672 research outputs found
Tumor-educated mesenchymal stem cells promote pro-metastatic phenotype
No full textMultipotent mesenchymal stem cells (MSCs) are recruited into tumor microenvironment in response to multiple signals produced by cancer cells. Molecules involved in their homing to tumors are the same inflammatory mediators produced by injured tissues: chemokines, cytokines and growth factors. When MSCs arrive into the tumor microenvironment these are “educated” to have pro-metastatic behaviour. Firstly, they promote cancer immunosuppression modulating both innate and adaptive immune systems. Moreover, tumor associated-MSCs trans-differentiating into cancer-associated fibroblasts can induce epithelial-mesenchymal-transition program in tumor cells. This process determinates a more aggressive phenotype of cancer cells by increasing their motility and invasiveness and favoring their dissemination to distant sites. In addition, MSCs are involved in the formation and modelling of pre-metastatic niches creating a supportive environment for colonization of circulating tumor cells.
The development of novel therapeutic approaches targeting the different functions of MSCs in promoting tumor progression as well as the mechanisms underlying their activities could enhance the efficacy of conventional and immune anti-cancer therapies.
Furthermore, many studies report the use of MSCs engineered to express different genes or as vehicle to specifically deliver novel drugs to tumors exploiting their strong tropism. Importantly, this approach can enhance local therapeutic efficacy and reduce the risk of systemic side effects
Online resources for mathematics in the scientific virtual reference desk
No full textThe present work briefly describes the Virtual Reference Desk for mathematics elaborated during the time I worked at the CERN Library (European Laboratory for Particle Physics or Laboratoire européen pour la physique des particules) in Geneva. This instrument is dedicated to the CERN librarians, with whom I have shared important moments of my professional career. In particular, I would like to gratefully acknowledge their valuable co-operation and assistance during our time spent working together. The Web metasource is comprised of three directories, annotated and interrelated with dual application: The first is intended as a work tool for librarians working in mathematics libraries, but above all for librarians of high energy physics, who more often than not must turn to mathematics and the use of mathematical applications and models for the physical sciences and in particular particle physics. The second is an on-line resource for mathematics; that is, a Virtual Reference Desk for the community of mathematicians, with whom I have been collaborating for some twenty years at the University of Padova. The bibliographical instrument is born from the need to have at our disposal a scientific Virtual Reference Desk created according to the needs of those working in physics and mathematics libraries – a tool which is comprised of materials collected during years of work as much as material available on-line through the use of new technologies
Intervista con Antonella De Robbio, Responsabile del Settore Progetti e Biblioteca Digitale del Centro d'Ateneo per le Biblioteche CAB dell' Università di Padova e Referente per il diritto d'autore del Sistema Bibliotecario di Ateneo
No full textThe interview with Antonella De Robbio – manager of the “Project Sector and Digital Library” for CAB (Centro di Ateneo per le Biblioteche) of the University of Padua and copyright expert for Sistema Bibliotecario di Ateneo – was published in Pinali news.
Antonella De Robbio answered the following questions:
1) How to deal with the issues of author’s intellectual and economic rights in the context of scientific publishing and digital library?
2) What is the influence of the digital approach on the traditional ways to create and disseminate scientific communication?
3) In your opinion, can the experiences of University Press and the Open Archives represent the path to follow in order to overcome the paradox that a scientific author is also the user of his publisher?
4) Which are the outcomes of the fight between copyright and copyleft?
5) Which of these approaches are more suitable to label the metaphor of the “Society of Knowledge”
Role of Aquaporins in the Physiological Functions of Mesenchymal Stem Cells
No full textAquaporins (AQPs) are a family of membrane water channel proteins that control osmotically-driven water transport across cell membranes. Recent studies have focused on the assessment of fluid flux regulation in relation to the biological processes that maintain mesenchymal stem cell (MSC) physiology. In particular, AQPs seem to regulate MSC proliferation through rapid regulation of the cell volume. Furthermore, several reports have shown that AQPs play a crucial role in modulating MSC attachment to the extracellular matrix, their spread, and migration. Shedding light on how AQPs are able to regulate MSC physiological functions can increase our knowledge of their biological behaviours and improve their application in regenerative and reparative medicine
Bone Marrow-Derived Mesenchymal Stem Cells Promote Growth and Migration of Osteosarcoma and Hepatocarcinoma Cells through CXCR4 and AQP1
No full textIncreasing evidences suggest that bone marrow-derived mesenchymal stem cells (BM-MSCs) are recruited into the stroma of developing
tumors where they contribute to progression by enhancing tumor growth and metastasis, or by inducing anticancer-drug resistance.
Although many experimental evidences exist supporting the therapeutic potential of MSCs, the mechanism of homing and recruitment of
MSCs into tumors and their potential role in malignant tissue progression is still not well understood.
The aim of this study was to elucidate the role of BM-MSCs to promote tumor cell proliferation and invasion. Therefore, we analyzed
whether chemokine receptor type 4 (CXCR4) and water channel molecule, aquaporin 1 (AQP1), both known to play a key role in cancer
metastases, could affect MSCs mediated osteosarcoma and hepacarcinoma progression.
We used human mesenchymal stem cell isolated from bone marrow aspirates by gradient centrifugation and seeded in standard cell
culture conditions. MSCs were grown for 48 h in medium with 1% fetal bovine serum to obtain conditioned medium (MSCs-CM) that
was collected, filtered and stored at -20 °C. CXCR4 and AQP1 protein level was evaluated in human hepatocarcinoma (SNU-398) and
osteosarcoma (U2OS) cells exposed to MSCs-CM. Proliferation of tumor cells co-cultured with MSCs or cultured in presence of MSCs-CM
was evaluated by MTT assay. Tumor migration and invasion were assayed in 24-well transwell chambers using 8 um pore membrane precoated
with collagen/fibronectin or matrigel, respectively. SNU-398 and U2OS cells, suspended in serum-free medium, were added to the
upper chamber and incubated for 24-48 h at 37 °C in presence of MSCs-CM or MSCs (lower chamber) used as chemoattractants. Tumor
cells pre-treated with a CXCR4 antagonist (AMD3100) or AQP1 antibody were also analyzed for proliferation, migration and invasion.
Furthermore, involvement of Akt and/or Erk signalling pathways in tumor progression MSCs-mediated was examined.
Our results showed that CXCR4 and AQP1 expression is increased in human hepatocarcinoma (SNU-398) and osteosarcoma (U2OS)
cells in presence of MSCs secreted factors. Conditioned medium from MSCs promoted proliferation, migration and invasion of tumor
cells, whereas inhibition of CXCR4 and AQP1 significantly down-regulated these effects. Furthermore, SNU-398 and U2OS cells showed an
enhancement of p-Akt and p-Erk levels when they were cultured in presence of MSCs-CM.
In conclusion these findings suggest that bone-marrow derived mesenchymal stem cells can promote the proliferation and invasion of
osteosarcoma and hepatocarcinoma cells through CXCR4 and AQP1 overexpression. In addition, we found that MSCs may contribute to
tumor progression by PI3K/Akt pathway and/or Ras/Erk cascade
Expression of aquaporin-1 and cxcr4 in ovine mesenchymal stem cell.
No full textMesenchymal stem cells (MSCs) are a well characterized and highly adaptable cell source for regenerative medicine and tissue
engineering. Ovine species is considered as a valuable model for human bone turnover and remodeling activity, due to the fact that adult
animals show similar bone structure and composition [1]. Therefore, in orthopedic research, sheep are frequently employed for critical-size
bone defects, which are then treated with different biomaterials combined with (predifferentiated) MSCs. Despite a considerable number
of reports employing ovine MSCs (oMSCs) in tissue engineering, their molecular characterization is limited to few studies. Unlike human
MSCs, ovine MSC are not well studied regarding isolation, expansion and surface antigen expression of oMSC.
Recently, a family of 13 water-transporting membrane channel proteins, called aquaporins (AQPs) known for their key role in fluid
transport in various epithelial and endothelial tissues, have been extensively studied [2]. Such proteins seem to have important functions in
diverse biological processes related to cell migration, proliferation, apoptosis and cell volume-regulation. Furthermore, many studies have
demonstrated that stem cell migration and organ-specific homing are regulated by chemokine and their receptors [3].
Therefore, the aim of this work was to determine whether water channel molecule, aquaporin 1 (AQP1) and chemokine receptor type 4
(CXCR4) could be expressed in o-MSCs to regulate some cellular events. MSC isolated from fresh bone marrow obtained from the posterior
iliac crest of sheep were cultured on flasks by incubation in a humidified atmosphere at 37 °C with 5% CO2 in culture medium (a-MEM)
supplemented with 10% fetal bovine serum (FBS). Further phenotypical characterization of MSC was performed via cytofluorimetric
analysis of cell surface markers at passage 2. MSC resulted positive for CD44, CD73, CD90, CD105, CD146 and negative for CD34 and
CD45. The analysis was performed using a FC500 flow cytometer (Beckman Coulter, Brea, CA, USA). To obtain conditionated Medium
(CM), oMSCs were grown for different times 24 h, 48 h and 72 h in cultured medium with 1% FBS. Then, CM was collected, filtered and
stored in aliquots at -20 °C until required, to investigate the impact of CM composition on AQP1 and CXCR4 expression. Morphological
changes of cells exposed to CM were observed by light microscope. Whole protein extracts were prepared and analyzed by western blotting.
Furthermore, oMSCs proliferation and migration analysis were performed also in presence of CM.
Our results showed that oMSCs cultured in 10% FCS medium express high level of AQP1 and CXCR4. Furthermore, CM after an
exposure to oMSCs for 48 h, causes an increase of AQP1 and CXCR4 expression as well as an enhancement of cell proliferation. In
conclusion, the results of this study suggest that oMSCs produce some regulatory factors (cytokines, chemokines or growth factors) that
promote their migration by autoctine pathways [4]. It is well known that these soluble mediators may act directly, triggering intracellular
mechanisms of injured cells, or indirectly, inducing secretion of functionally active mediators by neighboring cells. For these reasons, the
results of this study could improve the knowledge on oMSC characterization in consideration of their application in regenerative medicine
because of handling and housing, cost, and ethical acceptance
Literacy in Neapolitan Women's Convents in the Middle Ages and the Contribution of Digital Archives on Monasterium.Net
No full textAntonella Ambrosio seeks a viable way of carrying out research on this topic: the palaeographic analysis of the few available sources using a multidisciplinary approach that combines diplomatics, archival, and historical research. This approach ensures the appropriate contextualization of the source both historically and culturally. In "Literacy in Neapolitan Women's Convents: An Example of Female Handwriting in a Late Fifteenth-Century Accounts Ledger", Ambrosio provides a case study, analysing a single piece of handwriting evidence. The source is an accounts ledger from the Dominican convent of Santi Pietro e Sebastiano compiled in the second half of the fifteenth century, from 1485 to 1496. Using an analytical approach, the author has identified the handwriting of a particular (anonymous) nun from the convent; Ambrosio studies the script the nun used and formulates hypotheses about her cultural background and how she learned to write. The palaeographic analysis is fully contextualized thanks to the reconstruction of the old convent archive, a reconstruction helped by using digital technologies now accessible online at Monasterium.net. As Ambrosio's work demonstrates, technological advances may aid codicological work but careful palaeographic analysis is necessary to ascertain the participation of female scribes. In this case we witness the scribal development of a nun who began with a basic knowledge of writing and who went on to perform her practical task not well but adequately for the purpose
Inhibition of AQP1 Hampers Osteosarcoma and Hepatocellular Carcinoma Progression Mediated by Bone Marrow-Derived Mesenchymal Stem Cells
No full textThe complex cross-talk between tumor cells and their surrounding stromal environment
plays a key role in the pathogenesis of cancer. Among several cell types that constitute the tumor
stroma, bone marrow-derived mesenchymal stem cells (BM-MSCs) selectively migrate toward
the tumor microenvironment and contribute to the active formation of tumor-associated stroma.
Therefore, here we elucidate the involvement of BM-MSCs to promote osteosarcoma (OS) and
hepatocellular carcinoma (HCC) cells migration and invasion and deepening the role of specific
pathways. We analyzed the function of aquaporin 1 (AQP1), a water channel known to promote
metastasis and neoangiogenes. AQP1 protein levels were analyzed in OS (U2OS) and HCC (SNU-398)
cells exposed to conditioned medium from BM-MSCs. Tumor cell migration and invasion in response
to BM-MSC conditioned medium were evaluated through a wound healing assay and Boyden
chamber, respectively. The results showed that the AQP1 level was increased in both tumor cell
lines after treatment with BM-MSC conditioned medium. Moreover, BM-MSCs-mediated tumor cell
migration and invasion were hampered after treatment with AQP1 inhibitor. These data suggest that
the recruitment of human BM-MSCs into the tumor microenvironment might cause OS and HCC cell
migration and invasion through involvement of AQP1
Preclinical imaging evaluation of mirnas’ delivery and effects in breast cancer mouse models: A systematic review
No full textBackground: We have conducted a systematic review focusing on the advancements in preclinical molecular imaging to study the delivery and therapeutic efficacy of miRNAs in mouse models of breast cancer. Methods: A systematic review of English articles published in peer-reviewed journals using PubMed, EMBASE, BIOSISTM and Scopus was performed. Search terms included breast cancer, mouse, mice, microRNA(s) and miRNA(s). Results: From a total of 2073 records, our final data extraction was from 114 manuscripts. The most frequently used murine genetic background was Balb/C (46.7%). The most frequently used model was the IV metastatic model (46.8%), which was obtained via intravenous injection (68.9%) in the tail vein. Bioluminescence was the most used frequently used tool (64%), and was used as a surrogate for tumor growth for efficacy treatment or for the evaluation of tumorigenicity in miRNA-transfected cells (29.9%); for tracking, evaluation of engraftment and for response to therapy in metastatic models (50.6%). Conclusions: This review provides a systematic and focused analysis of all the information available and related to the imaging protocols with which to test miRNA therapy in an in vivo mice model of breast cancer, and has the purpose of providing an important tool to suggest the best preclinical imaging protocol based on available evidence
Cross-talk between bone marrow-derived mesenchymal stem cells and tumor cells: role of cxcr4 and aqp1 in osteosarcoma and hepatocarcinoma progression.
No full text- …
