Cristina Quintavalle
@ieos.cnr.it
IEOS-CNR
Scopus Publications
- Colorimetric aptasensor for exosome detection in breast cancer liquid biopsy
Bartolomeo Della Ventura, Cristina Quintavalle, Erica Cavaliere, Kristin Tkalčec, Paolo Aniello, et al.
Sensors and Actuators B Chemical, 2026 - Sex-related susceptibility to pulmonary fibrosis development in mice
Danilo D'Avino, Ida Cerqua, Lucianna Maruccio, Katharina P. L. Meyer, Cristina Quintavalle, et al.
British Journal of Pharmacology, 2026
Background and Purpose Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease, mainly affecting adult males. Although it exhibits a primarily fibrosing imprint, it serves as a model for understanding inflammation‐driven interstitial lung diseases that can evolve into PF. We analysed the interplay between inflammation and fibrosis, in relation to sex in a mouse model of PF. Experimental Approach Adult C57BL/6 mice of both sexes were treated with subcutaneous bleomycin injection (3 times a week for 1–4 weeks). We used RT‐PCR, western blotting and immunohistochemistry, along with ELISA, flow cytometry and mass spectrometry (UPLC‐MS/MS) to analyse our results. Key Results Male mice developed more severe fibrosis, with higher levels of collagen, and enhanced pulmonary epithelial–mesenchymal transition, compared with females. Males also showed early cell infiltration (neutrophils and macrophages) during the initial stages, followed by loss of lung architecture and an exacerbated development of fibrosis. In contrast, females exhibited physiological resolution of lung inflammation after 2 weeks of bleomycin treatment. In males, PF was associated with increased pro‐inflammatory/fibrotic mediators (TGF‐β and IL‐1β) and decreased anti‐inflammatory/anti‐fibrotic factors (IFN‐γ, miRNA‐214‐3p, miRNA‐96‐5p and PGE 2 ), particularly in the early phase of fibrosis. Pre‐treatment with pirfenidone reversed fibrosis features more effectively in males, impacting anti‐fibrotic miRNA‐214‐3p and miRNA‐96‐5p. Conclusions and Implications Our data suggest that while inflammation occurs in both males and females during the early stages of PF induction, exacerbated fibrosis is observed only in males. Additionally, pirfenidone demonstrated greater activity in male mice, highlighting the need to consider potential sex‐specific pharmacotherapy. - Operator-dependent and operator-independent contrast media minimization strategies to prevent acute kidney injury after percutaneous coronary intervention
Luca PAOLUCCI, Valeria CAVALIERE, Francesca DE MICCO, Mario SCARPELLI, Amelia FOCACCIO, et al.
Minerva Cardiology and Angiology, 2026 - Proteomic profiling of extracellular vesicles in ST-elevation acute myocardial infarction
Cristina Quintavalle, Giuseppina Roscigno, Gianluca Petrillo, Luca Paolucci, Mario Scarpelli, et al.
Cardiovascular Research, 2026 - Fibroblasts activated by miRs-185-5p, miR-652-5p, and miR-1246 shape the tumor microenvironment in triple-negative breast cancer via PATZ1 downregulation
Giada De Luca, Gianluca Petrillo, Iolanda Scognamiglio, Katia Pane, Lorenza Cocca, et al.
Cellular and Molecular Life Sciences, 2025 - Ex.50.T aptamer impairs tumor–stroma cross-talk in breast cancer by targeting gremlin-1
Cristina Quintavalle, Francesco Ingenito, Giuseppina Roscigno, Birlipta Pattanayak, Carla Lucia Esposito, et al.
Cell Death Discovery, 2025
The tumor microenvironment profoundly influences tumor complexity, particularly in breast cancer, where cancer-associated fibroblasts play pivotal roles in tumor progression and therapy resistance. Extracellular vesicles are involved in mediating communication within the TME, specifically highlighting their role in promoting the transformation of normal fibroblasts into cancer-associated fibroblasts. Recently, we identified an RNA aptamer, namely ex.50.T, that binds with remarkable affinity to extracellular vesicles shed from triple-negative breast cancer cells. Here, through in vitro assays and computational analyses, we demonstrate that the binding of ex.50.T to extracellular vesicles and parental breast cancer cells is mediated by recognition of gremlin-1 (GREM1), a bone morphogenic protein antagonist implicated in breast cancer aggressiveness and metastasis. Functionally, we uncover the role of ex.50.T as an innovative therapeutic agent in the process of tumor microenvironment re-modeling, impeding GREM1 signaling, blocking triple-negative breast cancer extracellular vesicles internalization in recipient cells, and counteracting the transformation of normal fibroblasts into cancer-associated fibroblasts. Altogether, our findings highlight ex.50.T as a novel therapeutical avenue for breast cancer and potentially other GREM1-dependent malignancies, offering insights into disrupting TME dynamics and enhancing cancer treatment strategies. - BH3 mimetic drugs overcome the microenvironment-induced resistance to crizotinib in ALK+ anaplastic large cell lymphoma
Claudia Pignataro, Pietro Zoppoli, Luca Vincenzo Cappelli, Liron Yoffe, Marta Moretti, et al.
Blood Advances, 2025
Resistance to first-line chemotherapies and crizotinib in anaplastic large cell lymphoma (ALCL) represents a significant challenge, often leading to a dismal outcome. Despite recent advancements, the dissection of the intrinsic and extrinsic molecular alterations underlying crizotinib resistance in ALCL is still poorly understood. Here, we transcriptionally unraveled the bidirectional interplay between anaplastic lymphoma kinase (ALK)-driven ALCL (ALK+ ALCL) and stromal cells in the presence of crizotinib at bulk and single-cell levels and identified that the microenvironment provides prosurvival signals leading to crizotinib persistence in ALK+ ALCL. We detected increased B-cell lymphoma 2 (BCL2) expression and downregulation of pathways related to apoptosis in crizotinib-persister ALK+ ALCL cells. Furthermore, we predicted in silico the ligand-receptor interactions between tumoral and stromal cells, supporting their contribution to ALCL pathogenesis mainly participating in the adhesion/membrane transport, triggering receptors, and promoting activation and microenvironment stimulation in lymphoma cells. Finally, we explored the effect of crizotinib in combination with BH3 mimetics. Pharmacologic and genetic ablation of anti-apoptotic targets displayed a significant synergistic effect with crizotinib, overcoming the stroma-mediated protection of lymphoma cells on drug treatment. Thus, BCL2/B-cell lymphoma-extra large (BCL-XL) targeting is synthetic lethal with crizotinib exposure in ALK+ ALCL and represents an intrinsic- and extrinsic-mediated targetable vulnerability in lymphoma cells challenged with crizotinib. Our data support the evaluation of BCL2 targeting in crizotinib-based regimens in the management of patients with ALK+ ALCL. - Targeting Glioblastoma Stem Cells via EphA2: Structural Insights into the RNA Aptamer A40s for Precision Therapy
Isidora Diakogiannaki, Vincenzo Maria D’Amore, Alessandra Affinito, Greta Donati, Elpidio Cinquegrana, et al.
Journal of Chemical Information and Modeling, 2025
EphA2 receptor tyrosine kinase is overexpressed in many solid tumors and serves as a key driver of tumorigenesis and metastasis. It is highly expressed in glioblastoma multiforme, the most aggressive brain tumor in adults, and in its stem cells [glioblastoma stem cells (GSCs)], which contribute to treatment resistance and tumor relapse. In a previous study, we used the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) procedure, a method for selecting high-affinity nucleic acids to specific targets via iterative selection and amplification, to identify the 2'-fluorinated EphA2-targeting RNA aptamer A40L and a truncated 30-mer derivative, A40s. Both aptamers were able to inhibit GSC growth, stemness, and migration upon EphA2 binding. Here, by integrating computational and experimental methods, the A40s structure was unraveled and its interaction with EphA2 was investigated. Our model offers a blueprint to accelerate the development of optimized A40s variants, advancing next-generation EphA2-targeted anticancer therapies. - Targeting Glioblastoma Stem Cells: A40s Aptamer-NIR-Dye Conjugate for Glioblastoma Visualization and Treatment
Alessandra Affinito, Francesco Ingenito, Sara Verde, Emanuele Musella, Birlipta Pattanayak, et al.
Biomolecules, 2025
Glioblastoma (GBM) is the most aggressive and challenging brain cancer, in terms of diagnosis and therapy. The highly infiltrative glioblastoma stem cells (GSCs) are difficult to visualize and surgically remove with the current diagnostic tools, which often lead to misdiagnosis and false-positive results. In this study, we focused on a groundbreaking tool for specifically visualizing and removing GSCs. We exploited the specific binding of A40s aptamer to EphA2 for the selective delivery of Near-Infrared Dyes (NIR-Dyes), like IR700DX and ICG, both in vitro and in vivo. The A40s aptamer, engineered through the NIR-Dye conjugation, did not affect aptamer binding ability; indeed, A40s-NIR-Dye conjugates bound GLI261 stem-like cells and patient-derived GSCs in vitro; moreover, they induced cell death upon photodynamic therapy treatment (PDT). Additionally, when systemically administrated, the A40s-NIR-Dye conjugates allowed GSC visualization and accumulated in tumor mass. This allows GSCs detection and treatment. Our findings demonstrate the potential use of A40s aptamer as a targeted therapeutic approach and imaging tool in vivo for GSCs, paving the way for improved, more effective, and less invasive GBM management. - The Interconnection Between UbcH10, p53, and EGFR in Lung Cancer Cells and Their Involvement in Treatment Response
Cristina Quintavalle, Umberto Malapelle, Marco De Martino, Danilo Rocco, Alfredo Fusco, et al.
Genes, 2025
Background/Objectives: The UbcH10 protein plays an important role in a variety of human malignancies, including thyroid, breast, ovarian, and colorectal carcinomas. It has been previously reported that UbcH10 is overexpressed in non-small cell lung cancer (NSCLC) compared to normal lungs and that its expression is directly and inversely correlated with the mutational status of p53 and EGFR, respectively. Methods: We transfected lung cancer cells with wild-type and mutant forms of EGFR, modulated the expression of UbcH10 and p53, and treated these cells with tyrosine kinase inhibitor (TKI) erlotinib. Using Western blotting, we evaluated the expression of UbcH10 induced by EGFR and p53. Finally, we employed immunohistochemistry to assess the levels of UbcH10 expression in a subset of NSCLC patients receiving TKI therapy. Results: We reported a possible modulation of UbcH10 expression by the overexpression of wild-type and mutant EGFR in H460 lung cancer cells, potentially through p53. The enforced expression of UbcH10 in cells transfected with mutant EGFR suggested a potential increase in resistance to erlotinib treatment. Finally, immunohistochemical analysis of samples from NSCLC patients with mutant EGFR indicated a possible connection between UbcH10 expression levels and progression-free survival. Conclusions: In NSCLC, UbcH10 may play a role in the regulation of TKI response via a molecular pathway potentially involving p53 and EGFR. However, further research is needed to fully understand this mechanism. - Extracellular vesicles and microRNAs in cancer progression
Advances in Clinical Chemistry, 2025 - MCT4-driven CAF-mediated metabolic reprogramming in breast cancer microenvironment is a vulnerability targetable by miR-425-5p
Alessandra Affinito, Cristina Quintavalle, Rosario Vincenzo Chianese, Giuseppina Roscigno, Danilo Fiore, et al.
Cell Death Discovery, 2024 - Essential gene screening identifies the bromodomain-containing protein BRPF1 as a new actionable target for endocrine therapy-resistant breast cancers
Annamaria Salvati, Giorgio Giurato, Jessica Lamberti, Ilaria Terenzi, Laura Crescenzo, et al.
Molecular Cancer, 2024 - Ultrasmall Carbon Nanodots as Theranostic Nanoheaters for Precision Breast Cancer Phototherapy: Establishing the Translational Potential in Tumor-in-a-Dish Models
Giuseppina Roscigno, Alessandra Affinito, Cristina Quintavalle, Roberta Cillari, Gerolama Condorelli, et al.
ACS Biomaterials Science and Engineering, 2024 - The FKBP51s Splice Isoform Predicts Unfavorable Prognosis in Patients with Glioblastoma
Carolina Giordano, Laura Marrone, Simona Romano, Giuseppe Maria Della Pepa, Carlo Maria Donzelli, et al.
Cancer Research Communications, 2024 - Erratum to: MicroRNA signatures of TRAIL resistance in human non-small cell lung cancer (Oncogene, (2008), 27, 27, (3845-3855), 10.1038/onc.2008.6)
M. Garofalo, C. Quintavalle, G. Di Leva, C. Zanca, G. Romano, et al.
Oncogene, 2024 - Kidney Injury After Minimal Radiographic Contrast Administration in Patients With Acute Coronary Syndromes
Carlo Briguori, Cristina Quintavalle, Enrica Mariano, Alessandro D’Agostino, Mario Scarpelli, et al.
Journal of the American College of Cardiology, 2024 - Selection of RNA aptamers targeting hypoxia in cancer
Silvia Nuzzo, Margherita Iaboni, Maria Luigia Ibba, Anna Rienzo, Domenica Musumeci, et al.
Frontiers in Molecular Biosciences, 2022 - Erratum: Exosomal microRNAs synergistically trigger stromal fibroblasts in breast cancer (Molecular Therapy - Nucleic Acids (2022) 28 (17–31), (S2162253122000415), (10.1016/j.omtn.2022.02.013))
Iolanda Scognamiglio, Lorenza Cocca, Ilaria Puoti, Francesco Palma, Francesco Ingenito, et al.
Molecular Therapy Nucleic Acids, 2022 - Exosomal microRNAs synergistically trigger stromal fibroblasts in breast cancer
Iolanda Scognamiglio, Lorenza Cocca, Ilaria Puoti, Francesco Palma, Francesco Ingenito, et al.
Molecular Therapy Nucleic Acids, 2022 - miR-579-3p Controls Hepatocellular Carcinoma Formation by Regulating the Phosphoinositide 3-Kinase–Protein Kinase B Pathway in Chronically Inflamed Liver
Cristina Quintavalle, Nathalie Meyer‐Schaller, Stephanie Roessler, Diego Calabrese, Romina Marone, et al.
Hepatology Communications, 2022 - Comparative Proteomic Profiling of Secreted Extracellular Vesicles from Breast Fibroadenoma and Malignant Lesions: A Pilot Study
Katia Pane, Cristina Quintavalle, Silvia Nuzzo, Francesco Ingenito, Giuseppina Roscigno, et al.
International Journal of Molecular Sciences, 2022 - The role of HMGA1 protein in gastroenteropancreatic neuroendocrine tumors
Marco De Martino, Simona Pellecchia, Francesco Esposito, Nadia Tosti, Cristina Quintavalle, et al.
Cell Cycle, 2022 - ZNF224 is a mediator of TGF-β pro-oncogenic function in melanoma
Elena Cesaro, Arianna Pastore, Alessia Polverino, Lorenzo Manna, Giuseppina Divisato, et al.
Human Molecular Genetics, 2021 - Interfering with the Tumor-Immune Interface: Making Way for Triazine-Based Small Molecules as Novel PD-L1 Inhibitors
Pasquale Russomanno, Giulia Assoni, Jussara Amato, Vincenzo Maria D’Amore, Riccardo Scaglia, et al.
Journal of Medicinal Chemistry, 2021
