1,720,962 research outputs found
Establishment and characterization of new breast cancer cell lines from A∆16HER2 transgenic mouse: A promising model to test innovative therapies
No full textThe human epidermal growth factor receptor 2 (HER2) is a validated therapeutic target in breast cancer therapy. However, increasing evidence points to a major role for the Δ16HER2 splice variant, which has been identified as a clinically important and tumor-specific HER2 molecular alteration promoting aggressive metastatic breast cancer and conferring resistance to anti-HER2 therapies. Δ16HER2 has an increased transforming potency compared to wild type HER2 receptor, since it promotes constitutive dimerization of the receptor and activation of Src-mediated oncogenic signaling pathways. Consistently, mice transgenic for the human Δ16HER2 isoform (Δ16HER2 mice) develop invasive mammary carcinomas with early onset and 100% penetrance. From these mice, an epithelial cancer cell line (CAM6 cells) was established and characterized. When injected in syngeneic mice, CAM6 cells give rise to tumours growing with a short latency time and able to metastasize to lung. Δ16HER2 mice and CAM6 cells represent, respectively, in vivo and in vitro models to investigate Δ16HER2 behavior in terms of oncogenicity and response to therapies. In this study, once confirmed the cooperation between Δ16HER2 and Src tyrosine kinase to promote breast tumorigenesis, we evaluated the ability of Saracatinib, a potent Src inhibitor, to suppress Δ16HER2-driven breast carcinogenesis. Saracatinib treatment resulted in a strong reduction of CAM6 cell migration and matrigel invasion, in a dose-dependent inhibition of CAM6 cell viability and in the induction of CAM6 cell death by apoptosis. In vivo experiments demonstrated that oral administration of Saracatinib reduced the development and growth of CAM6 transplantable tumors in FVB syngeneic mice and autochthonous mammary carcinogenesis in Δ16HER2 mice. Western blotting analysis revealed that suppression of Δ16HER2-positive breast cancer growth by Saracatinib was correlated exclusively with the inhibition Src activation, while the phosphorylation level of Δ16HER2 resulted unchanged. These results provided the rationale for targeting Src in Δ16HER2-positive breast cancer
Dorsomorphin reverses the mesenchymal phenotype of breast cancer initiating cells by inhibition of bone morphogenetic protein signaling
Get PDFIncreasing evidence supports the theory that tumor growth, homeostasis, and recurrence are dependent on a
small subset of cells with stem cell properties, redefined cancer initiating cells (CICs) or cancer stem cells. Bone
morphogenetic proteins (BMPs) are involved in cell-fate specification during embryogenesis, in the maintenance
of developmental potency in adult stem cells and may contribute to sustain CIC populations in breast carcinoma.
Using the mouse A17 cell model previously related to mesenchymal cancer stem cells and displaying properties
of CICs, we investigated the role of BMPs in the control of breast cancer cell plasticity. We showed that an autocrine
activation of BMP signaling is crucial for the maintenance of mesenchymal stem cell phenotype and tumorigenic
potential of A17 cells. Pharmacological inhibition of BMP signaling cascade by Dorsomorphin resulted in
the acquisition of epithelial-like traits by A17 cells, including expression of Citokeratin-18 and E-cadherin,
through downregulation of Snail and Slug transcriptional factors and Cyclooxygenase-2 (COX2) expression,
and in the loss of their stem-features and self-renewal ability. This phenotypic switch compromised A17 cell motility,
invasiveness and in vitro tumor growth. These results reveal that BMPs are key molecules at the crossroad
between stemness and cancer
The Second Ascoli Piceno Conference on Gene Vacciantion in Cancer, October 9-11 2013
No full textThis meeting brings together researchers and clinicians with an interest in gene vaccination in cancer prevention and management and seats them in the center of Italy, in the beautiful city of Ascoli Piceno.
The meeting will encourage participants to interact and discuss the pre-clinical and clinical application of gene vaccines
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Tailoring DNA vaccines: designing strategies against HER2-positive cancers
Get PDFThe crucial role of HER2 in epithelial transformation and its selective overexpression on
cancer tissues makes it an ideal target for cancer immunotherapies such as passive
immunotherapy withTrastuzumab.There are, however, a number of concerns regarding the
use of monoclonal antibodies which include resistance, repeated treatments, considerable
costs, and side effects that make active immunotherapies against HER2 desirable alternative
approaches.The efficacy of anti-HER2 DNA vaccination has been widely demonstrated
in transgenic cancer-prone mice, which recapitulate several features of human breast cancers.
Nonetheless, the rational design of a cancer vaccine able to trigger a long-lasting
immunity, and thus prevent tumor recurrence in patients, would require the understanding
of how tolerance and immunosuppression regulate antitumor immune responses and,
at the same time, the identification of the most immunogenic portions of the target protein.
We herein retrace the findings that led to our most promising DNA vaccines that, by
encoding human/rat chimeric forms of HER2, are able to circumvent peripheral tolerance.
Preclinical data obtained with these chimeric DNA vaccines have provided the rationale for
their use in an ongoing Phase I clinical trial (EudraCT 2011-001104-34)
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe 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
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe 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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