المؤلفون: Pepe, Francesco, Russo, Gianluca, Venuta, Alessandro, Scimone, Claudia, Nacchio, Mariantonia, Pisapia, Pasquale, Goteri, Gaia, Barbisan, Francesca, Chiappetta, Caterina, Pernazza, Angelina, Campagna, Domenico, Giordano, Marco, Perrone, Giuseppe, Sabarese, Giovanna, Altimari, Annalisa, de Biase, Dario, Tallini, Giovanni, Calistri, Daniele, Chiadini, Elisa, Capelli, Laura, Santinelli, Alfredo, Gulini, Anna Elisa, Pierpaoli, Elisa, Badiali, Manuela, Murru, Stefania, Murgia, Riccardo, Guerini Rocco, Elena, Venetis, Konstantinos, Fusco, Nicola, Morotti, Denise, Gianatti, Andrea, Furlan, Daniela, Rossi, Giulio, Melocchi, Laura, Russo, Maria, De Luca, Caterina, Palumbo, Lucia, Simonelli, Saverio, Maffè, Antonella, Francia di Celle, Paola, Venesio, Tiziana, Scatolini, Maria, Grosso, Enrico, Orecchia, Sara, Fassan, Matteo, Balistreri, Mariangela, Zulato, Elisabetta, Reghellin, Daniela, Lazzari, Elena, Santacatterina, Maria

المساهمون: Regione Campania, Ministero della Salute

المصدر: Oncology and Therapy ; ISSN 2366-1070 2366-1089

مصطلحات موضوعية: Oncology

الإتاحة: https://doi.org/10.1007/s40487-023-00252-5Test

المؤلفون: Liverani, Chiara, Spadazzi, Chiara, Ibrahim, Toni, Pieri, Federica, Foca, Flavia, Calabrese, Chiara, De Vita, Alessandro, Miserocchi, Giacomo, Cocchi, Claudia, Vanni, Silvia, Ercolani, Giorgio, Cavaliere, Davide, Ranallo, Nicoletta, Chiadini, Elisa, Prisinzano, Giovanna, Severi, Stefano, Sansovini, Maddalena, Martinelli, Giovanni, Bongiovanni, Alberto, Mercatali, Laura

المساهمون: Liverani, Chiara, Spadazzi, Chiara, Ibrahim, Toni, Pieri, Federica, Foca, Flavia, Calabrese, Chiara, De Vita, Alessandro, Miserocchi, Giacomo, Cocchi, Claudia, Vanni, Silvia, Ercolani, Giorgio, Cavaliere, Davide, Ranallo, Nicoletta, Chiadini, Elisa, Prisinzano, Giovanna, Severi, Stefano, Sansovini, Maddalena, Martinelli, Giovanni, Bongiovanni, Alberto, Mercatali, Laura

مصطلحات موضوعية: HRAS overexpression, Lenvatinib efficacy, nen, predictive marker, primary cultures

الوصف: IntroductionNeuroendocrine neoplasms (NENs) are a rare group of tumors exceptionally heterogeneous, with clinical presentation ranging from well differentiated more indolent tumors to poorly differentiated very aggressive forms. Both are often diagnosed after the metastatic spread and require appropriate medical treatment. A high priority need in the management of this disease is the identification of effective therapeutic strategies for advanced and metastatic patients. The recent TALENT trial demonstrated the efficacy of lenvatinib, a multi-tyrosine kinase inhibitor, in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) with no other treatment indication. Further development of this drug in advanced NETs is warranted. MethodsWe investigated potential clinical and molecular determinants of lenvatinib response in human primary cultures derived from patients with GEP-NET of different grades and sites of origin. We correlated response to treatment with patient clinical characteristics, with the mutational status of 161-cancer associated genes and with the expression levels of MKI-related genes. ResultsLenvatinib exerted a significant antitumor activity in primary GEP-NET cells, with median survival inhibitions similar or higher than those of standard frontline treatments. Of the 11 primary cultures analyzed in our case series, 6 were classified as responder showing a significant survival inhibition, and 5 as non-responder. We observed that the overexpression of HRAS in the original tumor tissue compared to the matched healthy tissue significantly correlated with responsiveness of primary cells to lenvatinib (p=.048). All 5 non-responder cultures showed normal HRAS expression, while of the 6 responder cultures, 4 had HRAS overexpression. Overexpression of HRAS was not associated with gene mutation. None of the other evaluated clinical variables (grade, Ki67, site of origin and syndromic disease) or molecular markers correlated with response. DiscussionLenvatinib appears to be a highly effective ...

وصف الملف: ELETTRONICO

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/36743926; info:eu-repo/semantics/altIdentifier/wos/WOS:000924369400001; volume:13; issue:2; firstpage:1; lastpage:12; numberofpages:12; journal:FRONTIERS IN ENDOCRINOLOGY; https://hdl.handle.net/11585/961500Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85147352201; https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.1045038/fullTest

الإتاحة: https://doi.org/10.3389/fendo.2022.1045038Test
https://hdl.handle.net/11585/961500Test

المؤلفون: Andrikou, Kalliopi, Ulivi, Paola, Petracci, Elisabetta, Azzali, Irene, Bertolini, Federica, Alberti, Giulia, Bettelli, Stefania, Calistri, Daniele, Chiadini, Elisa, Capelli, Laura, Cravero, Paola, Guaitoli, Giorgia, Zanelli, Francesca, Burgio, Marco Angelo, Pagano, Maria, Verlicchi, Alberto, Martinelli, Enrica, Di Emidio, Katia, Dominici, Massimo, Pinto, Carmine

المصدر: Diagnostics (2075-4418); May2024, Vol. 14 Issue 10, p1024, 15p

مصطلحات موضوعية: NON-small-cell lung carcinoma, GENETIC mutation

مصطلحات جغرافية: ITALY

مستخلص: The real-world, retrospective, NEROnE registry investigated the impact of next-generation sequencing (NGS) in advanced non-small-cell lung cancer (NSCLC) patients (pts) at three oncology units in the north of Italy between January 2020 and December 2022. We focused on the clinical characterization and outcomes of NSCLC with rare molecular alterations: EGFR exon 20 insertion, non-activating EGFR mutations, BRAF V600E and non-V600, ROS1 and RET rearrangements, MET, ErbB2, and FGFR mutations. Overall, these represented 6.4% (62/970) of the pts analysed with NGS in the daily practice. The most heavily represented rare alterations were ROS1 rearrangement (15 pts—24%) and MET exon 14 skipping mutation (11 pts—18%). No associations were found with the demographic and clinical features. Forty-nine pts received targeted therapies, of which 38.8% were first- and 9.8% were second-line. The remaining pts received chemotherapy and/or immunotherapy. In terms of the clinical outcomes, although not statistically significant, a tendency toward shorter OS was seen when therapies other than specific targeted therapies were used (HR: 1.84, 95% CI: 0.79–4.33, p = 0.158). The pts with co-mutations (19.4%) seemed to receive an advantage from the front-line chemotherapy-based regimen. Finally, an NLR score (a well-known inflammatory index) ≥ 4 seemed to be related to shorter OS among the pts treated with immunotherapy alone or in combination with chemotherapy (HR: 2.83, 95% CI: 1.08–7.40, p = 0.033). Prospective evaluations need to be performed to clarify whether these indexes may help to identify patients with oncogene-addicted NSCLC who could benefit from immunotherapy. [ABSTRACT FROM AUTHOR]

: Copyright of Diagnostics (2075-4418) is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Farolfi, Alberto, Altavilla, Amelia, Morandi, Luca, Capelli, Laura, Chiadini, Elisa, Prisinzano, Giovanna, Gurioli, Giorgia, Molari, Marianna, Calistri, Daniele, Foschini, Maria Pia, De Giorgi, Ugo

المصدر: Frontiers in Oncology ; volume 12 ; ISSN 2234-943X

الوصف: Endometriosis is a benign condition characterized by the presence of ectopic endometrial tissue. It is still debated whether endometriosis is a disease that can predispose to the pathogenesis of endometrial cancer outside the uterus. Deficiencies in mismatch repair (MMR) genes are a known risk factor for developing endometrioid cancer. Starting from two cases of patients with abnormal MMR endometrioid carcinoma of the uterus and synchronous endometrioid carcinoma in non-ovarian and ovarian endometriosis, we performed a somatic mutation profile and phylogenetic analysis of the lesions in order to identify if they were metastasis or primary de novo tumors. In the first case, we identified de novo activating mutations in PIK3CA and KRAS in endometrioid cancer lesions but not in endometriosis. Although the acquisition of a de novo mutation in ESR1 and a decrease in mutant allele fraction (MAF) from the endometrial tumor to the localizations in the endometriosis lesions, the clonal relationship was confirmed by the limited number of heteroplasmic mutations in D-loop mitochondrial DNA region. In the other case, the clonal behavior was demonstrated by the overlap of MAF at each site. Our data support the hypothesis of a retrograde dissemination of tumor cells, moving from the primary carcinoma in the endometrium to ectopic sites of endometriosis where localizations of tumor arise.

الإتاحة: https://doi.org/10.3389/fonc.2022.859510Test

المؤلفون: Ambrosini-Spaltro, Andrea, Rengucci, Claudia, Capelli, Laura, Chiadini, Elisa, Calistri, Daniele, Bennati, Chiara, Cravero, Paola, Limarzi, Francesco, Nosseir, Sofia, Panzacchi, Riccardo, Valli, Mirca, Ulivi, Paola, Rossi, Giulio

المصدر: Current Oncology; Nov2023, Vol. 30 Issue 11, p10019-10032, 14p

مصطلحات موضوعية: BRAF genes, LUNGS, PROGRESSION-free survival, CLINICAL pathology, NUCLEOTIDE sequencing

مستخلص: (1) Background: BRAF mutations affect 4–5% of lung adenocarcinomas. This study aimed to analyze the clinicopathological features of lung carcinomas with BRAF mutations, focusing on V600E vs. non-V600E and the presence of co-mutations. (2) Methods: All BRAF-mutated lung carcinomas were retrieved from a molecular diagnostic unit (the reference unit for four different hospitals). The samples were analyzed using next-generation sequencing. Statistical analyses included log-rank tests for overall survival (OS) and progression-free survival (PFS). (3) Results: In total, 60 BRAF-mutated lung carcinomas were retrieved: 24 (40.0%) with V600E and 36 (60.0%) with non-V600E mutations, and 21 (35.0%) with other co-mutations and 39 (65.0%) with only BRAF mutations. Survival data were available for 54/60 (90.0%) cases. Targeted therapy was documented in 11 cases. Patients with V600E mutations exhibited a better prognosis than patients with non-V600E mutations (p = 0.008 for OS, p = 0.018 for PFS); this was confirmed in PFS (p = 0.036) when considering only patients who received no targeted therapy. Patients with co-mutations displayed no prognostic difference compared to patients carrying only BRAF mutations (p = 0.590 for OS, p = 0.938 for PFS). (4) Conclusions: BRAF-mutated lung carcinomas with V600E (40.0%) had a better prognosis than those without V600E. Concomitant co-mutations (35.0%) did not affect the prognosis. [ABSTRACT FROM AUTHOR]

: Copyright of Current Oncology is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Pasini, Luigi, Notarangelo, Michela, Vagheggini, Alessandro, Burgio, Marco Angelo, Crinò, Lucio, Chiadini, Elisa, Prochowski, Andrea Iamurri, Delmonte, Angelo, Ulivi, Paola, D'Agostino, Vito Giuseppe

المساهمون: Fondazione Cassa Di Risparmio Di Trento E Rovereto

المصدر: Molecular Oncology ; volume 15, issue 9, page 2423-2438 ; ISSN 1574-7891 1878-0261

الوصف: The mutational status of the epidermal growth factor receptor ( EGFR ) guides the stratification of non‐small cell lung cancer (NSCLC) patients for treatment with tyrosine kinase inhibitors (TKIs). A liquid biopsy test on cell‐free DNA is recommended as a clinical decision‐supporting tool, although it has limited sensitivity. Here, we comparatively investigated the extracellular vesicle (EV)‐RNA as an independent source for multidimensional and longitudinal EGFR profiling in a cohort of 27 NSCLC patients. We introduced and validated a new rapid, highly specific EV‐RNA test with wild‐type (WT) and mutant‐sensitive probes (E746‐A750del, L858R, and T790M). We included a cohort of 20 NSCLC patients with EGFR WT tumor tissues and systematically performed molecular EV‐RNA and circulating tumor DNA analyses with clinical data statistics and biophysical profiles of EVs. At the single‐patient level, we detected variegated tumor heterogeneity dynamics supported by combinations of driver EGFR mutations. EV‐RNA‐based mutation analysis showed an unprecedented sensitivity of over 90%. The resistance‐associated mutation T790M frequently pre‐existed at baseline with a gained EV‐transcript copy number at progression, while the general mutational burden was mostly decreasing during the intermediate follow‐up. The biophysical profile of EVs and the quantitative assessment of T790M revealed an association with tumor size determined by the sum of the longest diameters in target lesions. Vesicular RNA provides a validated tool suitable for use in clinical practice to investigate the dynamics of common driver EGFR mutations in NSCLC patients receiving TKIs.

الإتاحة: https://doi.org/10.1002/1878-0261.12976Test

المؤلفون: Ulivi, Paola, Passardi, Alessandro, Marisi, Giorgia, Chiadini, Elisa, Molinari, Chiara, Canale, Matteo, Pasini, Luigi, Ferroni, Fabio, Frassineti, Giovanni Luca, Bartolini, Giulia, Monti, Manlio

المصدر: Frontiers in Pharmacology ; volume 12 ; ISSN 1663-9812

مصطلحات موضوعية: Pharmacology (medical), Pharmacology

الوصف: Liquid biopsy represents a valid strategy for tumor molecular characterization. It gives the opportunity to bypass tumor heterogeneity, to monitor tumor characteristics during the course of treatment, and to perform the analysis even when tumor tissue is not available or inadequate. In the clinical practice of metastatic colorectal cancer, tumor molecular characterization is crucial for patient management, as RAS and BRAF status could influence the treatment choice. Although for this type of cancer tumor tissue is usually available at diagnosis, liquid biopsy could give complementary information and could permit monitoring of the mutation status during the course of treatment. At present, there are no clinical indications for its use in clinical practice. However, we report four clinical cases for which liquid biopsy analysis gave integrative information with respect to tumor tissue characterization, which permits us to understand the unresponsiveness of patients to treatment, with potential implications in patient’s management.

الإتاحة: https://doi.org/10.3389/fphar.2021.745701Test

المؤلفون: Urbini, Milena, Marisi, Giorgia, Azzali, Irene, Bartolini, Giulia, Chiadini, Elisa, Capelli, Laura, Tedaldi, Gianluca, Angeli, Davide, Canale, Matteo, Molinari, Chiara, Rebuzzi, Francesca, Virga, Alessandra, Prochowski Iamurri, Andrea, Matteucci, Laura, Sullo, Francesco Giulio, Debonis, Silvia Angela, Gallio, Chiara, Frassineti, Giovanni Luca, Martinelli, Giovanni, Ulivi, Paola, Passardi, Alessandro

المساهمون: Urbini, Milena, Marisi, Giorgia, Azzali, Irene, Bartolini, Giulia, Chiadini, Elisa, Capelli, Laura, Tedaldi, Gianluca, Angeli, Davide, Canale, Matteo, Molinari, Chiara, Rebuzzi, Francesca, Virga, Alessandra, Prochowski Iamurri, Andrea, Matteucci, Laura, Sullo, Francesco Giulio, Debonis, Silvia Angela, Gallio, Chiara, Frassineti, Giovanni Luca, Martinelli, Giovanni, Ulivi, Paola, Passardi, Alessandro

مصطلحات موضوعية: liquid biopsy, RAS, mutations, cfDNA, mCRC, VAF

الوصف: Purpose: Plasma circulating tumor DNA (ctDNA) is a valuable resource for tumor characterization and for monitoring of residual disease during treatment; however, it is not yet introduced in metastatic colorectal cancer (mCRC) routine clinical practice. In this retrospective exploratory study, we evaluated the role of ctDNA in patients with mCRC treated with chemotherapy plus bevacizumab. Materials and methods: Fifty-three patients were characterized for RAS and BRAF status on tumor tissue before the start of treatment. Plasma was collected at baseline, at first clinical evaluation, and at disease progression. ctDNA analysis was performed using Oncomine Colon cfDNA Assay on the Ion S5 XL instrument. Results: At baseline, from a plasma sample, RAS, BRAF, or PIK3CA mutations were detected in 44 patients. A high correspondence was observed between ctDNA and tumor tissue mutations (KRAS 100%, NRAS 97.9%, BRAF 97.9%, PIK3CA 90%). Low baseline variant allele frequency (VAF) was found to be associated with longer median progression-free survival (PFS) compared with those with high VAF (15.9 v 12.2 months, P = .02). A higher PFS {12.29 months (95% CI, 9.03 to 17.9) v 8.15 months (95% CI, 2.76 to not available [NA]), P = .04} and overall survival (34.1 months [95% CI, 21.68 to NA] v 11.1 months [95% CI, 3.71 to NA], P = .003) were observed in patients with large decline in VAF at first evaluation. Conclusion: ctDNA analysis is useful for molecular characterization and tumor response monitoring in patients with mCRC. Quantitative variations of released ctDNA are associated with clinical outcomes.

وصف الملف: ELETTRONICO

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/37656949; volume:7; issue:7; firstpage:1; lastpage:16; numberofpages:16; journal:JCO PRECISION ONCOLOGY; https://hdl.handle.net/11585/953420Test

الإتاحة: https://doi.org/10.1200/PO.22.00694Test
https://hdl.handle.net/11585/953420Test

المؤلفون: Verlicchi, Alberto, Canale, Matteo, Chiadini, Elisa, Cravero, Paola, Urbini, Milena, Andrikou, Kalliopi, Pasini, Luigi, Flospergher, Michele, Burgio, Marco Angelo, Crinò, Lucio, Ulivi, Paola, Delmonte, Angelo

المصدر: Life (2075-1729); Sep2023, Vol. 13 Issue 9, p1915, 13p

مصطلحات موضوعية: CIRCULATING tumor DNA, NON-small-cell lung carcinoma

مستخلص: Lung cancer (LC) is the deadliest malignancy worldwide. In an operable stage I–III patient setting, the detection of minimal residual disease (MRD) after curative treatment could identify patients at higher risk of relapse. In this context, the study of circulating tumor DNA (ctDNA) is emerging as a useful tool to identify patients who could benefit from an adjuvant treatment, and patients who could avoid adverse events related to a more aggressive clinical management. On the other hand, ctDNA profiling presents technical, biological and standardization challenges before entering clinical practice as a decisional tool. In this paper, we review the latest advances regarding the role of ctDNA in identifying MRD and in predicting patients' prognosis, with a particular focus on clinical trials investigating the potential of ctDNA, the technical challenges to address and the biological parameters that influence the MRD detection. [ABSTRACT FROM AUTHOR]

: Copyright of Life (2075-1729) is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Ulivi, Paola, Scarpi, Emanuela, Chiadini, Elisa, Marisi, Giorgia, Valgiusti, Martina, Capelli, Laura, Casadei Gardini, Andrea, Monti, Manlio, Ruscelli, Silvia, Frassineti, Giovanni Luca, Calistri, Daniele, Amadori, Dino, Passardi, Alessandro

المساهمون: Ulivi, Paola, Scarpi, Emanuela, Chiadini, Elisa, Marisi, Giorgia, Valgiusti, Martina, Capelli, Laura, Casadei Gardini, Andrea, Monti, Manlio, Ruscelli, Silvia, Frassineti, Giovanni Luca, Calistri, Daniele, Amadori, Dino, Passardi, Alessandro

مصطلحات موضوعية: Bevacizumab, Left-sided colon, Metastatic colorectal cancer, Right-sided colon, Catalysi, Molecular Biology, Spectroscopy, Computer Science Applications1707 Computer Vision and Pattern Recognition, Physical and Theoretical Chemistry, Organic Chemistry, Inorganic Chemistry

الوصف: There is evidence of a different response to treatment with regard to the primary tumor localization (right-sided or left-sided) in patients with metastatic colorectal cancer (mCRC). We analyzed the different outcomes and biomolecular characteristics in relation to tumor localization in 122 of the 370 patients with metastatic colorectal cancer enrolled onto the phase III prospective multicenter “Italian Trial in Advanced Colorectal Cancer (ITACa)”, randomized to receive first-line chemotherapy (CT) or CT plus bevacizumab (CT + B). RAS and BRAF mutations; baseline expression levels of circulating vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), cyclooxygenase-2 (COX2), ephrin type-B receptor 4 (EPHB4), hypoxia-inducible factor 1-alpha (HIF-1α), lactate dehydrogenase (LDH), and high-sensitivity C reactive protein (hs-CRP); and inflammatory indexes such as the neutrophil-to-lymphocyte ratio, platelet-lymphocyte rate and systemic immune-inflammation index were evaluated. Patients with right-sided tumors showed a longer median progression-free survival in the CT + B arm than in the CT group (12.6 vs. 9.0 months, respectively, p = 0.017). Baseline inflammatory indexes were significantly higher in left-sided tumors, whereas eNOS and EPHB4 expression was significantly higher and BRAF mutation more frequent in right-sided tumors. Our data suggest a greater efficacy of the CT + B combination in right-sided mCRC, which might be attributable to the lower inflammatory status and higher expression of pro-angiogenic factors that appear to characterize these tumors.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/28598398; info:eu-repo/semantics/altIdentifier/wos/WOS:000404581500139; volume:18; issue:6; firstpage:1; lastpage:11; journal:INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; http://hdl.handle.net/11380/1177426Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85020814056; http://www.mdpi.com/1422-0067/18/6/1240/pdfTest

الإتاحة: https://doi.org/10.3390/ijms18061240Test
http://hdl.handle.net/11380/1177426Test
http://www.mdpi.com/1422-0067/18/6/1240/pdfTest