130 results on '"Cappelletti, Vera"'
Search Results
102. Accurate Data Processing Improves the Reliability of Affymetrix Gene Expression Profiles from FFPE Samples
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Callari, Maurizio, primary, Lembo, Antonio, additional, Bianchini, Giampaolo, additional, Musella, Valeria, additional, Cappelletti, Vera, additional, Gianni, Luca, additional, Daidone, Maria Grazia, additional, and Provero, Paolo, additional
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- 2014
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103. Oncogenic miR-181a/b affect the DNA damage response in aggressive breast cancer
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BISSO, Andrea, primary, Faleschini, Michela, additional, Zampa, Federico, additional, Capaci, Valeria, additional, De Santa, Jacopo, additional, Santarpia, Libero, additional, Piazza, Silvano, additional, Cappelletti, Vera, additional, Daidone, Mariagrazia, additional, Agami, Reuven, additional, and Del Sal, Giannino, additional
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- 2013
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104. Proliferation-, estrogen-, and T-cell-related metagenes to predict outcome after adjuvant/neoadjuvant chemotherapy for operable breast cancer in the ECTO trial.
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Bianchini, Giampaolo, primary, Cappelletti, Vera, additional, Callari, Maurizio, additional, Carcangiu, Maria Luisa, additional, Eiermann, Wolfgang, additional, Semiglazov, Vladimir, additional, Guillem, Vicente, additional, Lluch, Ana, additional, Mansutti, Mauro, additional, Zambetti, Milvia, additional, Mariani, Gabriella, additional, Magazzu, Domenico, additional, Valagussa, Pinuccia, additional, Paolini, Biagio, additional, Musella, Valeria, additional, Di Buduo, Eleonora, additional, Miodini, Patrizia, additional, Scuro, Manuela, additional, Daidone, Maria Grazia, additional, and Gianni, Luca, additional
- Published
- 2013
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105. Gene expression analysis reveals a different transcriptomic landscape in female and male breast cancer
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Callari, Maurizio, primary, Cappelletti, Vera, additional, De Cecco, Loris, additional, Musella, Valeria, additional, Miodini, Patrizia, additional, Veneroni, Silvia, additional, Gariboldi, Manuela, additional, Pierotti, Marco Alessandro, additional, and Daidone, Maria Grazia, additional
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- 2010
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106. Impact of biospecimens handling on biomarker research in breast cancer
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De Cecco, Loris, primary, Musella, Valeria, additional, Veneroni, Silvia, additional, Cappelletti, Vera, additional, Bongarzone, Italia, additional, Callari, Maurizio, additional, Valeri, Barbara, additional, Pierotti, Marco A, additional, and Daidone, Maria Grazia, additional
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- 2009
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107. PIK3CAcancer mutations display gender and tissue specificity patterns
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Benvenuti, Silvia, primary, Frattini, Milo, additional, Arena, Sabrina, additional, Zanon, Carlo, additional, Cappelletti, Vera, additional, Coradini, Danila, additional, Grazia Daidone, Maria, additional, Pilotti, Silvana, additional, Pierotti, Marco A., additional, and Bardelli, Alberto, additional
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- 2008
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108. Circulating Biomarkers for Prediction of Treatment Response.
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Cappelletti, Vera, Appierto, Valentina, Tiberio, Paola, Fina, Emanuela, Callari, Maurizio, and Daidone, Maria Grazia
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- 2015
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109. Modulation of estrogen receptor-β isoforms by phytoestrogens in breast cancer cells
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Cappelletti, Vera, primary, Miodini, Patrizia, additional, Di Fronzo, Giovanni, additional, and Daidone, Maria, additional
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- 2006
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110. Prospective evaluation of estrogen receptor-β in predicting response to neoadjuvant antiestrogen therapy in elderly breast cancer patients
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Cappelletti, Vera, primary, Celio, Luigi, additional, Bajetta, Emilio, additional, Allevi, Arianna, additional, Longarini, Raffaella, additional, Miodini, Patrizia, additional, Villa, Raffaella, additional, Fabbri, Alessandra, additional, Mariani, Luigi, additional, Giovanazzi, Riccardo, additional, Galante, Emanuele, additional, Greco, Marco, additional, and Grazia Daidone, Maria, additional
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- 2004
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111. Biomarkers for Breast Cancer: Towards the Proposition of Clinically Relevant Tools.
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Bombardieri, Emilio, Gianni, Luca, Bonadonna, Gianni, Daidone, Maria Grazia, Cappelletti, Vera, Paradiso, Angelo, Gion, Massimo, Harbeck, Nadia, Sweep, Fred, and Schmitt, Manfred
- Abstract
Breast cancer heterogeneity represents a major hurdle to improve patient survival. Notwithstanding its potential curability due to the availability of treatment modalities that are effective in the presence of favourable clinical or patho-biologic features, there is still a great deal of controversy in its clinical management. In the last decades, tumour biomarkers that are indicative of or related to cell traits characterising malignancy, such as self-sufficiency in proliferative growth signals, insensitivity to growth inhibitory signals, evasion of apoptosis, limitless replicative potential, activation of pathways leading to neo-angiogenesis, invasion and metastasis, have provided information that have proved to be associated with disease progression. However, when singly analysed, their prognostic relevance was modest, and the only clinically useful biomarkers that remained are cell proliferation and plasminogen activationrelated factors for prognosis, steroid hormone receptors and HER2/neu for prediction of response to hormonal or to the novel targeted anti-HER2/neu therapy, respectively. It therefore remains necessary to reduce the intrinsic complexity of breast cancer in order to improve its clinical outcome. One way to achieve this objective derives directly from the concept that cancer is a genetic disease at the somatic level and from the recent availability of high-throughput post-genomic analytical tools such as gene and protein expression techniques for global gene expression analysis. The knowledge derived from gene expression-profiling studies is impressive and challenges currently used breast cancer classification and existing theories about metastatic progression and breast cancer biology. Several studies employing this technology have been consistent in reproducing a molecular classification for breast cancer in which: (1) oestrogen receptor status and tumour grade are the most important discriminators of gene expression subgroups; (2) tumours can be grouped into at least four subsets according to steroid receptor and HER2/neu status; (3) each subset of tumours has a distinct clinical outcome and may therefore respond differentially to various treatments. Additionally, prognostic gene expression signatures have been proposed that outperform traditional clinical risk classification systems, suggesting the possibility to reduce over-treatment in early breast cancer, notwithstanding that the identification of high-risk patients still needs to be improved. A number of recent studies have been directed to answer different clinical and biological questions. However, despite initial enthusiasm doubts have been raised recently regarding the reliability of gene expression profiling for clinical applications, and the outcome of these novel studies still needs to be validated with the cooperation of different specialists and the integration between all the different skills involved in translational research in oncology. [ABSTRACT FROM AUTHOR]
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- 2008
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112. Estrogen Receptor-Beta Expression in Hereditary Breast Cancer
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Daidone, Maria Grazia, primary, Veneroni, Silvia, additional, Cappelletti, Vera, additional, Radice, Paolo, additional, Pierotti, Marco A., additional, Younes, Mamoun, additional, Scheuer, Lauren, additional, Kauff, Noah D., additional, Robson, Mark E., additional, and Offit, Kenneth, additional
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- 2002
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113. Genistein in the control of breast cancer cell growth: insights into the mechanism of action in vitro
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Fioravanti, Laura, primary, Cappelletti, Vera, additional, Miodini, Patrizia, additional, Ronchi, Enrico, additional, Brivio, Moreno, additional, and Di Fronzo, Giovanni, additional
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- 1998
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114. int-2 Oncogene amplification and prognosis in node-negative breast carcinoma
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Fioravanti, Laura, primary, Cappelletti, Vera, additional, Coradini, Danila, additional, Miodini, Patrizia, additional, Borsani, Giorgio, additional, Daidone, Maria Grazia, additional, and Di Fronzo, Giovanni, additional
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- 1997
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115. Oncogenic miR-181a/b affect the DNA damage response in aggressive breast cancer.
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Bisso, Andrea, Faleschini, Michela, Zampa, Federico, Capaci, Valeria, De Santa, Jacopo, Santarpia, Libero, Piazza, Silvano, Cappelletti, Vera, Daidone, Mariagrazia, Agami, Reuven, and Del Sal, Giannino
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- 2013
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116. Variations in Estrogen and Progesterone Receptor Content in Premenopausal Breast Cancer Patients Throughout the Menstrual Cycle
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Coradini, Danila, Cappelletti, Vera, Miodini, Patrizia, Ronchi, Enrico, Scavone, Gianfranco, and Di Fronzo, Giovanni
- Abstract
Estrogen (ER) and progesterone (PgR) receptor content was assayed in 290 premenopausal women with primary breast cancer, in order to investigate the influence of endogenous hormones on cytoplasmic receptor concentrations throughout the menstrual cycle, subdivided into four phases of ovarian function (early and late follicular phase, early and late luteal phase). Of the total population, 231 (79.7 %) patients were ER positive and 59 (20.3 %) were ER negative; 220 (75.9 %) were PgR positive and 70 (24.1 %) were PgR negative. The percentages of positive cases were almost constant in each phase. No significant difference in mean values of ER concentration was noted throughout the cycle. Instead, the PgR concentration significantly increased from the first to the third phase (P = 0.02) and decreased from the third to the fourth phase (P = 0.01). Our results suggest that ER- and PgR- cases are homogeneously distributed and not influenced by the phase of the cycle. Moreover, they suggest that PgR measurement in the luteal phase, rather than in other phases, prevents the occurrence of false low PgR levels and, at the same time, improves its prognostic significance and response rate to endocrine therapy.
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- 1984
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117. <TOGGLE>int</TOGGLE>-2 Oncogene amplification and prognosis in node-negative breast carcinoma
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Fioravanti, Laura, Cappelletti, Vera, Coradini, Danila, Miodini, Patrizia, Borsani, Giorgio, and Daidone, Maria Grazia
- Abstract
The role of int-2 oncogene amplification on the prognosis of breast cancer patients was investigated in 128 patients with node-negative primary breast cancers given first-line local-regional treatments until relapse and with a median follow-up of 65 months. Tumours had been previously characterised for oestrogen (ER) and progesterone receptor (PgR) status and proliferative activity (3H-thymidine labelling index). Amplification of the int-2 oncogene occurred in 18% of cases and was significantly related to the presence of hormone receptors and to menopausal status or age, but not to proliferative status. Patients with tumours exhibiting int-2 amplification had a lower probability of disease-free survival than patients with non-amplified tumours and frequently developed local-regional recurrence. Disease-free survival analysis, adjusted for the prognostic contribution provided by tumour size, steroid receptors and proliferative rate, indicated that the association between int-2 amplification and risk of relapse was maintained and remained constant even in the presence of the other co-variates. Interestingly, int-2 amplification was a further prognostic discriminant within subsets of patients with a putatively good (i.e., tumour size <20 mm, ER+ and PgR+) or poor prognosis (i.e., high labelling index). Our exploratory study suggests that within node-negative patients, int-2 amplification could be a valuable and independent prognosticator, useful to identify patients at high risk of local-regional recurrence. Int. J. Cancer 74:620624, 1997.© 1997 Wiley-Liss, Inc.
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- 1997
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118. Prognostic Significance of Progesterone Receptors Alone or in Association with Estrogen Receptors in Human Breast Cancer
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Di Fronzo, Giovanni, Cappelletti, Vera, Coradini, Danila, Ronchi, Enrico, and Scavone, Gianfranco
- Abstract
Estrogen (ER) and progesterone (PgR) receptors were measured simultaneously in 1144 consecutive breast cancer patients to determine the distribution of patients according to receptor and menopausal status when receptor occurrence rates were considered. The prognostic signicance of PgR, either alone or in association with ER, was studied on 187 consecutive breast cancer patients treated only by radical mastectomy. All the cases, as regards axillary node status, were pathologically assessed as node negative. These patients did not receive any adjuvant treatment after mastectomy. At 36 months after mastectomy, the follow-up indicated that PgR- patients have a worse prognosis than PgR+ ones. This is evident when PgR alone is considered as a prognostic factor as well as when it is used to identify, within ER+ cases, those with a higher probability of relapse. In conclusion, it can be stated that although PgR status is an independent prognostic factor, it is useful to evaluate ER and PgR simultaneously for better patient management.
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- 1984
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119. Distribution of Estrogen and Progesterone Receptors in Primary Tumor and Lymph Nodes in Individual Patients with Breast Cancer
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Coradini, Danila, Cappelletti, Vera, Miodini, Patrizia, Ronchi, Enrico, Scavone, Gianfranco, and Di Fronzo, Giovanni
- Abstract
Primary breast cancer tissue and lymph nodes were obtained from 48 patients. Estrogen receptors (ER) and progesterone receptors (PgR) were determined by a dextran-coated charcoal assay. ER were present in 72.9 % of the primary tumors and in 62.4 % of the malignant lymph nodes, whereas PgR were present in 73.0 % and 50.0 % of the cases, respectively. The primary tumor and the corresponding malignant lymph nodes showed an identical ER and PgR status, i.e., both tumor sites were receptor positive or both receptor negative in 89.6 % and 77.1 %, respectively. However, 10.4 % of the patients had ER-positive tumors but ER-negative lymph nodes and 22.9 % had PgR-positive primaries with PgR-negative lymph nodes. No receptor-positive lymph nodes showed a combination with receptor-negative primary tumor. This preliminary data shows that receptor-positive malignant lymph nodes mostly display the same receptor status as the corresponding primary tumor, whereas receptor-negative lymph nodes may have a receptor-positive primary tumor.
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- 1984
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120. Hormone Treatment and Sex Steroid Receptors in Metastatic Renal Cell Carcinoma: Report of a Multicentric Prospective Study
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Pizzocaro, Giorgio, Di Fronzo, Giovanni, Cappelletti, Vera, Piva, Luigi, Salvioni, Roberto, Ronchi, Enrico, Giongo, Alberto, Dormia, Enrico, Zanollo, Alberto, Giannoni, Roberto, Maffeis, Vincenzo, and Lasio, Edoardo
- Abstract
Twenty-eight patients with metastatic renal cell carcinoma entered a multicentric prospective study to evaluate the response to high-dose medroxyprogesterone acetate (MPA) and testosterone in MPA failures in relation to sex steroid receptors. No objective remission was seen in the 24 evaluable patients, and only disease stabilizations of short duration were achieved in one-third of treated patients. Stabilizations achieved with second line testosterone were all seen in patients unresponsive to MPA. Receptor studies demonstrated that estrogen, progesterone, or androgen receptors were found in low concentrations and in only 6 of 23 tumors (26%) and 13 normal tissue samples (56%). Surprisingly, no disease stabilization was achieved in patients positive for receptors. It can be concluded that the occasional objective responses to hormone therapy reported in the literature may have been due to some cytotoxic effect of hormone therapy rather than to a true hormonal mechanism.
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- 1983
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121. The Detection and Morphological Analysis of Circulating Tumor and Host Cells in Breast Cancer Xenograft Models.
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Cleris, Loredana, Daidone, Maria Grazia, Fina, Emanuela, and Cappelletti, Vera
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BREAST cancer ,HISTOCHEMISTRY ,CANCER cells ,CELL tumors - Abstract
Hematogenous dissemination may occur early in breast cancer (BC). Experimental models could clarify mechanisms, but in their development, the heterogeneity of this neoplasia must be considered. Here, we describe circulating tumor cells (CTCs) and the metastatic behavior of several BC cell lines in xenografts. MDA-MB-231, BT-474, MDA-MB-453 and MDA-MB-468 cells were injected at the orthotopic level in immunocompromised mice. CTCs were isolated using a size-based method and identified by cytomorphological criteria. Metastases were detected by COX IV immunohistochemistry. CTCs were detected in 90% of animals in each model. In MDA-MB-231, CTCs were observed after 5 weeks from the injection and step wisely increased at later time points. In animals injected with less aggressive cell lines, the load of single CTCs (mean ± SD CTCs/mL: 1.8 ± 1.3 in BT-474, 122.2 ± 278.5 in MDA-MB-453, 3.4 ± 2.5 in MDA-MB-468) and the frequency of CTC clusters (overall 38%) were lower compared to MDA-MB-231 (946.9 ± 2882.1; 73%). All models had lung metastases, MDA-MB-453 and MDA-MB-468 had ovarian foci too, whereas lymph nodal involvement was observed in MDA-MB-231 and MDA-MB-468 only. Interestingly, CTCs showed morphological heterogeneity and were rarely associated to host cells. Orthotopic xenograft of BC cell lines offers valid models of hematogenous dissemination and a possible experimental setting to study CTC-blood microenvironment interactions. [ABSTRACT FROM AUTHOR]
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- 2019
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122. Strategies to Translate Preclinical Information to Breast Cancer Patient Benefit
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Daidone, Maria Grazia, Zaffaroni, Nadia, and Cappelletti, Vera
- Abstract
Despite the progress in understanding breast cancer biology, translation of basic findings into clinical applications still appears to be a complex process, and few molecular markers/signatures are in routine clinical use or currently challenged for their clinical utility. Disease complexity, certainly, represents an obstacle to successful translation, but methodological pitfalls in development and validation steps also contribute. Translational research should be planned as a round-trip from the bench to the bedside and back. The preoperative/neoadjuvant setting represents an ideal model because it allows identification and validation of treatment response predictors and of pharmacodynamic markers associated with clinical downstaging, investigations on in vivo action mechanism of drugs, and indirect validation of findings from preclinical models. Availability of well-annotated, high-quality biospecimens; standardized, reproducible, and robust assays to detect molecular markers/signatures even on few cells; prospective planning of study design; and regulatory issues adequately fitting preclinical and clinical needs represent fundamental assets for translational studies.
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- 2011
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123. Gene Expression Profiling of Circulating Tumor Cells in Breast Cancer
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Daniele Generali, Vera Cappelletti, Carolina Reduzzi, Maria Grazia Daidone, Emanuela Fina, Maurizio Callari, Marco A. Pierotti, Francesca D'Aiuto, Gabriella Mariani, Fina, Emanuela, Callari, Maurizio, Reduzzi, Carolina, D'Aiuto, Francesca, Mariani, Gabriella, Generali, Daniele, Pierotti, Marco A., Daidone, Maria G., and Cappelletti, Vera
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Pathology ,medicine.medical_specialty ,Clinical Biochemistry ,Biochemistry (medical) ,Medicine (all) ,Cell Culture Techniques ,Breast Neoplasms ,chemistry.chemical_compound ,Circulating tumor cell ,medicine ,Humans ,MUC1 ,Whole blood ,biology ,Gene Expression Profiling ,Epithelial cell adhesion molecule ,Neoplastic Cells, Circulating ,Biomarker (cell) ,Gene expression profiling ,Gene Ontology ,chemistry ,Cell culture ,MCF-7 Cells ,Cancer research ,biology.protein ,Female ,Antibody ,Transcriptome ,Genome-Wide Association Study - Abstract
BACKGROUND Determining the transcriptional profile of circulating tumor cells (CTCs) may allow the acquisition of clinically relevant information while overcoming tumor heterogeneity-related biases associated with use of tissue samples for biomarker assessment. However, such molecular characterization is challenging because CTCs are rare and outnumbered by blood cells. METHODS Here, we describe a technical protocol to measure the expression of >29 000 genes in CTCs captured from whole blood with magnetic beads linked with antibodies against epithelial cell adhesion molecule (EpCAM) and the carcinoma-associated mucin, MUC1, designed to be used for CTC characterization in clinical samples. Low numbers of cells (5–200) from the MCF7 and MDA-MB-468 breast cancer cell lines were spiked in healthy donor blood samples and isolated with the AdnaTest EMT-1/Stem CellSelect kit. Gene expression profiles (GEPs) were obtained with the WG-DASL HT assay and compared with GEPs obtained from RNA isolated from cultured cell lines and unspiked samples. RESULTS GEPs from samples containing 25 or more spiked cells correlated (r = 0.95) with cognate 100-ng RNA input samples, clustered separately from blood control samples, and allowed MCF7 and MDA-MB-468 cells to be distinguished. GEPs with comparable technical quality were also obtained in a preliminary series of clinical samples. CONCLUSIONS Our approach allows technically reliable GEPs to be obtained from isolated CTCs for the acquisition of biologically useful information. It is reproducible and suitable for application in prospective studies to assess the clinical utility of CTC GEPs, provided that >25 CTCs can be isolated.
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- 2015
124. Can we define breast cancer HER2 status by liquid biopsy?
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Di Cosimo S, De Marco C, Silvestri M, Busico A, Vingiani A, Pruneri G, and Cappelletti V
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- Female, Humans, Biological Evolution, Liquid Biopsy, Breast Neoplasms drug therapy
- Abstract
Human Epidermal growth factor Receptor 2 (HER2) assessment is crucial for breast cancer treatment. Therapeutic decisions for recurrent cases often rely on primary tumor status. However, mounting evidence suggests that tumors show dynamic changes and up to 10% of breast cancer modify their initial status during progression. It is still debated whether these changes reflect a biological evolution of the disease or are secondary to primary tumor heterogeneity. Certainly, repeating HER2 assessment during breast cancer trajectory is important for the increasing availability of effective anti-HER2 drugs. In response to this need, circulating biomarkers such as circulating tumor cells (CTCs) and cell-free circulating tumor DNA (ctDNA) offer the potential to safely and repeatedly assess HER2 status over time. This chapter outlines current methods for testing HER2 in CTCs and ctDNA, and reviews clinical trials evaluating its prognostic and predictive value in patients with breast cancer, as well as recent advances in the field., (Copyright © 2023. Published by Elsevier Inc.)
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- 2023
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125. In-depth characterization of breast cancer tumor-promoting cell transcriptome by RNA sequencing and microarrays.
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Callari M, Guffanti A, Soldà G, Merlino G, Fina E, Brini E, Moles A, Cappelletti V, and Daidone MG
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- Alternative Splicing genetics, Blotting, Western, Breast Neoplasms genetics, Breast Neoplasms metabolism, Breast Neoplasms pathology, Estradiol pharmacology, Estrogens pharmacology, Gene Expression Regulation, Neoplastic drug effects, Humans, MCF-7 Cells, Reverse Transcriptase Polymerase Chain Reaction, Transcriptome drug effects, Gene Expression Profiling methods, Neoplastic Stem Cells metabolism, Oligonucleotide Array Sequence Analysis methods, Sequence Analysis, RNA methods, Transcriptome genetics
- Abstract
Numerous studies have reported the existence of tumor-promoting cells (TPC) with self-renewal potential and a relevant role in drug resistance. However, pathways and modifications involved in the maintenance of such tumor subpopulations are still only partially understood. Sequencing-based approaches offer the opportunity for a detailed study of TPC including their transcriptome modulation. Using microarrays and RNA sequencing approaches, we compared the transcriptional profiles of parental MCF7 breast cancer cells with MCF7-derived TPC (i.e. MCFS). Data were explored using different bioinformatic approaches, and major findings were experimentally validated. The different analytical pipelines (Lifescope and Cufflinks based) yielded similar although not identical results. RNA sequencing data partially overlapped microarray results and displayed a higher dynamic range, although overall the two approaches concordantly predicted pathway modifications. Several biological functions were altered in TPC, ranging from production of inflammatory cytokines (i.e., IL-8 and MCP-1) to proliferation and response to steroid hormones. More than 300 non-coding RNAs were defined as differentially expressed, and 2,471 potential splicing events were identified. A consensus signature of genes up-regulated in TPC was derived and was found to be significantly associated with insensitivity to fulvestrant in a public breast cancer patient dataset. Overall, we obtained a detailed portrait of the transcriptome of a breast cancer TPC line, highlighted the role of non-coding RNAs and differential splicing, and identified a gene signature with a potential as a context-specific biomarker in patients receiving endocrine treatment.
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- 2016
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126. Circulating Biomarkers for Prediction of Treatment Response.
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Cappelletti V, Appierto V, Tiberio P, Fina E, Callari M, and Daidone MG
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- Disease Progression, Humans, Neoplasms blood, Neoplasms diagnosis, Outcome Assessment, Health Care methods, Prognosis, Reproducibility of Results, Sensitivity and Specificity, Biomarkers, Tumor blood, DNA, Neoplasm blood, MicroRNAs blood, Neoplasms therapy, Neoplastic Cells, Circulating pathology
- Abstract
For cancer management, predicting and monitoring response to treatment and disease progression longitudinally is crucial due to changes in tumor biology and therapy responsiveness over time. However, solid tumors are usually sampled only at time of initial diagnosis, as obtaining tissue biopsies is an invasive procedures with associated risks. Thus, there is a pressing need for approaches able to serially detect function-related reliable biomarkers reflecting treatment response and/or disease progression through easy noninvasive procedures, amenable for longitudinal analysis of tumor molecular features. Recent evidences indicate that blood and other body fluids could replace invasive surgical biopsies and represent a "liquid biopsy" containing cells and nucleic acids released by primary and metastatic lesions, reflecting their biological features and allowing identification of clinically useful biomarkers and treatment-induced cancer adaption processes. The development of new and highly sensitive technologies that allow to detect and characterize circulating tumor cells, to identify cell-free nucleic acids (circulating tumor-associated microRNAs and cancer-specific mutations in circulating DNA) and to measure their eventual dynamic changes represents therefore a major achievement for disease monitoring. However, notwithstanding preliminary findings support the prognostic and/or predictive role of this new generation of biomarkers, there are a number of technical and biological caveats that still require additional studies to demonstrate and validate their clinical utility. A unique opportunity to rapidly assess the contribution of circulating tumor cells and cell-free nucleic acids to patient management and to personalized medicine could derive by their combined consideration in the neoadjuvant setting., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2015
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127. Clusterin: a potential target for improving response to antiestrogens.
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Toffanin S, Daidone MG, Miodini P, De Cecco L, Gandellini P, and Cappelletti V
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- Cell Line, Tumor, Cell Proliferation, Clusterin chemistry, Drug Synergism, Gene Silencing, Humans, Medical Oncology methods, Models, Biological, Neoplasm Metastasis, Tamoxifen pharmacology, Toremifene pharmacology, Breast Neoplasms drug therapy, Breast Neoplasms pathology, Clusterin metabolism, Drug Screening Assays, Antitumor, Estrogen Receptor Modulators pharmacology, Gene Expression Regulation, Neoplastic
- Abstract
Antiestrogens represent the first line of therapy in the treatment of estrogen receptor-positive (ER+) breast cancer patients. Unfortunately, up to 40% of patients develop resistance associated with progression and frequently die for metastatic breast cancer. The molecular events leading to pharmacological resistance are not completely understood. We attempted to verify in an experimental model the role of cytoplasmic clusterin (CLU), a cytoprotective protein found to be up-regulated in antiestrogen-resistant patients, following neoadjuvant treatment with toremifene. The role of cytoplasmic clusterin in modulating response to two antiestrogens (toremifene and tamoxifen) was studied in two ER+ anti-estrogen-sensitive cell lines (MCF-7, 734B) and one ER+ antiestrogen-resistant cell line (T47D) using siRNA strategy. Resistant cells were characterised by higher levels of cytoplasmic clusterin than sensitive cells, and antiestrogen treatments up-regulated clusterin levels in both sensitive and resistant cell lines. Treatment with siRNA completely abolished cytoplasmic clusterin expression in all cell lines, but its down-regulation resulted in a significant decrease of cell growth only in the resistant line. We therefore concluded that: i) basal clusterin levels are higher in antiestrogen resistant cells, ii) clusterin is up-regulated following antiestrogen treatment independently of the sensitivity of the cell line, iii) down-regulation of cytoplasmic clusterin restores sensitivity to toremifene in the antiestrogen-resistant cell line. Such results support the concept that targeting CLU could represent a promising therapeutic strategy in association with antiestrogen treatment in breast cancer patients.
- Published
- 2008
128. Patterns and changes in gene expression following neo-adjuvant anti-estrogen treatment in estrogen receptor-positive breast cancer.
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Cappelletti V, Gariboldi M, De Cecco L, Toffanin S, Reid JF, Lusa L, Bajetta E, Celio L, Greco M, Fabbri A, Pierotti MA, and Daidone MG
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- Aged, Biopsy, Breast Neoplasms pathology, Chemotherapy, Adjuvant, Clusterin genetics, Drug Resistance, Neoplasm genetics, Estrogen Receptor alpha genetics, Female, Humans, Oligonucleotide Array Sequence Analysis, RNA, Small Interfering, Reverse Transcriptase Polymerase Chain Reaction, Breast Neoplasms drug therapy, Breast Neoplasms genetics, Gene Expression Regulation, Neoplastic drug effects, Selective Estrogen Receptor Modulators therapeutic use, Toremifene therapeutic use
- Abstract
This study aimed to define a gene expression profile associated with response to anti-estrogen treatment in estrogen receptor alpha (ERalpha)-positive breast cancer from elderly patients and to identify possible candidate genes associated with resistance by detecting those modulated by treatment. Using cDNA microarrays containing 16 702 unique clones, 21 pre-treatment and 11 paired post-treatment samples collected in a neo-adjuvant toremifene trial on elderly patients with operable and locally advanced ERalpha-positive breast cancer were profiled. Gene expression profiles generated from pre-treatment samples were correlated with treatment-induced tumor shrinkage and compared with those obtained from post-treatment paired samples to define genes differentially modulated following anti-estrogen treatment. Correlation analysis on 21 pre-treatment samples highlighted 53 genes significantly related to treatment response (P<0.001). Genes involved in cell cycle and proliferation were more frequently upregulated in responders compared with non-responders. Class comparison analysis identified 101 genes significantly modulated independently of treatment response; 82 genes were modulated in non-responders, whereas only 8 genes were differently expressed after treatment in responders. Gene expression profiles appear to be more frequently modulated by anti-estrogen treatment in non-responding patients and may harbor interesting genes possibly involved in anti-estrogen resistance, including clusterin, MAPK6, and MMP2. This concept was corroborated by in vitro studies showing that silencing of CLU restored toremifene sensitivity in the ER anti-estrogen-resistant breast cancer cell line T47D. Integration between neo-adjuvant therapy and transcriptional profiling has therefore the potential to identify therapeutic targets to be challenged for overcoming treatment resistance.
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- 2008
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129. Modulation of estrogen receptor-beta isoforms by phytoestrogens in breast cancer cells.
- Author
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Cappelletti V, Miodini P, Di Fronzo G, and Daidone MG
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- Breast Neoplasms, Cell Line, Tumor, DNA Primers, Estrogen Receptor beta drug effects, Estrogen Receptor beta genetics, Female, Gene Expression Regulation, Neoplastic drug effects, Genistein pharmacology, Humans, Quercetin pharmacology, RNA, Messenger genetics, Reverse Transcriptase Polymerase Chain Reaction, Estrogen Receptor beta metabolism, Phytoestrogens pharmacology
- Abstract
High consumption of phytoestrogen-rich food correlates with reduced incidence of breast cancer. However, the effect of phytoestrogens on growth of pre-existing breast tumors presents concerns when planning the use of phytoestrogens as chemoprevention st rategy. Genistein, the active phytoestrogen in soy, displays weak estrogenic activity mediated by estrogen receptor (ER) with a preferential binding for the ER-beta species. However, no information is at present available on the interaction between phytoestrogens and the various isoforms generated by alternative splicing. In two human breast cancer cell lines, T47D and BT20, which express variable levels of ER-beta, the effect of genistein and quercetin was evaluated singly and in comparison with 17beta-estradiol, on mRNA expression of estrogen receptor-beta (ER-beta) isoforms evaluated by a triple primer RT-PCR assay. In T47D cells estradiol caused a 6-fold up-regulation of total ER-beta, and modified the relative expression pattern of the various isoforms, up-regulating the beta2 and down-regulating the beta5 isoform. Genistein up-regulated ER-beta2 and ER-beta1 in T47D cells, and after treatment the ER-beta2 isoform became prevalent, while in BT20 cells it almost doubled the percent contribution of ER-beta1 and ER-beta2 to total ER-beta. Quercetin did not alter the total levels nor the percent distribution of ER-beta isoforms in either cell line. Genistein, through the modulation of ER-beta isoform RNA expression inhibited estrogen-promoted cell growth, without interfering on estrogen-regulated transcription. ER-beta and its ER-beta mRNA isoforms may be involved in a self-limiting mechanism of estrogenic stimulation promoted either by the natural hormone or by weaker estrogen agonists like genistein.
- Published
- 2006
130. Prospective evaluation of estrogen receptor-beta in predicting response to neoadjuvant antiestrogen therapy in elderly breast cancer patients.
- Author
-
Cappelletti V, Celio L, Bajetta E, Allevi A, Longarini R, Miodini P, Villa R, Fabbri A, Mariani L, Giovanazzi R, Galante E, Greco M, and Grazia Daidone M
- Subjects
- Aged, Aged, 80 and over, Breast Neoplasms pathology, Carcinoma pathology, Estrogen Antagonists therapeutic use, Estrogen Receptor alpha genetics, Estrogen Receptor beta genetics, Female, Gene Expression Regulation, Neoplastic drug effects, Humans, Neoadjuvant Therapy, RNA, Messenger biosynthesis, Treatment Outcome, Tumor Burden, Antineoplastic Agents, Hormonal therapeutic use, Breast Neoplasms drug therapy, Carcinoma drug therapy, Estrogen Receptor alpha metabolism, Estrogen Receptor beta metabolism, Selective Estrogen Receptor Modulators therapeutic use, Toremifene therapeutic use
- Abstract
It has been proposed that knowledge of estrogen receptor beta (ER-beta) expression may refine estrogen receptor alpha (ER-alpha) predictivity of response to endocrine therapy. We challenged this hypothesis in ER-alpha-positive breast cancers subjected to preoperative antiestrogen treatment. Forty-seven elderly (> or =65 years old) women with nonmetastatic, ER-alpha-positive (by immunohistochemistry) primary breast cancers (> 2 cm in diameter) entered a neoadjuvant hormone therapy protocol (60 mg/day toremifene for 3 months). ER-alpha and ER-beta (ERs) mRNA was determined by semiquantitative RT-PCR, before (on core needle biopsy) and after (on surgical specimens) neoadjuvant treatment. Study end points included: (1) relation between treatment response and ER mRNA expression; and (2) changes in ER expression after treatment. The response was clinically assessed as tumor size change at the end of the preoperative treatment. ER mRNA expression was assessable before and after treatment in 38 and 20 cases respectively. ER-beta was co-expressed with ER-alpha at variable levels and significantly correlated only with progesterone receptor (P = 0.0285). Objective clinical response, including patients with minor change (> or =25-<50% tumor shrinkage after treatment), was documented in 68.4% of cases and was independent of ER-beta levels or changes. ER-alpha levels were higher in tumors from patients in complete remission than in those from women achieving partial response or minor change compared with non-responsive patients (median expression values: 801 versus 516 versus 320 arbitrary units) and were consistently down-regulated by preoperative treatment. We conclude that in this elderly patient population with ER-alpha-positive tumors, ER-beta mRNA was neither predictive of response to preoperative toremifene nor provided additional information to the knowledge of ER-alpha mRNA levels, which, conversely, were directly correlated with likelihood of response.
- Published
- 2004
- Full Text
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