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Prognostic and predictive biomarkers in metastatic colorectal cancer anti-EGFR therapy

World Journal of Gastroenterology 2016年第30期22卷 6944-6954页

作者： Cristiana Lo Nigro Vincenzo Ricci Daniela Vivenza cristina granetto Teresa Fabozzi Emanuela Miraglio Marco C Merlano Department of Oncology S. Croce and Carle Teaching Hospital Department of Oncology San Raffaele Institute

AIM: To reviewing genetic and epigenetic make-up of metastatic colorectal cancers (mCRCs) addicted to epidermal growth factor receptor (EGFR) ***: The present study summarizes the potential value of prognostic and predictive biomarkers in selecting mCRC patients treated with anti-EGFR therapy. A meta-analysis was performed using a systematic search of PubMed, Medline and Web of Science to identify eligible papers until March 21st, 2016 using these following terms: ‘‘colorectal cancer’’, “predictive biomarkers’’, “anti-EGFR therapy”, “KRAS”, “NRAS’’, “PIK3CA”, “TP53”, “PTEN”, ‘‘EGFR”, “MET”, “HER2”, “epiregulin”, “amphiregulin”, “prognostic biomarkers”, “BRAF”, “miRNA” and “antibody-dependent cell-mediated cytotoxicity (ADCC) activity”. Two investigators independently evaluated and extracted data from each identified studies based on selected criteria of inclusion and ***: The introduction of agents targeting EGFR such as cetuximab and panitumumab increased overall survival of mCRCs. Nevertheless, it has firstly became evident that response rates to cetuximab regimens in unselected patient populations were typically lower than 30%. Clinical data confirmed the predictive value of RAS mutations for resistance to cetuximab and panitumumab leading to the license of these monoclonal antibodies exclusively for the management of patients with RAS-wild type colorectal cancers. So far the identification of predictive biomarkers have generated interesting, though preliminary and, at times, conflicting data on the importance of tumour mRNA levels of EGFR ligands, of activating mutations in other genes such as NRAS and PIK3CA. The pr

关键词： Metastatic colorectal cancer Anti-epidermal growth factor receptor therapy KRAS Biomarkers Antibody-dependent cell-mediated cytotoxicity

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Circulating cytokines and outcome in metastatic colorectal cancer patients treated with regorafenib

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World Journal of Gastrointestinal Oncology 2020年第3期12卷 301-310页

作者： Vincenzo Ricci cristina granetto Antonella Falletta Matteo Paccagnella Andrea Abbona Elena Fea Teresa Fabozzi Cristiana Lo Nigro Marco Carlo Merlano Medical Oncology and Laboratory of Translational Oncology Oncology DepartmentS.Croce and Carle Teaching Hospital CuneoCuneo 12100Italy Arco Cuneo Foundation Cuneo 12100Italy Medical Oncology S.G.Bosco HospitalTorino 10154Italy S.Croce and Carle Teaching Hospital Cuneo Cuneo 12100Italy

BACKGROUND Regorafenib is an oral small-molecule multikinase inhibitor approved in third or later line of treatment for patients with metastatic colorectal cancer(mCRC).Regorafenib has shown significant benefits in overall survival and progression free survival in two phase III trials compared to placebo in patients with mCRC who had progressed on previous *** To identify an immune profile that might specifically correlate with the outcome in patients treated with *** Blood samples were collected from 17 patients before treatment with regorafenib and from 6 healthy *** proteins evaluated(TNF-α,TGF-β,VEGF,CCL-2,CCL-4,and CCL-5)were selected on the basis of their roles in angiogenesis and colorectal cancer *** We found that TNF-αbasal level was significantly higher in mCRC patients compared to healthy *** Responder(NR)patients showing progression of disease(n=12)had higher basal level of TGF-β,TNF-α,VEGF,CCL-2 and CCL-5 compared to Responder(R)patients(complete response CR,n=1;partial response PR,n=1;Stable Disease SD,n=3).On the contrary,plasma basal level of CCL-4 was higher in R compared to NR *** values of TGF-βand TNF-αnegatively correlated with progression free *** These results suggest a cytokine signature potentially able to discriminate between R and NR patients to treatment with regorafenib.

关键词： Colorectal cancer Multikinase inhibitor Cytokines Angiogenesis

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Evaluation of antibody-dependent cell-mediatedcy totoxicity activity and cetuximab response in KRAS wildtype metastatic colorectal cancer patients

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World Journal of Gastrointestinal Oncology 2016年第2期8卷 222-230页

作者： cristiana lo nigro vincenzo ricci daniela vivenza martino monteverde giuliana strola francesco lucio federica tonissi emanuela miraglio cristina granetto mirella fortunato marco carlo merlano laboratory of cancer genetics and translational oncology oncology departments.croce and carle teaching hospital12100 Cuneo Italy medical oncology oncology departments.croce and carle teaching hospital12100 Cuneo Italy laboratory department s.croce and carle teaching hospital12100 Cuneo Italy radiotherapy department s.croce and carle teaching hospital12100 Cuneo Italy pathology department s.croce and carle teaching hospital12100 Cuneo Italy

AIM:To investigate the prognostic role of invariant natural killer T(iNKT) cells and antibody-dependent cell-mediated cytotoxicity(ADCC) in wild type KRAS metastatic colorectal cancer(mC RC) patients treated with ***: Forty-one KRAS wt mC RC patients,treated with cetuximab and irinotecan-based chemotherapy in Ⅱ and Ⅲ lines were analyzed. Genotyping of single nucleotide polymorphism(SNP)s in the FCGR2A,FCGR3A and in the 3' untranslated regions of KRAS and mutational analysis for KRAS,BRAF and NRAS genes was determined either by sequencing or allelic discrimination assays. Enriched NK cells were obtained from lymphoprepperipheral blood mononuclear cell and iN KT cells were defined by co-expression of CD3,TCRVα24,TCRVβ11. ADCC was evaluated as ex vivo NK-dependent activity,measuring lactate dehydrogenase ***: At basal,mCRC patients performing ADCC activity above the median level(71%) showed an improved overall survival(OS) compared to patients with ADCC below(median 16 vs 8 mo;P=0.026). We did not find any significant correlation of iN KT cells with OS(P=0.19),albeit we observed a trend to a longer survival after 10 mo in patients with iN KT above median basal level(0.382 cells/microliter). Correlation of OS and progression-free survival(PFS) with interesting SNPs involved in ADCC ability revealed not to be significant. Patients carrying alleles both with A in FCGR2 A and TT in FCGR3A presented a trend of longer PFS(median 9 vs 5 mo;P=0.064). Chemotherapy impacted both iN KT cells and ADCC activity. Their prognostic values get lost when we analysed them after 2 and 4 mo of ***: Our results suggest a link between iN KT cells,basal ADCC activity,genotypes in FCGR2A and FCGR3A,and efficacy of cetuximab in KRAS wt mC RC patients.

关键词： Metastatic colorectal cancer Single nucleotidepolymorphism in Fc-γ receptors Cetuximab RAS family Antibody-dependent cell-mediated cytotoxicity Invariantnatural killer T cells

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Uncovering the multifaceted roles played by neutrophils in allogeneic hematopoietic stem cell transplantation

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Cellular & Molecular Immunology 2021年第4期18卷 905-918页

作者： cristina Tecchio Marco Antonio Cassatella Department of Medicine Section of Hem atology and Bone Marrow Transplant UnitUniversity of VeronaVeronaItaly Department of Medicine Section of General PathologyUniversity of VeronaVeronaItaly

Allogeneic hematopoietic stem cell transplantation(alloHSCT)is a life-saving procedure used for the treatment of selected hematological malignancies,inborn errors of metabolism,and bone marrow *** role of neutrophils in alloHSCT has been traditionally evaluated only in the context of their ability to act as a first line of defense against ***,recent evidence has highlighted neutrophils as key effectors of innate and adaptive immune responses through a wide array of newly discovered ***,neutrophils are emerging as highly versatile cells that are able to acquire different,often opposite,functional capacities depending on the microenvironment and their differentiation ***,we review the current knowledge on the multiple functions that neutrophils exhibit through the different stages of alloHSCT,from the hematopoietic stem cell(HSC)mobilization in the donor to the immunological reconstitution that occurs in the recipient following HSC *** also discuss the influence exerted on neutrophils by the immunosuppressive drugs delivered in the course of alloHSCT as part of graft-versushost disease(GVHD)***,the potential involvement of neutrophils in alloHSCT-related complications,such as transplant-associated thrombotic microangiopathy(TA-TMA),acute and chronic GVHD,and cytomegalovirus(CMV)reactivation,is also *** on the data reviewed herein,the role played by neutrophils in alloHSCT is far greater than a simple antimicrobial ***,much remains to be investigated in terms of the potential functions that neutrophils might exert during a highly complex procedure such as alloHSCT.

关键词： neutrophils allogeneic hematopoietic stem cell transplantation(alloHSCT) alloHSCT-associated complications lowdensity neutrophils(LDNs) normal-density neutrophils(NDNs)

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Serum response factor:Look into the gut

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World Journal of Gastroenterology 2010年第18期16卷 2195-2201页

作者： cristina Modak Department of Research(09-151) VA Long Beach Healthcare System

Serum response factor(SRF) is a transcription factor that regulates many genes involved in cellular activities such as proliferation,migration,differentiation,angiogenesis,and *** it has only been known for about two decades,SRF has been studied *** date,over a thousand SRF studies have been published,but it still remains a hot *** to its critical role in mesoderm-derived tissues,most of the SRF studies focused on muscle structure/function,cardiovascular development/maintenance,and smooth muscle generation/***,SRF has received more attention in the digestive field and several important discoveries have been *** review will summarize what we have learned about SRF in the gastrointestinal tract and provide insights into possible future directions in this area.

关键词： Angiogenesis Cell invasion Myofibroblast differentiation Smooth muscle contraction Serum response factor Wound healing

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Recent results from NA48/2

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Chinese Physics C 2010年第6期34卷 749-752页

作者： cristina Morales Morales Institut für Physik Universitt Mainz

Recent results on radiative K^± decays from the NA48/2 experiment are reported. From the full NA48/2 data set, about a million K^±→π^±π^γ decays were reconstructed. Based on this sample, the first measurement of the interference between direct photon emission and inner bremsstrahlung in K^±→π^±π^γ decays was performed. Stringent limits on CP violation in this decay were also set. In addition, a precise measurement of the branching fraction of K^±→π^±γγ is presented. This measurement was based on a data sample of more than 1000 event candidates. Also the related decay K^±→π^±e^＋e^-γ has first been observed. Results of the measurement of the decay rate and the decay parameter 5 are summarized.

关键词： radiative K^± decays NA48/2 CP violation

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Spatial modelling of deforestation in Romanian Carpathian Mountains using GIS and Logistic Regression

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Journal of Mountain Science 2019年第5期16卷 1005-1022页

作者： Gheorghe KUCSICSA cristina DUMITRICA Institute of Geography Romanian Academy

Deforestation process represents a wide concern mainly in the mountain environments due to its role in global warming, biodiversity loss, land degradation and natural hazards occurrence. Thus, the present study is focused on the largest afforested landform unit of Romania and, consequently, the most affected area by forest losses: Carpathian Mountains. The main goal of the paper is to examine and analyze the various explanatory variables associated with deforestation process and to model the probability of deforestation using GIS spatial analysis and logistic regression. The forest cover for 1990 and 2012, derived from CORINE Land Cover(CLC) database, were used to quantify historical forest cover change included in the modelling. To explain the biophysical and anthropogenic effects, this study considered several explanatory factors related to local topography, forest cover pattern, accessibility, urban growth and population density. Using ROC(Receiver Operating Characteristic) and 500 controlling sampling points, the statistical and spatial validations were assessed in order to evaluate the performance of the resulted data. The analysis showed that the area experienced a continuous forest cover change, leading to the loss of over 250,000 ha of forested area during the period 1990–2012. The most significant influence of the explanatory factors of deforestation were noticed in case of distance to forest edge(β=–4.215), forest fragmentation(β=2.231), slope declivity(β=–1.901), elevation(β=1.734) and distance to roads(β=–1.713). The statistical and spatial validation indicates a good accuracy of the model with reasonably AUC(0.736) and Kappa(0.739) values. The model's results suggest an intensification of the deforestation process in the area, designing numerous new clusters with high probability in the Apuseni Mountains, northern and central part of the Eastern Carpathians, western part of the Southern Carpathians and northern part of the Banat Mountains. The study cou

关键词： Deforestation probability Romanian Carpathians Logistic Regression

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Moderate/severe traumatic brain injury as a trigger of chronic neurodegeneration in humans

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Neural Regeneration Research 2020年第7期15卷 1247-1248页

作者： Sergio Bagnato cristina Boccagni Unit of Neurophysiology and Unit for Severe Acquired Brain Injuries Rehabilitation Department Giuseppe Giglio Foundation

Traumatic brain injury(TBI)is the paradigmatic example of acute brain injury,defined as sudden and unexpected structural and/or functional damage to the *** western countries,TBI is a main cause of prolonged disability,and it is even more impactful because it very often affects young *** to past belief,the cerebral damage caused by TBI is not limited to the short temporal phase following the mechanical ***,moderate/severe TBI can trigger several mechanisms of neuronal damage that operate for months or years after the acute injury,potentially leading to neuronal loss and brain atrophy.

关键词： acute damage injury

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Shaping Small Bioactive Molecules to Untangle Their Biological Function： A Focus on Fluorescent Plant Hormones

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Molecular Plant 2016年第8期9卷 1099-1118页

作者： Beatrice Lace cristina Prandi Department of Chemistry University of Turin Via P. Giuria 7 10125 Torino Italy

Modern biology overlaps with chemistry in explaining the structure and function of all cellular processes at the molecular level. Plant hormone research is perfectly located at the interface between these two disciplines, taking advantage of synthetic and computational chemistry as a tool to decipher the complex biological mechanisms regulating the action of plant hormones. These small signaling molecules regulate a wide range of developmental processes, adapting plant growth to ever changing environmental conditions. The synthesis of small bioactive molecules mimicking the activity of endogenous hormones allows us to unveil many molec- ular features of their functioning, giving rise to a new field, plant chemical biology. In this framework, fluores- cence labeling of plant hormones is emerging as a successful strategy to track the fate of these challenging molecules inside living organisms. Thanks to the increasing availability of new fluorescent probes as well as advanced and innovative imaging technologies, we are now in a position to investigate many of the dynamic mechanisms through which plant hormones exert their action. Such a deep and detailed comprehension is mandatory for the development of new green technologies for practical applications. In this review, we sum- marize the results obtained so far concerning the fluorescent labeling of plant hormones, highlighting the basic steps leading to the design and synthesis of these compelling molecular tools and their applications.

关键词： plant hormones fluorescent labeling fluorescent strigolactone analogs labeled bioactive com-pounds fluorescence imaging

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Resilience in action: The bottom up! architecture festival in Turin (Italy)

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Journal of Safety Science and Resilience 2023年第2期4卷 174-187页

作者： cristina Coscia Angioletta Voghera Department of Architecture and Design(DAD) Politecnico di Torinoviale Mattioli39Torino 10125Italy Responsble Riskresilience InteruniverstyDepartmentof Rgional and Urban Studies and Planing(DIST) Politecnico diTorinoviale Mattioli39Torino12 Italy

This article describes the practice of co-evolutionary and transformative resilience through a case study con-ducted in Turin(Italy).According to a broad definition,resilience includes performing actions of urban design and planning,innovating community-based project procedures,and creating positive financial outcomes that are assessable because of the monitoring process of short-and long-term outcomes and *** the Turin-based case of the Bottom Up!Architecture Festival,this article observes processes in which resilience is in action in metropolitan areas,feeding urban projects and practices of self-organization of the social and financial actors *** applying the definition of community projects,the festival manages to take territorial problems and crises(the pandemic,inequality,etc.)and view them as an opportunity to change the system,recommending in-tegrated action on the natural,cultural,financial,and social capital,innovating practices and holding society and institutions more *** transformation of spaces relies on collaborations between social and institu-tional actors,operating spatially concentrated transformations in the city of Turin,and using flexible governance tools based on co-planning and crowdfunding for project design and financing.

关键词： Resilience Bottom-up Co-evolution Crowdfunding AdaptiveGovernance Turin(Italy)

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