas Covered: In the current article, we will provide an overview of recent results and ongoing and future research directions of immunotherapy in BTC, with a special focus on recently published, practice-changing data, and ongoing active and recruiting clinical trials.

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Treatment options for intrahepatic cholangiocarcinoma (iCCA), a highly malignant tumor with poor prognosis, are limited. Recent developments in immunotherapy and immune checkpoint inhibitors (ICIs) have offered new hope for treating iCCA. However, several issues remain, including the identification of reliable biomarkers of response to ICIs and immune-based combinations.

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Article Synopsis
  • Early-stage gastric cancer often goes undetected due to a lack of specific symptoms, resulting in late diagnoses and advanced disease, highlighting the need for new biomarkers for early detection and treatment matching.
  • The study investigated the prognostic significance of ENPP2/Autotaxin (ATX) and lysophosphatidic acid (LPA) in Gastro-Esophageal Adenocarcinoma (GEA), finding that higher levels of these substances could indicate worse patient outcomes.
  • Results showed that while ENPP2 mutations are infrequent, they are linked to lower overall survival, and surgical removal of tumors significantly reduced serum ATX and LPA levels, suggesting potential for targeted therapies based on these biomarkers in future clinical trials.
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Article Synopsis
  • Cancer-associated fibroblasts (CAFs) contribute to the aggressive nature and treatment resistance of intrahepatic Cholangiocarcinoma (iCCA), prompting research into the effects of the Notch1 inhibitor Crenigacestat on this interaction.
  • Using both 2D and 3D in vitro models, along with a xenograft setup, the study found that CAFs enhance iCCA cell migration and growth, but Crenigacestat effectively inhibits this cross-talk and reduces tumor growth and fibrosis.
  • Overall, targeting the hCAF/iCCA interaction with Crenigacestat presents a promising approach to slowing cancer progression and altering critical cell cycle pathways.
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Inorganic Polyphosphate Promotes Colorectal Cancer Growth via TRPM8 Receptor Signaling Pathway.

Cancers (Basel)

September 2024

Personalized Medicine Laboratory, National Institute of Gastroenterology "S. de Bellis", IRCCS Research Hospital, Via Turi 27, Castellana Grotte, 70013 Bari, Italy.

Background: Colorectal cancer (CRC) is characterized by a pro-inflammatory microenvironment and features high-energy-supply molecules that assure tumor growth. A still less studied macromolecule is inorganic polyphosphate (iPolyP), a high-energy linear polymer that is ubiquitous in all forms of life. Made up of hundreds of repeated orthophosphate units, iPolyP is essential for a wide variety of functions in mammalian cells, including the regulation of proliferative signaling pathways.

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The etiology of Inflammatory Bowel Disease (IBD) is not fully understood but is believed to involve a dysregulated immune response to intestinal microbiota in genetically susceptible individuals. Individuals with IBD are at increased risk of infections due to immunosuppressive treatments, comorbidities, and advanced age. Current evidence indicates that IBD patients are not at higher risk of SARS-CoV-2 infection compared to the general population, though the risk of severe outcomes remains debated.

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Many patients with irritable bowel syndrome (IBS) have a compromised intestinal barrier associated with low-grade inflammation. Polyunsaturated fatty acids (PUFAs) are potential mediators of inflammation: omega-6 PUFAs are pro-inflammatory, while omega-3 PUFAs are antioxidant and anti-inflammatory. Zonulin is a potential biomarker for small intestinal permeability (s-IP).

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Role of Extracellular Vesicles in Crohn's Patients on Adalimumab Who Received COVID-19 Vaccination.

Int J Mol Sci

August 2024

Laboratory of Personalized Medicine, National Institute of Gastroenterology IRCCS "S. de Bellis", Research Hospital, Via Turi 27, Castellana Grotte, 70013 Bari, Italy.

Article Synopsis
  • Crohn's disease (CD) is an inflammatory bowel disease that can affect the gastrointestinal tract and cause complications outside of it, and some patients have shown adverse effects after receiving the Pfizer-BioNTech mRNA vaccine.
  • Following vaccination, some CD patients have experienced a reduced effectiveness of the biological drug Adalimumab and a worsening of their condition, correlated with changes in intestinal permeability and protein expression.
  • The study aims to explore the effects of the SARS-CoV-2 Spike protein, particularly through extracellular vesicles, on the onset of Crohn's disease exacerbations and the potential impact on existing treatments.
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Article Synopsis
  • - Cyclic nucleotide phosphodiesterases (PDEs), particularly PDE4, are important enzymes in inflammation, and inhibiting them can lessen inflammatory responses linked to diseases like inflammatory bowel disease (IBD).
  • - The study highlights that the microRNA miR-369-3p can reduce the expression of PDE4B, a common form found in immune cells, which helps to raise cAMP levels and enhance anti-inflammatory signaling pathways.
  • - Results show that PDE4B levels are higher in patients with ulcerative colitis (UC) than in healthy individuals, indicating its role in inflammation and establishing miR-369-3p as a potential therapeutic target for managing IBD.
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Extracellular Vesicles Modulate Liver Cells Viability and Reactive Oxygen Species in Patients Following a Very Low-Calorie Ketogenic Diet.

Nutrients

July 2024

Laboratory of Molecular Medicine, National Institute of Gastroenterology IRCCS "S. de Bellis", Research Hospital, Via Turi 27, 70013 Castellana Grotte, Italy.

The VLCKD is a diet recognized to promote rapid fat mobilization and reduce inflammation, hepatic steatosis, and liver fibrosis. Extracellular vesicles (EVs) mediate cell-to-cell communication. The aim of the study is to investigate the role of circulating EVs in cell proliferation, ketone bodies, and ROS production in patients on an 8-week VLCKD regimen.

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Autotaxin (ATX) is a member of the ectonucleotide pyrophosphate/phosphodiesterase () family; it is encoded by the gene. ATX is a secreted glycoprotein and catalyzes the hydrolysis of lysophosphatidylcholine to lysophosphatidic acid (LPA). LPA is responsible for the transduction of various signal pathways through the interaction with at least six G protein-coupled receptors, LPA Receptors 1 to 6 (LPAR1-6).

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Management of severe thrombocytopenia poses significant challenges in patients with chronic liver disease. Here, we aimed to evaluate the first real-world European post-marketing cohort of cirrhotic patients treated with lusutrombopag, a thrombopoietin receptor agonist, verifying the efficacy and safety of the drug. In the REAl-world Lusutrombopag treatment in ITalY (REALITY) study, we collected data from consecutive cirrhotic patients treated with lusutrombopag in 19 Italian hepatology centers, mostly joined to the "Club Epatologi Ospedalieri" (CLEO).

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Metabolic-dysfunction-associated steatotic liver disease (MASLD) affects 30% of adults worldwide and is associated with obesity and cardiovascular risk factors. If left untreated, it can progress to severe liver disease. Lifestyle changes such as physical activity and weight loss help to reduce the severity and risk of mortality.

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Purpose: To report response rates (using mRECIST), overall survival (OS), progression-free survival and local tumour recurrence-free survival (LRFS) of balloon-occluded transarterial chemoembolisation (bTACE) for hepatocellular carcinoma (HCC).

Materials And Methods: Patients from five European centres treated with conventional or drug-eluting microsphere bTACE for HCC were included, and patients already lost to follow-up before 12 months were excluded. Possible factors contributing to LRFS and OS were evaluated with Cox proportional hazards models.

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Identification of a Novel miR-195-5p/PNN Axis in Colorectal Cancer.

Int J Mol Sci

May 2024

National Institute of Gastroenterology S. De Bellis, IRCCS Research Hospital, Via Turi 27, 70013 Castellana Grotte, BA, Italy.

Pinin (PNN) is a desmosome-associated protein that reinforces the organization of keratin intermediate filaments and stabilizes the anchoring of the cytoskeleton network to the lateral surface of the plasma membrane. The aberrant expression of PNN affects the strength of cell adhesion as well as modifies the intracellular signal transduction pathways leading to the onset of CRC. In our previous studies, we characterized the role of miR-195-5p in the regulation of desmosome junctions and in CRC progression.

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Leisure-Time Physical Activity, Time Spent Sitting and Risk of Non-alcoholic Fatty Liver Disease: A Cross-Sectional Study in Puglia.

J Gen Intern Med

November 2024

Estadìstica y Bioestadìstica Escuela de Nutriciòn, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina.

Background: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world. The increasingly sedentary lifestyle in recent years may have accelerated the development of NAFLD, independent of the level of physical activity.

Objective: The purpose of this cross-sectional study was to determine the association between leisure-time physical activity (LTPA) and time spent sitting (TSS) and the likelihood of developing NAFLD in a sample of men and women aged 18-64 years, from southern Italy.

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Development and Validation of a Scoring System to Predict Response to Obeticholic Acid in Primary Biliary Cholangitis.

Clin Gastroenterol Hepatol

October 2024

Division of Gastroenterology, Centre for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, European Reference Network on Hepatological Diseases, San Gerardo Hospital, Monza, Italy. Electronic address:

Background & Aims: Obeticholic acid (OCA) is the only licensed second-line therapy for primary biliary cholangitis (PBC). With novel therapeutics in advanced development, clinical tools are needed to tailor the treatment algorithm. We aimed to derive and externally validate the OCA response score (ORS) for predicting the response probability of individuals with PBC to OCA.

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