Publications by authors named "Francesca Ricci"

206 Publications

Design-Based Stereology of the Lung in the Hyperoxic Preterm Rabbit Model of Bronchopulmonary Dysplasia.

Oxid Med Cell Longev 2021 6;2021:4293279. Epub 2021 Oct 6.

Institute of Functional and Applied Anatomy, Hannover Medical School, 30625 Hannover, Germany.

Bronchopulmonary dysplasia (BPD) is a complex condition frequently occurring in preterm newborns, and different animal models are currently used to mimic the pathophysiology of BPD. The comparability of animal models depends on the availability of quantitative data obtained by minimally biased methods. Therefore, the aim of this study was to provide the first design-based stereological analysis of the lungs in the hyperoxia-based model of BPD in the preterm rabbit. Rabbit pups were obtained on gestation day 28 (three days before term) by cesarean section and exposed to normoxic (21% O, = 8) or hyperoxic (95% O, = 8) conditions. After seven days of exposure, lung function testing was performed, and lungs were taken for stereological analysis. In addition, the ratio between pulmonary arterial acceleration and ejection time (PAAT/PAET) was measured. Inspiratory capacity and static compliance were reduced whereas tissue elastance and resistance were increased in hyperoxic animals compared with normoxic controls. Hyperoxic animals showed signs of pulmonary hypertension indicated by the decreased PAAT/PAET ratio. In hyperoxic animals, the number of alveoli and the alveolar surface area were reduced by one-third or by approximately 50% of control values, respectively. However, neither the mean linear intercept length nor the mean alveolar volume was significantly different between both groups. Hyperoxic pups had thickened alveolar septa and intra-alveolar accumulation of edema fluid and inflammatory cells. Nonparenchymal blood vessels had thickened walls, enlarged perivascular space, and smaller lumen in hyperoxic rabbits in comparison with normoxic ones. In conclusion, the findings are in line with the pathological features of human BPD. The stereological data may serve as a reference to compare this model with BPD models in other species or future therapeutic interventions.
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http://dx.doi.org/10.1155/2021/4293279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8514964PMC
October 2021

A Specific Host/Microbial Signature of Plasma-Derived Extracellular Vesicles Is Associated to Thrombosis and Marrow Fibrosis in Polycythemia Vera.

Cancers (Basel) 2021 Oct 2;13(19). Epub 2021 Oct 2.

Istituto di Ematologia "Seràgnoli", IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy.

Polycythemia vera is a myeloproliferative neoplasm with increased risk of thrombosis and progression to myelofibrosis. However, no disease-specific risk factors have been identified so far. Circulating extracellular vesicles (EVs) are mostly of megakaryocyte (MK-EVs) and platelet (PLT-EVs) origin and, along with phosphatidylethanolamine (PE)-EVs, play a role in cancer and thrombosis. Interestingly, circulating microbial components/microbes have been recently indicated as potential modifiers of inflammation and coagulation. Here, we investigated phenotype and microbial DNA cargo of EVs after isolation from the plasma of 38 patients with polycythemia vera. Increased proportion of MK-EVs and reduced proportion of PLT-EVs identify patients with thrombosis history. Interestingly, EVs from patients with thrombosis history were depleted in DNA but enriched in DNA from Actinobacteria members as well as . In addition, patients with thrombosis history had also lower levels of lipopolysaccharide-associated EVs. In regard to fibrosis, along with increased proportion of PE-EVs, the EVs of patients with marrow fibrosis were enriched in DNA from and . Here, we identified a polycythemia-vera-specific host/microbial EV-based signature associated to thrombosis history and marrow fibrosis. These data may contribute to refining PV prognosis and to identifying novel druggable targets.
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http://dx.doi.org/10.3390/cancers13194968DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8507916PMC
October 2021

The Potential Role of Cardiac CT in the Evaluation of Patients With Known or Suspected Cardiomyopathy: From Traditional Indications to Novel Clinical Applications.

Front Cardiovasc Med 2021 14;8:709124. Epub 2021 Sep 14.

Centro Cardologico Monzino, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS), Milan, Italy.

After 15 years from its advent in the clinical field, coronary computed tomography (CCTA) is now widely considered as the best first-step test in patients with low-to-moderate pre-test probability of coronary artery disease. Technological innovation was of pivotal importance for the extensive clinical and scientific interest in CCTA. Recently, the advent of last generation wide-coverage CT scans paved the way for new clinical applications of this technique beyond coronary arteries anatomy evaluation. More precisely, both biventricular volume and systolic function quantification and myocardial fibrosis identification appeared to be feasible with last generation CT. In the present review we would focus on potential applications of cardiac computed tomography (CCT), beyond CCTA, for a comprehensive assessment patients with newly diagnosed cardiomyopathy, from technical requirements to novel clinical applications.
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http://dx.doi.org/10.3389/fcvm.2021.709124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8476802PMC
September 2021

Cardiac Magnetic Resonance Tissue Characterization in Ischemic Cardiomyopathy.

J Thorac Imaging 2021 Sep 15. Epub 2021 Sep 15.

Cardiological Center Monzino, IRCCS, Milano Division of Diagnostic Imaging, Department of Biomedicine and Prevention, Tor Vergata University of Rome and Unit of Diagnostic Imaging, Policlinico Tor Vergata, Rome, Italy Division of Cardiothoracic Imaging, Department of Radiology and Imaging Sciences, Emory University Hospital, Atlanta, GA Loyola University of Chicago, Chicago Edward Hines Jr. VA Hospital, Hines, IL.

Ischemic cardiomyopathy (ICM) is one of the most common causes of congestive heart failure. In patients with ICM, tissue characterization with cardiac magnetic resonance imaging (CMR) allows for evaluation of myocardial abnormalities in acute and chronic settings. Myocardial edema, microvascular obstruction (MVO), intracardiac thrombus, intramyocardial hemorrhage, and late gadolinium enhancement of the myocardium are easily depicted using standard CMR sequences. In the acute setting, tissue characterization is mainly focused on assessment of ventricular thrombus and MVO, which are associated with poor prognosis. Conversely, in chronic ICM, it is important to depict late gadolinium enhancement and myocardial ischemia using stress perfusion sequences. Overall, with CMR's ability to accurately characterize myocardial tissue in acute and chronic ICM, it represents a valuable diagnostic and prognostic imaging method for treatment planning. In particular, tissue characterization abnormalities in the acute setting can provide information regarding the patients that may develop major adverse cardiac event and show the presence of ventricular thrombus; in the chronic setting, evaluation of viable myocardium can be fundamental for planning myocardial revascularization. In this review, the main findings on tissue characterization are illustrated in acute and chronic settings using qualitative and quantitative tissue characterization.
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http://dx.doi.org/10.1097/RTI.0000000000000621DOI Listing
September 2021

Feasibility of late gadolinium enhancement (LGE) in ischemic cardiomyopathy using 2D-multisegment LGE combined with artificial intelligence reconstruction deep learning noise reduction algorithm.

Int J Cardiol 2021 Nov 10;343:164-170. Epub 2021 Sep 10.

Centro Cardiologico Monzino, IRCCS, Milan, Italy. Electronic address:

Background: Despite the low spatial resolution of 2D-multisegment late gadolinium enhancement (2D-MSLGE) sequences, it may be useful in uncooperative patients instead of standard 2D single segmented inversion recovery gradient echo late gadolinium enhancement sequences (2D-SSLGE). The aim of the study is to assess the feasibility and comparison of 2D-MSLGE reconstructed with artificial intelligence reconstruction deep learning noise reduction (NR) algorithm compared to standard 2D-SSLGE in consecutive patients with ischemic cardiomyopathy (ICM).

Methods: Fifty-seven patients with known ICM referred for a clinically indicated CMR were enrolled in this study. 2D-MSLGE were reconstructed using a growing level of NR (0%,25%,50%,75%and 100%). Subjective image quality, signal to noise ratio (SNR) and contrast to noise ratio (CNR) were evaluated in each dataset and compared to standard 2D-SSLGE. Moreover, diagnostic accuracy, LGE mass and scan time were compared between 2D-MSLGE with NR and 2D-SSLGE.

Results: The application of NR reconstruction ≥50% to 2D-MSLGE provided better subjective image quality, CNR and SNR compared to 2D-SSLGE (p < 0.01). The best compromise in terms of subjective and objective image quality was observed for values of 2D-MSLGE 75%, while no differences were found in terms of LGE quantification between 2D-MSLGE versus 2D-SSLGE, regardless the NR applied. The sensitivity, specificity, negative predictive value, positive predictive value and accuracy of 2D-MSLGE NR 75% were 87.77%,96.27%,96.13%,88.16% and 94.22%, respectively. Time of acquisition of 2D-MSLGE was significantly shorter compared to 2D-SSLGE (p < 0.01).

Conclusion: When compared to standard 2D-SSLGE, the application of NR reconstruction to 2D-MSLGE provides superior image quality with similar diagnostic accuracy.
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http://dx.doi.org/10.1016/j.ijcard.2021.09.012DOI Listing
November 2021

A Novel Processing-Free Method for RNAseq Analysis of Spontaneous Sputum in Chronic Obstructive Pulmonary Disease.

Front Pharmacol 2021 19;12:704969. Epub 2021 Aug 19.

Global Clinical Development, Personalised Medicine and Biomarkers, Chiesi, Parma, Italy.

Assessments of airways inflammation in patients with chronic obstructive pulmonary disease (COPD) require semi-invasive procedures and specialized sample processing know-how. In this study we aimed to set up and validate a novel non-invasive processing-free method for RNA sequencing (RNAseq) of spontaneous sputum samples collected from COPD patients. Spontaneous sputum samples were collected and stabilized, with or without selection of plugs and with or without the use of a stabilizer specifically formulated for downstream diagnostic testing (PrimeStore® Molecular Transport Medium). After 8 days storage at ambient temperature RNA was isolated according to an optimized RNAzol® method. An average percentage of fragments longer than 200 nucleotides (DV) >30% and an individual yield >50 ng were required for progression of samples to sequencing. Finally, to assess if the transcriptome generated would reflect a true endotype of COPD inflammation, the outcome of single-sample gene-set enrichment analysis (ssGSEA) was validated using an independent set of processed induced sputum samples. Results: RNA extracted from spontaneous sputum using a stabilizer showed an average DV higher than 30%. 70% of the samples had a yield >50 ng and were submitted to downstream analysis. There was a straightforward correlation in terms of gene expression between samples handled with or without separation of plugs. This was also confirmed by principal component analysis and ssGSEA. The top ten enriched pathways resulting from spontaneous sputum ssGSEA were associated to features of COPD, namely, inflammation, immune responses and oxidative stress; up to 70% of these were in common within the top ten enriched pathways resulting from induced sputum ssGSEA. This analysis confirmed that the typical COPD endotype was represented within spontaneous sputum and supported the current method as a non-invasive processing-free procedure to assess the level of sputum cell inflammation in COPD patients by RNAseq analysis.
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http://dx.doi.org/10.3389/fphar.2021.704969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417251PMC
August 2021

Dose-dense ABVD as first-line therapy in early-stage unfavorable Hodgkin lymphoma: results of a prospective, multicenter double-step phase II study by Fondazione Italiana Linfomi.

Ann Hematol 2021 Oct 30;100(10):2547-2556. Epub 2021 Jul 30.

Hematology Department, Azienda Unità Sanitaria Locale IRCCS Di Reggio Emilia, Reggio Emilia, Italy.

We investigated the feasibility and activity of an intensified dose-dense ABVD (dd-ABVD) regimen in patients with early-stage unfavorable Hodgkin lymphoma (HL). This prospective, multicenter, phase II study enrolled 96 patients with newly diagnosed, unfavorable stage I or II classical HL. The patients received four cycles of dd-ABVD followed by radiotherapy. Interim PET (PET-2) was mandatory after two courses. Primary endpoints were the evaluation of dd-ABVD feasibility and activity (incidence of PET-2 negativity). The feasibility endpoint was achieved with 48/52 (92.3%) patients receiving > 85% of the programmed dose. The mean dose intensity in the overall patient population (n = 96) was 93.7%, and the median duration of dd-ABVD was 85 days (range, 14-115) versus an expected duration of 84 days. PET-2 was available for 92/96 (95.8%) patients, of whom 79 were PET-2 negative (85.9%). In total, 90 (93.8%) patients showed complete response at the end of treatment. With a follow-up of 80.9 months (3.3-103.2), the median progression-free survival (PFS) and overall survival (OS) were not reached. At 84 months, PFS and OS rates were 88.4% and 95.7%, respectively. No evidence for a difference in PFS or OS was observed for PET-2-negative and PET-2-positive patients. Infections were documented in 8.3% and febrile neutropenia in 6.2% of cases. Four patients died: one had alveolitis at cycle 3, one death was unrelated to treatment, and two died from a secondary cancer. dd-ABVD is feasible and demonstrates activity in early-stage unfavorable HL. The predictive role of PET-2 positivity in early-stage unfavorable HL remains controversial. The study was registered in the EudraCT (reference number, 2011-003,191-36) and the ClinicalTrials.gov (reference number, NCT02247869) databases.
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http://dx.doi.org/10.1007/s00277-021-04604-xDOI Listing
October 2021

Dose-Adjusted Epoch and Rituximab for the treatment of double expressor and double hit diffuse large B-cell lymphoma: impact of TP53 mutations on clinical outcome.

Haematologica 2021 Jul 22. Epub 2021 Jul 22.

Department of Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano; Chair of Hematology University of Milano.

Diffuse Large B-Cell Lymphoma (DLBCL) is a heterogeneous disease, including one-third of cases overexpressing MYC and BCL2 proteins (Double Expressor Lymphoma, DEL) and 5-10% of patients with chromosomal rearrangements of MYC, BCL2 and/or BCL-6 (Double/Triple-Hit Lymphomas, DH/TH). TP53 mutations are detected in 20-25% of DEL. We report the efficacy of dose-adjusted EPOCH and rituximab (DA-EPOCH-R) in a series of 122 consecutive patients, including DEL (n=81, 66%), DEL-MYC (n=9, 7%), DEL-BCL2 (n=13, 11%), or High-Grade Lymphomas (DH/TH) (n=19, 16%). Central nervous system (CNS) prophylaxis included intravenous methotrexate (n=66), intrathecal chemotherapy (IT) (n=40) or no prophylaxis (n=16). Sixty-seven pts (55%) had high-intermediate or high International Prognostic Index (IPI) and 30 (25%) had high CNS-IPI. The 2-year progressionfree survival (PFS) and overall survival (OS) for the entire study population were 74% and 84%, respectively. There was a trend for inferior OS for DH/TH (2-year OS: 66%, p=0.058) as compared to all the others. The outcome was significantly better for the IPI 0-2 versus IPI 3-5 (OS: 98% vs. 72%, p=0.002). DA-EPOCH-R did not overcome the negative prognostic value of TP53 mutations: 2-year OS of 62% versus 88% (p=0.036) were observed for mutated as compared to wild-type cases, respectively. Systemic CNS prophylaxis conferred a better 2-year OS (94%) as compared to IT or no prophylaxis (76% and 65%, respectively; p= 0.008). DA-EPOCH-R treatment resulted in a favorable outcome in patients with DEL and DEL with single rearrangement, whereas those with multiple genetic alterations such as DEL-DH/TH and TP53 mutated cases still have an inferior outcome.
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http://dx.doi.org/10.3324/haematol.2021.278638DOI Listing
July 2021

Additional diagnostic value of cardiac magnetic resonance feature tracking in patients with biopsy-proven arrhythmogenic cardiomyopathy.

Int J Cardiol 2021 Sep 7;339:203-210. Epub 2021 Jul 7.

Centro Cardiologico Monzino, IRCCS, Milan, Italy. Electronic address:

Background: We aim to evaluate the value of Cardiac magnetic resonance (CMR) feature tracking (CMR-FT) in addition to Task Force Criteria(TFC) in patients with (arrhythmogenic cardiomyopathy) AC biopsy-proved.

Methods: Thirty-five patients with AC histologically proven who performed CMR with late gadolinium enhancement (LGE) acquisition were enrolled. The study population was divided in Group1 (negative CMR TFC and LV ejection fraction≥55%) and Group2 (positive CMR TFC and/or LVEF<55%) and compared to an age and gender-matched control group. CMR datasets of all patients were analyzed to calculate LV indexed end-diastolic (LVEDi) and end-systolic (LVESi) volumes and RV indexed end-diastolic (RVEDi) and end-systolic (RVESi) volumes, both LV ejection fraction (LVEF) and RV ejection fraction (RVEF). Moreover, LV and RV global longitudinal (GLS), circumferential (GCS) and radial (GRS) strain were measured.

Results: The AC patients showed both higher LVEDi (p:0.002) and RVEDi (p:0.017) and lower LVEF (p: 0.016) as compared to control patients. Moreover, AC patients showed impaired LV-GLS (p < 0.001), LV-GRS (p < 0.001), LV-GCS (p < 0.001) and RV-GRS (p:0.026) as compared to control subjects. Group1 patients showed a significant reduction of LV-GRS (p < 0.05) and LV-GCS p < 0.01) as compared to control subjects. At univariate analysis LV-GCS was the most discriminatory parameter between Group1 vs heathy subjects with an optimal cut-off of -15.8 (Sensitivity: 74%; Specificity: 10%).

Conclusions: In patients with AC biopsy-proven, CMR-FT could improve the diagnostic yield in the subset of patients who results negative for imaging TFC criteria resulting as useful gatekeeper for indication of myocardial biopsy in case of equivocal clinical and imaging presentation.
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http://dx.doi.org/10.1016/j.ijcard.2021.06.052DOI Listing
September 2021

An ultrasound protocol for temporomandibular joint in juvenile idiopathic arthritis: a pilot study.

Dentomaxillofac Radiol 2021 Jul 8:20200399. Epub 2021 Jul 8.

Orthodontics, Dental School, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy.

Objectives: As it is well known, the diagnosis of temporomandibular joint (TMJ) involvement in patients affected by Juvenile Idiopathic Arthritis (JIA) is important to avoid the impairment of mandibular growth. In this context, Magnetic Resonance Imaging (MRI) is the gold-standard for detection of TMJ involvement, however it is expensive and requires patients' collaboration. The aim of this study was to evaluate if ultrasound may be used as an alternative tool to investigate the acute signs of TMJ involvement in JIA patients.

Methods: Lateral periarticular space (LPAS) and joint effusion were evaluated by ultrasound in a study Group A of 8 JIA children (11.6±3.5 years old) with 14 TMJs involved, as confirmed by MRI, and in a control Group B of 7 healthy children (9.3±1.2 years old) without temporomandibular disorders (TMD). The LPAS width values were compared between the two groups using the Mann-Whitney test. The ultrasound images of the JIA group were then matched with the corresponding MR images; the Spearman Rank Correlation test and the Bland-Altman test were used to evaluate the differences.

Results: The LPAS values in Group A were statistically significantly higher than those in Group B ( < 0.001). There was no overlap of the LPAS values confidence intervals (CIs) between the two groups. No signs of joint effusion were identified in groups A and B. The Spearman test applied to the values of LPAS measured in ultrasound and the corresponding MR images showed a proportional positive correlation with a ρ of 0.623 and a < 0.05.

Conclusions: Ultrasound can detect differences in the TMJ features between JIA patients and healthy patients and it might be used as a follow-up tool in the assessment of TMJ involvement in subject affected by JIA.
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http://dx.doi.org/10.1259/dmfr.20200399DOI Listing
July 2021

Immune checkpoint inhibitors in combination with radiotherapy as salvage treatment for relapsed/refractory classical Hodgkin lymphoma: A retrospective analysis in 12 patients.

Hematol Rep 2021 Jun 9;13(2):9080. Epub 2021 Jun 9.

Department of Radiotherapy, Azienda Sanitaria Universitaria Giuliano-Isontina, Trieste.

The rate of complete remission (CR) with the anti-PD1 immune checkpoint inhibitors (ICI) nivolumab (N) and pembrolizumab (P) in patients with relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL) is low (20-30%), and the majority of patients eventually relapse. One strategy to improve their outcome is to combine ICI with radiotherapy (ICI-RT), taking advantage of a supposed synergistic effect. We retrospectively collected data of 12 adult patients with R/R cHL treated with ICI-RT delivered during or within 8 weeks from the start or after the end of ICI. Median age at ICI-RT was 37 years, 50% had previously received an autologous stem cell transplantation (SCT) and 92% brentuximab vedotin. RT was given concurrently, before or after ICI in 4, 1 and 7 patients. Median RT dose was 30Gy, for a median duration of 22 days. Median number of ICI administrations was 15. Overall response and CR rate were 100% and 58%. Nine patients received subsequent SCT consolidation (7 allogeneic and 2 autologous). After a median follow-up of 18 months, 92% of patients were in CR. No major concerns about safety were reported. ICI-RT combination appears to be a feasible and highly active bridge treatment to transplant consolidation.
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http://dx.doi.org/10.4081/hr.2021.9080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215529PMC
June 2021

Merkel Cell Carcinoma.

Biomedicines 2021 Jun 23;9(7). Epub 2021 Jun 23.

Dermatology Department, IDI-IRCCS, 00167 Rome, Italy.

Merkel cell carcinoma (MCC) is a rare and extremely aggressive neuroendocrine carcinoma of the skin, with increasing incidence worldwide. This review intends to propose a comprehensive evaluation of MCC epidemiology, clinical features, pathogenetic mechanisms, diagnosis, and therapies. A section is dedicated to immunological aspects and another to the involvement of angiogenesis and angiogenic growth factors in MCC progression, proposing novel diagnostic and therapeutic approaches. Advanced MCC tumors have been treated with immune checkpoint inhibitors with effective results. Therefore, the state of art of this immunotherapy is also examined, reporting on the most recent clinical trials in the field. We conclude by underlining the achievements in the understanding of MCC pathology and indicating the present needs for effective diagnosis and therapeutic management of the disease.
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http://dx.doi.org/10.3390/biomedicines9070718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301416PMC
June 2021

Methodological framework for radiomics applications in Hodgkin's lymphoma.

Eur J Hybrid Imaging 2020 Jun 1;4(1). Epub 2020 Jun 1.

Humanitas University, Via Rita Levi Montalcini 4, MI 20090, Pieve Emanuele, Italy.

Background: According to published data, radiomics features differ between lesions of refractory/relapsing HL patients from those of long-term responders. However, several methodological aspects have not been elucidated yet.

Purpose: The study aimed at setting up a methodological framework in radiomics applications in Hodgkin's lymphoma (HL), especially at (a) developing a novel feature selection approach, (b) evaluating radiomic intra-patient lesions' similarity, and (c) classifying relapsing refractory (R/R) vs non-(R/R) patients.

Methods: We retrospectively included 85 patients (male:female = 52:33; median age 35 years, range 19-74). LIFEx (www.lifexsoft.org) was used for [F]FDG-PET/CT segmentation and feature extraction. Features were a-priori selected if they were highly correlated or uncorrelated to the volume. Principal component analysis-transformed features were used to build the fingerprints that were tested to assess lesions' similarity, using the silhouette. For intra-patient similarity analysis, we used patients having multiple lesions only. To classify patients as non-R/R and R/R, the fingerprint considering one single lesion (fingerprint_One) and all lesions (fingerprint_All) was tested using Random Undersampling Boosting of Tree Ensemble (RUBTE).

Results: HL fingerprints included up to 15 features. Intra-patient lesion similarity analysis resulted in mean/median silhouette values below 0.5 (low similarity especially in the non-R/R group). In the test set, the fingerprint_One classification accuracy was 62% (78% sensitivity and 53% specificity); the classification by RUBTE using fingerprint_All resulted in 82% accuracy (70% sensitivity and 88% specificity).

Conclusions: Lesion similarity analysis was developed, and it allowed to demonstrate that HL lesions were not homogeneous within patients in terms of radiomics signature. Therefore, a random target lesion selection should not be adopted for radiomics applications. Moreover, the classifier to predict R/R vs non-R/R performed the best when all the lesions were used.
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http://dx.doi.org/10.1186/s41824-020-00078-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218114PMC
June 2020

Mitochondrial structural alterations in ovarian cancer patient-derived xenografts resistant to cisplatin.

Am J Cancer Res 2021 15;11(5):2303-2311. Epub 2021 May 15.

Laboratory of Molecular Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri-IRCCS Via Mario Negri 2, Milan 20156, Italy.

Mitochondria have attracted attention in cancer research as organelles associated with tumor development and response to therapy. We recently reported acquisition of resistance to cisplatin (DDP) associated with a metabolic rewiring in ovarian cancer patient-derived xenografts (PDXs) models. DDP-resistant PDXs models were obtained mimicking the clinical setting, treating mice bearing sensitive-DDP tumors with multiple cycles of DDP until the development of resistance. To further characterize the metabolic rewiring, the present study focused on tumor mitochondria. We analysed by transmission electron microscopy the mitochondria structure in two models of DDP-resistant and the corresponding DDP-sensitive PDXs and evaluated tumor mDNA content, the expression of genes and proteins involved in mitochondria functionality, and mitochondria fitness-related processes, such as autophagy. We observed a decrease in the number of mitochondria paralleled by an increased volume in DDP-resistant versus DDP-sensitive PDXs. DDP-resistant PDXs presented a higher percentage of damaged mitochondria, in particular of type 2 (concave-shape), and type 3 (cristolysis) damage. We found no difference in the mDNA content, and the expression of genes involved in mitochondrial biogenesis was similar between the sensitive and resistant PDXs. An upregulation of some genes involved in mitochondrial fitness in DDP-R versus DDP-S PDXs was observed. At protein level, no difference in the expression of proteins involved in mitochondrial function and biogenesis, and in autophagy/mitophagy was found. We here reported that the acquisition of DDP resistance is associated with morphological alterations in mitochondria, even if we couldn't find any dysregulation in the studied genes/proteins that could explain the observed differences.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167697PMC
May 2021

Sample preparation strategy for the detection of steroid-like compounds using MALDI mass spectrometry imaging: pulmonary distribution of budesonide as a case study.

Anal Bioanal Chem 2021 Jul 17;413(16):4363-4371. Epub 2021 May 17.

Preclinical R&D, Chiesi Farmaceutici, 43122, Parma, Italy.

Corticosteroids as budesonide can be effective in reducing topic inflammation processes in different organs. Therapeutic use of budesonide in respiratory diseases, like asthma, chronic obstructive pulmonary disease, and allergic rhinitis is well known. However, the pulmonary distribution of budesonide is not well understood, mainly due to the difficulties in tracing the molecule in lung samples without the addition of a label. In this paper, we present a matrix-assisted laser desorption/ionization mass spectrometry imaging protocol that can be used to visualize the pulmonary distribution of budesonide administered to a surfactant-depleted adult rabbit. Considering that budesonide is not easily ionized by MALDI, we developed an on-tissue derivatization method with Girard's reagent P followed by ferulic acid deposition as MALDI matrix. Interestingly, this sample preparation protocol results as a very effective strategy to raise the sensitivity towards not only budesonide but also other corticosteroids, allowing us to track its distribution and quantify the drug inside lung samples.
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http://dx.doi.org/10.1007/s00216-021-03393-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222037PMC
July 2021

Cutaneous Squamous Cell Carcinoma: From Pathophysiology to Novel Therapeutic Approaches.

Biomedicines 2021 Feb 9;9(2). Epub 2021 Feb 9.

IDI-IRCCS, Dermatological Research Hospital, via di Monti di Creta 104, 00167 Rome, Italy.

Cutaneous squamous cell carcinoma (cSCC), a non-melanoma skin cancer, is a keratinocyte carcinoma representing one of the most common cancers with an increasing incidence. cSCC could be in situ (e.g., Bowen's disease) or an invasive form. A significant cSCC risk factor is advanced age, together with cumulative sun exposure, fair skin, prolonged immunosuppression, and previous skin cancer diagnoses. Although most cSCCs can be treated by surgery, a fraction of them recur and metastasize, leading to death. cSCC could arise de novo or be the result of a progression of the actinic keratosis, an in situ carcinoma. The multistage process of cSCC development and progression is characterized by mutations in the genes involved in epidermal homeostasis and by several alterations, such as epigenetic modifications, viral infections, or microenvironmental changes. Thus, cSCC development is a gradual process with several histological- and pathological-defined stages. Dermoscopy and reflectance confocal microscopy enhanced the diagnostic accuracy of cSCC. Surgical excision is the first-line treatment for invasive cSCC. Moreover, radiotherapy may be considered as a primary treatment in patients not candidates for surgery. Extensive studies of cSCC pathogenic mechanisms identified several pharmaceutical targets and allowed the development of new systemic therapies, including immunotherapy with immune checkpoint inhibitors, such as Cemiplimab, and epidermal growth factor receptor inhibitors for metastatic and locally advanced cSCC. Furthermore, the implementation of prevention measures has been useful in patient management.
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http://dx.doi.org/10.3390/biomedicines9020171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916193PMC
February 2021

Involvement of miR-30a-5p and miR-30d in Endothelial to Mesenchymal Transition and Early Osteogenic Commitment under Inflammatory Stress in HUVEC.

Biomolecules 2021 02 5;11(2). Epub 2021 Feb 5.

Laboratory of Clinical Pathology, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), St. Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy.

The endothelial to mesenchymal transition (End-MT) can be associated with vascular calcification, by providing mesengenic progenitors. In this study, we investigated a link between End-MT and the osteogenic process and explored the involvement of miR-30a-5p and miR-30d as potential regulators of these processes. End-MT was induced in Human Umbilical Vein Endothelial Cells (HUVEC) through transforming growth factor-β1 (TGF-β1), TGFβ-3 and tumor necrosis factor-α (TNF-α), for 24 h and 6 days. End-MT mediators, mesenchymal and osteo/chondrogenic markers were analyzed through Real-Time PCR, immunofluorescence, flow cytometry and Western Blot. miR-30a-5p and miR-30d over-expression was carried out in HUVEC to explore their effects on End-MT and osteogenic differentiation. HUVEC at 24 h and 6 days gained mesenchymal morphology markers, including matrix metalloproteinase 9 (MMP-9), SLUG, VIMENTIN and α-smooth muscle actin (α-SMA), and a significant migratory potential, notably with TNF-α. After 6 days, the osteo/chondrogenic markers runt-related transcription factor 2 (RUNX-2) and SRY box transcription factor 9 (SOX-9) were upregulated. At this time point, miR-30a-5p and miR-30d decreased. Over-expression of miR-30a-5p and miR-30d affected End-MT mediators and the osteogenic potency in HUVEC, by reducing SLUG, VIMENTIN and RUNX-2. Our data suggest that End-MT represents a key link between inflammation and vascular calcification. Further, miR-30a-5p and miR-30d can regulate both the End-MT and the osteogenic processes, prompting future studies for exploring their potential use as therapeutic targets or biomarkers in vascular diseases.
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http://dx.doi.org/10.3390/biom11020226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915105PMC
February 2021

Surfactant lung delivery with LISA and InSurE in adult rabbits with respiratory distress.

Pediatr Res 2021 Sep 15;90(3):576-583. Epub 2021 Jan 15.

Neonatal Intensive Care Unit, "V. Buzzi" Children's Hospital, ASST-FBF-Sacco, Milan, Italy.

Background: In preterm infants, InSurE (Intubation-Surfactant-Extubation) and LISA (less invasive surfactant administration) techniques allow for exogenous surfactant administration while reducing lung injury associated with mechanical ventilation. We compared the acute pulmonary response and lung deposition of surfactant by LISA and InSurE in surfactant-depleted adult rabbits.

Methods: Twenty-six spontaneously breathing surfactant-depleted adult rabbits (6-7 weeks old) with moderate RDS and managed with nasal continuous positive airway pressure were randomized to 3 groups: (1) 200 mg/kg of surfactant by InSurE; (2) 200 mg/kg of surfactant by LISA; (3) no surfactant treatment (Control). Gas exchange and lung mechanics were monitored for 180 min. After that, surfactant lung deposition and distribution were evaluated monitoring disaturated-phosphatidylcholine (DSPC) and surfactant protein C (SP-C), respectively.

Results: No signs of recovery were found in the untreated animals. After InSurE, oxygenation improved more rapidly compared to LISA. However, at 180' LISA and InSurE showed comparable outcomes in terms of gas exchange, ventilation parameters, and lung mechanics. Neither DSPC in the alveolar pool nor SP-C signal distributions in a frontal lung section were significantly different between InSurE and LISA groups.

Conclusions: In an acute setting, LISA demonstrated efficacy and surfactant lung delivery similar to that of InSurE in surfactant-depleted adult rabbits.

Impact: Although LISA technique is gaining popularity, there are still several questions to address. This is the first study comparing LISA and InSurE in terms of gas exchange, ventilation parameters, and lung mechanics as well as surfactant deposition and distribution. In our animal study, three hours post-treatment, LISA method seems to be as effective as InSurE and showed similar surfactant lung delivery. Our findings provide some clarifications on a fair comparison between LISA and InSurE techniques, particularly in terms of surfactant delivery. They should reassure some of the concerns raised by the clinical community on LISA adoption in neonatal units.
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http://dx.doi.org/10.1038/s41390-020-01324-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809896PMC
September 2021

Establishment and Characterization of Patient-Derived Xenografts (PDXs) of Different Histology from Malignant Pleural Mesothelioma Patients.

Cancers (Basel) 2020 Dec 20;12(12). Epub 2020 Dec 20.

Thoracic Surgery and Lung Transplant Unit, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, 20122 Milan, Italy.

Background: Malignant pleural mesothelioma (MPM) is a very aggressive tumor originating from mesothelial cells. Although several etiological factors were reported to contribute to MPM onset, environmental exposure to asbestos is certainly a major risk factor. The latency between asbestos (or asbestos-like fibers) exposure and MPM onset is very long. MPM continues to be a tumor with poor prognosis despite the introduction of new therapies including immunotherapy. One of the major problems is the low number of preclinical models able to recapitulate the features of human tumors. This impacts the possible discovery of new treatments and combinations.

Methods: In this work, we aimed to generate patient-derived xenografts (PDXs) from MPM patients covering the three major histotypes (epithelioid, sarcomatoid, and mixed) occurring in the clinic. To do this, we obtained fresh tumors from biopsies or pleurectomies, and samples were subcutaneously implanted in immunodeficient mice within 24 h.

Results: We successfully isolated different PDXs and particularly concentrated our efforts on three covering the three histotypes. The tumors that grew in mice compared well histologically with the tumors of origin, and showed stable growth in mice and a low response to cisplatin, as was observed in the clinic.

Conclusions: These models are helpful in testing new drugs and combinations that, if successful, could rapidly translate to the clinical setting.
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http://dx.doi.org/10.3390/cancers12123846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766019PMC
December 2020

Nebulization of High-Dose Poractant Alfa in Newborn Piglets on Nasal Continuous Positive Airway Pressure Yields Therapeutic Lung Doses of Phospholipids.

Am J Perinatol 2020 Nov 26. Epub 2020 Nov 26.

Pediatric Anesthesia and Intensive Care, Skåne University Hospital, Lund, Sweden.

Objective:  It is not known how much surfactant must be nebulized to reach a lung dose of phospholipids equivalent to that obtained by the instillation of 200 mg/kg of surfactant. We aimed to assess the feasibility of nebulizing a high-dose of poractant alfa with the eFlow-Neos investigational vibrating-membrane nebulizer in newborn piglets on nasal continuous positive airway pressure (nCPAP) and to determine whether this intervention would yield therapeutic lung doses of phospholipids.

Study Design:  Twelve 1-day-old piglets on nCPAP received 600 mg/kg of poractant alfa admixed with technetium-99m via nebulization. Six piglets receiving 200 mg/kg of instilled synthetic surfactant served as controls. Lung deposition (percentage of the nominal dose) was determined by gamma scintigraphy, and the phospholipids' lung dose was calculated.

Results:  The lung dose of phospholipids (mean ± standard deviation [SD]) was 138 ± 96 mg/kg with nebulization, and 172 ± 24 mg/kg with instillation ( = 0.42). Nebulization took 58 ± 12 minutes. The arterial partial pressure of carbon dioxide increased from 6.7 ± 1.1 to 7.2 ± 1.1 kPa during nebulization ( = 0.04). Cerebral oximetry remained stable, and there was no hemodynamic instability.

Conclusion:  Nebulization was well tolerated, and the mean lung dose of phospholipids was above 100 mg/kg, that is, not different from the instillation group. These experimental findings suggest that it may be feasible to reach therapeutic lung doses of phospholipids by surfactant nebulization during nCPAP.

Key Points: · It is not known if effective lung doses of surfactant can be delivered by nebulization.. · Nebulization of high-dose surfactant in newborn piglets on nCPAP was well tolerated.. · A high-dose of nebulized poractant alfa yielded therapeutic lung doses of phospholipids..
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http://dx.doi.org/10.1055/s-0040-1721392DOI Listing
November 2020

Chest Computed Tomography Scoring in Patients With Novel Coronavirus-infected Pneumonia: Correlation With Clinical and Laboratory Features and Disease Outcome.

In Vivo 2020 Nov-Dec;34(6):3735-3746

Department of Biomedicine and Prevention, Division of Diagnostic Imaging, Tor Vergata University, and Unit of Diagnostic Imaging, Policlinico Tor Vergata, Rome, Italy.

Background/aim: This study investigated the correlation of chest computed tomography (CT), findings, graded using two different scoring methods, with clinical and laboratory features and disease outcome, including a novel clinical predictive score, in patients with novel coronavirus-infected pneumonia (NCIP).

Patients And Methods: In this retrospective, observational study, CT scan of 92 NCIP patients admitted to Policlinico Tor Vergata, were analyzed using a quantitative, computed-based and a semiquantitative, radiologist-assessed scoring system. Correlations of the two radiological scores with clinical and laboratory features, the CALL score, and their association with a composite adverse outcome were assessed.

Results: The two scores correlated significantly with each other (ρ=0.637, p<0.0001) and were independently associated with age, LDH, estimated glomerular filtration rate, diabetes, and with the composite outcome, which occurred in 24 patients.

Conclusion: In NCIP patients, two different radiological scores correlated with each other and with several clinical, laboratory features, and the CALL score. The quantitative score was a better independent predictor of the composite adverse outcome than the semiquantitative score.
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http://dx.doi.org/10.21873/invivo.12223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811662PMC
November 2020

Basal Cell Carcinoma: From Pathophysiology to Novel Therapeutic Approaches.

Biomedicines 2020 Oct 23;8(11). Epub 2020 Oct 23.

Istituto Dermopatico dell'Immacolata-IRCCS, via dei Monti di Creta 104, 00167 Rome, Italy.

Basal cell carcinoma (BCC) is the most common human cancer worldwide, and is a subtype of nonmelanoma skin cancer, characterized by a constantly increasing incidence due to an aging population and widespread sun exposure. Although the mortality from BCC is negligible, this tumor can be associated with significant morbidity and cost. This review presents a literature overview of BCC from pathophysiology to novel therapeutic approaches. Several histopathological BCC subtypes with different prognostic values have been described. Dermoscopy and, more recently, reflectance confocal microscopy have largely improved BCC diagnosis. Although surgery is the first-line treatment for localized BCC, other nonsurgical local treatment options are available. BCC pathogenesis depends on the interaction between environmental and genetic characteristics of the patient. Specifically, an aberrant activation of Hedgehog signaling pathway is implicated in its pathogenesis. Notably, Hedgehog signaling inhibitors, such as vismodegib and sonidegib, are successfully used as targeted treatment for advanced or metastatic BCC. Furthermore, the implementation of prevention measures has demonstrated to be useful in the patient management.
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http://dx.doi.org/10.3390/biomedicines8110449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690754PMC
October 2020

Eosinophilic annular erythema: Report of four cases.

Dermatol Ther 2020 11 16;33(6):e14369. Epub 2020 Oct 16.

Dermatology Department, Istituto Dermopatico dell'Immacolata-IRCCS, Rome, Italy.

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http://dx.doi.org/10.1111/dth.14369DOI Listing
November 2020

Functional chimeric genes in ciliates: An instructive case from Euplotes raikovi.

Gene 2021 Jan 28;767:145186. Epub 2020 Sep 28.

Laboratory of Eukaryotic Microbiology and Animal Biology, School of Biosciences and Veterinary Medicine, University of Camerino, Camerino 62032, Italy. Electronic address:

In ciliates, with every sexual event the transcriptionally active genes of the sub-chromosomic somatic genome that resides in the cell macronucleus are lost. They are de novo assembled starting from 'Macronuclear Destined Sequences' that arise from the fragmentation of transcriptionally silent DNA sequences of the germline chromosomic genome enclosed in the cell micronucleus. The RNA-mediated epigenetic mechanism that drives the assembly of these sequences is subject to errors which result in the formation of chimeric genes. Studying a gene family that in Euplotes raikovi controls the synthesis of protein signal pheromones responsible for a self/not-self recognition mechanism, we identified the chimeric structure of an 851-bp macronuclear gene previously known to specify soluble and membrane-bound pheromone molecules through an intron-splicing mechanism. This chimeric gene, designated mac-er-1*, conserved the native pheromone-gene structure throughout its coding and 3' regions. Instead, its 5' region is completely unrelated to the pheromone gene structure at the level of a 360-bp sequence, which derives from the assembly with a MDS destined to compound a 2417-bp gene encoding a 696-amino acid protein with unknown function. This mac-er-1* gene characterization provides further evidence that ciliates rely on functional chimeric genes that originate in non-programmed phenomena of somatic MDS recombination to increase the species genetic variability independently of gene reshuffling phenomena of the germline genome.
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http://dx.doi.org/10.1016/j.gene.2020.145186DOI Listing
January 2021

Ascending aorta pseudoaneurysm simulating mediastinal lymphoma in computed tomography, a possible diagnostic error: a case report.

J Med Case Rep 2020 Sep 25;14(1):167. Epub 2020 Sep 25.

Department of Diagnostic Imaging and Interventional Radiology, Policlinico Tor Vergata, Rome, Italy.

Background: An ascending aortic pseudoaneurysm is a severe and rare complication following cardiothoracic surgery. This case report demonstrates its possible misinterpretation and the consequent importance of multidisciplinary evaluation.

Case Presentation: We present a case of an 18-year-old Caucasian man with Marfan syndrome who developed an ascending aortic pseudoaneurysm about 1 year after undergoing cardiac surgery with the Bentall procedure. Computed tomographic examination of the thoracic aorta and positron emission tomography-computed tomography initially suggested a lymphomatous pathology. However, these imaging results were in contrast to the transesophageal echocardiogram and the laboratory data that showed negative results for hematological pathology. A second computed tomographic scan redirected the diagnosis toward a pseudoaneurysm.

Conclusion: This case demonstrates the utility of close communication and interdisciplinary consultation between cardiovascular radiologists and the cardiac surgery team, which are mandatory in order to maximize their diagnostic skills in identifying postoperative complications.
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http://dx.doi.org/10.1186/s13256-020-02465-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7517812PMC
September 2020

The role of circulating monocytes and JAK inhibition in the infectious-driven inflammatory response of myelofibrosis.

Oncoimmunology 2020 06 23;9(1):1782575. Epub 2020 Jun 23.

Department of Experimental, Institute of Hematology "L. E A. "Seràgnoli", Diagnostic and Specialty Medicine, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.

Myelofibrosis (MF) is characterized by chronic inflammation and hyper-activation of the JAK-STAT pathway. Infections are one of the main causes of morbidity/mortality. Therapy with Ruxolitinib (RUX), a JAK1/2 inhibitor, may further increase the infectious risk. Monocytes are critical players in inflammation/immunity through cytokine production and release of bioactive extracellular vesicles. However, the functional behavior of MF monocytes, particularly during RUX therapy, is still unclear. In this study, we found that monocytes from JAK2V617F-mutated MF patients show an altered expression of chemokine (CCR2, CXCR3, CCR5) and cytokine (TNF-α-R, IL10-R, IL1β-R, IL6-R) receptors. Furthermore, their ability to produce and secrete free and extracellular vesicles-linked cytokines (IL1β, TNF-α, IL6, IL10) under lipopolysaccharides (LPS) stimulation is severely impaired. Interestingly, monocytes from RUX-treated patients show normal level of chemokine, IL10, IL1β, and IL6 receptors together with a restored ability to produce intracellular and to secrete extracellular vesicles-linked cytokines after LPS stimulation. Conversely, RUX therapy does not normalize TNF-R1/2 receptors expression and the LPS-driven secretion of free pro/anti-inflammatory cytokines. Accordingly, upon LPS stimulation, RUX treatment of monocytes from MF patients increases their secretion of extracellular vesicles-linked cytokines but inhibits the secretion of free pro/anti-inflammatory cytokines. In conclusion, we demonstrated that in MF the infection-driven response of circulating monocytes is defective. Importantly, RUX promotes their infection-driven cytokine production suggesting that infections following RUX therapy may not be due to monocyte failure. These findings contribute to better interpreting the immune vulnerability of MF and to envisaging strategies to improve the infection-driven immune response.
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http://dx.doi.org/10.1080/2162402X.2020.1782575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458658PMC
June 2020

Impact of ERCC1, XPF and DNA Polymerase β Expression on Platinum Response in Patient-Derived Ovarian Cancer Xenografts.

Cancers (Basel) 2020 Aug 24;12(9). Epub 2020 Aug 24.

Laboratory of Molecular Pharmacology, Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, Italy.

Platinum resistance is an unmet medical need in ovarian carcinoma. Molecular biomarkers to predict the response to platinum-based therapy could allow patient stratification and alternative therapeutic strategies early in clinical management. Sensitivity and resistance to platinum therapy are partially determined by the tumor's intrinsic DNA repair activities, including nucleotide excision repair (NER) and base excision repair (BER). We investigated the role of the NER proteins-ERCC1, XPF, ERCC1/XPF complex-and of the BER protein DNA polymerase β, as possible biomarkers of cisplatin (DDP) response in a platform of recently established patient-derived ovarian carcinoma xenografts (OC-PDXs). ERCC1 and DNA polymerase β protein expressions were measured by immunohistochemistry, the ERCC1/XPF foci number was detected by proximity ligation assay (PLA) and their mRNA levels by real-time PCR. We then correlated the proteins, gene expression and ERCC1/XPF complexes with OC-PDXs' response to platinum. To the best of our knowledge, this is the first investigation of the role of the ERCC1/XPF complex, detected by PLA, in relation to the response to DDP in ovarian carcinoma. None of the proteins in the BER and NER pathways studied predicted platinum activity in this panel of OC-PDXs, nor did the ERCC1/XPF foci number. These results were partially explained by the experimental evidence that the ERCC1/XPF complex increases after DDP treatment and this possibly better associates with the cancer cells' abilities to activate the NER pathway to repair platinum-induced damage than its basal level. Our findings highlight the need for DNA functional assays to predict the response to platinum-based therapy.
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http://dx.doi.org/10.3390/cancers12092398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564949PMC
August 2020

Association of plaque calcification pattern and attenuation with instability features and coronary stenosis and calcification grade.

Atherosclerosis 2020 10 6;311:150-157. Epub 2020 Jul 6.

Department of Biomedicine and Prevention, Division of Diagnostic Imaging, Tor Vergata University of Rome and Unit of Diagnostic Imaging, Policlinico Tor Vergata, Viale Oxford, 81, 00133, Rome, Italy.

Background And Aims: Coronary computed tomography (CT) allows calculating coronary artery calcium score (CACS). However, other CT features might be more strongly related to plaque vulnerability and risk of future coronary events. This study investigated the association of plaque calcification pattern and attenuation with plaque instability features, coronary artery disease (CAD) grade and CACS.

Methods: One-hundred patients with coronary stenosis associated with calcified plaques were considered for this analysis. CACS, CAD grade, calcification pattern and attenuation, features of plaque instability, and epicardial adipose tissue (EAT) thickness and attenuation were assessed with non-contrast and contrast-enhanced CT angiography.

Results: Of 373 calcified plaques, 131 were responsible for the highest degree of coronary stenosis (1.31 ± 0.53 per patient). Participants were stratified according to the features of the highest-grade lesion(s) into patients with large (35%), spotty (52%) or mixed (13%) calcification pattern and tertiles of plaque calcification attenuation (using the mean value for multiple lesions). Patients with large calcification pattern or higher plaque calcification attenuation had higher stenosis and CACS grade (and EAT attenuation), but lower plaque instability score, whereas those with spotty calcification pattern or lower plaque calcification attenuation had lower stenosis and CACS grade (and EAT attenuation), but higher plaque instability score. Among the instability features, low attenuation and napkin-ring sign, but not positive remodeling, were associated with a spotty pattern and a lower calcification attenuation.

Conclusions: Both the pattern and attenuation of calcification should be considered, in addition to CACS, for risk stratification of heavily calcified high-risk patients with non-critical coronary stenosis.
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http://dx.doi.org/10.1016/j.atherosclerosis.2020.06.021DOI Listing
October 2020

Sequential Strategy Including FFR Plus Stress-CTP Impacts on Management of Patients with Stable Chest Pain: The Stress-CTP RIPCORD Study.

J Clin Med 2020 Jul 8;9(7). Epub 2020 Jul 8.

Department of Diagnostic Imaging, Humanitas Research Hospital, Rozzano, 20089 Milan, Italy.

Stress computed tomography perfusion (Stress-CTP) and computed tomography-derived fractional flow reserve (FFR) are functional techniques that can be added to coronary computed tomography angiography (cCTA) to improve the management of patients with suspected coronary artery disease (CAD). This retrospective analysis from the PERFECTION study aims to assess the impact of their availability on the management of patients with suspected CAD scheduled for invasive coronary angiography (ICA) and invasive FFR. The management plan was defined as optimal medical therapy (OMT) or revascularization and was recorded for the following strategies: cCTA alone, cCTA+FFR, cCTA+Stress-CTP and cCTA+FFR+Stress-CTP. In 291 prospectively enrolled patients, cCTA+FFR, cCTA+Stress-CTP and cCTA+FFR+Stress-CTP showed a similar rate of reclassification of cCTA findings when FFR and Stress-CTP were added to cCTA. cCTA, cCTA+FFR, cCTA+Stress-CTP and cCTA+FFR+Stress-CTP showed a rate of agreement versus the final therapeutic decision of 63%, 71%, 89%, 84% (cCTA+Stress-CTP and cCTA+FFR+Stress-CTP vs cCTA and cCTA+FFR: < 0.01), respectively, and a rate of agreement in terms of the vessels to be revascularized of 57%, 64%, 74%, 71% (cCTA+Stress-CTP and cCTA+FFR+Stress-CTP vs cCTA and cCTA+FFR: < 0.01), respectively, with an effective radiation dose (ED) of 2.9 ± 1.3 mSv, 2.9 ± 1.3 mSv, 5.9 ± 2.7 mSv, and 3.1 ± 2.1 mSv. The addition of FFR and Stress-CTP improved therapeutic decision-making compared to cCTA alone, and a sequential strategy with cCTA+FFR+Stress-CTP represents the best compromise in terms of clinical impact and radiation exposure.
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http://dx.doi.org/10.3390/jcm9072147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408909PMC
July 2020
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