8 results on '"Ziranu A"'
Search Results
2. CD44: A New Prognostic Marker in Colorectal Cancer?
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Ziranu, Pina, Pretta, Andrea, Aimola, Valentina, Cau, Flaviana, Mariani, Stefano, D'Agata, Alessandra Pia, Codipietro, Claudia, Rizzo, Daiana, Dell'Utri, Veronica, Sanna, Giorgia, Moledda, Giusy, Cadoni, Andrea, Lai, Eleonora, Puzzoni, Marco, Pusceddu, Valeria, Castagnola, Massimo, Scartozzi, Mario, and Faa, Gavino
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PROTEINS , *EPITHELIAL-mesenchymal transition , *LIGANDS (Chemistry) , *CELL proliferation , *HYALURONIC acid , *COLORECTAL cancer , *TUMOR markers , *CELLULAR signal transduction , *GENE expression , *MEMBRANE glycoproteins , *STEM cells , *PATHOGENESIS , *CELL receptors - Abstract
Simple Summary: CD44 is a crucial factor in colorectal cancer, with specific isoforms demonstrating their significance in the development, progression, metastasis, and resistance to therapy. Given the clinical and pathological impact of CD44, it represents a promising molecular target for cancer therapy. In this review, we aim to highlight the predictive and prognostic significance of CD44 in various cancer types, with a particular focus on colorectal cancer. Moreover, we evaluate current therapeutic interventions that target CD44 or reduce its expression, thereby highlighting its potential as an effective therapeutic strategy. Cluster of differentiation 44 (CD44) is a non-kinase cell surface glycoprotein. It is overexpressed in several cell types, including cancer stem cells (CSCs). Cells overexpressing CD44 exhibit several CSC traits, such as self-renewal, epithelial–mesenchymal transition (EMT) capability, and resistance to chemo- and radiotherapy. The role of CD44 in maintaining stemness and the CSC function in tumor progression is accomplished by binding to its main ligand, hyaluronan (HA). The HA-CD44 complex activates several signaling pathways that lead to cell proliferation, adhesion, migration, and invasion. The CD44 gene regularly undergoes alternative splicing, resulting in the standard (CD44s) and variant (CD44v) isoforms. The different functional roles of CD44s and specific CD44v isoforms still need to be fully understood. The clinicopathological impact of CD44 and its isoforms in promoting tumorigenesis suggests that CD44 could be a molecular target for cancer therapy. Furthermore, the recent association observed between CD44 and KRAS-dependent carcinomas and the potential correlations between CD44 and tumor mutational burden (TMB) and microsatellite instability (MSI) open new research scenarios for developing new strategies in cancer treatment. This review summarises current research regarding the different CD44 isoform structures, their roles, and functions in supporting tumorigenesis and discusses its therapeutic implications. [ABSTRACT FROM AUTHOR]
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- 2024
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3. New Horizons in Metastatic Colorectal Cancer: Prognostic Role of CD44 Expression
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Ziranu, Pina, primary, Aimola, Valentina, additional, Pretta, Andrea, additional, Dubois, Marco, additional, Murru, Raffaele, additional, Liscia, Nicole, additional, Cau, Flaviana, additional, Persano, Mara, additional, Deias, Giulia, additional, Palmas, Enrico, additional, Loi, Francesco, additional, Migliari, Marco, additional, Pusceddu, Valeria, additional, Puzzoni, Marco, additional, Lai, Eleonora, additional, Cascinu, Stefano, additional, Faa, Gavino, additional, and Scartozzi, Mario, additional
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- 2023
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4. New Horizons in Metastatic Colorectal Cancer: Prognostic Role of CD44 Expression
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Pina Ziranu, Valentina Aimola, Andrea Pretta, Marco Dubois, Raffaele Murru, Nicole Liscia, Flaviana Cau, Mara Persano, Giulia Deias, Enrico Palmas, Francesco Loi, Marco Migliari, Valeria Pusceddu, Marco Puzzoni, Eleonora Lai, Stefano Cascinu, Gavino Faa, and Mario Scartozzi
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cancer stem cells ,Cancer Research ,Oncology ,metastatic colorectal cancer ,CD44 expression ,biomarkers - Abstract
Background: The transmembrane glycoprotein CD44, the major hyaluronan (HA) receptor, has been proven to regulate cell growth, survival, differentiation, and migration. It is therefore widely considered to be involved in carcinogenesis. Its role as a new therapeutic target in solid tumors is under evaluation in clinical trials. The prognostic value remains controversial. Here, we aimed to investigate the correlation between CD44 expression and the clinicopathological features and survival in metastatic colorectal cancer (mCRC) patients. Methods: Data from 65 mCRC patients of the Medical Oncology Unit, University Hospital and University of Cagliari were retrospectively collected from 2008 to 2021. Immunohistochemical analysis was performed at the Pathology Division, University Hospital of Cagliari on 3 μm thick sections obtained from paraffin blocks. The intensity of immunohistochemical staining was subclassified into four groups: score 0 if negative or weak membrane staining in less than 10% of tumor cells; score 1+ if weak membrane staining in at least 10% of tumor cells or moderate membrane staining in less than 10% of tumor cells; score 2+ if moderate membrane staining in at least 10% of tumor cells or intensive membrane staining in less than 10% of tumor cells; score 3+ if intense membrane staining in at least 10% of tumor cells. Based on this score, we distinguished patients into low CD44 expression (score 0, 1+, 2+) and high CD44 expression (score 3+). Statistical analysis was performed with MedCalc (survival distribution: Kaplan–Meier; survival comparison: log-rank test; association between categorical variables: Fisher’s exact test). Results: Patients’ median age was 66 years (range 49–85). Regarding CD44 expression, score was 0 in 18 patients, 1+ in 15 patients, 2+ in 18 patients, and 3+ in 14 patients. Median overall survival (mOS) was 28.1 months (95%CI: 21.3–101). CD44 overexpression (3+) was correlated with poor prognosis (p = 0.0011; HR = 0.2), with a mOS of 14.5 months (95%CI 11.7 to 35.9) versus 30.7 months (95%CI 27.8 to 101) in lower CD44 expression. Higher CD44 expression was associated with clinically poor prognostic features: age ≥ 70 years (p = 0.0166); inoperable disease (p = 0.0008); stage IV at diagnosis (p = 0.0241); BRAF mutated (p = 0.0111), high-grade tumor (p = 0.0084). Conclusions: CD44 markedly correlated with aggressive tumor behavior and contributed to the earlier progression of disease, thus suggesting its role as a novel prognostic marker and potential therapeutic target for mCRC patients.
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- 2023
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5. From CENTRAL to SENTRAL (SErum aNgiogenesis cenTRAL): Circulating Predictive Biomarkers to Anti-VEGFR Therapy
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Vittorina Zagonel, Maria Giulia Zampino, Carla Codecà, Pina Ziranu, Nicoletta Pella, Gerardo Rosati, M. Libertini, Domenico Germano, Bruno Daniele, Pietro Sozzi, Luigi Cavanna, Mariaelena Casagrande, Antonio Zizzi, Roberto Labianca, Alberto Zaniboni, Sara Lonardi, Mario Scartozzi, Stefano Cascinu, Riccardo Giampieri, Eleonora Lai, Marco Puzzoni, Daris Ferrari, Laura Demurtas, Valeria Pusceddu, Giampieri, R., Ziranu, P., Daniele, B., Zizzi, A., Ferrari, D., Lonardi, S., Zaniboni, A., Cavanna, L., Rosati, G., Casagrande, M., Pella, N., Demurtas, L., Zampino, M. G., Sozzi, P., Pusceddu, V., Germano, D., Lai, E., Zagonel, V., Codeca, C., Libertini, M., Puzzoni, M., Labianca, R., Cascinu, S., and Scartozzi, M.
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0301 basic medicine ,Oncology ,Placental growth factor ,Cancer Research ,medicine.medical_specialty ,Bevacizumab ,Circulating biomarkers ,Colorectal cancer ,FGF2 ,bevacizumab ,lcsh:RC254-282 ,Article ,03 medical and health sciences ,Folinic acid ,angiogenesis ,0302 clinical medicine ,Internal medicine ,medicine ,Progression-free survival ,business.industry ,circulating biomarkers ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,VEGF ,Colon cancer ,Irinotecan ,Regimen ,030104 developmental biology ,colon cancer ,PlGF ,030220 oncology & carcinogenesis ,FOLFIRI ,Angiogenesis ,business ,medicine.drug - Abstract
Background: In the last decade, a series of analyses failed to identify predictive biomarkers of resistance/susceptibility for anti-angiogenic drugs in metastatic colorectal cancer (mCRC). We conducted an exploratory preplanned analysis of serum pro-angiogenic factors (SErum aNgiogenesis-cenTRAL) in 72 mCRC patients enrolled in the phase II CENTRAL (ColorEctalavastiNTRiAlLdh) trial, with the aim to identify potential predictive factors for sensitivity/resistance to first line folinic acid-fluorouracil-irinotecan regimen (FOLFIRI) plus bevacizumab. Methods: First-line FOLFIRI/bevacizumab patients were prospectively assessed for the following circulating pro-angiogenic factors, evaluated with ELISA (enzyme-linked immunosorbent assay)-based technique at baseline and at every cycle: Vascular endothelial growth factor A (VEGF-A), hepatocyte growth factor (HGF), stromal derived factor-1 (SDF-1), placental derived growth factor (PlGF), fibroblast growth factor-2 (FGF-2), monocyte chemotactic protein-3 (MCP-3), interleukin-8 (IL-8). Results: Changes in circulating FGF-2 levels among different blood samples seemed to correlate with clinical outcome. Patients who experienced an increase in FGF-2 levels at the second cycle of chemotherapy compared to baseline, had a median Progression Free Survival (mPFS) of 12.85 vs. 7.57 months (Hazard Ratio&mdash, HR: 0.73, 95% Confidence Interval&mdash, CI: 0.43-1.27, p = 0.23). Similar results were seen when comparing FGF-2 concentrations between baseline and eight-week time point (mPFS 12.98 vs. 8.00 months, HR: 0.78, 95% CI: 0.46&ndash, 1.33, p = 0.35). Conclusions: Our pre-planned, prospective analysis suggests that circulating FGF-2 levels&rsquo, early increase could be used as a marker to identify patients who are more likely to gain benefit from FOLFIRI/bevacizumab first-line therapy.
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- 2020
6. From CENTRAL to SENTRAL (SErum aNgiogenesis cenTRAL): Circulating Predictive Biomarkers to Anti-VEGFR Therapy
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Giampieri, Riccardo, primary, Ziranu, Pina, additional, Daniele, Bruno, additional, Zizzi, Antonio, additional, Ferrari, Daris, additional, Lonardi, Sara, additional, Zaniboni, Alberto, additional, Cavanna, Luigi, additional, Rosati, Gerardo, additional, Casagrande, Mariaelena, additional, Pella, Nicoletta, additional, Demurtas, Laura, additional, Zampino, Maria Giulia, additional, Sozzi, Pietro, additional, Pusceddu, Valeria, additional, Germano, Domenico, additional, Lai, Eleonora, additional, Zagonel, Vittorina, additional, Codecà, Carla, additional, Libertini, Michela, additional, Puzzoni, Marco, additional, Labianca, Roberto, additional, Cascinu, Stefano, additional, and Scartozzi, Mario, additional
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- 2020
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7. Molecular-Biology-Driven Treatment for Metastatic Colorectal Cancer
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Lai, Eleonora, primary, Liscia, Nicole, additional, Donisi, Clelia, additional, Mariani, Stefano, additional, Tolu, Simona, additional, Pretta, Andrea, additional, Persano, Mara, additional, Pinna, Giovanna, additional, Balconi, Francesca, additional, Pireddu, Annagrazia, additional, Impera, Valentino, additional, Dubois, Marco, additional, Migliari, Marco, additional, Spanu, Dario, additional, Saba, Giorgio, additional, Camera, Silvia, additional, Musio, Francesca, additional, Ziranu, Pina, additional, Puzzoni, Marco, additional, Demurtas, Laura, additional, Pusceddu, Valeria, additional, Dettori, Manuela, additional, Massa, Elena, additional, Atzori, Francesco, additional, Dessì, Mariele, additional, Astara, Giorgio, additional, Madeddu, Clelia, additional, and Scartozzi, Mario, additional
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- 2020
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8. Molecular-Biology-Driven Treatment for Metastatic Colorectal Cancer
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Valentino Impera, Giorgio Astara, Pina Ziranu, Andrea Pretta, Mara Persano, Elena Massa, Marco Puzzoni, Clelia Madeddu, Manuela Dettori, Giorgio Saba, Laura Demurtas, Stefano Mariani, S. Camera, Dario Spanu, Mariele Dessì, Valeria Pusceddu, Francesca Balconi, Marco Dubois, Eleonora Lai, Francesca Musio, Annagrazia Pireddu, Mario Scartozzi, Francesco Atzori, S. Tolu, Nicole Liscia, Clelia Donisi, G. Pinna, and Marco Migliari
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,MICROSATELLITE INSTABILITY ,Colorectal cancer ,medicine.medical_treatment ,Review ,Disease ,lcsh:RC254-282 ,WILD-TYPE KRAS ,molecular biomarkers ,DOUBLE-BLIND ,03 medical and health sciences ,0302 clinical medicine ,Growth factor receptor ,Internal medicine ,PROGNOSTIC-SIGNIFICANCE ,Medicine ,tailored treatment ,FOLFIRI PLUS BEVACIZUMAB ,Science & Technology ,business.industry ,metastatic colorectal cancer ,ISLAND METHYLATOR PHENOTYPE ,Microsatellite instability ,Immunotherapy ,RANDOMIZED PHASE-III ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,OPEN-LABEL ,medicine.disease ,Precision medicine ,digestive system diseases ,Clinical trial ,1ST-LINE TREATMENT ,030104 developmental biology ,030220 oncology & carcinogenesis ,therapeutic implications ,DNA mismatch repair ,GROWTH-FACTOR RECEPTOR ,business ,Life Sciences & Biomedicine - Abstract
BACKGROUND: Metastatic CRC (mCRC) is a molecular heterogeneous disease. The aim of this review is to give an overview of molecular-driven treatment of mCRC patients. METHODS: A review of clinical trials, retrospective studies and case reports was performed regarding molecular biomarkers with therapeutic implications. RESULTS: RAS wild-type status was confirmed as being crucial for anti-epidermal growth factor receptor (EGFR) monoclonal antibodies and for rechallenge strategy. Antiangiogenic therapies improve survival in first- and second-line settings, irrespective of RAS status, while tyrosine kinase inhibitors (TKIs) remain promising in refractory mCRC. Promising results emerged from anti-HER2 drugs trials in HER2-positive mCRC. Target inhibitors were successful for BRAFV600E mutant mCRC patients, while immunotherapy was successful for microsatellite instability-high/defective mismatch repair (MSI-H/dMMR) or DNA polymerase epsilon catalytic subunit (POLE-1) mutant patients. Data are still lacking on NTRK, RET, MGMT, and TGF-β, which require further research. CONCLUSION: Several molecular biomarkers have been identified for the tailored treatment of mCRC patients and multiple efforts are currently ongoing to increase the therapeutic options. In the era of precision medicine, molecular-biology-driven treatment is the key to impro patient selection and patient outcomes. Further research and large phase III trials are required to ameliorate the therapeutic management of these patients. ispartof: CANCERS vol:12 issue:5 ispartof: location:Switzerland status: published
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- 2020
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