34 results on '"Brando, Chiara"'
Search Results
2. Clinical relevance of exosome-derived microRNAs in Ovarian Cancer: Looking for new tumor biological fingerprints
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Fanale, Daniele, Corsini, Lidia Rita, Bono, Marco, Randazzo, Ugo, Barraco, Nadia, Brando, Chiara, Cancelliere, Daniela, Contino, Silvia, Giurintano, Ambra, Magrin, Luigi, Pedone, Erika, Perez, Alessandro, Piraino, Paola, Pivetti, Alessia, Giovanni, Emilia Di, Russo, Tancredi Didier Bazan, Prestifilippo, Ornella, Gennusa, Vincenzo, Pantuso, Gianni, Russo, Antonio, and Bazan, Viviana
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- 2024
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3. Theranostic biomarkers and PARP-inhibitors effectiveness in patients with non-BRCA associated homologous recombination deficient tumors: Still looking through a dirty glass window?
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Incorvaia, Lorena, Perez, Alessandro, Marchetti, Claudia, Brando, Chiara, Gristina, Valerio, Cancelliere, Daniela, Pivetti, Alessia, Contino, Silvia, Di Giovanni, Emilia, Barraco, Nadia, Bono, Marco, Giurintano, Ambra, Bazan Russo, Tancredi Didier, Gottardo, Andrea, Cutaia, Sofia, Pedone, Erika, Peri, Marta, Corsini, Lidia Rita, Fanale, Daniele, Galvano, Antonio, Scambia, Giovanni, Badalamenti, Giuseppe, Russo, Antonio, and Bazan, Viviana
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- 2023
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4. Potential agnostic role of BRCA alterations in patients with several solid tumors: One for all, all for one?
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Fanale, Daniele, Corsini, Lidia Rita, Pedone, Erika, Randazzo, Ugo, Fiorino, Alessia, Di Piazza, Marianna, Brando, Chiara, Magrin, Luigi, Contino, Silvia, Piraino, Paola, Bazan Russo, Tancredi Didier, Cipolla, Calogero, Russo, Antonio, and Bazan, Viviana
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- 2023
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5. MUTYH-associated tumor syndrome: The other face of MAP
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Magrin, Luigi, Fanale, Daniele, Brando, Chiara, Corsini, Lidia Rita, Randazzo, Ugo, Di Piazza, Marianna, Gurrera, Vittorio, Pedone, Erika, Bazan Russo, Tancredi Didier, Vieni, Salvatore, Pantuso, Gianni, Russo, Antonio, and Bazan, Viviana
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- 2022
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6. BRCA1/2 variants of unknown significance in hereditary breast and ovarian cancer (HBOC) syndrome: Looking for the hidden meaning
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Fanale, Daniele, Pivetti, Alessia, Cancelliere, Daniela, Spera, Antonio, Bono, Marco, Fiorino, Alessia, Pedone, Erika, Barraco, Nadia, Brando, Chiara, Perez, Alessandro, Guarneri, Maria Francesca, Russo, Tancredi Didier Bazan, Vieni, Salvatore, Guarneri, Girolamo, Russo, Antonio, and Bazan, Viviana
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- 2022
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7. Can the tumor-agnostic evaluation of MSI/MMR status be the common denominator for the immunotherapy treatment of patients with several solid tumors?
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Fanale, Daniele, Corsini, Lidia Rita, Scalia, Raimondo, Brando, Chiara, Cucinella, Alessandra, Madonia, Giorgio, Dimino, Alessandra, Filorizzo, Clarissa, Barraco, Nadia, Bono, Marco, Fiorino, Alessia, Magrin, Luigi, Sciacchitano, Roberta, Perez, Alessandro, Russo, Tancredi Didier Bazan, Pantuso, Gianni, Russo, Antonio, and Bazan, Viviana
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- 2022
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8. BRCA-associated hereditary male cancers: can gender affect the prevalence and spectrum of germline pathogenic variants?
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Fanale, Daniele, Corsini, Lidia Rita, Brando, Chiara, Randazzo, Ugo, Bono, Marco, Pedone, Erika, Perez, Alessandro, Sciacchitano, Roberta, Cancelliere, Daniela, Piraino, Paola, Giurintano, Ambra, Bazan Russo, Tancredi Didier, Ferraro, Pietro, Rinaldi, Gaetana, Spinnato, Valeria, Gennusa, Vincenzo, Pernice, Gianfranco, Vieni, Salvatore, Pantuso, Gianni, and Russo, Antonio
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HEREDITARY cancer syndromes ,GERM cells ,CANCER susceptibility ,GENETIC testing ,MALE breast cancer ,BREAST cancer - Abstract
Introduction: Although hereditary male neoplasms are quite rare, individuals harbouring germline BRCA1/2 pathogenic variants (PVs) may have a risk of developing tumours associated with Hereditary Breast and Ovarian Cancer (HBOC) syndrome, including male breast (MBC), prostate (PCa) and pancreatic (PC) cancers, and melanoma. Women and men showed a comparable genetic architecture of cancer susceptibility, but there are some gender-specific features. Since little is known about cancer genetic susceptibility in male population, our study was aimed at investigating the frequency of BRCA1/2 PVs in men with HBOC syndrome-associated tumors, in order to understand whether differences in gender may reflect in the prevalence and spectrum of germline alterations. Patients and methods: We retrospectively collected and analysed clinical information of 352 HBOC-associated male cancer patients genetically tested for germline BRCA1/2 PVs by Next-Generation Sequencing analysis, enrolled, from February 2018 to January 2024, at the "Regional Center for the prevention, diagnosis and treatment of rare and heredo-familial tumors of adults" of the University-Hospital Policlinico "P. Giaccone" of Palermo (Italy). Results: Our investigation revealed that 7.4% of patients was carrier of a germline BRCA PV, with an almost total prevalence of BRCA2 alterations. In particular, 65.4% of BRCA-positive patients developed MBC, 19.2% had PC, 11.6% developed PCa, and only 3.8% had melanoma. Specifically, MBC individuals showed a BRCA-associated genetic predisposition in 17% of cases, whereas patients with PCa or PC exhibited a lower frequency of BRCA2 PVs, taking into account the current national criteria for access to germline genetic testing. Discussion: Our study showed a high heterogeneity in prevalence of germline BRCA2 PVs among men which could reflect a potential gender-specific genetic heterogeneity. Therefore, BRCA-associated male tumours could be due to BRCA2 PVs different from those usually detected in women. In the event that it is demonstrated, in future, that male cancers are genetically distinct entities from those female this could improve personalized risk evaluation and guide therapeutic choices for patients of both sexes, in order to obtain a gender equality in cancer care. [ABSTRACT FROM AUTHOR]
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- 2024
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9. POLE, POLD1, and NTHL1: the last but not the least hereditary cancer-predisposing genes
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Magrin, Luigi, Fanale, Daniele, Brando, Chiara, Fiorino, Alessia, Corsini, Lidia Rita, Sciacchitano, Roberta, Filorizzo, Clarissa, Dimino, Alessandra, Russo, Antonio, and Bazan, Viviana
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- 2021
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10. Challenges and advances for the treatment of renal cancer patients with brain metastases: From immunological background to upcoming clinical evidence on immune-checkpoint inhibitors
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Incorvaia, Lorena, Madonia, Giorgio, Corsini, Lidia Rita, Cucinella, Alessandra, Brando, Chiara, Gagliardo, Cesare, Santoni, Matteo, Fanale, Daniele, Inno, Alessandro, Fazio, Ivan, Foti, Giovanni, Galia, Massimo, Badalamenti, Giuseppe, Bazan, Viviana, Russo, Antonio, and Gori, Stefania
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- 2021
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11. Role of the HIPPO pathway as potential key player in the cross talk between oncology and cardiology
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Manno, Girolamo, Filorizzo, Clarissa, Fanale, Daniele, Brando, Chiara, Di Lisi, Daniela, Lunetta, Monica, Bazan, Viviana, Russo, Antonio, and Novo, Giuseppina
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- 2021
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12. KIT/PDGFRA Variant Allele Frequency as Prognostic Factor in Gastrointestinal Stromal Tumors (GISTs): Results From a Multi-Institutional Cohort Study.
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Incorvaia, Lorena, Biase, Dario De, Nannini, Margherita, Fumagalli, Elena, Vincenzi, Bruno, Luca, Ida De, Brando, Chiara, Perez, Alessandro, Pantaleo, Maria A, Gasperoni, Silvia, D'Ambrosio, Lorenzo, Grignani, Giovanni, Maloberti, Thais, Pedone, Erika, Russo, Tancredi Didier Bazan, Mazzocca, Alessandro, Algeri, Laura, Dimino, Alessandra, Barraco, Nadia, and Serino, Roberta
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GENETIC mutation ,CONFIDENCE intervals ,PATIENT selection ,CELL receptors ,RETROSPECTIVE studies ,GASTROINTESTINAL tumors ,DESCRIPTIVE statistics ,IMATINIB - Abstract
Background The patient selection for optimal adjuvant therapy in gastrointestinal stromal tumors (GISTs) is provided by nomogram based on tumor size, mitotic index, tumor location, and tumor rupture. Although mutational status is not currently used to risk assessment, tumor genotype showed a prognostic influence on natural history and tumor relapse. Innovative measures, such as KIT/PDGFRA -mutant-specific variant allele frequency (VAF) levels detection from next-generation sequencing (NGS), may act as a surrogate of tumor burden and correlate with prognosis and overall survival of patients with GIST, helping the choice for adjuvant treatment. Patients and Methods This was a multicenter, hospital-based, retrospective/prospective cohort study to investigate the prognostic role of KIT or PDGFRA -VAF of GIST in patients with radically resected localized disease. In the current manuscript, we present the results from the retrospective phase of the study. Results Two-hundred (200) patients with GIST between 2015 and 2022 afferent to 6 Italian Oncologic Centers in the EURACAN Network were included in the study. The receiver operating characteristic (ROC) curves analysis was used to classify "low" vs. "high" VAF values, further normalized on neoplastic cellularity (nVAF). When RFS between the low and high nVAF groups were compared, patients with GIST with KIT/PDGFRA nVAF > 50% showed less favorable RFS than patients in the group of nVAF ≤ 50% (2-year RFS, 72.6% vs. 93%, respectively; P =.003). The multivariable Cox regression model confirmed these results. In the homogeneous sub-population of intermediate-risk, patients with KIT -mutated GIST, the presence of nVAF >50% was statistically associated with higher disease recurrence. Conclusion In our study, we demonstrated that higher nVAF levels were independent predictors of GIST prognosis and survival in localized GIST patients with tumors harboring KIT or PDGFRA mutations. In the cohort of intermediate-risk patients, nVAF could be helpful to improve prognostication and the use of adjuvant imatinib. [ABSTRACT FROM AUTHOR]
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- 2024
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13. POTENTIAL APPLICATIONS OF LIQUID BIOPSY IN IMMUNOTHERAPY: ROLE OF EXOSOMES, MICRORNAS AND PLASMA EXPRESSION LEVELS OF IMMUNE CHECKPOINTS IN PATIENTS WITH SOLID TUMORS
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BRANDO, Chiara and RUSSO, Antonio
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liquid biopsy ,Immune checkpoint ,solid tumors - Published
- 2023
14. Body mass index and baseline platelet count as predictive factors in Merkel cell carcinoma patients treated with avelumab.
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Incorvaia, Lorena, Dimino, Alessandra, Algeri, Laura, Brando, Chiara, Magrin, Luigi, De Luca, Ida, Pedone, Erika, Perez, Alessandro, Sciacchitano, Roberta, Bonasera, Annalisa, Russo, Tancredi Didier Bazan, Pomi, Federica Li, Peri, Marta, Gristina, Valerio, Galvano, Antonio, Giuffrida, Dario, Fazio, Ivan, Toia, Francesca, Cordova, Adriana, and Florena, Ada Maria
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BODY mass index ,PLATELET count ,OBESITY paradox ,IMMUNE checkpoint inhibitors - Abstract
Background: Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer, associated with a worse prognosis. The Immune Checkpoint Inhibitors (ICIs) avelumab and pembrolizumab have been recently approved as first-line treatment in metastatic MCC (mMCC). The clinical observation of improved outcomes in obese patients following treatment with ICIs, known as the "obesity paradox", has been studied across many types of tumors. Probably due to the rarity of this tumor, data on mMMC patients are lacking. Patients and methods: This is an observational, hospital-based, study to investigate the role of Body Mass Index (BMI) as predictive biomarker of ICI response in mMCC patients treated with avelumab as first-line treatment. The study population included the patients treated from February 2019 to October 2022 in an Italian referral center for rare tumors. Clinico-pathological characteristics, BMI, laboratory parameters (NLR and platelet count), and response to avelumab were analyzed from a MCC System database prospectively collected. Results: Thirty-two (32) patients were included. Notably, the presence of pretreatment BMI ≥ 30 was significantly associated with longer PFS [BMI < 30 Group: median PFS, 4 months (95% CI: 2.5-5.4); BMI ≥ 30 Group: median PFS, not reached; p<0.001)[. Additionally, the median PFS was significantly higher in patients with higher PLT (median PFS: 10 months in the "low PLT" Group (95% CI: 4.9, 16.1) vs 33 months (95% CI: 24.3, 43.2) in the "high PLT" Group (p=0.006). The multivariable Cox regression model confirmed these results. Conclusion: To our knowledge, this is the first study that investigates the predictive role of BMI in MCC patients. Our data were consistent with the clinical observation of improved outcomes in obese patients across other tumor types. Thus, advanced age, a weakened immune system, and the obesity-associated "inflammaging", are key factors that could impact the cancer immune responses of mMCC patients.V [ABSTRACT FROM AUTHOR]
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- 2023
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15. Prognostic role of soluble PD-1 and BTN2A1 in overweight melanoma patients treated with nivolumab or pembrolizumab: finding the missing links in the symbiotic immune-metabolic interplay.
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Incorvaia, Lorena, Rinaldi, Gaetana, Badalamenti, Giuseppe, Cucinella, Alessandra, Brando, Chiara, Madonia, Giorgio, Fiorino, Alessia, Pipitone, Angela, Perez, Alessandro, Li Pomi, Federica, Galvano, Antonio, Gristina, Valerio, Barraco, Nadia, Bono, Marco, Bazan Russo, Tancredi Didier, Toia, Francesca, Cordova, Adriana, Fanale, Daniele, Russo, Antonio, and Bazan, Viviana
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Individual response to immune checkpoint inhibitors (ICIs) is currently unpredictable in patients with melanoma. Recent findings highlight a striking improvement in the clinical outcomes of overweight/obese patients treated with ICIs, which seems driven, at least in part, by programmed cell death protein 1 (PD-1)-mediated T-cell dysfunction. A putative role of butyrophilins (BTNs) is under investigation as a novel mechanism of cancer immune evasion and obesity-associated inflammation. This study investigates the role of baseline plasma levels of soluble PD-1 (sPD-1), soluble programmed cell death ligand 1 (sPD-L1), BTN2A1 (sBTN2A1), BTN3A1 (sBTN3A1), along with body mass index (BMI), as predictive biomarkers of immunotherapy response in metastatic melanoma patients treated with nivolumab or pembrolizumab as first-line treatment. In all, 41 patients were included in the study. The baseline plasma level of sPD-1 was significantly lower, and the sBTN2A1 was significantly higher, in long-responder patients to nivolumab or pembrolizumab (median sPD-1: 10.3 ng/ml versus 16.6 ng/ml, p = 0.001; median sBTN2A1: 4.4 ng/ml versus 3.77 ng/ml, p = 0.004). Lower levels of sPD-1 and higher levels of sBTN2A1 were also significantly associated with better overall response rate. Notably, when we further stratified the study cohort using BMI along with sPD-1, patients with BMI ⩾ 25 and sPD-1 < 11.24 ng/ml had longer time to treatment failure after PD-1 inhibitor than other subgroups of patients (p < 0.001). Circulating sPD-1 and sBTN2A1 detection, along with BMI, could give more insights into the immune-metabolic interactions underlying the benefit observed in overweight/obese patients, improving the use of dynamic, noninvasive, biomarkers for patient selection. [ABSTRACT FROM AUTHOR]
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- 2023
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16. Exploring the Dynamic Crosstalk between the Immune System and Genetics in Gastrointestinal Stromal Tumors.
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Dimino, Alessandra, Brando, Chiara, Algeri, Laura, Gristina, Valerio, Pedone, Erika, Peri, Marta, Perez, Alessandro, De Luca, Ida, Sciacchitano, Roberta, Magrin, Luigi, Bazan Russo, Tancredi Didier, Bono, Marco, Barraco, Nadia, Contino, Silvia, La Mantia, Maria, Galvano, Antonio, Badalamenti, Giuseppe, Russo, Antonio, Bazan, Viviana, and Incorvaia, Lorena
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BIOMARKERS , *GENETICS , *GENETIC mutation , *IMMUNE system , *GASTROINTESTINAL tumors , *GENE expression , *TREATMENT effectiveness , *PHENOTYPES , *IMMUNOTHERAPY , *SARCOMA - Abstract
Simple Summary: The effect of genetic alteration on the prognosis of patients affected by GIST has been extensively demonstrated. Unfortunately, not all GISTs could benefit from targeted therapies, underlining the need to deeply understand other predictive mechanisms. The link between immune checkpoints (especially PD-L1 expression), the tumor microenvironment, and the clinical behavior of GIST with different driver mutations is under investigation and represents an intriguing research field that could lead to improved prognostication in GIST. Gastrointestinal Stromal Tumors (GISTs) represent a paradigmatic model of oncogene addiction. Despite the well-known impact of the mutational status on clinical outcomes, we need to expand our knowledge to other factors that influence behavior heterogeneity in GIST patients. A growing body of studies has revealed that the tumor microenvironment (TME), mostly populated by tumor-associated macrophages (TAMs) and lymphocytes (TILs), and stromal differentiation (SD) have a significant impact on prognosis and response to treatment. Interestingly, even though the current knowledge of the role of immune response in this setting is still limited, recent pre-clinical and clinical data have highlighted the relevance of the TME in GISTs, with possible implications for clinical practice in the near future. Moreover, the expression of immune checkpoints, such as PD-L1, PD-1, and CTLA-4, and their relationship to the clinical phenotype in GIST are emerging as potential prognostic biomarkers. Looking forward, these variables related to the underlying tumoral microenvironment in GIST, though limited to still-ongoing trials, might lead to the potential use of immunotherapy, alone or in combination with targeted therapy, in advanced TKI-refractory GISTs. This review aims to deepen understanding of the potential link between mutational status and the immune microenvironment in GIST. [ABSTRACT FROM AUTHOR]
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- 2023
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17. Can circulating PD-1, PD-L1, BTN3A1, pan-BTN3As, BTN2A1 and BTLA levels enhance prognostic power of CA125 in patients with advanced high-grade serous ovarian cancer?
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Fanale, Daniele, Corsini, Lidia Rita, Brando, Chiara, Cutaia, Sofia, Di Donna, Mariano Catello, Filorizzo, Clarissa, Lisanti, Maria Chiara, Randazzo, Ugo, Magrin, Luigi, Romano, Raffaella, Russo, Tancredi Didier Bazan, Olive, Daniel, Vieni, Salvatore, Pantuso, Gianni, Chiantera, Vito, Russo, Antonio, Bazan, Viviana, and Iovanna, Juan Lucio
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PROGRAMMED death-ligand 1 ,PROGRAMMED cell death 1 receptors ,IMMUNE checkpoint proteins ,OVARIAN cancer ,PROGNOSIS ,PROGRESSION-free survival ,PERITONEAL cancer - Abstract
The most common subtype of ovarian cancer (OC) is the high-grade serous ovarian carcinoma (HGSOC), accounting for 70%-80% of all OC deaths. Although HGSOC is a potentially immunogenic tumor, clinical studies assessing the effectiveness of inhibitors of programmed death protein and its ligand (PD-1/PD-L1) in OC patients so far showed only response rates <15%. However, recent studies revealed an interesting prognostic role of plasma PD-1/PD-L1 and other circulating immunoregulatory molecules, such as the B- and T-lymphocyte attenuator (BTLA), butyrophilin sub-family 3A/CD277 receptors (BTN3A), and butyrophilin sub-family 2 member A1 (BTN2A1), in several solid tumors. Since evidence showed the prognostic relevance of pretreatment serum CA125 levels in OC, the aim of our study was to investigate if soluble forms of inhibitory immune checkpoints can enhance prognostic power of CA125 in advanced HGSOC women. Using specific ELISA tests, we examined the circulating PD-1, PD-L1, pan-BTN3As, BTN3A1, BTN2A1, and BTLA levels in 100 advanced HGSOC patients before treatment, correlating them with baseline serum CA125, age at diagnosis, body mass index (BMI), and peritoneal carcinomatosis. A multivariate analysis revealed that plasma BTN3A1 ≤4.75 ng/ml (HR, 1.94; 95% CI, 1.23-3.07; p=0.004), age at diagnosis ≤60 years (HR, 1.65; 95% CI, 1.05-2.59; p=0.03) and absence of peritoneal carcinomatosis (HR, 2.65; 95% CI, 1.66-4.22; p<0.0001) were independent prognostic factors for a longer progression-free survival (PFS) (≥30 months) in advanced HGSOC women. However, further two-factor multivariate analyses highlighted that baseline serum CA125 levels >401 U/ml and each soluble protein above respective concentration cutoff were covariates associated with shorter PFS (<30 months) and unfavorable clinical outcome, suggesting that contemporary measurement of both biomarkers than CA125 only could strengthen prognostic power of serum CA125 in predicting PFS of advanced HGSOC women. Plasma PD-L1, PD-1, BTN3A1, pan-sBTN3As, BTN2A1, or BTLA levels could be helpful biomarkers to increase prognostic value of CA125. [ABSTRACT FROM AUTHOR]
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- 2022
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18. Prognostic and Predictive Role of Tumor-Infiltrating Lymphocytes (TILs) in Ovarian Cancer.
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Fanale, Daniele, Dimino, Alessandra, Pedone, Erika, Brando, Chiara, Corsini, Lidia Rita, Filorizzo, Clarissa, Fiorino, Alessia, Lisanti, Maria Chiara, Magrin, Luigi, Randazzo, Ugo, Bazan Russo, Tancredi Didier, Russo, Antonio, and Bazan, Viviana
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PROGRAMMED cell death 1 receptors ,TRANSFORMING growth factors-beta ,OVARIAN tumors ,ENDOMETRIAL tumors ,CELL proliferation ,T cells ,TUMOR markers ,TUMORS ,IMMUNOTHERAPY ,PHENOTYPES - Published
- 2022
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19. Impact of Different Selection Approaches for Identifying Lynch Syndrome-Related Colorectal Cancer Patients: Unity Is Strength.
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Fanale, Daniele, Corsini, Lidia Rita, Brando, Chiara, Dimino, Alessandra, Filorizzo, Clarissa, Magrin, Luigi, Sciacchitano, Roberta, Fiorino, Alessia, Bazan Russo, Tancredi Didier, Calò, Valentina, Iovanna, Juan Lucio, Francini, Edoardo, Russo, Antonio, and Bazan, Viviana
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HEREDITARY nonpolyposis colorectal cancer ,COLORECTAL cancer ,CANCER patients ,GENETIC testing ,DNA mismatch repair ,CONCORD ,TUMOR suppressor genes ,TISSUE analysis - Abstract
Lynch syndrome (LS) is an inherited genetic condition associated with increased predisposition to colorectal cancer (CRC) and other tumors and is caused by germline mutations in Mismatch Repair (MMR) or EPCAM genes. The identification of LS carriers is currently based on germline testing of subjects with MMR-deficient (dMMR) tumors or fulfilling clinical criteria, but the most efficient strategies to select patients who should be offered genetic testing are yet not well defined. In order to assess the most suitable selection mode to identify LS-related CRC patients, we retrospectively collected and analyzed all clinical and molecular information of 854 CRC patients, recruited from 2013 to 2021 at the University Hospital Policlinico "P. Giaccone" of Palermo (Italy), 100 of which were selected based on revised Bethesda guidelines, Amsterdam criteria II, or tissue MMR deficiency, and genetically tested for germline variants in LS-susceptibility genes. Our study showed that 32 out of 100 CRC patients harbored germline likely pathogenic/pathogenic variants in MMR genes. The analysis of tissue microsatellite instability (MSI) status according to the revised Bethesda guidelines has been to be the best selection approach. However, using different selection approaches as complementary strategies is useful to identify LS carriers, reducing underdiagnosis of this syndrome. [ABSTRACT FROM AUTHOR]
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- 2022
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20. Not all KIT 557/558 codons mutations have the same prognostic influence on recurrence-free survival: breaking the exon 11 mutations in gastrointestinal stromal tumors (GISTs).
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Incorvaia, Lorena, Badalamenti, Giuseppe, Fanale, Daniele, Vincenzi, Bruno, Luca, Ida De, Algeri, Laura, Barraco, Nadia, Brando, Chiara, Bonasera, Annalisa, Bono, Marco, Castiglia, Marta, Cancelliere, Daniela, Cani, Massimiliano, Rita Corsini, Lidia, Fiorino, Alessia, Galvano, Antonio, Pedone, Erika, Perez, Alessandro, Pivetti, Alessia, and Graceffa, Giuseppa
- Abstract
Background: Although the gastrointestinal stromal tumor (GIST) genotype is not currently included in risk-stratification systems, a growing body of evidence shows that the pathogenic variant (PV) type and codon location hold a strong prognostic influence on recurrence-free survival (RFS). This information has particular relevance in the adjuvant setting, where an accurate prognostication could help to better identify high-risk tumors and guide clinical decision-making. Materials and Methods: Between January 2005 and December 2020, 96 patients with completely resected GISTs harboring a KIT proto-oncogene receptor tyrosine kinase (KIT) exon 11 PV were included in the study. We analyzed the type and codon location of the PV according to clinicopathological characteristics and clinical outcome; the metastatic sites in relapsed patients were also investigated. Results: Tumors harboring a KIT exon 11 deletion or deletion/insertion involving the 557 and/or 558 codons, showed a more aggressive clinical behavior compared with tumors carrying deletion/deletion/insertion in other codons, or tumors with duplication/insertion/single-nucleotide variant (SNV) (7-year RFS: 50% versus 73.1% versus 88.2%, respectively; p < 0.001). Notably, among 18 relapsed patients with 557 and/or 558 deletion or deletion/insertion, 14 patients (77.8%) harbored deletions simultaneously involving 557 and 558 codons, while only 4 patients (22.2%) harbored deletions involving only 1 of the 557/558 codons. Thus, when 557 or 558 deletions occurred separately, the tumor showed a prognostic behavior similar to the GIST carrying deletions outside the 557/558 position. Remarkably, patients with GISTs stratified as intermediate risk, but carrying the 557/558 deletion, showed a similar outcome to the high-risk patients with tumors harboring deletions in codons other than 557/558, or duplication/insertion/SNV. Conclusion: Our data support the inclusion of the PV type and codon location in routine risk prediction models, and suggest that intermediate-risk patients whose GISTs harbor 557/558 deletions may also need to be treated with adjuvant imatinib like the high-risk patients. [ABSTRACT FROM AUTHOR]
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- 2021
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21. Prevalence and Spectrum of Germline BRCA1 and BRCA2 Variants of Uncertain Significance in Breast/Ovarian Cancer: Mysterious Signals From the Genome.
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Fanale, Daniele, Fiorino, Alessia, Incorvaia, Lorena, Dimino, Alessandra, Filorizzo, Clarissa, Bono, Marco, Cancelliere, Daniela, Calò, Valentina, Brando, Chiara, Corsini, Lidia Rita, Sciacchitano, Roberta, Magrin, Luigi, Pivetti, Alessia, Pedone, Erika, Madonia, Giorgio, Cucinella, Alessandra, Badalamenti, Giuseppe, Russo, Antonio, and Bazan, Viviana
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BRCA genes ,OVARIAN cancer ,GERM cells ,GENETIC testing ,GENETIC mutation ,GENOMES - Abstract
About 10–20% of breast/ovarian (BC/OC) cancer patients undergoing germline BRCA1/2 genetic testing have been shown to harbor Variants of Uncertain Significance (VUSs). Since little is known about the prevalence of germline BRCA1/2 VUS in Southern Italy, our study aimed at describing the spectrum of these variants detected in BC/OC patients in order to improve the identification of potentially high-risk BRCA variants helpful in patient clinical management. Eight hundred and seventy-four BC or OC patients, enrolled from October 2016 to December 2020 at the "Sicilian Regional Center for the Prevention, Diagnosis and Treatment of Rare and Heredo-Familial Tumors" of University Hospital Policlinico "P. Giaccone" of Palermo, were genetically tested for germline BRCA1/2 variants through Next-Generation Sequencing analysis. The mutational screening showed that 639 (73.1%) out of 874 patients were BRCA - w.t. , whereas 67 (7.7%) were carriers of germline BRCA1/2 VUSs, and 168 (19.2%) harbored germline BRCA1/2 pathogenic/likely pathogenic variants. Our analysis revealed the presence of 59 different VUSs detected in 67 patients, 46 of which were affected by BC and 21 by OC. Twenty-one (35.6%) out of 59 variants were located on BRCA1 gene, whereas 38 (64.4%) on BRCA2. We detected six alterations in BRCA1 and two in BRCA2 with unclear interpretation of clinical significance. Familial anamnesis of a patient harboring the BRCA1 -c.3367G>T suggests for this variant a potential of pathogenicity, therefore it should be carefully investigated. Understanding clinical significance of germline BRCA1/2 VUS could improve, in future, the identification of potentially high-risk variants useful for clinical management of BC or OC patients and family members. [ABSTRACT FROM AUTHOR]
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- 2021
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22. BRCA1/2 pathogenic variants in triple-negative versus luminal-like breast cancers: genotype–phenotype correlation in a cohort of 531 patients.
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Incorvaia, Lorena, Fanale, Daniele, Bono, Marco, Calò, Valentina, Fiorino, Alessia, Brando, Chiara, Corsini, Lidia Rita, Cutaia, Sofia, Cancelliere, Daniela, Pivetti, Alessia, Filorizzo, Clarissa, La Mantia, Maria, Barraco, Nadia, Cusenza, Stefania, Badalamenti, Giuseppe, Russo, Antonio, and Bazan, Viviana
- Abstract
Background: Several available data suggest the association between specific molecular subtypes and BRCA1/2 mutational status. Previous investigations showed the association between BRCA1/2 pathogenic variants (PVs) in specific genomic regions and phenotypic variations of cancer relative risk, while the role of PV type and location in determining the breast cancer (BC) phenotypic features remains still unclear. The aim of this research was to describe the germline BRCA1/2 PVs in triple-negative breast cancer (TNBC) versus luminal-like BC and their potential leverage on BC phenotype. Patients & methods: We retrospectively collected and analyzed all clinical information of 531 patients with BC genetically tested for germline BRCA1/2 PVs by Next-Generation Sequencing analysis at University Hospital Policlinico "P. Giaccone" of Palermo (Sicily) from January 2016 to February 2020. Results: Our results corroborate the evidence that BRCA1 -related tumors often have a profile which resembles the TNBC subtype, whereas BRCA2 -associated tumors have a profile that resembles luminal-like BC, especially the Luminal B subtype. Interestingly, our findings suggest that the PVs identified in TNBC were not largely overlapping with those in luminal-like tumors. Differences in the frequency of two PVs potentially associated with different molecular tumor subtypes were observed. BRCA1 -633delC was detected with relatively higher prevalence in patients with TNBC, whereas BRCA2 -1466delT was found mainly in Luminal B tumors, but in no TNBC patient. Conclusion: Future studies examining the type and location of BRCA1/2 PVs within different molecular subtypes are required to verify our hypothesis and could provide an interesting insight into the complex topic of genotype–phenotype correlations. Additionally, a more in-depth understanding of the potential correlations between BRCA PVs and clinical and phenotypic features of hereditary BC syndrome patients could be the key to develop better strategies of prevention and surveillance in BRCA -positive carriers without disease. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
23. Baseline plasma levels of soluble PD-1, PD-L1, and BTN3A1 predict response to nivolumab treatment in patients with metastatic renal cell carcinoma: a step toward a biomarker for therapeutic decisions.
- Author
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Incorvaia, Lorena, Fanale, Daniele, Badalamenti, Giuseppe, Porta, Camillo, Olive, Daniel, De Luca, Ida, Brando, Chiara, Rizzo, Mimma, Messina, Carlo, Rediti, Mattia, Russo, Antonio, Bazan, Viviana, and Iovanna, Juan Lucio
- Subjects
RENAL cell carcinoma ,PROGRAMMED cell death 1 receptors ,PROGRAMMED death-ligand 1 ,BIOMARKERS ,RENAL cancer ,IPILIMUMAB - Abstract
Despite a proportion of renal cancer patients can experiment marked and durable responses to immune-checkpoint inhibitors, the treatment efficacy is widely variable and identifying the patient who will benefit from immunotherapy remains an issue. We performed a prospective study to investigate if soluble forms of the immune-checkpoints PD-1 (sPD-1), PD-L1 (sPD-L1), pan-BTN3As, BTN3A1, and BTN2A1, could be candidate to predict the response to immune-checkpoint blockade therapy. We evaluated the plasma levels in a learning cohort of metastatic clear cell renal carcinoma (mccRCC) patients treated with the anti-PD-1 agent nivolumab by ad hoc developed ELISA's. Using specific cut-offs determined through ROC curves, we showed that high baseline levels of sPD-1 (>2.11 ng/ml), sPD-L1 (>0.66 ng/ml), and sBTN3A1 (>6.84 ng/ml) were associated with a longer progression-free survival (PFS) to nivolumab treatment [median PFS, levels above thresholds: sPD-1, 20.7 months (p <.0001); sPD-L1, 19 months (p <.0001); sBTN3A1, 17.5 months (p =.002)]. High sPD-1 and sBTN3A1 levels were also associated with best overall response by RECIST and objective response of >20%. The results were confirmed in a validation cohort of 20 mccRCC patients. The analysis of plasma dynamic changes after nivolumab showed a statistically significant decrease of sPD-1 after 2 cycles (Day 28) in the long-responder patients. Our study revealed that the plasma levels of sPD-1, sPD-L1, and sBTN3A1 can predict response to nivolumab, discriminating responders from non-responders already at therapy baseline, with the advantages of non-invasive sample collection and real-time monitoring that allow to evaluate the dynamic changes during cancer evolution and treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
24. Real life use of biomarkers of homologous recombination deficiency (HRD) status beyond BRCA to predict the effectiveness of PARP inhibitors in ovarian cancer patients.
- Author
-
Incorvaia, Lorena, Brando, Chiara, Perez, Alessandro, Bono, Marco, Cancelliere, Daniela, Pivetti, Alessia, Barraco, Nadia, Contino, Silvia, Raso, Chiara Annamaria, Carreca, Anna Paola, Gristina, Valerio, Galvano, Antonio, Bazan Russo, Tancredi Didier, Castellana, Luisa, Insalaco, Lavinia, Fanale, Daniele, Marchetti, Claudia, Bazan, Viviana, Russo, Antonio, and Carreca, Ignazio
- Published
- 2023
- Full Text
- View/download PDF
25. CIRCULATING IMMUNE-CHECKPOINTS AND LYMPHOCYTE MICRORNAs IN RENAL CELL CARCINOMA AS A NOVEL BIOMARKERS OF IMMUNOTHERAPY RESPONSE.
- Author
-
BRANDO, Chiara, INCORVAIA, Lorena, FANALE, Daniele, ALGERI, Laura, DIMINO, Alessandra, SCALIA, Raimondo, BONASERA, Annalisa, BARRACO, Nadia, BONO, Marco, CALÒ, Valentina, CANCELLIERE, Daniela, CASTIGLIA, Marta, FIORINO, Alessia, PEDONE, Erika, PEREZ, Alessandro, PIVETTI, Alessia, RUSSO, Antonio, and BAZAN, Viviana
- Subjects
- *
RENAL cell carcinoma , *MEDICAL sciences , *WOUND healing , *BIOLOGICAL systems , *DEVELOPMENTAL biology , *BIOMARKERS , *WRINKLES (Skin) - Published
- 2021
26. Prognostic Role of Plasma PD-1, PD-L1, pan-BTN3As and BTN3A1 in Patients Affected by Metastatic Gastrointestinal Stromal Tumors: Can Immune Checkpoints Act as a Sentinel for Short-Term Survival?
- Author
-
Fanale, Daniele, Incorvaia, Lorena, Badalamenti, Giuseppe, De Luca, Ida, Algeri, Laura, Bonasera, Annalisa, Corsini, Lidia Rita, Brando, Chiara, Russo, Antonio, Iovanna, Juan Lucio, Bazan, Viviana, Roberta, Maestro, and Hohenberger, Peter
- Subjects
THERAPEUTIC use of antineoplastic agents ,PROGRAMMED cell death 1 receptors ,SURVIVAL ,SENTINEL health events ,BIOMARKERS ,PUBLIC health surveillance ,BUTYROPHILIN ,IMMUNE checkpoint inhibitors ,BLOOD plasma ,MULTIVARIATE analysis ,METASTASIS ,GASTROINTESTINAL tumors ,COMPARATIVE studies ,KAPLAN-Meier estimator ,DESCRIPTIVE statistics ,ENZYME-linked immunosorbent assay ,MEMBRANE proteins ,SENTINEL lymph nodes ,STATISTICAL correlation ,IMATINIB ,RECEIVER operating characteristic curves ,IMMUNOTHERAPY ,BLOOD ,THERAPEUTICS - Abstract
Simple Summary: Recently, it was shown that circulating PD-1 and PD-L1 are correlated with shorter survival in individuals with various types of solid tumors, including lung cancer and gastrointestinal solid tumors. Nevertheless, the correlation between shorter survival and elevated levels of sPD-1 and sPD-L1 has not yet been studied in gastrointestinal stromal tumor (GIST) patients. Our study aimed to understand if soluble forms of immune checkpoints, such as sPD-1, sPD-L1, sBTN3A1, and pan-sBTN3As, may be predictors of survival for metastatic GIST (mGIST) patients, in order to obtain useful information about the clinical evolution of disease. Using receiver operating characteristic (ROC) analysis, the optimal concentration thresholds for each biomarker were identified to discriminate mGIST patients with short (≤36 months) versus long (>36 months) progression-free survival (PFS). Kaplan–Meier analysis revealed that patients with plasma concentrations under thresholds exhibited a median PFS about 20 months longer compared to subjects with levels above cut-offs. Additionally, the impact of different baseline covariates was evaluated through a multivariate analysis, showing that plasma levels of sPD-L1 and pan-sBTN3As below respective concentration thresholds and the absence of KIT exon 11 deletions or delins at codons 557 and/or 558 were important prognostic biomarkers for a longer PFS in mGIST patients. Gastrointestinal stromal tumors (GISTs) represent 1% of all primary gastrointestinal tumors. Immune surveillance is often overcome by cancer cells due to the activation of immunoregulatory molecules such as programmed death protein (PD-1) and its ligand PD-L1, and butyrophilin sub-family 3A/CD277 receptors (BTN3A). Because several studies demonstrated that tumor PD-1 and PD-L1 expression may have a prominent prognostic function, this investigation aimed to discover if soluble forms of these molecules may be useful in predicting survival of metastatic GIST (mGIST) patients. Through specific ad hoc developed ELISA assays not yet available on the market, the circulating PD-1, PD-L1, BTN3A1, and pan-BTN3As levels were examined in 30 c-KIT exon 11-mutated mGIST patients, prior to imatinib therapy. Using specific thresholds derived by ROC analysis, we found that high baseline levels of sPD-1 (>8.1 ng/mL), sPD-L1 (>0.7 ng/mL), sBTN3A1 (>7.0 ng/mL), and pan-BTN3As (>5.0 ng/mL) were correlated with shorter progression-free survival (PFS) and poor prognosis. Contrariwise, subjects with lower plasma concentrations exhibited a median PFS about 20 months longer than to the earlier. Finally, an additional multivariate analysis revealed that circulating levels of sPD-L1 ≤ 0.7 ng/mL and pan-sBTN3As ≤ 5.0 ng/mL, and the absence of KIT exon 11 deletions or delins at codons 557 and/or 558 were associated with a longer PFS in mGIST patients. Our investigation, for the first time, revealed that evaluating the plasma concentration of some immune checkpoints may help prognosticate survival in mGIST patients, suggesting their potential use as prognostic biomarkers beyond the presence of KIT exon 11 Del or Delins at codons 557/558. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
27. WHAT ARE THE MULTIGENIC FINGERPRINT HALLMARKS IN TRIPLE-NEGATIVE BREAST CANCER?
- Author
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FIORINO, Alessia, INCORVAIA, Lorena, FANALE, Daniele, BONO, Marco, BARRACO, Nadia, BRANDO, Chiara, CALÒ, Valentina, CANCELLIERE, Daniela, CASTIGLIA, Marta, PEDONE, Erika, PEREZ, Alessandro, PIVETTI, Alessia, RUSSO, Antonio, and BAZAN, Viviana
- Subjects
TRIPLE-negative breast cancer - Published
- 2021
28. A "Lymphocyte MicroRNA Signature" as Predictive Biomarker of Immunotherapy Response and Plasma PD-1/PD-L1 Expression Levels in Patients with Metastatic Renal Cell Carcinoma: Pointing towards Epigenetic Reprogramming.
- Author
-
Incorvaia, Lorena, Fanale, Daniele, Badalamenti, Giuseppe, Brando, Chiara, Bono, Marco, De Luca, Ida, Algeri, Laura, Bonasera, Annalisa, Corsini, Lidia Rita, Scurria, Salvatore, Iovanna, Juan Lucio, Russo, Antonio, and Bazan, Viviana
- Subjects
TUMOR suppressor genes ,BIOMARKERS ,CANCER patients ,IMMUNOTHERAPY ,LYMPHOCYTES ,MEMBRANE proteins ,METASTASIS ,RENAL cell carcinoma ,PATIENT selection ,MICRORNA ,IMMUNE checkpoint inhibitors ,THERAPEUTICS - Abstract
Simple Summary: MicroRNAs are small molecules of non-coding RNAs which regulate gene expression at the post-transcriptional level. Normal miRNA expression and function can be deregulated in cancer. The comprehensive molecular characterization of Renal Cell Carcinoma shows several genes silenced and signaling pathways deregulated by epigenetic modifications, such as the abnormal expression of miRNAs. They can be secreted from malignant cells in whole-blood, plasma, serum, and urine samples, making miRNAs potential non-invasive tumor biomarkers. However, if a single miRNA can show low discriminatory power, the combination of miRNAs in a "miRNA signature", identified in the peripheral lymphocytes of patients, could function better with much higher probability to predict the response to immunotherapy and to discriminate responders from non-responders patients already at therapy baseline. Introduction of checkpoint inhibitors resulted in durable responses and improvements in overall survival in advanced RCC patients, but the treatment efficacy is widely variable, and a considerable number of patients are resistant to PD-1/PD-L1 inhibition. This variability of clinical response makes necessary the discovery of predictive biomarkers for patient selection. Previous findings showed that the epigenetic modifications, including an extensive microRNA-mediated regulation of tumor suppressor genes, are key features of RCC. Based on this biological background, we hypothesized that a miRNA expression profile directly identified in the peripheral lymphocytes of the patients before and after the nivolumab administration could represent a step toward a real-time monitoring of the dynamic changes during cancer evolution and treatment. Interestingly, we found a specific subset of miRNAs, called "lymphocyte miRNA signature", specifically induced in long-responder patients (CR, PR, or SD to nivolumab >18 months). Focusing on the clinical translational potential of miRNAs in controlling the expression of immune checkpoints, we identified the association between the plasma levels of soluble PD-1/PD-L1 and expression of some lymphocyte miRNAs. These findings could help the development of novel dynamic predictive biomarkers urgently needed to predict the potential response to immunotherapy and to guide clinical decision-making in RCC patients. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
29. Detection of Germline Mutations in a Cohort of 139 Patients with Bilateral Breast Cancer by Multi-Gene Panel Testing: Impact of Pathogenic Variants in Other Genes beyond BRCA1/2.
- Author
-
Fanale, Daniele, Incorvaia, Lorena, Filorizzo, Clarissa, Bono, Marco, Fiorino, Alessia, Calò, Valentina, Brando, Chiara, Corsini, Lidia Rita, Barraco, Nadia, Badalamenti, Giuseppe, Russo, Antonio, and Bazan, Viviana
- Subjects
BREAST tumors ,DISEASE susceptibility ,GENETIC techniques ,MEDICAL records ,GENETIC mutation ,ONCOGENES ,GENETIC testing ,BRCA genes ,RETROSPECTIVE studies ,ACQUISITION of data methodology - Abstract
Simple Summary: Many bilateral breast cancer patients with increased hereditary susceptibility to breast cancer result negative for BRCA1 or BRCA2 pathogenic variants and, thus, need a further genetic testing through a broader gene panel. Some patients with negative test result for BRCA1/2 pathogenic variants may harbor pathogenic variants in other breast cancer susceptibility genes, including ATM, CHEK2, PALB2, PTEN, TP53. Of course, the use of a multi-gene panel provides clinicians more information through a single test. Therefore, we focused on potential clinical impact of a NGS-based multi-gene panel testing in bilateral breast cancer patients, in order to evaluate the utility of perform a most comprehensive genetic analysis in these subjects, regardless the criteria concerning personal and family history of cancer established by the current guidelines. Our study revealed that the use of a NGS-based multiple-gene panel testing could increase the detection rates of germline alterations in bilateral breast cancer patients. Patients with unilateral breast cancer (UBC) have an increased risk of developing bilateral breast cancer (BBC). The annual risk of contralateral BC is about 0.5%, but increases by up to 3% in BRCA1 or BRCA2 pathogenic variant (PV) carriers. Our study was aimed to evaluate whether all BBC patients should be offered multi-gene panel testing, regardless their cancer family history and age at diagnosis. We retrospectively collected all clinical information of 139 BBC patients genetically tested for germline PVs in different cancer susceptibility genes by NGS-based multi-gene panel testing. Our investigation revealed that 52 (37.4%) out of 139 BBC patients harbored germline PVs in high- and intermediate-penetrance breast cancer (BC) susceptibility genes including BRCA1, BRCA2, PTEN, PALB2, CHEK2, ATM, RAD51C. Nineteen out of 53 positively tested patients harbored a PV in a known BC susceptibility gene (no-BRCA). Interestingly, in the absence of an analysis performed via multi-gene panel, a significant proportion (14.4%) of PVs would have been lost. Therefore, offering a NGS-based multi-gene panel testing to all BBC patients may significantly increase the detection rates of germline PVs in other cancer susceptibility genes beyond BRCA1/2, avoiding underestimation of the number of individuals affected by a hereditary tumor syndrome. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
30. Prognostic role of soluble PD-1 and BTN2A1 in overweight melanoma patients treated with nivolumab or pembrolizumab: finding the missing links in the symbiotic immune-metabolic interplay
- Author
-
Lorena Incorvaia, Gaetana Rinaldi, Giuseppe Badalamenti, Alessandra Cucinella, Chiara Brando, Giorgio Madonia, Alessia Fiorino, Angela Pipitone, Alessandro Perez, Federica Li Pomi, Antonio Galvano, Valerio Gristina, Nadia Barraco, Marco Bono, Tancredi Didier Bazan Russo, Francesca Toia, Adriana Cordova, Daniele Fanale, Antonio Russo, Viviana Bazan, Incorvaia, Lorena, Rinaldi, Gaetana, Badalamenti, Giuseppe, Cucinella, Alessandra, Brando, Chiara, Madonia, Giorgio, Fiorino, Alessia, Pipitone, Angela, Perez, Alessandro, Li Pomi, Federica, Galvano, Antonio, Gristina, Valerio, Barraco, Nadia, Bono, Marco, Bazan Russo, Tancredi Didier, Toia, Francesca, Cordova, Adriana, Fanale, Daniele, Russo, Antonio, and Bazan, Viviana
- Subjects
butyrophilins ,Oncology ,BTN2A1 ,PD-1 ,melanoma ,circulating immune checkpoints ,soluble immune checkpoints ,predictive biomarker - Abstract
Individual response to immune checkpoint inhibitors (ICIs) is currently unpredictable in patients with melanoma. Recent findings highlight a striking improvement in the clinical outcomes of overweight/obese patients treated with ICIs, which seems driven, at least in part, by programmed cell death protein 1 (PD-1)-mediated T-cell dysfunction. A putative role of butyrophilins (BTNs) is under investigation as a novel mechanism of cancer immune evasion and obesity-associated inflammation. This study investigates the role of baseline plasma levels of soluble PD-1 (sPD-1), soluble programmed cell death ligand 1 (sPD-L1), BTN2A1 (sBTN2A1), BTN3A1 (sBTN3A1), along with body mass index (BMI), as predictive biomarkers of immunotherapy response in metastatic melanoma patients treated with nivolumab or pembrolizumab as first-line treatment. In all, 41 patients were included in the study. The baseline plasma level of sPD-1 was significantly lower, and the sBTN2A1 was significantly higher, in long-responder patients to nivolumab or pembrolizumab (median sPD-1: 10.3 ng/ml versus 16.6 ng/ml, p = 0.001; median sBTN2A1: 4.4 ng/ml versus 3.77 ng/ml, p = 0.004). Lower levels of sPD-1 and higher levels of sBTN2A1 were also significantly associated with better overall response rate. Notably, when we further stratified the study cohort using BMI along with sPD-1, patients with BMI ⩾ 25 and sPD-1
- Published
- 2023
31. Exploring the Dynamic Crosstalk between the Immune System and Genetics in Gastrointestinal Stromal Tumors
- Author
-
Alessandra Dimino, Chiara Brando, Laura Algeri, Valerio Gristina, Erika Pedone, Marta Peri, Alessandro Perez, Ida De Luca, Roberta Sciacchitano, Luigi Magrin, Tancredi Didier Bazan Russo, Marco Bono, Nadia Barraco, Silvia Contino, Maria La Mantia, Antonio Galvano, Giuseppe Badalamenti, Antonio Russo, Viviana Bazan, Lorena Incorvaia, Dimino, Alessandra, Brando, Chiara, Algeri, Laura, Gristina, Valerio, Pedone, Erika, Peri, Marta, Perez, Alessandro, De Luca, Ida, Sciacchitano, Roberta, Magrin, Luigi, Bazan Russo, Tancredi Didier, Bono, Marco, Barraco, Nadia, Contino, Silvia, La Mantia, Maria, Galvano, Antonio, Badalamenti, Giuseppe, Russo, Antonio, Bazan, Viviana, and Incorvaia, Lorena
- Subjects
Cancer Research ,immune system ,Oncology ,target therapy ,tumor microenvironment ,immunotherapy ,immune checkpoints ,sarcomas ,GIST - Abstract
Gastrointestinal Stromal Tumors (GISTs) represent a paradigmatic model of oncogene addiction. Despite the well-known impact of the mutational status on clinical outcomes, we need to expand our knowledge to other factors that influence behavior heterogeneity in GIST patients. A growing body of studies has revealed that the tumor microenvironment (TME), mostly populated by tumor-associated macrophages (TAMs) and lymphocytes (TILs), and stromal differentiation (SD) have a significant impact on prognosis and response to treatment. Interestingly, even though the current knowledge of the role of immune response in this setting is still limited, recent pre-clinical and clinical data have highlighted the relevance of the TME in GISTs, with possible implications for clinical practice in the near future. Moreover, the expression of immune checkpoints, such as PD-L1, PD-1, and CTLA-4, and their relationship to the clinical phenotype in GIST are emerging as potential prognostic biomarkers. Looking forward, these variables related to the underlying tumoral microenvironment in GIST, though limited to still-ongoing trials, might lead to the potential use of immunotherapy, alone or in combination with targeted therapy, in advanced TKI-refractory GISTs. This review aims to deepen understanding of the potential link between mutational status and the immune microenvironment in GIST.
- Published
- 2022
32. Detection of Germline Mutations in a Cohort of 139 Patients with Bilateral Breast Cancer by Multi-Gene Panel Testing: Impact of Pathogenic Variants in Other Genes beyond BRCA1/2
- Author
-
Lidia Rita Corsini, Marco Bono, Chiara Brando, Valentina Calò, Lorena Incorvaia, Nadia Barraco, Fanale D, A. Fiorino, Antonio Russo, Viviana Bazan, Giuseppe Badalamenti, Clarissa Filorizzo, Fanale, Daniele, Incorvaia, Lorena, Filorizzo, Clarissa, Bono, Marco, Fiorino, Alessia, Calò, Valentina, Brando, Chiara, Corsini, Lidia Rita, Barraco, Nadia, Badalamenti, Giuseppe, Russo, Antonio, and Bazan, Viviana
- Subjects
0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,PTEN ,Settore MED/06 - Oncologia Medica ,PALB2 ,CHECK2 ,lcsh:RC254-282 ,Germline ,Article ,03 medical and health sciences ,0302 clinical medicine ,Germline mutation ,Breast cancer ,breast cancer ,Internal medicine ,medicine ,Cancer Family ,skin and connective tissue diseases ,bilateral breast cancer ,CHEK2 ,germline pathogenic variant ,biology ,business.industry ,ATM ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,BRCA1 ,BRCA2 ,030104 developmental biology ,030220 oncology & carcinogenesis ,biology.protein ,multi-gene panel testing ,RAD51C ,germline pathogenic variants ,business - Abstract
Simple Summary Many bilateral breast cancer patients with increased hereditary susceptibility to breast cancer result negative for BRCA1 or BRCA2 pathogenic variants and, thus, need a further genetic testing through a broader gene panel. Some patients with negative test result for BRCA1/2 pathogenic variants may harbor pathogenic variants in other breast cancer susceptibility genes, including ATM, CHEK2, PALB2, PTEN, TP53. Of course, the use of a multi-gene panel provides clinicians more information through a single test. Therefore, we focused on potential clinical impact of a NGS-based multi-gene panel testing in bilateral breast cancer patients, in order to evaluate the utility of perform a most comprehensive genetic analysis in these subjects, regardless the criteria concerning personal and family history of cancer established by the current guidelines. Our study revealed that the use of a NGS-based multiple-gene panel testing could increase the detection rates of germline alterations in bilateral breast cancer patients. Abstract Patients with unilateral breast cancer (UBC) have an increased risk of developing bilateral breast cancer (BBC). The annual risk of contralateral BC is about 0.5%, but increases by up to 3% in BRCA1 or BRCA2 pathogenic variant (PV) carriers. Our study was aimed to evaluate whether all BBC patients should be offered multi-gene panel testing, regardless their cancer family history and age at diagnosis. We retrospectively collected all clinical information of 139 BBC patients genetically tested for germline PVs in different cancer susceptibility genes by NGS-based multi-gene panel testing. Our investigation revealed that 52 (37.4%) out of 139 BBC patients harbored germline PVs in high- and intermediate-penetrance breast cancer (BC) susceptibility genes including BRCA1, BRCA2, PTEN, PALB2, CHEK2, ATM, RAD51C. Nineteen out of 53 positively tested patients harbored a PV in a known BC susceptibility gene (no-BRCA). Interestingly, in the absence of an analysis performed via multi-gene panel, a significant proportion (14.4%) of PVs would have been lost. Therefore, offering a NGS-based multi-gene panel testing to all BBC patients may significantly increase the detection rates of germline PVs in other cancer susceptibility genes beyond BRCA1/2, avoiding underestimation of the number of individuals affected by a hereditary tumor syndrome.
- Published
- 2020
33. Exploring the Dynamic Crosstalk between the Immune System and Genetics in Gastrointestinal Stromal Tumors.
- Author
-
Dimino A, Brando C, Algeri L, Gristina V, Pedone E, Peri M, Perez A, De Luca I, Sciacchitano R, Magrin L, Bazan Russo TD, Bono M, Barraco N, Contino S, La Mantia M, Galvano A, Badalamenti G, Russo A, Bazan V, and Incorvaia L
- Abstract
Gastrointestinal Stromal Tumors (GISTs) represent a paradigmatic model of oncogene addiction. Despite the well-known impact of the mutational status on clinical outcomes, we need to expand our knowledge to other factors that influence behavior heterogeneity in GIST patients. A growing body of studies has revealed that the tumor microenvironment (TME), mostly populated by tumor-associated macrophages (TAMs) and lymphocytes (TILs), and stromal differentiation (SD) have a significant impact on prognosis and response to treatment. Interestingly, even though the current knowledge of the role of immune response in this setting is still limited, recent pre-clinical and clinical data have highlighted the relevance of the TME in GISTs, with possible implications for clinical practice in the near future. Moreover, the expression of immune checkpoints, such as PD-L1, PD-1, and CTLA-4, and their relationship to the clinical phenotype in GIST are emerging as potential prognostic biomarkers. Looking forward, these variables related to the underlying tumoral microenvironment in GIST, though limited to still-ongoing trials, might lead to the potential use of immunotherapy, alone or in combination with targeted therapy, in advanced TKI-refractory GISTs. This review aims to deepen understanding of the potential link between mutational status and the immune microenvironment in GIST.
- Published
- 2022
- Full Text
- View/download PDF
34. Pompe disease: pathogenesis, molecular genetics and diagnosis.
- Author
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Taverna S, Cammarata G, Colomba P, Sciarrino S, Zizzo C, Francofonte D, Zora M, Scalia S, Brando C, Curto AL, Marsana EM, Olivieri R, Vitale S, and Duro G
- Subjects
- Humans, Phenotype, Glycogen Storage Disease Type II diagnosis, Glycogen Storage Disease Type II etiology, Glycogen Storage Disease Type II genetics, Glycogen Storage Disease Type II therapy
- Abstract
Pompe disease (PD) is a rare autosomal recessive disorder caused by mutations in the GAA gene, localized on chromosome 17 and encoding for acid alpha-1,4-glucosidase (GAA). Currently, more than 560 mutations spread throughout GAA gene have been reported. GAA catalyzes the hydrolysis of α-1,4 and α-1,6-glucosidic bonds of glycogen and its deficiency leads to lysosomal storage of glycogen in several tissues, particularly in muscle. PD is a chronic and progressive pathology usually characterized by limb-girdle muscle weakness and respiratory failure. PD is classified as infantile and childhood/adult forms. PD patients exhibit a multisystemic manifestation that depends on age of onset.Early diagnosis is essential to prevent or reduce the irreversible organ damage associated with PD progression. Here, we make an overview of PD focusing on pathogenesis, clinical phenotypes, molecular genetics, diagnosis, therapies, autophagy and the role of miRNAs as potential biomarkers for PD.
- Published
- 2020
- Full Text
- View/download PDF
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