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First-line erlotinib and fixed dose-rate gemcitabine for advanced pancreatic cancer

World Journal of Gastroenterology 2013年第28期19卷 4511-4519页

作者： vanja vaccaro Emilio Bria Isabella Sperduti Alain Gelibter Luca Moscetti Giovanni Mansueto Enzo Maria Ruggeri Teresa Gamucci Francesco Cognetti Michele Milella Department of Medical Oncology Regina Elena National Cancer Institute 00144 Rome Italy Medical Oncology Azienda Ospedaliera Universitaria Integrata 37134 Verona Italy Department of Biostatistics and Scientific Direction Regina Elena National Cancer Institute 00144 Rome Italy Medical Oncology Ospedale "Belcolle" 01100 Viterbo Italy S.S. Trinità Hospital Sora 03039 Frosinone Italy Department of Medical Oncology Regina Elena National Cancer Institute 00144 Rome Italy

AIM: To investigate activity, toxicity, and prognostic factors for survival of erlotinib and fixed dose-rate gemcitabine (FDR-Gem) in advanced pancreatic cancer.METHODS: We designed a single-arm prospective, multicentre, open-label phase II study to evaluate the combination of erlotinib (100 mg/d, orally) and weekly FDR-Gem (1000 mg/m2, infused at 10 mg/m2 per minute) in a population of previously untreated patients with locally advanced, inoperable, or metastatic pancreatic cancer. Primary endpoint was the rate of progression-free survival at 6 mo (PFS-6); secondary endpoints were overall response rate (ORR), response duration, tolerability, overall survival (OS), and clinical benefit. Treatment was not considered to be of further interest if the PFS-6 was 40% would be of considerable interest (p1 = 40%); with a 5% rejection error (α = 5%) and a power of 80%, 35 fully evaluable patients with metastatic disease were required to be enrolled in order to complete the study. Analysis of prognostic factors for survival was also carried out.RESULTS: From May 2007 to September 2009, 46 patients were enrolled (male/female: 25/21; median age: 64 years; median baseline carbohydrate antigen 19-9 (CA 19-9): 897 U/mL; locally advanced/metastatic disease: 5/41). PFS-6 and median PFS were 30.4% and 14 wk (95%CI: 10-19), respectively; 1-year and median OS were 20.2% and 26 wk (95%CI: 8-43). Five patients achieved an objective response (ORR: 10.9%, 95%CI: 1.9-19.9); disease control rate was 56.5% (95%CI: 42.2-70.8); clinical benefit rate was 43.5% (95%CI: 29.1-57.8). CA 19-9 serum levels were decreased by > 25% as compared to baseline in 14/23 evaluable patients (63.6%). Treatment was well-tolerated, with skin rash being the most powerful predictor of both longer PFS (P < 0.0001) and OS (P = 0.01) at multivariate analysis (median OS for patients with or without rash: 42 wk vs 15 wk, respectively, Log-rank P = 0.03). Additional predictors of bett

关键词： Pancreatic cancer Gemcitabine Fixed dose-rate Erlotinib Prognostic factors Cutaneous rash Phase II trial

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Recent advances of versatile reagents as controllable building blocks in organic synthesis

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Chinese Chemical Letters 2024年第2期35卷 24-43页

作者： Shaomin Chen Luigi vaccaro Yanlong Gu Key Laboratory of Material Chemistry for Energy Conversion and Storage Ministry of EducationHubei Key Laboratory of Material Chemistry and Service FailureSchool of Chemistry and Chemical EngineeringHuazhong University of Science and TechnologyWuhan 430074China Laboratory of Green S.O.C. Dipartimento di ChimicaBiologia e BiotecnologieUniversità degli Studi di PerugiaVia Elce di Sotto 8Perugia 06123Italy School of Chemistry and Chemical Engineering The Key Laboratory for Green Processing of Chemical Engineering of Xinjiang BingtuanShihezi UniversityShihezi 832004China

Diversity-oriented synthesis is a powerful and interesting synthetic tool for the rapid construction of structurally complex and privileged scaffolds from readily accessible starting *** date,diversity-oriented synthesis mostly relies on the employment of versatile *** reagents can be regulated as controllable and flexible building blocks for multipurpose *** the past decade,a variety of multifunctional reagents have been ***,most versatile reagents usually need multi-step synthesis,thus restricting their wide application to a large *** terms of the practicalities and universalities,we prefer to pay more attention to the utilization of simple and practical versatile reagents with multiple reactivities,mainly including atropaldehyde acetals,aryl methyl ketones,vinylene carbonate,vinyl azides,aryldiazonium salts,rongalite,halodifluoromethyl *** importantly,these versatile reagents can also play different roles simultaneously in the same reaction,in which their different reactivities are converged into the final target *** strategy can not only offer more possibilities for the synthesis of several active pharmaceutical ingredients,but also minimize the occurrence of some side reactions by lessening the varieties of ***,a perspective is given at the end of this review.

关键词： Versatile reagents Divergent synthesis Dual synthons Bond cleavage Tandem reactions

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Metastatic pancreatic cancer: Is there a light at the end of the tunnel?

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World Journal of Gastroenterology 2015年第16期21卷 4788-4801页

作者： vanja vaccaro Isabella Sperduti Sabrina Vari Emilio Bria Davide Melisi Carlo Garufi Carmen Nuzzo Aldo Scarpa Giampaolo Tortora Francesco Cognetti Michele Reni Michele Milella Medical Oncology A Regina Elena National Cancer Institute Medical Oncology A and Biostatistics Regina Elena National Cancer Institute Medical Oncology University of VeronaAzienda Ospedaliera Universitaria Integrata ARC-Net Research Centre and Department of Pathology Diagnostics and SurgeryUniversity of Verona Medical Oncology Unit Department of OncologySan Raffaele Scientific Institute

Due to extremely poor prognosis,pancreatic cancer(PDAC)represents the fourth leading cause of cancerrelated death in Western *** more than a decade,gemcitabine(Gem)has been the mainstay of first-line PDAC *** efforts aimed at improving single-agent Gem efficacy by either combining it with a second cytotoxic/molecularly targeted agent or pharmacokinetic modulation provided disappointing ***,the field of systemic therapy of advanced PDAC is finally moving *** has shown promise over single-agent Gem:regimens like PEFG-PEXG-PDXG and GTX provide significant potential advantages in terms of survival and/or disease control,although sometimes at the cost of poor *** PRODIGE 4/ACCORD 11 was the first phaseⅢtrial to provide unequivocal benefit using the polychemotherapy regimen FOLFIRINOX;however the less favorable safety profile and the characteristics of the enrolled population,restrict the use of FOLFIRINOX to young and fit PDAC *** nanoparticle albumin-bound paclitaxel(nab-Paclitaxel)formulation was developed to overcome resistance due to the desmoplastic stroma surrounding pancreatic cancer *** of whether or not this is its main mechanisms of action,the combination of nabPaclitaxel plus Gem showed a statistically and clinically significant survival advantage over single agent Gem and significantly improved all the secondary ***,recent findings on maintenance therapy are opening up potential new avenues in the treatment of advanced PDAC,particularly in a new era in which highly effective first-line regimens allow patients to experience prolonged disease ***,we provide an overview of recent advances in the systemic treatment of advanced PDAC,mostly focusing on recent findings that have set new standards in metastatic *** avenues for further development in the metastatic setting and current efforts to integratenew effective chemotherapy regimens

关键词： Pancreatic cancer Metastatic disease Chemotherapy Folfirinox nab -Paclitaxel

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A new perspective on intervertebral disc calcification—from bench to bedside

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Bone Research 2024年第1期12卷 50-61页

作者： Emanuel J.Novais Rajkishen Narayanan Jose A.Canseco Koen van de Wetering Christopher K.Kepler Alan S.Hilibrand Alexander R.vaccaro Makarand V.Risbud Department of Orthopaedic Surgery Sidney Kimmel Medical CollegeThomas Jefferson UniversityPhiladelphiaPAUSA Unidade Local de Saúde do Litoral Alentejano Orthopedic DepartmentSantiago do CacémPortugal Rothman Orthopedic Institute at Thomas Jefferson University PhiladelphiaPAUSA

Disc degeneration primarily contributes to chronic low back and neck ***,there is an urgent need to understand the spectrum of disc degeneration phenotypes such as fibrosis,ectopic calcification,herniation,or mixed *** these phenotypes,disc calcification is the least *** calcification,by definition,is the pathological mineralization of soft tissues,widely studied in the context of conditions that afflict vasculature,skin,and ***,disc calcification is associated with poor surgical outcomes and back pain refractory to conservative *** is frequently seen as a consequence of disc aging and progressive degeneration but exhibits unique molecular and morphological characteristics:hypertrophic chondrocyte-like cell differentiation;TNAP,ENPP1,and ANK upregulation;cell death;altered Pi and PPi homeostasis;and local *** studies in mouse models have provided a better understanding of the mechanisms underlying this *** is essential to recognize that the presentation and nature of mineralization differ between AF,NP,and EP ***,the combination of anatomic location,genetics,and environmental stressors,such as aging or trauma,govern the predisposition to ***,the systemic regulation of calcium and Pi metabolism is less important than the local activity of PPi modulated by the ANK-ENPP1 axis,along with disc cell death and differentiation *** there is limited understanding of this phenotype,understanding the molecular pathways governing local intervertebral disc calcification may lead to developing disease-modifying drugs and better clinical management of degeneration-related pathologies.

关键词： degeneration metabolism intervertebral

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“Targeting” renal cell carcinoma patients with “targeted” agents: Are we there yet?

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World Journal of Clinical Urology 2014年第1期3卷 9-19页

作者： Francesca Maines Sara Pilotto Michele Milella Francesco Massari vanja vaccaro Alessandra Felici Emilio Bria Giampaolo Tortora Medical Oncology Azienda Ospedaliera Universitaria Integrata University of Verona Medical Oncology Regina Elena National Cancer Institute

The rapid approval of several novel agents, targeting the vascular endothelial growth factor or mammalian target of rapamycin pathways(sunitinib, pazopanib, sorafenib, axitinib, bevacizumab, everolimus, temsirolimus) has given to metastatic renal cell carcinoma(m RCC) patients and their treating physicians many new and effective therapeutic options. The treatment paradigm for these patients is rapidly evolving, with future studies needed to defi ne the optimal sequencing of these new agents. Despite progresses, no validated biomarkers able to predict clinical outcome or useful to guide patient selection for treatment are currently available. Recent studies have suggested that some biomarkers, including cytokines, circulating proangio-genic factors, markers of hypoxia or targets of signaling pathways are potentially promising prognostic or predictive factors in m RCC. We present an overview of the most recent developments in identifying biomarkers for targeted therapies in advanced RCC.

关键词： Biomarkers Renal cell carcinoma Prognostic biomarker Predictive biomarker Vascular endothelial growth factor tyrosine kinase inhibitors Mammalian target of rapamycin inhibitors

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Sediment regime of the Danube River in Serbia

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International Journal of Sediment Research 2013年第4期28卷 470-485页

作者： Marina BABIC MLADENOVIC Vasiljka KOLAROV vanja DAMJANOVIC Jaroslav Cerni Institute for the Development of Water Resources Department for River Engineering

The total length of the Danube section in Serbia is 587.5 km,and it has three specific sections:(1) Pannonian Plain Danube(or the Middle Danube) has all characteristics of lowland *** stretch downstream of Novi Sad is under the influence of the Iron Gate 1 backwater during low water flows;(2) Iron Gate Danube,where the river is confined in the *** it is a reservoir,with completely altered natural characteristics.(3) Western Pontic Danube(or the Lower Danube),downstream of the *** paper presents the sediment regime in the Serbian sector of the Danube River,both upstream and within the Iron Gate *** field investigation data were used to describe the most important parameters of sediment transport and deposition processes,including riverbed composition and suspended sediment characteristics(grain size and concentration).The influence of large tributaries of the Danube(the Tisza,the Sava,and the Velika Morava) is also *** conducted in the Iron Gate 1reservoir under the Sediment Regime and Morphological Changes Monitoring Program is also *** obtained during implementation of the Program form the basis for the description of changes in the Danube sediment regime that occurred following erection of the Iron Gate *** revealed that the most important consequence of the Iron Gate I IIPNS Dam is permanent deposition of sediment in the Iron Gate Gorge portion of the reservoir,the water and environmental management implications of which are becoming increasingly ***,upstream stretches of the reservoir are not subject to uniform sedimentation processes;instead,the sediment regime depends on current hydrologic and hydraulic conditions within the watercourse and/or the hydro-power plant operating mode.

关键词： Sediment regime Morphological changes Danube Serbia

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Fungal spores and pollen in particulate matter collected during agricultural activities in the Po Valley(Italy)

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Journal of Environmental Sciences 2016年第8期28卷 229-240页

作者： Chiara Telloli Milvia Chicca Marilena Leis Carmela vaccaro Italian National Agency for New Technologies Energy and Sustainable Economic Development (ENEA) Technical Unit for Environmental Assessment Models Methods and Technologies (UTVALAMB) Air Quality Laboratory (AIR) Department of Life Science and Biotechnologies Ferrara University Department of Physics and Earth Sciences Ferrara University

Airborne particulate matter（PM） containing fungal spores and pollen grains was sampled within a monitoring campaign of wheat threshing, plowing and sowing agricultural operations. Fungal spores and pollen grains were detected and identified on morphological basis. No studies were previously available about fungal spore and pollen content in agricultural PM in the Po Valley. Sampling was conducted in a Po Valley farmland in Mezzano（Ferrara, Italy）. The organic particles collected were examined by scanning electron microscopy with energy dispersive X-ray spectrometer. Fungal spores and pollen grains were identified when possible at the level of species. The most frequent components of the organic particles sampled were spores of Aspergillus sp., which could represent a risk of developing allergies and aspergillosis for crop farmers.

关键词： Wheat Aspergillosis Emilia-Romagna Morphology SEM–EDS

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Cretaceous alkaline volcanism in south Marzanabad,northern central Alborz,Iran:Geochemistry and petrogenesis

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Geoscience Frontiers 2016年第6期7卷 937-951页

作者： Roghieh Doroozi Carmela vaccaro Fariborz Masoudi Riccardo Petrini Faculty of Earth Science Shahid Beheshti UniversityVelenjakTehranlran Department of Mineralogy University of FerraraCorso Ercole I d'Este 3244100 FerraraItaly Department of Mathematics and Geosciences University of TriesteVia Weiss8-34100 TriesteItaly

The alkali-basalt and basaltic trachy-andesites volcanic rocks of south Marzanabad were erupted during Cretaceous in central Alborz, which is regarded as the northern part of the Alpine-Himalayan orogenic belt. Based on petrography and geochemistry, en route fractional crystallization of ascending magma was an important process in the evolution of the volcanic rocks. Geochemical characteristics imply that the south Marzanabad alkaline basaltic magma was originated from the asthenospheric mantle source, whereas the high ratios of （La/Yb）N and （Dy/Yb）N are related to the low degree of partial melting from the garnet bearing mantle source. Enrichment pattern of Nb and depletion of Rb, K and Y, are similar to the OIB pattern and intraplate alkaline magmatic rocks. The K/Nb and Zr/Nb ratios of volcanic rocks range from 62 to 588 and from 4.27 to 9 respectively, that are some higher in more evolved samples which may reflect minor crustal contamination. The isotopic ratios of Sr and Nd respectively vary from 0.70370 to 0.704387 and from 0.51266 to 0.51281 that suggest the depleted mantle as a magma source. The development of south Marzanabad volcanic rocks could be related to the presence of extensional phase, upwelling and decompressional melting of asthenospheric mantle in the rift basin which made the alkaline magmatism in Cretaceous, in northern central Alborz of lran.

关键词： Volcanic rocks Cretaceous Marzanabad Central Alborz Iran

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Genetic differentiation in functional traits among wild cherry (Prunus avium L.) half-sib lines

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Journal of Forestry Research 2022年第3期33卷 991-1003页

作者： Srđan Stojnić Branislav Kovačević Marko Kebert Verica Vasić vanja Vuksanović Branislav Trudić Saša Orlović Institute of Lowland Forestry and Environment University of Novi SadAntonaČehova 13dNovi Sad21000Serbia Faculty of Agriculture University of Novi SadTrg Dositeja Obradovića 8Novi Sad21000Serbia Food and Agriculture Organization of the United Nations Viale delle Terme di Caracalla00153RomeItaly

Understanding intra-specific variation in leaf functional traits is one of the key requirements for the evaluation of species adaptive capacity to ongoing climate change, as well as for designing long-term breeding and conservation strategies. Hence, data of 19 functional traits describing plant physiology, antioxidant properties, anatomy and morphology were determined on 1-year-old seedlings of wild cherry (Prunus avium L.) half-sib lines. The variability within and among half-sib lines, as well as the estimation of multi-trait association, were examined using analysis of variance (ANOVA) followed by Tukey's honestly significant difference test and multivariate analyses: principal component analysis (PCA), canonical discriminant analysis (CDA) and stepwise discriminant analysis (SDA). Pearson’s correlation coefficient was used to evaluate linear correlation between the study parameters. The results of the ANOVA showed the presence of statistically significant differences (P < 0.01) among half-sib lines for all study traits. The differences within half-sib lines, observed through the contribution of the examined sources of variation to the total variance (%), had higher impact on total variation in the majority of the examined traits. Pearson’s correlation analysis and PCA showed strong relationships between gas exchange in plants and leaf size and stomatal density, as well as between leaf biomass accumulation, intercellular CO_(2) concentration and parameters related to antioxidant capacity of plants. Likewise, the results of SDA indicate that transpiration and stomatal conductance contributed to the largest extent, to the discrimination of the wild cherry half-sib lines. In addition, PCA and CDA showed separation of the wild cherry half-sib lines along the first principal component and first canonical variable with regards to humidity of their original sites. Multiple adaptive differences between the wild cherry half-sib lines indicate high potential of the specie

关键词： Wild cherry Common garden experiment Variability Multivariate statistics Leaf functional traits

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Properties of agricultural aerosol released during wheat harvest threshing,plowing and sowing

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Journal of Environmental Sciences 2014年第9期26卷 1903-1912页

作者： Chiara Telloli Antonella Malaguti Mihaela Mircea Renzo Tassinari Carmela vaccaro Massimo Berico ENEA National Agency for New TechnologiesEnergy and Sustainable Economic DevelopmentVia Martiri di Monte Sole 4Bologna 40129Italy Department of Earth Science Ferrara UniversityItaly

This study shows for the first time a chemical and morphological characterization of agricultural aerosols released during three important agricultural operations： threshing, plowing and sowing. The field campaigns were carried out in the eastern part of the Po Valley, Italy, in summer and autumn 2009. The aerosol particles were sampled on quartz fiber filters and polytetrafluoroethylene membranes in order to allow Inductively Coupled Plasma Mass Spectrometry （ICP-MS） analysis and Scanning Electron Microscopy equipped with an Energy Dispersive X-ray Spectrometer （SEM-EDS） investigations, respectively. The organic carbon mass concentrations were measured with a Sunset Laboratory Dual-Optical Organic Carbone/Elemental Carbon （OCEC） Aerosol analyzer. The morphological and chemical analyses by SEM-EDS allowed recognizing four main particle classes： organic, silica, calcite and clay minerals. The organic particles contribute to both fine and coarse aerosol fractions up to ca. 50% for all three agricultural activities. This was also confirmed by OCEC analysis for fine fraction. Most of the agricultural aerosols, about 60%, were single particles and the remaining 40% were agglomerations of particles. The ICP-MS results showed that threshing and plowing produce more aerosol particles than sowing, which was characterized by important amounts of clay minerals produced from land soils.

关键词： AerosolAgricultureSEM-EDSICP-MS and OCEC analyses

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