50 results on '"Denise Madeddu"'
Search Results
2. Supplementary Figures S1-S5 from Inhibition of PI3K Pathway Reduces Invasiveness and Epithelial-to-Mesenchymal Transition in Squamous Lung Cancer Cell Lines Harboring PIK3CA Gene Alterations
- Author
-
Andrea Ardizzoni, Pier Giorgio Petronini, Marcello Tiseo, Claudia Fumarola, Pietro Rossetti, Angela Falco, Costanza Annamaria Lagrasta, Caterina Frati, Denise Madeddu, Cristina Caffarra, Daniele Cretella, Maricla Galetti, Silvia La Monica, Federico Quaini, Roberta R. Alfieri, Francesca Saccani, Andrea Cavazzoni, and Mara A. Bonelli
- Abstract
Supplementary Figures S1-S5. Figure S1: p-AKT levels in PIK3CA transfected clones Figure S2: Induction of cell death after treatment with PI3K inhibitors Figure S3: Time course evaluation of PI3K/AKT/mTOR pathway activity after exposure to PI3K inhibitors Figure S4: Evaluation of cell migration after treatment with PI3K inhibitors Figure S5: CD133 expression in tumor spheres
- Published
- 2023
3. Data from Low PD-1 Expression in Cytotoxic CD8+ Tumor-Infiltrating Lymphocytes Confers an Immune-Privileged Tissue Microenvironment in NSCLC with a Prognostic and Predictive Value
- Author
-
Marcello Tiseo, Federico Quaini, Franco Aversa, Konrad Urbanek, Andrea Ardizzoni, Enrico Maria Silini, Michele Veneziani, Luca Ampollini, Roberta Alfieri, Caterina Frati, Rocchina Vilella, Chiara Mangiaracina, Bruno Lorusso, Costanza Annamaria Lagrasta, Giovanna Armani, Francesco Sogni, Matteo Goldoni, Giovanni Bocchialini, Angela Falco, Denise Madeddu, and Giulia Mazzaschi
- Abstract
Purpose: The success of immune checkpoint inhibitors strengthens the notion that tumor growth and regression are immune regulated. To determine whether distinct tissue immune microenvironments differentially affect clinical outcome in non–small cell lung cancer (NSCLC), an extended analysis of PD-L1 and tumor-infiltrating lymphocytes (TIL) was performed.Experimental Design: Samples from resected adenocarcinoma (ADC 42), squamous cell carcinoma (SCC 58), and 26 advanced diseases (13 ADC and 13 SCC) treated with nivolumab were analyzed. PD-L1 expression and the incidence of CD3, CD8, CD4, PD-1, CD57, FOXP3, CD25, and Granzyme B TILs were immunohistochemically assessed.Results: PD-L1 levels inversely correlated with N involvement, although they did not show a statistically significant prognostic value in resected patients. The incidence and phenotype of TILs differed in SCC versus ADC, in which EGFR and KRAS mutations conditioned a different frequency and tissue localization of lymphocytes. NSCLC resected patients with high CD8pos lymphocytes lacking PD-1 inhibitory receptor had a longer overall survival (OS: HR = 2.268; 95% CI, 1.056–4.871, P = 0.03). PD-1-to-CD8 ratio resulted in a prognostic factor both on univariate (HR = 1.952; 95% CI, 1.34–3.12, P = 0.001) and multivariate (HR = 1.943; 95% CI, 1.38–2.86, P = 0.009) analysis. Moreover, low PD-1 incidence among CD8pos cells was a distinctive feature of nivolumab-treated patients, showing clinical benefit with a prolonged progression-free survival (PFS: HR = 4.51; 95% CI, 1.45–13.94, P = 0.004).Conclusions: In the presence of intrinsic variability in PD-L1 expression, the reservoir of PD-1–negative effector T lymphocytes provides an immune-privileged microenvironment with a positive impact on survival of patients with resected disease and response to immunotherapy in advanced NSCLC. Clin Cancer Res; 24(2); 407–19. ©2017 AACR.
- Published
- 2023
4. Figure S1-S4 from Low PD-1 Expression in Cytotoxic CD8+ Tumor-Infiltrating Lymphocytes Confers an Immune-Privileged Tissue Microenvironment in NSCLC with a Prognostic and Predictive Value
- Author
-
Marcello Tiseo, Federico Quaini, Franco Aversa, Konrad Urbanek, Andrea Ardizzoni, Enrico Maria Silini, Michele Veneziani, Luca Ampollini, Roberta Alfieri, Caterina Frati, Rocchina Vilella, Chiara Mangiaracina, Bruno Lorusso, Costanza Annamaria Lagrasta, Giovanna Armani, Francesco Sogni, Matteo Goldoni, Giovanni Bocchialini, Angela Falco, Denise Madeddu, and Giulia Mazzaschi
- Abstract
Clinicopathological correlations. Figure S1: PD-L1 Expression and Clinicopathologic Parameters; Figure S2: PD-L1 Expression and TILs; Figure S3: TILs and Clinicopathological Parameters; Figure S4: NSCLC Immune Microenvironments Based on PD-L1 and TILs.
- Published
- 2023
5. Table S1-S3 from Low PD-1 Expression in Cytotoxic CD8+ Tumor-Infiltrating Lymphocytes Confers an Immune-Privileged Tissue Microenvironment in NSCLC with a Prognostic and Predictive Value
- Author
-
Marcello Tiseo, Federico Quaini, Franco Aversa, Konrad Urbanek, Andrea Ardizzoni, Enrico Maria Silini, Michele Veneziani, Luca Ampollini, Roberta Alfieri, Caterina Frati, Rocchina Vilella, Chiara Mangiaracina, Bruno Lorusso, Costanza Annamaria Lagrasta, Giovanna Armani, Francesco Sogni, Matteo Goldoni, Giovanni Bocchialini, Angela Falco, Denise Madeddu, and Giulia Mazzaschi
- Abstract
Table S1. Antibodies for Immunohistochemistry; Table S2. Magnitude of Sampling; Table S3. Magnitude of Sampling
- Published
- 2023
6. SDF-1 Molecularly Imprinted Biomimetic Scaffold as a Potential Strategy to Repair the Infarcted Myocardium
- Author
-
Federico Quaini, Costanza Lagrasta, Maria Grazia Cascone, Caterina Frati, Elisabetta Rosellini, Denise Madeddu, and Niccoletta Barbani
- Subjects
Stem cell ,food.ingredient ,biology ,Alginate ,Elastin ,Gelatin ,Nanotechnology ,Tissue engineering ,Chemistry ,Biomedical Engineering ,Medicine (miscellaneous) ,Bioengineering ,Biomimetic scaffold ,Cell biology ,food ,biology.protein - Abstract
Background: In situ cardiac tissue engineering aims to heal the infarcted myocardium by guiding tissue regeneration within the patient body. A key step in this approach is the design of a bioactive scaffold, able to stimulate tissue repair at the site of damage. In the development of bioactive scaffolds, molecular imprinting nanotechnology has been recently proposed as a new functionalization strategy. Objectives: In this work, Molecularly Imprinted Particles (MIP) with recognition properties towards the stromal-derived factor-1 (SDF-1) were synthesized, characterized and used for the functionalization of a biomimetic scaffold. MIP are expected to favor the enrichment of the SDF-1 bioactive molecule within the scaffold, thereby promoting myocardial regeneration. Methods: MIP were obtained by precipitation polymerization, using the SDF-1 molecule as a template. Alginate/gelatin/elastin sponges were fabricated by freeze-drying and functionalized by MIP deposition. Morphological, physicochemical and functional analyses were performed both on MIP and on MIP-modified scaffolds. A preliminary biological in vitro investigation was also carried out using rat cardiac progenitor cells (rCPCs). Results: Imprinted nanoparticles with an average diameter between 0.6 and 0.9 µm were obtained. Infrared analysis of MIP confirmed the expected chemical structure. Recognition and selectivity tests showed that MIP were able to selectively recognize and rebind the template, even after their deposition on the scaffold. In vitro biological tests showed that cell adhesion to the scaffold was promoted by MIP functionalization. Conclusion: Results obtained in the present study suggest that biomimetic alginate/gelatin/elastin sponges, functionalized by MIP with recognition properties towards SDF-1, could be successfully used for tissue engineering approaches to repair the infarcted heart.
- Published
- 2021
7. Β-blockers activate autophagy on infantile hemangioma-derived endothelial cells in vitro
- Author
-
Bruno Lorusso, Giuseppe Cerasoli, Angela Falco, Caterina Frati, Gallia Graiani, Denise Madeddu, Antonella Nogara, Emilia Corradini, Giovanni Roti, Elisa Cerretani, Andrea Gherli, Mariafrancesca Caputi, Letizia Gnetti, Francesco Paolo Pilato, Federico Quaini, and Costanza Lagrasta
- Subjects
Pharmacology ,Sirolimus ,Physiology ,Adrenergic beta-Antagonists ,Endothelial Cells ,Propranolol ,Atenolol ,Autophagy ,Molecular Medicine ,Humans ,Macrolides ,Amines ,Child ,Hemangioma ,Cell Proliferation ,Metoprolol - Abstract
The mechanisms underlying the success of propranolol in the treatment of infantile hemangioma (IH) remain elusive and do not fully explain the rapid regression of hemangiomatous lesions following drug administration. As autophagy is critically implicated in vascular homeostasis, we determined whether β-blockers trigger the autophagic flux on infantile hemangioma-derived endothelial cells (Hem-ECs) in vitro.Fresh tissue specimens, surgically removed for therapeutic purpose to seven children affected by proliferative IH, were subjected to enzymatic digestion. Cells were sorted with anti-human CD31 immunolabeled magnetic microbeads. Following phenotypic characterization, expanded Hem-ECs, at P2 to P6, were exposed to different concentrations (50 μM to 150 μM) of propranolol, atenolol or metoprolol alone and in combination with the autophagy inhibitor Bafilomycin A1. Rapamycin, a potent inducer of autophagy, was also used as control. Autophagy was assessed by Lysotracker Red staining, western blot analysis of LC3BII/LC3BI and p62, and morphologically by transmission electron microscopy.Hem-ECs treated with either propranolol, atenolol or metoprolol displayed positive LysoTracker Red staining. Increased LC3BII/LC3BI ratio, as well as p62 modulation, were documented in β-blockers treated Hem-ECs. Abundant autophagic vacuoles and multilamellar bodies characterized the cytoplasmic ultrastructural features of autophagy in cultured Hem-ECs exposed in vitro to β-blocking agents. Importantly, similar biochemical and morphologic evidence of autophagy were observed following rapamycin while Bafilomycin A1 significantly prevented the autophagic flux promoted by β-blockers in Hem-ECs.Our data suggest that autophagy may be ascribed among the mechanisms of action of β-blockers suggesting new mechanistic insights on the potential therapeutic application of this class of drugs in pathologic conditions involving uncontrolled angiogenesis.
- Published
- 2022
8. Integrated CT imaging and tissue immune features disclose a radio-immune signature with high prognostic impact on surgically resected NSCLC
- Author
-
Paolo Pagano, Gianluca Milanese, Bruno Lorusso, Giulia Mazzaschi, Francesca Trentini, Mario Silva, Caterina Frati, Denise Madeddu, Federico Quaini, Marcello Tiseo, Costanza Lagrasta, Angela Falco, Nicola Sverzellati, Roberta Minari, Giovanni Roti, Letizia Gnetti, and Luca Ampollini
- Subjects
0301 basic medicine ,Pulmonary and Respiratory Medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,Specific time ,Survival outcome ,03 medical and health sciences ,Lymphocytes, Tumor-Infiltrating ,0302 clinical medicine ,Immune system ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,Tumor Microenvironment ,medicine ,Humans ,Lung cancer ,Prognostic models ,Tumor-infiltrating lymphocytes ,business.industry ,Prognosis ,medicine.disease ,030104 developmental biology ,030220 oncology & carcinogenesis ,Ct imaging ,Tomography, X-Ray Computed ,business ,Validation cohort - Abstract
Qualitative and quantitative CT imaging features might intercept the multifaceted tumor immune microenvironment (TIME), providing a non-invasive approach to design new prognostic models in NSCLC patients.Our study population consisted of 100 surgically resected NSCLC patients among which 31 served as a validation cohort for quantitative image analysis. TIME was classified according to PD-L1 expression and the magnitude of Tumor Infiltrating Lymphocytes (TILs) and further defined as hot or cold by the tissue analysis of effector (CD8-to-CD3Specific CT-SFs (texture [TXT], effect [EFC] and margins [MRG]) strongly correlated to PD-L1 and TILs status and showed significant impact on survival outcome (TXT, HR:3.39, 95 % CI 1.12-10-27, P 0.05; EFC, HR:0.41, 95 % CI 0.18-0.93, P 0.05; MRG, HR:1.93, 95 % CI 0.88-4.25, P = 0.09). Seven CT derived radiomic features were able to sharply discriminate cases with hot (inflamed) vs cold (desert) TIME, which also exhibited opposite OS (long vs short, HR:0.09, 95 % CI 0.04-0.23, P 0.001) and DFS (long vs short, HR:0.31, 95 % CI 0.16-0.58, P 0.001). Moreover, we identified 6 prognostic radiomic features among which ClusterProminence displayed the highest statistical significance (HR:0.13, 95 % CI 0.06-0.31, P 0.001). These findings were independently validated in an additional cohort of NSCLC (HR:0.11, 95 % CI 0.03-0.40, P = 0.001). Finally, in our training cohort we developed a multiparametric prognostic model, interlacing TIME and clinico-pathological characteristics with CT-SFs (ROC curve AUC:0.83, 95 % CI 0.71-0.92, P 0.001) or CT-RFs (AUC: 0.91, 95 % CI 0.83-0.99, P 0.001), which appeared to outperform pTNM staging (AUC: 0.66, 95 % CI 0.51-0.80, P 0.05) in the risk assessment of NSCLC.Higher order CT extracted features associated with specific TIME profiles may reveal a radio-immune signature with prognostic impact on resected NSCLC.
- Published
- 2020
9. Effect of Nintedanib in a rat model of bleomycin-induced lung fibrosis: a transcriptome analysis
- Author
-
Gino Villetti, Costanza Lagrasta, Federico Quaini, Simone Ottonello, Maurizio Civelli, Paola Caruso, Vanessa Pitozzi, Maria Pittelli, Silvia Pontis, Denise Madeddu, Martina Bonatti, Marcello Trevisani, Barbara Montanini, and Caterina Frati
- Subjects
Transcriptome ,chemistry.chemical_compound ,chemistry ,business.industry ,Lung fibrosis ,Rat model ,Cancer research ,Medicine ,Nintedanib ,Bleomycin ,business - Published
- 2021
10. Inhibition of Human Malignant Pleural Mesothelioma Growth by Mesenchymal Stromal Cells
- Author
-
Silvia La Monica, Angela Marcianti, Daniela Lisini, Costanza Lagrasta, Giulio Alessandri, Francesca Paino, Roberta Alfieri, Augusto Pessina, Caterina Frati, Angela Falco, Aldo Bruno Giannì, Lorenzo Spaggiari, Lisa Flammini, Denise Madeddu, Mara Bonelli, Valentina Coccè, Giampietro Farronato, Eugenio Parati, and Francesco Petrella
- Subjects
Adult ,Adolescent ,QH301-705.5 ,Cell Survival ,Article ,Cell therapy ,Paracrine signalling ,Mice ,Young Adult ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Mesothelioma ,Biology (General) ,malignant pleural mesothelioma (MPM) ,Aged ,Cell Proliferation ,Mice, Inbred BALB C ,Cell growth ,business.industry ,Mesenchymal stem cell ,Cell Cycle ,Mesothelioma, Malignant ,Cancer ,Mesenchymal Stem Cells ,General Medicine ,Cell cycle ,Middle Aged ,medicine.disease ,Tumor progression ,mesothelioma ,Cancer research ,Female ,cell therapy ,business ,mesenchymal stromal cells - Abstract
Background: Malignant Pleural Mesothelioma (MPM) is an aggressive tumor that has a significant incidence related to asbestos exposure with no effective therapy and poor prognosis. The role of mesenchymal stromal cells (MSCs) in cancer is controversial due to their opposite effects on tumor growth and in particular, only a few data are reported on MSCs and MPM. Methods: We investigated the in vitro efficacy of adipose tissue-derived MSCs, their lysates and secretome against different MPM cell lines. After large-scale production of MSCs in a bioreactor, their efficacy was also evaluated on a human MPM xenograft in mice. Results: MSCs, their lysate and secretome inhibited MPM cell proliferation in vitro with S or G0/G1 arrest of the cell cycle, respectively. MSC lysate induced cell death by apoptosis. The efficacy of MSC was confirmed in vivo by a significant inhibition of tumor growth, similar to that produced by systemic administration of paclitaxel. Interestingly, no tumor progression was observed after the last MSC treatment, while tumors started to grow again after stopping chemotherapeutic treatment. Conclusions: These data demonstrated for the first time that MSCs, both through paracrine and cell-to-cell interaction mechanisms, induced a significant inhibition of human mesothelioma growth. Since the prognosis for MPM patients is poor and the options of care are limited to chemotherapy, MSCs could provide a potential new therapeutic approach for this malignancy.
- Published
- 2021
11. Validation of a radiomic approach to decipher NSCLC immune microenvironment in surgically resected patients
- Author
-
Claudio Pavone, Francesca Trentini, Bruno Lorusso, Caterina Frati, Federico Quaini, Giulia Mazzaschi, Costanza Lagrasta, Marcello Tiseo, Roberta Minari, Giovanni Roti, Denise Madeddu, Luca Ampollini, Nicola Sverzellati, Letizia Gnetti, Gianluca Milanese, Roberta Eufrasia Ledda, and Mario Silva
- Subjects
0301 basic medicine ,Oncology ,Male ,Cancer Research ,medicine.medical_specialty ,Immune microenvironment ,CD8 Antigens ,B7-H1 Antigen ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,Lymphocytes, Tumor-Infiltrating ,Radiomics ,Internal medicine ,Carcinoma, Non-Small-Cell Lung ,medicine ,Tumor Microenvironment ,Humans ,Lung ,Aged ,Neoplasm Staging ,Prognostic signature ,business.industry ,General Medicine ,Prognosis ,030104 developmental biology ,030220 oncology & carcinogenesis ,DECIPHER ,Female ,Ct imaging ,business ,Tomography, X-Ray Computed - Abstract
Radiomics has emerged as a noninvasive tool endowed with the potential to intercept tumor characteristics thereby predicting clinical outcome. In a recent study on resected non-small cell lung cancer (NSCLC), we identified highly prognostic computed tomography (CT) -derived radiomic features (RFs), which in turn were able to discriminate hot from cold tumor immune microenvironment (TIME). We aimed at validating a radiomic model capable of dissecting specific TIME profiles bearing prognostic power in resected NSCLC. The validation cohort included 31 radically resected NSCLCs clinicopathologically matched with the training set (n = 69). TIME was classified in hot and cold according to a multiparametric immunohistochemical analysis involving PD-L1 score and incidence of immune effector phenotypes among tumor infiltrating lymphocytes (TILs). High- throughput radiomic features (n = 841) extracted from CT images were correlated to TIME parameters to ultimately define prognostic classes. We confirmed PD-1 to CD8 ratio as best predictor of clinical outcome among TIME characteristics. Significantly prolonged overall survival (OS) was observed in patients carrying hot (median OS not reached) vs cold (median OS 22 months; hazard ratio 0.28, 95% confidence interval 0.09 -0.82; p = 0.015) immune background, thus validating the prognostic impact of these two TIME categories in resected NSCLC. Importantly, in the validation setting, three out of eight previously identified RFs sharply distinguishing hot from cold TIME were endorsed. Among signature-related RFs, Wavelet-HHH_gldm_HighGrayLevelEmphasis highly performed as descriptor of hot immune contexture (area under the receiver operating characteristic curve 0.94, 95% confidence interval 0.81 -1.00; p = 0.01). Based on our findings, Radiomics may decipher specific TIME profiles providing a noninvasive prognostic approach in resected NSCLC and an exploitable predictive strategy in advanced cases.
- Published
- 2021
12. Comparative analysis of collagen quantification in the bleomycin mouse model of lung fibrosis
- Author
-
Silvia Catinella, Costanza Lagrasta, Denise Madeddu, Caterina Frati, Vanessa Pitozzi, Martina Bonatti, Federico Quaini, Maria Laura Faietti, Barbara Pioselli, Gino Villetti, Marcello Trevisani, Paola Caruso, Maurizio Civelli, Maria Pittelli, and Silvia Pontis
- Subjects
Gene isoform ,Pathology ,medicine.medical_specialty ,Lung ,business.industry ,Lung fibrosis ,Bleomycin ,medicine.disease ,chemistry.chemical_compound ,Hydroxyproline ,medicine.anatomical_structure ,chemistry ,Fibrosis ,Expression analysis ,Medicine ,Nintedanib ,business - Abstract
Background: Evaluation of fibrosis and its severity is the commonest parameter to screen potential new medicines in rodents treated with bleomycin (BLM). Results are mainly reported by histological analysis and indirect measurement of collagen through hydroxyproline (HYP) quantification. Objectives: In the present study we performed a comparative analysis of different methods to assess collagens induced by BLM in the mouse lung. Methods: BLM (0.02 U/kg) was administered by oropharyngeal aspiration to male C57BL/6 mice on day 0 and day 4. Oral Nintedanib (60 mg/kg/day) started from day 7. Three and four weeks after the first BLM administration, histopathological examination and collagen genes expression analysis were applied. Moreover, HYP and collagen isoforms (LC-MS) quantification in lung homogenates were assessed. Results: Ashcroft score and automated measure of lung fibrosis revealed significant fibrotic lesions in BLM-treated animals. Specific collagen genes appeared up-regulated in BLM group. LC-MS quantification of collagen isoforms correlated with HYP levels although, interestingly, showed a higher therapeutic window between control and BLM group (1.5 vs. 0.5 fold, respectively). Nintedanib significantly affected all the evaluated readouts. Conclusions: Our study provides a comprehensive analysis of changes in collagen genes and proteins following BLM treatment in mice and the effect of Nintedanib. Importantly, our data indicate for the first time LC-MS as a sensitive and reliable method for collagen quantification in lung homogenate. This approach might implement the most employed HYP assay to achieve reliable predictions of efficacy for therapeutics in lung fibrosis.
- Published
- 2020
13. Functionalised peptide hydrogel for the delivery of cardiac progenitor cells
- Author
-
Aline F. Miller, Federico Quaini, Kate Meade, Caterina Frati, Delvac Oceandy, J. Gao, Kyle A. Burgess, L. Castillo Diaz, Alberto Saiani, Stefano Cavalli, Gallia Graiani, and Denise Madeddu
- Subjects
Scaffold ,Materials science ,Cell ,Myocardial Infarction ,Bioengineering ,Context (language use) ,02 engineering and technology ,Pharmacology ,010402 general chemistry ,01 natural sciences ,Hydrogel, Polyethylene Glycol Dimethacrylate ,Biomaterials ,medicine ,Animals ,Myocytes, Cardiac ,Myocardial infarction ,Regeneration (biology) ,Stem Cells ,Hydrogels ,021001 nanoscience & nanotechnology ,medicine.disease ,In vitro ,0104 chemical sciences ,Rats ,medicine.anatomical_structure ,Mechanics of Materials ,Cell culture ,Heart failure ,0210 nano-technology ,Peptides - Abstract
Heart failure (HF) remains one of the leading causes of death worldwide; most commonly developing after myocardial infarction (MI). Since adult cardiomyocytes characteristically do not proliferate, cells lost during MI are not replaced. As a result, the heart has a limited regenerative capacity. There is, therefore, a need to develop novel cell-based therapies to promote the regeneration of the heart after MI. The delivery and retention of cells at the injury site remains a significant challenge. In this context, we explored the potential of using an injectable, RGDSP-functionalised self-assembling peptide - FEFEFKFK - hydrogel as scaffold for the delivery and retention of rat cardiac progenitor cells (CPCs) into the heart. Our results show that culturing CPCs in vitro within the hydrogel for one-week promoted their spontaneous differentiation towards adult cardiac phenotypes. Injection of the hydrogel on its own, or loaded with CPCs, into the rat after injury resulted in a significant reduction in myocardial damage and left ventricular dilation.
- Published
- 2020
14. Dataset on the identification of a prognostic radio-immune signature in surgically resected Non Small Cell Lung Cancer
- Author
-
Francesca Trentini, Denise Madeddu, Angela Falco, Luca Ampollini, Bruno Lorusso, Marcello Tiseo, Nicola Sverzellati, Caterina Frati, Federico Quaini, Paolo Pagano, Giulia Mazzaschi, Giovanni Roti, Roberta Minari, Gianluca Milanese, Letizia Gnetti, Costanza Lagrasta, and Mario Silva
- Subjects
Oncology ,medicine.medical_specialty ,Immune contexture ,medicine.medical_treatment ,lcsh:Computer applications to medicine. Medical informatics ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Internal medicine ,medicine ,lcsh:Science (General) ,Lung cancer ,030304 developmental biology ,0303 health sciences ,Multidisciplinary ,Radiomics ,Tumor-infiltrating lymphocytes ,business.industry ,Prognostic signature ,Cancer ,Immunotherapy ,Medicine and Dentistry ,medicine.disease ,Cohort ,CT imaging ,lcsh:R858-859.7 ,Identification (biology) ,business ,030217 neurology & neurosurgery ,CD8 ,lcsh:Q1-390 - Abstract
The immune regulation of cancer growth and regression has been underscored by the recent success of immunotherapy. The possibility that immune microenvironmental factors may impact on clinical outcome and treatment response still requires intense investigations. Hereby, supporting data of the research article “Integrated CT Imaging and Tissue Immune Features Disclose a Radio-Immune Signature with High Prognostic Impact on Surgically Resected NSCLC” [1], are presented. With the ultimate aim to provide non-invasive prognostic scores, we report on our approach to correlate different Tumor Immune Microenvironment (TIME) profiles with CT imaging-derived qualitative (semantic, CT-SFs) and quantitative (radiomic, CT-RFs) features in a cohort of 60 surgically resected NSCLC. The renowned characterization of TIME, essentially based on the score evaluation of Programme Death Ligand-1 (PD-L1) and Tumor Infiltrating Lymphocytes (TILs), was implemented here by the assessment of effector and suppressor phenotypes including the analysis of Programme Death receptor 1 (PD-1). Thus, we defined two main TIME categories: hot inflamed (PD-L1high, CD8/CD3high and PD-1/CD8low) as opposed to cold inactive (PD-L1low, CD8/CD3lowand PD-1/CD8high). Importantly, as reported in the extended publication [1], these distinctive immune contextures identified different prognostic classes and were decoded by radiomics. To corroborate our radiomic approach, a comparative estimation of CT-RFs extracted from 60 NSCLC and 13 non neoplastic tissues was undertaken, documenting high discrimination ability. Moreover, we tested the potential association of qualitative radiologic features with clinico-pathological and TIME parameters. Taken together, our findings suggest that CT-SFs and CT-RFs may underlay specific patterns of lung cancer.
- Published
- 2020
15. Clinico-Immunological Profile of a 67-Year-Old Woman Affected by HER2-Positive Breast Cancer and Autoimmune Dermatomyositis
- Author
-
Benedetta Pellegrino, Giulia Mazzaschi, Denise Madeddu, Cristina Mori, Costanza Anna Maria Lagrasta, Gabriele Missale, Federico Quaini, and Antonino Musolino
- Subjects
0301 basic medicine ,Cancer Research ,dermatomyositis ,cross-reactivity ,medicine.medical_treatment ,Case Report ,lcsh:RC254-282 ,03 medical and health sciences ,breast cancer ,0302 clinical medicine ,Breast cancer ,Immune system ,Antigen ,Trastuzumab ,HER2 ,Medicine ,skin and connective tissue diseases ,neoplasms ,biology ,business.industry ,autoimmune ,Dermatomyositis ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Acquired immune system ,trastuzumab ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Immunology ,biology.protein ,Antibody ,business ,Adjuvant ,medicine.drug - Abstract
A patient with HER2-positive early breast cancer (BC) developed dermatomyositis (DM), which disappeared after the first administration of adjuvant trastuzumab. No HER2 overexpression/amplification was observed in DM skin biopsies. Both BC and skin immune infiltrates were composed mostly of CD3+ T-lymphocytes. Interestingly, tumor-infiltrating lymphocytes expressed PD-1, which was negligible in skin-infiltrating lymphocytes, while both BC cells and keratinocytes were PD-L1-positive. High serum levels of endogenous anti-HER2 antibodies were detected, confirming the induction of a HER2-specific adaptive immune response. It may be argued that HER2-specific T-lymphocytes cross-reacted with one or more unknown skin antigens, causing DM. Trastuzumab may have silenced skin cross-reaction by eliminating any residual HER2-positive micrometastatic disease and, thus, inducing DM remission.
- Published
- 2020
16. Reinforced alginate/gelatin sponges functionalized by avidin/biotin-binding strategy: a novel cardiac patch
- Author
-
Federico Quaini, Gallia Graiani, Elisabetta Rosellini, Angela Falco, Luigi Lazzeri, Denise Madeddu, Caterina Frati, Maria Grazia Cascone, and Niccoletta Barbani
- Subjects
Male ,food.ingredient ,insulin-like growth factor 1 ,Alginates ,Surface Properties ,Bioactive molecules ,0206 medical engineering ,Biomedical Engineering ,Biotin ,02 engineering and technology ,Gelatin ,Biomaterials ,Prosthesis Implantation ,Polydioxanone ,chemistry.chemical_compound ,cardiac tissue engineering ,food ,Biomimetic Materials ,Somatomedins ,suture retention ,Cell Adhesion ,Animals ,Humans ,Cell Proliferation ,integumentary system ,biology ,Tissue Engineering ,Tissue Scaffolds ,Viscosity ,Myocardium ,Stem Cells ,021001 nanoscience & nanotechnology ,Avidin ,020601 biomedical engineering ,Elasticity ,Porifera ,Rats ,chemistry ,Biophysics ,biology.protein ,0210 nano-technology ,Hydrophobic and Hydrophilic Interactions ,Porosity - Abstract
Adequate mechanical properties to withstand the surgical procedure and decoration with bioactive molecules promoting tissue regeneration are crucial aspects in the development of successful matrice...
- Published
- 2019
17. Influence of injectable microparticle size on cardiac progenitor cell response
- Author
-
Diana Nada Caterina Massai, Alberto Audenino, Federico Quaini, Niccoletta Barbani, Costanza Lagrasta, Angela Falco, Umberto Morbiducci, Luigi Lazzeri, Caterina Frati, Maria Grazia Cascone, Denise Madeddu, and Elisabetta Rosellini
- Subjects
ACID) ,food.ingredient ,0206 medical engineering ,Biomedical Engineering ,Biophysics ,gellan ,Biocompatible Materials ,Bioengineering ,02 engineering and technology ,SCAFFOLDS ,BLENDS ,Gelatin ,gelatin ,Biomaterials ,DELIVERY ,cardiac tissue engineering ,food ,Cardiac progenitor cells ,Cell Adhesion ,Animals ,Cardiac Progenitor Cell ,Myocytes, Cardiac ,Particle Size ,Microparticle ,Cells, Cultured ,Cell Proliferation ,Tissue Engineering ,Tissue Scaffolds ,Myocardial tissue ,Chemistry ,Myocardium ,Stem Cells ,Author Keywords: Cardiac progenitor cells ,Polysaccharides, Bacterial ,gellan KeyWords Plus: STEM-CELLS ,Cardiac progenitor cells, cardiac tissue engineering, gelatin, gellan ,General Medicine ,021001 nanoscience & nanotechnology ,020601 biomedical engineering ,Microspheres ,Rats ,MYOCARDIAL-INFARCTION ,RAT ,Emulsions ,GELLAN ,MICROSPHERES ,0210 nano-technology ,Porosity ,Biomedical engineering - Abstract
Introduction: Injectable scaffolds are emerging as a promising strategy in the field of myocardial tissue engineering. Among injectable scaffolds, microparticles have been poorly investigated. The goal of this study was the development of novel gelatin/gellan microparticles that could be used as an injectable scaffold to repair the infarcted myocardium. In particular, the effect of particle size on cardiac progenitor cell response was investigated. Methods: Particles were produced by a water-in-oil emulsion method. Phosphatidylcholine was used as a surfactant. Particles with different diameter ranges (125–300 µm and 350–450 µm) were fabricated using two different surfactant concentrations. Morphological, physicochemical, and functional characterizations were carried out. Cardiac progenitor cell adhesion and growth on microparticles were tested both in static and dynamic suspension culture conditions. Results: Morphological analysis of the produced particles showed a spherical shape and porous surface. The hydrophilicity of particle matrix and the presence of intermolecular interactions between gellan and gelatin were pointed out by the physicochemical characterization. A weight loss of 75 ± 5 % after 90 days of hydrolytic degradation was observed. Injectability through a narrow needle (26 G) and persistence of the microparticles at the injection site were preliminarily verified by ex vivo test. In vitro cell culture tests showed a preservation of rat cardiac progenitor biologic properties and indicated a preferential cell adherence to microparticles with a smaller size. Conclusion: Overall, the obtained results indicate that the produced gelatin/gellan microparticles could be potentially employed as injectable scaffolds for myocardial regeneration.
- Published
- 2018
18. Combined Inhibition of CDK4/6 and PI3K/AKT/mTOR Pathways Induces a Synergistic Anti-Tumor Effect in Malignant Pleural Mesothelioma Cells
- Author
-
Andrea Ravelli, Paola Ulivi, Angelo Delmonte, Daniele Cretella, Denise Madeddu, Claudia Fumarola, Federico Quaini, Marcello Tiseo, Daniele Calistri, Angela Falco, Luca Ampollini, Paolo Carbognani, Mara Bonelli, Andrea Cavazzoni, Pier Giorgio Petronini, Roberta Alfieri, Graziana Digiacomo, Silvia La Monica, and Michela Tebaldi
- Subjects
Mesothelioma ,0301 basic medicine ,Original article ,Cancer Research ,Lung Neoplasms ,Tumor suppressor gene ,Cell Survival ,Pyridines ,Antineoplastic Agents ,Palbociclib ,lcsh:RC254-282 ,Piperazines ,Phosphatidylinositol 3-Kinases ,03 medical and health sciences ,Cyclin-dependent kinase ,Cell Line, Tumor ,Humans ,SA-β-GAL, Senescence Associated β-Galactosidase ,Protein Kinase Inhibitors ,Protein kinase B ,Cellular Senescence ,PI3K/AKT/mTOR pathway ,Cell Proliferation ,biology ,Cyclin-dependent kinase 4 ,TOR Serine-Threonine Kinases ,Cell Cycle ,Mesothelioma, Malignant ,RB, Retinoblastoma Protein ,Cyclin-Dependent Kinase 4 ,Drug Synergism ,Cyclin-Dependent Kinase 6 ,Cell cycle ,BAP1, BRCA1 Associated Protein 1 ,CDK, Cyclin-dependent kinase ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,030104 developmental biology ,biology.protein ,Cancer research ,Cyclin-dependent kinase 6 ,Proto-Oncogene Proteins c-akt ,Signal Transduction ,MPM, Malignant Pleural Mesothelioma - Abstract
Malignant pleural mesothelioma (MPM) is a progressive malignancy associated to the exposure of asbestos fibers. The most frequently inactivated tumor suppressor gene in MPM is CDKN2A/ARF , encoding for the cell cycle inhibitors p16 INK4a and p14 ARF , deleted in about 70% of MPM cases. Considering the high frequency of alterations of this gene, we tested in MPM cells the efficacy of palbociclib (PD-0332991), a highly selective inhibitor of cyclin-dependent kinase (CDK) 4/6. The analyses were performed on a panel of MPM cell lines and on two primary culture cells from pleural effusion of patients with MPM. All the MPM cell lines, as well as the primary cultures, were sensitive to palbociclib with a significant blockade in G0/G1 phase of the cell cycle and with the acquisition of a senescent phenotype. Palbociclib reduced the phosphorylation levels of CDK6 and Rb, the expression of myc with a concomitant increased phosphorylation of AKT. Based on these results, we tested the efficacy of the combination of palbociclib with the PI3K inhibitors NVP-BEZ235 or NVP-BYL719. After palbociclib treatment, the sequential association with PI3K inhibitors synergistically hampered cell proliferation and strongly increased the percentage of senescent cells. In addition, AKT activation was repressed while p53 and p21 were up-regulated. Interestingly, two cycles of sequential drug administration produced irreversible growth arrest and senescent phenotype that were maintained even after drug withdrawal. These findings suggest that the sequential association of palbociclib with PI3K inhibitors may represent a valuable therapeutic option for the treatment of MPM.
- Published
- 2017
19. Spatial architecture of tumour-infiltrating lymphocytes as a prognostic parameter in resected non-small-cell lung cancer
- Author
-
Francesco Sogni, Gabriella Becchi, Luigi Ventura, Federico Quaini, Luca Ampollini, Davide Marturano, Costanza Lagrasta, Letizia Gnetti, Denise Madeddu, G. Bocchialini, Giulia Mazzaschi, Paolo Carbognani, Michele Rusca, Cesare Braggio, Enrico Maria Silini, and Marcello Tiseo
- Subjects
Pulmonary and Respiratory Medicine ,Lung Neoplasms ,Proliferative index ,CD3 ,medicine.medical_treatment ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Lymphocytes, Tumor-Infiltrating ,Carcinoma, Non-Small-Cell Lung ,Tumor Microenvironment ,Medicine ,Humans ,Lung cancer ,Receptor ,030304 developmental biology ,0303 health sciences ,biology ,business.industry ,General Medicine ,Immunotherapy ,medicine.disease ,Prognosis ,Immune checkpoint ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,Surgery ,Neoplasm Recurrence, Local ,Cardiology and Cardiovascular Medicine ,business ,CD8 - Abstract
OBJECTIVES Tumour-infiltrating lymphocytes (TILs) are critically implicated in the clinical outcome and response to immunotherapy in non-small-cell lung cancer (NSCLC) patients. The functional competence of lymphocyte subpopulations is strongly conditioned by their spatial arrangement within the tumour immune microenvironment. The aim of this study was to determine whether the tissue localization of specific TIL subpopulations might have an impact on the risk of recurrence in surgically resected NSCLC. METHODS High-speed scanning of whole slide images was performed on immunohistochemically stained tissue sections from 97 NSCLC patients to assess the number and ratio of CD3+, CD8+ and PD-1+ T-lymphocytes. TIL distribution was computed considering the intratumoural (proximal or distal) and peripheral (invasive margin) localization as well as their location within the fibrotic tissue (immune excluded). The tumour proliferative index was assessed by Ki67 labelling. The impact of TILs number and distribution on clinical-pathological characteristics and outcomes were statistically analysed. RESULTS High density and percentage of proximal CD8+ TILs and low PD-1-to-CD8 ratio had a positive impact on disease-free-survival (P = 0.03) and overall survival (P = 0.003). An inverse correlation was observed between the abundance of intratumoural CD8+ TILs carrying PD-1 inhibitory receptor and cancer cell proliferation. Cases with high compared to low fraction of immune excluded CD8+ TILs had significantly reduced 5-year overall survival (n events: 22 vs 12; P = 0.04) and disease-free survival (n events: 24 vs 16; P = 0.03) rates while the amount of CD3+ and CD8+ TILs located at the invasive margin had a favourable effect on the clinical course. CONCLUSIONS Mapping TIL subpopulations may implement the definition of prognostic parameters in surgically resected NSCLC.
- Published
- 2019
20. Therapeutic Anti-Fibrotic Effect of Nintedanib in a Rat Model of Lung Fibrosis Induced by a Double Bleomycin Intratracheal Administration
- Author
-
Maria Pittelli, Silvia Pontis, Vanessa Pitozzi, Maurizio Civelli, M. Bonatti, Marcello Trevisani, Caterina Frati, Federico Quaini, Gino Villetti, Costanza Lagrasta, Denise Madeddu, and Paola Caruso
- Subjects
chemistry.chemical_compound ,Anti fibrotic ,chemistry ,business.industry ,Rat model ,Lung fibrosis ,Medicine ,Nintedanib ,Pharmacology ,business ,Bleomycin - Published
- 2019
21. 88P Identification of prognostic radio-immune-genetic profiles in patients affected by glioblastoma
- Author
-
Caterina Frati, Costanza Lagrasta, A. Pavarani, Maria Michiara, Federico Quaini, Denise Madeddu, Marcello Tiseo, A. Olivari, Giulia Mazzaschi, Pellegrino Crafa, and S. Dall'Asta
- Subjects
Oncology ,medicine.medical_specialty ,Immune system ,business.industry ,Internal medicine ,medicine ,Identification (biology) ,In patient ,Hematology ,medicine.disease ,business ,Glioblastoma - Published
- 2020
22. The circulating pool of functionally competent NK and CD8+ cells predicts the outcome of anti-PD1 treatment in advanced NSCLC
- Author
-
Franco Aversa, Matteo Goldoni, Marcello Tiseo, Francesco Facchinetti, Sebastiano Buti, Andrea Ardizzoni, Gabriele Missale, Alessandra Zecca, Denise Madeddu, Giulia Mazzaschi, Diana Canetti, Paola Bordi, Michele Veneziani, Francesco Gelsomino, Federico Quaini, Mazzaschi, Giulia, Facchinetti, Francesco, Missale, Gabriele, Canetti, Diana, Madeddu, Denise, Zecca, Alessandra, Veneziani, Michele, Gelsomino, Francesco, Goldoni, Matteo, Buti, Sebastiano, Bordi, Paola, Aversa, Franco, Ardizzoni, Andrea, Quaini, Federico, and Tiseo, Marcello
- Subjects
0301 basic medicine ,Pulmonary and Respiratory Medicine ,Male ,Cancer Research ,Lung Neoplasms ,medicine.medical_treatment ,CD3 ,Antineoplastic Agents ,Circulating immune cell ,CD8-Positive T-Lymphocytes ,NSCLC ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Carcinoma, Non-Small-Cell Lung ,Biomarkers, Tumor ,Medicine ,Humans ,Prospective Studies ,Aged ,Aged, 80 and over ,biology ,business.industry ,Immunotherapy ,Biomarker ,Middle Aged ,NKG2D ,Flow Cytometry ,Prognosis ,Granzyme B ,Immune profile ,Killer Cells, Natural ,030104 developmental biology ,Nivolumab ,Treatment Outcome ,Perforin ,Oncology ,030220 oncology & carcinogenesis ,biology.protein ,Cancer research ,Female ,business ,CD8 - Abstract
Introduction: A prospective investigation of the circulating immune profile in NSCLC patients receiving nivolumab was performed to identify potentially predictive parameters. Methods: Flow Cytometry of peripheral blood (PB) CD3+, CD8+, CD4+, NK, Treg and MDSCs was prospectively performed in 31 consecutive advanced NSCLC patients at baseline (T0) and after 2 (T1) and 4 (T2) cycles of bi-weekly nivolumab. Functional molecules (PD-1, CD3ζ Granzyme B, Perforin), cell proliferation (Ki67) and NK receptors (NKG2 A, NKG2D, NKp30) were also explored. The immunohistochemical evaluation of PD-L1 and TILs was restricted to available tumor biopsies. Tissue and circulating parameters were correlated to clinico-pathological features and treatment outcomes. Results: KRAS mutations, active smoking, COPD and steroid treatment conditioned a different distribution of circulating phenotypes. At baseline, clinical benefit (CB, n = 19) group displayed higher number of phenotypically active NK and PD-1+CD8+ cells (p < 0.01) compared to non-responders (NR, n = 12). Prolonged survival outcomes (p < 0.01) were recorded in cases with high baseline circulating NK and PD-1+CD8+ cells. At tissue level, low PD-1 expression in CD8 + TILs was a positive prognostic feature (p < 0.001). Strikingly, high circulating NK and PD-1+CD8+ cells combined with low PD-1/CD8+ ratio in TILs characterized a privileged context able to provide a significantly prolonged (p < 0.01) progression-free survival (PFS). During PD-1 blockade, NKs progressively raised in CB while declined in NR (p < 0.05) and this phenomenon was counterbalanced by parallel changes in Treg. Conclusion: The functional pool of circulating NKs associated with a divergent PD-1 expression in blood and tissue CD8+ lymphocytes portrays an immune profile predictive of anti-PD1 treatment efficacy.
- Published
- 2018
23. Imatinib mesylate-induced cardiomyopathy involves resident cardiac progenitors
- Author
-
Gallia Graiani, Emilia Corradini, Serena Galati, Donato Cappetta, Federica Galaverna, Costanza Lagrasta, Giulia Mazzaschi, Liberato Berrino, Caterina Frati, Lucia Prezioso, Angela Falco, Annamaria Buschini, Denise Madeddu, Franco Aversa, Monia Savi, Antonella De Angelis, Federico Quaini, Stefano Cavalli, Konrad Urbanek, Savi, M, Frati, C, Cavalli, S, Graiani, G, Galati, S, Buschini, A, Madeddu, D, Falco, A, Prezioso, L, Mazzaschi, G, Galaverna, F, Lagrasta, Cam, Corradini, E, De Angelis, A, Cappetta, D, Berrino, L, Aversa, F, Quaini, F, Urbanek, K, Savi, Monia, Frati, Caterina, Cavalli, Stefano, Graiani, Gallia, Galati, Serena, Buschini, Annamaria, Madeddu, Denise, Falco, Angela, Prezioso, Lucia, Mazzaschi, Giulia, Galaverna, Federica, Lagrasta, Costanza Anna Maria, Corradini, Emilia, De Angelis, Antonella, Cappetta, Donato, Berrino, Liberato, Aversa, Franco, Quaini, Federico, and Urbanek, Konrad
- Subjects
0301 basic medicine ,Male ,Programmed cell death ,medicine.drug_class ,Cardiomyopathy ,Hemodynamics ,030204 cardiovascular system & hematology ,Pharmacology ,Tyrosine-kinase inhibitor ,Cardiac progenitor cell ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Animals ,Humans ,Cells, Cultured ,Cardiotoxicity ,Cell Death ,Dose-Response Relationship, Drug ,business.industry ,Myocardium ,Stem Cells ,Kit ,medicine.disease ,Rats ,030104 developmental biology ,Imatinib mesylate ,Imatinib Mesylate ,Myocardial fibrosis ,business ,Cardiomyopathies ,Tyrosine kinase - Abstract
Cardiovascular complications are included among the systemic effects of tyrosine kinase inhibitor (TKI)-based therapeutic strategies. To test the hypothesis that inhibition of Kit tyrosine kinase that promotes cardiac progenitor cell (CPC) survival and function may be one of the triggering mechanisms of imatinib mesylate (IM)-related cardiovascular effects, the anatomical, structural and ultrastructural changes in the heart of IM-treated rats were evaluated. Cardiac anatomy in IM-exposed rats showed a dose-dependent, restrictive type of remodeling and depressed hemodynamic performance in the absence of remarkable myocardial fibrosis. The effects of IM on rat and human CPCs were also assessed. IM induced rat CPC depletion, reduced growth and increased cell death. Similar effects were observed in CPCs isolated from human hearts. These results extend the notion that cardiovascular side effects are driven by multiple actions of IM. The identification of cellular mechanisms responsible for cardiovascular complications due to TKIs will enable future strategies aimed at preserving concomitantly cardiac integrity and anti-tumor activity of advanced cancer treatment.
- Published
- 2018
24. Injectable Thermoreversible Hydrogels Based on Amphiphilic Polyurethanes: Structure-Property Correlations
- Author
-
L. Sacarescu, F. Quaini, Angela Falco, Gallia Graiani, Caterina Frati, C. Ciobanu, Mioara Drobota, M. Bercea, Stelian Vlad, C. Lagrasta, Luiza Madalina Gradinaru, and Denise Madeddu
- Subjects
Polymer science ,Chemistry ,Amphiphile ,Self-healing hydrogels ,Structure property - Published
- 2015
25. F-066BLOOD AND LYMPHATIC VESSELS CONSTITUTE AN ESSENTIAL COMPONENT OF THE IMMUNE MICROENVIRONMENT AND ITS IMPACT ON NON-SMALL CELL LUNG CANCER CLINICAL OUTCOME
- Author
-
Eugenio Quaini, G. Armani, G. Bocchialini, Luca Ampollini, Paolo Carbognani, Bruno Lorusso, Angela Falco, Giulia Mazzaschi, Caterina Frati, C. Lagrasta, Konrad Urbanek, Francesco Sogni, Denise Madeddu, and Federico Quaini
- Subjects
Pulmonary and Respiratory Medicine ,Pathology ,medicine.medical_specialty ,business.industry ,Immune microenvironment ,medicine.disease ,Lymphatic system ,Component (UML) ,Medicine ,Surgery ,Non small cell ,Cardiology and Cardiovascular Medicine ,business ,Lung cancer - Published
- 2017
26. P-155SURGICAL SAMPLING IS AN EMERGING ISSUE IN THE ASSESSMENT OF THE IMMUNE CONTEXTURE IN NON-SMALL CELL LUNG CANCER
- Author
-
Letizia Gnetti, Eugenio Quaini, Luigi Ventura, Stefano Cavalli, Giovanni Bocchialini, Denise Madeddu, Paolo Carbognani, Enrico Maria Silini, Federico Quaini, Luca Ampollini, and Giulia Mazzaschi
- Subjects
Pulmonary and Respiratory Medicine ,Immune system ,business.industry ,Immunology ,Medicine ,Sampling (statistics) ,Surgery ,Non small cell ,Cardiology and Cardiovascular Medicine ,business ,Lung cancer ,medicine.disease - Published
- 2017
27. Low PD-1 Expression in Cytotoxic CD8
- Author
-
Giulia, Mazzaschi, Denise, Madeddu, Angela, Falco, Giovanni, Bocchialini, Matteo, Goldoni, Francesco, Sogni, Giovanna, Armani, Costanza Annamaria, Lagrasta, Bruno, Lorusso, Chiara, Mangiaracina, Rocchina, Vilella, Caterina, Frati, Roberta, Alfieri, Luca, Ampollini, Michele, Veneziani, Enrico Maria, Silini, Andrea, Ardizzoni, Konrad, Urbanek, Franco, Aversa, Federico, Quaini, and Marcello, Tiseo
- Subjects
Male ,Lung Neoplasms ,Programmed Cell Death 1 Receptor ,CD8-Positive T-Lymphocytes ,Middle Aged ,Prognosis ,Lymphocytes, Tumor-Infiltrating ,Carcinoma, Non-Small-Cell Lung ,Mutation ,Biomarkers, Tumor ,Tumor Microenvironment ,Humans ,Female ,Neoplasm Metastasis ,Aged ,Neoplasm Staging ,Proportional Hazards Models - Published
- 2017
28. Notch Activation Modulates Bevacizumab Activity by CD44 Positive Cancer Stem Cells in Advanced Colon Cancer
- Author
-
Giuseppe Pedrazzi, Cinzia Azzoni, Lorena Bottarelli, Rosa Porzio, Francesca Negri, Andrea Gervasi, I. Tamagnini, Cecilia Bozzetti, L. Gnetti, Stefano Cascinu, Pellegrino Crafa, Francesco Leonardi, Lagrasta C, Anna Squadrilli, A. Ardizzoni, Angela Falco, F. Quaini, Gianluca Tomasello, Roberto Sala, A. Bisagni, Denise Madeddu, and Ragazzi M
- Subjects
CD31 ,biology ,Bevacizumab ,Colorectal cancer ,Angiogenesis ,business.industry ,CD44 ,Notch signaling pathway ,medicine.disease ,Cancer stem cell ,medicine ,biology.protein ,Cancer research ,Stem cell ,business ,medicine.drug - Abstract
Background: Notch pathway is involved in regulating colon cancer stem cells (CSCs), which play an important role in angiogenesis and resistance to conventional therapies. CD44 and CD133 are transmembrane glycoproteins reported as putative markers for isolating CSCs. High expression of Notch Intracellular Cleaved Domain (NICD) has been associated with resistance to anti-vascular endothelial growth factor therapy. Based on these reports, we evaluated NICD, CD44 and CD133 expression in a series of consecutive metastatic colon cancer patients treated with bevacizumab-based chemotherapy within first-line clinical trials. Methods: Histological samples obtained from 45 primary adenocarcinomas were tested by immunohistochemistry for NICD, CD44 and CD133. A scoring system based on staining intensity and percentage of stained cells was used. Vessels density was measured in hot-spot areas by CD31 antibody. Results: CD44 levels were higher in high NICD cases than in low NICD cases (63% vs. 16%, respectively, p=0.014). High NICD and CD44 levels predicted shorter progression-free (p
- Published
- 2017
29. Lung mesenchymal cells function as an inductive microenvironment for human lung cancer propagating cells†
- Author
-
Denise Madeddu, Luca Ampollini, Roberta Alfieri, Paolo Carbognani, Francesca Saccani, Eugenio Quaini, Bruno Lorusso, Michele Rusca, Sabrina Bonomini, Caterina Frati, Pietro Rossetti, Angela Falco, Gallia Graiani, Costanza Lagrasta, Letizia Gnetti, Andrea Gervasi, P. G. Petronini, Enrico Maria Silini, and Federico Quaini
- Subjects
Adult ,Male ,Pulmonary and Respiratory Medicine ,Pathology ,medicine.medical_specialty ,Lung Neoplasms ,Carcinogenesis ,Mice, Nude ,medicine.disease_cause ,Mice ,Carcinoma, Non-Small-Cell Lung ,Cell Line, Tumor ,Tumor Microenvironment ,medicine ,Animals ,Humans ,CD90 ,Lung cancer ,Lung ,Aged ,Aged, 80 and over ,Mice, Inbred BALB C ,Tumor microenvironment ,biology ,business.industry ,CD44 ,Mesenchymal stem cell ,Mesenchymal Stem Cells ,General Medicine ,Middle Aged ,medicine.disease ,humanities ,Cancer cell ,Neoplastic Stem Cells ,biology.protein ,Heterografts ,Adenocarcinoma ,Female ,Surgery ,Cardiology and Cardiovascular Medicine ,business ,Neoplasm Transplantation - Abstract
OBJECTIVES: The aim of the present study was to characterize the biological properties and in vivo tumourigenic potential of mesenchymal cells (MCs) obtained from non-small-cell lung cancer (NSCLC) samples. METHODS: NSCLC samples (53 adenocarcinomas and 24 squamous-cell carcinomas) surgically removed from 46 males and 31 females were processed to identify mesenchymal cells from human lung cancer (hLc-MCs). hLc-MCs were separated from neoplastic epithelial cells, expanded and extensively characterized in vitro. Subsequently, female BALB/c nude mice were subcutaneously injected with either 10 6 or 2.5 × 10 6 Calu-3 (human adenocarcinoma cell line able to reproducibly induce xenografted tumours) alone or in combination with equal doses of hLc-MCs. Control animals were injected with the two doses of hLc-MCs only. RESULTS: Primary cultures of hLc-MCs were obtained from >80% of NSCLC specimens. The typical MCs immunophenotype was documented by the expression of CD90, CD105, CD73, CD13 and CD44 at fluorescence-activated cell sorting analysis. CD45, CD14, CD34 and epithelial antigens were negative while CD117 (c-kit) and CD133 (prominin) were partially expressed. Interestingly, nuclear transcription factors octamer-binding transcription factor 3/4 and sex determining region Y-box 2 involved in stemness, thyroid transcription factor 1 in bronchoalveolar commitment, and ETS1 in carcinogenesis, were expressed in hLc-MCs isolated from NSCLC. Specific conditioned media and cocultures confirmed the supportive role of hLc-MCs for cancer cells. In vivo experiments showed that at both doses Calu-3 xenografts doubled in size when hLc-MCs were coinjected. Cell tracking in xenografted tumours, by immunofluorescence combined with fluorescence in situ hybridization analysis, documented hX-chromosome-labelled, Calu-3-derived cytokeratin-positive adenocarcinoma structures surrounded by hLc-MCs. CONCLUSIONS: Tumour-propagating cells require the inductive interaction of resident mesenchymal cells to foster lung cancer development.
- Published
- 2014
30. Low vagally-mediated heart rate variability and increased susceptibility to ventricular arrhythmias in rats bred for high anxiety
- Author
-
Gallia Graiani, Denise Madeddu, Luca Carnevali, Rainer Landgraf, Mimosa Trombini, Inga D. Neumann, Federico Quaini, Andrea Sgoifo, and Eugene Nalivaiko
- Subjects
Male ,Cardiac function curve ,medicine.medical_specialty ,Vagus Nerve Stimulation ,High anxiety ,Experimental and Cognitive Psychology ,Muscarinic Antagonists ,Disease ,Anxiety ,Electrocardiography ,Behavioral Neuroscience ,Heart Rate ,Internal medicine ,Heart rate ,medicine ,Animals ,Heart rate variability ,Rats, Wistar ,Isoproterenol ,Arrhythmias, Cardiac ,Rats, Inbred Strains ,Vagus Nerve ,Adrenergic beta-Agonists ,N-Methylscopolamine ,medicine.disease ,Adrenergic beta-1 Receptor Antagonists ,Comorbidity ,Rats ,Autonomic nervous system ,Endocrinology ,Atenolol ,medicine.symptom ,Psychology - Abstract
In humans, there is a documented association between anxiety disorders and cardiovascular disease. Putative underlying mechanisms may include an impairment of the autonomic nervous system control of cardiac function. The primary objective of the present study was to characterize cardiac autonomic modulation and susceptibility to arrhythmias in genetic lines of rats that differ largely in their anxiety level. To reach this goal, electrocardiographic recordings were performed in high-anxiety behavior (HAB, n=10) and low-anxiety behavior (LAB, n=10) rats at rest, during stressful stimuli and under autonomic pharmacological manipulations, and analyzed by means of time- and frequency-domain indexes of heart rate variability. During resting conditions, HAB rats displayed a reduced heart rate variability, mostly in terms of lower parasympathetic (vagal) modulation compared to LAB rats. In HAB rats, this relatively low cardiac vagal control was associated with smaller heart rate responsiveness to acute stressors compared to LAB counterparts. In addition, beta-adrenergic pharmacological stimulation induced a larger incidence of ventricular tachyarrhythmias in HABs compared to LABs. At sacrifice, a moderate increase in heart-body weight ratio was observed in HAB rats. We conclude that high levels of anxiety-related behavior in rats are associated with signs of i) impaired autonomic modulation of heart rate (low vagally-mediated heart rate variability), ii) poor adaptive heart rate responsiveness to stressful stimuli, iii) increased arrhythmia susceptibility, and iv) cardiac hypertrophy. These results highlight the utility of the HAB/LAB model for investigating the mechanistic basis of the comorbidity between anxiety disorders and cardiovascular disease.
- Published
- 2014
31. Diabetes induces systemic microvascular remodelling
- Author
-
A. Zecca, Bruno Lorusso, Angela Falco, Caterina Frati, Federico Quaini, Denise Madeddu, R. Fioretzaky, Gallia Graiani, Costanza Lagrasta, and C. Mangiaracina
- Subjects
Pharmacology ,medicine.medical_specialty ,Physiology ,Diabetes mellitus ,Internal medicine ,medicine ,Cardiology ,Molecular Medicine ,medicine.disease - Published
- 2018
32. In vitro effects of caffeine on human umbilical artery and vein endothelial cells
- Author
-
D. Cretella, G. Armani, Gallia Graiani, Bruno Lorusso, A. Zecca, Caterina Frati, Denise Madeddu, Angela Falco, Costanza Lagrasta, R. Vilella, T. Frusca, C. Mangiaracina, Federico Quaini, and R. Fioretzaki
- Subjects
Pharmacology ,010405 organic chemistry ,Physiology ,Chemistry ,010401 analytical chemistry ,Umbilical artery ,01 natural sciences ,In vitro ,0104 chemical sciences ,chemistry.chemical_compound ,medicine.anatomical_structure ,medicine.artery ,medicine ,Molecular Medicine ,Vein ,Caffeine - Published
- 2018
33. Differentially regulated high-throughput CT imaging features correlate to distinct tumor immune contextures portraying a radiomic signature with prognostic impact on surgically resected NSCLC
- Author
-
Luca Ampollini, Nicola Sverzellati, G. Bocchialini, Marcello Tiseo, Márcio José da Silva, Giulia Mazzaschi, Denise Madeddu, G. Roti, Federico Quaini, Letizia Gnetti, Gianluca Milanese, and Costanza Lagrasta
- Subjects
Immune system ,Oncology ,business.industry ,Cancer research ,Medicine ,Hematology ,Ct imaging ,business ,Throughput (business) ,Signature (logic) - Published
- 2019
34. Advanced CT imaging features reflect distinct tissue immune profiles and exhibit high prognostic impact on NSCLC
- Author
-
Mario Silva, Denise Madeddu, Costanza Lagrasta, Nicola Sverzellati, G. Roti, Federico Quaini, Gianluca Milanese, Angela Falco, Marcello Tiseo, D. Marturano, G. Bocchialini, Bruno Lorusso, Luca Ampollini, G. Armani, P. Pagano, and Giulia Mazzaschi
- Subjects
0301 basic medicine ,Pathology ,medicine.medical_specialty ,business.industry ,Hematology ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Immune system ,Oncology ,030220 oncology & carcinogenesis ,Medical imaging ,Medicine ,Ct imaging ,business - Published
- 2018
35. Biomimetic poly(glycerol sebacate) (PGS) membranes for cardiac patch application
- Author
-
Stefano Cavalli, Judith A. Roether, Niccoletta Barbani, Aldo R. Boccaccini, Marwa Tallawi, Caterina Frati, Ranjana Rai, Denise Madeddu, Elisabetta Rosellini, Dirk W. Schubert, Gallia Graiani, and Federico Quaini
- Subjects
Glycerol ,Time Factors ,Polymers ,02 engineering and technology ,Mass Spectrometry ,chemistry.chemical_compound ,Biomimetic Materials ,Spectroscopy, Fourier Transform Infrared ,Myocytes, Cardiac ,chemistry.chemical_classification ,0303 health sciences ,biology ,Tissue Scaffolds ,Hydrolysis ,Temperature ,Adhesion ,Polymer ,Prostheses and Implants ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,Membrane ,Covalent bond ,Mechanics of Materials ,lipids (amino acids, peptides, and proteins) ,0210 nano-technology ,Oligopeptides ,Porosity ,Materials science ,Surface Properties ,Green Fluorescent Proteins ,Bioengineering ,Biomaterials ,03 medical and health sciences ,Materials Science(all) ,Polymer chemistry ,Animals ,Humans ,Sodium Hydroxide ,030304 developmental biology ,Tissue Engineering ,Mechanical Engineering ,Decanoates ,Chemical modification ,Membranes, Artificial ,Mesenchymal Stem Cells ,Rats ,Fibronectin ,chemistry ,biology.protein ,Biophysics ,Microscopy, Electron, Scanning ,Surface modification - Abstract
In this study biomimetic poly(glycerol sebacate) PGS matrix was developed for cardiac patch application. The rationale was that such matrices would provide conducive environment for the seeded cells at the interphase with PGS. From the microstructural standpoint, PGS was fabricated into dense films and porous PGS scaffolds. From the biological aspect, biomimetic PGS membranes were developed via covalently binding peptides Tyr-Ile-Gly-Ser-Arg (YIGSR) and Gly-Arg-Gly-Asp-Ser-Pro (GRGDSP), corresponding to the epitope sequences of laminin and fibronectin, respectively onto the surface. To improve and enhance homogenous binding of peptides onto the PGS surface, chemical modification of its surface was carried out. A sequential regime of alkaline hydrolysis with 0.01 M NaOH for 5 min and acidification with 0.01 M HCl for 25 s was optimal. More COOH chemical group was exposed without causing deleterious effect on the bulk properties of the polymer as revealed by the physicochemical analysis carried out. HPLC analysis, chemical imaging and ToF-SIMS were able to establish the successful homogenous functionalization of PGS membranes with the peptides. Finally, the developed biomimetic membranes supported the adhesion and growth of rat and human cardiac progenitor cells.
- Published
- 2013
- Full Text
- View/download PDF
36. Combination of Gefitinib and Pemetrexed Prevents the Acquisition of TKI Resistance in NSCLC Cell Lines Carrying EGFR-Activating Mutation
- Author
-
Roberta Alfieri, Costanza Lagrasta, Maricla Galetti, Nadia Naldi, Silvia La Monica, Valentina Vivo, Angela Falco, Mara Bonelli, Pier Giorgio Petronini, Andrea Ardizzoni, Denise Madeddu, Claudia Fumarola, Daniele Cretella, Andrea Cavazzoni, Elisabetta Barocelli, Federico Quaini, Marcello Tiseo, Andrea Gervasi, La Monica, Silvia, Madeddu, Denise, Tiseo, Marcello, Vivo, Valentina, Galetti, Maricla, Cretella, Daniele, Bonelli, Mara, Fumarola, Claudia, Cavazzoni, Andrea, Falco, Angela, Gervasi, Andrea, Lagrasta, Costanza Annamaria, Naldi, Nadia, Barocelli, Elisabetta, Ardizzoni, Andrea, Quaini, Federico, Petronini, Pier Giorgio, and Alfieri, Roberta
- Subjects
0301 basic medicine ,Pulmonary and Respiratory Medicine ,Oncology ,medicine.medical_specialty ,Epithelial-Mesenchymal Transition ,Lung Neoplasms ,EGFR ,Antineoplastic Agents ,Pemetrexed ,NSCLC ,03 medical and health sciences ,T790M ,0302 clinical medicine ,Gefitinib ,Internal medicine ,Carcinoma, Non-Small-Cell Lung ,Cell Line, Tumor ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,heterocyclic compounds ,Epidermal growth factor receptor ,skin and connective tissue diseases ,neoplasms ,Protein Kinase Inhibitors ,TKI resistance ,biology ,Cell growth ,business.industry ,Cell cycle ,respiratory tract diseases ,ErbB Receptors ,030104 developmental biology ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,Mutation ,Cancer research ,biology.protein ,Quinazolines ,EGFR Activating Mutation ,business ,Tyrosine kinase ,medicine.drug - Abstract
Introduction Development of resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors is a clinical issue in patients with epidermal growth factor receptor gene ( EGFR ) - mutated non–small cell lung cancer (NSCLC). The aim of this study was to investigate the potential of combining gefitinib and pemetrexed in preventing the acquisition of resistance to EGFR tyrosine kinase inhibitors in NSCLC cell lines harboring EGFR exon 19 deletion. Methods The effect of different combinatorial schedules of gefitinib and pemetrexed on cell proliferation, cell cycle, apoptosis, and acquisition of gefitinib resistance in PC9 and HCC827 NSCLC cell lines and in PC9 xenograft models was investigated. Results Simultaneous treatment with gefitinib and pemetrexed enhanced cell growth inhibition and cell death and prevented the appearance of gefitinib resistance mediated by T790M mutation or epithelial-to-mesenchymal transition (EMT) in PC9 and HCC827 cells, respectively. In PC9 cells and in PC9 xenografts the combination of gefitinib and pemetrexed, with different schedules, prevented gefitinib resistance only when pemetrexed was the first treatment, given alone or together with gefitinib. Conversely, when gefitinib alone was administered first and pemetrexed sequentially alternated, a negative interaction was observed and no prevention of gefitinib resistance was documented. The mechanisms of resistance that developed in vivo included T790M mutation and EMT. The induction of EMT was a feature of tumors treated with gefitinib when given before pemetrexed, whereas T790M was recorded only in tumors treated with gefitinib alone. Conclusions The combination of gefitinib and pemetrexed is effective in preventing gefitinib resistance; the application of intermittent treatments requires that gefitinib not be administered before pemetrexed.
- Published
- 2015
37. 1O Integration of tissue and circulating parameters identifies a favorable immune profile in NSCLC patients treated with nivolumab
- Author
-
F. Aversa, Marcello Tiseo, Francesco Facchinetti, Sebastiano Buti, G. Missale, Denise Madeddu, Francesco Gelsomino, Giulia Mazzaschi, Andrea Ardizzoni, and Federico Quaini
- Subjects
Pulmonary and Respiratory Medicine ,Oncology ,medicine.medical_specialty ,Immune system ,business.industry ,Internal medicine ,medicine ,Nivolumab ,business - Published
- 2018
38. In vitro biological and functional properties of human endothelial cells from different sources exposed to different beta-blockers
- Author
-
G. Cerasoli, V. Spigoni, S. Manni, Angela Falco, Federico Quaini, Andrea Gervasi, Bruno Lorusso, A. Nannetti, Laura Rinaldi, Caterina Frati, F.P. Pilato, T. Frusca, Denise Madeddu, L. Gnetti, and Costanza Lagrasta
- Subjects
Pharmacology ,Physiology ,Chemistry ,Molecular Medicine ,Beta (finance) ,In vitro - Published
- 2015
39. P3.01-050 Isolation and Characterization of Lymphatic Endothelial Cells from Neoplastic and Normal Human Lung
- Author
-
Stefano Cavalli, Andrea Gervasi, Angela Falco, Costanza Lagrasta, Denise Madeddu, Federico Quaini, Bruno Lorusso, G. Bocchialini, and Giulia Mazzaschi
- Subjects
Pulmonary and Respiratory Medicine ,Pathology ,medicine.medical_specialty ,Isolation (health care) ,business.industry ,government.form_of_government ,medicine.disease ,Human lung ,Lymphatic Endothelium ,medicine.anatomical_structure ,Oncology ,medicine ,government ,Lung cancer ,business - Published
- 2017
40. P2.01-062 Impact of the Tissue Distribution of Subpopulations of TILs and PD-L1 Expression on the Clinical Outcome of NSCLC
- Author
-
G. Bocchialini, Luca Ampollini, Paolo Carbognani, Marcello Tiseo, Andrea Gervasi, Denise Madeddu, Giulia Mazzaschi, Angela Falco, Bruno Lorusso, Caterina Frati, Federico Quaini, and Costanza Lagrasta
- Subjects
Pulmonary and Respiratory Medicine ,Oncology ,Pathology ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Thoracic cancer ,Outcome (game theory) ,Targeted therapy ,Internal medicine ,medicine ,Pd l1 expression ,Tissue distribution ,business ,Immune mechanisms - Published
- 2017
41. A suspension bioreactor for culturing and investigating tumor cell clusters
- Author
-
Diana Massai, GIUSEPPE ISU, Denise, Madeddu, Cerino Abdin, Giulia, Caterina, Frati, Angela, Falco, Diego Gallo, Alberto L. Audenino, Federico, Quaini, and Umberto Morbiducci
- Published
- 2014
42. Bone Marrow Remodelling and Topographic Redistribution of CD34 Positive Progenitors Characterize the Progression of Myelodysplastic Syndromes and Their Evolution to AML
- Author
-
Giannalisa Todaro, Angela Falco, Luisa Craviotto, Nicola Giuliani, Benedetta Cambò, Gallia Graiani, Cristina Mancini, Eugenia Martella, Monica Crugnola, Lucia Prezioso, Gabriella Sammarelli, Francesca Re, Denise Madeddu, Franco Aversa, Rodanthi Fioretzaki, and Federico Quaini
- Subjects
business.industry ,Myelodysplastic syndromes ,Immunology ,Azacitidine ,CD34 ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Haematopoiesis ,medicine.anatomical_structure ,hemic and lymphatic diseases ,Myeloproliferation ,medicine ,Cancer research ,Bone marrow ,Stem cell ,Progenitor cell ,business ,medicine.drug - Abstract
Myelodysplastic Syndrome (MDS) is a multifaceted disease of Hematopoietic Stem Cells characterized by myeloproliferation associated with mono- or pan-cytopenia, ultimately leading to an advantageous clonal growth of frankly leukemic cells. Although the disruption of bone marrow (BM) architecture and alterations of differentiated hematopoietic compartments have been repeatedly described, the potential involvement of the structural remodeling and redistribution of hematopoietic progenitors within the BM on the evolution of MDS has been poorly investigated. The aim of our study was to determine whether the number and localization of CD34pos progenitors and vascular structures are differentially affected in MDS subcategories and whether these changes are associated with disease progression. Thus, the morphometric evaluation of the number and linear distance from the endosteal surface (PT: paratrabecular 21mm) of capillaries, sinusoids, arterioles and CD34pos progenitors was performed by immunohistochemistry on BM biopsies from 97 consecutive MDS patients (12 RA; 2 RCUD; 19 RCMD; 3 RARS-T; 2 5q-; 20 RAEB-1; 27 RAEB-2; 12 U-MDS) in stable or evolving disease and in 15 cases that progressed to AML. Controls (CTR) were represented by 22 disease-free BM biopsies. Risk stratification was based on IPSS. Compared to CTR, capillary density linearly increased in IT marrow from RA thorough RAEB-1, with a subsequent progressive drop in RAEB-2 and AML. Sinusoid density was reduced in MDS and progressively declined from RAEB-1 through AML. PT and IT arterioles increased by more than 3-fold in MDS vs CTR although a progressive rarefaction associated with an increased thickness was measured from RA thorough RAEB-2. A marked rise in arteriolar number was also observed in AML. As expected, CD34pos cell number progressively increased with the severity of the disease, however, a sharp redistribution from PT to perisinusoid and fat areas within the IT marrow was documented (Figure). Intriguingly, the BM redistribution of vascular structures had higher impact than the increased number of CD34pos progenitors to identify high risk MDS and the subset of MDS patients who subsequently developed AML. Finally, patients responsive to azacytidine displayed a reduced number and a topographic redistribution of CD34pos cells together with an increased BM capillarization. BM structural remodelling and rearrangement of hematopoietic progenitors characterize the evolution of MDS. The prognostic significance and the predictive value of these parameters may be translated in new therapeutic approaches able to improve patient management. Figure Figure. Disclosures Giuliani: Janssen: Research Funding; Celgene: Research Funding.
- Published
- 2016
43. Parenchymal and Stromal Cells Contribute to Pro-Inflammatory Myocardial Environment at Early Stages of Diabetes: Protective Role of Resveratrol
- Author
-
Costanza Lagrasta, Daniele Del Rio, Caterina Frati, Monia Savi, Michele Miragoli, Letizia Bresciani, Serena Pollino, Leonardo Bocchi, Roberto Sala, Angela Falco, Denise Madeddu, Massimiliano Zaniboni, Federico Quaini, and Donatella Stilli
- Subjects
Male ,0301 basic medicine ,cardiac cell compartments ,medicine.medical_treatment ,030204 cardiovascular system & hematology ,Resveratrol ,chemistry.chemical_compound ,0302 clinical medicine ,Stilbenes ,Myocyte ,Macrophage ,Myocytes, Cardiac ,Cells, Cultured ,Nutrition and Dietetics ,diabetes ,cardiomyocyte mechanics ,Anti-Inflammatory Agents, Non-Steroidal ,Cytokine ,medicine.symptom ,lcsh:Nutrition. Foods and food supply ,medicine.medical_specialty ,Stromal cell ,intracellular calcium dynamics ,lcsh:TX341-641 ,Inflammation ,Biology ,Article ,Diabetes Mellitus, Experimental ,03 medical and health sciences ,Diabetes mellitus ,Internal medicine ,medicine ,Animals ,Rats, Wistar ,polyphenols ,Macrophages ,Myocardium ,Fibroblasts ,medicine.disease ,cytokines ,Rats ,030104 developmental biology ,Endocrinology ,Animals, Newborn ,chemistry ,Calcium ,Stromal Cells ,Ex vivo ,Food Science - Abstract
Background: Little information is currently available concerning the relative contribution of cardiac parenchymal and stromal cells in the activation of the pro-inflammatory signal cascade, at the initial stages of diabetes. Similarly, the effects of early resveratrol (RSV) treatment on the negative impact of diabetes on the different myocardial cell compartments remain to be defined. Methods: In vitro challenge of neonatal cardiomyocytes and fibroblasts to high glucose and in vivo/ex vivo experiments on a rat model of Streptozotocin-induced diabetes were used to specifically address these issues. Results: In vitro data indicated that, besides cardiomyocytes, neonatal fibroblasts contribute to generating initial changes in the myocardial environment, in terms of pro-inflammatory cytokine expression. These findings were mostly confirmed at the myocardial tissue level in diabetic rats, after three weeks of hyperglycemia. Specifically, monocyte chemoattractant protein-1 and Fractalkine were up-regulated and initial abnormalities in cardiomyocyte contractility occurred. At later stages of diabetes, a selective enhancement of pro-inflammatory macrophage M1 phenotype and a parallel reduction of anti-inflammatory macrophage M2 phenotype were associated with a marked disorganization of cardiomyocyte ultrastructural properties. RSV treatment inhibited pro-inflammatory cytokine production, leading to a recovery of cardiomyocyte contractile efficiency and a reduced inflammatory cell recruitment. Conclusion: Early RSV administration could inhibit the pro-inflammatory diabetic milieu sustained by different cardiac cell types.
- Published
- 2016
44. Differential pattern of myocardial remodelling in genetically determined and load-dependent hypertrophy in humans
- Author
-
Bruno Lorusso, Eugenio Quaini, Caterina Frati, Konrad Urbanek, Angela Falco, Denise Madeddu, Federico Quaini, Gallia Graiani, M. Iascone, Andrea Gervasi, C. Mangiaracina, Costanza Lagrasta, P. Ferrazzi, Pietro Rossetti, and S. Cavalli
- Subjects
Pharmacology ,medicine.medical_specialty ,Endocrinology ,Physiology ,Internal medicine ,medicine ,Molecular Medicine ,Biology ,Differential (mathematics) ,Muscle hypertrophy - Published
- 2015
45. Assessment of cardiac patches suitability for tissue engineering
- Author
-
Andrea Gervasi, Ranjana Rai, Angela Falco, Aldo R. Boccaccini, Bruno Lorusso, Gallia Graiani, Federico Quaini, Denise Madeddu, Caterina Frati, Costanza Lagrasta, and Elisabetta Rosellini
- Subjects
Pharmacology ,Engineering ,Tissue engineering ,Physiology ,business.industry ,Molecular Medicine ,business ,Biomedical engineering - Published
- 2015
46. Cancer treatment-induced cardiotoxicity: a cardiac stem cell disease?
- Author
-
Francesca Rossi, Eugenio Quaini, Federico Quaini, E. Lodi Rizzini, A. Maseri, Monia Savi, Gallia Graiani, Elena Piegari, E. Musso, Caterina Frati, Francesca Ferraro, Costanza Lagrasta, Lucia Prezioso, Donatella Stilli, A De Angelis, Stefano Cavalli, B. Testa, Federica Galaverna, Konrad Urbanek, Sara Galati, Silvia Tanzi, Denise Madeddu, Prezioso, L, Tanzi, S, Galaverna, F, Frati, C, Testa, B, Savi, M, Graiani, G, Lagrasta, C, Cavalli, S, Galati, S, Madeddu, D, Lodi Rizzini, E, Ferraro, F, Musso, E, Stilli, D, Urbanek, K, Piegari, E, De Angelis, A, Maseri, A, Rossi, F, Quaini, E, Quaini, F, LODI RIZZINI, E, Piegari, Elena, DE ANGELIS, Antonella, Rossi, Francesco, and Quaini, F.
- Subjects
Anthracycline ,Population ,Antineoplastic Agents ,Disease ,Bioinformatics ,Cardiotoxins ,Neoplasms ,Medicine ,Animals ,Humans ,Anthracyclines ,education ,Protein Kinase Inhibitors ,Cause of death ,Pharmacology ,Cardiotoxicity ,education.field_of_study ,Mechanism (biology) ,business.industry ,Myocardium ,Stem Cells ,Cancer ,Hematology ,Protein-Tyrosine Kinases ,medicine.disease ,Cardiovascular Diseases ,Immunology ,Stem cell ,Cardiology and Cardiovascular Medicine ,business - Abstract
Cardiovascular diseases and cancer represent respectively the first and second cause of death in industrialized countries. These two conditions may become synergistic when cardiovascular complications of anti-cancer therapy are considered. More than 70% of childhood and 50% of adult cancer patients can be cured, however this important success obtained by the biological and medical research is obfuscated by emerging findings of early and late morbidity due to cardiovascular events. Although anthracyclines are effective drugs against cancer a dose-dependent cardiotoxic effects whose mechanism has not been elucidated resulting in failure of therapeutic interventions limit their use. Unexpectedly, tyrosine/ kinase inhibitors (TKIs) aimed at molecularly interfering with oncogenic pathways, have been implicated in cardiac side effects. Possible explanations of this phenomenon have been ambiguous, further strengthening the need to deepen our understanding on the mechanism of cardiotoxicity. In addition to a detailed description of anthracyclines and TKIs-related cardiovascular effects, the present review highlights recent observations supporting the hypothesis that the cellular target of anthracyclines and TKIs may include myocardial compartments other than parenchymal cells. The demonstration that the adult mammalian heart possesses a cell turnover regulated by primitive cells suggests that this cell population may be implicated in the onset and development of cardiovascular effects of anti-cancer strategies. The possibility of preventing cardiotoxicity by preservation and/or expansion of the resident stem cell pool responsible for cardiac repair may open new therapeutic options to unravel an unsolved clinical issue.
- Published
- 2009
47. F-038 * LUNG MESENCHYMAL STEM CELLS FUNCTION AS THE INDUCTIVE MICROENVIRONMENT FOR HUMAN LUNG CANCER PROPAGATING CELLS
- Author
-
Denise Madeddu, Federico Quaini, Francesca Saccani, Angela Falco, Eugenio Quaini, Paolo Carbognani, Gallia Graiani, Bruno Lorusso, Caterina Frati, and Luca Ampollini
- Subjects
Pulmonary and Respiratory Medicine ,Lung ,business.industry ,Mesenchymal stem cell ,medicine.disease ,Epithelium ,Cell biology ,medicine.anatomical_structure ,Antigen ,Cancer stem cell ,Cell culture ,medicine ,Adenocarcinoma ,Surgery ,Cardiology and Cardiovascular Medicine ,Lung cancer ,business - Published
- 2014
48. Resident cardiac stem cells
- Author
-
C. Mangiaracina, F. Quaini, Francesca Rossi, Francesca Ferraro, Konrad Urbanek, Monia Savi, A De Angelis, Caterina Frati, Eugenio Quaini, Stefano Cavalli, Donatella Stilli, Costanza Lagrasta, Angela Falco, Annarosa Leri, Pietro Rossetti, Gallia Graiani, Alessandra Rossini, Jan Kajstura, Piero Anversa, Denise Madeddu, E. Musso, Lucia Prezioso, Frati, C, Savi, M, Graiani, G, Lagrasta, C, Cavalli, S, Prezioso, L, Rossetti, P, Mangiaracina, C, Ferraro, F, Madeddu, D, Musso, E, Stilli, D, Rossini, A, Falco, A, De Angelis, A, Rossi, F, Urbanek, K, Leri, A, Kajstura, J, Anversa, P, Quaini, E, Quaini, F., DE ANGELIS, Antonella, and Rossi, Francesco
- Subjects
Pathology ,medicine.medical_specialty ,Heart disease ,Cellular differentiation ,Cardiomyopathy ,Myocardial Ischemia ,Bone Marrow Cells ,Bioinformatics ,Cell therapy ,Drug Discovery ,Medicine ,Humans ,Regeneration ,Myocytes, Cardiac ,Progenitor cell ,Pharmacology ,Clinical Trials as Topic ,business.industry ,Myocardium ,Stem Cells ,Cell Differentiation ,Heart ,medicine.disease ,medicine.anatomical_structure ,Treatment Outcome ,Heart failure ,Bone marrow ,Stem cell ,business ,Cardiomyopathies ,Stem Cell Transplantation - Abstract
The introduction of stem cells in cardiology provides new tools in understanding the regenerative processes of the normal and pathologic heart and opens new options for the treatment of cardiovascular diseases. The feasibility of adult bone marrow autologous and allogenic cell therapy of ischemic cardiomyopathies has been demonstrated in humans. However, many unresolved questions remain to link experimental with clinical observations. The demonstration that the heart is a self-renewing organ and that its cell turnover is regulated by myocardial progenitor cells offers novel pathogenetic mechanisms underlying cardiac diseases and raises the possibility to regenerate the damaged heart. Indeed, cardiac stem progenitor cells (CSPCs) have recently been isolated from the human heart by several laboratories although differences in methodology and phenotypic profile have been described. The present review points to the potential role of CSPCs in the onset and development of congestive heart failure and its reversal by regenerative approaches aimed at the preservation and expansion of the resident pool of progenitors.
49. Favorable clinical outcome and response to immunotherapy share a common PD-L1/PD-1 based NSCLC immune contexture
- Author
-
Giulia Mazzaschi, G. Bocchialini, Denise Madeddu, G. Armani, Letizia Gnetti, A. Ardizzoni, Federico Quaini, Franco Aversa, Marcello Tiseo, and Francesco Sogni
- Subjects
0301 basic medicine ,biology ,business.industry ,medicine.medical_treatment ,Hematology ,Immunotherapy ,Outcome (game theory) ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Immune system ,Oncology ,030220 oncology & carcinogenesis ,PD-L1 ,Immunology ,biology.protein ,Medicine ,business
50. Divergent PD-1 expression in tissue and circulating CD8 lymphocytes defines an immune profile predictive of the response to nivolumab in advanced NSCLC
- Author
-
Francesco Sogni, G. Bocchialini, Marcello Tiseo, Francesco Facchinetti, G. Armani, Bruno Lorusso, Caterina Frati, Costanza Lagrasta, Angela Falco, C. Mangiaracina, Enrico Maria Silini, Federico Quaini, A. Ardizzoni, R. Vilella, Michele Veneziani, Gabriele Missale, Giulia Mazzaschi, and Denise Madeddu
- Subjects
Immune system ,Oncology ,business.industry ,Cancer research ,Medicine ,Hematology ,Nivolumab ,business ,CD8/Lymphocytes
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.