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  1. Article ; Online: Inhibition of the Wnt Signalling Pathway

    Lorenzo Castagnoli / Elda Tagliabue / Serenella M. Pupa

    International Journal of Molecular Sciences, Vol 21, Iss 9069, p

    An Avenue to Control Breast Cancer Aggressiveness

    2020  Volume 9069

    Abstract: Breast cancer (BC) is the most common tumour in women. Although the introduction of novel therapeutic approaches in clinical practice has dramatically improved the clinical outcome of BC patients, this malignant disease remains the second leading cause ... ...

    Abstract Breast cancer (BC) is the most common tumour in women. Although the introduction of novel therapeutic approaches in clinical practice has dramatically improved the clinical outcome of BC patients, this malignant disease remains the second leading cause of cancer-related death worldwide. The wingless/integrated (Wnt) signalling pathway represents a crucial molecular node relevantly implicated in the regulation of normal somatic stem cells as well as cancer stem cell (CSC) traits and the epithelial–mesenchymal transition cell program. Accordingly, Wnt signalling is heavily dysregulated in BC, and the altered expression of different Wnt genes is significantly associated with cancer-related aggressive behaviours. For all these reasons, Wnt signalling represents a promising therapeutic target currently under clinical investigation to achieve cancer eradication by eliminating CSCs , considered by most to be responsible for tumour initiation, relapse, and drug resistance. In this review, we summarized the current knowledge on the Wnt signalling pathway in BC and have presented evidence implicating the suitability of Wnt targeting in an attempt to improve the outcome of patients without affecting the normal somatic stem cell population.
    Keywords Wnt pathway ; breast cancer ; cancer stem cells ; epithelial-mesenchymaltransition ; resistance to therapy ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Language English
    Publishing date 2020-11-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Cancer Stem Cells

    Lorenzo Castagnoli / Francesca De Santis / Tatiana Volpari / Claudio Vernieri / Elda Tagliabue / Massimo Di Di Nicola / Serenella M Pupa

    Cells, Vol 9, Iss 3, p

    Devil or Savior—Looking behind the Scenes of Immunotherapy Failure

    2020  Volume 555

    Abstract: Although the introduction of immunotherapy has tremendously improved the prognosis of patients with metastatic cancers of different histological origins, some tumors fail to respond or develop resistance. Broadening the clinical efficacy of currently ... ...

    Abstract Although the introduction of immunotherapy has tremendously improved the prognosis of patients with metastatic cancers of different histological origins, some tumors fail to respond or develop resistance. Broadening the clinical efficacy of currently available immunotherapy strategies requires an improved understanding of the biological mechanisms underlying cancer immune escape. Globally, tumor cells evade immune attack using two main strategies: avoiding recognition by immune cells and instigating an immunosuppressive tumor microenvironment. Emerging data suggest that the clinical efficacy of chemotherapy or molecularly targeted therapy is related to the ability of these therapies to target cancer stem cells (CSCs). However, little is known about the role of CSCs in mediating tumor resistance to immunotherapy. Due to their immunomodulating features and plasticity, CSCs can be especially proficient at evading immune surveillance, thus potentially representing the most prominent malignant cell component implicated in primary or acquired resistance to immunotherapy. The identification of immunomodulatory properties of CSCs that include mechanisms that regulate their interactions with immune cells, such as bidirectional release of particular cytokines/chemokines, fusion of CSCs with fusogenic stromal cells, and cell-to-cell communication exerted by extracellular vesicles, may significantly improve the efficacy of current immunotherapy strategies. The purpose of this review is to discuss the current scientific evidence linking CSC biological, immunological, and epigenetic features to tumor resistance to immunotherapy.
    Keywords cancer stem cells ; immunotherapy ; tumor microenvironment ; immune checkpoint blockade ; Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2020-02-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Identification of relevant conformational epitopes on the HER2 oncoprotein by using Large Fragment Phage Display (LFPD).

    Federico Gabrielli / Roberto Salvi / Chiara Garulli / Cristina Kalogris / Serena Arima / Luca Tardella / Paolo Monaci / Serenella M Pupa / Elda Tagliabue / Maura Montani / Elena Quaglino / Lorenzo Stramucci / Claudia Curcio / Cristina Marchini / Augusto Amici

    PLoS ONE, Vol 8, Iss 3, p e

    2013  Volume 58358

    Abstract: We developed a new phage-display based approach, the Large Fragment Phage Display (LFPD), that can be used for mapping conformational epitopes on target molecules of immunological interest. LFPD uses a simplified and more effective phage-display approach ...

    Abstract We developed a new phage-display based approach, the Large Fragment Phage Display (LFPD), that can be used for mapping conformational epitopes on target molecules of immunological interest. LFPD uses a simplified and more effective phage-display approach in which only a limited set of larger fragments (about 100 aa in length) are expressed on the phage surface. Using the human HER2 oncoprotein as a target, we identified novel B-cell conformational epitopes. The same homologous epitopes were also detected in rat HER2 and all corresponded to the epitopes predicted by computational analysis (PEPITO software), showing that LFPD gives reproducible and accurate results. Interestingly, these newly identified HER2 epitopes seem to be crucial for an effective immune response against HER2-overexpressing breast cancers and might help discriminating between metastatic breast cancer and early breast cancer patients. Overall, the results obtained in this study demonstrated the utility of LFPD and its potential application to the detection of conformational epitopes on many other molecules of interest, as well as, the development of new and potentially more effective B-cell conformational epitopes based vaccines.
    Keywords Medicine ; R ; Science ; Q
    Subject code 500
    Language English
    Publishing date 2013-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: The human splice variant Δ16HER2 induces rapid tumor onset in a reporter transgenic mouse.

    Cristina Marchini / Federico Gabrielli / Manuela Iezzi / Santa Zenobi / Maura Montani / Lucia Pietrella / Cristina Kalogris / Anna Rossini / Valentina Ciravolo / Lorenzo Castagnoli / Elda Tagliabue / Serenella M Pupa / Piero Musiani / Paolo Monaci / Sylvie Menard / Augusto Amici

    PLoS ONE, Vol 6, Iss 4, p e

    2011  Volume 18727

    Abstract: Several transgenic mice models solidly support the hypothesis that HER2 (ERBB2) overexpression or mutation promotes tumorigenesis. Recently, a HER2 splice variant lacking exon-16 (Δ16HER2) has been detected in human breast carcinomas. This alternative ... ...

    Abstract Several transgenic mice models solidly support the hypothesis that HER2 (ERBB2) overexpression or mutation promotes tumorigenesis. Recently, a HER2 splice variant lacking exon-16 (Δ16HER2) has been detected in human breast carcinomas. This alternative protein, a normal byproduct of HER2, has an increased transforming potency compared to wild-type (wt) HER2 receptors. To examine the ability of Δ16HER2 to transform mammary epithelium in vivo and to monitor Δ16HER2-driven tumorigenesis in live mice, we generated and characterized a mouse line that transgenically expresses both human Δ16HER2 and firefly luciferase under the transcriptional control of the MMTV promoter. All the transgenic females developed multifocal mammary tumors with a rapid onset and an average latency of 15.11 weeks. Immunohistochemical analysis revealed the concurrent expression of luciferase and the human Δ16HER2 oncogene only in the mammary gland and in strict correlation with tumor development. Transgenic Δ16HER2 expressed on the tumor cell plasma membrane from spontaneous mammary adenocarcinomas formed constitutively active homodimers able to activate the oncogenic signal transduction pathway mediated through Src kinase. These new transgenic animals demonstrate the ability of the human Δ16HER2 isoform to transform "per se" mammary epithelium in vivo. The high tumor incidence as well as the short latency strongly suggests that the Δ16HER2 splice variant represents the transforming form of the HER2 oncoprotein.
    Keywords Medicine ; R ; Science ; Q
    Subject code 500 ; 572
    Language English
    Publishing date 2011-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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    Inter-library loan at ZB MED

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