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Impairment of ghrelin synthesis in Helicobacter pyloricolonized stomach:New clues for the pathogenesis of ***-related gastric inflammation

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World Journal of Gastroenterology 2014年第3期20卷 639-646页

作者： Omero Alessandro Paoluzi Giovanna Del Vecchio Blanco Roberta Caruso Ivan monteleone giovanni monteleone Francesco Pallone Department of Systems Medicine University of Rome "Tor Vergata"

Ghrelin,the ligand of growth hormone secretagogue receptor 1a,takes part in several functions of the digestive system,including regulation of appetite,energy homeostasis,gastric acid secretion and *** has also immunoregulatory properties and is supposed to inhibit some inflammatory pathways that can mediate gastric ***,ghrelin synthesis is reduced in the gastric mucosa of patients with Helicobacter pylori(***)infection,a worldwide condition inducing a T helper(Th)1/Th17 cell responsedriven gastritis,which may evolve towards gastric atrophy and *** this article,we review the available data on the expression of ghrelin in *** infection and discuss how the defective ghrelin synthesis may contribute to sustain the ongoing inflammatory response in this disease.

关键词： Gastritis Ghrelin Helicobacter pylori T helper 1 cells

Proteinase activated-receptors-associated signaling in the control of gastric cancer

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World Journal of Gastroenterology 2014年第34期20卷 11977-11984页

作者： Silvia Sedda Irene Marafini Roberta Caruso Francesco Pallone giovanni monteleone Dipartimento di Medicina dei Sistemi Università Tor Vergata00133 RomeItaly

Gastric cancer(GC)is the fourth most common cancer in the world and the second cause of cancer-related *** carcinogenesis is a multifactorial process,in which environmental and genetic factors interact to activate multiple intracellular signals thus leading to uncontrolled growth and survival of GC *** such a pathway is regulated by proteinase activated-receptors(PARs),seven transmembrane-spanning domain G protein-coupled receptors,which comprise four receptors(i.e.,PAR-1,PAR-2,PAR-3,and PAR-4)activated by various *** PAR-1 and PAR-2 are over-expressed on GC cells and their activation triggers and/or amplifies intracellular pathways,which sustain gastric *** is also evidence that expression of either PAR-1 or PAR-2 correlates with depth of wall invasion and metastatic dissemination and inversely with the overall survival of ***,data emerging from experimental models of GC suggest that both these receptors can be important targets for therapeutic interventions in GC *** contrast,PAR-4levels are down-regulated in GC and correlate inversely with the aggressiveness of GC,thus suggesting a negative role of this receptor in the control of *** this article we review the available data on the expression and role of PARs in GC and discuss whether manipulation of PAR-driven signals may be useful for interfering with GC cell behavior.

关键词： Proteinase activated-receptors Gastric cancer Helicobacter pylori infection

Common immunologic mechanisms in inflammatory bowel disease and spondylarthropathies

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World Journal of Gastroenterology 2009年第20期15卷 2472-2478页

作者： Massimo C Fantini Francesco Pallone giovanni monteleone Department of Internal Medicine University of Rome "Tor Vergata" Rome 00133 Italy

Spondyloarthropathies （SPA） are commonly observed extra-intestinal manifestations of both Crohn＇s disease （CD） and ulcerative colitis （UC）, the two major forms of inflammatory bowel diseases （[BD）. However, the immunological link between these two clinical entities is still poorly understood. Several lines of evidence indicate that SpA may originate from the relocation to the joints of the immune process primarily induced in the gut. The transfer of the intestinal inflammatory process into the joints implicates that immune cells activated in the gut-draining lymph nodes can localize, at a certain point of the intestinal disease, either into the gut or into the joints. This is indicated by the overlapping expression of adhesion molecules observed on the surface of intestinal and synovial endothelial cells during inflammation. Moreover bacterial antigens and HLA-B27 expression may be implicated in the reactivation of T cells at the articular level. Finally, accumulating evidence indicates that a T helper 17 cell-mediated immune response may contribute to IBD and IBD-related SpA with a crucial role played by tumor necrosis factor-α in CD and to a lesser extent in UC.

关键词： Cell adhesion molecules Antigens Th17 Helper T-cells Tumor necrosis factor-α

Lumen-apposing metal stents for malignant biliary obstruction: Is this the ultimate horizon of our experience?

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World Journal of Gastroenterology 2019年第29期25卷 3857-3869页

作者： Andrea Anderloni Edoardo Troncone Alessandro Fugazza Annalisa Cappello Giovanna Del Vecchio Blanco giovanni monteleone Alessandro Repici Digestive Endoscopy Unit Division of Gastroenterology Humanitas Research Hospital Milan 20089 Italy Department of Systems Medicine University of Rome “Tor Vergata” Rome 00133 Italy Digestive Endoscopy Unit Division of Gastroenterology Humanitas University Milan 20089 Italy

In the last years, endoscopic ultrasonography (EUS) has evolved from a purely diagnostic technique to a more and more complex interventional procedure, with the possibility to perform several type of therapeutic interventions. Among these, EUS-guided biliary drainage (BD) is gaining popularity as a therapeutic approach after failed endoscopic retrograde cholangiopancreatography in distal malignant biliary obstruction (MBO), due to the avoidance of external drainage, a lower rate of adverse events and re-interventions, and lower costs compared to percutaneous trans-hepatic BD. Initially, devices created for luminal procedures (e.g., luminal biliary stents) have been adapted to the new trans-luminal EUSguided interventions, with predictable shortcomings in technical success, outcome and adverse events. More recently, new metal stents specifically designed for transluminal drainage, namely lumen-apposing metal stents (LAMS), have been made available for EUS-guided procedures. An electrocautery enhanced delivery system (EC-LAMS), which allows direct access of the delivery system to the target lumen, has subsequently simplified the classic multi-step procedure of EUS-guided drainages. EUS-BD using LAMS and ECLAMS has been demonstrated effective and safe, and currently seems one of the most performing techniques for EUS-BD. In this Review, we summarize the evolution of the EUS-BD in distal MBO, focusing on the novelty of LAMS and analyzing the unresolved questions about the possible role of EUS as the first therapeutic option to achieve BD in this setting of patients.

关键词： Interventional endoscopic ultrasonography Endoscopic ultrasonography-guided biliary drainage Endoscopic ultrasonography-guided choledocho-duodenostomy Biliary metal stent Lumen-apposing metal stent

Role of Smad7 in inflammatory bowel diseases

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World Journal of Gastroenterology 2012年第40期18卷 5664-5668页

作者： giovanni monteleone Roberta Caruso Francesco Pallone Department of Internal Medicine University Tor Vergata of Rome

Crohn's disease and ulcerative colitis,the major forms of inflammatory bowel diseases(IBD) in man,are complex diseases in which genetic and environmental factors interact to promote an excessive mucosal immune response directed against normal components of the bacterial *** is also evidence that the pathologic process is due to defects in counterregulatory mechanisms,such as those involving the immunosuppressive cytokine transforming growth factor(TGF)-***,studies in human IBD tissues and murine models of colitis have documented a disruption of TGF-1 signalling marked by a block in the phosphorylation of Smad3,a signalling molecule associated with the activated TGF-receptor,due to up-regulation of Smad7,an intracellular inhibitor of Smad3 ***-down of Smad7 with a specific antisense oligonucleotide restores TGF-1/Smad3 signalling,thus resulting in a marked suppression of inflammatory cytokine production and attenuation of murine *** findings together with the demonstration that Smad7 antisense oligonucleotide is not toxic when administered in mice have paved the way for the development of a Smad7 antisense oligonucleotidebased pharmaceutical compound that is now ready to enter the *** this article we review the available data supporting the pathogenic role of Smad7 in IBD and discuss whether and how Smad7 antisense therapy could help dampen the ongoing inflammation in IBD.

关键词： Inflammatory bowel diseases Gut inflam-mation Transforming growth factor-β1 Smad7 Anti-sense oligonucleotides

Emerging role of IL-23/IL-17 axis in H pylori-associated pathology

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World Journal of Gastroenterology 2007年第42期13卷 5547-5551页

作者： Roberta Caruso Francesco Pallone giovanni monteleone Department of Internal Medicine & Centre of Excellence for Genomic Risk Assessment in Multifactorial and Complex Diseases University "Tor Vergata" of Rome Rome Italy

Colonization of stomach by H pylori is followed by a marked infiltration of the mucosa with polymorphonuclear leukocytes, macrophages, and lymphocytes that very often remains asymptomatic, but in some circumstances can lead to the development of gastroduodenal ulceration, gastric carcinoma, and mucosa-associated lymphoid tissue lymphoma. The molecular mechanisms by which H pylori triggers and maintains the local immune response are complex, but there is evidence that cytokines produced by both immune and non-immune cells contribute to amplify the ongoing inflammation. H pylori infection is associated with a marked mucosal induction of T helper (Th) type 1 and Th17-type cytokines that is governed by specific antigen-presenting cell-derived molecules, such as interleukin (IL)-12 and IL-23. In this paper, we will review the available data on the expression and role of IL-23 and IL-17 in H pylori- related gastritis.

关键词： IL-23 IL-17 Hpylori

Intestinal inflammation and colorectal cancer:A doubleedged sword?

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World Journal of Gastroenterology 2011年第26期17卷 3092-3100页

作者： Angelamaria Rizzo Francesco Pallone giovanni monteleone Massimo Claudio Fantini Department of Internal Medicine University of Rome "Tor Vergata"

Chronic inflammation is thought to be the leading cause of many human cancers including colorectal cancer(CRC).Accordingly,epidemiologic and clinical studies indicate that patients affected by ulcerative colitis and Crohn's disease,the two major forms of inflammatory bowel disease,have an increased risk of developing *** recent years,the role of immune cells and their products have been shown to be pivotal in initiation and progression of colitis-associated *** the other hand,activation of the immune system has been shown to cause dysplastic cell elimination and cancer suppression in other *** and experimental data herein reviewed,while confirming chronic inflammation as a risk factor for colon carcinogenesis,do not completely rule out the possibility that under certain conditions the chronic activation of the mucosal immune system might protect from colonic dysplasia.

关键词： Colorectal cancer Inflammation T cells Cytokines Immunosurveillance

Interleukin-12 and Th1 immune response in Crohn’s disease: Pathogenetic relevance and therapeutic inplication

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World Journal of Gastroenterology 2006年第35期12卷 5606-5610页

作者： Ilaria Peluso Francesco Pallone giovanni monteleone Di-partimento di Medicina Interna Università Tor Vergata Rome Italy

Crohn’s disease (CD) and ulcerative colitis (UC) are chronic inflammatory disorders of the gastrointestinal tract that share clinical and pathological characteristics. The most accredited hypothesis is that both CD and UC result from a deregulated mucosal immune response to normal constituents of the gut microflora. Evidence, however, indicates that the main pathological processes in these two diseases are distinct. In CD, the tissue- damaging inflammatory reaction is driven by activated type 1 helper T-cell (Th1), whereas a humoral response predominates in UC. Consistently, a marked accumulation of macrophages making interleukin (IL)-12, the major Th1-inducing factor, is seen in CD but not in UC mucosa. Preliminary studies also indicate that administration of a monoclonal antibody blocking the IL-12/p40 subunit can be useful to induce and maintain clinical remission in CD patients. Notably, the recently described IL-23 shares the p40 subunit with IL-12, raising the possibility that the clinical benefit of the anti-IL-12/p40 antibody in CD may also be due to the neutralization of IL-23 activity. This review summarizes the current information on the expression and functional role of IL-12 and IL- 12-associated signaling pathways both in patients with CD and experimental models of colitis, thus emphasizing major differences between IL-12 and IL-23 activity on the development of intestinal inflammation.

关键词： Interleukin-12 Type 1 helper T-cell cytokines Inflammatory bowel disease

Post-endoscopic retrograde cholangio-pancreatography pancreatitis:Is time for a new preventive approach?

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World Journal of Gastroenterology 2012年第34期18卷 4635-4638页

作者： Stella Tammaro Roberta Caruso Francesco Pallone giovanni monteleone Division of Gastroenterology Azienda Ospedaliera Universitaria84131 SalernoItaly Department of Systems Medicine Division of GastroenterologyUniversity of Rome Tor Vergata00133 RomeItaly

Acute pancreatitis is the most common serious complication of endoscopic retrograde cholangio-pancre-atography (ERCP) and its incidence may exceed 25% in some high-risk patient subsets. In some patients, pancreatitis may follow a severe course with pancreatic necrosis, multiorgan failure, permanent disability and even death. Hence, approaches which minimize both the incidence and severity of post-ERCP pancreatitis are worth pursuing. Pancreatic stents have been used with some success in the prevention of post-ERCP, while so far pharmacological trials have yielded disappointing results. A recent multicenter, randomized, placebo-controlled, double-blind trial has shown that rectally administered indomethacin is effective in reducing the incidence of post-ERCP pancreatitis, the occurrence of episodes of moderate-to-severe pancreatitis and the length of hospital stay in high-risk patients. These results together with the demonstration that rectal administration of indomethacin is not associated with en-hanced risk of bleeding strongly support the use of this drug in the prophylaxis of post-ERCP pancreatitis.

关键词： Endoscopic retrograde cholangiopancrea-tography Post-endoscopic retrograde cholangiopancre-atography pancreatitis Non-steroidal anti-inflammatorydrugs Indomethacin Pancreatitis prevention