Publications by authors named "Luca Russo"

80 Publications

CT-Based Radiomics and Deep Learning for BRCA Mutation and Progression-Free Survival Prediction in Ovarian Cancer Using a Multicentric Dataset.

Cancers (Basel) 2022 May 31;14(11). Epub 2022 May 31.

Department of Bioimaging, Radiation Oncology and Hematology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy.

Purpose: Build predictive radiomic models for early relapse and BRCA mutation based on a multicentric database of high-grade serous ovarian cancer (HGSOC) and validate them in a test set coming from different institutions.

Methods: Preoperative CTs of patients with HGSOC treated at four referral centers were retrospectively acquired and manually segmented. Hand-crafted features and deep radiomics features were extracted respectively by dedicated software (MODDICOM) and a dedicated convolutional neural network (CNN). Features were selected with and without prior harmonization (ComBat harmonization), and models were built using different machine learning algorithms, including clinical variables.

Results: We included 218 patients. Radiomic models showed low performance in predicting both BRCA mutation (AUC in test set between 0.46 and 0.59) and 1-year relapse (AUC in test set between 0.46 and 0.56); deep learning models demonstrated similar results (AUC in the test of 0.48 for BRCA and 0.50 for relapse). The inclusion of clinical variables improved the performance of the radiomic models to predict BRCA mutation (AUC in the test set of 0.74).

Conclusions: In our multicentric dataset, representative of a real-life clinical scenario, we could not find a good radiomic predicting model for PFS and BRCA mutational status, with both traditional radiomics and deep learning, but the combination of clinical and radiomic models improved model performance for the prediction of BRCA mutation. These findings highlight the need for standardization through the whole radiomic pipelines and robust multicentric external validations of results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers14112739DOI Listing
May 2022

Detection of parametrial invasion in women with uterine cervical cancer using diffusion tensor imaging at 1.5T MRI.

Diagn Interv Imaging 2022 May 28. Epub 2022 May 28.

Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, UOC, di Radiologia, Fondazione Policlinico Universitario A. Gemelli IRCSS, Largo A. Gemelli, 8, 00168 Rome, Italy; Istituto di Radiologia, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Rome, Italy.

Purpose: The purpose of this study was to prospectively evaluate the capability of diffusion tensor imaging (DTI) of the lumbosacral plexus to identify parametrial invasion by uterine cervical cancer.

Materials And Methods: Twenty-seven women with biopsy-proven cervical cancer were prospectively enrolled and underwent DTI at 1.5 TMRI. Fractional anisotropy (FA) values were calculated at the level of right and left L5 and S1 roots. The two sides of each patient were considered independently in two groups, according to the presence or absence of parametrial invasion. Differences between FA values of invaded parametria and those of non-invaded parametria were searched using Student t-test. Receiver operating characteristic (ROC) analysis was performed to identify the cut-off value of FA that yielded best sensitivity, specificity and accuracy for the diagnosis of parametrial invasion.

Results: A total of 54 parametria in 27 participants (mean age, 52.9 ± 12 years; age range, 30-81 years) were analyzed. Invasion was present in 37/54 (68%) parametria and absent in 17/54 (31%) parametria. FA was greater in parametrial invasion (mean, 0.321 ± 0.036; range: 0.285-0.357) than in the absence of parametrial invasion (0.292 ± 0.02; range: 0.272-0.312) (P = 0.01). At ROC analysis, best cut-off value of FA for the diagnosis of parametrial invasion was >0.3099 (AUC, 0.681; 95% CI: 0.583- 0.768), yielding 62% sensitivity (95% CI: 50.3-73.64), 73% specificity (95% CI: 50.6-85.27) and 66% accuracy (95% CI: 54.62-73.91).

Conclusion: Using >0.3099 as cut off-value for FA of L5-S1 roots, DTI has an accuracy of 73% in the diagnosis of parametrial invasion by uterine cervical cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.diii.2022.05.005DOI Listing
May 2022

MRI in uterine cancers with uncertain origin: Endometrial or cervical? Radiological point of view with review of the literature.

Eur J Radiol 2022 Aug 13;153:110357. Epub 2022 May 13.

Dipartimento Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; Università Cattolica del Sacro Cuore, Dipartimento Universitario di Scienze Radiologiche ed Ematologiche, Rome, Italy.

Therapeutic options and clinical management of cervical and endometrial cancers differs significantly. When clinical and histological analysis of a uterine mass are unable to differentiate between an endocervical or endometrial origin, magnetic resonance imaging (MRI) plays a pivotal role in discriminating the anatomical origin, supporting the clinician in the treatment planning. Cervical adenocarcinomas are more likely to be centered in the cervical region and involving both cervical canal and stromal ring, with possible parametrial invasion. Endometrial adenocarcinomas usually present an elongated morphology and are centered in the endometrial cavity predominantly involving endometrium and myometrium. On contrast-enhanced sequences, cervical cancers are more frequently hypervascular compared to endometrial cancers. In cases of uncertain findings, diffusion-weighted imaging (DWI) can provide additional helpful information with significantly higher apparent coefficient diffusion (ADC) values in cervical adenocarcinomas compared to endometrial adenocarcinomas. However, even when MRI cannot precisely reveal the origin of the tumor, it provides valuable information on several prognostic factors that can help treatment planning.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejrad.2022.110357DOI Listing
August 2022

Radiomics-based prediction of two-year clinical outcome in locally advanced cervical cancer patients undergoing neoadjuvant chemoradiotherapy.

Radiol Med 2022 May 24;127(5):498-506. Epub 2022 Mar 24.

Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, 00168, Roma, Italy.

Purpose: The aim of this study is to determine if radiomics features extracted from staging magnetic resonance (MR) images could predict 2-year long-term clinical outcome in patients with locally advanced cervical cancer (LACC) after neoadjuvant chemoradiotherapy (NACRT).

Materials And Methods: We retrospectively enrolled patients with LACC diagnosis who underwent NACRT followed by radical surgery in two different institutions. Radiomics features were extracted from pre-treatment 1.5 T T2w MR images. The predictive performance of each feature was quantified in terms of Wilcoxon-Mann-Whitney test. Among the significant features, Pearson correlation coefficient (PCC) was calculated to quantify the correlation among the different predictors. A logistic regression model was calculated considering the two most significant features at the univariate analysis showing the lowest PCC value. The predictive performance of the model created was quantified out using the area under the receiver operating characteristic curve (AUC).

Results: A total of 175 patients were retrospectively enrolled (142 for the training cohort and 33 for the validation one). 1896 radiomic feature were extracted, 91 of which showed significance (p < 0.05) at the univariate analysis. The radiomic model showing the highest predictive value combined the features calculated starting from the gray level co-occurrence-based features. This model achieved an AUC of 0.73 in the training set and 0.91 in the validation set.

Conclusions: The proposed radiomic model showed promising performances in predicting 2-year overall survival before NACRT. Nevertheless, the observed results should be tested in larger studies with consistent external validation cohorts, to confirm their potential clinical use.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11547-022-01482-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9098600PMC
May 2022

Biochemical and biophysical features of disease-associated tau mutants V363A and V363I.

Biochim Biophys Acta Proteins Proteom 2022 03 5;1870(3):140755. Epub 2022 Jan 5.

Department of Molecular Biochemistry and Pharmacology, Mario Negri Institute of Pharmacological Research IRCCS, Milano, Italy. Electronic address:

The comprehension of pathogenetic mechanisms in tauopathy-associated neurodegenerative diseases can be improved by the knowledge of the biochemical and biophysical features of mutated tau proteins. Here, we used the full-length, wild-type tau, the V363A and V363I mutated species, associated with pathology, and the P301L mutated tau as a benchmark. Using several techniques, including small-angle X-ray scattering, atomic force microscopy, thioflavin T binding, and electrophoretic separation, we compared their course from intrinsically disordered monomers in solution to early-stage recruitment in complexes and then aggregates of increasing size over long periods up to the asymptotic aggregative behavior of full-length tau proteins. We showed that diversity in the kinetics of recruitment and aggregate structure occurs from the beginning and spreads all over their pathway to very large objects. The different extents of conformational changes and types of molecular assemblies among the proteins were also reflected in their in vitro toxicity; this variation could correlate with physiopathology in humans, considering that the P301L mutation is more aggressive than V363A, especially V363I. This study identified the presence of aggregation intermediates and corroborated the oligomeric hypothesis of tauopathies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbapap.2022.140755DOI Listing
March 2022

Validation analysis of the novel imaging-based prognostic radiomic signature in patients undergoing primary surgery for advanced high-grade serous ovarian cancer (HGSOC).

Br J Cancer 2022 04 18;126(7):1047-1054. Epub 2021 Dec 18.

Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte, Henricistr.92, 45136, Essen, Germany.

Background: Predictive models based on radiomics features are novel, highly promising approaches for gynaecological oncology. Here, we wish to assess the prognostic value of the newly discovered Radiomic Prognostic Vector (RPV) in an independent cohort of high-grade serous ovarian cancer (HGSOC) patients, treated within a Centre of Excellence, thus avoiding any bias in treatment quality.

Methods: RPV was calculated using standardised algorithms following segmentation of routine preoperative imaging of patients (n = 323) who underwent upfront debulking surgery (01/2011-07/2018). RPV was correlated with operability, survival and adjusted for well-established prognostic factors (age, postoperative residual disease, stage), and compared to previous validation models.

Results: The distribution of low, medium and high RPV scores was 54.2% (n = 175), 33.4% (n = 108) and 12.4% (n = 40) across the cohort, respectively. High RPV scores independently associated with significantly worse progression-free survival (PFS) (HR = 1.69; 95% CI:1.06-2.71; P = 0.038), even after adjusting for stage, age, performance status and residual disease. Moreover, lower RPV was significantly associated with total macroscopic tumour clearance (OR = 2.02; 95% CI:1.56-2.62; P = 0.00647).

Conclusions: RPV was validated to independently identify those HGSOC patients who will not be operated tumour-free in an optimal setting, and those who will relapse early despite complete tumour clearance upfront. Further prospective, multicentre trials with a translational aspect are warranted for the incorporation of this radiomics approach into clinical routine.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41416-021-01662-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8979975PMC
April 2022

MRI Staging in Locally Advanced Vulvar Cancer: From Anatomy to Clinico-Radiological Findings. A Multidisciplinary VulCan Team Point of View.

J Pers Med 2021 Nov 18;11(11). Epub 2021 Nov 18.

Area Diagnostica per Immagini, Dipartimento Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.

MR imaging provides excellent spatial and contrast resolution to stage locally advanced vulvar cancer (LAVC) for tumor and nodal evaluation in order to facilitate the planning of treatment. Although there are no standard indications for how to estimate the clinical stage of International Federation of Gynecology and Obstetrics at diagnosis, MR imaging can depict the tumor and its extension to the vulvar region and adjacent organs, such as the vagina, urethra, and anus. Optimizing the MR imaging protocol and technique is fundamental for correct staging. The aim of this overview was to focus on the role of MR imaging in LAVC staging. We define vulvar anatomy and corresponding MR imaging findings, MR imaging protocol, and technique. Moreover, we describe the MR imaging findings of LAVC with example cases stage by stage. Key imaging findings based on signal intensity, diffusion restriction, and enhancement are portrayed to correctly identify and stage vulvar cancer. A structured report for LAVC staging is reported in order to give all necessary information to the clinicians and to facilitate MR imaging comprehension.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jpm11111219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8624255PMC
November 2021

Immunization With Bovine Herpesvirus-4-Based Vector Delivering PPRV-H Protein Protects Sheep From PPRV Challenge.

Front Immunol 2021 14;12:705539. Epub 2021 Sep 14.

Centro de Investigación en Sanidad Animal (CISA-INIA), Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Consejo Superior de Investigaciones Científicas (CSIC), Valdeolmos, Spain.

The peste des petits ruminants virus (PPRV) is the causal agent of a highly contagious disease that mostly affects sheep and goats and produces considerable losses in developing countries. Current PPRV control strategies rely on live-attenuated vaccines, which are not ideal, as they cannot differentiate infected from vaccinated animals (DIVA). Recombinant vector-based vaccines expressing viral subunits can provide an alternative to conventional vaccines, as they can be easily paired with DIVA diagnostic tools. In the present work, we used the bovine herpesvirus-4-based vector (BoHV-4-A) to deliver PPRV hemagglutinin H antigen (BoHV-4-A-PPRV-H-ΔTK). Vaccination with BoHV-4-A-PPRV-H-ΔTK protected sheep from virulent PPRV challenge and prevented virus shedding. Protection correlated with anti-PPRV IgGs, neutralizing antibodies and IFN-γ-producing cells induced by the vaccine. Detection of antibodies exclusively against H-PPRV in animal sera and not against other PPRV viral proteins such as F or N could serve as a DIVA diagnostic test when using BoHV-4-A-PPRV-H-ΔTK as vaccine. Our data indicate that BoHV-4-A-PPRV-H-ΔTK could be a promising new approach for PPRV eradication programs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2021.705539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8476865PMC
December 2021

Birds seen and not seen during the COVID-19 pandemic: The impact of lockdown measures on citizen science bird observations.

Biol Conserv 2021 Apr 27;256:109079. Epub 2021 Mar 27.

Biological Station of Doñana-CSIC, c/Américo Vespucio 26, E-41092 Sevilla, Spain.

In early 2020, the rapid spread of the novel coronavirus disease 2019 (COVID-19) led multiple countries to introduce strict lockdown measures to contain the pandemic. Movement restrictions may have influenced the ability of the public to contribute to citizen science projects. We investigated how stay-at-home orders affected data submitted by birdwatchers in Italy, Spain and the United Kingdom (UK) to a widely-used citizen science platform, iNaturalist, depending on whether observations were collected in urban or non-urban areas. We found significant trends in the daily number of observations in all three countries, indicating a surge in urban observation during lockdowns. We found an increase in the mean daily number of urban observations during the lockdown in Italy and Spain, compared to previous years. The mean daily number of non-urban observations decreased in Italy and Spain, while remained similar to previous years in the UK. We found a general decrease of new records during the lockdowns both in urban and non-urban areas in all countries. Our results suggest that the citizen science community remained active during the lockdowns and kept reporting birds from home. However, limitations to movements may have hampered the possibility of birdwatchers to explore natural areas and collect new records. Our findings suggest that future research and conservation applications of citizen science data should carefully consider the bias and gaps in data series caused by the pandemic. Furthermore, our study highlights the potential of urban areas for nature activities, such as birdwatching, and its relevance for sustainable urban planning.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biocon.2021.109079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8457629PMC
April 2021

Doxycycline Inhibition of a Pseudotyped Virus Transduction Does Not Translate to Inhibition of SARS-CoV-2 Infectivity.

Viruses 2021 09 1;13(9). Epub 2021 Sep 1.

Department of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milano, Italy.

The rapid spread of the pandemic caused by the SARS-CoV-2 virus has created an unusual situation, with rapid searches for compounds to interfere with the biological processes exploited by the virus. Doxycycline, with its pleiotropic effects, including anti-viral activity, has been proposed as a therapeutic candidate for COVID-19 and about twenty clinical trials have started since the beginning of the pandemic. To gain information on the activity of doxycycline against SARS-CoV-2 infection and clarify some of the conflicting clinical data published, we designed in vitro binding tests and infection studies with a pseudotyped virus expressing the spike protein, as well as a clinically isolated SARS-CoV-2 strain. Doxycycline inhibited the transduction of the pseudotyped virus in Vero E6 and HEK-293 T cells stably expressing human receptor angiotensin-converting enzyme 2 but did not affect the entry and replication of SARS-CoV-2. Although this conclusion is apparently disappointing, it is paradigmatic of an experimental approach aimed at developing an integrated multidisciplinary platform which can shed light on the mechanisms of action of potential anti-COVID-19 compounds. To avoid wasting precious time and resources, we believe very stringent experimental criteria are needed in the preclinical phase, including infectivity studies with clinically isolated SARS-CoV-2, before moving on to (futile) clinical trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/v13091745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8473150PMC
September 2021

Super-resolution study of PIAS SUMO E3-ligases in hippocampal and cortical neurons.

Eur J Histochem 2021 Aug 11;65(s1). Epub 2021 Aug 11.

mario negri institute.

The SUMOylation machinery is a regulator of neuronal activity and synaptic plasticity. It is composed of SUMO isoforms and specialized enzymes named E1, E2 and E3 SUMO ligases. Recent studies have highlighted how SUMO isoforms and E2 enzymes localize with synaptic markers to support previous functional studies but less information is available on E3 ligases. PIAS proteins - belonging to the protein inhibitor of activated STAT (PIAS) SUMO E3-ligase family - are the best-characterized SUMO E3-ligases and have been linked to the formation of spatial memory in rodents. Whether however they exert their function co-localizing with synaptic markers is still unclear. In this study, we applied for the first time structured illumination microscopy (SIM) to PIAS ligases to investigate the co-localization of PIAS1 and PIAS3 with synaptic markers in hippocampal and cortical murine neurons. The results indicate partial co-localization of PIAS1 and PIAS3 with synaptic markers in hippocampal neurons and much rarer occurrence in cortical neurons. This is in line with previous super-resolution reports describing the co-localization with synaptic markers of other components of the SUMOylation machinery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4081/ejh.2021.3241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419632PMC
August 2021

Letter to Editor about 'Kiss goodbye to the "kissing knees": no association between frontal plane inward knee motion and risk of future non-contact ACL injury in elite female athletes'.

Sports Biomech 2021 Aug 29:1-3. Epub 2021 Aug 29.

Department of Musculoskeletal Disorders, Faculty of Medicine and Surgery, University of Salerno, Salerno, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14763141.2021.1968024DOI Listing
August 2021

Persistency of Mesenchymal Stromal/Stem Cells in Lungs.

Front Cell Dev Biol 2021 16;9:709225. Epub 2021 Jul 16.

Department of Veterinary Science, University of Parma, Parma, Italy.

Mesenchymal stromal/stem cells (MSCs) are a fibroblast-like cell population with high regenerative potential that can be isolated from many different tissues. Several data suggest MSCs as a therapeutic tool capable of migrating to a site of injury and guide tissue regeneration mainly through their secretome. Pulmonary first-pass effect occurs during intravenous administration of MSCs, where 50 to 80% of the cells tend to localize in the lungs. This phenomenon has been exploited to study MSC potential therapeutic effects in several preclinical models of lung diseases. Data demonstrated that, regardless of the lung disease severity and the delivery route, MSCs were not able to survive longer than 24 h in the respiratory tract but still surprisingly determined a therapeutic effect. In this work, two different mouse bone marrow-derived mesenchymal stromal/stem cell (mBM-MSC) lines, stably transduced with a third-generation lentiviral vector expressing luciferase and green fluorescent protein reporter genes tracking MSCs biodistribution and persistency, have been generated. Cells within the engrafted lung were traced using the high-throughput bioluminescence imaging (BLI) technique, with no invasiveness on animal, minimizing biological variations and costs. BLI analysis allowed the detection and monitoring of the mBM-MSC clones up to 28 days after implantation independently from the delivery route. This longer persistency than previously observed (24 h) could have a strong impact in terms of pharmacokinetics and pharmacodynamics of MSCs as a therapeutic tool.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcell.2021.709225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322774PMC
July 2021

The role of MRI in cervical cancer > 2 cm (FIGO stage IB2-IIA1) conservatively treated with neoadjuvant chemotherapy followed by conization: a pilot study.

Radiol Med 2021 Aug 31;126(8):1055-1063. Epub 2021 May 31.

UOC Radiologia Generale ed Interventistica generale, Area Diagnostica per Immagini, Dipartimento Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Introduction: MRI is very accurate in selecting young women with cervical cancer for fertility-sparing surgery (FSS), in particular radical hysterectomy (RH). In order to improve obstetrical outcomes, neoadjuvant chemotherapy (NACT) followed by cold knife conization (CKC) has been proposed as alternative technique.

Objective: To investigate the role of MRI in evaluation of response to treatment after neoadjuvant chemotherapy (NACT), followed by CKC, in patients with cervical cancer FIGO stage IB2-IIA1 with tumor size 2 - 4 cm, desiring to preserve their fertility.

Methods: 13 young women (23-36 years old) with cervical cancer stage IB2-IIA1 desiring to preserve their fertility were included. Tumor diameter at baseline and after treatment was detected on 1.5 T MRI. Treatment response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and then compared to histopathology result.

Results: MRI correctly assessed 11 out of 13 cases, according to RECIST 1.1, compared to histopathology. Among these 7 patients with partial response (PR), 2 cases of CR, 1 SD and 1 PD with persistence or enlargement of primary tumor.

Conclusion: Our pilot study supports the usefulness of MRI in assessment of treatment response after NACT, followed by CKC.

Trial Registration Number: ClinicalTrials.gov: NCT02323841.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11547-021-01377-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292245PMC
August 2021

Immunotherapy-Related Imaging Findings in Patients with Gynecological Malignancies: What Radiologists Need to Know.

Korean J Radiol 2021 08 20;22(8):1310-1322. Epub 2021 May 20.

UOC Radiologia Generale ed Interventistica Generale, Dipartimento Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Area Diagnostica per Immagini, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Immunotherapy is an effective treatment option for gynecological malignancies. Radiologists dealing with gynecological patients undergoing treatment with immune checkpoint inhibitors should be aware of unconventional immune-related imaging features for the evaluation of tumor response and immune-related adverse events. In this paper, immune checkpoint inhibitors used for gynecological malignancies and their mechanisms of action are briefly presented. In the second part, patterns of pseudoprogression are illustrated, and different forms of immune-related adverse events are discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3348/kjr.2020.1299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316780PMC
August 2021

Organosilica Cages Target Hepatic Sinusoidal Endothelial Cells Avoiding Macrophage Filtering.

ACS Nano 2021 06 19;15(6):9701-9716. Epub 2021 May 19.

Department of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri, IRCCS, Via Mario Negri 2, 20156 Milano, Italy.

Over the last years, advancements in the use of nanoparticles for biomedical applications have clearly showcased their potential for the preparation of improved imaging and drug-delivery systems. However, compared to the vast number of currently studied nanoparticles for such applications, only a few successfully translate into clinical practice. A common "barrier" that prevents nanoparticles from efficiently delivering their payload to the target site after administration is related to liver filtering, mainly due to nanoparticle uptake by macrophages. This work reports the physicochemical and biological investigation of disulfide-bridged organosilica nanoparticles with cage-like morphology, OSCs, assessing in detail their bioaccumulation . The fate of intravenously injected 20 nm OSCs was investigated in both healthy and tumor-bearing mice. Interestingly, OSCs exclusively colocalize with hepatic sinusoidal endothelial cells (LSECs) while avoiding Kupffer-cell uptake (less than 6%) under both physiological and pathological conditions. Our findings suggest that organosilica nanocages hold the potential to be used as nanotools for LSECs modulation, potentially impacting key biological processes such as tumor cell extravasation and hepatic immunity to invading metastatic cells or a tolerogenic state in intrahepatic immune cells in autoimmune diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsnano.1c00316DOI Listing
June 2021

Marathon shoes vs. track spikes: a crossover pilot study on metabolic demand at different speeds in experienced runners.

Res Sports Med 2021 May 14:1-8. Epub 2021 May 14.

Department of Biomedical Sciences for Health, Università Degli Studi Di Milano, Milan, Italy.

The aim of this study was to assess the metabolic cost (Cr) with marathon shoes (Adidas Adizero 3 [AA]) vs. track spikes (Nike Zoom Matumbo 3 [NZM]) on track. For this, five experienced runners were randomly assessed (NZM/AA) on a running track at 73% and 85% of best performance speed on 1500-m race. At first, speed (4.39 ± 0.53 m·s), Crs with AA and NZM resulted 3.63 ± 0.29 and 3.64 ± 0.43 J·kg·m (+0.3% with NZM, effect size [ES] small and = 0.951), respectively. Besides, at second speed (5.20 ± 0.18 m·s), Crs were 4.09 ± 0.28 and 4.07 ± 0.22 J·kg·m (-0.5% with NZM, ES small and = 0.919) with AA and NZM, respectively. It resulted in an increased Cr (+12.2%) between s1 and s2 with both shoe conditions (ES large and = 0.009 and 0.011 with AA and NZM, respectively). There is a pattern yet to be confirmed for track spikes to become more beneficial at higher speeds (when duty factor becomes lower and therefore grip on track is crucial).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15438627.2021.1929225DOI Listing
May 2021

A Simplified SARS-CoV-2 Pseudovirus Neutralization Assay.

Vaccines (Basel) 2021 Apr 15;9(4). Epub 2021 Apr 15.

Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy.

COVID-19 is an ongoing pandemic caused by the highly infectious coronavirus SARS-CoV-2 that is engaging worldwide scientific research to find a timely and effective eradication strategy. Great efforts have been put into anti-COVID-19 vaccine generation in an effort to protect the world population and block SARS-CoV-2 spread. To validate the protective efficacy of the vaccination campaign and effectively control the pandemic, it is necessary to quantify the induction of neutralizing antibodies by vaccination, as they have been established to be a correlate of protection. In this work, a SARS-CoV-2 pseudovirus neutralization assay, based on a replication-incompetent lentivirus expressing an adapted form of CoV-2 S protein and an ACE2/TMPRSS2 stably expressing cell line, has been minimized in terms of protocol steps without loss of accuracy. The goal of the present simplified neutralization system is to improve SARS-CoV-2 vaccination campaign by means of an easy and accessible approach to be performed in any medical laboratory, maintaining the sensitivity and quantitative reliability of classical serum neutralization assays. Further, this assay can be easily adapted to different coronavirus variants by simply modifying the pseudotyping vector.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/vaccines9040389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071407PMC
April 2021

Pretreatment MRI Radiomics Based Response Prediction Model in Locally Advanced Cervical Cancer.

Diagnostics (Basel) 2021 Mar 31;11(4). Epub 2021 Mar 31.

Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, 00168 Roma, Italy.

The aim of this study was to create a radiomics model for Locally Advanced Cervical Cancer (LACC) patients to predict pathological complete response (pCR) after neoadjuvant chemoradiotherapy (NACRT) analysing T2-weighted 1.5 T magnetic resonance imaging (MRI) acquired before treatment start. Patients with LACC and an International Federation of Gynecology and Obstetrics stage from IB2 to IVA at diagnosis were retrospectively enrolled for this study. All patients underwent NACRT, followed by radical surgery; pCR-assessed on surgical specimen-was defined as absence of any residual tumour. Finally, 1889 features were extracted from MR images; features showing statistical significance in predicting pCR at the univariate analysis were selected following an iterative method, which was ad-hoc developed for this study. Based on this method, 15 different classifiers were trained considering the most significant features selected. Model selection was carried out using the area under the receiver operating characteristic curve (AUC) as target metrics. One hundred eighty-three patients from two institutions were analysed. The model, showing the highest performance with an AUC of 0.80, was the random forest method initialised with default parameters. Radiomics appeared to be a reliable tool in pCR prediction for LACC patients undergoing NACRT, supporting the identification of patient risk groups, which paves treatment pathways tailored according to the predicted outcome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/diagnostics11040631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066099PMC
March 2021

C. elegans detects toxicity of traumatic brain injury generated tau.

Neurobiol Dis 2021 06 10;153:105330. Epub 2021 Mar 10.

Department of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy. Electronic address:

Traumatic brain injury (TBI) is associated with widespread tau pathology in about 30% of patients surviving late after injury. We previously found that TBI in mice induces the formation of an abnormal form of tau (tau) which progressively spreads from the site of injury to remote brain regions. Intracerebral inoculation of TBI brain homogenates into naïve mice induced progressive tau pathology, synaptic loss and late cognitive decline, suggesting a pivotal role of tau in post-TBI neurodegeneration. However, the possibility that tau was a marker of TBI-associated neurodegeneration rather than a toxic driver of functional decline could not be excluded. Here we employed the nematode C. elegans as a biosensor to test the pathogenic role of TBI generated tau. The motility of this nematode depends on efficient neuromuscular transmission and is exceptionally sensitive to the toxicity of amyloidogenic proteins, providing a tractable model for our tests. We found that worms exposed to brain homogenates from chronic but not acute TBI mice, or from mice in which tau had been transmitted by intracerebral inoculation, had impaired motility and neuromuscular synaptic transmission. Results were similar when worms were given brain homogenates from transgenic mice overexpressing tau P301L, a tauopathy mouse model, suggesting that TBI-induced and mutant tau have similar toxic properties. P301L brain homogenate toxicity was similar in wild-type and ptl-1 knock-out worms, indicating that the nematode tau homolog protein PTL-1 was not required to mediate the toxic effect. Harsh protease digestion to eliminate the protein component of the homogenates, pre-incubation with anti-tau antibodies or tau depletion by immunoprecipitation, abolished the toxicity. Homogenates of chronic TBI brains from tau knock-out mice were not toxic to C. elegans, whereas oligomeric recombinant tau was sufficient to impair their motility. This study indicates that tau impairs motor activity and synaptic transmission in C. elegans and supports a pathogenic role of tau in the long-term consequences of TBI. It also sets the groundwork for the development of a C. elegans-based platform for screening anti-tau compounds.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nbd.2021.105330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039186PMC
June 2021

External Responsiveness of the SuperOp Device to Assess Recovery After Exercise: A Pilot Study.

Front Sports Act Living 2020 14;2:67. Epub 2020 Jul 14.

Faculty of Kinesiology, University of Split, Split, Croatia.

Post-exercise recovery is a complex process involving a return of performance and a physiological or perceptual feeling close to pre-exercise . The hypothesis of this study is that the device investigated here is effective in evaluating the recovery state of professional cyclists in order to plan effective training. Ten professional male cyclists belonging to the same team were enrolled in this study. Participants performed a 7-day exercise program [D1, D4, and D7: low-intensity training; D2 and D5: passive recovery; D3: oxygen consumption (VO) test (for mechanical power assessment only); and D6: constant load test]. During the week of monitoring, each morning before getting up, the device assessed each participant's so-called Organic Readiness {OR [arbitrary unit (a.u.)]}, based on blood pressure (BP), heart rate (HR), features of past exercise session, and following self-perceived condition. Based on its readings and algorithm, the device graphically displayed four different colors/values, indicating general exercise recommendations: green/3 = "you can train hard," yellow/2 = "you can train averagely," orange/1 = "you can train lightly," or red/0 = "you should recover passively." During the week of research, morning OR values and Bonferroni comparisons showed significant differences between days and, namely, values (1) D2 (after low intensity training) was higher than D4 (after VO test; = 0.033 and = 1.296) and (2) D3 and D6 (after passive recovery) were higher than D4 (after VO test; = 0.006 and = 2.519) and D5 (after low intensity training; = 0.033 and = 1.341). The receiver operating characteristic analysis area under curve (AUC) recorded a result of 0.727 and could differentiate between D3 and D4 with a sensitivity and a specificity of 80%. Preliminarily, the device investigated is a sufficiently effective and sensitive/specific device to assess the recovery state of athletes in order to plan effective training.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fspor.2020.00067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7739672PMC
July 2020

Super-Resolution Imaging to Study Co-Localization of Proteins and Synaptic Markers in Primary Neurons.

J Vis Exp 2020 10 31(164). Epub 2020 Oct 31.

Department of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS;

Synapses are the functional elements of neurons and their defects or losses are at the basis of several neurodegenerative and neurological disorders. Imaging studies are widely used to investigate their function and plasticity in physiological and pathological conditions. Because of their size and structure, localization studies of proteins require high-resolution imaging techniques. In this protocol, we describe a procedure to study in primary neurons the co-localization of target proteins with synaptic markers at a super-resolution level using structured illumination microscopy (SIM). SIM is a patterned-light illumination technique that doubles the spatial resolution of wide-field microscopy, reaching a detail of around 100 nm. The protocol indicates the required controls and settings for robust co-localization studies and an overview of the statistical methods to analyze the imaging data properly.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3791/61434DOI Listing
October 2020

Neuronal Localization of SENP Proteins with Super Resolution Microscopy.

Brain Sci 2020 Oct 25;10(11). Epub 2020 Oct 25.

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

SUMOylation of proteins plays a key role in modulating neuronal function. For this reason, the balance between protein SUMOylation and deSUMOylation requires fine regulation to guarantee the homeostasis of neural tissue. While extensive research has been carried out on the localization and function of small ubiquitin-related modifier (SUMO) variants in neurons, less attention has been paid to the SUMO-specific isopeptidases that constitute the human SUMO-specific isopeptidase (SENP)/Ubiquitin-Specific Protease (ULP) cysteine protease family (SENP1-3 and SENP5-7). Here, for the first time, we studied the localization of SENP1, SENP6, and SENP7 in cultured hippocampal primary neurons at a super resolution detail level, with structured illumination microscopy (SIM). We found that the deSUMOylases partially colocalize with pre- and post-synaptic markers such as synaptophysin and drebrin. Thus, further confirming the presence with synaptic markers of the negative regulators of the SUMOylation machinery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/brainsci10110778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693135PMC
October 2020

Cellulose nanocrystals: a multimodal tool to enhance the targeted drug delivery against bone disorders.

Nanomedicine (Lond) 2020 08 11;15(23):2271-2285. Epub 2020 Sep 11.

Department of Molecular Biochemistry & Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156, Milano, Italy.

We investigated the use of cellulose nanocrystals (CNCs) as drug nanocarriers combining an anti-osteoporotic agent, alendronate (ALN), and an anti-cancer drug, doxorubicin (DOX). CNC physicochemical characterization, imaging coupled with histology and  uptake and toxicity assays were carried out. CNC-ALN did not modify bone tropism and lung penetration, whereas its liver and kidney accumulation was slightly higher compared with CNCs alone. studies showed that CNC-ALN did not impair ALN's effect on osteoclasts, whereas CNC-DOX confirmed the therapeutic potential against bone metastatic cancer cells. This study provides robust proof of the potential of CNCs as easy, flexible and specific carriers to deliver compounds to the bone.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2217/nnm-2020-0139DOI Listing
August 2020

Denning in brown bears.

Ecol Evol 2020 Jul 25;10(13):6844-6862. Epub 2020 May 25.

Research Unit of Biodiversity (UMIB, CSIC-UO-PA) Mieres Spain.

Hibernation represents an adaptation for coping with unfavorable environmental conditions. For brown bears , hibernation is a critical period as pronounced temporal reductions in several physiological functions occur.Here, we review the three main aspects of brown bear denning: (1) den chronology, (2) den characteristics, and (3) hibernation physiology in order to identify (a) proximate and ultimate factors of hibernation as well as (b) research gaps and conservation priorities.Den chronology, which varies by sex and reproductive status, depends on environmental factors, such as snow, temperature, food availability, and den altitude. Significant variation in hibernation across latitudes occurs for both den entry and exit.The choice of a den and its surroundings may affect individual fitness, for example, loss of offspring and excessive energy consumption. Den selection is the result of broad- and fine-scale habitat selection, mainly linked to den insulation, remoteness, and availability of food in the surroundings of the den location.Hibernation is a metabolic challenge for the brown bears, in which a series of physiological adaptations in tissues and organs enable survival under nutritional deprivation, maintain high levels of lipids, preserve muscle, and bone and prevent cardiovascular pathologies such as atherosclerosis. It is important to understand: (a) proximate and ultimate factors in denning behavior and the difference between actual drivers of hibernation (i.e., factors to which bears directly respond) and their correlates; (b) how changes in climatic factors might affect the ability of bears to face global climate change and the human-mediated changes in food availability; (c) hyperphagia (period in which brown bears accumulate fat reserves), predenning and denning periods, including for those populations in which bears do not hibernate every year; and (d) how to approach the study of bear denning merging insights from different perspectives, that is, physiology, ecology, and behavior.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ece3.6372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7381752PMC
July 2020

Shoes and Insoles: The Influence on Motor Tasks Related to Walking Gait Variability and Stability.

Int J Environ Res Public Health 2020 06 25;17(12). Epub 2020 Jun 25.

Department of Biomedical Sciences for Health, Università degli Studi di Milano, 20133 Milan, Italy.

The rhythmic control of the lower limb muscles influences the cycle-to-cycle variability during a walking task. The benefits of insoles, commonly used to improve the walking gait, have been little studied. Therefore, the aim of this study was to assess the walking gait variability and stability on different walking conditions (without shoes, WTS, with shoes, WS, with shoes and insoles, WSI) related to brain activity. Twelve participants randomly (WTS/WS/WSI) walked on a treadmill at 4 km/h for 10 min. Kinematic analysis (i.e., footstep and gait variability), brain activation (beta wave signal), rating of perceived exertion (RPE, CR-10 scale), and time domain measures of walking variability were assessed. The maximum Lyapunov exponent (LyE) on the stride cycle period's datasets was also calculated. Stride length and cycle calculated for all walking conditions were 61.59 ± 2.53/63.38 ± 1.43/64.09 ± 2.40 cm and 1.11 ± 0.03/1.14 ± 0.03/1.15 ± 0.04 s (F = 4.941/ = 0.01, F = 4.938/ = 0.012) for WTS, WS, WSI, respectively. Beta wave (F = 564.201/ = 0.0001) was higher in WTS compared to WS and WSI. Analysis of variance's (ANOVA) LyE showed a F = 3.209/ = 0.056, while post hoc analysis showed a significant effect between WS and WSI with = 0.023, and nonsignificant effects between WTS and WS/WSI ( = 0.070/0.607), respectively. Small perturbations of the foot can influence the control of gait rhythmicity by increasing the variability in a dissipative deterministic regimen.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijerph17124569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7345333PMC
June 2020

Validity and Reliability of Isometric-Bench for Knee Isometric Assessment.

Int J Environ Res Public Health 2020 06 17;17(12). Epub 2020 Jun 17.

Department of Biotechnology and Applied Clinical Science, University of L'Aquila, 67100 L'Aquila, Italy.

There is a strong need for a new, probably cheaper, smaller, and more portable isometric dynamometer. With this aim, we investigated the concurrent validity and reliability of a low-cost portable dynamometer to measure the isometric strength of the lower limb. Seventeen young participants (age 16.47 ± 0.51 years) were randomly assessed on three different days for knee flexion and extension isometric forces with two different devices: a commonly used isokinetic dynamometer (ISOC) and a portable isometric dynamometer prototype (ISOM). No significant differences were observed between the ISOC and the ISOM (all comparisons > 0.05). Test-retest comparison showed the ISOM to have high reliability (ICC 0.879-0.990). This study showed that measurements with the ISOM could be performed without systematic bias and with high reliability. The ISOM is a device that is able to assess knee isometric strength with excellent concurrent validity and reliability.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijerph17124326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7345336PMC
June 2020

Immunotargeting of the xCT Cystine/Glutamate Antiporter Potentiates the Efficacy of HER2-Targeted Immunotherapies in Breast Cancer.

Cancer Immunol Res 2020 08 12;8(8):1039-1053. Epub 2020 Jun 12.

Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.

Despite HER2-targeted therapies improving the outcome of HER2 breast cancer, many patients experience resistance and metastatic progression. Cancer stem cells (CSC) play a role in this resistance and progression, thus combining HER2 targeting with CSC inhibition could improve the management of HER2 breast cancer. The cystine-glutamate antiporter, xCT, is overexpressed in mammary CSCs and is crucial for their redox balance, self-renewal, and resistance to therapies, representing a potential target for breast cancer immunotherapy. We developed a combined immunotherapy targeting HER2 and xCT using the Bovine Herpes virus-4 vector, a safe vaccine that can confer immunogenicity to tumor antigens. Mammary cancer-prone BALB-neuT mice, transgenic for rat , were immunized with the single or combined vaccines. Anti-HER2 vaccination slowed primary tumor growth, whereas anti-xCT vaccination primarily prevented metastasis formation. The combination of the two vaccines exerted a complementary effect by mediating the induction of cytotoxic T cells and of HER2 and xCT antibodies that induce antibody-dependent cell-mediated cytotoxicity and hinder cancer cell proliferation. Antibodies targeting xCT, but not those targeting HER2, directly affected CSC viability, self-renewal, and migration, inducing the antimetastatic effect of xCT vaccination. Our findings present a new therapy for HER2 breast cancer, demonstrating that CSC immunotargeting via anti-xCT vaccination synergizes with HER2-directed immunotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/2326-6066.CIR-20-0082DOI Listing
August 2020

Local Structural Effects Due to Micronization and Amorphization on an HIV Treatment Active Pharmaceutical Ingredient.

Mol Pharm 2020 07 22;17(7):2370-2389. Epub 2020 May 22.

Department of Applied Physics and Applied Mathematics, Columbia University, New York, New York 10027, United States.

Processing procedures for inducing domain size reduction and/or amorphous phase generation can be crucial for enhancing the bioavailability of active pharmaceutical ingredients (APIs). It is important to quantify these reduced coherence phases and to detect and characterize associated structural changes, to ensure that no deleterious effects on safety, function, or stability occur. Here, X-ray powder diffraction (XRPD), total scattering pair distribution function (TSPDF) analysis, and solid-state nuclear magnetic resonance spectroscopy (SSNMR) have been performed on samples of GSK2838232B, an investigational drug for the treatment of human immunodeficiency virus (HIV). Preparations were obtained through different mechanical treatments resulting in varying extents of domain size reduction and amorphous phase generation. Completely amorphous formulations could be prepared by milling and microfluidic injection processes. Microfluidic injection was shown to result in a different local structure due to dispersion with dichloromethane (DCM). Implications of combined TSPDF and SSNMR studies to characterize molecular compounds are also discussed, in particular, the possibility to obtain a thorough structural understanding of disordered samples from different processes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.molpharmaceut.0c00122DOI Listing
July 2020

Ecological assessment of anthropogenic impact in marine ecosystems: The case of Bagnoli Bay.

Mar Environ Res 2020 Jun 10;158:104953. Epub 2020 Mar 10.

Stazione Zoologica Anton Dohrn, Villa Comunale 80121, Naples, Italy.

Pollutants alter marine systems, interfering with provisioning of ecosystem services; understanding their interaction with ecological communities is therefore critical to inform environmental management. Here we propose a joint compositional- and interaction-based analysis for ecological status assessment and apply it on the benthic communities of the Bagnoli Bay. We found that contamination differentially affects the communities' composition in the bay, with prokaryotes influenced only by depth, and benthos not following the environmental gradient at all. This result is confirmed by analyses of the community structure, whose network structure suggest fast carbon flow and cycling, especially promoted by nematodes and polychaetes; the benthic prey/predator biomass ratio, adjusted for competition, successfully synthesise the status of predator taxa. We found demersal fish communities to separate into a deep, pelagic-like community, and two shallow communities where a shift from exclusive predators to omnivores occurs, moving from the most polluted to the least polluted sampling units. Finally, our study indicate that indices based on interspecific interactions are better indicators of environmental gradients than those defined based on species composition exclusively.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.marenvres.2020.104953DOI Listing
June 2020
-->