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Murine models based on acute myeloid leukemia-initiating stem cells xenografting

World Journal of Stem Cells 2018年第6期10卷 57-65页

作者： cristina mambet Mihaela Chivu-Economescu Lilia Matei Laura Georgiana Necula Denisa Laura Dragu Coralia Bleotu Carmen cristina Diaconu Cellular and Molecular Pathology Department Stefan S. Nicolau Institute of Virology Nicolae Cajal Institute Titu Maiorescu University

Acute myeloid leukemia(AML) is an aggressive malignant disease defined by abnormal expansion of myeloid blasts. Despite recent advances in understanding AML pathogenesis and identifying their molecular subtypes based on somatic mutations, AML is still characterized by poor outcomes, with a 5-year survival rate of only 30%-40%, the majority of the patients dying due to AML relapse. Leukemia stem cells(LSC) are considered to be at the root of chemotherapeutic resistance and AML relapse. Although numerous studies have tried to better characterize LSCs in terms of surface and molecular markers, a specific marker of LSC has not been found, and still the most universally accepted phenotypic signature remains the surface antigens CD34+CD38- that is shared with normal hematopoietic stem cells. Animal models provides the means to investigate the factors responsible for leukemic transformation, the intrinsic differences between secondary post-myeloproliferative neoplasm AML and de novo AML, especially the signaling pathways involved in inflammation and hematopoiesis. However, AML proved to be one of the hematological malignancies that is difficult to engraft even in the most immunodeficient mice strains, and numerous ongoing attempts are focused to develop "humanized mice" that can support the engraftment of LSC. This present review is aiming to in-troduce the field of AML pathogenesis and the concept of LSC, to present the current knowledge on leukemic blasts surface markers and recent attempts to develop best AML animal models.

关键词： Acute myeloid leukemia Leukemia-initiating stem cells Antigen markers Murine models Xenografts

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Cancer stem cells: Involvement in pancreatic cancer pathogenesis and perspectives on cancer therapeutics

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World Journal of Gastroenterology 2014年第31期20卷 10790-10801页

作者： Cristiana Pistol Tanase Ana Iulia Neagu Laura Georgiana Necula cristina mambet Ana-Maria Enciu Bogdan Calenic Maria Linda Cruceru Radu Albulescu Department of Biochemistry-Proteomics Victor Babes National Institute of Pathology Stefan S Nicolau Institute of Virology Carol Davila University of Medicine and Pharmacy National Institute for Chemical Pharmaceutical Research and Development

Pancreatic cancer is one of the most aggressive and lethal malignancies. Despite remarkable progress in understanding pancreatic carcinogenesis at the molecular level, as well as progress in new therapeutic approaches, pancreatic cancer remains a disease with a dismal prognosis. Among the mechanisms responsible for drug resistance, the most relevant are changes in individual genes or signaling pathways and the presence of highly resistant cancer stem cells(CSCs). In pancreatic cancer, CSCs represent 0.2%-0.8% of pancreatic cancer cells and are considered to be responsible for tumor growth, invasion, metastasis and recurrence. CSCs have been extensively studied as of late to identify specific surface markers to ensure reliable sorting and for signaling pathways identified to play a pivotal role in CSC self-renewal. Involvement of CSCs in pancreatic cancer pathogenesis has also highlighted these cells as the preferential targets for therapy. The present review is an update of the results in two main fields of research in pancreatic cancer, pathogenesis and therapy, focused on the narrow perspective of CSCs.

关键词： Cancer stem cells Pancreatic cancer Cancer stem cells signaling pathways Targeted therapy miRNA

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Recent advances in gastric cancer early diagnosis

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World Journal of Gastroenterology 2019年第17期25卷 2029-2044页

作者： Laura Necula Lilia Matei Denisa Dragu Ana I Neagu cristina mambet Saviana Nedeianu Coralia Bleotu Carmen C Diaconu Mihaela Chivu-Economescu Department of Cellular and Molecular Pathology Stefan S.Nicolau Institute of Virology Faculty of Medicine Titu Maiorescu University

Gastric cancer(GC) remains an important cause of cancer death worldwide with a high mortality rate due to the fact that the majority of GC cases are diagnosed at an advanced stage when the prognosis is poor and the treatment options are limited. Unfortunately, the existing circulating biomarkers for GC diagnosis and prognosis display low sensitivity and specificity and the GC diagnosis is based only on the invasive procedures such as upper digestive endoscopy. There is a huge need for less invasive or non-invasive tests but also highly specific biomarkers in case of GC. Body fluids such as peripheral blood, urine or saliva,stomach wash/gastric juice could be a source of specific biomarkers, providing important data for screening and diagnosis in GC. This review summarized the recently discovered circulating molecules such as microRNAs, long non-coding RNAs, circular RNAs, which hold the promise to develop new strategies for early diagnosis of GC.

关键词： Biomarkers Gastric cancer Early diagnosis Genetic and epigenetic alterations Circulating molecules

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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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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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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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Blood extracellular vesicles (EVs) of central nervous system origin: a window into the brain

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Neural Regeneration Research 2020年第1期15卷 55-56页

作者： cristina Agliardi Mario Clerici IRCCS Fondazione Don Carlo Gnocchi MilanoItaly(Agliardi CClerici M) Department of Pathophisiology and Transplantation University of MilanMilanoItaly(Clerici M)

Extracellular vesicles(EVs)are heterogeneous nano-sized vesicles of endocytic origin shed into blood and other body fluids such as urine,saliva,seminal fluid,ascites,amniotic liquid,synovial fluid,breast milk and cerebrospinal fluid(CSF)by quite all cell *** actively contribute to intercellular communication as they carry bioactive molecules that are selectively incorporated by the originating cell and are delivered to recipient cells over long and short distances(Simons and Raposo,2009).EVs can be divided into three main groups according to their size and cellular origin:1)exosomes(40–120 nm),that have an endocytic origin and are formed by inward budding of the limiting membrane of multivescicular bodies,which fuse with the plasma membrane and release exosomes into the extracellular space;2)microvesicles(50–1000 nm),budding directly off the plasma membrane;3)apoptotic bodies(>1000 nm),which are released during *** originating via distinct processes,different subtypes of EVs carry different proteins within their membrane and luminal compartments that reflect the phenotype of the tissue of origin.

关键词： Blood urine origin

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