117,322 research outputs found
The Angiogenic Switch: Implications in the Regulation of Tumor Dormancy
No full textAngiogenesis plays an established role in the growth promotion of dormant micrometastasis, because blood vessels deliver oxygen and nutrients into the tumor microenvironment. A discrete event termed "the angiogenic switch" has been recognized as key in promoting the transition towards a clinically aggressive tumor. This concept generally describes a permanent change in the angiogenic capacity of the tumor sustained by genetic events occurring in cancer cells. Recent evidence, however, indicates that a transient angiogenic switch delivered by components of the tumor microenvironment can also convey tumorigenic properties to tumor cells. Why is the angiogenic switch so fundamental in the promotion of tumor growth? In addition to the recognized feeding function of blood vessels, there is accumulating evidence suggesting that endothelial cells - and perhaps other cellular components of the microenvironment - communicate both positive and negative signals to tumor cells. This cross-talk between heterogeneous cell types could turn out to be important in the regulation of cancer cells' behaviour. In this review, we discuss the possible implications of the angiogenic switch on our understanding of the regulation of tumor dormancy
Angiogenesis meets immunology: Cytokine gene therapy of cancer
No full textDelivery of cytokine genes at the tumor site in pre-clinical models has been shown to recruit host inflammatory cells followed by inhibition of tumor growth. This local effect is often accompanied by systemic protection mediated by the immune system, mainly by CD8+ T and NK cells. On this basis, cytokine gene-transduced tumor cells have widely been used as vaccines in clinical trials, which have shown good safety profiles and some local responses but substantial lack of systemic efficacy. Are these findings the end of the story? Possibly not, if major improvements will be attained in the coming years. These should be directed at the level of gene selection and delivery, in order to identify the optimal cytokine and achieve efficient and durable cytokine expression, and at the level of improving immune stimulation, i.e. by co-administration of co-stimulatory molecules including B7 and CD40, or boosting the expression of tumor antigens or MHC class I molecules. Interestingly, some of the..
Side population and cancer stem cells: Therapeutic implications
No full textNew studies indicate that the side population (SP) and cancer stem cells (CSC) drive and maintain many types of human malignancies. SP and CSC appear to be highly resistant to chemo- and radio-therapy and this knowledge is now reshaping our therapeutic approach to cancer. Several studies have pioneered the possibility of specifically targeting CSC and SP cells by exploiting pathways involved in drug resistance, or forcing these cells to proliferate and differentiate thus converting them into a target of conventional therapies. Moreover, certain cytokines - such as IFN-alpha - appear to modulate SP and stem cell functions, and this associates with remarkable therapeutic activity in animal models. These recent findings underscore the need of a more comprehensive view of the interactions between cytokines and key regulatory pathways in SP and CSC
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Interferon-alpha-engineered Multipotent Mesenchymal Stromal Cells for the treatment of myeloma
No full textBone marrow mesenchymal stromal cells (BM-MSCs) are nonhematopoietic progenitor cells with multilineage differentiation potential. Exogenously administered BM-MSCs have been shown to survive and proliferate in the presence of malignant cells, becoming stromal cells and supporting tumor growth. Thus, BM-MSCs are attractive candidates to deliver biologically active molecules in the tumor environment in vivo and to enhance specific immune responses. Interferon-a (IFN-a) has been used for years for the maintenance treatment of multiple myeloma (MM), but its administration is limited by the temporary efficacy and the toxicity. We analyzed the in vivo effects of mouse BM-MSCs transduced with IFN-a cDNA in the Sp6 plasmacytoma mouse model. BM-MSCs were transduced with a lentiviral vector containing EGFP cDNA or murine IFN-a cDNA (efficiency = 70%). Two months-old Balb/c mice (Balb/cByJIco, Charles River Italia, Calco, LC, Italy) (H-2d), were injected subcutaneously (s.c.) with the tumorigenic dose of 0.5x106 Sp6 cells (H-2d). The same mice were then weekly injected with 0.5x106 BMMSCs/ IFN-a (1, 4 or 8 doses), in the same anatomical quarter. Some mice was injected s.c. with Sp6 and with BM-MSCs/EGFP s.c. or intravenously
(i.v.) to test in vivo homing. Tumor immunohistochemistry was performed with anti-von Willebrand factor, anti- a -smooth muscle actin, anti-CD4, anti-CD8, anti-asialo GM1, anti-CD45, anti-CD90, anti-murine IFN-a. BM-MSCs were capable of homing into Sp6 tumor, forming clusters of cells. Treatment with BM-MSCs/IFN-a resulted in a significant delay in the onset of palpable tumors (event free survival, EFS, of 50% at day +17 for 1 dose, +20 for 4 doses and +64, for 8 doses, whereas Sp6 alone or coinjected with BM-MSCs showed tumor incidence
of 100% 10-13 days after injection). Weekly delivery of BMMSCs/ IFN-a induced a significant decrease of kinetics tumor growth and an increment of overall survival (OS) (median OS in controls: 19 days, animals receiving BM-MSCs: 17 days, mice treated with 1 and 4 doses of BM-MSCs/IFN-a: 30-31 days, mice treated with 8 doses:77 days). The antitumor effect is associated with tumor necrosis, reduction in microvessel density, and NK cell infiltration. These findings indicate that transduced BM-MSCs could be useful to deliver anti-cancer molecules in the microenvironment of myeloma and become a promising tool for specific, low-toxic, and long-lasting anti-myeloma therapy
Square Dancing with the Stars to Enhance Dynamic Hirschman Linkages?
No full textIn this Presidential Address, the author takes the reader on a reconnaissance of his life and time as a regional scientist. He points out scenery he found scintillating along the way, hoping that some may pick up the banner and chew on a few of the ideas for a while. He suggests a revisit to Albert O. Hirschman’s notion of key sectors and more empirical analysis related to Marcus Berliant’s and Masahisa Fujita’s notion of knowledge creation and transfer.Presidential Address, San Antonio, Texas, March 29, 2014 (53rd Meetings of the Southern Regional Science Association
Appropriate Similarity Measures for Author Cocitation Analysis
No full textWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Notch3-mediated regulation of MKP-1 levels promotes survival of T acute lymphoblastic leukemia cells
No full textActivation of the Notch pathway occurs commonly in T acute lymphoblastic leukemia (T-ALL) because of mutations in Notch1 or Fbw7 and is involved in the regulation of cell proliferation and survival. Deregulated Notch3 signalling has also been shown to promote leukemogenesis in transgenic mice, but the targets of Notch3 in human T-ALL cells remain poorly characterized. Here, we show that Notch3 controls levels of mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1). In a model of T-ALL cell dormancy, both Notch3 activation and MKP-1 expression were upregulated in aggressive compared with dormant tumors, and this inversely correlated with the levels of phosphorylated p38 and extracellular signal-regulated kinase1/2 (ERK1/2) MAPKs, two canonical MKP-1 targets. We demonstrate that MKP-1 protein levels are regulated by Notch3 in T-ALL cell lines because its silencing by RNA interference or treatment with γ-secretase inhibitors induced strong MKP-1 reduction whereas activation of Notch3 signalling had the opposite effect. Furthermore, MKP-1 has an important role in T-ALL cell survival because its attenuation by short hairpin RNA significantly increased cell death under stress conditions. This protective function has a key role in vivo, as MKP-1-deficient cells showed impaired tumorigenicity. These results elucidate a novel mechanism downstream of Notch3 that controls the survival of T-ALL cells
Letter from unknown writer to Jesse L. Boyce
No full textLetter to Jesse L. Boyce from unknown author (possibly Jack) about the investigation into the powder magazine located in the Grand Canyon. Some personal news is included in the letter such as the writer's marriage to the daughter of C.A. Taylor, former Supervisor of Cochise County
Dispelling the Myths Behind First-author Citation Counts
No full textWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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