288 results on '"Ricci-Vitiani L"'
Search Results
2. Sox2-dependent maintenance of mouse oligodendroglioma involves the Sox2-mediated downregulation of Cdkn2b, Ebf1, Zfp423, and Hey2
- Author
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Barone, C, Buccarelli, M, Alessandrini, F, Pagin, M, Rigoldi, L, Sambruni, I, Favaro, R, Ottolenghi, S, Pallini, R, Ricci-Vitiani, L, Malatesta, P, Nicolis, S, Barone C., Buccarelli M., Alessandrini F., Pagin M., Rigoldi L., Sambruni I., Favaro R., Ottolenghi S., Pallini R., Ricci-Vitiani L., Malatesta P., Nicolis S. K., Barone, C, Buccarelli, M, Alessandrini, F, Pagin, M, Rigoldi, L, Sambruni, I, Favaro, R, Ottolenghi, S, Pallini, R, Ricci-Vitiani, L, Malatesta, P, Nicolis, S, Barone C., Buccarelli M., Alessandrini F., Pagin M., Rigoldi L., Sambruni I., Favaro R., Ottolenghi S., Pallini R., Ricci-Vitiani L., Malatesta P., and Nicolis S. K.
- Abstract
Cancer stem cells (CSC) are essential for tumorigenesis. The transcription factor Sox2 is overexpressed in brain gliomas, and is essential to maintain CSC. In mouse high-grade glioma pHGG cells in culture, Sox2 deletion causes cell proliferation arrest and inability to reform tumors after transplantation in vivo; in Sox2-deleted cells, 134 genes are derepressed. To identify genes mediating Sox2 deletion effects, we overexpressed into pHGG cells nine among the most derepressed genes, and identified four genes, Ebf1, Hey2, Zfp423, and Cdkn2b, that strongly reduced cell proliferation in vitro and brain tumorigenesis in vivo. CRISPR/Cas9 mutagenesis of each gene, individually or in combination (Ebf1 + Cdkn2b), significantly antagonized the proliferation arrest caused by Sox2 deletion. The same genes also repressed clonogenicity in primary human glioblastoma-derived CSC-like lines. These experiments identify a network of critical tumor suppressive Sox2-targets whose inhibition by Sox2 is involved in glioma CSC maintenance, defining new potential therapeutic targets.
- Published
- 2021
3. Development and Validation of a HPLC–MS/MS Method to Measure Nifuroxazide and Its Application in Healthy and Glioblastoma-Bearing Mice
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Ceruti, T., D'Alessandris, Quintino Giorgio, Frapolli, R., Gopalakrishnan, J., Buccarelli, M., Meroni, M., Lauretti, Liverana, Ricci-Vitiani, L., Pallini, Roberto, Zucchetti, M., D'Alessandris Q. G., Lauretti L. (ORCID:0000-0002-6463-055X), Pallini R. (ORCID:0000-0002-4611-8827), Ceruti, T., D'Alessandris, Quintino Giorgio, Frapolli, R., Gopalakrishnan, J., Buccarelli, M., Meroni, M., Lauretti, Liverana, Ricci-Vitiani, L., Pallini, Roberto, Zucchetti, M., D'Alessandris Q. G., Lauretti L. (ORCID:0000-0002-6463-055X), and Pallini R. (ORCID:0000-0002-4611-8827)
- 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 µL 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
4. Development and Validation of a HPLC–MS/MS Method to Measure Nifuroxazide and Its Application in Healthy and Glioblastoma-Bearing Mice
- Author
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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
5. Glioblastoma Stem-Like Cells (GSCs) with Mesenchymal Signature: Lipid Profiles of Mobile Lipids Obtained with MRS before and after Radio/Chemical Treatments
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Grande, S., Palma, A., Luciani, A. M., Anello, P., Ricci-Vitiani, L., Buccarelli, M., D'Alessandris, Quintino Giorgio, Pallini, Roberto, Guidoni, L., Viti, V., Rosi, A., D'Alessandris Q. G. (ORCID:0000-0002-2953-9291), Pallini R. (ORCID:0000-0002-4611-8827), Grande, S., Palma, A., Luciani, A. M., Anello, P., Ricci-Vitiani, L., Buccarelli, M., D'Alessandris, Quintino Giorgio, Pallini, Roberto, Guidoni, L., Viti, V., Rosi, A., D'Alessandris Q. G. (ORCID:0000-0002-2953-9291), and Pallini R. (ORCID:0000-0002-4611-8827)
- Abstract
Glioblastoma is the most common and lethal primary malignant brain tumor in adults. Glioblastoma stem cells (GSCs) promote and are responsible for glioblastoma intratumoral heterogeneity and therapy resistance, due to their two main features: self-renewal and differentiation. Lipids have important biological and physiological functions that are critical for understanding the regulation and control of stem cell fate; lipid metabolism and related unsaturation levels play a possible role as the target of therapeutics to overcome glioblastoma radioresistance. This paper aimed at an in-depth analysis of 13 GSC mesenchymal (MES) lines, two subclones, and a stabilized glioblastoma line (T98G) by magnetic resonance spectroscopy (MRS). Particularly, 2D MRS was used to investigate lipid unsaturation behavior during growth in culture and after treatment with etomoxir and photon beams. MES lines, although belonging to the same genetic and metabolic cluster, showed metabolic heterogeneity when observed by MRS, focusing on lipid signals. Nonetheless, the observed unsaturation level stability for two representative lines after stressful treatments suggests unusual robustness of the unsaturation levels for each line, as a peculiar and intrinsic characteristic of GSCs.
- Published
- 2022
6. Analysis of the combined action of miR-143 and miR-145 on oncogenic pathways in colorectal cancer cells reveals a coordinate program of gene repression
- Author
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Pagliuca, A, Valvo, C, Fabrizi, E, di Martino, S, Biffoni, M, Runci, D, Forte, S, De Maria, R, and Ricci-Vitiani, L
- Published
- 2013
- Full Text
- View/download PDF
7. Short tandem repeat profiling for the authentication of cancer stem-like cells
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Visconti, P., Parodi, F., Parodi, B., Casarino, L., Romano, P., Buccarelli, M., Pallini, Roberto, D'Alessandris, Quintino Giorgio, Montori, A., Pilozzi, E., Ricci-Vitiani, L., Pallini R. (ORCID:0000-0002-4611-8827), D'Alessandris Q. G. (ORCID:0000-0002-2953-9291), Visconti, P., Parodi, F., Parodi, B., Casarino, L., Romano, P., Buccarelli, M., Pallini, Roberto, D'Alessandris, Quintino Giorgio, Montori, A., Pilozzi, E., Ricci-Vitiani, L., Pallini R. (ORCID:0000-0002-4611-8827), and D'Alessandris Q. G. (ORCID:0000-0002-2953-9291)
- 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.
- Published
- 2021
8. Inhibition of mitochondrial translation suppresses glioblastoma stem cell growth
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Sighel, D., Notarangelo, M., Aibara, S., Re, A., Ricci, Giuseppe, Guida, M., Soldano, A., Adami, V., Ambrosini, C., Broso, F., Rosatti, E. F., Longhi, S., Buccarelli, M., D'Alessandris, Quintino Giorgio, Giannetti, Stefano, Pacioni, Simone, Ricci-Vitiani, L., Rorbach, J., Pallini, Roberto, Roulland, S., Amunts, A., Mancini, I., Modelska, A., Quattrone, A., Ricci G., D'Alessandris Q. G. (ORCID:0000-0002-2953-9291), Giannetti S. (ORCID:0000-0002-9456-8865), Pacioni S., Pallini R. (ORCID:0000-0002-4611-8827), Sighel, D., Notarangelo, M., Aibara, S., Re, A., Ricci, Giuseppe, Guida, M., Soldano, A., Adami, V., Ambrosini, C., Broso, F., Rosatti, E. F., Longhi, S., Buccarelli, M., D'Alessandris, Quintino Giorgio, Giannetti, Stefano, Pacioni, Simone, Ricci-Vitiani, L., Rorbach, J., Pallini, Roberto, Roulland, S., Amunts, A., Mancini, I., Modelska, A., Quattrone, A., Ricci G., D'Alessandris Q. G. (ORCID:0000-0002-2953-9291), Giannetti S. (ORCID:0000-0002-9456-8865), Pacioni S., and Pallini R. (ORCID:0000-0002-4611-8827)
- 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
9. Effects of the combined treatment with a g‐quadruplex‐stabilizing ligand and photon beams on glioblastoma stem‐like cells: A magnetic resonance study
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Palma, A., Grande, S., Luciani, A. M., Ricci-vitiani, L., Buccarelli, M., Pallini, Roberto, Triveri, A., Pirota, V., Doria, F., D'Alessandris, Quintino Giorgio, Berardinelli, F., Antoccia, A., Rosi, A., Pallini R. (ORCID:0000-0002-4611-8827), D'alessandris Q. G. (ORCID:0000-0002-2953-9291), Palma, A., Grande, S., Luciani, A. M., Ricci-vitiani, L., Buccarelli, M., Pallini, Roberto, Triveri, A., Pirota, V., Doria, F., D'Alessandris, Quintino Giorgio, Berardinelli, F., Antoccia, A., Rosi, A., Pallini R. (ORCID:0000-0002-4611-8827), and D'alessandris Q. G. (ORCID:0000-0002-2953-9291)
- Abstract
Glioblastoma multiforme is a malignant primary brain tumor with a poor prognosis and high rates of chemo‐radiotherapy failure, mainly due to a small cell fraction with stem‐like properties (GSCs). The mechanisms underlying GSC response to radiation need to be elucidated to enhance sensitivity to treatments and to develop new therapeutic strategies. In a previous study, two GSC lines, named line #1 and line #83, responded differently to carbon ions and photon beams, with the differences likely attributable to their own different metabolic fingerprint rather than to radiation type. Data from the literature showed the capability of RHPS4, a G‐quadruplex stabilizing ligand, to sensitize the glioblastoma radioresistant U251MG cells to X‐rays. The combined metabolic effect of ligand #190, a new RHPS4‐derivative showing reduced cardiotoxicity, and a photon beam has been monitored by magnetic resonance (MR) spectroscopy for the two GSC lines, #1 and #83, to reveal whether a synergistic response occurs. MR spectra from both lines were affected by single and combined treatments, but the variations of the analysed metabolites were statistically significant mainly in line #1, without synergistic effects due to combination. The multivariate analysis of ten metabolites shows a separation between control and treated samples in line #1 regardless of treatment type, while separation was not detected in line #83.
- Published
- 2021
10. Dilation of Brain Veins and Perivascular Infiltration by Glioblastoma Cells in an in Vivo Assay of Early Tumor Angiogenesis
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D'Alessandris, Q. G., Pacioni, S., Stumpo, V., Buccarelli, M., Lauretti, L., Giordano, M., Di Bonaventura, R., Martini, M., Larocca, L. M., Giannetti, S., Montano, N., Falchetti, M. L., Ricci-Vitiani, L., Pallini, R., D'Alessandris Q. G. (ORCID:0000-0002-2953-9291), Pacioni S., Lauretti L. (ORCID:0000-0002-6463-055X), Di Bonaventura R., Martini M. (ORCID:0000-0002-6260-6310), Larocca L. M. (ORCID:0000-0003-1739-4758), Giannetti S. (ORCID:0000-0002-9456-8865), Montano N. (ORCID:0000-0002-4965-1950), Pallini R. (ORCID:0000-0002-4611-8827), D'Alessandris, Q. G., Pacioni, S., Stumpo, V., Buccarelli, M., Lauretti, L., Giordano, M., Di Bonaventura, R., Martini, M., Larocca, L. M., Giannetti, S., Montano, N., Falchetti, M. L., Ricci-Vitiani, L., Pallini, R., D'Alessandris Q. G. (ORCID:0000-0002-2953-9291), Pacioni S., Lauretti L. (ORCID:0000-0002-6463-055X), Di Bonaventura R., Martini M. (ORCID:0000-0002-6260-6310), Larocca L. M. (ORCID:0000-0003-1739-4758), Giannetti S. (ORCID:0000-0002-9456-8865), Montano N. (ORCID:0000-0002-4965-1950), and Pallini R. (ORCID:0000-0002-4611-8827)
- 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.
- Published
- 2021
11. Loss of pericentromeric DNA methylation pattern in human glioblastoma is associated with altered DNA methyltransferases expression and involves the stem cell compartment
- Author
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Fanelli, M, Caprodossi, S, Ricci-Vitiani, L, Porcellini, A, Tomassoni-Ardori, F, Amatori, S, Andreoni, F, Magnani, M, De Maria, R, Santoni, A, Minucci, S, and Pelicci, P G
- Published
- 2008
- Full Text
- View/download PDF
12. Colon cancer stem cells
- Author
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Ricci-Vitiani, L., Pagliuca, A., Palio, E., Zeuner, A., and De Maria, R.
- Subjects
Colon cancer -- Development and progression ,Stem cells -- Genetic aspects ,Stem cells -- Identification and classification ,Health - Published
- 2008
13. Rapid and Efficient Invasion Assay of Glioblastoma in Human Brain Organoids
- Author
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Goranci-Buzhala, G., Mariappan, A., Gabriel, E., Ramani, A., Ricci-Vitiani, L., Buccarelli, M., D'Alessandris, Quintino Giorgio, Pallini, Roberto, Gopalakrishnan, J., D'Alessandris Q. G. (ORCID:0000-0002-2953-9291), Pallini R. (ORCID:0000-0002-4611-8827), Goranci-Buzhala, G., Mariappan, A., Gabriel, E., Ramani, A., Ricci-Vitiani, L., Buccarelli, M., D'Alessandris, Quintino Giorgio, Pallini, Roberto, Gopalakrishnan, J., D'Alessandris Q. G. (ORCID:0000-0002-2953-9291), and Pallini R. (ORCID:0000-0002-4611-8827)
- Abstract
Glioblastoma (GBM) possesses glioma stem cells (GSCs) that exhibit aggressive invasion behavior in the brain. Current preclinical GBM invasion assays using mouse brain xenografts are time consuming and less efficient. Here, we demonstrate an array of methods that allow rapid and efficient assaying of GSCs invasion in human brain organoids. The assays are versatile to characterize various aspects of GSCs, such as invasion, integration, and interaction with mature neurons of brain organoids. Tissue clearing and quantitative 3D imaging of GSCs in host organoids reveal that invasiveness is inversely correlated with the organoids' age. Importantly, the described invasion assays can distinguish the invasive behaviors of primary and recurrent GSCs. The assays are also amenable to test pharmacological agents. As an example, we show that GI254023X, an inhibitor of ADAM10, could prevent the integration of GSCs into the organoids.
- Published
- 2020
14. 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
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Lulli, V., Buccarelli, M., Ilari, R., Castellani, G., De Dominicis, C., Di Giamberardino, A., D'Alessandris, Quintino Giorgio, Giannetti, Stefano, Martini, Maurizio, Stumpo, V., Boe, A., De Luca, G., Biffoni, M., Marziali, G., Pallini, Roberto, Ricci-Vitiani, L., Giannetti S. (ORCID:0000-0002-9456-8865), Martini M. (ORCID:0000-0002-6260-6310), Pallini R. (ORCID:0000-0002-4611-8827), Lulli, V., Buccarelli, M., Ilari, R., Castellani, G., De Dominicis, C., Di Giamberardino, A., D'Alessandris, Quintino Giorgio, Giannetti, Stefano, Martini, Maurizio, Stumpo, V., Boe, A., De Luca, G., Biffoni, M., Marziali, G., Pallini, Roberto, Ricci-Vitiani, L., Giannetti S. (ORCID:0000-0002-9456-8865), Martini M. (ORCID:0000-0002-6260-6310), and Pallini R. (ORCID:0000-0002-4611-8827)
- Abstract
Glioblastoma (GBM) is the most aggressive and prevalent form of a human brain tumor in adults. Several data have demonstrated the implication of microRNAs (miRNAs) in tumorigenicity of GBM stem-like cells (GSCs). The regulatory functions of miRNAs in GSCs have emerged as potential therapeutic candidates for glioma treatment. The current study aimed at investigating the function of miR-370-3p in glioma progression, as aberrant expression of miR-370-3p, is involved in various human cancers, including glioma. Analyzing our collection of GBM samples and patient-derived GSC lines, we found the expression of miR-370-3p significantly downregulated compared to normal brain tissues and normal neural stem cells. Restoration of miR-370-3p expression in GSCs significantly decreased proliferation, migration, and clonogenic abilities of GSCs, in vitro, and tumor growth in vivo. Gene expression analysis performed on miR-370-3p transduced GSCs, identified several transcripts involved in Epithelial to Mesenchymal Transition (EMT), and Hypoxia signaling pathways. Among the genes downregulated by the restored expression of miR-370-3p, we found the EMT-inducer high-mobility group AT-hook 2 (HMGA2), the master transcriptional regulator of the adaptive response to hypoxia, Hypoxia-inducible factor (HIF)1A, and the long non-coding RNAs (lncRNAs) Nuclear Enriched Abundant Transcript (NEAT)1. NEAT1 acts as an oncogene in a series of human cancers including gliomas, where it is regulated by the Epidermal Growth Factor Receptor (EGFR) pathways, and contributes to tumor growth and invasion. Noteworthy, the expression levels of miR-370-3p and NEAT1 were inversely related in both GBM tumor specimens and GSCs, and a dual-luciferase reporter assay proved the direct binding between miR-370-3p and the lncRNAs NEAT1. Our results identify a critical role of miR-370-3p in the regulation of GBM development, indicating that miR-370-3p acts as a tumor-suppressor factor inhibiting glioma cell growth, migra
- Published
- 2020
15. C-myc expression is a possible keystone in the colorectal cancer resistance to egfr inhibitors
- Author
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Strippoli, Antonia, Cocomazzi, Alessandra, Basso, Michele, Cenci, Tonia, Ricci, Riccardo, Pierconti, Francesco, Cassano, Alessandra, Fiorentino, Vincenzo, Barone, Carlo Antonio, Bria, Emilio, Ricci-Vitiani, L., Tortora, Giampaolo, Larocca, Luigi Maria, Martini, Maurizio, Strippoli A., Cocomazzi A., Basso M., Cenci T., Ricci R. (ORCID:0000-0002-9089-5084), Pierconti F. (ORCID:0000-0003-0951-4131), Cassano A. (ORCID:0000-0002-3311-7163), Fiorentino V., Barone C., Bria E. (ORCID:0000-0002-2333-704X), Tortora G. (ORCID:0000-0002-1378-4962), Larocca L. M. (ORCID:0000-0003-1739-4758), Martini M. (ORCID:0000-0002-6260-6310), Strippoli, Antonia, Cocomazzi, Alessandra, Basso, Michele, Cenci, Tonia, Ricci, Riccardo, Pierconti, Francesco, Cassano, Alessandra, Fiorentino, Vincenzo, Barone, Carlo Antonio, Bria, Emilio, Ricci-Vitiani, L., Tortora, Giampaolo, Larocca, Luigi Maria, Martini, Maurizio, Strippoli A., Cocomazzi A., Basso M., Cenci T., Ricci R. (ORCID:0000-0002-9089-5084), Pierconti F. (ORCID:0000-0003-0951-4131), Cassano A. (ORCID:0000-0002-3311-7163), Fiorentino V., Barone C., Bria E. (ORCID:0000-0002-2333-704X), Tortora G. (ORCID:0000-0002-1378-4962), Larocca L. M. (ORCID:0000-0003-1739-4758), and Martini M. (ORCID:0000-0002-6260-6310)
- Abstract
Alterations in the transcriptional factor c-MYC could be involved in the anti-EGFR resistance in metastatic colorectal cancer (mCRC). The c-MYC expression was evaluated in 121 RAS and BRAF wild-type mCRC before treatment with anti-EGFR+Folfiri therapy and in 33 subsequent metastases collected during target therapy (TT) or in TT resistance phase. We analyzed the expression and the functional role of some c-MYC linked miRNAs (miR-31-3p, miR-143 and miR-145) in our patient group and in two CRC cell lines, also performing a c-MYC target PCR array. Patients with higher c-MYC expression (HME) showed a significant lower PFS and OS when compared to those with low c-MYC expression (LME). HME pattern was significantly more frequent in the metastases after TT and significantly associated to anti-EGFR molecular resistance alterations. We also found a significant correlation between the expression of the above-mentioned c-MYC linked miRNAs, c-MYC level and anti-EGFR resistance. Moreover, expression gene profiling pointed out the pivotal role of c-MYC in CRC-related cell-cycle, apoptosis, signal transduction and cell-growth pathways. c-MYC expression might distinguish patients with a lower PFS and OS in anti-EGFR treated mCRC. The individuation of some miRNAs involved in the c-MYC pathway regulation and the downstream c-MYC effector genes could provide a new possible target to overcome the anti-EGFR resistance in mCRC.
- Published
- 2020
16. Brain invasion along perivascular spaces by glioma cells: Relationship with blood–brain barrier
- Author
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Pacioni, Simone, D'Alessandris, Quintino Giorgio, Buccarelli, M., Boe, A., Martini, Maurizio, Larocca, Luigi Maria, Bolasco, G., Ricci-Vitiani, L., Falchetti, M. L., Pallini, Roberto, Pacioni S., D'alessandris Q. G. (ORCID:0000-0002-2953-9291), Martini M. (ORCID:0000-0002-6260-6310), Larocca L. M. (ORCID:0000-0003-1739-4758), Pallini R. (ORCID:0000-0002-4611-8827), Pacioni, Simone, D'Alessandris, Quintino Giorgio, Buccarelli, M., Boe, A., Martini, Maurizio, Larocca, Luigi Maria, Bolasco, G., Ricci-Vitiani, L., Falchetti, M. L., Pallini, Roberto, Pacioni S., D'alessandris Q. G. (ORCID:0000-0002-2953-9291), Martini M. (ORCID:0000-0002-6260-6310), Larocca L. M. (ORCID:0000-0003-1739-4758), and Pallini R. (ORCID:0000-0002-4611-8827)
- Abstract
The question whether perivascular glioma cells invading the brain far from the tumor bulk may disrupt the blood–brain barrier (BBB) represents a crucial issue because under this condition tumor cells would be no more protected from the reach of chemotherapeutic drugs. A recent in vivo study that used human xenolines, demonstrated that single glioma cells migrating away from the tumor bulk are sufficient to breach the BBB. Here, we used brain xenografts of patient-derived glioma stem-like cells (GSCs) to show by immunostaining that in spite of massive perivascular invasion, BBB integrity was preserved in the majority of vessels located outside the tumor bulk. Interestingly, the tumor cells that invaded the brain for the longest distances traveled along vessels with retained BBB integrity. In surgical specimens of malignant glioma, the area of brain invasion showed several vessels with preserved BBB that were surrounded by tumor cells. On transmission electron microscopy, the cell inter-junctions and basal lamina of the brain endothelium were preserved even in conditions in which the tumor cells lay adjacently to blood vessels. In conclusion, BBB integrity associates with extensive perivascular invasion of glioma cells.
- Published
- 2020
17. CD95/CD95L interactions and their role in autoimmunity
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Ricci-Vitiani, L., Conticello, C., Zeuner, A., and De Maria, R.
- Published
- 2000
- Full Text
- View/download PDF
18. mGLU3 Metabotropic Glutamate Receptors Modulate the Differentiation of SVZ-Derived Neural Stem Cells Towards the Astrocytic Lineage
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CICERONI, C., MOSILLO, P., MASTRANTONI, E., SALE, P., RICCI-VITIANI, L., BIAGIONI, F., STOCCHI, F., NICOLETTI, F., and MELCHIORRI, D.
- Published
- 2010
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19. Zika virus infection induces MiR34c expression in glioblastoma stem cells: new perspectives for brain tumor treatments
- Author
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Iannolo, G., Sciuto, M. R., Cuscino, N., Pallini, R., Douradinha, B., Ricci Vitiani, L., De Maria, R., Conaldi, P. G., Pallini R. (ORCID:0000-0002-4611-8827), De Maria R. (ORCID:0000-0003-2255-0583), Iannolo, G., Sciuto, M. R., Cuscino, N., Pallini, R., Douradinha, B., Ricci Vitiani, L., De Maria, R., Conaldi, P. G., Pallini R. (ORCID:0000-0002-4611-8827), and De Maria R. (ORCID:0000-0003-2255-0583)
- Abstract
Zika virus (ZIKV) is a flavivirus with a marked effect on fetal nervous system development. ZIKV treatment has recently been found to also have a benefit against glioblastoma, a highly aggressive brain tumor with a poor prognosis. The reported data do not completely explain the mechanism beyond this effect. Nevertheless, in the majority of the cases no adverse effect has been found in healthy adult humans. In this study, we characterized the ZIKV infection mechanism on glioblastoma stem cells, which are considered responsible for the tumor progression and resistance to conventional therapies. Moreover, we explain why the action of this virus is directed to the stem cells in the nervous system counterpart. Our results confirm the effectiveness of ZIKV treatment against glioblastoma, indicating novel molecular targets that can be introduced for more powerful therapies.
- Published
- 2019
20. The discovery of RNA-aptamers that selectively bind and inhibit glioblastoma stem cells by targeting EphA2
- Author
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Affinito, A., primary, Quintavalle, C., additional, Esposito, C.L., additional, Roscigno, G., additional, Vilardo, C., additional, Nuzzo, S., additional, Ricci Vitiani, L., additional, De Luca, G., additional, Minic, Z., additional, Giannetti, S., additional, Pallini, R., additional, Berezovski, M.V., additional, Kichkailo, A.S., additional, Lapin, I.N., additional, De Franciscis, V., additional, and Condorelli, G., additional
- Published
- 2019
- Full Text
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21. 307. Metabolic heterogeneity among Glioblastoma stem-like cells reflects differences in response to drug treatments
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Palma, A., primary, Grande, S., additional, Ricci-Vitiani, L., additional, Luciani, A.M., additional, Buccarelli, M., additional, Biffoni, M., additional, Molinari, A., additional, Calcabrini, A., additional, D’Amore, E., additional, Guidoni, L., additional, Pallini, R., additional, Viti, V., additional, and Rosi, A., additional
- Published
- 2018
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22. A three-microRNA signature identifies two subtypes of glioblastoma patients with different clinical outcomes
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Marziali, G, Buccarelli, M, Giuliani, A, Ilari, R, Grande, S, Palma, A, D'Alessandris, Quintino Giorgio, Martini, Maurizio, Biffoni, M, Pallini, Roberto, Ricci Vitiani, L., Martini, Maurizio (ORCID:0000-0002-6260-6310), Pallini, Roberto (ORCID:0000-0002-4611-8827), Marziali, G, Buccarelli, M, Giuliani, A, Ilari, R, Grande, S, Palma, A, D'Alessandris, Quintino Giorgio, Martini, Maurizio, Biffoni, M, Pallini, Roberto, Ricci Vitiani, L., Martini, Maurizio (ORCID:0000-0002-6260-6310), and Pallini, Roberto (ORCID:0000-0002-4611-8827)
- Abstract
Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumor in adults, characterized by aggressive growth, limited response to therapy, and inexorable recurrence. Because of the extremely unfavorable prognosis of GBM, it is important to develop more effective diagnostic and therapeutic strategies based on biologically and clinically relevant patient stratification systems. Analyzing a collection of patient-derived GBM stem-like cells (GSCs) by gene expression profiling, nuclear magnetic resonance (NMR) spectroscopy and signal transduction pathway activation, we identified two GSC clusters characterized by different clinical features. Due to the widely documented role played by microRNAs (miRNAs) in the tumorigenesis process, in this study we explored whether these two GBM patient subtypes could also be discriminated by different miRNA signatures. Global miRNA expression pattern was analyzed by oblique principal component (OPC) analysis and principal component analysis (PCA). By a combined inferential strategy on PCA results, we identified a reduced set of three miRNAs - miR-23a, miR-27a and miR-9* (miR-9-3p) - able to discriminate the proneural- and mesenchymal-like GSC phenotypes as well as mesenchymal and proneural subtypes of primary GBM included in The Cancer Genome Atlas (TCGA) dataset. Kaplan-Meier analysis showed a significant correlation between the selected miRNAs and overall survival in 429 GBM specimens from TCGA-identifying patients who had an unfavorable outcome. The survival prognostic capability of the three miRNA signatures could have important implications for the understanding of the biology of GBM subtypes and could be useful in patient stratification to facilitate interpretation of results from clinical trials.
- Published
- 2017
23. Integrin a7 Is a Functional Marker and Potential Therapeutic Target in Glioblastoma
- Author
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Haas, Tobias Longin, Sciuto, Maria Rita, Brunetto, L, Valvo, Cecilia, Signore, M, Fiori, Micol Eleonora, Di Martino, Susanna, Giannetti, Stefano, Morgante, Liliana, Boe, A, Patrizii, M, Warnken, U, Schnölzer, M, Ciolfi, A, Di Stefano, C, Biffoni, M, Ricci-Vitiani, L, Pallini, Roberto, De Maria Marchiano, Ruggero, Haas TL (ORCID:0000-0003-2336-0263), Sciuto MR, Valvo C, Fiori ME, di Martino S, Giannetti S (ORCID:0000-0002-9456-8865), Morgante L, Pallini R (ORCID:0000-0002-4611-8827), De Maria Marchiano R. (ORCID:0000-0003-2255-0583), Haas, Tobias Longin, Sciuto, Maria Rita, Brunetto, L, Valvo, Cecilia, Signore, M, Fiori, Micol Eleonora, Di Martino, Susanna, Giannetti, Stefano, Morgante, Liliana, Boe, A, Patrizii, M, Warnken, U, Schnölzer, M, Ciolfi, A, Di Stefano, C, Biffoni, M, Ricci-Vitiani, L, Pallini, Roberto, De Maria Marchiano, Ruggero, Haas TL (ORCID:0000-0003-2336-0263), Sciuto MR, Valvo C, Fiori ME, di Martino S, Giannetti S (ORCID:0000-0002-9456-8865), Morgante L, Pallini R (ORCID:0000-0002-4611-8827), and De Maria Marchiano R. (ORCID:0000-0003-2255-0583)
- Abstract
Functionally relevant markers of glioblastoma stem- like cells (GSCs) have potential for therapeutic tar- geting to treat this aggressive disease. Here we used generation and screening of thousands of monoclonal antibodies to search for receptors and signaling pathways preferentially enriched in GSCs. We identified integrin a7 (ITGA7) as a major laminin receptor in GSCs and in primary high-grade glioma specimens. Analyses of mRNA profiles in compre- hensive datasets revealed that high ITGA7 expres- sion negatively correlated with survival of patients with both low- and high-grade glioma. In vitro and in vivo analyses showed that ITGA7 plays a key functional role in growth and invasiveness of GSCs. We also found that targeting of ITGA7 by RNAi or blocking mAbs impaired laminin-induced signaling, and it led to a significant delay in tumor engraftment plus a strong reduction in tumor size and invasion. Our data, therefore, highlight ITGA7 as a glioblastoma biomarker and candidate thera- peutic target.
- Published
- 2017
24. Emerging role for USP1 in glioblastoma stem cell maintenance and radioresistance: A potential target for glioblastoma therapy
- Author
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D'Alessandris, Quintino Giorgio, Ricci-Vitiani, L., D'Alessandris Q. G. (ORCID:0000-0002-2953-9291), D'Alessandris, Quintino Giorgio, Ricci-Vitiani, L., and D'Alessandris Q. G. (ORCID:0000-0002-2953-9291)
- Abstract
N.A.
- Published
- 2016
25. Metabolic/Proteomic Signature Defines Two Glioblastoma Subtypes with Different Clinical Outcome
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Marziali, G., Signore, M., Buccarelli, M., Grande, S., Palma, A., Biffoni, M., Rosi, A., D'Alessandris, Q. G., Martini, M., Larocca, L. M., De Maria Marchiano, R., Pallini, R., Ricci-Vitiani, L., D'Alessandris, Q. G. (ORCID:0000-0002-2953-9291), Martini, M. (ORCID:0000-0002-6260-6310), Larocca, L. M. (ORCID:0000-0003-1739-4758), De Maria Marchiano, R. (ORCID:0000-0003-2255-0583), Pallini, R. (ORCID:0000-0002-4611-8827), Marziali, G., Signore, M., Buccarelli, M., Grande, S., Palma, A., Biffoni, M., Rosi, A., D'Alessandris, Q. G., Martini, M., Larocca, L. M., De Maria Marchiano, R., Pallini, R., Ricci-Vitiani, L., D'Alessandris, Q. G. (ORCID:0000-0002-2953-9291), Martini, M. (ORCID:0000-0002-6260-6310), Larocca, L. M. (ORCID:0000-0003-1739-4758), De Maria Marchiano, R. (ORCID:0000-0003-2255-0583), and Pallini, R. (ORCID:0000-0002-4611-8827)
- Abstract
Glioblastoma (GBM) is one of the deadliest human cancers. Because of the extremely unfavorable prognosis of GBM, it is important to develop more effective diagnostic and therapeutic strategies based on biologically and clinically relevant subclassification systems. Analyzing a collection of seventeen patient-derived glioblastoma stem-like cells (GSCs) by gene expression profiling, NMR spectroscopy and signal transduction pathway activation, we identified two GSC clusters, one characterized by a pro-neural-like phenotype and the other showing a mesenchymal-like phenotype. Evaluating the levels of proteins differentially expressed by the two GSC clusters in the TCGA GBM sample collection, we found that SRC activation is associated with a GBM subgroup showing better prognosis whereas activation of RPS6, an effector of mTOR pathway, identifies a subgroup with a worse prognosis. The two clusters are also differentiated by NMR spectroscopy profiles suggesting a potential prognostic stratification based on metabolic evaluation. Our data show that the metabolic/proteomic profile of GSCs is informative of the genomic/proteomic GBM landscape, which differs among tumor subtypes and is associated with clinical outcome.
- Published
- 2016
26. Metabolic/Proteomic Signature Defines Two Glioblastoma Subtypes With Different Clinical Outcome
- Author
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Marziali, G, Signore, M, Buccarelli, M, Grande, S, Palma, Alessandro, Biffoni, M, Rosi, A, D'Alessandris, Quintino Giorgio, Martini, Maurizio, Larocca, Luigi Maria, De Maria Marchiano, Ruggero, Pallini, Roberto, Ricci-Vitiani, L, Martini, M (ORCID:0000-0002-6260-6310), Larocca, L M (ORCID:0000-0003-1739-4758), De Maria Marchiano, R (ORCID:0000-0003-2255-0583), Pallini, R (ORCID:0000-0002-4611-8827), Marziali, G, Signore, M, Buccarelli, M, Grande, S, Palma, Alessandro, Biffoni, M, Rosi, A, D'Alessandris, Quintino Giorgio, Martini, Maurizio, Larocca, Luigi Maria, De Maria Marchiano, Ruggero, Pallini, Roberto, Ricci-Vitiani, L, Martini, M (ORCID:0000-0002-6260-6310), Larocca, L M (ORCID:0000-0003-1739-4758), De Maria Marchiano, R (ORCID:0000-0003-2255-0583), and Pallini, R (ORCID:0000-0002-4611-8827)
- Abstract
Glioblastoma (GBM) is one of the deadliest human cancers. Because of the extremely unfavorable prognosis of GBM, it is important to develop more effective diagnostic and therapeutic strategies based on biologically and clinically relevant subclassification systems. Analyzing a collection of seventeen patient-derived glioblastoma stem-like cells (GSCs) by gene expression profiling, NMR spectroscopy and signal transduction pathway activation, we identified two GSC clusters, one characterized by a pro-neural-like phenotype and the other showing a mesenchymal-like phenotype. Evaluating the levels of proteins differentially expressed by the two GSC clusters in the TCGA GBM sample collection, we found that SRC activation is associated with a GBM subgroup showing better prognosis whereas activation of RPS6, an effector of mTOR pathway, identifies a subgroup with a worse prognosis. The two clusters are also differentiated by NMR spectroscopy profiles suggesting a potential prognostic stratification based on metabolic evaluation. Our data show that the metabolic/proteomic profile of GSCs is informative of the genomic/proteomic GBM landscape, which differs among tumor subtypes and is associated with clinical outcome.
- Published
- 2016
27. 1998P - The discovery of RNA-aptamers that selectively bind and inhibit glioblastoma stem cells by targeting EphA2
- Author
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Affinito, A., Quintavalle, C., Esposito, C.L., Roscigno, G., Vilardo, C., Nuzzo, S., Ricci Vitiani, L., De Luca, G., Minic, Z., Giannetti, S., Pallini, R., Berezovski, M.V., Kichkailo, A.S., Lapin, I.N., De Franciscis, V., and Condorelli, G.
- Published
- 2019
- Full Text
- View/download PDF
28. High Nitric Oxide production, secondary to high inducible-nitric oxide synthase expression, is essential in regulating tumor initiating properties of colon cancer stem cells
- Author
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1Puglisi A., 2Tesori V., 3 Ricci-Vitiani L., 3Cappellari M., 4Cenciarelli C., 5Martini M., 6Giorda E., 6Carsetti R., 2Gasbarrini G., 7Pani GB., and 1Gasbarrini A.
- Abstract
INTRODUCTION Several studies have indicated that continuous exposure to high concentrations of Nitric Oxide (NO), produced by inducibile-NO synthase (iNOS), promote neoplastic transformation in many human cancers and especially in colon cancer (CC). Recently, it has also been suggested that high NO synthesis is a distinctive feature of "cancer stem cells" (CSC), a tumor subpopulation with self-renewal capacity, that may be identified by the expression of the CD133 surface marker. AIMS & METHODS Aims of this study were to explore the contribution of NO in the definition of colon CSC features and evaluate potential strategies to treat CC by modulating NO production. By immunohistochemistry analysis we evaluated iNOS and CD133 expression in 30 samples of human CC. Using the DAF-2DA detection system, we assayed the production of intracellular NO in 5 colon CSC lines obtained from human CC tissues. By FACS sorter, we purified the NOhigh and NOlow fractions from all colon CSC lines. We compared the tumorigenic potential of both cell fractions by in vitro and in vivo assays. To tested the potential antitumor effects of iNOS modulation, we treated colon CSCs with the selective iNOS inhibitor 1400W or we stably transfected these cells with two distinct iNOS-directed short-harpin RNA(shRNAs). RESULTS NOhigh CSCs display an overespression of stem cell markers and higher expression levels of iNOS than NOlow cells. Interestingly, immunohistochemistry analysis confirmed that, regardless of tumor differentiation grade and TNM stage, there was a significant association between iNOS overexpression and higher expression level of the stem cell marker CD133, in human CC. Moreover, we demonstrated, by in vitro and in vivo assays, that NOhigh cells displayed higher tumorigenic abilities than NOlow fractions. The blockade of endogenous NO availability using a specific iNOS inhibitor and genetic knock-down of iNOS resulted in a significant reduction of colon CSC growth and tumorigenic capacity: a lower capacity to give rise to colonies in soft agar, a dramatic decrease of invasivness and in vivo tumor growth (xenotransplantations in nude mice). These data confirmed an integral role for endogenous NO and iNOS activity in the biology of colon CSCs. Interestingly, analysis of the genes altered by iNOS-directed shRNA showed that the knockdown of iNOS expression was associated with a significant down regulation of a wide range of signaling pathways in colon CSCs, especially genes involved in stemness and tumor progression (such as CD133, BMI, b-Catenin and NF-kB pathway). CONCLUSION These findings have demonstrated for the first time that endogenous NO plays an important role in defining the stemness properties of colon CSCs through cross-regulation of several cellular signaling pathways. This discovery could shed light on the mechanisms by which NO induces the growth and invasiveness of CC gathering new insights on the link between inflammation and colon tumorigenesis.
- Published
- 2014
29. Metabolic/Proteomic Signature Defines Two Glioblastoma Subtypes With Different Clinical Outcome
- Author
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Marziali, G., primary, Signore, M., additional, Buccarelli, M., additional, Grande, S., additional, Palma, A., additional, Biffoni, M., additional, Rosi, A., additional, D’Alessandris, Q.G., additional, Martini, M., additional, Larocca, L. M., additional, De Maria, R., additional, Pallini, R., additional, and Ricci-Vitiani, L., additional
- Published
- 2016
- Full Text
- View/download PDF
30. PED mediates AKT dependent chemoresistance in human breast cancer cells
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STASSI G, GAROFALO M, ZERILLI M, RICCI VITIANI L, ZANCA C, TODARO M, ARAGONA F, LIMITE G, CONDORELLI, GEROLAMA, Stassi, G, Garofalo, M, Zerilli, M, RICCI VITIANI, L, Zanca, C, Todaro, M, Aragona, F, Limite, G, and Condorelli, Gerolama
- Published
- 2005
31. A BMP7 Variant Inhibits Tumor Angiogenesis In Vitro and In Vivo through Direct Modulation of Endothelial Cell Biology.
- Author
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Tate, CM, Mc Entire, J, PALLINI, ROBERTO, Vakana, E, Wyss,L, Blosser, W, Ricci-Vitiani, L, D'alessandris, QG, MORGANTE, LILIANA, GIANNETTI, STEFANO, LAROCCA, LUIGI MARIA, Todaro, M, Benfante, A, Colorito, ML, Stassi, G, DeMaria, R, Rowlinson, S, Stancato, L, Tate, CM, Mc Entire, J, PALLINI, ROBERTO, Vakana, E, Wyss,L, Blosser, W, Ricci-Vitiani, L, D'alessandris, QG, MORGANTE, LILIANA, GIANNETTI, STEFANO, LAROCCA, LUIGI MARIA, Todaro, M, Benfante, A, Colorito, ML, Stassi, G, DeMaria, R, Rowlinson, S, and Stancato, L
- Published
- 2015
32. Cannabidiol stimulates Aml-1a-dependent glial differentiation and inhibits glioma stem-like cells proliferation by inducing autophagy in a TRPV2-dependent manner
- Author
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Nabissi, M, Morelli, Mb, Amantini, C, Liberati, S, Santoni, M, Ricci-Vitiani, L, Pallini, Roberto, Santoni, G, Pallini, R (ORCID:0000-0002-4611-8827), Nabissi, M, Morelli, Mb, Amantini, C, Liberati, S, Santoni, M, Ricci-Vitiani, L, Pallini, Roberto, Santoni, G, and Pallini, R (ORCID:0000-0002-4611-8827)
- Abstract
Glioma stem-like cells (GSCs) correspond to a tumor cell subpopulation, involved in glioblastoma multiforme (GBM) tumor initiation and acquired chemoresistance. Currently, drug-induced differentiation is considered as a promising approach to eradicate this tumor-driving cell population. Recently, the effect of cannabinoids (CBs) in promoting glial differentiation and inhibiting gliomagenesis has been evidenced. Herein, we demonstrated that cannabidiol (CBD) by activating transient receptor potential vanilloid-2 (TRPV2) triggers GSCs differentiation activating the autophagic process and inhibits GSCs proliferation and clonogenic capability. Above all, CBD and carmustine (BCNU) in combination overcome the high resistance of GSCs to BCNU treatment, by inducing apoptotic cell death. Acute myeloid leukemia (Aml-1) transcription factors play a pivotal role in GBM proliferation and differentiation and it is known that Aml-1 control the expression of several nociceptive receptors. So, we evaluated the expression levels of Aml-1 spliced variants (Aml-1a, b and c) in GSCs and during their differentiation. We found that Aml-1a is upregulated during GSCs differentiation, and its downregulation restores a stem cell phenotype in differentiated GSCs. Since it was demonstrated that CBD induces also TRPV2 expression and that TRPV2 is involved in GSCs differentiation, we evaluated if Aml-1a interacted directly with TRPV2 promoters. Herein, we found that Aml-1a binds TRPV2 promoters and that Aml-1a expression is upregulated by CBD treatment, in a TRPV2 and PI3K/AKT dependent manner. Altogether, these results support a novel mechanism by which CBD inducing TRPV2-dependent autophagic process stimulates Aml-1a-dependent GSCs differentiation, abrogating the BCNU chemoresistance in GSCs.
- Published
- 2015
33. Absence of caspase 8 and high expression of PED protect primitive neural cells from cell death
- Author
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Ricci Vitiani L, Pedini F, Mollinari C, Bonci D, Bez A, Colombo A, Parati E, Peschle C, De Maria R., CONDORELLI, GEROLAMA, Ricci Vitiani, L, Pedini, F, Mollinari, C, Condorelli, Gerolama, Bonci, D, Bez, A, Colombo, A, Parati, E, Peschle, C, and De Maria, R.
- Subjects
apoptosis - Abstract
The mechanisms that control neural stem and progenitor cell survival are unknown. In several pathological conditions, death receptor (DR) ligands and inflammatory cytokines exert a deleterious effect on neurons, whereas primitive neural cells migrate and survive in the site of lesion. Here, we show that even in the presence of inflammatory cytokines, DRs are unable to generate death signals in primitive neural cells. Neural stem and progenitor cells did not express caspase 8, the presence of which is required for initiating the caspase cascade. However, exogenous or cytokine-mediated expression of caspase 8 was not sufficient to restore their DR sensitivity. Searching for molecules potentially able to block DR death-inducing signaling complex (DISC), we found that primitive neural cells expressed high levels of the death effector domain-containing protein PED (also known as PEA-15). PED localized in the DISC and prevented caspase 8 recruitment and activation. Moreover, lentiviral-mediated delivery of PED antisense DNA resulted in dramatic down-regulation of the endogenous gene expression and sensitization of primitive neural cells to apoptosis mediated by inflammatory cytokines and DRs. Thus, absence of caspase 8 and high expression of PED constitute two levels of protection from apoptosis induced by DRs and inflammatory cytokines in neural stem and progenitor cells.
- Published
- 2004
34. Gene expression analysis of PTEN positive glioblastoma stem cells identifies DUB3 and Wee1 modulation in a cell differentiation model
- Author
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Forte, S, Pagliuca, Alfredo, Maniscalchi, Et, Gulino, Rosario Alfio, Calabrese, Giorgio, Ricci-Vitiani, L, Pallini, Roberto, Signore, M, Parenti, R, De Maria Marchiano, Ruggero, R, and Gulisano, Mario Domenico
- Subjects
Genetics and Molecular Biology (all) ,Adult ,Male ,Cellular differentiation ,Population ,Settore MED/27 - NEUROCHIRURGIA ,lcsh:Medicine ,Cell Cycle Proteins ,Biochemistry ,Settore MED/04 - PATOLOGIA GENERALE ,Glioma ,Endopeptidases ,medicine ,PTEN ,Humans ,education ,Aged ,Cell Differentiation ,Female ,Gene Expression Profiling ,Gene Expression Regulation, Neoplastic ,Middle Aged ,Neoplastic Stem Cells ,Nuclear Proteins ,PTEN Phosphohydrolase ,Protein-Tyrosine Kinases ,lcsh:Science ,PI3K/AKT/mTOR pathway ,education.field_of_study ,Neoplastic ,Multidisciplinary ,biology ,Cancer stem cells ,Medicine (all) ,lcsh:R ,Cell cycle ,medicine.disease ,Cell biology ,Agricultural and Biological Sciences (all) ,Biochemistry, Genetics and Molecular Biology (all) ,Wee1 ,Gene Expression Regulation ,Cancer research ,biology.protein ,lcsh:Q ,Stem cell ,Glioblastoma ,Research Article - Abstract
The term astrocytoma defines a quite heterogeneous group of neoplastic diseases that collectively represent the most frequent brain tumors in humans. Among them, glioblastoma multiforme represents the most malignant form and its associated prognosis is one of the poorest among tumors of the central nervous system. It has been demonstrated that a small population of tumor cells, isolated from the brain neoplastic tissue, can reproduce the parental tumor when transplanted in immunodeficient mouse. These tumor initiating cells are supposed to be involved in cancer development and progression and possess stem cell-like features; like their normal counterpart, these cells remain quiescent until they are committed to differentiation. Many studies have shown that the role of the tumor suppressor protein PTEN in cell cycle progression is fundamental for tumor dynamics: in low grade gliomas, PTEN contributes to maintain cells in G1 while the loss of its activity is frequently observed in high grade gliomas. The mechanisms underlying the above described PTEN activity have been studied in many tumors, but those involved in the maintenance of tumor initiating cells quiescence remain to be investigated in more detail. The aim of the present study is to shed light on the role of PTEN pathway on cell cycle regulation in Glioblastoma stem cells, through a cell differentiation model. Our results suggest the existence of a molecular mechanism, that involves DUB3 and WEE1 gene products in the regulation of Cdc25a, as functional effector of the PTEN/Akt pathway.
- Published
- 2013
35. Epigenetic silencing of Id4 identifies a glioblastoma subgroup with a better prognosis as a consequence of an inhibition of angiogenesis
- Author
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Martini, Maurizio, Cenci, Tonia, D'Alessandris, Gq, Cesarini, V, Cocomazzi, Alessandra, Ricci-Vitiani, L, De Maria Marchiano, Ruggero, R, Pallini, Roberto, and Larocca, Luigi Maria
- Subjects
Adult ,Vascular Endothelial Growth Factor A ,Cancer Research ,Angiogenesis ,temozolomide ,Biology ,chemistry.chemical_compound ,Young Adult ,Id4 ,Settore MED/04 - PATOLOGIA GENERALE ,Matrix gla protein ,80 and over ,Humans ,Transcription factor ,Neovascularization ,Aged ,Pathologic ,Aged, 80 and over ,Neovascularization, Pathologic ,vascular endothelial growth factor ,Settore MED/08 - ANATOMIA PATOLOGICA ,Brain Neoplasms ,Medicine (all) ,adjuvant radiotherapy ,glioblastoma ,Glioblastoma ,Inhibitor of Differentiation Proteins ,Middle Aged ,Prognosis ,DNA Methylation ,Oncology ,Methylation ,Transforming growth factor beta ,Molecular biology ,Vascular endothelial growth factor ,Vascular endothelial growth factor A ,chemistry ,DNA methylation ,biology.protein ,glioblastoma, Id4, vascular endothelial growth factor, adjuvant radiotherapy, temozolomide - Abstract
BACKGROUND: Inhibitors of DNA binding/differentiation (Id1 to Id4) are a family of helix-loop-helix transcription factors, which are highly expressed during embryogenesis and at lower levels in mature tissues. Id4 plays an important role in neuronal stem cell differentiation, and its deregulation has been implicated in glial neoplasia. METHODS: The methylation status of Id4 was analyzed by methylation-specific polymerase chain reaction (PCR) in 62 glioblastoma (GBM) cases and in 20 normal brain tissues. Methylation status of Id4 was confirmed by sequencing after subcloning and messenger RNA (mRNA) and protein expression. We also evaluated the mRNA expression of MGP (matrix GLA protein), TGF-β1 (transforming growth factor beta 1), and VEGF (vascular endothelial growth factor) by real-time PCR analysis. Clinical and histological assessment of tumor angiogenesis was performed by evaluating the relative enhancing tumor ratio on magnetic resonance imaging and microvessel density on von Willebrand factor–stained sections, respectively. RESULTS: The promoter of Id4 was methylated in 23 of 62 (37%) GBMs. In methylated GBMs, Id4 mRNA was significantly reduced, compared with unmethylated GBMs (P = .0002). A significant reduction of protein expression was detected in all hypermethylated cases. GBMs with methylated Id4 showed a significant reduction of MGP, TGF-β1, and VEGF mRNA expression and had significantly lower relative enhancing tumor ratio (P = .0108) and microvessel density (P = .0241) values with respect to unmethylated GBMs. Finally, Id4 methylation was significantly associated with a favorable clinical outcome (P = .0006). CONCLUSIONS: These data suggest that methylation of Id4 may be involved in the pathogenesis of GBM and in the resistance of this neoplasm to conventional treatment throughout MGP-mediated neoangiogenesis. Cancer 2013. © 2012 American Cancer Society
- Published
- 2013
36. A BMP7 variant inhibits the tumorigenic potential of glioblastoma stem-like cells
- Author
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Tate, Cm, Pallini, Roberto, Ricci Vitiani, L, Dowless, M, Shiyanova, T, D'Alessandris, Gq, Morgante, Liliana, Giannetti, Stefano, Larocca, Luigi Maria, Di Martino, S., Rowlinson, Sw, De Maria, R, Stancato, L., and De Maria Marchiano, Ruggero
- Subjects
cancer stem cells ,Cell type ,Pathology ,medicine.medical_specialty ,Angiogenesis ,Cellular differentiation ,Bone Morphogenetic Protein 7 ,Transplantation, Heterologous ,Settore MED/27 - NEUROCHIRURGIA ,Population ,Biology ,Stem cell marker ,Cell Line ,Astrocyte differentiation ,Mice ,Cancer stem cell ,Settore MED/04 - PATOLOGIA GENERALE ,Cell Line, Tumor ,bone morphogenetic protein ,medicine ,Glioblastoma ,Animals ,Brain Neoplasms ,Cell Differentiation ,Cell Proliferation ,Cytokines ,HCT116 Cells ,Humans ,Neoplastic Stem Cells ,Neovascularization, Pathologic ,Molecular Biology ,Cell Biology ,education ,Neovascularization ,Pathologic ,Original Paper ,education.field_of_study ,Transplantation ,Heterologous ,Tumor ,medicine.anatomical_structure ,Cancer research ,Astrocyte - Abstract
Glioblastoma multiforme (GBM) is among the most aggressive tumor types and is essentially an incurable malignancy characterized by resistance to chemo-, radio-, and immunotherapy. GBM is maintained by a hierarchical cell organization that includes stem-like, precursor, and differentiated cells. Recurrence and maintenance of the tumor is attributed to a small population of undifferentiated tumor-initiating cells, defined as glioblastoma stem-like cells (GSLCs). This cellular hierarchy offers a potential treatment to induce differentiation of GSLCs away from tumor initiation to a more benign phenotype or to a cell type more amenable to standard therapies. Bone morphogenetic proteins (BMPs), members of the TGF-β superfamily, have numerous biological activities including control of growth and differentiation. In vitro, a BMP7 variant (BMP7v) decreased primary human GSLC proliferation, endothelial cord formation, and stem cell marker expression while enhancing neuronal and astrocyte differentiation marker expression. In subcutaneous and orthotopic GSLC xenografts, which closely reproduce the human disease, BMP7v decreased tumor growth and stem cell marker expression, while enhancing astrocyte and neuronal differentiation compared with control mice. In addition, BMP7v reduced brain invasion, angiogenesis, and associated mortality in the orthotopic model. Inducing differentiation of GSLCs and inhibiting angiogenesis with BMP7v provides a potentially powerful and novel approach to the treatment of GBM.
- Published
- 2012
37. The selective mGluR2/3 antagonist, LY341495, enhances chemosensitivity of colon cancer stem cells to standard chemotherapy
- Author
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Mosillo, Paola, Spinsanti, Paola, Serone, F., Azzollini, F., Turriziani, B., Noviello, Lia, Ricci Vitiani, L., Nicoletti, Ferdinando, and Melchiorri, Daniela
- Published
- 2011
38. Pharmacological blockade of type II mGlu receptors increases the sensitivity of cancer stem cells isolated from colorectal cancer specimens to standard chemotherapy
- Author
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Mosillo, Paola, Spinsanti, Paola, Serone, F., Azzollini, F., Cinque, L., Turriziani, B., Noviello, Lia, Ricci Vitiani, L., Nicoletti, Ferdinando, and Melchiorri, Daniela
- Published
- 2011
39. Pharmacological blockade of mGlu2/3 receptors amplifies the sensitivity of colorectal cancer stem cells to standard chemotherapy
- Author
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Mosillo, Paola, Spinsanti, Paola, Serone, F., Azzollini, F., Cinque, L., Turriziani, B., Noviello, Lia, Cappuccio, Irene, Battaglia, G., Ricci Vitiani, L., Nicoletti, Ferdinando, and Melchiorri, Daniela
- Published
- 2011
40. VEGF isoforms as outcome biomarker for anti-angiogenic therapy in recurrent glioblastoma
- Author
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D'Alessandris, Q. G., primary, Martini, M., additional, Cenci, T., additional, Capo, G., additional, Ricci-Vitiani, L., additional, Larocca, L. M., additional, and Pallini, R., additional
- Published
- 2015
- Full Text
- View/download PDF
41. Combined PDK1 and CHK1 inhibition is required to kill glioblastoma stem-like cells in vitro and in vivo
- Author
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Signore, M, Pelacchi, F, Di Martino, Susanna, Runci, D, Biffoni, M, Giannetti, Stefano, Morgante, Liliana, De Majo, M, Petricoin, Ef, Stancato, L, Larocca, Luigi Maria, De Maria Marchiano, Ruggero, Pallini, Roberto, Ricci-Vitiani, L., di Martino S, Giannetti S (ORCID:0000-0002-9456-8865), Morgante L, Larocca LM (ORCID:0000-0003-1739-4758), De Maria Marchiano R (ORCID:0000-0003-2255-0583), Pallini R (ORCID:0000-0002-4611-8827), Signore, M, Pelacchi, F, Di Martino, Susanna, Runci, D, Biffoni, M, Giannetti, Stefano, Morgante, Liliana, De Majo, M, Petricoin, Ef, Stancato, L, Larocca, Luigi Maria, De Maria Marchiano, Ruggero, Pallini, Roberto, Ricci-Vitiani, L., di Martino S, Giannetti S (ORCID:0000-0002-9456-8865), Morgante L, Larocca LM (ORCID:0000-0003-1739-4758), De Maria Marchiano R (ORCID:0000-0003-2255-0583), and Pallini R (ORCID:0000-0002-4611-8827)
- Abstract
Glioblastoma (GBM) is the most common and deadly adult brain tumor. Despite aggressive surgery, radiation, and chemotherapy, the life expectancy of patients diagnosed with GBM is ∼14 months. The extremely aggressive nature of GBM results from glioblastoma stem-like cells (GSCs) that sustain GBM growth, survive intensive chemotherapy, and give rise to tumor recurrence. There is accumulating evidence revealing that GSC resilience is because of concomitant activation of multiple survival pathways. In order to decode the signal transduction networks responsible for the malignant properties of GSCs, we analyzed a collection of GSC lines using a dual, but complementary, experimental approach, that is, reverse-phase protein microarrays (RPPMs) and kinase inhibitor library screening. We treated GSCs in vitro with clinically relevant concentrations of temozolomide (TMZ) and performed RPPM to detect changes in phosphorylation patterns that could be associated with resistance. In addition, we screened GSCs in vitro with a library of protein and lipid kinase inhibitors to identify specific targets involved in GSC survival and proliferation. We show that GSCs are relatively insensitive to TMZ treatment in terms of pathway activation and, although displaying heterogeneous individual phospho-proteomic profiles, most GSCs are resistant to specific inhibition of the major signaling pathways involved in cell survival and proliferation. However, simultaneous multipathway inhibition by the staurosporin derivative UCN-01 results in remarkable inhibition of GSC growth in vitro. The activity of UCN-01 on GSCs was confirmed in two in vivo models of GBM growth. Finally, we used RPPM to study the molecular and functional effects of UCN-01 and demonstrated that the sensitivity to UCN-01 correlates with activation of survival signals mediated by PDK1 and the DNA damage response initiated by CHK1. Taken together, our results suggest that a combined inhibition of PDK1 and CHK1 represents a poten
- Published
- 2014
42. Combined PDK1 and CHK1 inhibition is required to kill glioblastoma stem-like cells in vitro and in vivo
- Author
-
Signore, M., Pelacchi, F., Di Martino, Susanna, Runci, D., Biffoni, M., Giannetti, Stefano, Morgante, Liliana, De Majo, M., Petricoin, E. F., Stancato, L., Larocca, Luigi Maria, De Maria Marchiano, Ruggero, Pallini, Roberto, Ricci-Vitiani, L., Di Martino, S., Giannetti, S. (ORCID:0000-0002-9456-8865), Morgante, L., Larocca, L. M. (ORCID:0000-0003-1739-4758), De Maria Marchiano, R. (ORCID:0000-0003-2255-0583), Pallini, R. (ORCID:0000-0002-4611-8827), Signore, M., Pelacchi, F., Di Martino, Susanna, Runci, D., Biffoni, M., Giannetti, Stefano, Morgante, Liliana, De Majo, M., Petricoin, E. F., Stancato, L., Larocca, Luigi Maria, De Maria Marchiano, Ruggero, Pallini, Roberto, Ricci-Vitiani, L., Di Martino, S., Giannetti, S. (ORCID:0000-0002-9456-8865), Morgante, L., Larocca, L. M. (ORCID:0000-0003-1739-4758), De Maria Marchiano, R. (ORCID:0000-0003-2255-0583), and Pallini, R. (ORCID:0000-0002-4611-8827)
- Abstract
Glioblastoma (GBM) is the most common and deadly adult brain tumor. Despite aggressive surgery, radiation, and chemotherapy, the life expectancy of patients diagnosed with GBM is â1⁄414 months. The extremely aggressive nature of GBM results from glioblastoma stem-like cells (GSCs) that sustain GBM growth, survive intensive chemotherapy, and give rise to tumor recurrence. There is accumulating evidence revealing that GSC resilience is because of concomitant activation of multiple survival pathways. In order to decode the signal transduction networks responsible for the malignant properties of GSCs, we analyzed a collection of GSC lines using a dual, but complementary, experimental approach, that is, reverse-phase protein microarrays (RPPMs) and kinase inhibitor library screening. We treated GSCs in vitro with clinically relevant concentrations of temozolomide (TMZ) and performed RPPM to detect changes in phosphorylation patterns that could be associated with resistance. In addition, we screened GSCs in vitro with a library of protein and lipid kinase inhibitors to identify specific targets involved in GSC survival and proliferation. We show that GSCs are relatively insensitive to TMZ treatment in terms of pathway activation and, although displaying heterogeneous individual phospho-proteomic profiles, most GSCs are resistant to specific inhibition of the major signaling pathways involved in cell survival and proliferation. However, simultaneous multipathway inhibition by the staurosporin derivative UCN-01 results in remarkable inhibition of GSC growth in vitro. The activity of UCN-01 on GSCs was confirmed in two in vivo models of GBM growth. Finally, we used RPPM to study the molecular and functional effects of UCN-01 and demonstrated that the sensitivity to UCN-01 correlates with activation of survival signals mediated by PDK1 and the DNA damage response initiated by CHK1. Taken together, our results suggest that a combined inhibition of PDK1 and CHK1 represents a
- Published
- 2014
43. Pharmacological inhibition of poly(ADP-ribose) polymerase-1 modulates resistance of human glioblastoma stem cells to temozolomide
- Author
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Tentori, L, Ricci Vitiani, L, Muzi, A, Ciccarone, F, Pelacchi, F, Calabrese, R, Runci, D, Pallini, Roberto, Caiafa, P, Graziani, G., Pallini, Roberto (ORCID:0000-0002-4611-8827), Tentori, L, Ricci Vitiani, L, Muzi, A, Ciccarone, F, Pelacchi, F, Calabrese, R, Runci, D, Pallini, Roberto, Caiafa, P, Graziani, G., and Pallini, Roberto (ORCID:0000-0002-4611-8827)
- Abstract
BACKGROUND: Chemoresistance of glioblastoma multiforme (GBM) has been attributed to the presence within the tumor of cancer stem cells (GSCs). The standard therapy for GBM consists of surgery followed by radiotherapy and the chemotherapeutic agent temozolomide (TMZ). However, TMZ efficacy is limited by O6-methylguanine-DNA-methyltransferase (MGMT) and Mismatch Repair (MMR) functions. Strategies to counteract TMZ resistance include its combination with poly(ADP-ribose) polymerase inhibitors (PARPi), which hamper the repair of N-methylpurines. PARPi are also investigated as monotherapy for tumors with deficiency of homologous recombination (HR). We have investigated whether PARPi may restore GSC sensitivity to TMZ or may be effective as monotherapy. METHODS: Ten human GSC lines were assayed for MMR proteins, MGMT and PARP-1 expression/activity, MGMT promoter methylation and sensitivity to TMZ or PARPi, alone and in combination. Since PTEN defects are frequently detected in GBM and may cause HR dysfunction, PTEN expression was also analyzed. The statistical analysis of the differences in drug sensitivity among the cell lines was performed using the ANOVA and Bonferroni's post-test or the non-parametric Kruskal-Wallis analysis and Dunn's post-test for multiple comparisons. Synergism between TMZ and PARPi was analyzed by the median-effect method of Chou and Talalay. Correlation analyses were done using the Spearman's rank test. RESULTS: All GSCs were MMR-proficient and resistance to TMZ was mainly associated with high MGMT activity or low proliferation rate. MGMT promoter hypermethylation of GSCs correlated both with low MGMT activity/expression (Spearman's test, P = 0.004 and P = 0.01) and with longer overall survival of GBM patients (P = 0.02). Sensitivity of each GSC line to PARPi as single agent did not correlate with PARP-1 or PTEN expression. Notably, PARPi and TMZ combination exerted synergistic antitumor effects in eight out of ten GSC lines and the TMZ dose redu
- Published
- 2014
44. Cancer Treatment and test
- Author
-
De Maria, R. 1, Garaci E. 2, Mollinari C. 3, Ricci-Vitiani L. 1, and Merlo D. 3.
- Published
- 2008
45. Inhibition of telomerase in the endothelial cells disrupts tumor angiogenesis in glioblastoma xenografts
- Author
-
Falchetti M.L. 1, Mongiardi M.P. 1, Fiorenzo P. 1, Petrucci G. 2, Pierconti F. 2, DAgnano I. 1, DAlessandris G. 3, Alessandri G. 4, Gelati M. 4, Ricci-Vitiani L. 5, Maira G. 3, Larocca L.M. 2, Levi A. 1, and Pallini R. 3
- Subjects
Graft ,Transplantation ,Surgery ,Central nervous system disease ,Nervous system diseases - Abstract
Tumor angiogenesis is a complex process that involves a series of interactions between tumor cells and endothelial cells (ECs). In vitro, glioblastoma multiforme (GBM) cells are known to induce an increase in proliferation, migration and tube formation by the ECs. We have previously shown that in human GBM specimens the proliferating ECs of the tumor vasculature express the catalytic component of telomerase, hTERT, and that telomerase can be upregulated in human ECs by exposing these cells to GBM in vitro. Here, we developed a controlled in vivo assay of tumor angiogenesis in which primary human umbilical vascular endothelial cells (HUVECs) were subcutaneously grafted with or without human GBM cells in immunocompromised mice as Matrigel implants. We found that primary HUVECs did not survive in Matrigel implants, and that telomerase upregulation had little effect on HUVEC survival. In the presence of GBM cells, however, the grafted HUVECs not only survived in Matrigel implants but developed tubule structures that integrated with murine microvessels. Telomerase upregulation in HUVECs enhanced such effect. More importantly, inhibition of telomerase in HUVECs completely abolished tubule formation and greatly reduced survival of these cells in the tumor xenografts. Our data demonstrate that telomerase upregulation by the ECs is a key requisite for GBM tumor angiogenesis.
- Published
- 2008
46. Inhibition of telomerase in the endothelial cells disrupts tumor angiogenesis in glioblastoma xenografts
- Author
-
Falchetti, Ml, Mongiardi, Mp, Fiorenzo, Paolo, Petrucci, Giovanna, Pierconti, Francesco, D'Agnano, I, D'Alessandris, G, Alessandri, G, Gelati, M, Ricci Vitiani, L, Maira, Giulio, Larocca, Luigi Maria, Levi, A, and Pallini, Roberto
- Subjects
Pathologic ,Neovascularization, Pathologic ,Brain Neoplasms ,Reverse Transcriptase Polymerase Chain Reaction ,Settore MED/27 - NEUROCHIRURGIA ,Flow Cytometry ,Immunohistochemistry ,Microscopy, Fluorescence ,Cell Line, Tumor ,Humans ,Endothelium, Vascular ,Glioblastoma ,Telomerase ,Neovascularization - Published
- 2008
47. Role of Thymoisn beta4 in normal and tumoral stem cells
- Author
-
Mollinari C. 1 Ricci-Vitiani L. 2, Rinaldi AM. 3, Merlo D. 1, 4, and Garaci E. 5.
- Published
- 2007
48. Human neural progenitor cells display limited cytotoxicity and increased oligodendrogenesis during inflammation [2]
- Author
-
Ricci-Vitiani, L., Lombardi, D. G., Signore, M., Biffoni, M., Pallini, Roberto, Parati, E., Peschle, C., and De Maria Marchiano, Ruggero
- Subjects
Inflammation ,Cultured ,Cells ,Cytotoxicity ,Stem Cells ,Animals ,Cells, Cultured ,Cytotoxicity, Immunologic ,Demyelinating Autoimmune Diseases, CNS ,Humans ,Mice ,Nerve Tissue Proteins ,Oligodendroglia ,Tumor Necrosis Factor Receptor-Associated Peptides and Proteins ,Cell Biology ,Demyelinating Autoimmune Diseases ,Immunologic ,Settore MED/04 - PATOLOGIA GENERALE ,CNS - Published
- 2007
49. Chemotherapy resistance of glioblastoma stem cells [2]
- Author
-
Eramo, A., Ricci-Vitiani, L., Zeuner, A., Pallini, Roberto, Lotti, F., Sette, Giovanni, Pilozzi, E., Larocca, Luigi Maria, Peschle, C., and De Maria Marchiano, Ruggero
- Subjects
Time Factors ,Cultured ,Brain Neoplasms ,Nude ,Animals ,Antineoplastic Agents ,Apoptosis ,Cisplatin ,Doxorubicin ,Etoposide ,Glioblastoma ,Humans ,Jurkat Cells ,Mice ,Mice, Nude ,Neoplastic Stem Cells ,Tumor Cells, Cultured ,Xenograft Model Antitumor Assays ,Drug Resistance, Multiple ,Drug Resistance, Neoplasm ,Cell Biology ,Drug Resistance ,Tumor Cells ,Settore MED/04 - PATOLOGIA GENERALE ,Neoplasm ,Multiple - Published
- 2006
50. influence of local environment on the differentiation of neuronal stem cells engrafted onto the injured spinal cord
- Author
-
Ricci Vitiani, L, Casalbore, P, Petrucci, Giovanna, Lauretti, Liverana, Montano, Nicola, Larocca, Luigi Maria, Falchetti, Ml, Lombardi, Dg, Gerevini, Vd, Cenciarelli, C, D'Alessandris, Quintino Giorgio, Fernandez, E, De Maria Marchiano, Ruggero, Maira, Giulio, Peschle, C, Parati, E, and Pallini, Roberto
- Subjects
Settore BIO/14 - FARMACOLOGIA ,Settore MED/27 - NEUROCHIRURGIA ,spinal cord ,neural stem cells - Published
- 2006
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