124 results on '"Marilena V"'
Search Results
2. Data from Plasma miRNA Levels for Predicting Therapeutic Response to Neoadjuvant Treatment in HER2-positive Breast Cancer: Results from the NeoALTTO Trial
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Maria Grazia Daidone, Paolo Verderio, Giovanni Apolone, Filippo G. de Braud, Martine Piccart, José Baselga, Jens Huober, Miguel Izquierdo, Lorena de la Peña, Evandro de Azambuja, Florentine Hilbers, Marilena V. Iorio, Paola Tiberio, Sara Pizzamiglio, Valentina Appierto, and Serena Di Cosimo
- Abstract
Purpose:To investigate the potential of circulating-miRNAs (ct-miRNA) as noninvasive biomarkers to predict the efficacy of single/dual HER2-targeted therapy in the NeoALTTO study.Experimental Design:Patients with plasma samples at baseline (T0) and/or after 2 weeks (T1) of treatment were randomized into training (n = 183) and testing (n = 246) sets. RT-PCR–based high-throughput miRNA profiling was employed in the training set. After normalization, ct-miRNAs associated with pathologic complete response (pCR) were identified by univariate analysis. Multivariate logistic regression models were implemented to generate treatment-specific signatures at T0 and T1, which were evaluated by RT-PCR in the testing set. Event-free survival (EFS) according to ct-miRNA signatures was estimated by Kaplan–Meier method and Cox regression model.Results:In the training set, starting from 51 ct-miRNAs associated with pCR, six signatures with statistically significant predictive capability in terms of area under the ROC curve (AUC) were identified. Four signatures were confirmed in the testing set: lapatinib at T0 and T1 [AUC 0.86; 95% confidence interval (CI), 0.73–0.98 and 0.71 (0.55–0.86)], respectively; trastuzumab at T1 (0.81; 0.70–0.92); lapatinib + trastuzumab at T1 (0.67; 0.51–0.83). These signatures were confirmed predictive after adjusting for known variables, including estrogen receptor status. ct-miRNA signatures failed to correlate with EFS. However, the levels of ct-miR-140-5p, included in the trastuzumab signature, were associated with EFS (HR 0.43; 95% CI, 0.22–0.84).Conclusions:ct-miRNAs discriminate patients with and without pCR after neoadjuvant lapatinib- and/or trastuzumab-based therapy. ct-miRNAs at week two could be valuable to identify patients responsive to trastuzumab, to avoid unnecessary combination with other anti-HER2 agents, and finally to assist deescalating treatment strategies.
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- 2023
3. Supplementary Figures from Plasma miRNA Levels for Predicting Therapeutic Response to Neoadjuvant Treatment in HER2-positive Breast Cancer: Results from the NeoALTTO Trial
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Maria Grazia Daidone, Paolo Verderio, Giovanni Apolone, Filippo G. de Braud, Martine Piccart, José Baselga, Jens Huober, Miguel Izquierdo, Lorena de la Peña, Evandro de Azambuja, Florentine Hilbers, Marilena V. Iorio, Paola Tiberio, Sara Pizzamiglio, Valentina Appierto, and Serena Di Cosimo
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Suppl figures without legends modified on feb 20th
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- 2023
4. Supplementary Figure S1 from miR-9 and miR-200 Regulate PDGFRβ-Mediated Endothelial Differentiation of Tumor Cells in Triple-Negative Breast Cancer
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Marilena V. Iorio, Claudio Tripodo, Gianpiero Di Leva, Filippo De Braud, Anna Tessari, Sara Cresta, Anna Rossini, Annunziata Gloghini, Ambra V. Gualeni, Rosaria Orlandi, Claudia Piovan, Sara Baroni, Patrizia Casalini, Lucia Bongiovanni, Ilaria Plantamura, and Elvira D'Ippolito
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MiR-9 regulates PDGFRbeta expression in TNBC cell lines
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- 2023
5. Data from miR-9 and miR-200 Regulate PDGFRβ-Mediated Endothelial Differentiation of Tumor Cells in Triple-Negative Breast Cancer
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Marilena V. Iorio, Claudio Tripodo, Gianpiero Di Leva, Filippo De Braud, Anna Tessari, Sara Cresta, Anna Rossini, Annunziata Gloghini, Ambra V. Gualeni, Rosaria Orlandi, Claudia Piovan, Sara Baroni, Patrizia Casalini, Lucia Bongiovanni, Ilaria Plantamura, and Elvira D'Ippolito
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Organization of cancer cells into endothelial-like cell-lined structures to support neovascularization and to fuel solid tumors is a hallmark of progression and poor outcome. In triple-negative breast cancer (TNBC), PDGFRβ has been identified as a key player of this process and is considered a promising target for breast cancer therapy. Thus, we aimed at investigating the role of miRNAs as a therapeutic approach to inhibit PDGFRβ-mediated vasculogenic properties of TNBC, focusing on miR-9 and miR-200. In MDA-MB-231 and MDA-MB-157 TNBC cell lines, miR-9 and miR-200 promoted and inhibited, respectively, the formation of vascular-like structures in vitro. Induction of endogenous miR-9 expression, upon ligand-dependent stimulation of PDGFRβ signaling, promoted significant vascular sprouting of TNBC cells, in part, by direct repression of STARD13. Conversely, ectopic expression of miR-200 inhibited this sprouting by indirectly reducing the protein levels of PDGFRβ through the direct suppression of ZEB1. Notably, in vivo miR-9 inhibition or miR-200c restoration, through either the generation of MDA-MB-231–stable clones or peritumoral delivery in MDA-MB-231 xenografted mice, strongly decreased the number of vascular lacunae. Finally, IHC and immunofluorescence analyses in TNBC specimens indicated that PDGFRβ expression marked tumor cells engaged in vascular lacunae. In conclusion, our results demonstrate that miR-9 and miR-200 play opposite roles in the regulation of the vasculogenic ability of TNBC, acting as facilitator and suppressor of PDGFRβ, respectively. Moreover, our data support the possibility to therapeutically exploit miR-9 and miR-200 to inhibit the process of vascular lacunae formation in TNBC. Cancer Res; 76(18); 5562–72. ©2016 AACR.
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- 2023
6. Supplementary Data from Plasma miRNA Levels for Predicting Therapeutic Response to Neoadjuvant Treatment in HER2-positive Breast Cancer: Results from the NeoALTTO Trial
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Maria Grazia Daidone, Paolo Verderio, Giovanni Apolone, Filippo G. de Braud, Martine Piccart, José Baselga, Jens Huober, Miguel Izquierdo, Lorena de la Peña, Evandro de Azambuja, Florentine Hilbers, Marilena V. Iorio, Paola Tiberio, Sara Pizzamiglio, Valentina Appierto, and Serena Di Cosimo
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Including legends of Suppl Figures introduced on Feb 20th
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- 2023
7. Supplementary Figure S3 from miR-9 and miR-200 Regulate PDGFRβ-Mediated Endothelial Differentiation of Tumor Cells in Triple-Negative Breast Cancer
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Marilena V. Iorio, Claudio Tripodo, Gianpiero Di Leva, Filippo De Braud, Anna Tessari, Sara Cresta, Anna Rossini, Annunziata Gloghini, Ambra V. Gualeni, Rosaria Orlandi, Claudia Piovan, Sara Baroni, Patrizia Casalini, Lucia Bongiovanni, Ilaria Plantamura, and Elvira D'Ippolito
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MiR-200 family inhibits tube formation ability through PDGFRbeta repression
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- 2023
8. Supplementary Figure S4 from miR-9 and miR-200 Regulate PDGFRβ-Mediated Endothelial Differentiation of Tumor Cells in Triple-Negative Breast Cancer
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Marilena V. Iorio, Claudio Tripodo, Gianpiero Di Leva, Filippo De Braud, Anna Tessari, Sara Cresta, Anna Rossini, Annunziata Gloghini, Ambra V. Gualeni, Rosaria Orlandi, Claudia Piovan, Sara Baroni, Patrizia Casalini, Lucia Bongiovanni, Ilaria Plantamura, and Elvira D'Ippolito
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Supplementary Figure S4. PDGFRbeta identifies vascular lacunae in TNBC tissues
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- 2023
9. Supplementary Tables 1 through 4 from miR-9 and miR-200 Regulate PDGFRβ-Mediated Endothelial Differentiation of Tumor Cells in Triple-Negative Breast Cancer
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Marilena V. Iorio, Claudio Tripodo, Gianpiero Di Leva, Filippo De Braud, Anna Tessari, Sara Cresta, Anna Rossini, Annunziata Gloghini, Ambra V. Gualeni, Rosaria Orlandi, Claudia Piovan, Sara Baroni, Patrizia Casalini, Lucia Bongiovanni, Ilaria Plantamura, and Elvira D'Ippolito
- Abstract
The file contains all the supplementary tables (S1-S4): - Supplementary Table S1. Clinicopathologic features of 78 breast cancer patients (set 1) and 85 TNBC (set 2). - Supplementary Table S2. Relation between miR-9 expression and clinicopathologic characteristics in human breast cancer. - Supplementary Table S3. Top 40 genes predicted as miR-9 target and statistically significant down-modulated in basal versus luminal breast cancer. - Supplementary Table S4. Relation between clinicopathologic characteristics and miR-9 and miR-200c in TNBC human tissues.
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- 2023
10. Supplementary Figure 5 from microRNA-205 Regulates HER3 in Human Breast Cancer
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Elda Tagliabue, Carlo M. Croce, Sylvie Ménard, Tiziana Triulzi, Andrea Merlo, Gianpiero Di Leva, Claudia Piovan, Patrizia Casalini, and Marilena V. Iorio
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Supplementary Figure 5 from microRNA-205 Regulates HER3 in Human Breast Cancer
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- 2023
11. Supplementary Figure 2 from microRNA-205 Regulates HER3 in Human Breast Cancer
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Elda Tagliabue, Carlo M. Croce, Sylvie Ménard, Tiziana Triulzi, Andrea Merlo, Gianpiero Di Leva, Claudia Piovan, Patrizia Casalini, and Marilena V. Iorio
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Supplementary Figure 2 from microRNA-205 Regulates HER3 in Human Breast Cancer
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- 2023
12. Supplementary Table 5 from MicroRNA Signatures in Human Ovarian Cancer
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Carlo M. Croce, Sylvie Ménard, George A. Calin, Hansjuerg Alder, Chang-Gong Liu, Stefano Volinia, Cristian Taccioli, Patrizia Casalini, Fabio Petrocca, Valentina Donati, Gianpiero Di Leva, Rosa Visone, and Marilena V. Iorio
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Supplementary Table 5 from MicroRNA Signatures in Human Ovarian Cancer
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- 2023
13. Supplementary Figure 3 from microRNA-205 Regulates HER3 in Human Breast Cancer
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Elda Tagliabue, Carlo M. Croce, Sylvie Ménard, Tiziana Triulzi, Andrea Merlo, Gianpiero Di Leva, Claudia Piovan, Patrizia Casalini, and Marilena V. Iorio
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Supplementary Figure 3 from microRNA-205 Regulates HER3 in Human Breast Cancer
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- 2023
14. Supplementary Table 3 from MicroRNA Signatures in Human Ovarian Cancer
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Carlo M. Croce, Sylvie Ménard, George A. Calin, Hansjuerg Alder, Chang-Gong Liu, Stefano Volinia, Cristian Taccioli, Patrizia Casalini, Fabio Petrocca, Valentina Donati, Gianpiero Di Leva, Rosa Visone, and Marilena V. Iorio
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Supplementary Table 3 from MicroRNA Signatures in Human Ovarian Cancer
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- 2023
15. Supplementary Table 2 from MicroRNA Signatures in Human Ovarian Cancer
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Carlo M. Croce, Sylvie Ménard, George A. Calin, Hansjuerg Alder, Chang-Gong Liu, Stefano Volinia, Cristian Taccioli, Patrizia Casalini, Fabio Petrocca, Valentina Donati, Gianpiero Di Leva, Rosa Visone, and Marilena V. Iorio
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Supplementary Table 2 from MicroRNA Signatures in Human Ovarian Cancer
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- 2023
16. Supplementary Table 1 from MicroRNA Signatures in Human Ovarian Cancer
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Carlo M. Croce, Sylvie Ménard, George A. Calin, Hansjuerg Alder, Chang-Gong Liu, Stefano Volinia, Cristian Taccioli, Patrizia Casalini, Fabio Petrocca, Valentina Donati, Gianpiero Di Leva, Rosa Visone, and Marilena V. Iorio
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Supplementary Table 1 from MicroRNA Signatures in Human Ovarian Cancer
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- 2023
17. Data from MicroRNA Signatures in Human Ovarian Cancer
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Carlo M. Croce, Sylvie Ménard, George A. Calin, Hansjuerg Alder, Chang-Gong Liu, Stefano Volinia, Cristian Taccioli, Patrizia Casalini, Fabio Petrocca, Valentina Donati, Gianpiero Di Leva, Rosa Visone, and Marilena V. Iorio
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Epithelial ovarian cancer (EOC) is the sixth most common cancer in women worldwide and, despite advances in detection and therapies, it still represents the most lethal gynecologic malignancy in the industrialized countries. Unfortunately, still relatively little is known about the molecular events that lead to the development of this highly aggressive disease. The relatively recent discovery of microRNAs (miRNA), a class of small noncoding RNAs targeting multiple mRNAs and triggering translation repression and/or RNA degradation, has revealed the existence of a new level of gene expression regulation. Multiple studies involving various types of human cancers proved that miRNAs have a causal role in tumorigenesis. Here we show that, in comparison to normal ovary, miRNAs are aberrantly expressed in human ovarian cancer. The overall miRNA expression could clearly separate normal versus cancer tissues. The most significantly overexpressed miRNAs were miR-200a, miR-141, miR-200c, and miR-200b, whereas miR-199a, miR-140, miR-145, and miR-125b1 were among the most down-modulated miRNAs. We could also identify miRNAs whose expression was correlated with specific ovarian cancer biopathologic features, such as histotype, lymphovascular and organ invasion, and involvement of ovarian surface. Moreover, the levels of miR-21, miR-203, and miR-205, up-modulated in ovarian carcinomas compared with normal tissues, were significantly increased after 5-aza-2′-deoxycytidine demethylating treatment of OVCAR3 cells, suggesting that the DNA hypomethylation could be the mechanism responsible for their overexpression. Our results indicate that miRNAs might play a role in the pathogenesis of human EOC and identify altered miRNA gene methylation as a possible epigenetic mechanism involved in their aberrant expression. [Cancer Res 2007;67(18):8699–707]
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- 2023
18. Supplementary Table 4 from MicroRNA Signatures in Human Ovarian Cancer
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Carlo M. Croce, Sylvie Ménard, George A. Calin, Hansjuerg Alder, Chang-Gong Liu, Stefano Volinia, Cristian Taccioli, Patrizia Casalini, Fabio Petrocca, Valentina Donati, Gianpiero Di Leva, Rosa Visone, and Marilena V. Iorio
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Supplementary Table 4 from MicroRNA Signatures in Human Ovarian Cancer
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- 2023
19. Supplementary Figure 2 from MicroRNA Signatures in Human Ovarian Cancer
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Carlo M. Croce, Sylvie Ménard, George A. Calin, Hansjuerg Alder, Chang-Gong Liu, Stefano Volinia, Cristian Taccioli, Patrizia Casalini, Fabio Petrocca, Valentina Donati, Gianpiero Di Leva, Rosa Visone, and Marilena V. Iorio
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Supplementary Figure 2 from MicroRNA Signatures in Human Ovarian Cancer
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- 2023
20. Supplementary Figure 1 from microRNA-205 Regulates HER3 in Human Breast Cancer
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Elda Tagliabue, Carlo M. Croce, Sylvie Ménard, Tiziana Triulzi, Andrea Merlo, Gianpiero Di Leva, Claudia Piovan, Patrizia Casalini, and Marilena V. Iorio
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Supplementary Figure 1 from microRNA-205 Regulates HER3 in Human Breast Cancer
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- 2023
21. Supplementary Figure 4 from microRNA-205 Regulates HER3 in Human Breast Cancer
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Elda Tagliabue, Carlo M. Croce, Sylvie Ménard, Tiziana Triulzi, Andrea Merlo, Gianpiero Di Leva, Claudia Piovan, Patrizia Casalini, and Marilena V. Iorio
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Supplementary Figure 4 from microRNA-205 Regulates HER3 in Human Breast Cancer
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- 2023
22. sSupplementary Legends for Figures 1-5 from microRNA-205 Regulates HER3 in Human Breast Cancer
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Elda Tagliabue, Carlo M. Croce, Sylvie Ménard, Tiziana Triulzi, Andrea Merlo, Gianpiero Di Leva, Claudia Piovan, Patrizia Casalini, and Marilena V. Iorio
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sSupplementary Legends for Figures 1-5 from microRNA-205 Regulates HER3 in Human Breast Cancer
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- 2023
23. Supplementary Table S1 from MicroRNA Gene Expression Deregulation in Human Breast Cancer
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Carlo M. Croce, Massimo Negrini, Patrizia Querzoli, George A. Calin, Italo Nenci, Stefano Volinia, Piero Musiani, Anne Rosenberg, Juan P. Palazzo, Sylvie Ménard, Manuela Campiglio, Muller Fabbri, Massimo Pedriali, Eros Magri, Silvia Sabbioni, Riccardo Spizzo, Angelo Veronese, Chang-Gong Liu, Manuela Ferracin, and Marilena V. Iorio
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Supplementary Table S1 from MicroRNA Gene Expression Deregulation in Human Breast Cancer
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- 2023
24. Data from microRNA-205 Regulates HER3 in Human Breast Cancer
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Elda Tagliabue, Carlo M. Croce, Sylvie Ménard, Tiziana Triulzi, Andrea Merlo, Gianpiero Di Leva, Claudia Piovan, Patrizia Casalini, and Marilena V. Iorio
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An increasing amount of experimental evidence shows that microRNAs can have a causal role in breast cancer tumorigenesis as a novel class of oncogenes or tumor suppressor genes, depending on the targets they regulate. HER2 overexpression is a hallmark of a particularly aggressive subset of breast tumors, and its activation is strictly dependent on the trans-interaction with other members of HER family; in particular, the activation of the PI3K/Akt survival pathway, so critically important in tumorigenesis, is predominantly driven through phosphorylation of the kinase-inactive member HER3. Here, we show that miR-205, down-modulated in breast tumors compared with normal breast tissue, directly targets HER3 receptor, and inhibits the activation of the downstream mediator Akt. The reintroduction of miR-205 in SKBr3 cells inhibits their clonogenic potential and increases the responsiveness to tyrosine-kinase inhibitors Gefitinib and Lapatinib, abrogating the HER3-mediated resistance and restoring a potent proapoptotic activity. Our data describe miR-205 as a new oncosuppressor gene in breast cancer, able to interfere with the proliferative pathway mediated by HER receptor family. Our study also provides experimental evidence suggesting that miR-205 can improve the responsiveness to specific anticancer therapies. [Cancer Res 2009;69(6):2195–200]
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- 2023
25. Data from MicroRNA Gene Expression Deregulation in Human Breast Cancer
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Carlo M. Croce, Massimo Negrini, Patrizia Querzoli, George A. Calin, Italo Nenci, Stefano Volinia, Piero Musiani, Anne Rosenberg, Juan P. Palazzo, Sylvie Ménard, Manuela Campiglio, Muller Fabbri, Massimo Pedriali, Eros Magri, Silvia Sabbioni, Riccardo Spizzo, Angelo Veronese, Chang-Gong Liu, Manuela Ferracin, and Marilena V. Iorio
- Abstract
MicroRNAs (miRNAs) are a class of small noncoding RNAs that control gene expression by targeting mRNAs and triggering either translation repression or RNA degradation. Their aberrant expression may be involved in human diseases, including cancer. Indeed, miRNA aberrant expression has been previously found in human chronic lymphocytic leukemias, where miRNA signatures were associated with specific clinicobiological features. Here, we show that, compared with normal breast tissue, miRNAs are also aberrantly expressed in human breast cancer. The overall miRNA expression could clearly separate normal versus cancer tissues, with the most significantly deregulated miRNAs being mir-125b, mir-145, mir-21, and mir-155. Results were confirmed by microarray and Northern blot analyses. We could identify miRNAs whose expression was correlated with specific breast cancer biopathologic features, such as estrogen and progesterone receptor expression, tumor stage, vascular invasion, or proliferation index.
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- 2023
26. End-of-neoadjuvant treatment circulating microRNAs and HER2-positive breast cancer patient prognosis: An exploratory analysis from NeoALTTO
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Serena Di Cosimo, Chiara M. Ciniselli, Sara Pizzamiglio, Vera Cappelletti, Marco Silvestri, Sarra El-Abed, Miguel Izquierdo, Mohammed Bajji, Paolo Nuciforo, Jens Huober, David Cameron, Stephen Chia, Henry L. Gomez, Marilena V. Iorio, Andrea Vingiani, Giancarlo Pruneri, Paolo Verderio, Institut Català de la Salut, [Di Cosimo S, Cappelletti V, Silvestri M] Department of Advanced Diagnostics, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Ciniselli CM, Pizzamiglio S] Unit of Bioinformatics and Biostatistics, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [El-Abed S] Breast International Group, Brussels, Belgium. [Nuciforo P] Molecular Oncology Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
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Cancer Research ,Mama - Càncer - Prognosi ,MicroARN ,Therapeutics::Combined Modality Therapy::Neoadjuvant Therapy [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES] ,Oncology ,Nucleic Acids, Nucleotides, and Nucleosides::Antisense Elements (Genetics)::RNA, Antisense::MicroRNAs [CHEMICALS AND DRUGS] ,Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES] ,Mama - Càncer - Tractament ,Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] ,terapéutica::tratamiento combinado::tratamiento neoadyuvante [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,nucleótidos y nucleósidos de ácidos nucleicos::elementos antisentido (genética)::ARN antiparalelo::microARN [COMPUESTOS QUÍMICOS Y DROGAS] ,Other subheadings::Other subheadings::/drug therapy [Other subheadings] - Abstract
Cáncer de mama HER2 positivo; MicroARN circulante; Tratamiento neoadyuvante Càncer de mama HER2-positiu; MicroARN circulant; Tractament neoadjuvant HER2-positive breast cancer; Circulating microRNA; Neoadjuvant treatment Background: The absence of breast cancer cells in surgical specimens, i.e., pathological complete response (pCR), is widely recognized as a favorable prognostic factor after neoadjuvant therapy. In contrast, the presence of disease at surgery characterizes a prognostically heterogeneous group of patients. Here, we challenged circulating microRNAs (miRNAs) at the end of neoadjuvant therapy as potential prognostic biomarkers in the NeoALTTO study. Methods: Patients treated within the trastuzumab arm (i.e., pre-operative weekly trastuzumab for 6 weeks followed by the addition of weekly paclitaxel for 12 weeks; post-operative FEC for 3 cycles followed by trastuzumab up to complete 1 year of treatment) were randomized into a training (n= 54) and testing (n= 72) set. RT-PCR-based high-throughput miRNA profile was performed on plasma samples collected at the end of neoadjuvant treatment of both sets. After normalization, circulating miRNAs associated with event free survival (EFS) were identified by univariate and multivariate Cox regression model. Results: Starting from 23 circulating miRNAs associated with EFS in the training set, we generated a 3-circulating miRNA prognostic signature consisting of miR-185-5p, miR-146a-5p, miR-22-3p, which was confirmed in the testing set. The 3-circulating miRNA signature showed a C-statistic of 0.62 (95% confidence interval [95%CI] 0.53-0.71) in the entire study cohort. By resorting to a multivariate Cox regression model we found a statistical significant interaction between the expression values of miR-194-5p and pCR status (p.interaction =0.005) with an estimate Hazard Ratio (HR) of 1.83 (95%CI 1.14- 2.95) in patients with pCR, and 0.87 (95%CI 0.69-1.10) in those without pCR. Notably, the model including this interaction along with the abovementioned 3-circulating miRNA signature provided the highest discriminatory capability with a C-statistic of 0.67 (95%CI 0.58-0.76). Conclusions: Circulating miRNAs are informative to identify patients with different prognosis among those with heterogeneous response after trastuzumab-based neoadjuvant treatment, and may be an exploitable tool to select candidates for salvage adjuvant therapy. The NeoALTTO study was sponsored by GlaxoSmithKline; Lapatinib is an asset of Novartis AG as of March 2, 2015. This sub-study was supported by the Italian Ministry of Health to SC. No grant number is applicable, funds were obtained through a law that allows tax-payers to allocate the 5 × 1000 share of their payments to research.
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- 2023
27. The Role of MicroRNAs in HER2-Positive Breast Cancer: Where We Are and Future Prospective
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Valentina Fogazzi, Marcel Kapahnke, Alessandra Cataldo, Ilaria Plantamura, Elda Tagliabue, Serena Di Cosimo, Giulia Cosentino, and Marilena V. Iorio
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Cancer Research ,Oncology - Abstract
Breast cancer that highly expresses human epidermal growth factor receptor 2 (HER2+) represents one of the major breast cancer subtypes, and was associated with a poor prognosis until the introduction of HER2-targeted therapies such as trastuzumab. Unfortunately, up to 30% of patients with HER2+ localized breast cancer continue to relapse, despite treatment. MicroRNAs (miRNAs) are small (approximately 20 nucleotides long) non-coding regulatory oligonucleotides. They function as post-transcriptional regulators of gene expression, binding complementarily to a target mRNA and leading to the arrest of translation or mRNA degradation. In the last two decades, translational research has focused on these small molecules because of their highly differentiated expression patterns in blood and tumor tissue, as well as their potential biological function. In cancer research, they have become pivotal for the thorough understanding of oncogenic biological processes. They might also provide an efficient approach to early monitoring of tumor progression or response to therapy. Indeed, changes in their expression patterns can represent a flag for deeper biological changes. In this review, we sum up the recent literature regarding miRNAs in HER2+ breast cancer, taking into account their potential as powerful prognostic and predictive biomarkers, as well as therapeutic tools.
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- 2022
28. A combination of extracellular matrix‐ and interferon‐associated signatures identifies high‐grade breast cancers with poor prognosis
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Serenella M. Pupa, Mara Lecchi, Elda Tagliabue, Melissa Anna Teresa Monica, Filippo de Braud, Paolo Verderio, Giovanni Fucà, Marilena V. Iorio, Massimo Di Nicola, Francesca De Santis, Giulia Bianchi, Sabina Sangaletti, Vera Cappelletti, Massimiliano Gennaro, and Biagio Paolini
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Adult ,0301 basic medicine ,Cancer Research ,Breast Neoplasms ,Disease ,gene signature ,Cohort Studies ,Diagnosis, Differential ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Breast cancer ,Interferon ,Gene expression ,Biomarkers, Tumor ,Genetics ,medicine ,Humans ,tumor microenvironment ,high‐grade breast cancer ,Research Articles ,RC254-282 ,Aged ,Tumor microenvironment ,business.industry ,Gene Expression Profiling ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,General Medicine ,Middle Aged ,Gene signature ,Prognosis ,medicine.disease ,Extracellular Matrix ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,Molecular Medicine ,Biomarker (medicine) ,Female ,Interferons ,Neoplasm Grading ,Transcriptome ,business ,prognostic marker ,Research Article ,medicine.drug - Abstract
Breast cancer (BC) is a heterogeneous disease in which the tumor microenvironment (TME) seems to impact the clinical outcome. Here, we investigated whether a combination of gene expression signatures relating to both the structural and immune TME aspects can help predict prognosis in women with high‐grade BC (HGBC). Thus, we focused on a combined molecular biomarker variable that involved extracellular matrix (ECM)‐associated gene expression (ECM3 signature) and interferon (IFN)‐associated metagene (IFN metagene) expression. In 97 chemo‐naive HGBCs from the METABRIC dataset, the dichotomous ECM3/IFN (dECIF) variable identified a group of high‐risk patients (ECM3+/IFN− vs other; hazard ratio = 3.2, 95% confidence interval: 1.5–6.7). Notably, ECM3+/IFN− tumors showed low tumor‐infiltrating lymphocytes, high levels of CD33‐positive cells, absence of PD‐1 expression, or low expression of PD‐L1, as suggested by immune profiles and immune‐histochemical analysis on an independent cohort of 131 HGBCs. To make our results transferable to clinical use, we refined the dECIF biomarker using reduced ECM3 and IFN signatures; notably, the prognostic value of this reduced dECIF was comparable to that of the original dECIF. After validation in a new BC cohort, reduced dECIF was translated into a robust qPCR classifier for real‐world clinical use., This study investigates the combination of two relevant molecular signatures of the tumor microenvironment (TME) in identifying aggressive high‐grade breast cancers (HGBCs). The novel molecular biomarker described here highlighted patients with worst HGBC prognosis and a peculiar TME. Finally, to improve the potential of the identified biomarker in the clinic, we reduced the two original signatures and technically validated the biomarker's expression through a qPCR‐based assay.
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- 2021
29. Pathophysiology rolesr and translational opportunities of miRNAs in breast cancer
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Giulia Cosentino, Ilaria Plantamura, and Marilena V. Iorio
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- 2022
30. microRNA in Human Malignancies
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Samuel, Akanksha, Alessandra, Allione, Juan Carlos Álvarez-Perez, Alvaro, Andrades, Arenas, Alberto M., Carlos, Baliñas-Gavira, Barth, Dominik A., Anna, Bielowski, Roopa, Biswas, Mattia, Boeri, Elisabetta, Broseghini, Calin, George A., Calura, Enrica, Elisabetta, Casalone, Vera, Constâncio, Giulia, Cosentino, Costa, Marina C., Croce, Carlo M., Marta, Cuadros, Cutucache, Christine E., Ben, Davidson, Emi, Dika, Sayra, Dilmac, Dragomir, Mihnea P., Rares, Drula, Enguita, Francisco J., Zhaohui, Feng, Manuela, Ferracin, Francesca, Fornari, Orazio, Fortunato, Gabriel, André F., García, Daniel J., Laura, Gramantieri, Rui, Henrique, Wenwei, Hu, Iorio, Marilena V., Carmen, Jerónimo, Sakshi, Kamboj, Manoj, Kumar, Charles Henderson Lawrie, Ana Lúcia Leitão, Juan, Liu, Francesca, Lovat, Masatti, Laura, Medina, Pedro P., Swati, Mohapatra, Vlad, Moisoiu, Massimo, Negrini, Vu Hong Loan Nguyen, Jacob Anderson O’Brien, Bulent, Ozpolat, Barbara, Pardini, Juan Rodrigo Patiño-Mercau, Laura, Pazzaglia, Paola, Peinado, Yuri, Pekarsky, Chun, Peng, Petrescu, George E. D., Martin, Pichler, Ilaria, Plantamura, Reuven, Reich, Maria Isabel Rodriguez, Romualdi, Chiara, Juan, Sanjuan-Hidalgo, Katia, Scotlandi, Shankaraiah, Ram C., Ondrej, Slaby, Carla, Solé, Dharmendra Kumar Soni, Gabriella, Sozzi, Anamika, Thakur, Angelo, Veronese, Rosa, Visone, Petra, Vychytilova-Faltejskova, and Cen, Zhang
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- 2022
31. Contributors
- Author
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Samuel Akanksha, Alessandra Allione, Juan Carlos Álvarez-Perez, Alvaro Andrades, Alberto M. Arenas, Carlos Baliñas-Gavira, Dominik A. Barth, Anna Bielowski, Roopa Biswas, Mattia Boeri, Elisabetta Broseghini, George A. Calin, Enrica Calura, Elisabetta Casalone, Vera Constâncio, Giulia Cosentino, Marina C. Costa, Carlo M. Croce, Marta Cuadros, Christine E. Cutucache, Ben Davidson, Emi Dika, Sayra Dilmac, Mihnea P. Dragomir, Rares Drula, Francisco J. Enguita, Zhaohui Feng, Manuela Ferracin, Francesca Fornari, Orazio Fortunato, André F. Gabriel, Daniel J. García, Laura Gramantieri, Rui Henrique, Wenwei Hu, Marilena V. Iorio, Carmen Jerónimo, Sakshi Kamboj, Manoj Kumar, Charles Henderson Lawrie, Ana Lúcia Leitão, Juan Liu, Francesca Lovat, Laura Masatti, Giuseppe Matullo, Pedro P. Medina, Swati Mohapatra, Vlad Moisoiu, Massimo Negrini, Vu Hong Loan Nguyen, Jacob Anderson O’Brien, Bulent Ozpolat, Barbara Pardini, Juan Rodrigo Patiño-Mercau, Laura Pazzaglia, Paola Peinado, Yuri Pekarsky, Chun Peng, George E.D. Petrescu, Martin Pichler, Ilaria Plantamura, Reuven Reich, Maria Isabel Rodriguez, Chiara Romualdi, Juan Sanjuan-Hidalgo, Katia Scotlandi, Ram C. Shankaraiah, Ondrej Slaby, Carla Solé, Dharmendra Kumar Soni, Gabriella Sozzi, Anamika Thakur, Angelo Veronese, Rosa Visone, Petra Vychytilova-Faltejskova, and Cen Zhang
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- 2022
32. Circulating miRNAs as Novel Non-Invasive Biomarkers to Aid the Early Diagnosis of Suspicious Breast Lesions for Which Biopsy Is Recommended
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Rosaria Orlandi, Massimiliano Gennaro, Mario P. Colombo, Marialuisa Sensi, Mara Lecchi, Marilena V. Iorio, Loris De Cecco, Chiara Gargiuli, Gabriella Sozzi, Biagio Paolini, Paolo Verderio, Silvia Veneroni, E. Mancinelli, Marta Giussani, Catherine Depretto, Chiara Maura Ciniselli, M. Dugo, Elda Tagliabue, Claudio Ferranti, Gianfranco Scaperrotta, Giulia Cosentino, and Andrea Mariancini
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,diagnosis ,Population ,Malignancy ,Article ,Breast cancer ,breast cancer ,Internal medicine ,Biopsy ,medicine ,education ,Prospective cohort study ,RC254-282 ,education.field_of_study ,medicine.diagnostic_test ,business.industry ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,circulating biomarkers ,Retrospective cohort study ,medicine.disease ,microRNAs ,Cohort ,Breast disease ,business - Abstract
Simple Summary In population-based screens, tissue biopsy remains the standard practice for women with imaging that suggests breast cancer. We examined circulating microRNAs as minimally invasive diagnostic biomarkers to discriminate malignant from benign breast lesions. A retrospective cohort of plasma samples divided into training and testing sets and a prospective cohort of women with suspicious imaging findings who underwent tissue biopsy were investigated through a global microRNA profile by OpenArray. Seven signatures, involving 5 specific miRNAs (miR-625, miR-423-5p, miR-370-3p, miR-181c, and miR-301b), were identified and validated in the testing set. Among the 7 signatures, the discriminatory performances of 5 of them were confirmed in the prospective cohort. Abstract In population-based screens, tissue biopsy remains the standard practice for women with imaging that suggests breast cancer. We examined circulating microRNAs as minimally invasive diagnostic biomarkers to discriminate malignant from benign breast lesions. miRNAs were analyzed by OpenArray in a retrospective cohort of plasma samples including 100 patients with malignant (T), 89 benign disease (B), and 99 healthy donors (HD) divided into training and testing sets and a prospective cohort (BABE) of 289 women with suspicious imaging findings who underwent tissue biopsy. miRNAs associated with disease status were identified by univariate analysis and then combined into signatures by multivariate logistic regression models. By combining 16 miRNAs differentially expressed in the T vs. HD comparison, 26 signatures were also able to significantly discriminate T from B disease. Seven of them, involving 5 specific miRNAs (miR-625, miR-423-5p, miR-370-3p, miR-181c, and miR-301b), were statistically validated in the testing set. Among the 7 signatures, the discriminatory performances of 5 were confirmed in the prospective BABE Cohort. This study identified 5 circulating miRNAs that, properly combined, distinguish malignant from benign breast disease in women with a high likelihood of malignancy.
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- 2021
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33. Expression of long non‐coding RNA ENSG00000226738 (LncKLHDC7B) is enriched in the immunomodulatory triple‐negative breast cancer subtype and its alteration promotes cell migration, invasion, and resistance to cell death
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Fredy Omar Beltrán‐Anaya, Sandra Romero‐Córdoba, Rosa Rebollar‐Vega, Oscar Arrieta, Verónica Bautista‐Piña, Carlos Dominguez‐Reyes, Felipe Villegas‐Carlos, Alberto Tenorio‐Torres, Luis Alfaro‐Riuz, Silvia Jiménez‐Morales, Alberto Cedro‐Tanda, Magdalena Ríos‐Romero, Juan Pablo Reyes‐Grajeda, Elda Tagliabue, Marilena V. Iorio, and Alfredo Hidalgo‐Miranda
- Subjects
ENSG00000226738 ,triple‐negative breast cancer ,long non‐coding RNA ,LncKLHDC7B ,invasion ,migration ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,lcsh:RC254-282 - Abstract
Triple negative breast cancer (TNBC) represents an aggressive phenotype with poor prognosis compared with ER, PR, and HER2‐positive tumors. TNBC is a heterogeneous disease, and gene expression analysis has identified seven molecular subtypes. Accumulating evidence demonstrates that long non‐coding RNA (lncRNA) are involved in regulation of gene expression and cancer biology, contributing to essential cancer cell functions. In this study, we analyzed the expression profile of lncRNA in TNBC subtypes from 156 TNBC samples, and then characterized the functional role of LncKLHDC7B (ENSG00000226738). A total of 710 lncRNA were found to be differentially expressed between TNBC subtypes, and a subset of these altered lncRNA were independently validated. We discovered that LncKLHDC7B (ENSG00000226738) acts as a transcriptional modulator of its neighboring coding gene KLHDC7B in the immunomodulatory subtype. Furthermore, LncKLHDC7B knockdown enhanced migration and invasion, and promoted resistance to cellular death. Our findings confirmed the contribution of LncKLHDC7B to induction of apoptosis and inhibition of cell migration and invasion, suggesting that TNBC tumors with enrichment of LncKLHDC7B may exhibit distinct regulatory activity, or that this may be a generalized process in breast cancer. Additionally, in silico analysis confirmed for the first time that the low expression of KLHDC7B and LncKLHDC7B is associated with poor prognosis in patients with breast cancer.
- Published
- 2019
34. Expression of long non‐coding <scp>RNA ENSG</scp> 00000226738 (Lnc <scp>KLHDC</scp> 7B) is enriched in the immunomodulatory triple‐negative breast cancer subtype and its alteration promotes cell migration, invasion, and resistance to cell death
- Author
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Magdalena Ríos-Romero, Alberto Tenorio-Torres, Marilena V. Iorio, Alberto Cedro-Tanda, Oscar Arrieta, Elda Tagliabue, Luis Alfaro-Riuz, Sandra Romero-Cordoba, Felipe Villegas-Carlos, Carlos Domínguez-Reyes, Rosa Rebollar-Vega, Juan Pablo Reyes-Grajeda, Fredy Omar Beltrán-Anaya, Verónica Bautista-Piña, Alfredo Hidalgo-Miranda, and Silvia Jiménez-Morales
- Subjects
0301 basic medicine ,Regulation of gene expression ,Cancer Research ,Gene knockdown ,General Medicine ,Biology ,medicine.disease ,Long non-coding RNA ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Breast cancer ,Oncology ,030220 oncology & carcinogenesis ,Cancer cell ,Gene expression ,Genetics ,Cancer research ,medicine ,Molecular Medicine ,Gene ,Triple-negative breast cancer - Abstract
Triple negative breast cancer (TNBC) represents an aggressive phenotype with poor prognosis compared with ER, PR, and HER2-positive tumors. TNBC is a heterogeneous disease, and gene expression analysis has identified seven molecular subtypes. Accumulating evidence demonstrates that long non-coding RNA (lncRNA) are involved in regulation of gene expression and cancer biology, contributing to essential cancer cell functions. In this study, we analyzed the expression profile of lncRNA in TNBC subtypes from 156 TNBC samples, and then characterized the functional role of LncKLHDC7B (ENSG00000226738). A total of 710 lncRNA were found to be differentially expressed between TNBC subtypes, and a subset of these altered lncRNA were independently validated. We discovered that LncKLHDC7B (ENSG00000226738) acts as a transcriptional modulator of its neighboring coding gene KLHDC7B in the immunomodulatory subtype. Furthermore, LncKLHDC7B knockdown enhanced migration and invasion, and promoted resistance to cellular death. Our findings confirmed the contribution of LncKLHDC7B to induction of apoptosis and inhibition of cell migration and invasion, suggesting that TNBC tumors with enrichment of LncKLHDC7B may exhibit distinct regulatory activity, or that this may be a generalized process in breast cancer. Additionally, in silico analysis confirmed for the first time that the low expression of KLHDC7B and LncKLHDC7B is associated with poor prognosis in patients with breast cancer.
- Published
- 2019
35. WNT signaling modulates PD-L1 expression in the stem cell compartment of triple-negative breast cancer
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Lorenzo Castagnoli, Marilena V. Iorio, Matteo Milani, Sabina Sangaletti, Claudio Tripodo, Sandra L. Cordoba-Romero, Tatiana Volpari, Valeria Cancila, Alfredo Hidalgo-Miranda, Claudia Chiodoni, Elda Tagliabue, Beatrice Belmonte, Simona Faraci, Serenella M. Pupa, Giovanna Talarico, Massimo Di Nicola, Castagnoli L., Cancila V., Cordoba-Romero S.L., Faraci S., Talarico G., Belmonte B., Iorio M.V., Milani M., Volpari T., Chiodoni C., Hidalgo-Miranda A., Tagliabue E., Tripodo C., Sangaletti S., Di Nicola M., and Pupa S.M.
- Subjects
0301 basic medicine ,Cell biology ,Cancer Research ,Triple Negative Breast Neoplasm ,Immunology ,Down-Regulation ,Triple Negative Breast Neoplasms ,Article ,B7-H1 Antigen ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Stem Cell ,Cell Line, Tumor ,Biomarkers, Tumor ,Genetics ,medicine ,Animals ,Humans ,Wnt Signaling Pathway ,Molecular Biology ,Triple-negative breast cancer ,Mice, Inbred BALB C ,biology ,Animal ,Stem Cells ,CD44 ,Wnt signaling pathway ,Cancer ,Aldehyde Dehydrogenase ,medicine.disease ,Hyaluronan Receptor ,Up-Regulation ,ALDH1A1 ,Hyaluronan Receptors ,030104 developmental biology ,030220 oncology & carcinogenesis ,biology.protein ,Cancer research ,Female ,Stem cell ,Human - Abstract
Triple-negative breast cancers (TNBCs) are characterized by a poor prognosis and lack of targeted treatments, and thus, new therapeutic strategies are urgently needed. Inhibitors against programmed death-1 (PD-1)/PD-1 ligand (PD-L1) have shown significant efficacy in various solid cancers, but their activity against TNBCs remains limited. Here, we report that human TNBCs molecularly stratified for high levels of PD-L1 (PD-L1High) showed significantly enriched expression of immune and cancer stemness pathways compared with those with low PD-L1 expression (PD-L1Low). In addition, the PD-L1High cases were significantly associated with a high stemness score (SSHigh) signature. TNBC cell lines gated for aldehyde dehydrogenase (ALDH) and CD44 stemness markers exhibited increased levels of PD-L1 versus their ALDH-negative and CD44Low counterparts, and PD-L1High cells generated significantly more mammospheres than PD-L1Low cells. Murine mammary SCA-1-positive tumor cells with PD-L1High expression generated tumors in vivo with higher efficacy than PD-L1Low cells. Furthermore, treatment of TNBC cells with selective WNT inhibitors or activators downregulated or upregulated PD-L1 expression, respectively, implying a functional cross-talk between WNT activity and PD-L1 expression. Remarkably, human TNBC samples contained tumor elements co-expressing PD-L1 with ALDH1A1 and/or CD44v6. Additionally, both PD-L1-/SCA1-positive and ALDH1A1-positive tumor elements were found in close contact with CD3-, and PD-1-positive T cells in murine and human tumor samples. Overall, our study suggests that PD-L1-positive tumor elements with a stemness phenotype may participate in the complex dynamics of TNBC-related immune evasion, which might be targeted through WNT signaling inhibition.
- Published
- 2019
36. Abstract 1229: miRNA and response to trastuzumab
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Giulia Cosentino, Sara Pizzamiglio, Chiara M. Ciniselli, Loris De Cecco, Alessandra Cataldo, Ilaria Plantamura, Tiziana Triulzi, Sarra El-abed, Yingbo Wang, Mohammed Bajji, Paolo Nuciforo, Jens Huober, Susan L. Ellard, David L. Rimm, Andrea Gombos, Mariagrazia Daidone, Paolo Verderio, Elda Tagliabue, Serena Di Cosimo, and Marilena V. Iorio
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Cancer Research ,Oncology - Abstract
The implementation of trastuzumab has revolutionized the clinical management of HER2 positive breast cancers. Unfortunately, 50% of patients are resistant to the treatment. Researchers have already designed alternative anti-HER2 agents, such as pertuzumab and lapatinib. Still, predicting which patients will benefit from the therapy would prevent overtreatment and avoid unnecessary risks of side effects. MiRNAs are small non-coding RNAs involved in post-transcriptional gene regulation, and participate in almost all biological processes, including cancer. Since aberrant miRNA levels can be detected both at tissue level and in the circulation, they are good candidates as predictive and prognostic biomarkers. This study had access to tumor tissue samples from the phase III NeoALTTO trial, aimed at evaluating the efficacy of a HER2 dual blockade with trastuzumab and Lapatinib vs single blocking, in concomitance with chemotherapy, in a pre-operative setting. The primary end-point of the study was pathologic complete response (pCR); the secondary end-point event-free survival (EFS). Focusing on the trastuzumab arm, we identified both a predictive signature (hsa-miR-31-3p, OR 0.70, 95%CI: 0.53-0.92 and hsa-miR-382-3p, OR 1.39, 95%CI: 1.01-1.91) with an AUC value of 0.73 (95%CI: 0.60-0.87), and a prognostic signature (miR-153-3p, HR 1.83, 95%CI: 1.34-2.50 and miR-219a-5p, HR 0.629, 95%CI: 0.51-0.79) leading to a C-statistics of 0.730 (95%CI: 0.63-0.83). Moreover, we identified 2 miRNAs (miR-215-5p and miR-30c-2-3p) associated to EFS with a statistically significant interaction term with pCR (p.interaction: 0.017 and 0.038, respectively). Aiming at deepening the understanding of resistance mechanism, we modulated the expression of miR-31-3p and miR-382-3p in vitro, upon trastuzumab treatment in HER2 positive breast cancer cell lines. Given that miR-31-3p negatively correlates with pCR, we transfected it in HER2-addicted SKBr3 cells to appreciate a possible gain of resistance to trastuzumab; conversely, miR-382-3p positively correlates with pCR and was transfected in HER2 non-addicted HCC1954 cells. Western blot analysis of HER2 signaling pathway highlighted that overexpression of miR-31-3p was able to counteract the reduction of phosphorylated HER2 levels induced by trastuzumab treatment in SKBR3 cells compared to control. Interestingly, miR-31-3p upmodulation increased the proliferation of both treated and non-treated SKBr3 cell in a 3D setting. Conversely, miR-382-3p overexpression in HCC1954 cells only slightly increased responsiveness to trastuzumab in the 3D setting, compared to control. Trastuzumab efficacy also relies on the immune system reaction, thus, in vivo experiments will likely provide further insights into the mechanism of action of these miRNAs. Citation Format: Giulia Cosentino, Sara Pizzamiglio, Chiara M. Ciniselli, Loris De Cecco, Alessandra Cataldo, Ilaria Plantamura, Tiziana Triulzi, Sarra El-abed, Yingbo Wang, Mohammed Bajji, Paolo Nuciforo, Jens Huober, Susan L. Ellard, David L. Rimm, Andrea Gombos, Mariagrazia Daidone, Paolo Verderio, Elda Tagliabue, Serena Di Cosimo, Marilena V. Iorio. miRNA and response to trastuzumab [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1229.
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- 2022
37. Worldwide SARS-CoV-2 haplotype distribution in early pandemic
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Andrea Cairo, Marilena V. Iorio, Silvia Spena, Elda Tagliabue, and Flora Peyvandi
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Multidisciplinary ,SARS-CoV-2 ,Science ,COVID-19 ,Genetic Variation ,Genome, Viral ,Genomics ,Evolution, Molecular ,Phylogeography ,Haplotypes ,Mutation ,Spike Glycoprotein, Coronavirus ,Medicine ,Humans ,Pandemics ,Phylogeny - Abstract
The world is experiencing one of the most severe viral outbreaks in the last few years, the pandemic infection by SARS-CoV-2, the causative agent of COVID-19 disease. As of December 10th 2021, the virus has spread worldwide, with a total number of more than 267 million of confirmed cases (four times more in the last year), and more than 5 million deaths. A great effort has been undertaken to molecularly characterize the virus, track the spreading of different variants across the globe with the aim to understand the potential effects in terms of transmission capability and different fatality rates. Here we focus on the genomic diversity and distribution of the virus in the early stages of the pandemic, to better characterize the origin of COVID-19 and to define the geographical and temporal evolution of genetic clades. By performing a comparative analysis of 75401 SARS-CoV-2 reported sequences (as of December 2020), using as reference the first viral sequence reported in Wuhan in December 2019, we described the existence of 26538 genetic variants, the most frequent clustering into four major clades characterized by a specific geographical distribution. Notably, we found the most frequent variant, the previously reported missense p.Asp614Gly in the S protein, as a single mutation in only three patients, whereas in the large majority of cases it occurs in concomitance with three other variants, suggesting a high linkage and that this variant alone might not provide a significant selective advantage to the virus. Moreover, we evaluated the presence and the distribution in our dataset of the mutations characterizing the so called “british variant”, identified at the beginning of 2021, and observed that 9 out of 17 are present only in few sequences, but never in linkage with each other, suggesting a synergistic effect in this new viral strain. In summary, this is a large-scale analysis of SARS-CoV-2 deposited sequences, with a particular focus on the geographical and temporal evolution of genetic clades in the early phase of COVID-19 pandemic.
- Published
- 2021
38. Mexican Ganoderma Lucidum Extracts Decrease Lipogenesis Modulating Transcriptional Metabolic Networks and Gut Microbiota in C57BL/6 Mice Fed with a High-Cholesterol Diet
- Author
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Myrna Bonilla, Giulia Cosentino, Sandra Romero-Cordoba, Mónica Sánchez-Tapia, Armando R. Tovar, Ivan Salido-Guadarrama, Beatriz Petlacalco, Elda Tagliabue, Marilena V. Iorio, Nimbe Torres, Maria E. Meneses, Daniel Martínez-Carrera, and Ivan Castillo
- Subjects
Male ,0301 basic medicine ,Reishi ,medicine.medical_treatment ,lcsh:TX341-641 ,Ganoderma lucidum ,transcriptional profiles ,Pharmacology ,Gut flora ,Kidney ,Article ,Cholesterol, Dietary ,Transcriptome ,Mice ,03 medical and health sciences ,Lipid biosynthesis ,Lactobacillus ,medicine ,microbiota ,Animals ,Nutrition and Dietetics ,030102 biochemistry & molecular biology ,biology ,hypercholesterolemia ,Anticholesteremic Agents ,Lipogenesis ,Prebiotic ,lipid catabolism ,Lipid Metabolism ,biology.organism_classification ,Gastrointestinal Microbiome ,Mice, Inbred C57BL ,Metabolic pathway ,Prebiotics ,RAW 264.7 Cells ,030104 developmental biology ,Liver ,Simvastatin ,lcsh:Nutrition. Foods and food supply ,Metabolic Networks and Pathways ,Food Science ,medicine.drug - Abstract
Prevention of hyperlipidemia and associated diseases is a health priority. Natural products, such as the medicinal mushroom Ganoderma lucidum (Gl), have demonstrated hypocholesterolemic, prebiotic and antidiabetic properties. However, the underlying transcriptomic mechanisms by which Gl exerts bioactivities are not completely understood. We report a comprehensive hepatic and renal transcriptome profiling of C57BL/6 mice under the consumption of a high-cholesterol diet and two standardized Gl extracts obtained from basidiocarps cultivated on conventional substrate (Gl-1) or substrate containing acetylsalicylic acid (ASA, Gl-2). We showed that Gl extracts modulate relevant metabolic pathways involving the restriction of lipid biosynthesis and the enrichment of lipid degradation and secretion. The Gl-2 extract exerts a major modulation over gene expression programs showing the highest similarity with simvastatin druggable-target-genes and these are enriched more in processes related to human obesity alterations in the liver. We further show a subset of Gl-modulated genes correlated with Lactobacillus enrichment and the reduction of circulating cholesterol-derived fats. Moreover, Gl extracts induce a significant decrease of macrophage lipid storage, which occurs concomitantly with the down-modulation of Fasn and Elovl6. Collectively, this evidence suggests a new link between Gl hypocholesterolemic and prebiotic activity, revealing thereby that standardized Mexican Gl extracts are a novel transcriptome modulator to prevent metabolic disorders associated with hypercholesterolemia.
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- 2020
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39. Author response for 'A combination of extracellular matrix‐ and interferon‐associated signatures identifies high‐grade breast cancers with poor prognosis'
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S. Sangaletti, Massimo Di Nicola, Melissa Anna Teresa Monica, Serenella M. Pupa, Biagio Paolini, Mara Lecchi, Marilena V. Iorio, Massimiliano Gennaro, Elda Tagliabue, Giulia Bianchi, Giovanni Fucà, Vera Cappelletti, Filippo de Braud, Francesca De Santis, and Paolo Verderio
- Subjects
Extracellular matrix ,Poor prognosis ,business.industry ,Interferon ,Cancer research ,Medicine ,business ,medicine.drug - Published
- 2020
40. miR-9-Mediated Inhibition of EFEMP1 Contributes to the Acquisition of Pro-Tumoral Properties in Normal Fibroblasts
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Ilaria Plantamura, Marilena V. Iorio, Sandra Romero-Cordoba, Alessandra Cataldo, and Giulia Cosentino
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Stromal cell ,Primary Cell Culture ,Antineoplastic Agents ,Triple Negative Breast Neoplasms ,Mice, SCID ,Article ,Extracellular matrix protein 1 ,Mice ,Cancer-Associated Fibroblasts ,Cell Movement ,medicine ,Gene silencing ,tumor microenvironment ,Animals ,Humans ,RNA, Small Interfering ,education ,Fibroblast ,lcsh:QH301-705.5 ,miRNA ,Cell Line, Transformed ,education.field_of_study ,Tumor microenvironment ,Extracellular Matrix Proteins ,EFEMP1 ,Chemistry ,miR-9 ,chemoresistance ,General Medicine ,Transfection ,Fibroblasts ,Xenograft Model Antitumor Assays ,Cell biology ,Fibulin ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,medicine.anatomical_structure ,Cell Transformation, Neoplastic ,HEK293 Cells ,lcsh:Biology (General) ,triple-negative breast cancer ,Female ,Cisplatin ,Signal Transduction - Abstract
Tumor growth and invasion occurs through a dynamic interaction between cancer and stromal cells, which support an aggressive niche. MicroRNAs are thought to act as tumor messengers to &ldquo, corrupt&rdquo, stromal cells. We previously demonstrated that miR-9, a known metastamiR, is released by triple negative breast cancer (TNBC) cells to enhance the transition of normal fibroblasts (NFs) into cancer-associated fibroblast (CAF)-like cells. EGF containing fibulin extracellular matrix protein 1 (EFEMP1), which encodes for the ECM glycoprotein fibulin-3, emerged as a miR-9 putative target upon miRNA&rsquo, s exogenous upmodulation in NFs. Here we explored the impact of EFEMP1 downmodulation on fibroblast&rsquo, s acquisition of CAF-like features, and how this phenotype influences neoplastic cells to gain chemoresistance. Indeed, upon miR-9 overexpression in NFs, EFEMP1 resulted downmodulated, both at RNA and protein levels. The luciferase reporter assay showed that miR-9 directly targets EFEMP1 and its silencing recapitulates miR-9-induced pro-tumoral phenotype in fibroblasts. In particular, EFEMP1 siRNA-transfected (si-EFEMP1) fibroblasts have an increased ability to migrate and invade. Moreover, TNBC cells conditioned with the supernatant of NFs transfected with miR-9 or si-EFEMP1 became more resistant to cisplatin. Overall, our results demonstrate that miR-9/EFEMP1 axis is crucial for the conversion of NFs to CAF-like cells under TNBC signaling.
- Published
- 2020
41. Worldwide SARS-COV-2 haplotype distribution
- Author
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Elda Tagliabue, Marilena V. Iorio, Flora Peyvandi, Andrea Cairo, and S Spena
- Subjects
Genetics ,viruses ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Haplotype ,Distribution (pharmacology) ,Biology - Abstract
The world is experiencing one of the most severe viral outbreaks in the last years, the pandemic infection by SARS-COV-2, causative agent of COVID-19 disease. The virus reached over 120 countries, with a total number of 6.5 million infected, and 320000 deaths. A deeper understanding of its genomic diversity is mandatory.We analyzed 21296 SARS-COV-2 reported sequences, defining the existence of recurrent haplotypes and their specific geographical distribution.
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- 2020
42. MiR-302b as a Combinatorial Therapeutic Approach to Improve Cisplatin Chemotherapy Efficacy in Human Triple-Negative Breast Cancer
- Author
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Elda Tagliabue, Giulia Cosentino, Ilaria Plantamura, Marilena V. Iorio, Sandra Romero-Cordoba, Alessandra Cataldo, and Alfredo Hidalgo-Miranda
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0301 basic medicine ,Cancer Research ,drug response ,cisplatin ,lcsh:RC254-282 ,Article ,03 medical and health sciences ,0302 clinical medicine ,microRNA ,Medicine ,E2F1 ,Gene silencing ,Transcription factor ,Triple-negative breast cancer ,E2F2 ,Cisplatin ,business.industry ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,microRNAs ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,triple-negative breast cancer ,business ,ITGA6 ,medicine.drug - Abstract
Introduction: Chemotherapy is still the standard of care for triple-negative breast cancers (TNBCs). Here, we investigated miR-302b as a therapeutic tool to enhance cisplatin sensitivity in vivo and unraveled the molecular mechanism. Materials and Methods: TNBC-xenografted mice were treated with miR-302b or control, alone or with cisplatin. Genome-wide transcriptome analysis and independent-validation of Integrin Subunit Alpha 6 (ITGA6) expression was assessed on mice tumor samples. Silencing of ITGA6 was performed to evaluate cisplatin response in vitro. Further, potential transcription factors of ITGA6 (E2F transcription facor 1 (E2F1), E2F transcription factor 2 (E2F2), and Yin Yang 1 (YY1)) were explored to define the miRNA molecular mechanism. The miR-302b expression was also assessed in TNBC patients treated with chemotherapy. Results: The miR&ndash, 302b-cisplatin combination significantly impaired tumor growth versus the control through indirect ITGA6 downregulation. Indeed, ITGA6 was downmodulated in mice treated with miR-302b&ndash, cisplatin, and ITGA6 silencing increased drug sensitivity in TNBC cells. In silico analyses and preclinical assays pointed out the regulatory role of the E2F family and YY1 on ITGA6 expression under miR-302b&ndash, cisplatin treatment. Finally, miR-302b enrichment correlated with better overall survival in 118 TNBC patients. Conclusion: MiR-302b can be exploited as a new therapeutic tool to improve the response to chemotherapy, modulating the E2F family, YY1, and ITGA6 expression. Moreover, miR-302b could be defined as a new prognostic factor in TNBC patients.
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- 2020
43. Early modulation of circulating MicroRNAs levels in HER2-positive breast cancer patients treated with trastuzumab-based neoadjuvant therapy
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Evandro de Azambuja, Anne Vincent-Salomon, Jens Huober, Maria Grazia Daidone, Miguel Izquierdo, Paolo Verderio, Valentina Appierto, Fraser Symmans, Marilena V. Iorio, Florentine Hilbers, Giovanni Apolone, Michael Untch, Paolo Nuciforo, Serena Di Cosimo, Marco Silvestri, José Baselga, Filippo de Braud, Kathleen I. Pritchard, Martine Piccart, Lorena de la Peña, Sara Pizzamiglio, Lajos Pusztai, Institut Català de la Salut, [Di Cosimo S, Appierto V, Silvestri M] Biomarker Unit, Department of Applied Research and Technological Development, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Pizzamiglio S] Bioinformatics and Biostatistics Unit, Department of Applied Research and Technological Development, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Baselga J, Nuciforo P] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Piccart M] Department of Medical Oncology, Institut Jules Bordet and l’Université Libre de Bruxelles (U.L.B), Brussels, Belgium, and Vall d'Hebron Barcelona Hospital Campus
- Subjects
Oncology ,Receptor, ErbB-2 ,medicine.medical_treatment ,Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES] ,Medicaments antineoplàstics - Ús terapèutic ,Informatique appliquée logiciel ,fenómenos genéticos::regulación de la expresión génica::regulación de la expresión génica neoplásica [FENÓMENOS Y PROCESOS] ,lcsh:Chemistry ,Physico-chimie générale ,ErbB-2 ,Mama - Càncer ,Trastuzumab ,Biomarkers ,Breast cancer ,Circulating microRNAs ,Ct-miR-148a-3p ,HER2 ,Adult ,Aged ,Breast Neoplasms ,Cell Line, Tumor ,Circulating MicroRNA ,Female ,Gene Expression Regulation, Neoplastic ,Gene Regulatory Networks ,Humans ,Logistic Models ,Middle Aged ,Multivariate Analysis ,Neoadjuvant Therapy ,Brustkrebs ,Estrogen Receptor Status ,lcsh:QH301-705.5 ,Spectroscopy ,Neoadjuvant therapy ,neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES] ,Tumor ,General Medicine ,Computer Science Applications ,Therapeutics::Combined Modality Therapy::Neoadjuvant Therapy [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,medicine.drug ,Receptor ,medicine.medical_specialty ,Genetic Phenomena::Gene Expression Regulation::Gene Expression Regulation, Neoplastic [PHENOMENA AND PROCESSES] ,Chimie inorganique ,miRNS ,Catalysis ,Article ,Cell Line ,Inorganic Chemistry ,breast cancer ,Internal medicine ,microRNA ,Regulació genètica ,medicine ,Breast neoplasms ,Drug therapy ,Spectroscopie [état condense] ,ddc:610 ,Physical and Theoretical Chemistry ,KEGG ,Molecular Biology ,Pathological ,Neoplastic ,business.industry ,Organic Chemistry ,Biologie moléculaire ,Chimie théorique ,Biomarker ,ct-miR-148a-3p ,medicine.disease ,Chimie organique ,MicroRNAs ,Spectroscopie [électromagnétisme, optique, acoustique] ,lcsh:Biology (General) ,lcsh:QD1-999 ,Gene Expression Regulation ,circulating microRNAs ,terapéutica::tratamiento combinado::tratamiento neoadyuvante [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,business ,Catalyses hétérogène et homogène ,DDC 610 / Medicine & health - Abstract
Circulating microRNA (ct-miRNAs) are able to identify patients with differential response to HER2-targeted therapy. However, their dynamics are largely unknown. We assessed 752 miRNAs from 52 NeoALTTO patients with plasma pairs prior and two weeks after trastuzumab. Increased levels of ct-miR-148a-3p and ct-miR-374a-5p were significantly associated with pathological complete response (pCR) (p = 0.008 and 0.048, respectively). At a threshold &ge, the upper limit of the 95%CI of the mean difference, pCR resulted 45% (95%CI 24%&ndash, 68%), and 44% (95%CI 22%&ndash, 69%) for ct-miR-148a-3p and ct-miR-374a-5p, respectively. Notably, ct-miR-148a-3p retained its predictive value (OR 3.42, 95%CI 1.23&ndash, 9.46, p = 0.018) in bivariate analysis along with estrogen receptor status. Combined information from ct-miR-148a-3p and ct-miR140-5p, which we previously reported to identify trastuzumab-responsive patients, resulted in greater predictive capability over each other, with pCR of 54% (95%CI 25%&ndash, 81%) and 0% (95%CI 0%&ndash, 31%) in ct-miR-148a/ct-miR-140-5p high/present and low/absent, respectively. GO and KEGG analyses showed common enriched terms between the targets of these ct-miRNAs, including cell metabolism regulation, AMPK and MAPK signaling, and HCC progression. In conclusion, early modulated ct-miR-148-3p may inform on the functional processes underlying treatment response, integrate the information from already available predictive biomarkers, and identify patients likely to respond to single agent trastuzumab-based neoadjuvant therapy.
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- 2020
44. MiR-205 as predictive biomarker and adjuvant therapeutic tool in combination with trastuzumab
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Olivier Deas, Patrizia Casalini, Ilaria Plantamura, Alessandra Cataldo, Jean-Gabriel Judde, Elda Tagliabue, Stefano Cairo, Elvira D'Ippolito, Marta Giussani, Marilena V. Iorio, Simone Camelliti, and Claudia Piovan
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,medicine.medical_treatment ,Disease ,Lapatinib ,03 medical and health sciences ,breast cancer ,0302 clinical medicine ,Breast cancer ,Gefitinib ,Trastuzumab ,Internal medicine ,medicine ,Gene silencing ,skin and connective tissue diseases ,microRNA ,business.industry ,Standard treatment ,biomarkers ,HER2-3 ,medicine.disease ,trastuzumab ,030104 developmental biology ,030220 oncology & carcinogenesis ,business ,Adjuvant ,Research Paper ,medicine.drug - Abstract
Trastuzumab is the standard treatment for HER2+ breast cancer (BC) patients, and even though it significantly improved their clinical outcome, 50% of them do not benefit from this drug and disease recurs, underlining the need of reliable predictive biomarkers and new therapeutic strategies. Strikingly, despite all the molecular analyses performed to identify the escape mechanisms behind this resistance, it still represents a question point. MiRNAs have been correlated with occurrence and progression of human cancer, and their potential as clinical tools has emerged in the last years. We previously reported that oncosuppressive miR-205 targets HER3, thus increasing the responsiveness to TKIs lapatinib and gefitinib in preclinical models. Here we demonstrate that HER3 inhibition by miR-205 ectopic expression or siRNA-mediated silencing improves the responsiveness to Trastuzumab in vitro in HER2+ BC cell lines, and that this effect is exerted through impairment of AKT-mediated pathway. Moreover, evaluating a series of 52 HER2+ BC patients treated with adjuvant Trastuzumab, we observed that higher miR-205 expression is significantly associated with better outcome (disease-free survival). In summary, our data indicate that miR-205 could predict Trastuzumab efficacy and that its modulation might be useful as adjuvant treatment to improve the response to the drug.
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- 2018
45. Breast Cancer Drug Resistance: Overcoming the Challenge by Capitalizing on MicroRNA and Tumor Microenvironment Interplay
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Ilaria Plantamura, Elda Tagliabue, Alessandra Cataldo, Giulia Cosentino, and Marilena V. Iorio
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0301 basic medicine ,Cancer Research ,Stromal cell ,drug response ,Context (language use) ,Review ,03 medical and health sciences ,breast cancer ,0302 clinical medicine ,Breast cancer ,Trastuzumab ,microRNA ,medicine ,RC254-282 ,Triple-negative breast cancer ,Tumor microenvironment ,business.industry ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,microenvironment ,microRNAs ,Crosstalk (biology) ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,business ,medicine.drug - Abstract
Simple Summary The cross-talk between neoplastic cells and microenvironment is known to play a crucial role in tumor development as well as in the phenomenon of resistance to anticancer therapies. MicroRNAs, involved in the pathogenesis of human tumors, are among the molecules exploited in this aberrant cross-talk. Indeed, microRNAs play a crucial function both in the induction of pro-tumoral traits in stromal cells and in the stroma-mediated fueling of tumor aggressiveness. Here, we reviewed the most recent literature concerning the role of miRNAs in shaping the tumor microenvironment, and the consequences on responsiveness to therapies. Abstract The clinical management of breast cancer reaches new frontiers every day. However, the number of drug resistant cases is still high, and, currently, this constitutes one of the major challenges that cancer research has to face. For instance, 50% of women affected with HER2 positive breast cancer presents or acquires resistance to trastuzumab. Moreover, for patients affected with triple negative breast cancer, standard chemotherapy is still the fist-line therapy, and often patients become resistant to treatments. Tumor microenvironment plays a crucial role in this context. Indeed, cancer-associated stromal cells deliver oncogenic cues to the tumor and vice versa to escape exogenous insults. It is well known that microRNAs are among the molecules exploited in this aberrant crosstalk. Indeed, microRNAs play a crucial function both in the induction of pro-tumoral traits in stromal cells and in the stroma-mediated fueling of tumor aggressiveness. Here, we summarize the most recent literature regarding the involvement of miRNAs in the crosstalk between tumor and stromal cells and their capability to modulate tumor microenvironment characteristics. All up-to-date findings suggest that microRNAs in the TME could serve both to reverse malignant phenotype of stromal cells, modulating response to therapy, and as predictive/prognostic biomarkers.
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- 2021
46. Editorial: From 'Junk DNA' to Clinically Relevant Tools for Cancer Diagnosis, Staging, and Tailored Therapies: The Incredible Case of Non-Coding RNAs
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Marilena V. Iorio and Dario Palmieri
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Cancer Research ,microRNA ,business.industry ,Coding (therapy) ,Cancer ,Computational biology ,Non-coding RNA ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Noncoding DNA ,ncRNA ,lcsh:RC254-282 ,cancer diagnosis and intervention ,resistance ,Editorial ,Oncology ,Medicine ,circRNA ,business - Published
- 2019
47. Editorial to the Special Issue 'MicroRNA Dysregulation in Tumor Occurrence, Progression and Response to Therapy'
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Marilena V. Iorio
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0301 basic medicine ,Response to therapy ,media_common.quotation_subject ,Bioinformatics ,Radiation Tolerance ,Catalysis ,lcsh:Chemistry ,Inorganic Chemistry ,03 medical and health sciences ,0302 clinical medicine ,Neoplasms ,microRNA ,Biomarkers, Tumor ,Humans ,Medicine ,Physical and Theoretical Chemistry ,lcsh:QH301-705.5 ,Molecular Biology ,Spectroscopy ,Skepticism ,media_common ,business.industry ,Organic Chemistry ,General Medicine ,Computer Science Applications ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,n/a ,Editorial ,030104 developmental biology ,lcsh:Biology (General) ,lcsh:QD1-999 ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,business - Abstract
In the last 20 years, the involvement of microRNAs in the biology of human tumors has been clearly demonstrated, and the scientific community has switched from an initial skepticism to an increasing interest toward what was called the “dark side” of DNA [...]
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- 2021
48. miR-205 in Breast Cancer: State of the Art
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Ilaria Plantamura, Alessandra Cataldo, Giulia Cosentino, and Marilena V. Iorio
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0301 basic medicine ,Epithelial-Mesenchymal Transition ,Estrogen receptor ,Breast Neoplasms ,Review ,Catalysis ,Metastasis ,lcsh:Chemistry ,Inorganic Chemistry ,03 medical and health sciences ,breast cancer ,0302 clinical medicine ,Breast cancer ,microRNA ,Tumor Microenvironment ,medicine ,Humans ,Physical and Theoretical Chemistry ,skin and connective tissue diseases ,lcsh:QH301-705.5 ,Molecular Biology ,Spectroscopy ,Triple-negative breast cancer ,Cell Proliferation ,therapy ,Tumor microenvironment ,business.industry ,Gene Expression Profiling ,Organic Chemistry ,Cancer ,miR-205 ,General Medicine ,medicine.disease ,Computer Science Applications ,Biomarker (cell) ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,030104 developmental biology ,lcsh:Biology (General) ,lcsh:QD1-999 ,030220 oncology & carcinogenesis ,Disease Progression ,Cancer research ,Female ,business ,oncogenic pathways - Abstract
Despite its controversial roles in different cancer types, miR-205 has been mainly described as an oncosuppressive microRNA (miRNA), with some contrasting results, in breast cancer. The role of miR-205 in the occurrence or progression of breast cancer has been extensively studied since the first evidence of its aberrant expression in tumor tissues versus normal counterparts. To date, it is known that the expression of miR-205 in the different subtypes of breast cancer is decreasing from the less aggressive subtype, estrogen receptor/progesterone receptor positive breast cancer, to the more aggressive, triple negative breast cancer, influencing metastasis capability, response to therapy and patient survival. In this review, we summarize the most important discoveries that have highlighted the functional role of this miRNA in breast cancer initiation and progression, in stemness maintenance, in the tumor microenvironment, its potential role as a biomarker and its relevance in normal breast physiology—the still open questions. Finally, emerging evidence reveals the role of some lncRNAs in breast cancer progression as sponges of miR-205. Here, we also reviewed the studies in this field.
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- 2020
49. The Therapeutic Potential of MicroRNAs in Cancer: Illusion or Opportunity?
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Marilena V. Iorio and Orazio Fortunato
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therapy ,microRNA ,business.industry ,lcsh:R ,lcsh:Medicine ,lcsh:RS1-441 ,Pharmaceutical Science ,Cancer ,Review ,Bioinformatics ,medicine.disease ,Tissue penetration ,lcsh:Pharmacy and materia medica ,Clinical trial ,Tolerability ,Drug Discovery ,cancer ,Molecular Medicine ,Medicine ,Tumor growth ,business - Abstract
The functional involvement of microRNAs in human neoplasia has raised in the last years an increasing interest in the scientific community toward the potential application in clinics as therapeutic tools. Indeed, the possibility to modulate their expression to re-establish a lost equilibrium and counteract tumor growth and dissemination, and/or to improve responsiveness to standard therapies, is promising and fascinating. However, several issues need to be taken into account such as factors related to miRNA stability in the blood, tissue penetration and potential off-target effects, which might affect safety, tolerability and efficacy of an miRNA-based therapy. Here we describe the most relevant challenges related to miRNA-based therapy, review the delivery strategies exploited to date and the on-going clinical trials.
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- 2020
50. Plasma miRNA Levels for Predicting Therapeutic Response to Neoadjuvant Treatment in HER2-positive Breast Cancer: Results from the NeoALTTO Trial
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Giovanni Apolone, Maria Grazia Daidone, Paolo Verderio, Marilena V. Iorio, Paola Tiberio, Florentine Hilbers, Filippo de Braud, Sara Pizzamiglio, Serena Di Cosimo, Jens Huober, Evandro de Azambuja, Martine Piccart, Lorena de la Peña, José Baselga, Valentina Appierto, and Miguel Izquierdo
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0301 basic medicine ,Oncology ,Adult ,Cancer Research ,medicine.medical_specialty ,Receptor, ErbB-2 ,Breast Neoplasms ,Lapatinib ,Logistic regression ,03 medical and health sciences ,0302 clinical medicine ,Trastuzumab ,Internal medicine ,HER2 Positive Breast Cancer ,microRNA ,medicine ,Biomarkers, Tumor ,Humans ,Circulating MicroRNA ,Molecular Targeted Therapy ,skin and connective tissue diseases ,Estrogen Receptor Status ,Aged ,Neoplasm Staging ,Univariate analysis ,business.industry ,Proportional hazards model ,Gene Expression Profiling ,Middle Aged ,Prognosis ,Neoadjuvant Therapy ,Tumor Burden ,030104 developmental biology ,Treatment Outcome ,ROC Curve ,030220 oncology & carcinogenesis ,Female ,business ,medicine.drug - Abstract
Purpose: To investigate the potential of circulating-miRNAs (ct-miRNA) as noninvasive biomarkers to predict the efficacy of single/dual HER2-targeted therapy in the NeoALTTO study. Experimental Design: Patients with plasma samples at baseline (T0) and/or after 2 weeks (T1) of treatment were randomized into training (n = 183) and testing (n = 246) sets. RT-PCR–based high-throughput miRNA profiling was employed in the training set. After normalization, ct-miRNAs associated with pathologic complete response (pCR) were identified by univariate analysis. Multivariate logistic regression models were implemented to generate treatment-specific signatures at T0 and T1, which were evaluated by RT-PCR in the testing set. Event-free survival (EFS) according to ct-miRNA signatures was estimated by Kaplan–Meier method and Cox regression model. Results: In the training set, starting from 51 ct-miRNAs associated with pCR, six signatures with statistically significant predictive capability in terms of area under the ROC curve (AUC) were identified. Four signatures were confirmed in the testing set: lapatinib at T0 and T1 [AUC 0.86; 95% confidence interval (CI), 0.73–0.98 and 0.71 (0.55–0.86)], respectively; trastuzumab at T1 (0.81; 0.70–0.92); lapatinib + trastuzumab at T1 (0.67; 0.51–0.83). These signatures were confirmed predictive after adjusting for known variables, including estrogen receptor status. ct-miRNA signatures failed to correlate with EFS. However, the levels of ct-miR-140-5p, included in the trastuzumab signature, were associated with EFS (HR 0.43; 95% CI, 0.22–0.84). Conclusions: ct-miRNAs discriminate patients with and without pCR after neoadjuvant lapatinib- and/or trastuzumab-based therapy. ct-miRNAs at week two could be valuable to identify patients responsive to trastuzumab, to avoid unnecessary combination with other anti-HER2 agents, and finally to assist deescalating treatment strategies.
- Published
- 2018
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