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Molecular targeting agents associated with transarterial chemoembolization or radiofrequency ablation in hepatocarcinoma treatment

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World Journal of Gastroenterology 2014年第2期20卷 486-497页

作者： Girolamo Ranieri ilaria marech Vito Lorusso Veronica Goffredo Angelo Paradiso Domenico Ribatti Cosmo Damiano Gadaleta Interventional Radiology Unit with Integrated Section of Translational Medical Oncology National Cancer Research CentreCancer Institute "Giovanni Paolo Ⅱ"70124 BariItaly Medical Oncology Unit National Cancer Research CentreCancer Institute "Giovanni Paolo Ⅱ"70124 BariItaly Medical Oncology with Experimental Unit National Cancer Research CentreCancer Institute "Giovanni Paolo Ⅱ"70124 BariItaly Department of Basic Medical Sciences Neurosciences and Sensory OrgansSection of Human Anatomy and HistologyUniversity of Bari70124 BariItaly

Hepatocellular carcinoma(HCC)is the fifth most common cause of cancer in the *** to Barcelona Clinic Liver Cancer modified criteria,patients with early stage disease are candidate to radiofrequency ablation(RFA),while patients with intermediate stage HCC are usually treated by transarterial chemoembolization(TACE).TACE and RFA induce a transient devascularisation effect followed by strong neoangiogenic *** fact,after these procedures,it has been demonstrated an up-regulation of pro-angiogenic and growth factors such as vascular endothelial growth factor-A,which might contribute to accelerated progression in patients with incomplete *** studies have demonstrated that MAP-kinase and AKT pathways,in addition to neo-angiogenesis,have an important role in the development of *** advanced HCC,anti-angiogenic therapy and tyrosine kinases inhibitors showed potential clinical ***,a number of clinical studies are ongoing testing these agents in combination with TACE or *** this paper,we have reviewed the most recent preclinical and clinical results of such trials.

关键词： Hepatocellular carcinoma Molecular targeting agents Angiogenesis Chemoembolization therapeutic Radiofrequency treatment Sorafenib

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Possible biological and translational significance of mast cells density in colorectal cancer

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World Journal of Gastroenterology 2014年第27期20卷 8910-8920页

作者： ilaria marech Michele Ammendola Claudia Gadaleta Nicola Zizzo Caroline Oakley Cosmo Damiano Gadaleta Girolamo Ranieri Interventional Radiology Unit with Integrated Section of Translational Medical Oncology National Cancer Research Centre Istituto Tumori "Giovanni Paolo Ⅱ" 70124 BariItaly Department of Clinical Surgery University of Catanzaro "Magna Graecia" Medical School 88100 Catanzaro Italy Department of Pathology Veterinary Medical School University of Bari Valenzano 70010 Bari Italy

Mast cells (MCs), located ubiquitously near blood vessels, are descended from CD34+ hematopoietic stem cells. Initially, although their role has been well defined in hypersensitivity reactions, the discovery of their sharing in both innate and adaptive immunity has allowed to redefine their crucial interplay on the regulatory function between inflammatory and tumor cells through the release of mediators granule-associated (mainly tryptase and vascular endothelial growth factor). In particular, in several animal and human malignancies it has been well demonstrated that activated c-Kit receptor (c-KitR) and tryptase (an agonist of the proteinase-activated receptor-2) take pivotal part in tumor angiogenesis after the MCs activation, contributing to tumor cells invasion and metastasis. In this review, we focused on crucial MCs density (MCD) role in colorectal cancer (CRC) development and progression angiogenesis-mediated; then, we will analyze the principal studies that have focused on MCD as possible prognostic factor. Finally, we will consider a possible role of MCD as novel therapeutic target mainly by c-KitR tyrosine kinase inhibitors (imatinib, masitinib) and tryptase inhibitors (gabexate and nafamostat mesylate) with the aim to prevent CRC progression.

关键词： Tryptase Mast cell density Proteinase-activated receptor-2 c-Kit receptor Vascular endothelial growth factor Angiogenesis Colorectal cancer Tumor progression Tryptase inhibitors c-Kit receptor tyrosine kinase inhibitors

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Lapatinib, a TKI Dual Inhibitor of Her1 and Her2 Receptors: Review of the Literature

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Journal of Cancer Therapy 2012年第6期3卷 1132-1139页

作者： Vito Lorusso ilaria marech Marianna Giampaglia Antonio Gnoni Andrea Tinelli Gynecology and Obstetrics Department Vito Fazzi Hospital Lecce Italy. Medical Oncology Unit Vito Fazzi Hospital Lecce Italy National Cancer Research Center Medical Oncology Unit Istituto Tumori “Giovanni Paolo II” Bari Italy

Lapatinib ditosylate (Tyverb?) is a potent and selective oral dual receptor tyrosine kinase inhibitor (TKI), preventing autophosphorylation of epidermal growth factor receptor (EGFR/ErbB1) and human epidermal growth factor receptor 2 (HER2/ErbB2) intracellular domain. This interference blocks the Ras/Raf MAPKs and PI3K/Akt pathways, that lead to uncontrolled cellular proliferation and survival. After the demonstration of its effectiveness and safety in HER2-overexpressed breast cancer, in 2007 the US Food and Drug Administration (FDA) approved this molecule in combination with capecitabine, in patients with locally advanced or metastatic disease, that progressed after previous treatment with anthracyclines, taxanes and trastuzumab. In 2010, Lapatinib received approval for the treatment of postmenopausal women with hormone receptor positive metastatic breast cancer in combination with letrozole. The most common adverse events (AE) are: anorexia, insomnia, diarrhea and skin rash and mild cardiovascular toxicity. This paper reviews the most important studies on Lapatinib in advanced breast cancer. However, promising results were recently reported on this drug, also in adjuvant setting and in combination with other target drugs, which warrant further investigation for the future.

关键词： Lapatinib Tyverb^(■) HER2 Breast Cancer TKI

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Vascular endothelial growth factor and tryptase changes after chemoembolization in hepatocarcinoma patients

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World Journal of Gastroenterology 2015年第19期21卷 6018-6025页

作者： Girolamo Ranieri Michele Ammendola ilaria marech Annamaria Laterza Ines Abbate Caroline Oakley Angelo Vacca Rosario Sacco Cosmo Damiano Gadaleta Diagnostic and Interventional Radiology Unit with Integrated Section of Translational Medical Oncology National Cancer Research Centre Department of Medical and Surgical Sciences Clinical Surgery Unit University of "Magna Graecia" Department of Experimental Oncology Laboratory of Analyses Cancer Institute "Giovanni Paolo II" Department of Internal Medicine and Clinical Oncology University of Bari Medical School

AIM: To evaluate vascular endothelial growth factor(VEGF) and tryptase in hepatocellular cancer(HCC)before and after trans-arterial chemoembolization(TACE).METHODS: VEGF and tryptase serum concentrations were assessed from 71 unresectable HCC patients before and after hepatic TACE performed by binding DC-Beads?to doxorubicin. VEGF levels were examined for each serum sample using the Quantikine Human VEGF-enzyme-linked immuno-absorbent assay(ELISA),whereas tryptase serum concentrations were assessed for each serum sample by means of fluoro-enzyme immunoassay(FEIA) using the Uni-CAP100 *** between serum VEGF and tryptase values before and after TACE were evaluated using Student t test. Person's correlation was used to assess the degree of association between the two ***: VEGF levels and serum tryptase in HCCpatients before TACE had a mean value and standard deviation(SD) of 114.31 ± 79.58 pg/mL and 8.13± 3.61 μg/L, respectively. The mean levels and SD of VEGF levels and serum tryptase in HCC patients after TACE were 238.14 ± 109.41 pg/mL and 4.02 ±3.03 μg/L. The changes between the mean values of concentration of VEGF and tryptase before treatment and after treatment was statistically significant(P <0.000231 and P < 0.00124, by Wilcoxon-Mann-Whitney respectively). A significant correlation between VEGF levels before and after TACE and between tryptase levels before and after TACE was demonstrated(r =0.68, P = 0.003; r = 0.84, P = 0.000 respectively).CONCLUSION: Our pilot results suggest that the higher serum VEGF levels and the lower tryptase levels following TACE may be potential biomarkers changing in response to therapy.

关键词： Serum levels Tryptase Vascular endothelialgrowth factor Hepatocellular cancer Chemoembolization

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Disentangling brain PrP^(C)proteoforms and their roles in physiology and disease

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Neural Regeneration Research 2024年第5期19卷 963-965页

作者： ilaria Vanni Nonno Romolo Department of Food Safety Nutrition and Veterinary Public HealthIstituto Superiore di SanitàRomeItaly

The cellular prion protein(PrPC),a cell surface glycoprotein of 209 amino acids,has been considerably studied over the decades mainly due to its critical involvement in transmissible spongiform encephalopathies,or prion ***,it is the misfolding and aggregation of PrPC into pathological assemblies-named PrPSc-that constitute prions,the agents causing these unusual neurodegenerative diseases affecting humans and animals(Prusiner,1982).Furthermore,increasing evidence support its relevance also in other neurodegenerative diseases(NDDs),such as Alzheimer’s and Parkinson’s diseases(Corbett et al.,2020).

关键词： diseases involvement glycoprotein

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Targeting mast cells in gastric cancer with special reference to bone metastases

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World Journal of Gastroenterology 2015年第37期21卷 10493-10501页

作者： Christian Leporini Michele Ammendola ilaria marech Giuseppe Sammarco Rosario Sacco Cosmo Damiano Gadaleta Caroline Oakley Emilio Russo Giovambattista De Sarro Girolamo Ranieri Department of Health Science Clinical Pharmacologyand Pharmacovigilance Unit and Pharmacovigilance’s Centre Calabria Region University of Catanzaro "Magna Graecia"Medical School Department of Medical and Surgery Sciences Clinical Surgery Unit University of Catanzaro "Magna Graecia" Medical School Diagnostic and Interventional Radiology Unit with Integrated Section of Translational Medical Oncology National Cancer Research Centre

Bone metastases from gastric cancer(GC) are considered a relatively uncommon finding; however, they are related to poorer prognosis. Both primary GC and its metastatic progression rely on angiogenesis. Several lines of evidence from GC patients strongly support the involvement of mast cells(MCs) positive to tryptase(MCPT) in primary gastric tumor angiogenesis. Recently,we analyzed infiltrating MCs and neovascularization in bone tissue metastases from primary GC patients, and observed a significant correlation between infiltrating MCPT and angiogenesis. Such a finding suggested the involvement of peritumoral MCPT by infiltrating surrounding tumor cells, and in bone metastasis angiogenesis from primary GC. Thus, an MCPT-stimulated angiogenic process could support the development of metastases in bone tissue. From this perspective, we aim to review the hypothetical involvement of tumorinfiltrating,peritumoral MCPT in angiogenesis-mediated GC cell growth in the bone microenvironment and in tumor-induced osteoclastic bone resorption. We also focus on the potential use of MCPT targeting agents,such as MCs tryptase inhibitors(gabexate mesylate,nafamostat mesylate) or c-KitR tyrosine kinase inhibitors(imatinib, masitinib), as possible new anti-angiogenic and anti-resorptive strategies for the treatment of GC patientsaffected by bone metastases.

关键词： Bone metastases Gastric cancer receptor activator

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Frequency stabilization of C-band semiconductor lasers through a SiN photonic integrated circuit

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Photonics Research 2024年第8期12卷 1619-1626页

作者： ALESSANDRO BRUGNONI ALI EMRE KAPLAN VALERIO VITALI KYLE BOTTRILL MICHELE RE PERIKLIS PETROPOULOS COSIMO LACAVA ilaria CRISTIANI Photonics Group Department of ElectricalComputer and Biomedical EngineeringUniversity of PaviaPavia 27100Italy Optoelectronics Research Centre University of SouthamptonSouthampton SO171BJUK Huawei Technologies Italia S.r.l Centro direzionale MilanoSegrate 20054Italy

Integrated semiconductor lasers represent essential building blocks for integrated optical components and circuits and their stability in frequency is fundamental for the development of numerous frontier applications and engineering *** dense optical circuits are considered,the stability of integrated laser sources can be impaired by the thermal cross-talk generated by the action of neighboring components,leading to a deterioration of the long-term system performance(on the scale of seconds).In this work we show the design and the experimental characterization of a silicon nitride photonic integrated circuit(PIC)that is able to frequency stabilize 16semiconductor lasers,simultaneously.A stabilized 50 GHz-spaced two-channel system is demonstrated through the detection of the related beating note and the stability of the resulting waveform is characterized via the use of artificially induced thermal cross-talk stimuli.

关键词： stabilization stability impaired

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Advancing immunosuppression in liver transplantation: A narrative review

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Hepatobiliary & Pancreatic Diseases International 2024年第5期23卷 441-448页

作者： Samuele Iesari Francesca Laura Nava ilaria Elena Zais Laurent Coubeau Mariano Ferraresso Evaldo Favi Jan Lerut General Surgery and Kidney Transplantation Fondazione IRCCS Ca’Granda Ospedale Maggiore Policlinico15 Via della Commenda20122 MilanItaly Institut de Recherche Expérimentale et Clinique Universitécatholique de Louvain10 Avenue Hippocrate1200 BrusselsBelgium Service de Chirurgie et Transplantation Abdominale Cliniques Universitaires Saint-Luc55 Avenue Hippocrate1200 BrusselsBelgium Department of Clinical Sciences and Community Health Universitàdegli Studi di Milano19 Via della Commenda20122 MilanItaly

Immunosuppression is essential to ensure recipient and graft survivals after liver transplantation(LT). However, our understanding and management of the immune system remain suboptimal. Current immunosuppressive therapy cannot selectively inhibit the graft-specific immune response and entails a significant risk of serious side effects, i.e., among others, de novo cancers, infections, cardiovascular events, renal failure, metabolic syndrome, and late graft fibrosis, with progressive loss of graft function. Pharmacological research, aimed to develop alternative immunosuppressive agents in LT, is behind other solidorgan transplantation subspecialties, and, therefore, the development of new compounds and strategies should get priority in LT. The research trajectories cover mechanisms to induce T-cell exhaustion, to inhibit co-stimulation, to mitigate non-antigen-specific inflammatory response, and, lastly, to minimize the development and action of donor-specific antibodies. Moreover, while cellular modulation techniques are complex, active research is underway to foster the action of T-regulatory cells, to induce tolerogenic dendritic cells, and to promote the function of B-regulatory cells. We herein discuss current lines of research in clinical immunosuppression, particularly focusing on possible applications in the LT setting.

关键词： Liver transplantation Immunosuppression Drug development Long-term results Clinical operational tolerance

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Does the provision of live black soldier fly and yellow mealworm larvae improve Muscovy duck welfare?

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Journal of Animal Science and Biotechnology 2024年第1期15卷 442-455页

作者： Marta Gariglio Sihem Dabbou Manuela Renna ilaria Biasato Sara Bellezza Oddon Marco Meneguz Raul Daniel Miazzo Stefania Bergagna Elena Colombino Elisabetta Macchi Achille Schiavone Department of Veterinary Sciences University of TurinLargo Paolo Braccini 2GrugliascoTorino(TO)10095Italy Center Agriculture Food Environment(C3A) University of TrentoVia Edmund Mach 1San Michele All’AdigeTrento(TN)38098Italy Department of Agricultural Forest and Food SciencesUniversity of TurinLargo Paolo Braccini 2GrugliascoTorino(TO)10095Italy BEF Biosystems s.r.l Via Tancredi Canonico 18/CTorino(TO)10156Italy Unidad de Investigacion Aviar Produccion AvicolaFac.Agr.y Vet.Universidad Nacional de Rio CuartoCordobaArgentina Veterinary Medical Research Institute for Piemonte Liguria and Valle d’AostaVia Bologna 148Torino(TO)10154Italy

Background The provision of environmental enrichments to Muscovy ducks could reduce the expression of the aggressive *** aim of the present study was to evaluate the effects of black soldier fly(BSF)and yellow mealworm(YM)live larva provision on Muscovy duck performance,excreta corticosterone metabolites(ECM),behavior,and blood *** A total of 1263-day-old female Muscovy ducklings were allotted to 18 pens(6 replicates/treatment,7 birds/pen)and assigned to 3 experimental treatments:a control group fed commercial feed,and two experimental treatments fed commercial feed plus the 5%(based on the expected daily feed intake,as fed basis)of BSF and YM live larvae(BSF and YM groups,respectively).A two-phase feeding program was applied:starter(from 3 to 31 days of age)and grower-finisher(from 32 to 55 days of age).The live weight,average daily gain,average daily feed intake,and feed conversion ratio were *** consumption times were collected,and video recordings were performed during 3 periods(P)each day:the hour before(P1),during(P2),and after(P3)the larva *** were evaluated at 3,31,and ***,the total red and white blood cell counts,serum proteins,lipids,and liver and renal function serum enzymes were evaluated on 12 birds/*** The experimental treatment did not affect the growth performance of the birds(P>0.05).Larva consumption times were always similar between the two insect species,except at 14–18 days of age,were BSF larvae were consumed faster than YM larvae(PP3;P<0.05).Finally,the provision of live BSF and YM larvae significantly reduced the ECM at 55 days of age and the heterophil to lymphocyte ratio(P<0.05).Conclusions Live BSF and YM larva supplementatio

关键词： Behavior Cairina moschata Environmental enrichment Hermetia illucens Poultry Tenebrio molitor Welfare

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Multifaceted superoxide dismutase 1 expression in amyotrophic lateral sclerosis patients:a rare occurrence?

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Neural Regeneration Research 2025年第1期20卷 130-138页

作者： ilaria Martinelli Jessica Mandrioli Andrea Ghezzi Elisabetta Zucchi Giulia Gianferrari Cecilia Simonini Francesco Cavallieri Franco Valzania Department of Neurosciences Azienda Ospedaliero Universitaria di ModenaModenaItaly Clinical and Experimental Medicine Ph.D.Program University of Modena and Reggio EmiliaModenaItaly Department of Biomedical Metabolic and Neural SciencesUniversity of Modena and Reggio EmiliaModenaItaly Neurology Unit Neuromotor&Rehabilitation DepartmentAzienda USL-IRCCS di Reggio EmiliaReggio EmiliaItaly

Amyotrophic lateral sclerosis(ALS)is a neuromuscular condition resulting from the progressive degeneration of motor neurons in the cortex,brainstem,and spinal *** the typical clinical phenotype of ALS involves both upper and lower motor neurons,human and animal studies over the years have highlighted the potential spread to other motor and non-motor regions,expanding the phenotype of *** superoxide dismutase 1(SOD1)mutations represent a minority of ALS cases,the SOD1 gene remains a milestone in ALS research as it represents the first genetic target for personalized *** numerous single case reports or case series exhibiting extramotor symptoms in patients with ALS mutations in SOD1(SOD1-ALS),no studies have comprehensively explored the full spectrum of extramotor neurological manifestations in this *** this narrative review,we analyze and discuss the available literature on extrapyramidal and non-motor features during *** multifaceted expression of SOD1 could deepen our understanding of the pathogenic mechanisms,pointing towards a multidisciplinary approach for affected patients in light of new therapeutic strategies for SOD1-ALS.

关键词： amyotrophic lateral sclerosis(ALS) autonomic extramotor genotype-phenotype multisystem involvement Parkinson’s disease sensory SOD1 superoxide dismutase 1 urinary vocal cord palsy

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