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Chemotherapy for Hepatocellular Carcinoma: Current Evidence and Future Perspectives

Journal of Clinical and Translational Hepatology 2017年第3期5卷 235-248页

作者： Emanuele Rinninella lucia Cerrito Irene Spinelli Marco Cintoni maria Cristina Mele Maurizio Pompili Antonio Gasbarrini Internal Medicine and Gastroenterology Unit Gastroenterology Area Fondazione Policlinico Universitario Agostino GemelliCatholic University of Sacred Heart Rome Italy Clinical Nutrition Unit Gastroenterology Area Fondazione Policlinico Universitario Agostino Gemelli Catholic University of Sacred Heart Rome Italy Internal Medicine and Gastroenterology Unit Gastroenterology Area Fondazione Policlinico Universitario Agostino GemelliCatholic University of Sacred Heart Rome Italy Clinical Nutrition Unit Gastroenterology Area Fondazione Policlinico Universitario Agostino Gemelli Catholic University of Sacred Heart Rome Italy

Hepatocarcinogenesis is a multistep process,heralded by abnormalities in cell differentiation and proliferation and sustained by an aberrant *** the underlying molecular pathogenesis leading to hepatocellular carcinoma is a prerequisite to develop new drugs that will hamper or block the steps of these *** hepatocellular carcinoma has higher arterial vascularization than normal liver,this could be a good target for novel molecular *** of the antiangiogenic drug sorafenib into clinical practice since 2008 has led to new perspectives in the management of this *** importance of this drug lies not only in the modest gain of patients' survival,but in having opened a roadmap towards the development of new molecules and ***,after the introduction of sorafenib,during the last years,a wide number of clinical trials on antiangiogenic therapies failed in achieving significant ***,many of these trials are still ongoing and promise to improve overall survival and progression-free survival.A recent clinical trial has proven regorafenib effective in patients showing tumor progression under sorafenib,thus opening new interesting therapeutic *** other expectations have been borne from the discovery of the immune checkpoint blockade,already known in other solid ***,a potential role in hepatocellular carcinoma therapy may derive from the use of branched-chain amino acids and of nutritional *** review analyses the biomolecular pathways of hepatocellular carcinoma and the ongoing studies,the actual evidence and the future perspectives concerning drug therapy in this open field.

关键词： Hepatocellular carcinoma Molecular target therapies Immunotherapy Branched-chain amino acids

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Titanium dioxide induced inflammation in the small intestine

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World Journal of Gastroenterology 2012年第34期18卷 4729-4735页

作者： Carolina Maciel Nogueira Walter Mendes de Azevedo maria lucia Zaidan Dagli Sérgio Hiroshi Toma AndréZonetti de Arruda Leite maria Laura Lordello Iêda Nishitokukado Carmen Lúcia Ortiz-Agostinho maria IrmaSeixas Duarte Marcelo Alves Ferreira Aytan Miranda Sipahi Department of Gastroenterology Laboratory of Clinical and Experimental Gastroen-terologySchool of MedicineUniversity of So PauloCerqueira César01246-900 So PauloBrazil Department of Fundamental Chemistry Federal University of PernambucoCidade Universitária50670-901 RecifeBrazil Department of Pathology Veterinary Medicine SchoolUniversity of So PauloCidade Universitária05508-270 So PauloBrazil Laboratory of Supramolecular Chemistry and Nanotechnology Chemistry InstituteUniversity of So PauloCidade Universitária05513-970 So PauloBrazil Laboratory of Transmissible Disease Medicine SchoolUniversity of So PauloCerqueira César01246-900 So PauloBrazil Laboratory of Cellular Biology Medicine SchoolUniversity of So PauloCerqueira César01246-900 So PauloBrazil

AIM:To investigate the effects of titanium dioxide (TiO2) nanoparticles (NPTiO 2 ) and microparticles (MPTiO 2 ) on the inflammatory response in the small intestine of mice. METHODS: Bl 57/6 male mice received distilled water suspensions containing TiO 2 (100 mg/kg body weight) as NPTiO 2 (66 nm), or MPTiO 2 (260 nm) by gavage for 10 d, once a day; the control group received only distilled water. At the end of the treatment the duodenum, jejunum and ileum were extracted for assessment of cytokines, inflammatory cells and titanium content. The cytokines interleukin (IL)-1b, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, IL-17, IL-23, tumor necrosis factor-α (TNF-α), intracellular interferon-γ (IFN-γ) and transforming growth factor-β (TGF-β) were evaluated by enzyme-linked immunosorbent assay in segments of jejunum and ileum (mucosa and underlying muscular tissue). CD4 + and CD8 + T cells, natural killer cells, and dendritic cells were evaluated in duodenum, jejunum and ileum samples fixed in 10% formalin by immuno-histochemistry. The titanium content was determined by inductively coupled plasma atomic emission spectrometry. RESULTS: We found increased levels of T CD4 + cells (cells/mm 2 ) in duodenum:NP 1240 ± 139.4, MP 1070 ± 154.7 vs 458 ± 50.39 (P < 0.01); jejunum:NP 908.4 ± 130.3, MP 813.8 ± 103.8 vs 526.6 ± 61.43 (P < 0.05); and ileum:NP 818.60 ± 123.0, MP 640.1 ± 32.75 vs 466.9 ± 22.4 (P < 0.05). In comparison to the control group, the groups receiving TiO 2 showed a statistically significant increase in the levels of the inflammatory cytokines IL-12, IL-4, IL-23, TNF-α, IFN-γ and TGF-β. The cytokine production was more pronounced in the ileum (mean ± SE):IL-12: NP 33.98 ± 11.76, MP 74.11 ± 25.65 vs 19.06 ± 3.92 (P < 0.05); IL-4: NP 17.36 ± 9.96, MP 22.94 ± 7.47 vs 2.19 ± 0.65 (P < 0.05); IL-23: NP 157.20 ± 75.80, MP 134.50 ± 38.31 vs 22.34 ± 5.81 (P < 0.05); TNFα: NP 3.71 ± 1.33, MP 5.44 ± 1.67 vs 0.99± 019 (P < 0.05); IFNγ: NP 15.85 ± 9.99, MP 34.08 ± 11.44 vs 2.81 ±

关键词： Titanium dioxide Microparticles Nanopar-tides Immune response Small intestine Mice

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Effect of Carbonation on Microbiologic Parameters of Refrigerated Bovine Raw Milk

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Journal of Food Science and Engineering 2013年第10期3卷 557-563页

作者： marianne Ayumi Shirai maria lucia Masson Department of Food Technology and Engineering Universidade Tecnol6gica Federal do Parancl Via Rosalina Maria dos SantosCampo Mour6o 87031-899 Brazil Department of Chemical Engineering Universidade Federal do Parana Curitiba 81531-980 Brazil

This study evaluated the effect of carbon dioxide addition on microbiological quality during refrigerated storage of raw milk collected in Curitiba city, brazil. A three factor-two level full factorial design was used to investigate the effect of the pH （5.8-6.4）, storage time （0-10 days） and storage temperature （5-10 ℃）, on the responses, namely, mesophiles, psychrotrophs, lipolytic psychrotrophs and proteolytic psychrotrophs counts. Results showed that increase in pH and storage time had significant effect on the microbial count. No significant effect of storage temperature was observed for all the microorganisms studied. All responses were well predicted by selected mathematical models, as denoted by coefficient of determination above 0.95.

关键词： Carbon dioxide microbiology shelf life bovine raw milk storage.

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Assessment of Genetic Stability Among In Vitro Plants of Arachis retusa Using RAPD and AFLP Markers for Germplasm Preservation

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Journal of Integrative Plant Biology 2007年第3期49卷 307-312页

作者： Rachel Fatima Gagliardi Luiz Ricardo Hanai Georgia Pacheco Carlos Alberto Oliveira Leonardo Alves Carneiro José Francisco Montenegro Valls Elisabeth Mansur maria lucia Carneiro Vieira Laboratório de Micropropagacao e Transformacao de Plantas Universidade do Estado do Rio de Janeiro postal code 20550-013 Maracana Rio de Janeiro Brazil Departamento de Genética - Escola Superior de Agricultura Luiz de Queiroz Universidade de Sao Paulo postal code 13418-900 Piracicaba Brazil Embrapa Recursos Genéticos e Biotecnologia postal code 70770-901 Brasilia Brazil

Arachis retusa Krapov. et W. C. Gregory et Valls is endemic in the West-central region of brazil, occurring In areas endangered by human actions. The establishment of in vitro preservation methods for wild species of Arachis is an alternative to seed banks for germplasm storage, multiplication and distribution. The risk of genetic changes Induced by tissue culture and the monitoring of the genetic stability of the biological material before, during and after storage must be considered In the context of conservation. Random amplified polymorphlc ONA （RAPO） and amplified fragment length polymorphism （AFLP） fingerprinting were used to evaluate the genetic stability of in vitro plants originated from cotyledons and embryo axes of A. retusa. Cotyledons originated shoots through direct organogenesls and embryo axes displayed muItishoot formation Induced by 110 mmol/L and 8.8 mmol/L BAP, respectively. Ninety genomlc regions （loci） generated from RAPO and 372 from AFLP analyses were evaluated. All amplified fragments detected by both techniques in plants derived from the two explant types were monomorphic. The results Indicate that the recovered shoots are genetically stable at the assessed genomic regions.

关键词： amplified fragment length polymorphism Arachis retusa in vitro preservation micropropagation random amplifiedpolymorphic DNA somaclonal variation

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Coupling effects in QD dimers at sub-nanometer interparticle distance

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Nano Research 2020年第4期13卷 1071-1080页

作者： Carlo Nazareno Dibenedetto Elisabetta Fanizza Rosaria Brescia Yuval Kolodny Sergei Remennik Annamaria Panniello Nicoletta Depalo Shira Yochelis Roberto Comparelli Angela Agostiano maria lucia Curri Yossi Paltiel Marinella Striccoli CNR-Istituto per i Processi Chimico-Fisici SS Bari Via Orabona 470125-BariItaly Dipartimento di Chimica Universita degli Studi di Bari Aldo MoroVia Orabona 470125-BariItaly Electron Microscopy Facility Istituto Italiano di Tecnologiavia Morego 3016163 GenovaItaly Department of Applied Physics and the Center for Nanoscience and Nanotechnology Hebrew University of JerusalemJerusalem 9190401Israel

Currently,intensive research efforts focus on the fabrication of meso-structures of assembled colloidal quantum dots(QDs)with original optical and electronic *** collective features originate from the QDs coupling,depending on the number of connected units and their ***,the development of general methodologies to assemble colloidal QD with precise stoichiometry and particle-particle spacing remains a key ***,we demonstrate that dimers of CdSe QDs,stable in solution,can be obtained by engineering QD surface chemistry,reducing the surface steric hindrance and favoring the link between two *** connection is made by using alkyl dithiols as bifunctional linkers and different chain lengths are used to tune the interparticle distance from few nm down to 0.5 *** spectroscopic investigation highlights that coupling phenomena between the QDs in dimers are strongly dependent on the interparticle distance and QD size,ultimately affecting the exciton dissociation efficiency.

关键词： quantum dots dimers surface chemistry dithiols coupling

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Motor Development as a Potential Marker to Monitor Infantile Pompe Disease on Enzyme Replacement Therapy

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Open Journal of Clinical Diagnostics 2017年第1期7卷 8-19页

作者： Paula de almeida Thomazinho Fernanda Bertao Scalco maria lucia Costa de Oliveira Dafne Dain Gandelman Horovitz Juan Clinton Llerena Jr Fisioterapia Motora Instituto Nacional de Saude da Mulherda Crianca e do Adolescente Fernandes Figueira/FIOCRUZRio de JaneiroBrasil Departamento de Bioquimica Universidade Federal do Rio de JaneiroRio de JaneiroBrasil Area de Centro de Genetica Medica Instituto Nacional de Saude da Mulherda Crianca e do Adolescente Fernandes Figueira/FIOCRUZRio de JaneiroBrasil

After Enzyme Replacement Therapy (ERT) using recombinant human acid alpha-glucosidase (rhGAA), survival of Infantile Pompe Disease (IPD) patients through the first 18 months of age has been documented and acquisitions of motor development are an important outcome, but description of its course is scarce. Objective: To describe the motor development in an IPD patient and its correlation with clinical conditions during the first 18 months on ERT with rhGAA. Methods: By longitudinal observational study of an IPD case at early stage. Clinical and biochemical characteristics were obtained from patient records. Echocardiogram assessed cardiac indexes and the urinary biomarker—glucose tetrasaccharide (Glc4)—was obtained by HPLC/UV, following sample derivatization with butyl 4-amino benzoate and analysis on a C18 stationary phase column. Motor skills were evaluated with Alberta Infant of Motor Scale (AIMS) and motor delay was considered as motor percentile (p) below 10. Descriptive statistical analysis was carried out and t-test was used to calculate the differences among means, with significance level defined as p value < 0.05. Results: After ERT beginning amelioration of the cardiomyopathy with reduced left ventricle mass index (LVMI) from the 2nd month onwards was observed, but above the upper normal limit for healthy children and CRIM-positive IPD patients. Although GAA antibodies level remained above the recommended titers and fluctuating elevation of Glc4 quantified, motor development analysis showed an ascendant curve expected for age within achievement of independent ambulation. Motor delay after pneumonia and maintenance of hypotonia were noted. Variation of Glc4 appeared long after a transitory intercurrence. Conclusion: In an IPD case, motor development can have normal evolution despite hypotonia. Motor analysis seems to be sensitive to follow-up clinical intercurrences. To elucidate the interaction among prognostic factors and outcomes, further clinical studies

关键词： Infantile Pompe Disease Motor Development Enzyme Replacement Therapy Glc4 Biomarker

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Integrin-targeting with peptide-bioconjugated semiconductor-magnetic nanocrystalline heterostructures

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Nano Research 2016年第3期9卷 644-662页

作者： Gianpiero Valente Nicoletta Depalo Ivan de Paola Rosa maria lacobazzi Nunzio Denora Valentino Laquintana Roberto Comparelli Emiliano Altamura Tiziana Latronico Michele Altomare Elisabetta Fanizza Marinella Striccoli Angela Agostiano Michele Saviano Annarita Del Gatto Laura Zaccaro maria lucia Curri Universita degli Studi di Bari Aldo Moro Dipartimento di Chimica Via Orabona 4 70125 - Bari Italy Istituto per i Processi Chimico-Fisici-CNR UOS Bari Via Orabona 4 70125 - Bari Italy Istituto di Biostrutture e Bioimmagini-CNR Via Mezzocannone 16 80134 - Napoli Italy Universita degli Studi di Bari Aldo Moro Dipartimento di Farmacia - Scienze del Farmaco Via Orabona 4 70125 - Bari Italy Universita degli Studi di BariAIdo Moro Dipartimento di Bioscienze Biotecnologie e Biofarmaceutica Via Orabona 4 70125 - Bari Italy lstituto di Cristallografia-CNR Via Amendola 122/0 70126 Bari Italy

Binary asymmetric nanocrystals （BNCs）, composed of a photoactive TiO2 nanorod joined with a superparamagnetic γ-Fe203 spherical domain, were embedded in polyethylene glycol modified phospholipid micelle and successfully bioconjugated to a suitably designed peptide containing an RGD motif. BNCs represent a relevant multifunctional nanomaterial, owing to the coexistence of two distinct domains in one particle, characterized by high photoactivity and magnetic properties, that is particularly suited for use as a phototherapy and hyperthermia agent as well as a magnetic probe in biological imaging. We selected the RGD motif in order to target integrin expressed on activated endothelial cells and several types of cancer cells. The prepared RGD-peptide/BNC conjugates, comprehensively monitored by using complementary optical and structural techniques, demon- strated a high stability and uniform dispersibility in biological media. The cytotoxicity of the RGD-peptide/BNC conjugates was studied in vitro. The cellular uptake of RGD-peptide conjugates in the cells, assessed by means of two distinct approaches, namely confocal microscopy analysis and emission spectroscopy determination in cell lysates, displayed selectivity of the RGD-peptide-BNC conjugate for the cw]33 integrin. These RGD-peptide-BNC conjugates have a high potential for theranostic treatment of cancer.

关键词： nanocrystallineheterostructures photoactive semiconductor magnetic nanostructure cyclic RGD peptide αvβ3 integrin active targeting

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Central nervous system vasculitis and polyneuropathy as first manifestations of hepatitis C

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World Journal of Gastroenterology 2012年第2期18卷 188-191页

作者： Roberto J Carvalho-Filho Janaína Luz Narciso-Schiavon luciano HL Tolentino Leonardo L Schiavon maria lucia G Ferraz Antonio Eduardo B Silva Division of Gastroenterology Hepatitis SectionFederal University of Sao Paulo04037-003 Sao PauloBrazil

Sensory or motor peripheral neuropathy may be observed in a significant proportion of hepatitis C virus (HCV)-infected ***,central nervous system (CNS) involvement is uncommon,especially in cryoglobulin-negative *** describe a case of peripheral neuropathy combined with an ischemic CNS event as primary manifestations of chronic HCV infection without *** improvement was observed after antiviral *** discuss the spectrum of neurological manifestations of HCV infection and review the literature.

关键词： Hepatitis C Central nervous system Poly-neuropathy Interferon-α

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Interpreting Results of Ethanol, Carbamazepine and Topiramate in Putrefied Postmortem Specimens： A Case Report

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Journal of Pharmacy and Pharmacology 2016年第2期4卷 45-51页

作者： maria Chiara David lucia Broccoli Luana Lionetto PhD Forensic Science-Department of Public Healthy Legal Medicine - University of Tor Vergata 00133 Rome Italy PhD Legal Medicine and Forensic Science 00157 Rome ltaly PhD Advanced Molecular Diagnostics Unit (DiMA) IDI-IRCCS Istituto Dermopatico dell 'lmmacolata 00167 Rome Italy

CBZ （carbamazepine）, CBZ-epox （carbamazepine-10,11-epoxide）, TPR （topiramate） and ethanol were detected in 37-year-old woman buried in the wall founded eighteen months after death. The woman was in treatment with anticonvulsants. The cause of death was strangulation investigated by immunohistochemical with GPA （glycophorin A）. Routine analyses for drugs of abuse, therapeutic drugs and volatiles were conducted. Carbamazepine, Topiramate and Alcohol were quantified in abdominal effusion, gastric wall, spleen, douglas fluid, skeletal muscles, endothoracic fluid, kidney, liver, heart and bone marrow. CBZ, CBZ-epox and TPR were recovered in samples deproteinized by acetonitrile spiked with DNSnVal as Internal Standard. Compounds were detected by HPLC-MS/MS. Alcohol was detected in any specimens by HS-GC/FID. CBZ concentrations were ranged from 0.49 in liver to 13.6 ~tg/g in endothoracic fluid; CBZ-Epox 0.46 in skeletal muscle, and 1.13 pg/g in Douglas fluid; TPR 0.11 in gastric wall and 1.23 Ixg/g in endothoracic fluid; alcohol from 0.17 in bone marrow to 0,75 mg/g in Douglas fluid. To our knowledge this is the first report of the presence of carbamazepine, topiramate, and alcohol in post mortem putrefied specimens.

关键词： Carbamazepine topimarate HPLC-MS/MS postmortem putrefied saponified.

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Robot-assisted kidney transplantation:Is it getting ready for prime time?

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World Journal of Transplantation 2022年第7期12卷 163-174页

作者： Vincenzo Li Marzi Alessio Pecoraro maria lucia Gallo Leonardo Caroti Adriano Peris Graziano Vignolini Sergio Serni Riccardo Campi Department of Minimally Invasive and Robotic Urologic Surgery Careggi University HospitalUniversity of FlorenceFlorence 50134Italy Nephrology Unit Careggi HospitalFlorence 50134Italy Intensive Care Unit and Regional ECMO Referral Centre Careggi HospitalFlorence 50134Italy Department of Minimally Invasive and Robotic Urologic Surgery University of FlorenceFlorence 50134Italy Department of Experimental and Clinical Medicine University of FlorenceFlorence 50134Italy

Kidney transplantation(KT)is the treatment of choice for patients with end-stage renal disease,providing a better survival rate and quality of life compared to *** the progress in the medical management of KT patients,from a purely surgical standpoint,KT has resisted innovations during the last 50 ***,robot-assisted KT(RAKT)has been proposed as an alternative approach to open surgery,especially due to its potential benefits for fragile and immunocompromised *** was not until 2014 that the role of RAKT has found value thanks to the pioneering Vattikuti Urology Institute-Medanta collaboration that conceptualized and developed a new surgical technique for RAKT following the Idea,Development,Exploration,Assessment,Long-term follow-up recommendations for introducing surgical innovations into real-life *** the last years,mirroring the Vattikuti-Medanta technique,several centers developed RAKT program worldwide,providing strong evidence about the safety and the feasibility of this ***,the majority of RAKT are still performed in the living donor setting,as an“eligible”procedure,while only a few centers have realized KT through a robotic approach in the challenging scenario of cadaver *** addition,despite the spread of minimally-invasive(predominantly robotic)surgery worldwide,many KTs are still performed in an open *** of the type of incision employed by surgeons,open KT may lead to nonnegligible risks of wound complications,especially among obese ***,the assessment for KT should consider not only the added surgical technical challenges but also the higher risk of postoperative *** this context,robotic surgery could offer several benefits,including providing a better exposure of the surgical field and better instrument maneuverability,as well as the possibility to integrate other technological nuances,such as the use of intraoperative fluorescence vascular imagi

关键词： Deceased donors Living donors Kidney transplantation Minimally invasive surgery Robotics

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