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Article ; Online: Novel metabolomics-biohumoral biomarkers model for predicting survival of metastatic soft-tissue sarcomas.

Vignoli, Alessia / Miolo, Gianmaria / Tenori, Leonardo / Buonadonna, Angela / Lombardi, Davide / Steffan, Agostino / Scalone, Simona / Luchinat, Claudio / Corona, Giuseppe

iScience

2023 Volume 26, Issue 10, Page(s) 107678

Abstract: Soft tissue sarcomas (STSs) are rare malignant tumors that are difficult to prognosticate using currently available instruments. Omics sciences could provide more accurate and individualized survival predictions for patients with metastatic STS. In this ... ...

Abstract	Soft tissue sarcomas (STSs) are rare malignant tumors that are difficult to prognosticate using currently available instruments. Omics sciences could provide more accurate and individualized survival predictions for patients with metastatic STS. In this pilot, hypothesis-generating study, we integrated clinicopathological variables with proton nuclear magnetic resonance (
Language	English
Publishing date	2023-08-19
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2023.107678
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Article: Pharmacometabolomics of trabectedin in metastatic soft tissue sarcoma patients.

Corona, Giuseppe / Di Gregorio, Emanuela / Buonadonna, Angela / Lombardi, Davide / Scalone, Simona / Steffan, Agostino / Miolo, Gianmaria

Frontiers in pharmacology

2023 Volume 14, Page(s) 1212634

Abstract: Objective: ...

Abstract	Objective:
Language	English
Publishing date	2023-08-11
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2023.1212634
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Article: Metabolic Clues to Bile Acid Patterns and Prolonged Survival in Patients with Metastatic Soft-Tissue Sarcoma Treated with Trabectedin.

Miolo, Gianmaria / Buonadonna, Angela / Scalone, Simona / Lombardi, Davide / Della Puppa, Lara / Steffan, Agostino / Corona, Giuseppe

Metabolites

2023 Volume 13, Issue 10

Abstract: Metastatic soft-tissue sarcomas (mSTS) encompass a highly heterogeneous group of rare tumours characterized by different clinical behaviours and outcomes. Currently, prognostic factors for mSTS are very limited, posing significant challenges in ... ...

Abstract	Metastatic soft-tissue sarcomas (mSTS) encompass a highly heterogeneous group of rare tumours characterized by different clinical behaviours and outcomes. Currently, prognostic factors for mSTS are very limited, posing significant challenges in predicting patient survival. Within a cohort of 39 mSTS patients undergoing trabectedin treatment, it was remarkable to find one patient who underwent 73 cycles of trabectedin achieving an unforeseen clinical outcome. To identify contributing factors to her exceptional long-term survival, we have explored circulation metabolomics and biohumoral biomarkers to uncover a potential distinct host biochemical phenotype. The long-term survival patient compared with the other mSTS patients exhibited a distinctive metabolic profile characterized by remarkably higher levels of ursodeoxycholic acid (UDCA) derivatives and vitamin D and lower levels of lithocholic acid (LCA) derivatives, as well as reduced levels of inflammatory C-Reactive Protein 4 (C-RP4) biomarker. Despite its exploratory nature, this study reveals a potential association between specific bile acid metabolic profiles and mSTS patients' prognosis. Enhanced clinical understanding of the interplay between bile acid metabolism and disease progression could pave the way for new targeted therapeutic interventions which may improve the overall survival of mSTS patients.
Language	English
Publishing date	2023-09-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662251-8
ISSN	2218-1989
ISSN	2218-1989
DOI	10.3390/metabo13101035
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Article: Prospective, Multicenter Phase II Trial of Non-Pegylated Liposomal Doxorubicin Combined with Ifosfamide in First-Line Treatment of Advanced/Metastatic Soft Tissue Sarcomas.

Buonadonna, Angela / Scalone, Simona / Lombardi, Davide / Fumagalli, Arianna / Guglielmi, Alessandra / Lestuzzi, Chiara / Polesel, Jerry / Canzonieri, Vincenzo / Lamon, Stefano / Giovanis, Petros / Gagno, Sara / Corona, Giuseppe / Mascarin, Maurizio / Belluco, Claudio / De Paoli, Antonino / Fasola, Gianpiero / Puglisi, Fabio / Miolo, Gianmaria

Cancers

2023 Volume 15, Issue 20

Abstract: Doxorubicin is a widely used anticancer agent as a first-line treatment for various tumor types, including sarcomas. Its use is hampered by adverse events, among which is the risk of dose dependence. The potential cardiotoxicity, which increases with ... ...

Abstract	Doxorubicin is a widely used anticancer agent as a first-line treatment for various tumor types, including sarcomas. Its use is hampered by adverse events, among which is the risk of dose dependence. The potential cardiotoxicity, which increases with higher doses, poses a significant challenge to its safe and effective application. To try to overcome these undesired effects, encapsulation of doxorubicin in liposomes has been proposed. Caelyx and Myocet are different formulations of pegylated (PLD) and non-pegylated liposomal doxorubicin (NPLD), respectively. Both PLD and NPLD have shown similar activity compared with free drugs but with reduced cardiotoxicity. While the hand-foot syndrome exhibits a high occurrence among patients treated with PLD, its frequency is notably reduced in those receiving NPLD. In this prospective, multicenter, one-stage, single-arm phase II trial, we assessed the combination of NPLD and ifosfamide as first-line treatment for advanced/metastatic soft tissue sarcoma (STS). Patients received six cycles of NPLD (50 mg/m
Language	English
Publishing date	2023-10-18
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15205036
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Article ; Online: KIR-HLA Functional Repertoire Influences Trastuzumab Efficiency in Patients With HER2-Positive Breast Cancer.

Muraro, Elena / De Zorzi, Mariangela / Miolo, Gianmaria / Lombardi, Davide / Scalone, Simona / Spazzapan, Simon / Massarut, Samuele / Perin, Tiziana / Dolcetti, Riccardo / Steffan, Agostino / De Re, Valli

Frontiers in immunology

2022 Volume 12, Page(s) 791958

Abstract: Trastuzumab induced a high rate of pathological Complete Response (pCR) in patients affected by locally advanced HER2-positive Breast Cancer (HER2-BC), by exploiting immune-mediated mechanisms as Antibody-Dependent Cell Cytotoxicity (ADCC) involving ... ...

Abstract	Trastuzumab induced a high rate of pathological Complete Response (pCR) in patients affected by locally advanced HER2-positive Breast Cancer (HER2-BC), by exploiting immune-mediated mechanisms as Antibody-Dependent Cell Cytotoxicity (ADCC) involving Natural Killer (NK) cells. Host's immune genetics could influence the response to therapy, through the expression of variants that characterize NK receptors involved in ADCC effectiveness. Killer cell immunoglobin-like receptors (KIRs) modulate NK cell activity through their binding to class-I Human Leukocyte Antigens (HLA). The impact of the KIR/HLA repertoire in HER2-BC is under study. We characterized KIR genotypes of 36 patients with locally advanced HER2-BC treated with neoadjuvant chemotherapy including trastuzumab. We monitored pCR achievement before surgery and Disease-Free Survival (DFS) and Overall Survival (OS) after adjuvant therapy. HLA, and Fc gamma receptor IIIa (FcγR3A) and IIa (FcγR2A) were genotyped through targeted PCR and Sanger sequencing in 35/36 patients. The KIR-HLA combinations were then described as functional haplotypes and divided in two main categories as inhibitory tel A and stimulatory tel B. Trastuzumab-dependent ADCC activity was monitored with an
MeSH term(s)	Adult ; Aged ; Antibodies, Monoclonal, Humanized/therapeutic use ; Antibody-Dependent Cell Cytotoxicity/drug effects ; Breast Neoplasms/drug therapy ; Breast Neoplasms/metabolism ; Female ; HLA Antigens/metabolism ; Histocompatibility Antigens Class I/metabolism ; Humans ; Killer Cells, Natural/drug effects ; Killer Cells, Natural/metabolism ; Middle Aged ; Neoadjuvant Therapy/methods ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, KIR/metabolism ; Trastuzumab/therapeutic use ; Young Adult
Chemical Substances	Antibodies, Monoclonal, Humanized ; HLA Antigens ; Histocompatibility Antigens Class I ; Receptors, KIR ; ERBB2 protein, human (EC 2.7.10.1) ; Receptor, ErbB-2 (EC 2.7.10.1) ; Trastuzumab (P188ANX8CK)
Language	English
Publishing date	2022-01-12
Publishing country	Switzerland
Document type	Clinical Trial, Phase II ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.791958
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Article: Integration of Serum Metabolomics into Clinical Assessment to Improve Outcome Prediction of Metastatic Soft Tissue Sarcoma Patients Treated with Trabectedin.

Miolo, Gianmaria / Di Gregorio, Emanuela / Saorin, Asia / Lombardi, Davide / Scalone, Simona / Buonadonna, Angela / Steffan, Agostino / Corona, Giuseppe

Cancers

2020 Volume 12, Issue 7

Abstract: Soft tissue sarcomas (STS) are a group of rare and heterogeneous cancers with few diagnostic or prognostic biomarkers. This metabolomics study aimed to identify new serum prognostic biomarkers to improve the prediction of overall survival in patients ... ...

Abstract	Soft tissue sarcomas (STS) are a group of rare and heterogeneous cancers with few diagnostic or prognostic biomarkers. This metabolomics study aimed to identify new serum prognostic biomarkers to improve the prediction of overall survival in patients with metastatic STS. The study enrolled 24 patients treated with the same trabectedin regimen. The baseline serum metabolomics profile, targeted to 68 metabolites encompassing amino acids and bile acids pathways, was quantified by liquid chromatography-tandem mass spectrometry. Correlations between individual metabolomics profiles and overall survival were examined and a risk model to predict survival was built by Cox multivariate regression. The median overall survival of the studied patients was 13.0 months (95% CI, 5.6-23.5). Among all the metabolites investigated, only citrulline and histidine correlated significantly with overall survival. The best Cox risk prediction model obtained integrating metabolomics and clinical data, included citrulline, hemoglobin and patients' performance status score. It allowed to distinguish patients into a high-risk group with a low median overall survival of 2.1 months and a low- to moderate-risk group with a median overall survival of 19.1 months (
Language	English
Publishing date	2020-07-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers12071983
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Article ; Online: An Exceptional Response to Dostarlimab in Mismatch Repair Deficient, Microsatellite Instability-High and Platinum Refractory Endometrial Cancer.

Bartoletti, Michele / Giorda, Giorgio / Viel, Alessandra / Fornasarig, Mara / Zdjelar, Adrian / Segatto, Enrica / Sorio, Roberto / Corsetti, Serena / Scalone, Simona / Nicoloso, Milena Sabrina / Pivetta, Tania / Lucia, Emilio / Clemente, Nicolò / Palazzari, Elisa / Canzonieri, Vincenzo / Puglisi, Fabio

Current oncology (Toronto, Ont.)

2022 Volume 29, Issue 8, Page(s) 5209–5212

Abstract: Until recently, effective therapies for advanced endometrial cancer progressing to a platinum-based combination were lacking. In this setting, immunotherapy with anti PD-1/PDL-1 monoclonal antibodies is rising as a new paradigm in particular for patients ...

Abstract	Until recently, effective therapies for advanced endometrial cancer progressing to a platinum-based combination were lacking. In this setting, immunotherapy with anti PD-1/PDL-1 monoclonal antibodies is rising as a new paradigm in particular for patients with microsatellites instability/mismatch repair deficiency. In this case report, we describe an exceptional and rapid response to dostarlimab in a platinum refractory endometrial cancer patient with high disease burden harboring a mismatch repair deficiency.
MeSH term(s)	Antibodies, Monoclonal, Humanized ; Brain Neoplasms ; Colorectal Neoplasms ; DNA Mismatch Repair ; Endometrial Neoplasms/drug therapy ; Endometrial Neoplasms/genetics ; Female ; Humans ; Immune Checkpoint Inhibitors ; Microsatellite Instability ; Neoplastic Syndromes, Hereditary ; Platinum/therapeutic use ; Programmed Cell Death 1 Receptor
Chemical Substances	Antibodies, Monoclonal, Humanized ; Immune Checkpoint Inhibitors ; Programmed Cell Death 1 Receptor ; dostarlimab ; Platinum (49DFR088MY)
Language	English
Publishing date	2022-07-22
Publishing country	Switzerland
Document type	Case Reports ; Research Support, Non-U.S. Gov't
ZDB-ID	1236972-x
ISSN	1718-7729 ; 1198-0052
ISSN (online)	1718-7729
ISSN	1198-0052
DOI	10.3390/curroncol29080413
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Article ; Online: Bevacizumab or PARP-Inhibitors Maintenance Therapy for Platinum-Sensitive Recurrent Ovarian Cancer: A Network Meta-Analysis.

Bartoletti, Michele / Pelizzari, Giacomo / Gerratana, Lorenzo / Bortot, Lucia / Lombardi, Davide / Nicoloso, Milena / Scalone, Simona / Giorda, Giorgio / Baldassarre, Gustavo / Sorio, Roberto / Puglisi, Fabio

International journal of molecular sciences

2020 Volume 21, Issue 11

Abstract: Introduction: Targeted agents such as bevacizumab (BEV) or poly (ADP-ribose) polymerase inhibitors (PARPi) which have been added as concomitant or maintenance therapies have been shown to improve progression-free survival (PFS) in patients with platinum- ...

Abstract	Introduction: Targeted agents such as bevacizumab (BEV) or poly (ADP-ribose) polymerase inhibitors (PARPi) which have been added as concomitant or maintenance therapies have been shown to improve progression-free survival (PFS) in patients with platinum-sensitive recurrent ovarian cancer (PS rOC). In the absence of direct comparison, we performed a network meta-analysis considering Methods: We searched PubMed, EMBASE, and MEDLINE for trials involving patients with PS rOC treated with BEV or PARPi. Different comparisons were performed for patients included in the PARPi trials, according to Results: In the overall population, PARPi prolonged PFS with respect to BEV (hazard ratio (HR) = 0.70, 95% CI 0.54-0.91). In the Conclusions: PARPi performed better as compared with BEV in terms of PFS for the treatment of PS rOC, especially in BRCAm patients who had not previously received PARPi.
MeSH term(s)	Antineoplastic Agents, Immunological/therapeutic use ; BRCA1 Protein/genetics ; BRCA2 Protein/genetics ; Bevacizumab/therapeutic use ; Carboplatin/therapeutic use ; Drug Resistance, Neoplasm ; Female ; Heterozygote ; Humans ; Mutation ; Neoplasm Recurrence, Local/drug therapy ; Neoplasm Recurrence, Local/genetics ; Neoplasm Recurrence, Local/pathology ; Ovarian Neoplasms/drug therapy ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/pathology ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use
Chemical Substances	Antineoplastic Agents, Immunological ; BRCA1 Protein ; BRCA1 protein, human ; BRCA2 Protein ; BRCA2 protein, human ; Poly(ADP-ribose) Polymerase Inhibitors ; Bevacizumab (2S9ZZM9Q9V) ; Carboplatin (BG3F62OND5)
Language	English
Publishing date	2020-05-27
Publishing country	Switzerland
Document type	Journal Article ; Meta-Analysis
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21113805
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Article ; Online: Pharmacogenetic score predicts overall survival, progression-free survival and platinum sensitivity in ovarian cancer.

Gagno, Sara / Bartoletti, Michele / Romualdi, Chiara / Poletto, Elena / Scalone, Simona / Sorio, Roberto / Zanchetta, Martina / De Mattia, Elena / Roncato, Rossana / Cecchin, Erika / Giorda, Giorgio / Toffoli, Giuseppe

Pharmacogenomics

2020 Volume 21, Issue 14, Page(s) 995–1010

Abstract: Aim: ...

Abstract	Aim:
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Disease-Free Survival ; Female ; Humans ; Middle Aged ; Organoplatinum Compounds/therapeutic use ; Ovarian Neoplasms/drug therapy ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/mortality ; Ovarian Neoplasms/pathology ; Pharmacogenetics/methods ; Polymorphism, Genetic/genetics ; Prognosis ; Progression-Free Survival ; Young Adult
Chemical Substances	Organoplatinum Compounds
Language	English
Publishing date	2020-09-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2019513-8
ISSN	1744-8042 ; 1462-2416
ISSN (online)	1744-8042
ISSN	1462-2416
DOI	10.2217/pgs-2020-0049
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Zs.A 5247: Show issues

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Article ; Online: Characteristics and outcome of BRCA mutated epithelial ovarian cancer patients in Italy: A retrospective multicenter study (MITO 21).

Artioli, Grazia / Giannone, Gaia / Valabrega, Giorgio / Maggiorotto, Furio / Genta, Sofia / Pignata, Sandro / Lorusso, Domenica / Cormio, Gennaro / Scalone, Simona / Nicoletto, Maria Ornella / Greco, Filippo / Rossi, Emanuela / Spagnoletti, Ilaria / De Giorgi, Ugo / Orditura, Michele / Mosconi, Anna Maria / Kardhashi, Anila / Bogliolo, Stefano / Borgato, Lucia

Gynecologic oncology

2021 Volume 161, Issue 3, Page(s) 755–761

Abstract: Objective: Around 15% of epithelial ovarian cancer (EOC) patients (pts) harbor a germline BRCA1 or 2 mutation, showing different features than BRCA wild-type pts. The clinical and pathological features of an Italian BRCA mutated EOC cohort were ... ...

Abstract	Objective: Around 15% of epithelial ovarian cancer (EOC) patients (pts) harbor a germline BRCA1 or 2 mutation, showing different features than BRCA wild-type pts. The clinical and pathological features of an Italian BRCA mutated EOC cohort were described. Methods: We retrospectively analyzed clinical, pathological and mutational data from a cohort of Italian BRCA mutated EOC pts. treated in 15 MITO centers between 1995 and 2017. Results: Three-hundred thirty-one pts. were recorded. Two-hundred forty (72%) and 91 (27.5%) pts. harbored a BRCA1 and BRCA2 mutation, respectively. Median age at diagnosis was 52 years. The most frequent diagnosis was a high grade serous FIGO III or IV EOC and platinum doublet in first-line was administered to almost all pts. Fifty-three % of them had no residual disease (R = 0) at surgery. Median progression-free-survival (mPFS) after first-line chemotherapy was 29 months. Expected percentage of pts. alive at 5 years was 72.5% (CI 60.2-80.8%) and R = 0 predicted a significantly longer overall survival (OS). Sixty-six pts. (19,9%) had both an EOC and a breast cancer (BC) diagnosis. The first diagnosis was BC in 81,8% of cases with a mean interval between the two diagnoses (IBTDs) of 132.4 months. Mutational data show that the founder mutation c.5266dupC in BRCA1 was the most frequently recorded. Conclusions: This is the largest Italian BRCA mutEOC cohort. The only predictor of longer OS was R = 0. EOC pts. that developed subsequently a BC are long-term survivors.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; BRCA1 Protein/genetics ; Carcinoma, Ovarian Epithelial/genetics ; Carcinoma, Ovarian Epithelial/mortality ; Carcinoma, Ovarian Epithelial/pathology ; Demography ; Female ; Genetic Predisposition to Disease ; Humans ; Italy ; Middle Aged ; Neoplasm Staging ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/mortality ; Ovarian Neoplasms/pathology ; Progression-Free Survival ; Retrospective Studies
Chemical Substances	BRCA1 Protein ; BRCA1 protein, human
Language	English
Publishing date	2021-04-20
Publishing country	United States
Document type	Journal Article ; Multicenter Study
ZDB-ID	801461-9
ISSN	1095-6859 ; 0090-8258
ISSN (online)	1095-6859
ISSN	0090-8258
DOI	10.1016/j.ygyno.2021.04.014
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