Search

Your search keyword '"Buccarelli, Mariachiara"' showing total 145 results
Start Over Author "Buccarelli, Mariachiara"
145 results on '"Buccarelli, Mariachiara"'

1. Extracellular vesicles produced by irradiated endothelial or Glioblastoma stem cells promote tumor growth and vascularization modulating tumor microenvironment

Author

Castellani, Giorgia, Buccarelli, Mariachiara, D’Alessandris, Quintino Giorgio, Ilari, Ramona, Cappannini, Andrea, Pedini, Francesca, Boe, Alessandra, Lulli, Valentina, Parolini, Isabella, Giannetti, Stefano, Biffoni, Mauro, Zappavigna, Vincenzo, Marziali, Giovanna, Pallini, Roberto, and Ricci-Vitiani, Lucia

Published
2024
Full Text
View/download PDF

2. N‐Acetyl‐L‐Cysteine (NAC) Blunts Axitinib‐Related Adverse Effects in Preclinical Models of Glioblastoma.

Author

Formato, Alessia, Salbini, Maria, Orecchini, Elisa, Pellegrini, Manuela, Buccarelli, Mariachiara, Vitiani, Lucia Ricci, Giannetti, Stefano, Pallini, Roberto, D'Alessandris, Quintino Giorgio, Lauretti, Liverana, Martini, Maurizio, De Falco, Valentina, Levi, Andrea, Falchetti, Maria Laura, and Mongiardi, Maria Patrizia

Subjects
VASCULAR endothelial growth factor receptors, STEM cell treatment, ATAXIA telangiectasia, RENAL cell carcinoma, CELLULAR aging
Abstract

Objective: Axitinib is a tyrosine kinase inhibitor characterized by a strong affinity for Vascular Endothelial Growth Factor Receptors (VEGFRs). It was approved in 2012 by Food and Drug Administration and European Medicines Agency as a second line treatment for advanced renal cell carcinoma and is currently under evaluation in clinical trial for the treatment of other cancers. Glioblastoma IDH‐wild type (GBM) is a highly malignant brain tumor characterized by diffusely infiltrative growth pattern and by a prominent neo‐angiogenesis. In GBM, axitinib has demonstrated a limited effectiveness as a monotherapy, while it was recently shown to significantly improve its efficacy in combination treatments. In preclinical models, axitinib has been reported to trigger cellular senescence both in tumor as well as in normal cells, through a mechanism involving intracellular reactive oxygen species (ROS) accumulation and activation of Ataxia Telangiectasia Mutated kinase (ATM). Limiting axitinib‐dependent ROS increase by antioxidants prevents senescence specifically in normal cells, without affecting tumor cells. Methods: We used brain tumor xenografts obtained by engrafting Glioma Stem Cells (GSCs) into the brain of immunocompromised mice, to investigate the hypothesis that the antioxidant molecule N‐Acetyl‐L‐Cysteine (NAC) might be used to reduce senescence‐associated adverse effects of axitinib treatment without altering its anti‐tumor activity. Results: We demonstrate that the use of the antioxidant molecule N‐Acetyl‐Cysteine (NAC) in combination with axitinib stabilizes tumor microvessels in GBM tumor orthotopic xenografts, eventually resulting in vessel normalization, and protects liver vasculature from axitinib‐dependent toxicity. Conclusion: Overall, we found that NAC co‐treatment allows vessel normalization in brain tumor vessels and exerts a protective effect on liver vasculature, therefore minimizing axitinib‐dependent toxicity. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

3. Pervasive structural heterogeneity rewires glioblastoma chromosomes to sustain patient-specific transcriptional programs

Author

Xie, Ting, primary, Danieli-Mackay, Adi, additional, Buccarelli, Mariachiara, additional, Barbieri, Mariano, additional, Papadionysiou, Ioanna, additional, D’Alessandris, Q. Giorgio, additional, Robens, Claudia, additional, Übelmesser, Nadine, additional, Vinchure, Omkar Suhas, additional, Lauretti, Liverana, additional, Fotia, Giorgio, additional, Schwarz, Roland F., additional, Wang, Xiaotao, additional, Ricci-Vitiani, Lucia, additional, Gopalakrishnan, Jay, additional, Pallini, Roberto, additional, and Papantonis, Argyris, additional

Published
2024
Full Text
View/download PDF

5. FMRP modulates the Wnt signalling pathway in glioblastoma

Author

Pedini, Giorgia, Buccarelli, Mariachiara, Bianchi, Fabrizio, Pacini, Laura, Cencelli, Giulia, D’Alessandris, Quintino Giorgio, Martini, Maurizio, Giannetti, Stefano, Sasso, Franceschina, Melocchi, Valentina, Farace, Maria Giulia, Achsel, Tilmann, Larocca, Luigi M., Ricci-Vitiani, Lucia, Pallini, Roberto, and Bagni, Claudia

Published
2022
Full Text
View/download PDF

6. CD8+CD103+PD1+TIM3+ T cells in glioblastoma microenvironment correlate with prognosis

Author

Romagnoli, Giulia, D'Alessandris, Quintino Giorgio, Capone, Imerio, Tavilla, Andrea, Canini, Irene, Lapenta, Caterina, Buccarelli, Mariachiara, Giordano, Martina, Tirelli, Valentina, Sanchez, Massimo, Fragale, Alessandra, Giannetti, Stefano, Di Bonaventura, Rina, Lauretti, Liverana, Biffoni, Mauro, Ricci‐vitiani, Lucia, Pallini, Roberto, Gabriele, Lucia, D'Alessandris, Quintino Giorgio (ORCID:0000-0002-2953-9291), Giannetti, Stefano (ORCID:0000-0002-9456-8865), Lauretti, Liverana (ORCID:0000-0002-6463-055X), Pallini, Roberto (ORCID:0000-0002-4611-8827), Romagnoli, Giulia, D'Alessandris, Quintino Giorgio, Capone, Imerio, Tavilla, Andrea, Canini, Irene, Lapenta, Caterina, Buccarelli, Mariachiara, Giordano, Martina, Tirelli, Valentina, Sanchez, Massimo, Fragale, Alessandra, Giannetti, Stefano, Di Bonaventura, Rina, Lauretti, Liverana, Biffoni, Mauro, Ricci‐vitiani, Lucia, Pallini, Roberto, Gabriele, Lucia, D'Alessandris, Quintino Giorgio (ORCID:0000-0002-2953-9291), Giannetti, Stefano (ORCID:0000-0002-9456-8865), Lauretti, Liverana (ORCID:0000-0002-6463-055X), and Pallini, Roberto (ORCID:0000-0002-4611-8827)

Abstract

Glioblastoma, isocitrate dehydrogenase-wildtype (GB), is the most common and aggressive primary brain malignancy with poor outcome. Immune checkpoint inhibitors (ICIs) have been tested in GB and, despite disappointing results, the identification of a small subgroup of responders underlies the need to improve our understanding of the tumour microenvironment (TME) immunity. This study aimed to determine whether the expression of selected immune checkpoints on tissue-resident memory T cells (Trm) may predict patient outcome. We conducted a single cohort observational study. Tumour samples were collected from 45 patients with histologically confirmed GB (WHO grade 4) and processed to obtain single-cell suspensions. Patients were assessed for the correlation of Trm phenotype with overall survival (OS) or progression-free survival (PFS) using multiparametric flow cytometry and uni/multivariate analyses. Levels of Trm expressing programmed cell death protein 1 (PD1) and T cell immunoglobulin and mucin domain-containing protein 3 (TIM3) were found to be linked to clinical outcome. Low frequency of Trm expressing PD1 or TIM3 or both markers defined subgroups as independent positive prognostic factors for patient survival. On multivariate analysis, low CD8+CD103+PD1+TIM3+ Trm and Karnofsky performance status (KPS) >= 70 were confirmed to be the most predictive independent factors associated with longer OS (hazard ratios-HR [95%CI]: 0.14 [0.04-0.52] p < 0.001, 0.39 [0.16-0.96] p = 0.04, respectively). The CD8+CD103+ Trm subgroups were also age-related predictors for survival in GB.

Published
2024

8. CD8+CD103+PD1+TIM3+ T cells in glioblastoma microenvironment correlate with prognosis

Author

Romagnoli, Giulia, primary, D'Alessandris, Quintino Giorgio, additional, Capone, Imerio, additional, Tavilla, Andrea, additional, Canini, Irene, additional, Lapenta, Caterina, additional, Buccarelli, Mariachiara, additional, Giordano, Martina, additional, Tirelli, Valentina, additional, Sanchez, Massimo, additional, Fragale, Alessandra, additional, Giannetti, Stefano, additional, Di Bonaventura, Rina, additional, Lauretti, Liverana, additional, Biffoni, Mauro, additional, Ricci‐Vitiani, Lucia, additional, Pallini, Roberto, additional, and Gabriele, Lucia, additional

Published
2023
Full Text
View/download PDF

9. CD8+CD103+PD1+TIM3+ T cells in glioblastoma microenvironment correlate with prognosis.

Author

Gabriele, Lucia, primary, Romagnoli, Giulia, additional, D'Alessandris, Quintino Giorgio, additional, Capone, Imerio, additional, Tavilla, Andrea, additional, Canini, Irene, additional, Lapenta, Caterina, additional, Buccarelli, Mariachiara, additional, Giordano, Martina, additional, Tirelli, Valentina, additional, Sanchez, Massimo, additional, Fragale, Alessandra, additional, Giannetti, Stefano, additional, Bonaventura, Rina Di, additional, Lauretti, Liverana, additional, Biffoni, Mauro, additional, Ricci-Vitiani, Lucia, additional, and Pallini, Roberto, additional

Published
2023
Full Text
View/download PDF

11. Extreme structural heterogeneity rewires glioblastoma chromosomes to sustain patient-specific transcriptional programs

Author

Xie, Ting, primary, Danieli-Mackay, Adi, additional, Buccarelli, Mariachiara, additional, Barbieri, Mariano, additional, Papadionysiou, Ioanna, additional, Giorgio D’Alessandris, Q., additional, Übelmesser, Nadine, additional, Vinchure, Omkar Suhas, additional, Lauretti, Liverana, additional, Fotia, Giorgio, additional, Wang, Xiaotao, additional, Ricci-Vitiani, Lucia, additional, Gopalakrishnan, Jay, additional, Pallini, Roberto, additional, and Papantonis, Argyris, additional

Published
2023
Full Text
View/download PDF

15. Characterization of Glioblastoma Cells Response to Regorafenib

Author

Mongiardi, Maria Patrizia, primary, Buccarelli, Mariachiara, additional, Formato, Alessia, additional, Orecchini, Elisa, additional, Salbini, Maria, additional, Ricci, Valentina, additional, Orsini, Tiziana, additional, Putti, Sabrina, additional, Chiesa, Silvia, additional, Ricci-Vitiani, Lucia, additional, D’Alessandris, Quintino Giorgio, additional, Pallini, Roberto, additional, Levi, Andrea, additional, and Falchetti, Maria Laura, additional

Published
2022
Full Text
View/download PDF

17. Development and Validation of a HPLC–MS/MS Method to Measure Nifuroxazide and Its Application in Healthy and Glioblastoma-Bearing Mice

Author

Ceruti, Tommaso, primary, D’Alessandris, Quintino Giorgio, additional, Frapolli, Roberta, additional, Gopalakrishnan, Jay, additional, Buccarelli, Mariachiara, additional, Meroni, Marina, additional, Lauretti, Liverana, additional, Ricci-Vitiani, Lucia, additional, Pallini, Roberto, additional, and Zucchetti, Massimo, additional

Published
2022
Full Text
View/download PDF

19. Glioblastoma Stem-Like Cells (GSCs) with Mesenchymal Signature: Lipid Profiles of Mobile Lipids Obtained with MRS before and after Radio/Chemical Treatments

Author

Grande, Sveva, primary, Palma, Alessandra, additional, Luciani, Anna Maria, additional, Anello, Pasqualino, additional, Ricci-Vitiani, Lucia, additional, Buccarelli, Mariachiara, additional, D’Alessandris, Quintino Giorgio, additional, Pallini, Roberto, additional, Guidoni, Laura, additional, Viti, Vincenza, additional, and Rosi, Antonella, additional

Published
2022
Full Text
View/download PDF

20. MiR-378a-3p Acts as a Tumor Suppressor in Colorectal Cancer Stem-Like Cells and Affects the Expression of MALAT1 and NEAT1 lncRNAs

Author

Castellani, Giorgia, primary, Buccarelli, Mariachiara, additional, Lulli, Valentina, additional, Ilari, Ramona, additional, De Luca, Gabriele, additional, Pedini, Francesca, additional, Boe, Alessandra, additional, Felli, Nadia, additional, Biffoni, Mauro, additional, Pilozzi, Emanuela, additional, Marziali, Giovanna, additional, and Ricci-Vitiani, Lucia, additional

Published
2022
Full Text
View/download PDF

21. Development and Validation of a HPLC–MS/MS Method to Measure Nifuroxazide and Its Application in Healthy and Glioblastoma-Bearing Mice

Author

Ceruti, T, D’Alessandris, Q, Frapolli, R, Gopalakrishnan, J, Buccarelli, M, Meroni, M, Lauretti, L, Ricci-Vitiani, L, Pallini, R, Zucchetti, M, Ceruti, Tommaso, D’Alessandris, Quintino Giorgio, Frapolli, Roberta, Gopalakrishnan, Jay, Buccarelli, Mariachiara, Meroni, Marina, Lauretti, Liverana, Ricci-Vitiani, Lucia, Pallini, Roberto, Zucchetti, Massimo, Ceruti, T, D’Alessandris, Q, Frapolli, R, Gopalakrishnan, J, Buccarelli, M, Meroni, M, Lauretti, L, Ricci-Vitiani, L, Pallini, R, Zucchetti, M, Ceruti, Tommaso, D’Alessandris, Quintino Giorgio, Frapolli, Roberta, Gopalakrishnan, Jay, Buccarelli, Mariachiara, Meroni, Marina, Lauretti, Liverana, Ricci-Vitiani, Lucia, Pallini, Roberto, and Zucchetti, Massimo

Abstract

Nifuroxazide (NAZ), a nitrofuran derivative used to treat diarrhea, has been recently shown to possess anticancer activity. However, its pharmacokinetic profile is poorly known. The pharmacokinetic profile of NAZ was thus investigated in mice using a newly developed method based on high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). We determined the concentrations of NAZ in the plasma and brain tissue of mice treated with the drug. The method proved to be specific, reproducible, precise, and accurate. It also demonstrated high sensitivity, reaching an LOQ in the order of ppb for both matrices, using samples of 100 mu L or 0.2 g. The new HPLC-MS/MS assay was successfully applied to study the pharmacokinetics of NAZ after chronic intraperitoneal administration in mice at a dose of 30 mg/kg. One hour after treatment, plasma concentrations of NAZ were in the range of 336-2640 ng/mL. Moreover, unlike the brains of healthy mice or those with healed mechanical injuries, we found that NAZ was able to cross the injured blood-brain barrier of tumor-infiltrated brains. Thus, following i.p. administration, NAZ reaches systemic levels suitable for testing its efficacy in preclinical models of glioblastoma. Overall, these pharmacokinetic data provide robust evidence supporting the repositioning of NAZ as an antitumor drug.

Published
2022

23. Effects of the Combined Treatment with a G-Quadruplex-Stabilizing Ligand and Photon Beams on Glioblastoma Stem-like Cells: A Magnetic Resonance Study

Author

Palma, Alessandra, primary, Grande, Sveva, additional, Luciani, Anna Maria, additional, Ricci-Vitiani, Lucia, additional, Buccarelli, Mariachiara, additional, Pallini, Roberto, additional, Triveri, Alice, additional, Pirota, Valentina, additional, Doria, Filippo, additional, D’Alessandris, Quintino Giorgio, additional, Berardinelli, Francesco, additional, Antoccia, Antonio, additional, and Rosi, Antonella, additional

Published
2021
Full Text
View/download PDF

24. Additional file 1 of Elesclomol-induced increase of mitochondrial reactive oxygen species impairs glioblastoma stem-like cell survival and tumor growth

Author

Buccarelli, Mariachiara, D’Alessandris, Quintino Giorgio, Matarrese, Paola, Mollinari, Cristiana, Signore, Michele, Cappannini, Andrea, Martini, Maurizio, D’Aliberti, Pierluigi, De Luca, Gabriele, Pedini, Francesca, Boe, Alessandra, Biffoni, Mauro, Pallini, Roberto, and Ricci-Vitiani, Lucia

Abstract

Additional file 1: Supplementary Table 1. List of drugs used for small-molecule kinase inhibitor screening (10 mM in DMSO). Supplementary Table 2. List of antibodies used for Reverse-Phase Protein microArrays (RPPA) analysis. Supplementary Table 3. Patient and GSC line characteristics. Supplementary Table 4. List of genes corresponding to significant antibodies and grouped using the Venn diagram in Fig. 4C. Supplementary Figure S1. A-D. Morphological changes of the four GSC lines used in the study (A, GSC#1; B, GSC#61; C, GSC#83; D, GSC#163) after being induced to transdifferentiate for 2 weeks. Left panel, tumorspheres in stem cell medium; right panel, net-like structures under endothelial conditions (magnification 10X). Supplementary Figure S2. (A) Fluorescent-activated cell sorting dot plots of CD34−/low and CD34high GSC#163 after two weeks of culture in endothelial conditions under hypoxia. Percentage and squares indicate the sorted subpopulations of cells with different CD34-expression levels (left, IgG1 isotype control sample; right, CD34 sample). (B-C) Immunohistochemical analysis of CD34low (B) and CD34high (C) GdEC subcutaneous tumor xenografts based on the expression of the astrocytic marker glial fibrillary acidic protein (GFAP, right panels), showing tumors with different levels of differentiation. (Left panels, haematoxylin and eosin staining; magnification 200X). Supplementary Figure S3. Concentration-response assays on U87MG and all the four glial cell lines derived from the selected GSC lines. Supplementary Figure S4. Cytofluorimetric cell-by-cell analysis of viability in four different GSC lines treated with 10, 100, or 1000 nM elesclomol in the presence or absence of the following cell death inhibitors: z-VAD, necrostatin-1, ferrostatin-1, 3-MA, NAC, and CoQ at the indicated concentrations. Results obtained from four independent experiments are expressed as percentage vs control untreated cells and reported as means ± SD. Supplementary Figure S5. Cytofluorimetric cell-by-cell analysis of cell viability (A), mitochondrial ROS production (B), mitochondrial membrane potential (C), and GSH (D) in four different GSC lines treated with 10, 100, or 1000 nM elesclomol in the presence or absence of the copper chelating agent TTM. Results obtained from four independent experiments are expressed as percentage vs control untreated cells and reported as means ± SD. Supplementary Figure S6. Cytofluorimetric cell-by-cell analysis of cell viability, mitochondrial ROS production, mitochondrial membrane potential, and GSH in HMVECs, used as a control of nontumoral endothelial cell line, treated with 10, 100, or 1000 nM Elesclomol in the presence or absence of the copper chelating agent TTM. Results obtained from four independent experiments are expressed as percentage vs control untreated cells and reported as means ± SD. Supplementary Figure S7. Illustration of the rationale suitable for the choice of rank k, a critical parameter that defines the number of metagenes used to approximate the target matrix (Gaujoux & Seoighe, 2010). A) Measurements are applied to both real data (circles) and randomized data (triangles). The rationale for choosing rank stems on diverse metrics, i) trend of the cophenetic coefficient: Brunet et al. (2004) suggest choosing the smallest value of k for which there is a decrease in the trend of the cophenetic; ii) trend of the dispersion coefficient introduced by Kim & Park. (2007); iii) explained variance by increasing rank; iv) trend of residuals; v) trend of RSS: Hutchins et al. (2008) suggest taking the first rank value for which we have an inflection point. Frigyesi et al. (2008) instead consider the first rank value for which the decrease of the RSS on real data is less than the decrease of the RSS on the random data; vi) silhouette values measured on the matrices of the base, of the coefficients and the consensus matrix; vii) trend of the sparseness introduced by Hoyer (2004). B) Multiple consensus maps corresponding to different value of k. Supplementary Figure S8. Heatmap of the most important antibodies in each of the k = 6 metagenes resulting from the model. Supplementary Figure S9. Principal Component Analysis (PCA) algorithm applied to Elesclomol data, whereby each cell line is considered as a function of the antibodies. A) Scree plot. Given the low amount of variance explained by the variables above the fifth, we considered up to 5 principal components. B) Biplots using cell lines and growth conditions as scores. Ellipses represent the 95% probability of finding sample score values. Supplementary Figure S10. Principal Component Analysis (PCA) biplots of components of the antibodies using (A) Time and (B) treatment, respectively. Ellipses represent the 95% probability of finding sample score values. Supplementary Figure S11. Concent ration-response assays on all the four selected GSC lines for setting the dose of Elesclomol most suitable for the combination with TMZ.

Published
2021
Full Text
View/download PDF

25. Inhibition of mitochondrial translation suppresses glioblastoma stem cell growth

Author

Sighel, Denise, Notarangelo, Michela, Aibara, Shintaro, Re, Angela, Ricci, Gianluca, Guida, Marianna, Soldano, Alessia, Adami, Valentina, Ambrosini, Chiara, Broso, Francesca, Rosatti, Emanuele Filiberto, Longhi, Sara, Buccarelli, Mariachiara, D'Alessandris, Quintino G., Giannetti, Stefano, Pacioni, Simone, Ricci-Vitiani, Lucia, Rorbach, Joanna, Pallini, Roberto, Roulland, Sandrine, Amunts, Alexey, Mancini, Ines, Modelska, Angelika, Quattrone, Alessandro, Sighel, Denise, Notarangelo, Michela, Aibara, Shintaro, Re, Angela, Ricci, Gianluca, Guida, Marianna, Soldano, Alessia, Adami, Valentina, Ambrosini, Chiara, Broso, Francesca, Rosatti, Emanuele Filiberto, Longhi, Sara, Buccarelli, Mariachiara, D'Alessandris, Quintino G., Giannetti, Stefano, Pacioni, Simone, Ricci-Vitiani, Lucia, Rorbach, Joanna, Pallini, Roberto, Roulland, Sandrine, Amunts, Alexey, Mancini, Ines, Modelska, Angelika, and Quattrone, Alessandro

Abstract

Glioblastoma stem cells (GSCs) resist current glioblastoma (GBM) therapies. GSCs rely highly on oxidative phosphorylation (OXPHOS), whose function requires mitochondrial translation. Here we explore the therapeutic potential of targeting mitochondrial translation and report the results of high-content screening with putative blockers of mitochondrial ribosomes. We identify the bacterial antibiotic quinupristin/dalfopristin (Q/D) as an effective suppressor of GSC growth. Q/D also decreases the clonogenicity of GSCs in vitro, consequently dysregulating the cell cycle and inducing apoptosis. Cryoelectron microscopy (cryo-EM) reveals that Q/D binds to the large mitoribosomal subunit, inhibiting mitochondrial protein synthesis and functionally dysregulating OXPHOS complexes. These data suggest that targeting mitochondrial translation could be explored to therapeutically suppress GSC growth in GBM and that Q/D could potentially be repurposed for cancer treatment.

Published
2021
Full Text
View/download PDF

26. Inhibition of mitochondrial translation suppresses glioblastoma stem cell growth

Author

Sighel, Denise, primary, Notarangelo, Michela, additional, Aibara, Shintaro, additional, Re, Angela, additional, Ricci, Gianluca, additional, Guida, Marianna, additional, Soldano, Alessia, additional, Adami, Valentina, additional, Ambrosini, Chiara, additional, Broso, Francesca, additional, Rosatti, Emanuele Filiberto, additional, Longhi, Sara, additional, Buccarelli, Mariachiara, additional, D’Alessandris, Quintino G., additional, Giannetti, Stefano, additional, Pacioni, Simone, additional, Ricci-Vitiani, Lucia, additional, Rorbach, Joanna, additional, Pallini, Roberto, additional, Roulland, Sandrine, additional, Amunts, Alexey, additional, Mancini, Ines, additional, Modelska, Angelika, additional, and Quattrone, Alessandro, additional

Published
2021
Full Text
View/download PDF

27. Dilation of Brain Veins and Perivascular Infiltration by Glioblastoma Cells in an In Vivo Assay of Early Tumor Angiogenesis

Author

D’Alessandris, Quintino Giorgio, primary, Pacioni, Simone, additional, Stumpo, Vittorio, additional, Buccarelli, Mariachiara, additional, Lauretti, Liverana, additional, Giordano, Martina, additional, Di Bonaventura, Rina, additional, Martini, Maurizio, additional, Larocca, Luigi M., additional, Giannetti, Stefano, additional, Montano, Nicola, additional, Falchetti, Maria Laura, additional, Ricci-Vitiani, Lucia, additional, and Pallini, Roberto, additional

Published
2021
Full Text
View/download PDF

28. Deregulated expression of the imprinted DLK1-DIO3 region in Glioblastoma Stem-like Cells: tumor suppressor role of lncRNA MEG3

Author

Buccarelli, Mariachiara, Lulli, Valentina, Giuliani, Alessandro, Signore, Michele, Martini, Maurizio, D'Alessandris, Quintino Giorgio, Giannetti, Stefano, Novelli, Agnese, Ilari, Ramona, Giurato, Giorgio, Boe, Alessandra, Castellani, Giorgia, Spartano, Serena, Marangi, Giuseppe, Biffoni, Mauro, Genuardi, Maurizio, Pallini, Roberto, Marziali, Giovanna, Ricci-Vitiani, Lucia, Martini, Maurizio (ORCID:0000-0002-6260-6310), D'Alessandris, Quintino G (ORCID:0000-0002-2953-9291), Giannetti, Stefano (ORCID:0000-0002-9456-8865), Marangi, Giuseppe (ORCID:0000-0002-6898-8882), Genuardi, Maurizio (ORCID:0000-0002-7410-8351), Pallini, Roberto (ORCID:0000-0002-4611-8827), Buccarelli, Mariachiara, Lulli, Valentina, Giuliani, Alessandro, Signore, Michele, Martini, Maurizio, D'Alessandris, Quintino Giorgio, Giannetti, Stefano, Novelli, Agnese, Ilari, Ramona, Giurato, Giorgio, Boe, Alessandra, Castellani, Giorgia, Spartano, Serena, Marangi, Giuseppe, Biffoni, Mauro, Genuardi, Maurizio, Pallini, Roberto, Marziali, Giovanna, Ricci-Vitiani, Lucia, Martini, Maurizio (ORCID:0000-0002-6260-6310), D'Alessandris, Quintino G (ORCID:0000-0002-2953-9291), Giannetti, Stefano (ORCID:0000-0002-9456-8865), Marangi, Giuseppe (ORCID:0000-0002-6898-8882), Genuardi, Maurizio (ORCID:0000-0002-7410-8351), and Pallini, Roberto (ORCID:0000-0002-4611-8827)

Abstract

Background: Glioblastoma (GBM) stem-like cells (GSCs) are thought to be responsible for the maintenance and aggressiveness of GBM, the most common primary brain tumor in adults. This study aims at elucidating the involvement of deregulations within the imprinted DLK-DIO3 region on chromosome 14q32 in GBM pathogenesis. Methods: RT-PCR analyses were performed on GSCs and GBM tissues. Methylation analyses, gene expression and Reverse-Phase protein Array profiles were used to investigate the tumor suppressor function of MEG3. Results: Loss of expression of genes and non-coding RNAs within the DLK1-DIO3 region was observed in GSCs and GBM tissues compared to normal brain. This down-regulation is mainly mediated by epigenetic silencing. Kaplan-Meier analysis indicated that low expression of MEG3 and MEG8 lncRNAs significantly correlated with short survival in GBM patients. MEG3 restoration impairs tumorigenic abilities of GSCs in vitro by inhibiting cell growth, migration and colony formation and decreases in vivo tumor growth reducing infiltrative growth. These effects were associated with modulation of genes involved in cell adhesion and Epithelial to Mesenchymal Transition (EMT). Conclusions: In GBM, MEG3 acts as a tumor-suppressor mainly regulating cell adhesion, EMT and cell proliferation, thus providing a potential candidate for novel GBM therapies.

Published
2020

29. Anticancer Properties of the Antipsychotic Drug Chlorpromazine and Its Synergism With Temozolomide in Restraining Human Glioblastoma Proliferation In Vitro

Author

Matteoni, Silvia, primary, Matarrese, Paola, additional, Ascione, Barbara, additional, Buccarelli, Mariachiara, additional, Ricci-Vitiani, Lucia, additional, Pallini, Roberto, additional, Villani, Veronica, additional, Pace, Andrea, additional, Paggi, Marco G., additional, and Abbruzzese, Claudia, additional

Published
2021
Full Text
View/download PDF

30. Short tandem repeat profiling for the authentication of cancer stem‐like cells

Author

Visconti, Paola, primary, Parodi, Federica, additional, Parodi, Barbara, additional, Casarino, Lucia, additional, Romano, Paolo, additional, Buccarelli, Mariachiara, additional, Pallini, Roberto, additional, D'Alessandris, Quintino Giorgio, additional, Montori, Andrea, additional, Pilozzi, Emanuela, additional, and Ricci‐Vitiani, Lucia, additional

Published
2020
Full Text
View/download PDF

31. Sox2‐dependent maintenance of mouse oligodendroglioma involves the Sox2‐mediated downregulation of Cdkn2b, Ebf1, Zfp423, and Hey2

Author

Barone, Cristiana, primary, Buccarelli, Mariachiara, additional, Alessandrini, Francesco, additional, Pagin, Miriam, additional, Rigoldi, Laura, additional, Sambruni, Irene, additional, Favaro, Rebecca, additional, Ottolenghi, Sergio, additional, Pallini, Roberto, additional, Ricci‐Vitiani, Lucia, additional, Malatesta, Paolo, additional, and Nicolis, Silvia K., additional

Published
2020
Full Text
View/download PDF

32. Different Mechanisms Underlie the Metabolic Response of GBM Stem-Like Cells to Ionizing Radiation: Biological and MRS Studies on Effects of Photons and Carbon Ions

Author

Palma, Alessandra, primary, Grande, Sveva, additional, Ricci-Vitiani, Lucia, additional, Luciani, Anna Maria, additional, Buccarelli, Mariachiara, additional, Biffoni, Mauro, additional, Dini, Valentina, additional, Cirrone, Giuseppe A. P., additional, Ciocca, Mario, additional, Guidoni, Laura, additional, Pallini, Roberto, additional, Viti, Vincenza, additional, and Rosi, Antonella, additional

Published
2020
Full Text
View/download PDF

34. Deregulated expression of the imprinted DLK1-DIO3 region in glioblastoma stemlike cells: tumor suppressor role of lncRNA MEG3

Author

Buccarelli, Mariachiara, primary, Lulli, Valentina, additional, Giuliani, Alessandro, additional, Signore, Michele, additional, Martini, Maurizio, additional, D’Alessandris, Quintino G, additional, Giannetti, Stefano, additional, Novelli, Agnese, additional, Ilari, Ramona, additional, Giurato, Giorgio, additional, Boe, Alessandra, additional, Castellani, Giorgia, additional, Spartano, Serena, additional, Marangi, Giuseppe, additional, Biffoni, Mauro, additional, Genuardi, Maurizio, additional, Pallini, Roberto, additional, Marziali, Giovanna, additional, and Ricci-Vitiani, Lucia, additional

Published
2020
Full Text
View/download PDF

35. Mir-370-3p Impairs Glioblastoma Stem-Like Cell Malignancy Regulating a Complex Interplay between HMGA2/HIF1A and the Oncogenic Long Non-Coding RNA (lncRNA) NEAT1

Author

Lulli, Valentina, primary, Buccarelli, Mariachiara, additional, Ilari, Ramona, additional, Castellani, Giorgia, additional, De Dominicis, Chiara, additional, Di Giamberardino, Alessandra, additional, D′Alessandris, Quintino Giorgio, additional, Giannetti, Stefano, additional, Martini, Maurizio, additional, Stumpo, Vittorio, additional, Boe, Alessandra, additional, De Luca, Gabriele, additional, Biffoni, Mauro, additional, Marziali, Giovanna, additional, Pallini, Roberto, additional, and Ricci-Vitiani, Lucia, additional

Published
2020
Full Text
View/download PDF

38. Glioblastoma endothelium drives bevacizumab-induced infiltrative growth via modulation of PLXDC1

Author

Falchetti, Maria Laura, D'Alessandris, Quintino Giorgio, Pacioni, Simone, Buccarelli, Mariachiara, Morgante, Liliana, Giannetti, Stefano, Lulli, Valentina, Martini, Maurizio, Larocca, Luigi Maria, Vakana, Eliza, Stancato, Loui, Ricci-Vitiani, Lucia, Pallini, Roberto, D'Alessandris, Quintino Giorgio (ORCID:0000-0002-2953-9291), Giannetti, Stefano (ORCID:0000-0002-9456-8865), Martini, Maurizio (ORCID:0000-0002-6260-6310), Larocca, Luigi Maria (ORCID:0000-0003-1739-4758), Pallini, Roberto (ORCID:0000-0002-4611-8827), Falchetti, Maria Laura, D'Alessandris, Quintino Giorgio, Pacioni, Simone, Buccarelli, Mariachiara, Morgante, Liliana, Giannetti, Stefano, Lulli, Valentina, Martini, Maurizio, Larocca, Luigi Maria, Vakana, Eliza, Stancato, Loui, Ricci-Vitiani, Lucia, Pallini, Roberto, D'Alessandris, Quintino Giorgio (ORCID:0000-0002-2953-9291), Giannetti, Stefano (ORCID:0000-0002-9456-8865), Martini, Maurizio (ORCID:0000-0002-6260-6310), Larocca, Luigi Maria (ORCID:0000-0003-1739-4758), and Pallini, Roberto (ORCID:0000-0002-4611-8827)

Abstract

Bevacizumab, a VEGF-targeting monoclonal antibody, may trigger an infiltrative growth pattern in glioblastoma. We investigated this pattern using both a human specimen and rat models. In the human specimen, a substantial fraction of infiltrating tumor cells were located along perivascular spaces in close relationship with endothelial cells. Brain xenografts of U87MG cells treated with bevacizumab were smaller than controls (p = 0.0055; Student t-test), however, bands of tumor cells spread through the brain farther than controls (p < 0.001; Student t-test). Infiltrating tumor Cells exhibited tropism for vascular structures and propensity to form tubules and niches with endothelial cells. Molecularly, bevacizumab triggered an epithelial to mesenchymal transition with over-expression of the receptor Plexin Domain Containing 1 (PLXDC1). These results were validated using brain xenografts of patient-derived glioma stem-like cells. Enforced expression of PLXDC1 in U87MG cells promoted brain infiltration along perivascular spaces. Importantly, PLXDC1 inhibition prevented perivascular infiltration and significantly increased the survival of bevacizumab-treated rats. Our study indicates that bevacizumab-induced brain infiltration is driven by vascular endothelium and depends on PLXDC1 activation of tumor cells.

Published
2019

40. Glioblastoma endothelium drives bevacizumab‐induced infiltrative growth via modulation of PLXDC1

Author

Falchetti, Maria Laura, primary, D'Alessandris, Quintino Giorgio, additional, Pacioni, Simone, additional, Buccarelli, Mariachiara, additional, Morgante, Liliana, additional, Giannetti, Stefano, additional, Lulli, Valentina, additional, Martini, Maurizio, additional, Larocca, Luigi Maria, additional, Vakana, Eliza, additional, Stancato, Louis, additional, Ricci‐Vitiani, Lucia, additional, and Pallini, Roberto, additional

Published
2018
Full Text
View/download PDF

41. Short tandem repeat profiling for the authentication of cancer stem‐like cells.

Author

Visconti, Paola, Parodi, Federica, Parodi, Barbara, Casarino, Lucia, Romano, Paolo, Buccarelli, Mariachiara, Pallini, Roberto, D'Alessandris, Quintino Giorgio, Montori, Andrea, Pilozzi, Emanuela, and Ricci‐Vitiani, Lucia

Subjects
MICROSATELLITE repeats, CANCER cells, CELL lines
Abstract

Colorectal and glioblastoma cancer stem‐like cells (CSCs) are essential for translational research. Cell line authentication by short tandem repeat (STR) profiling ensures reproducibility of results in oncology research. This technique enables to identify mislabeling or cross‐contamination of cell lines. In our study, we provide a reference dataset for a panel of colorectal and glioblastoma CSCs that allows authentication. Each cell line was entered into the cell Line Integrated Molecular Authentication database 2.1 to be compared to the STR profiles of 4485 tumor cell lines. This article also provides clinical data of patients from whom CSCs arose and data on the parent tumor stage and mutations. STR profiles and information of our CSCs are also available in the Cellosaurus database (ExPASy) as identified by unique research resource identifier codes. What's new?: Human cell lines obtained from cancer stem‐like cells represent an invaluable model for studying tumor properties. Cell line authentication by short tandem repeat (STR) profiling is an important tool to identify the potential mislabeling or cross‐contamination of cell lines. Here, the authors characterized 18 colorectal cancer stem‐like cell lines from 17 patients and 103 glioblastoma cancer stem‐like cell lines from 95 patients by STR profiling to create a reference dataset that allows the authentication of these cell lines and their identification through a unique research resource identifier. The results will help further ensure the reliability and reproducibility of research experiments. [ABSTRACT FROM AUTHOR]

Published
2021
Full Text
View/download PDF

42. Dilation of Brain Veins and Perivascular Infiltration by Glioblastoma Cells in an In Vivo Assay of Early Tumor Angiogenesis.

Author

D'Alessandris, Quintino Giorgio, Pacioni, Simone, Stumpo, Vittorio, Buccarelli, Mariachiara, Lauretti, Liverana, Giordano, Martina, Di Bonaventura, Rina, Martini, Maurizio, Larocca, Luigi M., Giannetti, Stefano, Montano, Nicola, Falchetti, Maria Laura, Ricci-Vitiani, Lucia, and Pallini, Roberto

Subjects
BRAIN, GLIOMAS, VASODILATION, PATHOLOGIC neovascularization, NEUROGLIA, CELL lines
Abstract

The cranial window (CW) technique provides a simple and low-cost method to assess tumor angiogenesis in the brain. The CW combined with histology using selective markers for tumor and endothelial cells can allow a sensitive monitoring of novel antiangiogenesis therapies in preclinical models. The CW was established in cyclosporine immunosuppressed rats that were stereotactically grafted with fluorescent U87MG glioblastoma cells. One to 3 weeks after grafting, brain vasculature was visualized in vivo and assessed by immunofluorescence microscopy using antibodies against endothelial and smooth-muscle cells and blood brain barrier. At 1-2 weeks after grafting, the CW reliably detected the hypertrophy of venous-venous anastomoses and cortical veins. These structures increased highly significantly their pregrafting diameter. Arterialized veins and hemorrhages were seen by three weeks after grafting. Immunofluorescence microscopy showed significant branching and dilation of microvessels, particularly those surrounded by tumor cells. Mechanistically, these changes lead to loss of vascular resistance, increased venous outflow, and opening of venous-venous anastomoses on the cortical surface. Data from the present study, namely, the hypertrophy of cortical venous-venous anastomoses, microvessel branching, and dilation of the microvessels surrounded by tumor cells, indicate the power of this in vivo model for the sensitive monitoring of early tumor angiogenesis. [ABSTRACT FROM AUTHOR]

Published
2021
Full Text
View/download PDF

44. Metabolic Heterogeneity Evidenced by MRS among Patient-Derived Glioblastoma Multiforme Stem-Like Cells Accounts for Cell Clustering and Different Responses to Drugs

Author

Grande, Sveva, primary, Palma, Alessandra, additional, Ricci-Vitiani, Lucia, additional, Luciani, Anna Maria, additional, Buccarelli, Mariachiara, additional, Biffoni, Mauro, additional, Molinari, Agnese, additional, Calcabrini, Annarica, additional, D’Amore, Emanuela, additional, Guidoni, Laura, additional, Pallini, Roberto, additional, Viti, Vincenza, additional, and Rosi, Antonella, additional

Published
2018
Full Text
View/download PDF

45. The clinical value of patient-derived glioblastoma tumorspheres in predicting treatment response

Author

D'Alessandris, Quintino Giorgio, Biffoni, Mauro, Martini, Maurizio, Runci, Daniele, Buccarelli, Mariachiara, Cenci, Tonia, Signore, Michele, Stancato, Loui, Olivi, Alessandro, De Maria Marchiano, Ruggero, Larocca, Luigi M., Ricci-Vitiani, Lucia, Pallini, Roberto, D'Alessandris, Quintino Giorgio (ORCID:0000-0002-2953-9291), Martini, Maurizio (ORCID:0000-0002-6260-6310), Olivi, Alessandro (ORCID:0000-0002-4489-7564), De Maria Marchiano, Ruggero (ORCID:0000-0003-2255-0583), Larocca, Luigi M. (ORCID:0000-0003-1739-4758), Pallini, Roberto (ORCID:0000-0002-4611-8827), D'Alessandris, Quintino Giorgio, Biffoni, Mauro, Martini, Maurizio, Runci, Daniele, Buccarelli, Mariachiara, Cenci, Tonia, Signore, Michele, Stancato, Loui, Olivi, Alessandro, De Maria Marchiano, Ruggero, Larocca, Luigi M., Ricci-Vitiani, Lucia, Pallini, Roberto, D'Alessandris, Quintino Giorgio (ORCID:0000-0002-2953-9291), Martini, Maurizio (ORCID:0000-0002-6260-6310), Olivi, Alessandro (ORCID:0000-0002-4489-7564), De Maria Marchiano, Ruggero (ORCID:0000-0003-2255-0583), Larocca, Luigi M. (ORCID:0000-0003-1739-4758), and Pallini, Roberto (ORCID:0000-0002-4611-8827)

Abstract

Background. Advances from glioma stemlike cell (GSC) research, though increasing our knowledge of glioblastoma (GBM) biology, do not influence clinical decisions yet. We explored the translational power of GSC-enriched cultures from patient-derived tumorspheres (TS) in predicting treatment response. Methods. The relationship between TS growth and clinical outcome was investigated in 52 GBMs treated with surgical resection followed by radiotherapy and temozolomide (TMZ). The effect on TS of radiation (6 to 60 Gy) and of TMZ (3.9 Î1⁄4M to 1 mM) was related with patients' survival. Results. Generation of TS was an independent factor for poor overall survival (OS) and poor progression-free survival (PFS) (P < .0001 and P = .0010, respectively). Growth rate and clonogenicity of TS predicted poor OS. In general, TS were highly resistant to both radiation and TMZ. Resistance to TMZ was stronger in TS with high clonogenicity and fast growth (P < .02). Shorter PFS was associated with radiation LD50 (lethal dose required to kill 50% of TS cells) >12 Gy of matched TS (P = .0484). A direct relationship was found between sensitivity of TS to TMZ and patients' survival (P = .0167 and P = .0436 for OS and PFS, respectively). Importantly, values for TMZ half-maximal inhibitory concentration <50 Î1⁄4M, which are in the range of plasma levels achieved in vivo, identified cases with longer OS and PFS (P = .0020 and P = .0016, respectively). Conclusions. Analysis of TS holds translational relevance by predicting the response of parent tumors to radiation and, particularly, to TMZ. Dissecting the clonogenic population from proliferating progeny in TS can guide therapeutic strategies to a more effective drug selection and treatment duration.

Published
2017

46. Human mesenchymal stromal cells inhibit tumor growth in orthotopic glioblastoma xenografts

Author

Pacioni, Simone, D'Alessandris, Quintino Giorgio, Giannetti, Stefano, Morgante, Liliana, Coccè, Valentina, Bonomi, Arianna, Buccarelli, Mariachiara, Pascucci, Luisa, Alessandri, Giulio, Pessina, Augusto, Ricci Vitiani, Lucia, Falchetti, Maria Laura, Pallini, Roberto, D'Alessandris, Quintino Giorgio (ORCID:0000-0002-2953-9291), Giannetti, Stefano (ORCID:0000-0002-9456-8865), Pallini, Roberto (ORCID:0000-0002-4611-8827), Pacioni, Simone, D'Alessandris, Quintino Giorgio, Giannetti, Stefano, Morgante, Liliana, Coccè, Valentina, Bonomi, Arianna, Buccarelli, Mariachiara, Pascucci, Luisa, Alessandri, Giulio, Pessina, Augusto, Ricci Vitiani, Lucia, Falchetti, Maria Laura, Pallini, Roberto, D'Alessandris, Quintino Giorgio (ORCID:0000-0002-2953-9291), Giannetti, Stefano (ORCID:0000-0002-9456-8865), and Pallini, Roberto (ORCID:0000-0002-4611-8827)

Abstract

Background: Mesenchymal stem/stromal cells (MSCs) represent an attractive tool for cell-based cancer therapy mainly because of their ability to migrate to tumors and to release bioactive molecules. However, the impact of MSCs on tumor growth has not been fully established. We previously demonstrated that murine MSCs show a strong tropism towards glioblastoma (GBM) brain xenografts and that these cells are able to uptake and release the chemotherapeutic drug paclitaxel (PTX), maintaining their tropism towards the tumor. Here, we address the therapy-relevant issue of using MSCs from human donors (hMSCs) for local or systemic administration in orthotopic GBM models, including xenografts of patient-derived glioma stem cells (GSCs). Methods: U87MG or GSC1 cells expressing the green fluorescent protein (GFP) were grafted onto the striatum of immunosuppressed rats. Adipose hMSCs (Ad-hMSCs), fluorescently labeled with the mCherry protein, were inoculated adjacent to or into the tumor. In rats bearing U87MG xenografts, systemic injections of Ad-hMSCs or bone marrow (BM)-hMSCs were done via the femoral vein or carotid artery. In each experiment, either PTX-loaded or unloaded hMSCs were used. To characterize the effects of hMSCs on tumor growth, we analyzed survival, tumor volume, tumor cell proliferation, and microvascular density. Results: Overall, the AD-hMSCs showed remarkable tropism towards the tumor. Intracerebral injection of Ad-hMSCs significantly improved the survival of rats with U87MG xenografts. This effect was associated with a reduction in tumor growth, tumor cell proliferation, and microvascular density. In GSC1 xenografts, intratumoral injection of Ad-hMSCs depleted the tumor cell population and induced migration of resident microglial cells. Overall, PTX loading did not significantly enhance the antitumor potential of hMSCs. Systemically injected Ad- and BM-hMSCs homed to tumor xenografts. The efficiency of hMSC homing ranged between 0.02 and 0.5% of the inje

Published
2017

47. Human mesenchymal stromal cells inhibit tumor growth in orthotopic glioblastoma xenografts

Author

Pacioni, Simone, primary, D’Alessandris, Quintino Giorgio, additional, Giannetti, Stefano, additional, Morgante, Liliana, additional, Coccè, Valentina, additional, Bonomi, Arianna, additional, Buccarelli, Mariachiara, additional, Pascucci, Luisa, additional, Alessandri, Giulio, additional, Pessina, Augusto, additional, Ricci-Vitiani, Lucia, additional, Falchetti, Maria Laura, additional, and Pallini, Roberto, additional

Published
2017
Full Text
View/download PDF

48. The clinical value of patient-derived glioblastoma tumorspheres in predicting treatment response

Author

D’Alessandris, Quintino Giorgio, primary, Biffoni, Mauro, additional, Martini, Maurizio, additional, Runci, Daniele, additional, Buccarelli, Mariachiara, additional, Cenci, Tonia, additional, Signore, Michele, additional, Stancato, Louis, additional, Olivi, Alessandro, additional, De Maria, Ruggero, additional, Larocca, Luigi M., additional, Ricci-Vitiani, Lucia, additional, and Pallini, Roberto, additional

Published
2017
Full Text
View/download PDF

50. IFN-α potentiates the direct and immune-mediated antitumor effects of epigenetic drugs on both metastatic and stem cells of colorectal cancer

Author

Buoncervello, Maria, primary, Romagnoli, Giulia, additional, Buccarelli, Mariachiara, additional, Fragale, Alessandra, additional, Toschi, Elena, additional, Parlato, Stefania, additional, Lucchetti, Donatella, additional, Macchia, Daniele, additional, Spada, Massimo, additional, Canini, Irene, additional, Sanchez, Massimo, additional, Falchi, Mario, additional, Musella, Martina, additional, Biffoni, Mauro, additional, Belardelli, Filippo, additional, Capone, Imerio, additional, Sgambato, Alessandro, additional, Vitiani, Lucia Ricci, additional, and Gabriele, Lucia, additional

Published
2016
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results