1,720,974 research outputs found
Role of neural cancer stem cells in angiogenesis
No full textGrowing evidence indicates the existence of small population of cells endowed with distinctive self-renewal capacity, tumorigenesis and resistance to conventional treatments, defined as cancer stem cells (CSCs) or tumor initiating cells. In addition, it is widely appreciated that the growth of new blood vessels and lymphatic vasculature, which occurs during angiogenesis and limphoangiogenesis, plays a key role in the process of the tumor growth. To this regards, an increasing number of studies showed that the employment of angiogenesis inhibitors might have significant therapeutic advantages. Fashinatingly, recent evidence demonstrated that CSCs play a role in angiogenesis, in particular in glioma, which, to date, represents a highly letal tumor tough to treat. We demonstrated that CSCs isoleted from both tumor (GCSCs) and peritumoral tissue (PCSCs) express a number of angiogenesis-related molecules, such as VEGF, HIF1alpha and HIF2alpha. In addition, VEGFR1 expression was found significantly reduced in PCSCs vs GCSCs whereas VGFR2 appeard to be largely heterogeneous in both stem cell types. With the aim to investigate the aptitude of CSCs derived neurospheres to regulate the angiogenesis process we performed in vitro migration analysis by means of boiden chamber assay. The results of this experiments indicate that ECs migration was stimulated in the presence of PCSCs but remained almost unaffected when endothelial cells where co-coltured with GCSCs. In conclusion, our data suggest that GCSCs and PCSCs contribute differently to tumor angiogenesis by activating distinct molecular mechanisms. PCSCs might therefore a key role in the recruiment as well as activation of ECs in peritumoral tissue
Epithelium-stroma reciprocal influence in breast cancer. Focus on plasma membrane features related to cell migratory/invasive ability
No full textInteractions occurring between malignant cells and stromal microenvi-ronment greatly influence progression of breast cancer. In a previous study, we co-cultured mammary cancer cells exhibiting different degrees of metastatic potential (MDA-MB-231>MCF-7) with fibroblasts isolated from breast healthy skin (normal fibroblasts, NFs) or breast tumor stroma (cancer-associated fibroblasts, CAFs). In this system, we demonstrated the influence exerted in particular by CAFs on malignant cells, leading to the acquisition of a more aggressive/invasive phenotype (i.e. reduced adhesion, epithelial-mesenchymal transition, enhanced plasma membrane fluidity and migration velocity/directness).
In the present study, we evaluated the reciprocal effect of breast tumor cells and fibroblasts in co-culture on the expression of the main enzyme regulating the fatty acids membrane composition, Stearoyl-CoA desaturase 1 (SCD1). Abnormally high levels of SCD1 have been reported in different cancers and transformed cells and the enzyme has been recently raised to the role of key regulator of cell growth, programmed cell death and car-cinogenesis. In our experience, Western blot analysis demonstrated a strong increase in SCD1 expression in both MCF-7 and MDA-MB-231 cells, resulting from their interaction with CAFs and, at a lesser extent, with NFs. High levels of SCD1 were also observed in both NFs and CAFs when co-cultured with MCF-7 cells. MDA-MB-231 cells more slightly up-regulated the enzyme expression in NFs or even induced a certain inhi-bition in CAFs.
The fibroblast-triggered up-regulation of SCD1 in cancer cells could rea-sonably be considered the molecular event underlying the increase of membrane fluidity, previously observed in tumor cells co-cultured with NFs and, notably, with CAFs. This change might downstream promote the pre-viously described increase in tumor cell motility
Expression of angiogenesis-related factors in glioblastoma and peritumor tissue
No full textGlioblastoma (GBM) is characterized by extensive angiogenesis, mostly triggered by tumor hypoxia. We previously reported that in GBM and peritumor tissue microvessels show a similar morphology and endothelial cells express CD105, the best marker for newly-formed tumor vessels. In this study, to better understand the role played by angiogenesis in GBM progression, the expression of HIF-1α and -2α, VEGF and its receptors (VEGFR-1 and -2) in GBM and in peritumor tissue was investigated. Tissue samples were obtained from fifty patients. In paraffin-embedded specimens, derived from enhanced lesions (first area) of GBM and white matter at a distance ≤1 mm from the tumor edge (second area), the expression of HIF-1α and -2α, VEGF, VEGFR-1 and -2 was evaluated by immunohistochemistry.
Immunoreactivity for all markers was detected not only in the tumor, but also in the peritumor tissue and it was present in neoplastic cells, in endothelium and in apparently normal glial cells. HIF-1α and -2α expression was mainly confined in the nuclei. VEGF, localized in the cytoplasm, showed diffused expression with intense staining in the first area. VEGFR-1 and -2 immunopositivity was dominantly observed at the membrane level. A significant difference in the expression of VEGF and VEGFR-2 between GBM and peritumor tissue was observed. The high heterogeneity in the expression of the other molecules might explain the absence of significant differences between the first and second area. No correlation was observed between the analyzed molecules and survival time. Our study demonstrates that HIF-1α, HIF-2α, VEGF and its receptors are present in peritumor areas, probably reflecting the reduced oxygen availability. Since the response to anti-VEGF therapy is transient and the majority of patients relapse, our findings may lead to consider the molecules expressed in the peritumor tissue as a target for new treatments counteracting angiogenesis.
Supported by FIRB Accordi di Programma 201
CANCER STEM CELLS FROM GBM AND PERITUMOR TISSUE
No full textIt has been reported that distinct cancer stem cell-like (CSC) populations can be isolated from different regions of the same human glioblastoma (GBM), namely from the tumor core or from peritumor tissue. Although originating from common ancestor cells, these populations can exhibit different characteristics in terms of growth properties, genetic anomalies, and their tumor initiating ability. In particular, CSCs deriving from the GBM core (GCSCs) induced tumors in immunodeficent mice with an efficiency of 95% while CSCs isolated from peritumor tissue (PCSCs) have much less, if any, tumorigenic potential. In this study, we aimed at gaining a deeper insight into the features of both GCSC and PCSC populations. By means of immunocytochemical and Western blot analysis, we investigated the expression of stem cell markers such as nestin, Sox2, Musashi-1, CD133, and also NG2 and GD3 (associated with invasion and angiogenesis), as well as markers linked to proliferation (i.e., pJNK). Immunocytochemistry showed that all these molecules are expressed in both GCSCs and PCSCs. Furthermore, Western blot analysis on nestin, Musashi-1, and pJNK proteins, revealed a higher expression in GCSCs than in PCSCs. The Sox2 protein was equally expressed in GCSCs and PCSCs, probably because Sox2 is critical for the maintenance of broader stem cell potential. Yet, GCSCs that grew as neurospheres showed a higher growth rate than PCSCs, which were generally found to grow as adherent cells or floating neurospheres. TEM showed differences between GCSCs and PCSCs in terms of cytoskeletal component expression and presence of cell-cell junctions. Taken together, our data confirm that, at least in some instances, GCSCs can be more aggressive than PCSCs which are likely to begin their malignant transformation in a microenvironment that may be influenced by various factors deriving from the main tumor mass.
Supported by FIRB “Accordi di Programma” 201
Glioblastoma cancer stem cells and angiogenesis
No full textIt is widely accepted that glioblastoma (GBM) develops from cancer stem cells (CSCs), a subset of stem-like cells displaying high resistance to treatment. Our recent findings showed the existence of a CSC type, residing in GBM peritumor tissue (PCSCs), that bears distinct characteristics from CSCs of the tumor mass (GCSCs) and that, after surgical resection, might represent a reservoir of cells able to recapitulate the tumor. In this setting, characterization of PCSCs appears to be crucial in order to identify novel effective therapeutic targets. Thus, our aim was to investigate GCSCs and PCSCs role in angiogenesis, a key event in both GBM and peritumor tissue, whose vasculature shows features similar to those found in the tumor mass.
In particular, we analyzed, by immunocytochemistry (ICC), Western blotting or real-time PCR, the expression of molecules involved in hypoxia and angiogenesis, such as HIF1α, HIF2α, and VEGF along with its receptors (VEGFR1, VEGFR2). ICC has highlighted the presence and the specific localization of these molecules in both GCSCs and PCSCs. The two cell populations showed comparable levels of VEGF. The transcript of VEGFR1 was in general expressed at higher levels in GCSCs than in PCSCs, while VEGFR2 mRNA and protein did not show a unique trend of expression.
The presence of VEGF and its receptors in both GCSCs and PCSCs suggests that, besides well-known paracrine loops, autocrine signalings are also involved in tumor angiogenesis. Moreover, the expression of angiogenesis markers in PCSCs suggests these cells to have a direct role in peritumor tissue new vessel formation. In this regard, PCSCs should be considered a promising therapeutic target to counteract the angiogenesis-supported tumor progression.
Supported by FIRB Accordi di Programma 201
CANCER STEM CELLS FROM GLIOBLASTOMA AND PERITUMOR TISSUE
No full textIt has been reported that distinct cancer stem cell-like (CSC) populations can be isolated from different regions of the same human glioblastoma (GBM), namely from the tumor core or from peritumor tissue. Although originating from common ancestor cells, these populations can exhibit different characteristics in terms of growth properties, genetic anomalies, and their tumor initiating ability. In particular, CSCs deriving from the GBM core (GCSCs) induced tumors in immunodeficient mice with an efficiency of 95% while CSCs isolated from peritumor tissue (PCSCs) have much less, if any, tumorigenic potential. In this study, we aimed at gaining a deeper insight into the features of both GCSC and PCSC populations. By means of immunocytochemical and Western blot analysis, we investigated the expression of stem cell markers such as nestin, Sox2, Musashi-1, CD133, and also NG2 and GD3 (associated with invasion and angiogenesis), as well as markers linked to proliferation (i.e., pJNK). Immunocytochemistry showed that all these molecules are expressed in both GCSCs and PCSCs. Furthermore, Western blot analysis on nestin, Musashi-1, and pJNK proteins, revealed a higher expression in GCSCs than in PCSCs. The Sox2 protein was equally expressed in GCSCs and PCSCs, probably because Sox2 is critical for the maintenance of broader stem cell potential. Yet, GCSCs that grew as neurospheres showed a higher growth rate than PCSCs, which were generally found to grow as adherent cells or floating neurospheres. TEM showed differences between GCSCs and PCSCs in terms of cytoskeletal component expression and presence of cell-cell junctions. Taken together, our data confirm that, at least in some instances, GCSCs can be more aggressive than PCSCs which are likely to begin their malignant transformation in a microenvironment that may be influenced by various factors deriving from the main tumor mass.
Supported by FIRB “Accordi di Programma” 201
Involvement of cancer stem cells in glioblastoma angiogenesis
No full textIt is widely accepted that glioblastoma (GBM) develops from cancer stem cells (CSCs), a subset of stem-like cells displaying high resistance to treatment. In fact, despite aggressive therapy, 90% of patients relapse within 2 cm from tumor edge. Our recent findings showed the existence of a CSC type, residing in GBM peritumor tissue (PCSCs), that bears distinct characteristics from CSCs of the tumor mass (GCSCs). It should be considered the possibility that, after surgical resection, PCSCs might represent a reservoir of cells able to recapitulate the tumor. In this setting, characterization of PCSCs appears to be crucial in order to identify novel effective therapeutic targets. Thus, our aim was to investigate GCSCs and PCSCs role in angiogenesis, a key event in both GBM and peritumor tissue, whose vasculature shows features similar to those found in the tumor mass.
In particular, we analyzed, by immunocytochemistry (ICC), Western blotting or real-time PCR, the expression of molecules involved in hypoxia and angiogenesis, such as HIF1α, HIF2α, and VEGF along with its receptors (VEGFR1, VEGFR2). ICC has highlighted the presence and the specific localization of these molecules in both GCSCs and PCSCs. The two cell populations showed comparable levels of VEGF. The transcript of VEGFR1 was in general expressed at higher levels in GCSCs than in PCSCs, while VEGFR2 mRNA and protein did not show a unique trend of expression.
The expression of VEGF and its receptors in both GCSCs and PCSCs suggests that, besides well-known paracrine loops, autocrine signalings are also involved in tumor angiogenesis. Moreover, the expression of angiogenesis markers in PCSCs suggests these cells to have a direct role in peritumor tissue new vessel formation. In this regard, PCSCs should be considered a promising therapeutic target to counteract the angiogenesis-supported tumor progression.
Supported by FIRB Accordi di Programma 201
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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