المؤلفون: Carlo Cattrini, Marcello Manfredi, Paola Barboro, Marco Ghirimoldi, Alessia Mennitto, Veronica Martini, Alessio Battioni, Marco Le Van, Simone Gobbato, Carmen Branni, Rahma Ben Ayed, David James Pinato, Fabio Catalano, Elisa Zanardi, Francesco Boccardo, Alessandra Gennari

المصدر: Scientific Reports, Vol 13, Iss 1, Pp 1-10 (2023)

مصطلحات موضوعية: Medicine, Science

الوصف: Abstract Emerging evidence highlights the potential prognostic relevance of circulating lipids in metastatic castration-resistant prostate cancer (mCRPC), with a proposed 3-lipid signature. This study aims to analyze the lipidomic profiles of individuals with mCRPC to identify lipid species that could serve as predictive indicators of prognosis and therapeutic response. Plasma samples were collected from mCRPC patients initiating first-line treatment (1 L) (n = 29) and those previously treated with at least two lines of therapy (> 2 L) (n = 19), including an androgen-receptor signaling inhibitor and a taxane. Employing an untargeted lipidomic approach, lipids were extracted from the plasma samples and subjected to analysis. A comprehensive identification and quantification of 789 plasma lipids was achieved. Notably, 75 species displayed significant dysregulation in > 2 L patients in comparison to the 1 L group. Among these, 63 species exhibited elevated levels, while 12 were reduced. Patients included in > 2 L cohort showed elevated levels of acylcarnitines (CAR), diacylglycerols (DG), phosphatidylethanolamines (PE), triacylglycerols (TG), and ceramides (Cer). Notably, some upregulated lipids, including CAR 14:0, CAR 24:1, Cer d18:1/16:0, Cer d18:1/18:0 (C18 Cer), Cer d18:2/18:0, Cer d18:1/24:1, and Cer d20:1/24:1, showed significant associations with overall survival (OS) in univariate models. Specifically, increased levels of C18 Cer remained significantly associated with poorer OS in the multivariate model, even after adjusting for treatment line and PSA levels (Hazard Ratio: 3.59 [95% Confidence Interval 1.51–8.52], p = 0.004). Employing quantitative mass spectrometry, our findings underscore the independent prognostic significance of C18 Cer in individuals with mCRPC. This discovery opens avenues for further studies within this field.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2045-2322Test

الوصول الحر: https://doaj.org/article/1b1cebe48fc64c2f8ca1ec5827bdd380Test

المؤلفون: Mennitto, Roberto

المساهمون: Brandani, Stefano, Friedrich, Daniel

مصطلحات موضوعية: adsorption, straight-channel monoliths, multicomponent fluid phase, kinetics information for adsorbents, thermodynamic model, adsorption optimisation

الوصف: Straight-channel monoliths are a promising means to achieve process intensification of adsorption processes compared to conventional packed beds. Their main benefits are handling of high throughputs and good thermal management. The efficiency of a straight-channel monolith can be assessed via the definition of its height equivalent to a theoretical plate (HETP) and pressure drop. This thesis aims at developing a systematic procedure for the derivation of HETP correlations for industrially relevant straight-channel monoliths and review the pressure drop correlations for monoliths available in the literature. The HETP correlations derived are validated against full 3D numerical simulations of the single representative channel of each straight-channel monolith under analysis. The HETP correlations predict with great accuracy the HETP from numerical simulations. Moreover, simplified reduced order models are developed. The models are able to capture the overall dynamics of the 3D simulations for both isothermal and linear conditions, and non-isothermal and non-linear ones. The reduced order models are fully predictive, and strongly rely on accurate equilibrium and kinetic parameters. Given the relevance of reliable equilibrium and kinetic parameters for the simulation of monoliths, this thesis further investigates how to model multicomponent adsorption on heterogeneous solids, and how to extract kinetic parameters from experiments. The second part of this work presents the multisite rigid adsorbent lattice fluid (multi-RALF) model, a novel thermodynamic theory to model multicomponent adsorption on heterogeneous adsorbents. The parameterisation of multi-RALF is analysed in regard to the azeotropic adsorption of benzene and propene on silicalite and to the adsorption of CO2 on the flexible synthetic zeolite (Na,TEA)-ZSM-25. The former study is carried out using molecular simulations, while the latter uses experimental data. The results of the molecular simulations show that the azeotrope is caused by steric hindrance of benzene in the adsorbent framework. Once correctly parametrised using single component isotherms, multi-RALF can predict the azeotrope of the system. Multi-RALF has been proven to be an effective model for the flexibility of (Na,TEA)-ZSM-25 upon CO2 adsorption, as well. Experimental isotherms of CO2 adsorption on (Na,TEA)-ZSM-25 always present an inflection at a constant adsorbed amount. This has been explained as a gate opening effect. The adsorbent is made of two sites, α and β. The site β becomes accessible only after a critical uptake of 0.6 mol/kg. At this uptake, the cations blocking the site β interact with the adsorbate and move away from the windows of the β site. This effect leads to the inflection in the isotherm and a relaxation of the solid framework with a small breathing effect. The breathing behaviour effect on the system kinetics is then investigated using the zero length column (ZLC) technique. The ZLC curves at different flowrates and temperatures always present a transition between an equilibrium controlled regime at high partial pressures of CO2, while becoming kinetically controlled in the limit of zero-loading. The transition between the two regimes is related to the cation movement, and it is carefully accounted for in a ZLC numerical model which successfully fits the experimental data. Finally, thermal frequency response (TFR) measurements for air separation on the zeolite LiLSX are presented. This is a fast diffusing system, difficult to study with commercial equipment. Hence, the purpose-built dual piston pressure swing adsorption apparatus is used for the experiments. Two models are developed to analyse both single- and multi-component measurements. From the single component model, a tortuosity of 3.3 is regressed, while the multicomponent data show a N2/O2 selectivity of 6. Both values are in accordance with the available literature. TFR has proven to be a powerful technique to handle challenging diffusing systems, able to effectively discriminate the relevant mass and heat transfer time constants as shown from experiments at conditions relevant to process application. The work here presented aimed at providing a reliable methodology for modelling of monoliths and derivation of the relevant equilibrium and kinetic parameters. In future, the combination of the monoliths' models and multi-RALF could become a robust and reliable tool for the deployment of monoliths for process intensification.

الوصول الحر: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.853195Test

المؤلفون: Pierangela Sepe, Giuseppe Procopio, Chiara Carlotta Pircher, Umberto Basso, Orazio Caffo, Vera Cappelletti, Melanie Claps, Ugo De Giorgi, Lucia Fratino, Valentina Guadalupi, Patrizia Miodini, Cinzia De Marco, Bruno Perrucci, Alessia Mennitto, Daniele Santini, Francesco Spina, Marco Stellato, Filippo de Braud, Elena Verzoni

المصدر: Therapeutic Advances in Medical Oncology, Vol 16 (2024)

مصطلحات موضوعية: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Background: Up to 30% of patients with metastatic castration-resistant prostate cancer (mCRPC) develop visceral metastases, which are associated with a poor prognosis. Objectives: Efficacy of enzalutamide in mCRPC patients with measurable metastases, including visceral and/or extra-regional lymph nodes. Methods: In this phase II multicenter study, patients with mCRPC and measurable metastases received enzalutamide as the first line. Primary endpoint: 3-month (mo) disease control rate (DCR) defined as the proportion of patients with complete (CR) or partial response (PR) or stable disease (SD) as per Response Evaluation Criteria in Solid Tumors 1.1. Secondary endpoint: safety. Exploratory endpoint: the association between ARv7 splicing variants in basal circulating tumor cell (CTC)-enriched blood samples and treatment response/resistance using the AdnaTest ProstateCancerSelect kit and the AdnaTest ProstateCancer Panel AR-V7. Results: From March 2017 to January 2021, 68 patients were enrolled. One patient never started treatment. Median age: 72 years. A total of 52 patients (78%) received enzalutamide as a first line for mCRPC. The median follow-up was 32 months. At the 3-month assessment, 24 patients presented an SD, 1 patient achieved a CR, and 23 patients had a PR (3-mo-DCR of 72%). Discontinuations due to adverse events (AEs), disease-related death, or disease progression occurred in 9%, 6%, and 48% of patients. All patients reported at least one grade (G) 1–2 AE: the most common were fatigue (49%) and hypertension (33%). Six G3 AEs were reported: two hypertension, one seizure, one fatigue, one diarrhea, and one headache. Basal detection of ARv7 was significantly associated with poor treatment response (p = 0.034) and a nonsignificant association (p = 0.15) was observed between ARv7 detection and response assessments. At month 3, ARv7 was detected in 57%, 25%, and 15% of patients undergoing progressive disease, SD, and PR, respectively. Conclusion: The study met its primary endpoint, showing the efficacy of enzalutamide in men with mCRPC and measurable metastatic lesions in visceral and/or lymph node sites. Trial registration: ClinicalTrials.gov Identifier: NCT03103724. First Posted: 6 April 2017. First patient enrollment: 19 April 2017.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1758-8359Test

الوصول الحر: https://doaj.org/article/21ea7ba220ad4b319c9536d754e3134fTest

المؤلفون: Sepe, Pierangela, Procopio, Giuseppe, Pircher, Chiara Carlotta, Basso, Umberto, Caffo, Orazio, Cappelletti, Vera, Claps, Melanie, De Giorgi, Ugo, Fratino, Lucia, Guadalupi, Valentina, Miodini, Patrizia, De Marco, Cinzia, Perrucci, Bruno, Mennitto, Alessia, Santini, Daniele, Spina, Francesco, Stellato, Marco, de Braud, Filippo, Verzoni, Elena

المساهمون: Astellas Pharma

المصدر: Therapeutic Advances in Medical Oncology ; volume 16 ; ISSN 1758-8359 1758-8359

مصطلحات موضوعية: Oncology

الوصف: Background: Up to 30% of patients with metastatic castration-resistant prostate cancer (mCRPC) develop visceral metastases, which are associated with a poor prognosis. Objectives: Efficacy of enzalutamide in mCRPC patients with measurable metastases, including visceral and/or extra-regional lymph nodes. Methods: In this phase II multicenter study, patients with mCRPC and measurable metastases received enzalutamide as the first line. Primary endpoint: 3-month (mo) disease control rate (DCR) defined as the proportion of patients with complete (CR) or partial response (PR) or stable disease (SD) as per Response Evaluation Criteria in Solid Tumors 1.1. Secondary endpoint: safety. Exploratory endpoint: the association between ARv7 splicing variants in basal circulating tumor cell (CTC)-enriched blood samples and treatment response/resistance using the AdnaTest ProstateCancerSelect kit and the AdnaTest ProstateCancer Panel AR-V7. Results: From March 2017 to January 2021, 68 patients were enrolled. One patient never started treatment. Median age: 72 years. A total of 52 patients (78%) received enzalutamide as a first line for mCRPC. The median follow-up was 32 months. At the 3-month assessment, 24 patients presented an SD, 1 patient achieved a CR, and 23 patients had a PR (3-mo-DCR of 72%). Discontinuations due to adverse events (AEs), disease-related death, or disease progression occurred in 9%, 6%, and 48% of patients. All patients reported at least one grade (G) 1–2 AE: the most common were fatigue (49%) and hypertension (33%). Six G3 AEs were reported: two hypertension, one seizure, one fatigue, one diarrhea, and one headache. Basal detection of ARv7 was significantly associated with poor treatment response (p = 0.034) and a nonsignificant association (p = 0.15) was observed between ARv7 detection and response assessments. At month 3, ARv7 was detected in 57%, 25%, and 15% of patients undergoing progressive disease, SD, and PR, respectively. Conclusion: The study met its primary endpoint, showing the efficacy of ...

الإتاحة: https://doi.org/10.1177/17588359231217958Test

المؤلفون: Chiara Tommasi, Giulia Scartabellati, Diana Giannarelli, Ugo De Giorgi, Nicole Brighi, Giuseppe Fornarini, Sara Elena Rebuzzi, Silvia Puglisi, Orazio Caffo, Stefania Kinspergher, Alessia Mennitto, Carlo Cattrini, Matteo Santoni, Elena Verzoni, Alessandro Rametta, Marco Stellato, Andrea Malgeri, Giandomenico Roviello, Matteo Brunelli, Sebastiano Buti

المصدر: Therapeutic Advances in Urology, Vol 15 (2023)

مصطلحات موضوعية: Diseases of the genitourinary system. Urology, RC870-923

الوصف: Background: Tyrosine-kinase inhibitors (TKIs) and immunotherapy represent the backbone treatment for metastatic renal cell carcinoma (mRCC) patients. The aim of the present study was to describe mean corpuscular volume (MCV) and red cell distribution width (RDW) in mRCC patients treated with pazopanib or cabozantinib, and to explore their potential impact on oncological outcomes. Materials and methods: We conducted a multicenter retrospective observational study in mRCC patients treated with pazopanib or cabozantinib between January 2012 and December 2020 in nine Italian centers. Descriptive statistics, univariate, and multivariate analyses were performed. Objectives: The primary endpoints were the incidence and trend over time of anemia, macrocytosis (elevated MCV), and anisocytosis (elevated RDW). The secondary endpoints were the correlations of MCV and RDW with objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results: A total of 301 patients were enrolled; mean Hb value was 12.5 g/dl, a mean increase of 1 g/dl was observed at day 15 and maintained at 3 months. Most patients had baseline macrocytosis (MCV levels > 87 fl), with a significant mean increase after 3 months of treatment. At univariate analysis patients with macrocytosis had better ORR, longer PFS, and OS. About one third of patients had baseline anisocytosis (RDW > 16%), with a significant mean increase after 3 months of treatment. At univariate analysis, patients with RDW values ⩽ 16% had higher ORR, longer PFS, and OS. At multivariate analysis, baseline macrocytosis was significantly associated with better PFS in patients treated with pazopanib and baseline anisocytosis with shorter OS in all patients. Conclusions: mRCC patients treated with pazopanib or cabozantinib may have baseline macrocytosis and anisocytosis. A significant increase of Hb, MCV, and RDW after TKIs start was observed. Baseline macrocytosis is positively correlated with PFS in patients treated with pazopanib and baseline anisocytosis affects survival of patients treated with TKIs.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1756-2880Test

الوصول الحر: https://doaj.org/article/2c36da92decd496ba6b3b43f3902e571Test

المؤلفون: Maria Rescigno, Chiara Agrati, Carlo Salvarani, Diana Giannarelli, Massimo Costantini, Alberto Mantovani, Raffaella Massafra, Pier Luigi Zinzani, Aldo Morrone, Stefania Notari, Giulia Matusali, Giuseppe Lauria Pinter, Antonio Uccelli, Gennaro Ciliberto, Fausto Baldanti, Franco Locatelli, Nicola Silvestris, Valentina Sinno, Elena Turola, Maria Teresa Lupo-Stanghellini, Giovanni Apolone, the VAX4FRAIL study Group, Fabio Ciceri, Massimo Tommasino, Giuseppe Lauri Pinter, Paolo Corradini, Daniela Fenoglio, Roberta Mortarini, Laura Conti, Chiara Mandoj, Michela Lizier, Stefania Croci, Vito Garrisi, Fulvio Baggi, Tiziana Lazzarotto, Francesca Bonifazi, Concetta Quintarelli, Rita Carsetti, Enrico Girardi, Aurora Bettini, Veronica Bordoni, Concetta Castilletti, Eleonora Cimini, Rita Casetti, Francesca Colavita, Flavia Cristofanelli, Massimo Francalancia, Simona Gili, Delia Goletti, Giulia Gramigna, Germana Grassi, Daniele Lapa, Sara Leone, Davide Mariotti, Silvia Meschi, Enzo Puro, Marika Rubino, Alessandra Sacchi, Eleonora Tartaglia, Silvia Damian, Vincenzo Marasco, Filippo de Braud, Maria Teresa Lupo Stanghellini, Lorenzo Dagna, Francesca Ogliari, Massimo Filippi, Alessandro Bruno, Gloria Catalano, Rosamaria Nitti, Andrea Mengarelli, Francesco Marchesi, Giancarlo Paoletti e Gabriele Minuti, Elena Papa, Elena Azzolini, Luca Germagnoli, Carlo Selmi, Maria De Santis, Carmelo Carlo-Stella, Alexia Bertuzzi, Francesca Motta, Angela Ceribelli, Chiara Miggiano, Giulia Fornasa, Sara Monti, Carlo Maurizio Montecucco, Dario Graceffa, Maria Grazia Catanoso, Monica Guberti, Carmine Pinto, Francesco Merli, Franco Valzania, Rosa Divella, Antonio Tufaro, Sabina Delcuratolo, Mariana Miano, Carlo Antozzi, Silvia Bonanno Rita Frangiamore, Lorenzo Maggi, Paolo Pronzato, Matilde Inglese, Carlo Genova, Caterina Lapucci, Alice Laroni, Ilaria Poiré, Marco Fusconi, Vittorio Stefoni, Maria Abbondanza Pantaleo, Serena Di Cosimo, Iolanda Pulice, Roberta Mennitto Fondazione, Stefania Trinca, Giulia Piaggio, Chiara Pozzi, Irene Cassaniti, Alessandro Barberini, Rinaldi Elena, Federica Bortone, Maria Giovanna Dal Bello, Silvia Corazza

المصدر: Frontiers in Immunology, Vol 14 (2023)

مصطلحات موضوعية: SARS-CoV-2 mRNA vaccine, humoral response, T cell response, immunocompromised patients, Omicron neutralization, cross immunity, Immunologic diseases. Allergy, RC581-607

الوصف: IntroductionImmunocompromised patients have been shown to have an impaired immune response to COVID-19 vaccines.MethodsHere we compared the B-cell, T-cell and neutralizing antibody response to WT and Omicron BA.2 SARS-CoV-2 virus after the fourth dose of mRNA COVID-19 vaccines in patients with hematological malignancies (HM, n=71), solid tumors (ST, n=39) and immune-rheumatological (IR, n=25) diseases. The humoral and T-cell responses to SARS-CoV-2 vaccination were analyzed by quantifying the anti-RBD antibodies, their neutralization activity and the IFN-γ released after spike specific stimulation.ResultsWe show that the T-cell response is similarly boosted by the fourth dose across the different subgroups, while the antibody response is improved only in patients not receiving B-cell targeted therapies, independent on the pathology. However, 9% of patients with anti-RBD antibodies did not have neutralizing antibodies to either virus variants, while an additional 5.7% did not have neutralizing antibodies to Omicron BA.2, making these patients particularly vulnerable to SARS-CoV-2 infection. The increment of neutralizing antibodies was very similar towards Omicron BA.2 and WT virus after the third or fourth dose of vaccine, suggesting that there is no preferential skewing towards either virus variant with the booster dose. The only limited step is the amount of antibodies that are elicited after vaccination, thus increasing the probability of developing neutralizing antibodies to both variants of virus.DiscussionThese data support the recommendation of additional booster doses in frail patients to enhance the development of a B-cell response directed against Omicron and/or to enhance the T-cell response in patients treated with anti-CD20.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fimmu.2023.1104124/fullTest; https://doaj.org/toc/1664-3224Test

الوصول الحر: https://doaj.org/article/a00ef900915647aea19566921473db22Test

المؤلفون: Marco Stellato, Sebastiano Buti, Marco Maruzzo, Melissa Bersanelli, Francesco Pierantoni, Ugo De Giorgi, Marilena Di Napoli, Roberto Iacovelli, Maria Giuseppa Vitale, Paola Ermacora, Andrea Malgeri, Brigida Anna Maiorano, Veronica Prati, Alessia Mennitto, Alessia Cavo, Matteo Santoni, Claudia Carella, Lucia Fratino, Giuseppe Procopio, Elena Verzoni, Daniele Santini

المصدر: International Journal of Molecular Sciences; Volume 24; Issue 2; Pages: 1096

مصطلحات موضوعية: non-clear renal cell carcinoma, cromophobe renal cell carcinoma, papillary renal cell carcinoma, pembrolizumab, axitinib, renal cell carcinoma, combination

جغرافية الموضوع: agris

الوصف: Non-clear cell renal cell carcinoma (nccRCC) represents a heterogeneous histological group which is 20–25% of those with renal cell carcinoma (RCC). Patients with nccRCC have limited therapeutic options due to their exclusion from phase III randomized trials. The aim of the present study was to investigate the effectiveness and tolerability of pembrolizumabaxitinib combination in chromophobe and papillary metastatic RCC (mRCC) patients enrolled in the I-RARE (Italian Registry on rAre genitor-uRinary nEoplasms) observational ongoing study (Meet-URO 23). Baseline characteristics, objective response rate (ORR), disease control rate (DCR) and progression-free survival (PFS) and toxicities were retrospectively and prospectively collected from nccRCC patients treated in 14 Italian referral centers adhering to the Meet-Uro group, from December 2020 to April 2022. Only patients with chromophobe and papillary histology were considered eligible for the present pre-specified analysis. There were 32 eligible patients who received pembrolizumab-axitinib as first-line treatment, of whom 13 (40%) had chromophobe histology and 19 (60%) were classified as papillary RCC. The DCR was 78.1% whereas ORR was 43.7% (11 patients achieved stable disease and 14 patients obtained partial response: 9/19 papillary, 5/13 chromophobe). Six patients (18.7%) were primary refractory. Median PFS was 10.8 months (95%CI 1.7–11.5). Eleven patients (34.3%) interrupted the full treatment due to immune-related adverse events (irAEs): G3 hepatitis (n = 5), G3 hypophisitis (n = 1), G3 diarrhea (n = 1), G3 pancreatitis (n = 1), G3 asthenia (n = 1). Twelve patients (37.5%) temporarily interrupted axitinib only due to persistent G2 hand-foot syndrome or G2 hypertension. Pembrolizumab-axitinib combination could be an active and feasible first-line treatment option for patients with papillary or chromophobe mRCC.

وصف الملف: application/pdf

العلاقة: Molecular Pathology, Diagnostics, and Therapeutics; https://dx.doi.org/10.3390/ijms24021096Test

الإتاحة: https://doi.org/10.3390/ijms24021096Test

المؤلفون: Giulia Mazzaschi, Alessandro Lazzarin, Matteo Santoni, Francesca Trentini, Ugo De Giorgi, Nicole Brighi, Chiara Tommasi, Silvia Puglisi, Orazio Caffo, Stefania Kinspergher, Alessia Mennitto, Carlo Cattrini, Elena Verzoni, Alessandro Rametta, Marco Stellato, Andrea Malgeri, Giandomenico Roviello, Enrico Maria Silini, Pasquale Rescigno, Sara Elena Rebuzzi, Giuseppe Fornarini, Federico Quaini, Giulia Claire Giudice, Giuseppe Luigi Banna, Sebastiano Buti

المصدر: Frontiers in Bioscience-Elite, Vol 15, Iss 3, p 20 (2023)

مصطلحات موضوعية: metastatic renal cell carcinoma (mrcc), macrocytosis, anisocytosis, anemia, hif, tyrosine-kinase inhibitors, prognostic score, mcv, hb, rdw, Environmental sciences, GE1-350, Microbiology, QR1-502

الوصف: Background: The advent of immune checkpoint inhibitors (ICIs) has revolutionized the metastatic renal cell carcinoma (mRCC) therapeutic landscape. Nevertheless, tyrosine-kinase inhibitors (TKIs) targeting the vascular endothelial growth factor (VEGF) axis still play a key role. The aim of the present study was to explore the prognostic performance of an integrated blood score, based on hemoglobin (Hb) concentration, mean corpuscular volume (MCV), and red cell distribution width (RDW), in mRCC patients treated with anti-VEGF TKIs. The primary endpoint was to correlate Hb, MCV, and RDW with progression-free survival (PFS) and overall survival (OS). Materials and Methods: Our multicenter retrospective observational study involved mRCC patients treated with pazopanib or cabozantinib from January 2012 to December 2020 in nine Italian centers. Clinical records and laboratory data, including Hb levels, MCV, and RDW, were collected at baseline. Descriptive statistics and univariate and multivariate analyses were performed. Results: We enrolled 301 mRCC patients of which 179 (59%) underwent pazopanib, and 122 (41%) cabozantinib. We considered baseline Hb ≥12 g/dL, MCV >87 fL, and RDW ≤16% as good prognostic factors; hence, developing a multiparametric score capable of delineating 4 different categories. The number of good prognostic factors was associated with significantly longer PFS and OS (p < 0.001 for both). Therefore, we developed a red blood cell-based score by stratifying cases into two groups (2–3 versus 0–1, good factors). The impact on PFS and OS was even more striking (median PFS (mPFS): 16.3 vs 7.9 months; median OS (mOS): 33.7 vs 14.1 months)), regardless of the TKI agent. When challenged with univariate and multivariate analysis, the blood score maintained its high prognostic significance in terms of OS (multivariate analysis HR for OS: 0.53, 95% CI 0.39–0.75; p < 0.001, respectively), while the impact on PFS resulted in borderline significance. Conclusions: Our analyses demonstrate the prognostic ...

العلاقة: https://www.imrpress.com/journal/FBE/15/3/10.31083/j.fbe1503020Test; https://doaj.org/toc/1945-0494Test; https://doaj.org/article/922e18e923f6408ebcb291c324656551Test

الإتاحة: https://doi.org/10.31083/j.fbe1503020Test
https://doaj.org/article/922e18e923f6408ebcb291c324656551Test

المؤلفون: Cattrini, Carlo, Manfredi, Marcello, Barboro, Paola, Ghirimoldi, Marco, Mennitto, Alessia, Martini, Veronica, Battioni, Alessio, Le Van, Marco, Gobbato, Simone, Branni, Carmen, Ayed, Rahma Ben, Pinato, David James, Catalano, Fabio, Zanardi, Elisa, Boccardo, Francesco, Gennari, Alessandra

المساهمون: Onco-AGING Project funds – Department of Excellence – DIMET, University of Eastern Piedmont, 5X1000 and “Ricerca corrente” funds of IRCCS Ospedale Policlinico San Martino

المصدر: Scientific Reports ; volume 13, issue 1 ; ISSN 2045-2322

مصطلحات موضوعية: Multidisciplinary

الوصف: Emerging evidence highlights the potential prognostic relevance of circulating lipids in metastatic castration-resistant prostate cancer (mCRPC), with a proposed 3-lipid signature. This study aims to analyze the lipidomic profiles of individuals with mCRPC to identify lipid species that could serve as predictive indicators of prognosis and therapeutic response. Plasma samples were collected from mCRPC patients initiating first-line treatment (1 L) (n = 29) and those previously treated with at least two lines of therapy (> 2 L) (n = 19), including an androgen-receptor signaling inhibitor and a taxane. Employing an untargeted lipidomic approach, lipids were extracted from the plasma samples and subjected to analysis. A comprehensive identification and quantification of 789 plasma lipids was achieved. Notably, 75 species displayed significant dysregulation in > 2 L patients in comparison to the 1 L group. Among these, 63 species exhibited elevated levels, while 12 were reduced. Patients included in > 2 L cohort showed elevated levels of acylcarnitines (CAR), diacylglycerols (DG), phosphatidylethanolamines (PE), triacylglycerols (TG), and ceramides (Cer). Notably, some upregulated lipids, including CAR 14:0, CAR 24:1, Cer d18:1/16:0, Cer d18:1/18:0 (C18 Cer), Cer d18:2/18:0, Cer d18:1/24:1, and Cer d20:1/24:1, showed significant associations with overall survival (OS) in univariate models. Specifically, increased levels of C18 Cer remained significantly associated with poorer OS in the multivariate model, even after adjusting for treatment line and PSA levels (Hazard Ratio: 3.59 [95% Confidence Interval 1.51–8.52], p = 0.004). Employing quantitative mass spectrometry, our findings underscore the independent prognostic significance of C18 Cer in individuals with mCRPC. This discovery opens avenues for further studies within this field.

الإتاحة: https://doi.org/10.1038/s41598-023-44157-9Test
https://www.nature.com/articles/s41598-023-44157-9.pdfTest
https://www.nature.com/articles/s41598-023-44157-9Test

المؤلفون: Tommasi, Chiara, Scartabellati, Giulia, Giannarelli, Diana, Giorgi, Ugo De, Brighi, Nicole, Fornarini, Giuseppe, Rebuzzi, Sara Elena, Puglisi, Silvia, Caffo, Orazio, Kinspergher, Stefania, Mennitto, Alessia, Cattrini, Carlo, Santoni, Matteo, Verzoni, Elena, Rametta, Alessandro, Stellato, Marco, Malgeri, Andrea, Roviello, Giandomenico, Brunelli, Matteo, Buti, Sebastiano

المصدر: Therapeutic Advances in Urology ; volume 15 ; ISSN 1756-2872 1756-2880

مصطلحات موضوعية: Urology

الوصف: Background: Tyrosine-kinase inhibitors (TKIs) and immunotherapy represent the backbone treatment for metastatic renal cell carcinoma (mRCC) patients. The aim of the present study was to describe mean corpuscular volume (MCV) and red cell distribution width (RDW) in mRCC patients treated with pazopanib or cabozantinib, and to explore their potential impact on oncological outcomes. Materials and methods: We conducted a multicenter retrospective observational study in mRCC patients treated with pazopanib or cabozantinib between January 2012 and December 2020 in nine Italian centers. Descriptive statistics, univariate, and multivariate analyses were performed. Objectives: The primary endpoints were the incidence and trend over time of anemia, macrocytosis (elevated MCV), and anisocytosis (elevated RDW). The secondary endpoints were the correlations of MCV and RDW with objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results: A total of 301 patients were enrolled; mean Hb value was 12.5 g/dl, a mean increase of 1 g/dl was observed at day 15 and maintained at 3 months. Most patients had baseline macrocytosis (MCV levels > 87 fl), with a significant mean increase after 3 months of treatment. At univariate analysis patients with macrocytosis had better ORR, longer PFS, and OS. About one third of patients had baseline anisocytosis (RDW > 16%), with a significant mean increase after 3 months of treatment. At univariate analysis, patients with RDW values ⩽ 16% had higher ORR, longer PFS, and OS. At multivariate analysis, baseline macrocytosis was significantly associated with better PFS in patients treated with pazopanib and baseline anisocytosis with shorter OS in all patients. Conclusions: mRCC patients treated with pazopanib or cabozantinib may have baseline macrocytosis and anisocytosis. A significant increase of Hb, MCV, and RDW after TKIs start was observed. Baseline macrocytosis is positively correlated with PFS in patients treated with pazopanib and baseline ...

الإتاحة: https://doi.org/10.1177/17562872231187216Test