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Clinical management of advanced gastric cancer: The role of new molecular drugs

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World Journal of Gastroenterology 2014年第40期20卷 14537-14558页

作者： Ferdinando De Vita Natale Di Martino Alessio Fabozzi maria maddalena laterza Jole Ventriglia Beatrice Savastano Angelica Petrillo Valentina Gambardella Vincenzo Sforza Luigi Marano Annamaria Auricchio Gennaro Galizia Fortunato Ciardiello Michele Orditura Division of Medical Oncology Department of Clinical and Experimental Medicine and Surgery Second University of Naples School of Medicine 80131 Naples Italy Ⅷ General and Gastrointestinal Surgery School of Medicine Second University of Naples School of Medicine 80138 Naples Italy Divisions of Surgical Oncology Department of Clinical and Experimental Medicine and Surgery Second University of Naples School of Medicine 80131 Naples Italy

Gastric cancer is the fourth most common malignant neoplasm and the second leading cause of death for cancer in Western countries with more than 20000 new cases yearly diagnosed in the United States. Surgery represents the main approach for this disease but, notwithstanding the advances in surgical techniques, we observed a minimal improvement in terms of overall survival with a significant increasing of relapsing disease rates. Despite the development of new drugs has significantly improved the effectiveness of chemotherapy, the prognosis of patients with unresectable or metastatic gastric adenocarcinoma remains poor. Recently, several molecular target agents have been investigated; in particular, trastuzumab represents the first target molecule showing improvements in overall survival in human epithelial growth factor 2-positive gastric cancer patients. New molecules targeting vascular epithelial growth factor, mammalian target of rapamycin, and anti hepatocyte growth factor-c-Met pathway are also under investigation, with interesting results. Anyway, it seems necessary to select more accurately the population to treat with new agents by the identification of new biomarkers in order to optimize the results. In this paper we review the actual “scenario” of targeted treatments, also focusing on the new agents in development for gastric cancer and gastro-esophageal carcinoma, discussing their efficacy and potential applications in clinical practice.

关键词： Advanced gastric cancer Gastrointestinal cancer Targeted therapy Monoclonal antibodies Tyrosine-kinase inhibitor Gastric cancer

The role of defects association in structural and transport properties of the Ce_(1-x)(Nd_(0.74)Tm_(0.26))_xO_(2-x/2) system

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Journal of Energy Chemistry 2021年第9期30卷 494-502页

作者： Cristina Artini Sabrina Presto Massimo Viviani Sara Massardo maria maddalena Carnasciali Lara Gigli Marcella Pani DCCI Department of Chemistry and Industrial ChemistryUniversity of GenovaVia Dodecaneso 3116146 GenovaItaly Institute of Condensed Matter Chemistry and Technologies for Energy National Research CouncilCNR-ICMATEVia De Marini 616149 GenovaItaly Institute of Condensed Matter Chemistry and Technologies for Energy National Research CouncilCNR-ICMATEc/o DICCA-UNIGEVia all’Opera Pia 1516145 GenovaItaly INSTM Genova Research UnitVia Dodecaneso 3116146 GenovaItaly Elettra-Sincrotrone Trieste S.C.p.A. ss 14km 163.534149 BasovizzaTriesteItaly CNR-SPIN Genova Corso Perrone 2416152 GenovaItaly

An experimental investigation of the crystallographic,Raman and transport properties of the Ce_(1-x)(Nd_(0.74)Tm_(0.26))_xO_(2-x/2)(0.1≤x≤0.6) doped ceria system was performed with the aim of setting out correlations between structural features and ionic conductivity of the *** chosen composition ensures that the average size of the Nd^(3+) and Tm^(3+) doping ions coincides with the one of Sm^(3+);even so,the studied system presents larger cell parameters and a wider compositional extent of the CeO_(2)-based solid solution than Sm-doped ***,the occurrence of two different activation energies to ionic conduction below and above ~750 K determines the existence of two distinct conduction *** described experimental results agree with the formation below the threshold temperature of1 V_O2 Tm'_(Ce) trimers,which promote the incorporation of Nd'_(Ce) isolated defects into the CeO_(2)-based solid *** the high temperature range the dissociation of trimers induces the appearance of a lower activation energy;the extrapolation of its value at infinite dilution provides a result in good accordance with the expected binding energy of 1 V_ORE'_(Ce) dimers,pointing at their stability even in the high temperature conduction regime.

关键词： Solid oxide fuel cells RE-doped ceria High resolution X-ray powder diffraction Rietveld refinement μ-Raman spectroscopy Impedance spectroscopy

Early and long-term postoperative management following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

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World Journal of Gastrointestinal Oncology 2010年第1期2卷 36-43页

作者： Dario Baratti Shigeki Kusamura Barbara laterza maria Rosaria Balestra Marcello Deraco Department of Surgery National Cancer Institute Via Venezian 1

Peritoneal surface malignancies have been traditionally regarded as end-stage conditions amenable to merely palliative options. The combination of aggressive cytoreductive surgery (CRS), involving peritonectomy procedures and multivisceral resections, with intra-operative hyperthermic intra-peritoneal chemotherapy (HIPEC) and/or early postoperative intra-peritoneal chemotherapy (EPIC) to treat the microscopic residual tumor is a new concept. In recent years, promising results have been reported for peritoneal mesothelioma and carcinomatosis of gastrointestinal and gynaecologic origin treated by this combined protocol. However, CRS with HIPEC and/or EPIC is a complex procedure associated with high rates of potentially life-threatening complications. Furthermore, disease progression following comprehensive treatment is not uncommon and represents a relevant cause of treatment failure. The present paper reviews the available information on early postoperative management and long-term follow-up in patients treated with CRS and intraperitoneal chemotherapy. The peculiar clinical and biological alterations that can be expected during an uncomplicated postoperative course, as compared to standard digestive surgery, are discussed. Early recognition and appropriate management of the most common adverse events are addressed, in order to minimize the impact of treatment-related morbidity on survival and quality of life results. Since re-operative surgery with additional HIPEC, has proven to be useful in selected patients with recurrent disease, long-term surveillance aiming at early detection of postoperative disease progression has become a relevant issue. Current results on follow-up investigations are presented.

关键词： Peritoneal surface malignancies Cytoreductive surgery Hyperthermic intraperitoneal chemotherapy Hyperthermic intra-peritoneal chemotherapy Follow-up

Hepatitis C virus micro-elimination:Where do we stand?

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World Journal of Gastroenterology 2021年第16期27卷 1728-1737页

作者： Alessandra Mangia Rosa Cotugno Giovanna Cocomazzi maria maddalena Squillante Valeria Piazzolla Liver Unit Department of Medical SciencesIRCCS Casa Sollievo della SofferenzaSan Giovanni Rotondo 71013FgItaly

Hepatitis C virus (HCV) elimination by 2030, using direct-acting antiviraltreatments, has been promoted by the World Health Organization. Thisachievement is not attainable, however, particularly after the 2020 pandemic ofthe coronavirus disease 2019. Consequently, the more realistic objective ofeliminating HCV from population segments for which targeted strategies ofprevention and treatment are easily attained has been promoted in Europe, as avalid alternative. The underlying idea is that micro-elimination will ultimatelylead to macro-elimination. The micro-elimination strategy may target differentspecific populations and at-risk groups. Different settings, including prisons andhospitals, have also been identified as micro-elimination scenarios. In addition,dedicated micro-elimination strategies have been designed that are tailored at thegeographical level according to HCV epidemiology and individual country’sincome. The main elements of a valid and successful micro-elimination project arereliable epidemiological data and active involvement of all the *** involvement represents another essential component for a successfulprogram.

关键词： Hepatitis C virus antibodies Hepatitis C virus elimination Hepatitis C virus epidemiology Hepatitis C virus RNA Hepatitis C virus diagnosis Hepatitis C virus infection

ABCB1 and ABCB19 auxin transporters have synergistic effects on early and late Arabidopsis anther development

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Journal of Integrative Plant Biology 2015年第12期57卷 1089-1098页

作者： Valentina Cecchetti Patrizia Brunetti Nadia Napoli Laura Fattorini maria maddalena Altamura Paolo Costantino Maura Cardarelli IBPM-CNR Institute of Molecular Biology and Pathology National Research Council Sapienza University of Rome Department of Biology and Biotechnology Sapienza University of Rome Department of Environmental Biology Sapienza University of Rome

Arabidopsis abcbl abcb19 double mutants defective in the auxin transporters ABCB1/PGP1 and ABCB19/PGP19 are altered in stamen elongation, anther dehiscence and pollen maturation. To assess the contribution of these transporters to stamen development we performed phenotypic, histological analyses, and in situ hybridizations on abcbl and abcbl9 single mutant flowers. We found that pollen maturation and anther dehiscence are precocious in the abcbl but not in the abcb19 mutant. Accordingly, endothecium ligniflcation is altered only in abcbl anthers. Both abcbl and abcb1 abcb19 stamens also show altered early development, with asynchronous anther Iocules and a multilayer tapetum. DAPI staining showed that the timing of meiosis is asynchronous in abcbl abcb19 anther Iocules, while only a small percentage of pollen grains are non- viable according to Alexander＇s staining. In agreement, TAM （TARDY ASYNCHRONOUS MEIOSIS）, as well as BAM2 （BARELY ANY MERISTEM）involved in tapetal cell development--areoverexpressed in abcbl abcb19 young flower buds. Corre- spondingly, ABCB1 and ABCB19 mRNA localization supports the observed phenotypes of abcbl and abcbl abcb19 mutant anthers. In conclusion, we provide evidence that auxin transport plays a significant role both in early and late stamen development： ABCB1 plays a major role during anther development, while ABCB19 has a synergistic role.

关键词： Anther development Arabidopsis auxin transport endothecium lignification tapetum differentiation

Pathophysiology and biology of peritoneal carcinomatosis

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World Journal of Gastrointestinal Oncology 2010年第1期2卷 12-18页

作者： Shigeki Kusamura Dario Baratti Nadia Zaffaroni Raffaella Villa Barbara laterza maria Rosaria Balestra Marcello Deraco Department of Surgery National Cancer Institute of MilanVia Venezian 1 Department of Experimental Oncology National Cancer Institute of Milan

Peritoneal carcinomatosis represents a devastating form of cancer progression with a very poor *** complex pathogenesis is represented by a dynamic process comprising several *** the best of our knowledge pathogenesis can be partly explained by 3 major molecular pathways: (1) dissemination from the primary tumor;(2) primary tumor of peritoneum;and (3) independent origins of the primary tumor and peritoneal *** are not mutually exclusive and combinations of different mechanisms could occur inside a single *** are still several aspects which need explanation by future studies.A comprehensive understanding of molecular events involved in peritoneal carcinomatosis is of paramount importance and should be systematically pursued not only to identify novel strategies for the prevention of the condition,but also to obtain therapeutic advances,through the identification of surrogate markers of prognosis and development of future molecular targeted therapies.

关键词： Pathophysiology Peritoneal carcinomatosis Peritoneal mesothelioma Pseudomyxoma peritonei Ovarian cancer Gastric and colorectal cancer

Interaction of major genes predisposing to hepatocellular carcinoma with genes encoding signal transduction pathways influences tumor phenotype and prognosis

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World Journal of Gastroenterology 2008年第43期14卷 6601-6615页

作者： Francesco Feo maddalena Frau Rosa maria Pascale Department of Biomedical Sciences Division of Experimental Pathology and OntologyUniversity of SassariSassari 07100Italy

Studies on rodents and humans demonstrate an inherited predisposition to hepatocellular carcinoma （HCC）. Analysis of the molecular alterations involved in the acquisition of a phenotype resistant or susceptible to hepatocarcinogenesis showed a deregulation of G1 and S phases in HCC of genetically susceptible F344 rats and a G1-S block in lesions of resistant Brown norway （BN） rats. Unrestrained extracellular signal-regulated kinase （ERK） activity linked to proteasomal degradation of dual-specificity phosphatase 1 （DUSP1）, a specific ERK inhibitor, by the CKS1-SKP2 ubiquitin ligase complex occurs in more aggressive HCC of F344 rats and humans. This mechanism is less active in HCC of BN rats and human HCC with better prognosis. Upregulation of iNos cross-talk with IKK/NF-KB and RAS/ERK pathways occurs in rodent liver lesions at higher levels in the most aggressive models represented by HCC of F344 rats and c-Myc-TGF-α transgenic mice. iNOS, IKK/NF-κB, and RAS/ERK upregulation is highest in human HCC with a poorer prognosis and positively correlates with tumor proliferation, genomic instability and microvascularization, and negatively with apoptosis. Thus, cell cycle regulation and the activity of signal transduction pathways seem to be modulated by HCC modifier genes, and differences in their efficiency influence the susceptibility to hepatocarcinogenesis and probably the prognosis of human HCC.

关键词： Hepatocarcinogenesis Genetic predisposition Polygenic disease, Redifferentiation Signal transduction pathways Cell cycle Cell proliferation Apoptosis Proteasomal degradation

Nodular lymphoid hyperplasia: A marker of low-grade inflammation in irritable bowel syndrome?

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World Journal of Gastroenterology 2016年第46期22卷 10198-10209页

作者： Anna Chiara Piscaglia Lucrezia laterza Valentina Cesario Viviana Gerardi Rosario Landi Loris Riccardo Lopetuso Giovanni Calò Giovanna Fabbretti Massimo Brisigotti maria Loredana Stefanelli Antonio Gasbarrini Endoscopy and Gastroenterology Unit Depatment of Internal Medicine State Hospital School of Gastroenterology Dept. of Internal Medicine and Gastroenterology "Gemelli" Hospital Catholic University Depatment of Pathology "Infermi" Hospital

AIM To evaluate the prevalence of nodular lymphoid hyperplasia(NLH) in adult patients undergoing colonoscopy and its association with known diseases. METHODS We selected all cases showing NLH at colonoscopy in a three-year timeframe, and stratified them into symptomatic patients with irritable bowel syndrome(IBS)-type symptoms or suspected inflammatory bowel disease(IBD), and asymptomatic individuals undergoing endoscopy for colorectal cancer *** collection included medical history and final diagnosis. As controls, we considered all colonoscopies performed for the aforementioned indications during the same *** One thousand and one hundred fifty colonoscopies were selected. NLH was rare in asymptomatic individuals(only 3%), while it was significantly more prevalent in symptomatic cases(32%). Among organic conditions associated with NLH, the most frequent was IBD, followed by infections and diverticular disease. Interestingly, 31% of IBS patients presented diffuse colonic NLH. NLH cases shared some distinctive clinical features among IBS patients: they were younger, more often female, and had a higher frequency of abdominal pain, bloating, diarrhoea, unspecific inflammation, self-reported lactose intolerance and metal contact dermatitis. CONCLUSION About 1/3 of patients with IBS-type symptoms or suspected IBD presented diffuse colonic NLH, which could be a marker of low-grade inflammation in a conspicuous subset of IBS patients.

关键词： Inflammatory bowel diseases Functional gastrointestinal diseases Irritable bowel syndrome Colonoscopy Inflammation

Genetic analysis of Italian patients with congenital tufting enteropathy

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世界儿科杂志:英文版 2016年第2期12卷 219-224页

作者： maria d'Apolito Daniela Pisanelli Flavio Faletra Ida Giardino maddalena Gigante Massimo Pettoello-Mantovani Olivier Goulet Paolo Gasparini Angelo Campanozzi Unit of Pediatrics Department of Medical and Surgical SciencesUniversity of FoggiaItaly Institute for Maternal and Child Health-IRCCS"BurloGarofolo" TriesteItaly Laboratory Medicine Department of Clinical and Experimental MedicineUniversity of FoggiaFoggiaItaly Department of Medical and Surgical Sciences University of FoggiaFoggiaItaly Department of Pediatric Gastroenterology-Hepatology and Nutrition and Reference Center for Rare Digestive Disease Hopital Necker-EnfantsMaladesParisFrance

Background:Congenital tufting enteropathy(CTE),an inherited autosomal recessive rare disease,is a severe diarrhea of infancy which is clinically characterized by absence of infl ammation and presence of intestinal villous *** in the EpCAM gene were identified to cause *** cases of syndromic tufting enteropathy harboring the SPINT2(19q13.2)mutation were ***:Four CTE Italian patients were clinically and immunohistochemically *** DNA sequencing of EpCAM and SPINT2 genes was ***:All patients were of Italian *** different mutations were detected(***219Metfs*15,Tyr186Phefs*6 and ***146Asn)in the EpCAM gene;one of them is novel(***146Asn).Two patients(P1 and P2)showed compound heterozygosity revealing two mutations in separate alleles.A third patient(P3)was heterozygous for only one novel EpCAM missense mutation(***146Asn).In a syndromic patient(P4),no deleterious EpCAM mutation was *** SPINT2 mutational analysis was performed.P4 showed a homozygous SPINT2 mutation(p.Y163C).No SPINT2 mutation was found in ***7 was also evaluated as a candidate gene by mutational screening in P3 but no mutation was identifi ***:This study presented a molecular characterization of CTE Italian patients,and identified three mutations in the EpCAM gene and one in the SPINT2 *** of EpCAM mutations was novel,therefore increasing the mutational spectrum of allelic variants of the EpCAM *** analysis of the SPINT2 gene also allowed us to identify a SPINT2 substitution mutation(c.488A>G)recently found to be associated with syndromic CTE subjects.

关键词： diarrhea gastroenterology gene mutation