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Ethanol injection is highly effective for hepatocellular carcinoma smaller than 2cm

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World Journal of Gastroenterology 2011年第26期17卷 3126-3132页

作者： Maurizio Pompili Erica Nicolardi Valeria Abbate Luca Miele Laura Riccardi Marcello Covino Nicoletta De Matthaeis Antonio Grieco Raffaele Landolfi Gian Ludovico Rapaccini Department of Internal Medicine Università Cattolica del Sacro Cuore Department of Emergency Università Cattolica del Sacro Cuore

AIM： To analyze the long-term prognosis in a cohort of western cirrhotic patients with single hepatocellular carcinoma treated with ethanol injection.METHODS： One-hundred forty-eight patients with solitan/hepatocellular carcinoma were enrolled. The tumor diameter was lower than 2 cm in 47 patients but larger in the remaining 101 patients. The impact of some pre- treatment clinical and laboratory parameters and of tu- mor recurrence on patients＇ survival was assessed.RESULTS： Among the pre-treatment parameters, only a tumor diameter of less than 2 cm was an independent prognostic factor of survival. The occurrence of new nodules in other liver segments and the neoplastic portal invasion were linked to a poorer prognosis at univariate analysis. Patients with a single hepatocellular carcinoma smaller than 2 cm showed a better 5-year cumulative survival （73.0% vs 47.9%）（P = 0.009）, 3-year local re- currence rate （29.1% vs 51.5%）（P = 0.011）, and 5-year distant intrahepatic recurrence rate （52.g% vs 62.8%）（P = 0.054） compared to patients with a larger tumor. CONCLUSION： The 5-year survival rate of patients with single hepatocellular carcinoma 〈 2 cm undergoing ethanol injection is excellent and comparable to that achieved using radiofrequency ablation.

关键词： Hepatocellular carcinoma Cirrhosis Percutaneous ethanol injection Prognosis

Cutaneous manifestations in celiac disease

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World Journal of Gastroenterology 2006年第6期12卷 843-852页

作者： LAbenavoli LLeggio AFerrulli LVonghia GGasbarrini GAddolorato IProietti RCapizzi MRotoli PLAmerio Institute of Internal Medicine Università Cattolica del Sacro Cuore RomeItaly Institute of Internal Medicine università cattolica del sacro cuore RomeItaly Institute of Dermatology UniversitàCattolica del Sacro Cuore RomeItaly

Celiac disease （CD） is an autoimmune gluten-dependent enteropathy characterized by atrophy of intestinal villi that improves after gluten-free diet （GFD）. CD is often associated with extra-intestinal manifestations; among them, several skin diseases are described in CD patients. The present review reports all CD-associated skin manifestations described in the literature and tries to analyze the possible mechanisms involved in this association. The opportunity to evaluate the possible presence of CD in patients affected by skin disorders is discussed.

关键词： Celiac disease Dermatological disease AGA EmA TrG

Changes in cellular mechanical properties during onset or progression of colorectal cancer

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World Journal of Gastroenterology 2016年第32期22卷 7203-7214页

作者： Gabriele Ciasca Massimiliano Papi Eleonora Minelli Valentina Palmieri Marco De Spirito Istituto di Fisica Università Cattolica del Sacro Cuore

Colorectal cancer(CRC) development represents a multistep process starting with specific mutations that affect proto-oncogenes and tumour suppressor *** mutations confer a selective growth advantage to colonic epithelial cells that form first dysplastic crypts, and then malignant tumours and metastases. All these steps are accompanied by deep mechanical changes at the cellular and the tissue level. A growing consensus is emerging that such modifications are not merely a byproduct of the malignant progression, but they could play a relevant role in the cancer onset and accelerate its progression. In this review, we focus on recent studies investigating the role of the biomechanical signals in the initiation and the development of CRC. We show that mechanical cues might contribute to early phases of the tumour initiation by controlling the Wnt pathway, one of most important regulators of cell proliferation in various systems. We highlight how physical stimuli may be involved in the differentiation of non-invasive cells into metastatic variants and how metastatic cells modify their mechanical properties, both stiffness and adhesion, to survive the mechanical stress associated with intravasation, circulation and extravasation. A deep comprehension of these mechanical modifications may help scientist to define novel molecular targets for the cure of CRC.

关键词： Colorectal cancer Biomechanics Pressure Mechanical signalling Atomic force microscopy Wnt

Cancer stem cells in colorectal cancer from pathogenesis to therapy: Controversies and perspectives

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World Journal of Gastroenterology 2014年第4期20卷 923-942页

作者： Caterina Fanali Donatella Lucchetti Marisa Farina Maddalena Corbi Valerio Cufino Achille Cittadini Alessandro Sgambato Istituto di Patologia Generale Università Cattolica del Sacro Cuore

Colorectal cancer remains one of the most common and lethal malignancies worldwide despite the use of various therapeutic strategies. A better understanding of the mechanisms responsible for tumor initiation and progression is essential for the development of novel, more powerful therapies. The traditional, so-called “stochastic model” of tumor development, which assumes that each cancer cell is tumorigenic, has been deeply challenged during the past decade by the identification of cancer stem cells (CSCs), a biologically distinct subset of cells within the bulk of tumor mass. This discovery led to the development of the hierarchical model of tumorigenesis which assumes that only CSCs have the ability to initiate tumor growth, both at primary and metastatic sites. This model implies that the elimination of all CSCs is fundamental to eradicate tumors and that failure to do so might be responsible for the occurrence of relapses and/or metastases frequently observed in the clinical management of colorectal cancer patients. Identification and isolation of CSCs is essential for a better understanding of their role in the tumorigenetic process and for the development of CSC-specific therapies. Several methods have been used for this purpose and many efforts have been focused on the identification of specific CSC-surface markers. This review provides an overview of the proposed roles of CSC in human colorectal tumorigenesis focusing on the most important molecules identified as CSC-specific markers in colorectal cancer and on the potential strategies for the development of CSC-targeted therapy.

关键词： Colorectal cancer Cancer stem cells Tumorigenesis Cancer therapy Prognostic marker

Role of nutraceuticals during the transition period of dairy cows: a review

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Journal of Animal Science and Biotechnology 2021年第1期12卷 64-81页

作者： Vincenzo Lopreiato Matteo Mezzetti Luca Cattaneo Giulia Ferronato Andrea Minuti Erminio Trevisi Department of Animal Sciences Food and NutritionFaculty of AgricultureFood and Environmental ScienceUniversitàCattolica del Sacro Cuore29122 PiacenzaItaly PRONUTRIGEN-Centro di Ricerca Nutrigenomica e Proteomica UniversitàCattolica del Sacro CuorePiacenzaItaly

The transition period of dairy cattle is characterized by a number of metabolic, endocrine, physiologic, and immune adaptations, including the occurrence of negative energy balance, hypocalcemia, liver dysfunction, overt systemic inflammatory response, and oxidative stress status. The degree and length of time during which these systems remain out of balance could render cows more susceptible to disease, poor reproductive outcomes, and less efficient for milk production and quality. Studies on both monogastrics and ruminants have reported the health benefits of nutraceuticals(e.g. probiotics, prebiotics, dietary lipids, functional peptides, phytoextracts) beyond nutritional value, interacting at different levels of the animal's physiology. From a physiological standpoint, it seems unrealistic to disregard any systemic inflammatory processes. However, an alternate approach is to modulate the inflammatory process per se and to resolve the systemic response as quickly as *** this aim, a growing body of literature underscores the efficacy of nutraceuticals(active compounds) during the critical phase of the transition period. Supplementation of essential fatty acids throughout a 2-month period(i.e. a month before and a month after calving) successfully attenuates the inflammatory status with a quicker resolution of phenomenon. In this context, the inflammatory and immune response scenario has been recognized to be targeted by the beneficial effect of methyl donors, such as methionine and choline, directly and indirectly modulating such response with the increase of antioxidants GSH and taurine. Indirectly by the establishment of a healthy gastrointestinal tract, yeast and yeast-based products showed to modulate the immune response, mitigating negative effects associated with parturition stress and consequent *** use of phytoproducts has garnered high interest because of their wide range of actions on multiple tissue targets encompassing a series of anti

关键词： Dairy cow Essential fatty acid Immunometabolism Methyl donor Nutraceuticals Nutrition Peripartum Phytoproduct Yeast culture

Tumor necrosis factor-α inhibitors and chronic hepatitis C:A comprehensive literature review

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World Journal of Gastroenterology 2013年第44期19卷 7867-7873页

作者： Maurizio Pompili Marco Biolato Luca Miele Antonio Grieco Department of Internal Medicine Università Cattolica del Sacro Cuore 8-00168 Roma Italy

Tumor necrosis factor-α(TNF-α)inhibitors are known to increase reactivation of concurrent chronic hepatitis B,but their impact on the hepatitis C virus(HCV)is *** conditions of immunosuppression,such as liver transplantation,typically cause an increase in the rate of HCV *** of TNF-α,a cytokine involved in the apoptotic signaling pathway of hepatocytes infected by HCV,could potentially increase viral *** available clinical data appear to contradict this hypothesis.A review of medical literature revealed that a total of 216 patients with HCV were exposed to one or more treatments with TNF-αinhibitors,with a median observation time of 1.2 years and 260 cumulative patient-years of *** three cases of drug withdrawal due to suspected HCV liver disease recrudescence were *** with TNF-αinhibitors in patients with HCV infection appears to be safe in the short term,but there are insufficient data to assess their long-term *** screening for HCV before beginning treatment with TNF-αinhibitors is currently *** presence of HCV is not a contraindication to therapy with TNF-αinhibitors,with the exception of cirrhotic *** cases of cirrhosis,the benefit/risk ratio should be evaluated at the individual *** to treatment with TNF-αinhibitors,patients with HCV should be referred to a hepatologist to determine the necessity of hepatic disease assessment,using liver biopsy or noninvasive methods,and the potential indication for antiviral *** patients with HCV infection who are treated with TNF-αinhibitors,liver function monitoring every three months is advised.

关键词： Infliximab Etanercept Adalimumab Hepatitis C virus Rheumatoid arthritis Inflammatory bowel disease Psoriasis

Resveratrol corrects aberrant splicing of RYR1 pre-mRNA and Ca2+ signal in myotonic dystrophy type 1 myotubes

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Neural Regeneration Research 2020年第9期15卷 1757-1766页

作者： Massimo Santoro Roberto Piacentini Alessia Perna Eugenia Pisano Anna Severino Anna Modoni Claudio Grassi Gabriella Silvestri IRCCS Fondazione Don Carlo Gnocchi MilanItaly Department of Neuroscience Universita Cattolica del Sacro CuoreRomeItaly Department of Cardiovascular and Thoracic Sciences Universita Cattolica del Sacro CuoreRomeItaly Fondazione Policlinico universitario A.Gemelli IRCCS RomeItaly

Myotonic dystrophy type 1(DM1) is a spliceopathy related to the mis-splicing of several genes caused by sequestration of nuclear transcriptional RNA-binding factors from non-coding CUG repeats of DMPK pre-mRNAs. Dysregulation of ryanodine receptor 1(RYR1), sarcoplasmatic/endoplasmatic Ca^2+-ATPase(SERCA) and α1 S subunit of voltage-gated Ca^2+ channels(Cav1.1) is related to Ca^2+ homeostasis and excitation-contraction coupling impairment. Though no pharmacological treatment for DM1 exists, aberrant splicing correction represents one major therapeutic target for this disease. Resveratrol(RES, 3,5,4′-trihydroxy-trans-stilbene) is a promising pharmacological tools for DM1 treatment for its ability to directly bind the DNA and RNA influencing gene expression and alternative splicing. Herein, we analyzed the therapeutic effects of RES in DM1 myotubes in a pilot study including cultured myotubes from two DM1 patients and two healthy controls. Our results indicated that RES treatment corrected the aberrant splicing of RYR1, and this event appeared associated with restoring of depolarization-induced Ca^2+ release from RYR1 dependent on the electro-mechanical coupling between RYR1 and Cav1.1. Interestingly, immunoblotting studies showed that RES treatment was associated with a reduction in the levels of CUGBP Elav-like family member 1, while RYR1, Cav1.1 and SERCA1 protein levels were unchanged. Finally, RES treatment did not induce any major changes either in the amount of ribonuclear foci or sequestration of muscleblind-like splicing regulator 1. Overall, the results of this pilot study would support RES as an attractive compound for future clinical trials in DM1. Ethical approval was obtained from the Ethical Committee of IRCCS Fondazione Policlinico universitario A. Gemelli, Rome, Italy(rs9879/14) on May 20, 2014.

关键词： alternative splicing calcium homeostasis CUG-BP1 foci MBNL1 myotonic dystrophy type 1 myotubes resveratrol

Management of perianal fistulas in Crohn's disease:An upto-date review

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World Journal of Gastroenterology 2015年第5期21卷 1394-1403页

作者： Manuela Marzo Carla Felice Daniela Pugliese Gianluca Andrisani Giammarco Mocci Alessandro Armuzzi Luisa Guidi IBD Unit Complesso Integrato ColumbusUniversità Cattolica del Sacro Cuore00168 RomeItaly

Perianal disease is one of the most disabling manifestations of Crohn's disease.A multidisciplinary approach of gastroenterologist,colorectal surgeon and radiologist is necessary for its management.A correct diagnosis,based on endoscopy,magnetic resonance imaging,endoanal ultrasound and examination under anesthesia,is crucial for perianal fistula *** medical and surgical therapies are discussedin this review,including new local treatment modalities that are under investigation.

关键词： Crohn’s disease Perianal fistula Surgery Drug ther

Liver toxicity of rosuvastatin therapy

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World Journal of Gastroenterology 2007年第8期13卷 1286-1288页

作者： Giuseppe Famularo Luca Miele Giovanni Minisola Antonio Grieco Internal Medicine San Camillo Hospital RomeItaly Internal Medicine Università Cattolica Sacro Cuore Rome Italy

We report here a case of clinically significant liver toxicity after a brief course of rosuvastatin, which is the first statin approved by the regulatory authorities since the withdrawal of cerivastatin. Whether rosuvastatin has a greater potential compared with other statins to damage the liver is unclear and the involved mechanisms are also unknown. However, rosuvastatin is taken up by hepatocytes more selectively and more efficiently than other statins, and this may reasonably represent an important variable to explain the hepatotoxic potential of rosuvastatin. Our report supports the view that a clinically significant risk of liver toxicity should be considered even when rosuvastatin is given at the range of doses used in common clinical practice.

关键词： Rosuvastatin Liver Toxicity Hepatitis Statins