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2. Growth factor independence underpins a paroxysmal, aggressive Wnt5aHigh/EphA2Low phenotype in glioblastoma stem cells, conducive to experimental combinatorial therapy

Author

Trivieri, N, Visioli, A, Mencarelli, G, Cariglia, M, Marongiu, L, Pracella, R, Giani, F, Soriano, A, Barile, C, Cajola, L, Copetti, M, Palumbo, O, Legnani, F, Dimeco, F, Gorgoglione, L, Vescovi, A, Binda, E, Trivieri N., Visioli A., Mencarelli G., Cariglia M. G., Marongiu L., Pracella R., Giani F., Soriano A. A., Barile C., Cajola L., Copetti M., Palumbo O., Legnani F., DiMeco F., Gorgoglione L., Vescovi A. L., Binda E., Trivieri, N, Visioli, A, Mencarelli, G, Cariglia, M, Marongiu, L, Pracella, R, Giani, F, Soriano, A, Barile, C, Cajola, L, Copetti, M, Palumbo, O, Legnani, F, Dimeco, F, Gorgoglione, L, Vescovi, A, Binda, E, Trivieri N., Visioli A., Mencarelli G., Cariglia M. G., Marongiu L., Pracella R., Giani F., Soriano A. A., Barile C., Cajola L., Copetti M., Palumbo O., Legnani F., DiMeco F., Gorgoglione L., Vescovi A. L., and Binda E.

Abstract

Background: Glioblastoma multiforme (GBM) is an incurable tumor, with a median survival rate of only 14–15 months. Along with heterogeneity and unregulated growth, a central matter in dealing with GBMs is cell invasiveness. Thus, improving prognosis requires finding new agents to inhibit key multiple pathways, even simultaneously. A subset of GBM stem-like cells (GSCs) may account for tumorigenicity, representing, through their pathways, the proper cellular target in the therapeutics of glioblastomas. GSCs cells are routinely enriched and expanded due to continuous exposure to specific growth factors, which might alter some of their intrinsic characteristic and hide therapeutically relevant traits. Methods: By removing exogenous growth factors stimulation, here we isolated and characterized a subset of GSCs with a “mitogen-independent” phenotype (I-GSCs) from patient’s tumor specimens. Differential side-by-side comparative functional and molecular analyses were performed either in vitro or in vivo on these cells versus their classical growth factor (GF)-dependent counterpart (D-GSCs) as well as their tissue of origin. This was performed to pinpoint the inherent GSCs’ critical regulators, with particular emphasis on those involved in spreading and tumorigenic potential. Transcriptomic fingerprints were pointed out by ANOVA with Benjamini-Hochberg False Discovery Rate (FDR) and association of copy number alterations or somatic mutations was determined by comparing each subgroup with a two-tailed Fisher’s exact test. The combined effects of interacting in vitro and in vivo with two emerging GSCs’ key regulators, such as Wnt5a and EphA2, were then predicted under in vivo experimental settings that are conducive to clinical applications. In vivo comparisons were carried out in mouse-human xenografts GBM model by a hierarchical linear model for repeated measurements and Dunnett’s multiple comparison test with the distribution of survival compared by Kaplan–Meier method. R

Published
2022

3. Posterior fossa syndrome in a population of children and young adults with medulloblastoma: a retrospective, multicenter Italian study on incidence and pathophysiology in a histologically homogeneous and consecutive series of 136 patients

Author

de Laurentis, C, Cristaldi, P, Rebora, P, Valsecchi, M, Biassoni, V, Schiavello, E, Carrabba, G, Trezza, A, Dimeco, F, Ferroli, P, Cinalli, G, Locatelli, M, Cenzato, M, Talamonti, G, Fontanella, M, Spena, G, Stefini, R, Bernucci, C, Bellocchi, S, Locatelli, D, Massimino, M, Giussani, C, de Laurentis C., Cristaldi P. M. F., Rebora P., Valsecchi M. G., Biassoni V., Schiavello E., Carrabba G. G., Trezza A., DiMeco F., Ferroli P., Cinalli G., Locatelli M., Cenzato M., Talamonti G., Fontanella M. M., Spena G., Stefini R., Bernucci C., Bellocchi S., Locatelli D., Massimino M., Giussani C., de Laurentis, C, Cristaldi, P, Rebora, P, Valsecchi, M, Biassoni, V, Schiavello, E, Carrabba, G, Trezza, A, Dimeco, F, Ferroli, P, Cinalli, G, Locatelli, M, Cenzato, M, Talamonti, G, Fontanella, M, Spena, G, Stefini, R, Bernucci, C, Bellocchi, S, Locatelli, D, Massimino, M, Giussani, C, de Laurentis C., Cristaldi P. M. F., Rebora P., Valsecchi M. G., Biassoni V., Schiavello E., Carrabba G. G., Trezza A., DiMeco F., Ferroli P., Cinalli G., Locatelli M., Cenzato M., Talamonti G., Fontanella M. M., Spena G., Stefini R., Bernucci C., Bellocchi S., Locatelli D., Massimino M., and Giussani C.

Abstract

Introduction: Posterior fossa syndrome (PFS) is a set of debilitating complications that can occur after surgery for posterior fossa tumors. This study aimed to assess the preoperative radiological and surgical risk factors for the onset of PFS in a histologically homogeneous population of children with medulloblastoma and compare it to a similar population of young adults. Methods: Included patients underwent posterior fossa surgery for medulloblastoma at 11 Italian neurosurgical wards (2003–2019) and were referred to Fondazione IRCCS Istituto Nazionale dei Tumori in Milan (INT) for postoperative treatments. We collected patients’ pre- and post-operative clinical, surgical and radiological data from the INT charts. To compare the distribution of variables, we used the Mann–Whitney and Fisher tests for continuous and categorical variables, respectively. Results: 136 patients (109 children and 27 young adults) were included in the study. Among children, 29 (27%) developed PFS, and all of them had tumors at midline site with invasion of the fourth ventricle. Radiological evidence of involvement of the right superior (39% versus 12%; p = 0.011) or middle cerebellar peduncles (52% versus 18%; p = 0.002) seemed more common in children who developed PFS. Young adults showed an expected lower incidence of PFS (4 out of 27; 15%), that may be due to anatomical, physiological and oncological elements. Conclusions: This study confirmed some factors known to be associated with PFS onset and shed light on other debated issues. Our findings enhance an already hypothesized role of cerebellar language lateralization. The analysis of a population of young adults may shed more light on the often-neglected existence of PFS in non-pediatric patients.

Published
2022

4. Towards a common language in neurosurgical outcome evaluation: the NEON (NEurosurgical Outcome Network) proposal

Author

Ferroli, P, Schiavolin, S, Mariniello, A, Acerbi, F, Restelli, F, Schiariti, M, LA Corte, E, Falco, J, Levi, V, Dimeco, F, Assietti, R, Bongetta, D, Colombo, E, Bellocchi, S, Sangiorgi, S, Bistazzoni, S, Polosa, M, Orru, M, Spena, G, Bernucci, C, Sicignano, A, Fanti, A, Brembilla, C, Resmini, B, Costi, E, Cenzato, M, Talamonti, G, Bottini, G, Scarpa, P, Bollani, A, Querzola, M, Palmas, G, DE Gonda, F, Bosio, L, Egidi, M, Tardivo, V, Fioravanti, A, Subacchi, S, Fontanella, M, Biroli, A, Cereda, C, Panciani, P, Bergomi, R, Pertichetti, M, Tancioni, F, Bona, A, Tartara, F, Fornari, M, Pessina, F, Lasio, G, Cardia, A, Servadei, F, Riva, M, Casarotti, A, Giussani, C, Fiori, L, Mazzoleni, F, Vaiani, S, Carrabba, G, DI Cristofori, A, Sganzerla, E, Vimercati, A, Isella, V, Mauri, I, Incerti, M, Sicuri, G, Miramonti, V, Stefini, R, Spagnoli, D, Piparo, M, Grimod, G, Regazzoni, R, Vismara, D, Mazzeo, L, Monti, E, Franzin, A, Vivaldi, O, Maietti, A, Pini, E, Servello, D, Zekaj, E, DE Michele, S, Locatelli, M, Borsa, S, Grimoldi, N, Caroli, M, Tariciotti, L, Abete-Fornara, G, Vitale, M, Leonardi, M, Broggi, M, Ferroli, Paolo, Schiavolin, Silvia, Mariniello, Arianna, Acerbi, Francesco, Restelli, Francesco, Schiariti, Marco, LA Corte, Emanuele, Falco, Jacopo, Levi, Vincenzo, Dimeco, Francesco, Assietti, Roberto, Bongetta, Daniele, Colombo, Elena V, Bellocchi, Silvio, Sangiorgi, Simone, Bistazzoni, Simona, Polosa, Maria, Orru, Maria I, Spena, Giannantonio, Bernucci, Claudio, Sicignano, Angelo M, Fanti, Andrea, Brembilla, Carlo, Resmini, Bruno, Costi, Emanuele, Cenzato, Marco, Talamonti, Giuseppe, Bottini, Gabriella, Scarpa, Pina, Bollani, Alessandra, Querzola, Matteo, Palmas, Giulio, DE Gonda, Federico, Bosio, Lorenzo, Egidi, Marcello, Tardivo, Valentina, Fioravanti, Antonio, Subacchi, Sara, Fontanella, Marco, Biroli, Antonio, Cereda, Claudio, Panciani, Pier Paolo, Bergomi, Riccardo, Pertichetti, Marta, Tancioni, Flavio, Bona, Alberto, Tartara, Fulvio A, Fornari, Maurizio, Pessina, Federico, Lasio, Giovanni, Cardia, Andrea, Servadei, Franco, Riva, Marco, Casarotti, Alessandra, Giussani, Carlo, Fiori, Leonardo, Mazzoleni, Fabio, Vaiani, Simona, Carrabba, Giorgio, DI Cristofori, Andrea, Sganzerla, Erik P, Vimercati, Alberto, Isella, Valeria, Mauri, Ilaria, Incerti, Michele, Sicuri, Giovanni, Miramonti, Valentina, Stefini, Roberto, Spagnoli, Diego, Piparo, Maurizio, Grimod, Gianluca, Regazzoni, Rossana, Vismara, Daniela, Mazzeo, Lucio, Monti, Emanuele, Franzin, Alberto, Vivaldi, Oscar, Maietti, Alessandra, Pini, Elisa, Servello, Domenico, Zekaj, Edvin, DE Michele, Sara, Locatelli, Marco, Borsa, Stefano, Grimoldi, Nadia, Caroli, Manuela, Tariciotti, Leonardo, Abete-Fornara, Giorgia, Vitale, Mario, Leonardi, Matilde, Broggi, Morgan, Ferroli, P, Schiavolin, S, Mariniello, A, Acerbi, F, Restelli, F, Schiariti, M, LA Corte, E, Falco, J, Levi, V, Dimeco, F, Assietti, R, Bongetta, D, Colombo, E, Bellocchi, S, Sangiorgi, S, Bistazzoni, S, Polosa, M, Orru, M, Spena, G, Bernucci, C, Sicignano, A, Fanti, A, Brembilla, C, Resmini, B, Costi, E, Cenzato, M, Talamonti, G, Bottini, G, Scarpa, P, Bollani, A, Querzola, M, Palmas, G, DE Gonda, F, Bosio, L, Egidi, M, Tardivo, V, Fioravanti, A, Subacchi, S, Fontanella, M, Biroli, A, Cereda, C, Panciani, P, Bergomi, R, Pertichetti, M, Tancioni, F, Bona, A, Tartara, F, Fornari, M, Pessina, F, Lasio, G, Cardia, A, Servadei, F, Riva, M, Casarotti, A, Giussani, C, Fiori, L, Mazzoleni, F, Vaiani, S, Carrabba, G, DI Cristofori, A, Sganzerla, E, Vimercati, A, Isella, V, Mauri, I, Incerti, M, Sicuri, G, Miramonti, V, Stefini, R, Spagnoli, D, Piparo, M, Grimod, G, Regazzoni, R, Vismara, D, Mazzeo, L, Monti, E, Franzin, A, Vivaldi, O, Maietti, A, Pini, E, Servello, D, Zekaj, E, DE Michele, S, Locatelli, M, Borsa, S, Grimoldi, N, Caroli, M, Tariciotti, L, Abete-Fornara, G, Vitale, M, Leonardi, M, Broggi, M, Ferroli, Paolo, Schiavolin, Silvia, Mariniello, Arianna, Acerbi, Francesco, Restelli, Francesco, Schiariti, Marco, LA Corte, Emanuele, Falco, Jacopo, Levi, Vincenzo, Dimeco, Francesco, Assietti, Roberto, Bongetta, Daniele, Colombo, Elena V, Bellocchi, Silvio, Sangiorgi, Simone, Bistazzoni, Simona, Polosa, Maria, Orru, Maria I, Spena, Giannantonio, Bernucci, Claudio, Sicignano, Angelo M, Fanti, Andrea, Brembilla, Carlo, Resmini, Bruno, Costi, Emanuele, Cenzato, Marco, Talamonti, Giuseppe, Bottini, Gabriella, Scarpa, Pina, Bollani, Alessandra, Querzola, Matteo, Palmas, Giulio, DE Gonda, Federico, Bosio, Lorenzo, Egidi, Marcello, Tardivo, Valentina, Fioravanti, Antonio, Subacchi, Sara, Fontanella, Marco, Biroli, Antonio, Cereda, Claudio, Panciani, Pier Paolo, Bergomi, Riccardo, Pertichetti, Marta, Tancioni, Flavio, Bona, Alberto, Tartara, Fulvio A, Fornari, Maurizio, Pessina, Federico, Lasio, Giovanni, Cardia, Andrea, Servadei, Franco, Riva, Marco, Casarotti, Alessandra, Giussani, Carlo, Fiori, Leonardo, Mazzoleni, Fabio, Vaiani, Simona, Carrabba, Giorgio, DI Cristofori, Andrea, Sganzerla, Erik P, Vimercati, Alberto, Isella, Valeria, Mauri, Ilaria, Incerti, Michele, Sicuri, Giovanni, Miramonti, Valentina, Stefini, Roberto, Spagnoli, Diego, Piparo, Maurizio, Grimod, Gianluca, Regazzoni, Rossana, Vismara, Daniela, Mazzeo, Lucio, Monti, Emanuele, Franzin, Alberto, Vivaldi, Oscar, Maietti, Alessandra, Pini, Elisa, Servello, Domenico, Zekaj, Edvin, DE Michele, Sara, Locatelli, Marco, Borsa, Stefano, Grimoldi, Nadia, Caroli, Manuela, Tariciotti, Leonardo, Abete-Fornara, Giorgia, Vitale, Mario, Leonardi, Matilde, and Broggi, Morgan

Abstract

Background: The aim of this study was to achieve a consensus on the minimum set of outcome measures and predictors to be used in the neurosurgical practice and on the timing of outcome assessment. Methods: A consensus building approach was employed. All neurosurgical departments in Lombardy (Italy) were invited to participate by the Carlo Besta Neurologic Institute IRCCS Foundation. Three workshops were organized during which a multidisciplinary group called Neurosurgical Outcome Network (NEON) was created and the methodology to select outcome measures, predictors, and timing of outcome assessment was established. Eight working groups were created for the different neurosurgical diseases (neuro-oncological, skull base, vascular, traumatic, spinal, peripheral nervous system, malformation, functional) and 8 workshops were organized to identify the outcome measures and predictors specific for each of the neurosurgical diseases based on the experts' clinical practice and the existing literature. Results: A total of 20 neurosurgical departments participated in this study. Specific outcome measures, predictors and the timing of outcome assessment were identified for each of the 8 neurosurgical diseases. Moreover, a list of variables common to all pathologies were identified by the NEON group as further data to be collected. Conclusions: A consensus on the minimum set of outcome measures and predictors and the timing of outcome assessments for 8 neurosurgical diseases was achieved by a group of neurosurgeons of the Lombardy region, called NEON. These sets could be used in future studies for a more homogeneous data collection and as a starting point to reach further agreement also at national and international level.

Published
2023

6. Reactivation of COVID-19 in a neurosurgical patient with early neuropsychiatric presentation. Does seroconversion mean immunity?

Author

Bonomo, G, Caldiroli, D, Bonomo, R, Pugliese, R, Dimeco, F, Zoia, C, Bonomo G., Caldiroli D., Bonomo R., Pugliese R., DiMeco F., Zoia C., Bonomo, G, Caldiroli, D, Bonomo, R, Pugliese, R, Dimeco, F, Zoia, C, Bonomo G., Caldiroli D., Bonomo R., Pugliese R., DiMeco F., and Zoia C.

Abstract

Background: In the aftermath of COVID-19 outbreak, there is a strong need to find strategies to monitor SARSCoV-2 transmission. While the application of screening techniques plays a major role to this end, there is evidence challenging the real significance of seroconversion. We reported a case of COVID-19 reactivation associated with a neurosurgical operation with early neuropsychiatric involvement presumably promoted by olfactory and gustatory impairment in the first infection. Case Descriptio: A 57-year-old man was referred for a 2-month history of progressive development of imbalance, dizziness, and vomiting. Magnetic resonance imaging showed two bilateral hemispheric cerebellar lesions. In line with our triage protocol, the patient underwent a nasopharyngeal swab for RNA of SARS-CoV-2 detection, which resulted positive. Of note, the patient had reported in the previous month hyposmia and hypogeusia. After a period of 14 days, three new swabs were performed with negative results, leading the way to surgery. In the early post-operative period, the patient manifested acute onset of psychotic symptoms with hyperactive delirium, followed by fever and acute respiratory failure. A chest computed tomography revealed a specific pattern of ground-glass opacities in the lower lobes bilaterally, suggesting a viral pneumonia. Serological tests demonstrated the seroconversion and a new nasopharyngeal swab confirmed SARS-CoV-2 infection. Conclusion: Our report highlights the importance of comprehensive screening assessments in sensitive cases highly susceptible to COVID-19 recurrence.

Published
2021

8. May we deliver neuro-oncology in difficult times (e.g. COVID-19)?

Author

Perin, A, Servadei, F, Dimeco, F, Locatelli, M, Benazzo, M, Spena, G, Bernucci, C, Sganzerla, E, Egidi, M, Spagnoli, D, Giussani, C, Incerti, M, Lorusso, G, Stefini, R, Assietti, R, Bellocchi, S, Fornari, M, Skrap, M, Tartara, F, Vitale, M, Ferroli, P, Franzini, A, Silvani, A, Fontanella, M, Cenzato, M, Perin A., Servadei F., DiMeco F., Locatelli M., Benazzo M., Spena G., Bernucci C., Sganzerla E., Egidi M., Spagnoli D., Giussani C., Incerti M., Lorusso G., Stefini R., Assietti R., Bellocchi S., Fornari M., Skrap M., Tartara F., Vitale M., Ferroli P., Franzini A., Silvani A., Fontanella M., Cenzato M., Perin, A, Servadei, F, Dimeco, F, Locatelli, M, Benazzo, M, Spena, G, Bernucci, C, Sganzerla, E, Egidi, M, Spagnoli, D, Giussani, C, Incerti, M, Lorusso, G, Stefini, R, Assietti, R, Bellocchi, S, Fornari, M, Skrap, M, Tartara, F, Vitale, M, Ferroli, P, Franzini, A, Silvani, A, Fontanella, M, Cenzato, M, Perin A., Servadei F., DiMeco F., Locatelli M., Benazzo M., Spena G., Bernucci C., Sganzerla E., Egidi M., Spagnoli D., Giussani C., Incerti M., Lorusso G., Stefini R., Assietti R., Bellocchi S., Fornari M., Skrap M., Tartara F., Vitale M., Ferroli P., Franzini A., Silvani A., Fontanella M., and Cenzato M.

Published
2020

9. Molecular and translational advances in meningiomas

Author

Suppiah S., Nassiri F., Bi W. L., Dunn I. F., Hanemann C. O., Horbinski C. M., Hashizume R., James C. D., Mawrin C., Noushmehr H., Perry A., Sahm F., Sloan A., Von Deimling A., Wen P. Y., Aldape K., Zadeh G., Au K., Barnhartz-Sloan J., Brastianos P. K., Butowski N., Carlotti C., Cusimano M. D., Dimeco F., Drummond K., Galanis E., Giannini C., Goldbrunner R., Griffith B., Herold-Mende C., Huang R. Y., James D., Jenkinson M. D., Jungk C., Kaufman T. J., Krischek B., Lachance D., Lafougere C., Lee I., Liu J. C., Mamatjan Y., Mansouri A., McDermott M., Munoz D., Ng H. -K., Pirouzmand F., Poisson L. M., Pollo B., Raleigh D., Saladino A., Santarius T., Schichor C., Schultz D., Schmidt N. O., Selman W., Spears J., Snyder J., Tabatabai G., Tatagiba M., Tirapelli D., Tonn J. C., Tsang D., Vogelbaum M. A., Deimling A. V., Walbert T., Westphal M., Workewych A. M., Suppiah S., Nassiri F., Bi W.L., Dunn I.F., Hanemann C.O., Horbinski C.M., Hashizume R., James C.D., Mawrin C., Noushmehr H., Perry A., Sahm F., Sloan A., Von Deimling A., Wen P.Y., Aldape K., Zadeh G., Au K., Barnhartz-Sloan J., Brastianos P.K., Butowski N., Carlotti C., Cusimano M.D., Dimeco F., Drummond K., Galanis E., Giannini C., Goldbrunner R., Griffith B., Herold-Mende C., Huang R.Y., James D., Jenkinson M.D., Jungk C., Kaufman T.J., Krischek B., Lachance D., Lafougere C., Lee I., Liu J.C., Mamatjan Y., Mansouri A., McDermott M., Munoz D., Ng H.-K., Pirouzmand F., Poisson L.M., Pollo B., Raleigh D., Saladino A., Santarius T., Schichor C., Schultz D., Schmidt N.O., Selman W., Spears J., Snyder J., Tabatabai G., Tatagiba M., Tirapelli D., Tonn J.C., Tsang D., Vogelbaum M.A., Deimling A.V., Walbert T., Westphal M., and Workewych A.M.

Subjects
Cancer Research, Supplement Articles, Genomics, Intracranial Neoplasm, sporadic meningioma, Bioinformatics, World health, Translational Research, Biomedical, Meningioma, 03 medical and health sciences, biomolecular, 0302 clinical medicine, Meningeal Neoplasms, otorhinolaryngologic diseases, medicine, Recurrent disease, Humans, Meningeal Neoplasm, Molecular Targeted Therapy, xenograft, Stage (cooking), neoplasms, MENINGIOMA, business.industry, cell line, Prognosis, medicine.disease, Combined Modality Therapy, nervous system diseases, 3. Good health, Clinical trial, Oncology, 030220 oncology & carcinogenesis, Neurology (clinical), genetic, business, epigenetic, 030217 neurology & neurosurgery
Abstract

Meningiomas are the most common primary intracranial neoplasm. The current World Health Organization (WHO) classification categorizes meningiomas based on histopathological features, but emerging molecular data demonstrate the importance of genomic and epigenomic factors in the clinical behavior of these tumors. Treatment options for symptomatic meningiomas are limited to surgical resection where possible and adjuvant radiation therapy for tumors with concerning histopathological features or recurrent disease. At present, alternative adjuvant treatment options are not available in part due to limited historical biological analysis and clinical trial investigation on meningiomas. With advances in molecular and genomic techniques in the last decade, we have witnessed a surge of interest in understanding the genomic and epigenomic landscape of meningiomas. The field is now at the stage to adopt this molecular knowledge to refine meningioma classification and introduce molecular algorithms that can guide prediction and therapeutics for this tumor type. Animal models that recapitulate meningiomas faithfully are in critical need to test new therapeutics to facilitate rapid-cycle translation to clinical trials. Here we review the most up-to-date knowledge of molecular alterations that provide insight into meningioma behavior and are ready for application to clinical trial investigation, and highlight the landscape of available preclinical models in meningiomas.

Published
2019
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10. Life after surgical resection of a meningioma: a prospective cross-sectional study evaluating health-related quality of life

Author

Nassiri F., Price B., Shehab A., Au K., Cusimano M. D., Jenkinson M. D., Jungk C., Mansouri A., Santarius T., Suppiah S., Teng K. X., Toor G. S., Zadeh G., Walbert T., Drummond K. J., Aldape K., Barnhartz-Sloan J., Bi W. L., Brastianos P. K., Butowski N., Carlotti C., Dimeco F., Dunn I. F., Galanis E., Giannini C., Goldbrunner R., Griffith B., Hashizume R., Hanemann C. O., Herold-Mende C., Horbinski C., Huang R. Y., James D., Kaufman T. J., Krischek B., Lachance D., Lafougere C., Lee I., Liu J. C., Mamatjan Y., Mawrin C., McDermott M., Munoz D., Noushmehr H., Ng H. -K., Perry A., Pirouzmand F., Poisson L. M., Pollo B., Raleigh D., Sahm F., Saladino A., Schichor C., Schultz D., Schmidt N. O., Selman W., Sloan A., Spears J., Snyder J., Tabatabai G., Tatagiba M., Tirapelli D., Tonn J. C., Tsang D., Vogelbaum M. A., Deimling A. V., Wen P. Y., Westphal M., Workewych A. M., Nassiri F., Price B., Shehab A., Au K., Cusimano M.D., Jenkinson M.D., Jungk C., Mansouri A., Santarius T., Suppiah S., Teng K.X., Toor G.S., Zadeh G., Walbert T., Drummond K.J., Aldape K., Barnhartz-Sloan J., Bi W.L., Brastianos P.K., Butowski N., Carlotti C., Dimeco F., Dunn I.F., Galanis E., Giannini C., Goldbrunner R., Griffith B., Hashizume R., Hanemann C.O., Herold-Mende C., Horbinski C., Huang R.Y., James D., Kaufman T.J., Krischek B., Lachance D., Lafougere C., Lee I., Liu J.C., Mamatjan Y., Mawrin C., McDermott M., Munoz D., Noushmehr H., Ng H.-K., Perry A., Pirouzmand F., Poisson L.M., Pollo B., Raleigh D., Sahm F., Saladino A., Schichor C., Schultz D., Schmidt N.O., Selman W., Sloan A., Spears J., Snyder J., Tabatabai G., Tatagiba M., Tirapelli D., Tonn J.C., Tsang D., Vogelbaum M.A., Deimling A.V., Wen P.Y., Westphal M., and Workewych A.M.

Subjects
Male, cognition, Cancer Research, medicine.medical_specialty, Cross-sectional study, insomnia, Population, Neurosurgery, Supplement Articles, meningioma, surgery, Meningioma, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Surveys and Questionnaires, Internal medicine, Meningeal Neoplasms, otorhinolaryngologic diseases, medicine, Humans, Longitudinal Studies, Prospective Studies, Prospective cohort study, education, education.field_of_study, business.industry, COGNIÇÃO, Cognition, Middle Aged, Prognosis, medicine.disease, humanities, 3. Good health, health-related quality of life, Cross-Sectional Studies, Oncology, 030220 oncology & carcinogenesis, Quality of Life, Female, fatigue, Neurology (clinical), business, 030217 neurology & neurosurgery, Follow-Up Studies, Cohort study
Abstract

Background Few studies have evaluated the health-related quality of life (HRQoL) of patients with meningiomas. Here, we report the largest prospective, longitudinal cross-sectional cohort study of HRQoL in meningiomas to date, in order to identify possible actionable determinants of global HRQoL. Methods Adults who had undergone resection of a grade I intracranial meningioma and were in routine follow-up at a single large tertiary center underwent HRQoL assessment using the QLQ-C30 questionnaire administered opportunistically at follow-up visits. Averaged transformed QLQ-C30 scores at 12-month intervals were compared with scores from a normative reference population, with reference to known minimal clinically meaningful difference (CMD) in scores. To evaluate for possible determinants of changes in global HRQoL, global HRQoL scores were correlated (Spearman's Rho) with subdomain and symptom scores and with interval time from surgical resection. Results A total of 291 postoperative patients with histologically confirmed and surgically treated grade I meningiomas consented to participation and a total of 455 questionnaires were included for analysis. Patients with meningiomas reported reduced global HRQoL at nearly every 12-month interval with clinically and statistically significant impairments at 12, 48, 108, and 120 months postoperative compared with the normative population (P < 0.05). Meningioma patients at the 12-month interval also reported a reduction of each subdomain of HRQoL assessment (P < 0.05); however, a CMD was only seen in cognitive functioning. Physical, emotional, cognitive, and social subdomains, as well as fatigue and sleep/insomnia, were significantly associated with global HRQoL at the first 12-month interval. Overall, there was no significant correlation between time from surgery and global HRQoL or the subdomain functional or symptom sections of the QLQ-C30. Conclusions Meningioma patients report considerable limitations in HRQoL for more than 120 months after surgery, particularly in cognitive, emotional, and social function, as well as suffering significant fatigue and sleep impairment compared with a normative reference population. The majority of these reported functional impairments and symptoms are strongly associated with global HRQoL and thus can be considered determinants of global HRQoL that if treated, have the potential to improve HRQoL for our meningioma patients. This hypothesis requires future study of targeted interventions to determine their efficacy.

Published
2019
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13. May we deliver neuro-oncology in difficult times (e.g. COVID-19)?

Author

Perin, A., Servadei, F., Dimeco, F., Locatelli, M., Benazzo, M., Spena, G., Bernucci, C., Sganzerla, E., Egidi, M., Spagnoli, D., Giussani, C., Incerti, M., Lorusso, G., Stefini, R., Assietti, R., Bellocchi, S., Fornari, M., Skrap, M., Tartara, F., Vitale, M., Ferroli, P., Franzini, A., Silvani, A., Fontanella, M., Cenzato, M., Perin, A, Servadei, F, Dimeco, F, Locatelli, M, Benazzo, M, Spena, G, Bernucci, C, Sganzerla, E, Egidi, M, Spagnoli, D, Giussani, C, Incerti, M, Lorusso, G, Stefini, R, Assietti, R, Bellocchi, S, Fornari, M, Skrap, M, Tartara, F, Vitale, M, Ferroli, P, Franzini, A, Silvani, A, Fontanella, M, and Cenzato, M

Subjects
medicine.medical_specialty, 2019-20 coronavirus outbreak, Cancer Research, Coronavirus disease 2019 (COVID-19), Neuro oncology, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Pneumonia, Viral, Viral transmission, Clinical Neurology, Medical Oncology, Brain Neoplasm, Betacoronavirus, medicine, Disease Transmission, Infectious, Humans, Medical physics, Pandemics, Betacoronaviru, Pandemic, business.industry, Brain Neoplasms, Coronavirus Infection, SARS-CoV-2, COVID-19, Oncology, Disease Transmission, Infectiou, Neurology, Neurology (clinical), business, Coronavirus Infections, Disease transmission, Delivery of Health Care, Human
Published
2020

16. Radiation and adjuvant drug-loaded liposomes target glioblastoma stem cells and trigger in-situ immune response

Author

Pizzocri, M, Re, F, Stanzani, E, Formicola, B, Tamborini, M, Lauranzano, E, Ungaro, F, Rodighiero, S, Francolini, M, Gregori, M, Perin, A, Dimeco, F, Masserini, M, Matteoli, M, Passoni, L, Pizzocri, M, Re, F, Stanzani, E, Formicola, B, Tamborini, M, Lauranzano, E, Ungaro, F, Rodighiero, S, Francolini, M, Gregori, M, Perin, A, Dimeco, F, Masserini, M, Matteoli, M, and Passoni, L

Abstract

Background. The radio- and chemo-resistance of glioblastoma stem-like cells (GSCs), together with their innate tumor-initiating aptitude, make this cell population a crucial target for effective therapies. However, targeting GSCs is hardly difficult and complex, due to the presence of the blood-brain barrier (BBB) and the infiltrative nature of GSCs arousing their dispersion within the brain parenchyma. Methods. Liposomes (LIPs), surface-decorated with an Apolipoprotein E-modified peptide (mApoE) to enable BBB crossing, were loaded with doxorubicin (DOXO), as paradigm of cytotoxic drug triggering immunogenic cell death (ICD). Patient-derived xenografts (PDXs) obtained by GSC intracranial injection were treated with mApoE-DOXOLIPs alone or concomitantly with radiation. Results. Our results indicated that mApoE, through the engagement of the low-density lipoprotein receptor (LDLR), promotes mApoE-DOXO-LIPs transcytosis across the BBB and confers target specificity towards GSCs. Irradiation enhanced LDLR expression on both BBB and GSCs, thus further promoting LIP diffusion and specificity. When administered in combination with radiations, mApoE-DOXO-LIPs caused a significant reduction of in vivo tumor growth due to GSC apoptosis. GSC apoptosis prompted microglia/macrophage phagocytic activity, together with the activation of the antigen-presenting machinery crucially required for anti-tumor adaptive immune response. Conclusions. Our results advocate for radiotherapy and adjuvant administration of drug-loaded, mApoE-targeted nanovectors as an effective strategy to deliver cytotoxic molecules to GSCs at the surgical tumor margins, the forefront of glioblastoma (GBM) recurrence, circumventing BBB hurdles. DOXO encapsulation proved in situ immune response activation within GBM microenvironment.

Published
2021

18. Oncogenic signaling pathways in the Cancer Genome Atlas

Author

Sanchez-Vega, F., Mina, M., Armenia, J., Chatila, W. K., Luna, A., La, K. C., Dimitriadoy, S., Liu, D. L., Kantheti, H. S., Saghafinia, S., Chakravarty, D., Daian, F., Gao, Q., Bailey, M. H., Liang, W. -W., Foltz, S. M., Shmulevich, I., Ding, L., Heins, Z., Ochoa, A., Gross, B., Gao, J., Zhang, H., Kundra, R., Kandoth, C., Bahceci, I., Dervishi, L., Doğrusöz, Uğur, Zhou, W., Shen, H., Laird, P. W., Way, G. P., Greene, C. S., Liang, H., Xiao, Y., Wang, C., Iavarone, A., Berger, A. H., Bivona, T. G., Lazar, A. J., Hammer, G. D., Giordano, T., Kwong, L. N., McArthur, G., Huang, C., Tward, A. D., Frederick, M. J., McCormick, F., Meyerson, M., Caesar-Johnson, S. J., Demchok, J. A., Felau, I., Kasapi, M., Ferguson, M. L., Hutter, C. M., Sofia, H. J., Tarnuzzer, R., Wang, Z., Yang, L., Zenklusen, J. C., Zhang, J. J., Chudamani, S., Liu, J., Lolla, L., Naresh, R., Pihl, T., Sun, Q., Wan, Y., Wu, Y., Cho, J., DeFreitas, T., Frazer, S., Gehlenborg, N., Getz, G., Heiman, D. I., Kim, J., Lawrence, M. S., Lin, P., Meier, S., Noble, M. S., Saksena, G., Voet, D., Bernard, B., Chambwe, N., Dhankani, V., Knijnenburg, T., Kramer, R., Leinonen, K., Liu, Y., Miller, M., Reynolds, S., Thorsson, V., Zhang, W., Akbani, R., Broom, B. M., Hegde, A. M., Ju, Z., Kanchi, R. S., Korkut, A., Li, J., Ling, S., Liu W., Lu, Y., Mills, G. B., Ng, K. -S., Rao, A., Ryan, M., Wang, J., Weinstein, J. N., Zhang, J., Abeshouse, A., de, Bruijn, I., Gross, B. E., Heins, Z. J., La, K., Ladanyi, M., Nissan, M. G., Phillips, S. M., Reznik, E., Sander, C., Schultz, N., Sheridan, R., Sumer, S. O., Sun, Y., Taylor, B. S., Anur, P., Peto, M., Spellman, P., Benz, C., Stuart, J. M., Wong, C. K., Yau, C., Hayes, D. N., Parker, J. S., Wilkerson, M. D., Ally, A., Balasundaram, M., Bowlby, R., Brooks, D., Carlsen, R., Chuah, E., Dhalla, N., Holt, R., Jones, S. J. M., Kasaian, K., Lee, D., Ma, Y., Marra, M. A., Mayo, M., Moore, R. A., Mungall, A. J., Mungall, K., Robertson, A. G., Sadeghi, S., Schein, J. E., Sipahimalani, P., Tam, A., Thiessen, N., Tse, K., Wong, T., Berger, A. C., Beroukhim, R., Cherniack, A. D., Cibulskis, C., Gabriel, S. B., Gao, G. F., Ha, G., Schumacher, S. E., Shih, J., Kucherlapati, M. H., Kucherlapati, R. S., Baylin, S., Cope, L., Danilova, L., Bootwalla, M. S., Lai, P. H., Maglinte, D. T., Van, Den, Berg, D. J., Weisenberger, D. J., Auman, J. T., Balu, S., Bodenheimer, T., Fan, C., Hoadley, K. A., Hoyle, A. P., Jefferys, S. R., Jones, C. D., Meng, S., Mieczkowski, P. A., Mose, L. E., Perou, A. H., Perou, C. M., Roach, J., Shi, Y., Simons, J. V., Skelly, T., Soloway, M. G., Tan, D., Veluvolu, U., Fan, H., Hinoue, T., Bellair, M., Chang, K., Covington, K., Creighton, C. J., Dinh, H., Doddapaneni, H., Donehower, L. A., Drummond, J., Gibbs, R. 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Subjects
0301 basic medicine, cancer genome atlas, cancer genomics, combination therapy, pan-cancer, PanCanAtlas, precision oncology, signaling pathways, TCGA, therapeutics, whole exome sequencing, Signaling pathways, Somatic cell, Wnt Protein, Cancer Genome Atlas Research Network, Biochemistry, Medical and Health Sciences, Phosphatidylinositol 3-Kinases, Transforming Growth Factor beta, Neoplasms, Databases, Genetic, LS2_1, Cancer genomics, LS4_6, 610 Medicine & health, 11 Medical and Health Sciences, Cancer, biology, Wnt signaling pathway, cancer genomic, Precision oncology, Biological Sciences, Cell cycle, DNA methylation, Signal transduction, CICLO CELULAR, Life Sciences & Biomedicine, Genes, Neoplasm, Humans, Neoplasms/genetics, Neoplasms/pathology, Phosphatidylinositol 3-Kinases/genetics, Phosphatidylinositol 3-Kinases/metabolism, Signal Transduction/genetics, Transforming Growth Factor beta/genetics, Transforming Growth Factor beta/metabolism, Tumor Suppressor Protein p53/genetics, Tumor Suppressor Protein p53/metabolism, Wnt Proteins/genetics, Wnt Proteins/metabolism, Biotechnology, Human, Signal Transduction, signaling pathway, EXPRESSION, Biochemistry & Molecular Biology, GENES, Pan-cancer, Therapeutics, General Biochemistry, Genetics and Molecular Biology, NO, Databases, 03 medical and health sciences, Genetic, Genetics, Combination therapy, Protein kinase B, Gene, SIGNATURES, Cancer genome atlas, Science & Technology, LANDSCAPE, MUTATIONS, Biochemistry, Genetics and Molecular Biology(all), Human Genome, Whole exome sequencing, Cell Biology, Transforming growth factor beta, cancer genome atla, 06 Biological Sciences, COMPREHENSIVE MOLECULAR CHARACTERIZATION, Wnt Proteins, therapeutic, Good Health and Well Being, 030104 developmental biology, Genes, PanCanAtla, biology.protein, Cancer research, Neoplasm, Phosphatidylinositol 3-Kinase, Tumor Suppressor Protein p53, Digestive Diseases, Genetics and Molecular Biology(all), Developmental Biology
Abstract

Genetic alterations in signaling pathways that control cell-cycle progression, apoptosis, and cell growth are common hallmarks of cancer, but the extent, mechanisms, and co-occurrence of alterations in these pathways differ between individual tumors and tumor types. Using mutations, copy-number changes, mRNA expression, gene fusions and DNA methylation in 9,125 tumors profiled by The Cancer Genome Atlas (TCGA), we analyzed the mechanisms and patterns of somatic alterations in ten canonical pathways: cell cycle, Hippo, Myc, Notch, Nrf2, PI-3-Kinase/Akt, RTK-RAS, TGFβ signaling, p53 and β-catenin/Wnt. We charted the detailed landscape of pathway alterations in 33 cancer types, stratified into 64 subtypes, and identified patterns of co-occurrence and mutual exclusivity. Eighty-nine percent of tumors had at least one driver alteration in these pathways, and 57% percent of tumors had at least one alteration potentially targetable by currently available drugs. Thirty percent of tumors had multiple targetable alterations, indicating opportunities for combination therapy. An integrated analysis of genetic alterations in 10 signaling pathways in >9,000 tumors profiled by TCGA highlights significant representation of individual and co-occurring actionable alterations in these pathways, suggesting opportunities for targeted and combination therapies. Michael Seiler, Peter G. Smith, Ping Zhu, Silvia Buonamici, and Lihua Yu are employees of H3 Biomedicine, Inc. Parts of this work are the subject of a patent application: WO2017040526 titled “Splice variants associated with neomorphic sf3b1 mutants.” Shouyoung Peng, Anant A. Agrawal, James Palacino, and Teng Teng are employees of H3 Biomedicine, Inc. Andrew D. Cherniack, Ashton C. Berger, and Galen F. Gao receive research support from Bayer Pharmaceuticals. Gordon B. Mills serves on the External Scientific Review Board of Astrazeneca. Anil Sood is on the Scientific Advisory Board for Kiyatec and is a shareholder in BioPath. Jonathan S. Serody receives funding from Merck, Inc. Kyle R. Covington is an employee of Castle Biosciences, Inc. Preethi H. Gunaratne is founder, CSO, and shareholder of NextmiRNA Therapeutics. Christina Yau is a part-time employee/consultant at NantOmics. Franz X. Schaub is an employee and shareholder of SEngine Precision Medicine, Inc. Carla Grandori is an employee, founder, and shareholder of SEngine Precision Medicine, Inc. Robert N. Eisenman is a member of the Scientific Advisory Boards and shareholder of Shenogen Pharma and Kronos Bio. Daniel J. Weisenberger is a consultant for Zymo Research Corporation. Joshua M. Stuart is the founder of Five3 Genomics and shareholder of NantOmics. Marc T. Goodman receives research support from Merck, Inc. Andrew J. Gentles is a consultant for Cibermed. Charles M. Perou is an equity stock holder, consultant, and Board of Directors member of BioClassifier and GeneCentric Diagnostics and is also listed as an inventor on patent applications on the Breast PAM50 and Lung Cancer Subtyping assays. Matthew Meyerson receives research support from Bayer Pharmaceuticals; is an equity holder in, consultant for, and Scientific Advisory Board chair for OrigiMed; and is an inventor of a patent for EGFR mutation diagnosis in lung cancer, licensed to LabCorp. Eduard Porta-Pardo is an inventor of a patent for domainXplorer. Han Liang is a shareholder and scientific advisor of Precision Scientific and Eagle Nebula. Da Yang is an inventor on a pending patent application describing the use of antisense oligonucleotides against specific lncRNA sequence as diagnostic and therapeutic tools. Yonghong Xiao was an employee and shareholder of TESARO, Inc. Bin Feng is an employee and shareholder of TESARO, Inc. Carter Van Waes received research funding for the study of IAP inhibitor ASTX660 through a Cooperative Agreement between NIDCD, NIH, and Astex Pharmaceuticals. Raunaq Malhotra is an employee and shareholder of Seven Bridges, Inc. Peter W. Laird serves on the Scientific Advisory Board for AnchorDx. Joel Tepper is a consultant at EMD Serono. Kenneth Wang serves on the Advisory Board for Boston Scientific, Microtech, and Olympus. Andrea Califano is a founder, shareholder, and advisory board member of DarwinHealth, Inc. and a shareholder and advisory board member of Tempus, Inc. Toni K. Choueiri serves as needed on advisory boards for Bristol-Myers Squibb, Merck, and Roche. Lawrence Kwong receives research support from Array BioPharma. Sharon E. Plon is a member of the Scientific Advisory Board for Baylor Genetics Laboratory. Beth Y. Karlan serves on the Advisory Board of Invitae.

Published
2018
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20. DNA methylation profiling to predict recurrence risk in meningioma: development and validation of a nomogram to optimize clinical management

Author

Nassiri F., Mamatjan Y., Suppiah S., Badhiwala J. H., Mansouri S., Karimi S., Saarela O., Poisson L., Gepfner-Tuma I., Schittenhelm J., Ng H. -K., Noushmehr H., Harter P., Baumgarten P., Weller M., Preusser M., Herold-Mende C., Tatagiba M., Tabatabai G., Sahm F., Von Deimling A., Aldape K., Au K., Barnhartz-Sloan J., Bi W. L., Brastianos P. K., Butowski N., Carlotti C., Cusimano M. D., Dimeco F., Drummond K., Dunn I. F., Galanis E., Giannini C., Goldbrunner R., Griffith B., Hashizume R., Hanemann C. O., Horbinski C., Huang R. Y., James D., Jenkinson M. D., Jungk C., Kaufman T. J., Krischek B., Lachance D., Lafougere C., Lee I., Liu J. C., Malta T. M., Mawrin C., McDermott M., Munoz D., Perry A., Pirouzmand F., Poisson L. M., Pollo B., Raleigh D., Saladino A., Santarius T., Schichor C., Schultz D., Schmidt N. O., Selman W., Sloan A., Spears J., Snyder J., Tirapelli D., Tonn J. C., Tsang D., Vogelbaum M. A., Wen P. Y., Walbert T., Westphal M., Workewych A. M., Zadeh G., Aldape K. D., Nassiri F., Mamatjan Y., Suppiah S., Badhiwala J.H., Mansouri S., Karimi S., Saarela O., Poisson L., Gepfner-Tuma I., Schittenhelm J., Ng H.-K., Noushmehr H., Harter P., Baumgarten P., Weller M., Preusser M., Herold-Mende C., Tatagiba M., Tabatabai G., Sahm F., Von Deimling A., Aldape K., Au K., Barnhartz-Sloan J., Bi W.L., Brastianos P.K., Butowski N., Carlotti C., Cusimano M.D., Dimeco F., Drummond K., Dunn I.F., Galanis E., Giannini C., Goldbrunner R., Griffith B., Hashizume R., Hanemann C.O., Horbinski C., Huang R.Y., James D., Jenkinson M.D., Jungk C., Kaufman T.J., Krischek B., Lachance D., Lafougere C., Lee I., Liu J.C., Malta T.M., Mawrin C., McDermott M., Munoz D., Perry A., Pirouzmand F., Poisson L.M., Pollo B., Raleigh D., Saladino A., Santarius T., Schichor C., Schultz D., Schmidt N.O., Selman W., Sloan A., Spears J., Snyder J., Tirapelli D., Tonn J.C., Tsang D., Vogelbaum M.A., Wen P.Y., Walbert T., Westphal M., Workewych A.M., Zadeh G., and Aldape K.D.

Subjects
Oncology, Cancer Research, medicine.medical_specialty, recurrence, predictor, ESTUDOS DE VALIDAÇÃO, Meningioma, nomogram, Internal medicine, medicine, Biomarkers, Tumor, Meningeal Neoplasms, Humans, Survival rate, Retrospective Studies, Oncotype DX Breast Cancer Assay, business.industry, Hazard ratio, Cancer, Disease Management, Retrospective cohort study, Nomogram, DNA Methylation, medicine.disease, Prognosis, Gene Expression Regulation, Neoplastic, Survival Rate, Clinical research, Basic and Translational Investigations, Neurology (clinical), methylation, Neoplasm Recurrence, Local, business, Follow-Up Studies
Abstract

Background Variability in standard-of-care classifications precludes accurate predictions of early tumor recurrence for individual patients with meningioma, limiting the appropriate selection of patients who would benefit from adjuvant radiotherapy to delay recurrence. We aimed to develop an individualized prediction model of early recurrence risk combining clinical and molecular factors in meningioma. Methods DNA methylation profiles of clinically annotated tumor samples across multiple institutions were used to develop a methylome model of 5-year recurrence-free survival (RFS). Subsequently, a 5-year meningioma recurrence score was generated using a nomogram that integrated the methylome model with established prognostic clinical factors. Performance of both models was evaluated and compared with standard-of-care models using multiple independent cohorts. Results The methylome-based predictor of 5-year RFS performed favorably compared with a grade-based predictor when tested using the 3 validation cohorts (ΔAUC = 0.10, 95% CI: 0.03–0.018) and was independently associated with RFS after adjusting for histopathologic grade, extent of resection, and burden of copy number alterations (hazard ratio 3.6, 95% CI: 1.8–7.2, P < 0.001). A nomogram combining the methylome predictor with clinical factors demonstrated greater discrimination than a nomogram using clinical factors alone in 2 independent validation cohorts (ΔAUC = 0.25, 95% CI: 0.22–0.27) and resulted in 2 groups with distinct recurrence patterns (hazard ratio 7.7, 95% CI: 5.3–11.1, P < 0.001) with clinical implications. Conclusions The models developed and validated in this study provide important prognostic information not captured by previously established clinical and molecular factors which could be used to individualize decisions regarding postoperative therapeutic interventions, in particular whether to treat patients with adjuvant radiotherapy versus observation alone.

Published
2019

21. Advances in multidisciplinary therapy for meningiomas

Author

Brastianos P. K., Galanis E., Butowski N., Chan J. W., Dunn I. F., Goldbrunner R., Herold-Mende C., Ippen F. M., Mawrin C., McDermott M. W., Sloan A., Snyder J., Tabatabai G., Tatagiba M., Tonn J. C., Wen P. Y., Aldape K., Nassiri F., Zadeh G., Jenkinson M. D., Raleigh D. R., Au K., Barnhartz-Sloan J., Bi W. L., Carlotti C., Cusimano M. D., Dimeco F., Drummond K., Giannini C., Griffith B., Hashizume R., Hanemann C. O., Horbinski C., Huang R. Y., James D., Jungk C., Kaufman T. J., Krischek B., Lachance D., Lafougere C., Lee I., Liu J. C., Mamatjan Y., Mansouri A., Munoz D., Noushmehr H., Ng H. -K., Perry A., Pirouzmand F., Poisson L. M., Pollo B., Sahm F., Saladino A., Santarius T., Schichor C., Schultz D., Schmidt N. O., Selman W., Spears J., Suppiah S., Tirapelli D., Tsang D., Vogelbaum M. A., Deimling A. V., Walbert T., Westphal M., Workewych A. M., Brastianos P.K., Galanis E., Butowski N., Chan J.W., Dunn I.F., Goldbrunner R., Herold-Mende C., Ippen F.M., Mawrin C., McDermott M.W., Sloan A., Snyder J., Tabatabai G., Tatagiba M., Tonn J.C., Wen P.Y., Aldape K., Nassiri F., Zadeh G., Jenkinson M.D., Raleigh D.R., Au K., Barnhartz-Sloan J., Bi W.L., Carlotti C., Cusimano M.D., Dimeco F., Drummond K., Giannini C., Griffith B., Hashizume R., Hanemann C.O., Horbinski C., Huang R.Y., James D., Jungk C., Kaufman T.J., Krischek B., Lachance D., Lafougere C., Lee I., Liu J.C., Mamatjan Y., Mansouri A., Munoz D., Noushmehr H., Ng H.-K., Perry A., Pirouzmand F., Poisson L.M., Pollo B., Sahm F., Saladino A., Santarius T., Schichor C., Schultz D., Schmidt N.O., Selman W., Spears J., Suppiah S., Tirapelli D., Tsang D., Vogelbaum M.A., Deimling A.V., Walbert T., Westphal M., and Workewych A.M.

Subjects
Oncology, Cancer Research, medicine.medical_treatment, Supplement Articles, meningioma, Systemic therapy, surgery, 0302 clinical medicine, Meningeal Neoplasms, Trabectedin, Cancer, clinical trial, targeted therapy, Prognosis, Combined Modality Therapy, 3. Good health, 6.1 Pharmaceuticals, 030220 oncology & carcinogenesis, International Consortium on Meningiomas, Patient Safety, Meningioma, medicine.drug, medicine.medical_specialty, Oncology and Carcinogenesis, Antineoplastic Agents, Radiosurgery, 03 medical and health sciences, Internal medicine, medicine, otorhinolaryngologic diseases, Humans, Meningeal Neoplasm, Oncology & Carcinogenesis, neoplasms, business.industry, Neurosciences, Evaluation of treatments and therapeutic interventions, medicine.disease, RADIOTERAPIA, Brain Disorders, nervous system diseases, Clinical trial, Radiation therapy, radiation, Neurology (clinical), Cranial Irradiation, business, 030217 neurology & neurosurgery
Abstract

Surgery has long been established as the first-line treatment for the majority of symptomatic and enlarging meningiomas, and evidence for its success is derived from retrospective case series. Despite surgical resection, a subset of meningiomas display aggressive behavior with early recurrences that are difficult to treat. The decision to radically resect meningiomas and involved structures is balanced against the risk for neurological injury in patients. Radiation therapy has largely been used as a complementary and safe therapeutic strategy in meningiomas with evidence primarily stemming from retrospective, single-institution reports. Two of the first cooperative group studies (RTOG 0539 and EORTC 22042) evaluating the outcomes of adjuvant radiation therapy in higher-risk meningiomas have shown promising preliminary results. Historically, systemic therapy has resulted in disappointing results in meningiomas. However, several clinical trials are under way evaluating the efficacy of chemotherapies, such as trabectedin, and novel molecular agents targeting Smoothened, AKT1, and focal adhesion kinase in patients with recurrent meningiomas.

Published
2019

22. Imaging and diagnostic advances for intracranial meningiomas

Author

Huang R. Y., Bi W. L., Griffith B., Kaufmann T. J., La Fougere C., Schmidt N. O., Tonn J. C., Vogelbaum M. A., Wen P. Y., Aldape K., Nassiri F., Zadeh G., Dunn I. F., Au K., Barnhartz-Sloan J., Brastianos P. K., Butowski N., Carlotti C., Cusimano M. D., Dimeco F., Drummond K., Galanis E., Giannini C., Goldbrunner R., Hashizume R., Hanemann C. O., Herold-Mende C., Horbinski C., James D., Jenkinson M. D., Jungk C., Kaufman T. J., Krischek B., Lachance D., Lafougere C., Lee I., Liu J. C., Mamatjan Y., Mansouri A., Mawrin C., McDermott M., Munoz D., Noushmehr H., Ng H. -K., Perry A., Pirouzmand F., Poisson L. M., Pollo B., Raleigh D., Sahm F., Saladino A., Santarius T., Schichor C., Schultz D., Selman W., Sloan A., Spears J., Snyder J., Suppiah S., Tabatabai G., Tatagiba M., Tirapelli D., Tsang D., Deimling A. V., Walbert T., Westphal M., Workewych A. M., Huang R.Y., Bi W.L., Griffith B., Kaufmann T.J., La Fougere C., Schmidt N.O., Tonn J.C., Vogelbaum M.A., Wen P.Y., Aldape K., Nassiri F., Zadeh G., Dunn I.F., Au K., Barnhartz-Sloan J., Brastianos P.K., Butowski N., Carlotti C., Cusimano M.D., Dimeco F., Drummond K., Galanis E., Giannini C., Goldbrunner R., Hashizume R., Hanemann C.O., Herold-Mende C., Horbinski C., James D., Jenkinson M.D., Jungk C., Kaufman T.J., Krischek B., Lachance D., Lafougere C., Lee I., Liu J.C., Mamatjan Y., Mansouri A., Mawrin C., McDermott M., Munoz D., Noushmehr H., Ng H.-K., Perry A., Pirouzmand F., Poisson L.M., Pollo B., Raleigh D., Sahm F., Saladino A., Santarius T., Schichor C., Schultz D., Selman W., Sloan A., Spears J., Snyder J., Suppiah S., Tabatabai G., Tatagiba M., Tirapelli D., Tsang D., Deimling A.V., Walbert T., Westphal M., and Workewych A.M.

Subjects
Cancer Research, medicine.medical_specialty, Neuroimaging, Supplement Articles, Multimodal Imaging, perfusion, Meningioma, 03 medical and health sciences, 0302 clinical medicine, Medical imaging, medicine, Meningeal Neoplasms, Humans, Meningeal Neoplasm, Radiation treatment planning, medicine.diagnostic_test, business.industry, imaging, Magnetic resonance imaging, medicine.disease, radiology, 3. Good health, Tumor detection, RADIOLOGIA, PET, Oncology, 030220 oncology & carcinogenesis, Radiological weapon, Neurology (clinical), Radiology, business, 030217 neurology & neurosurgery, CT, MRI
Abstract

The archetypal imaging characteristics of meningiomas are among the most stereotypic of all central nervous system (CNS) tumors. In the era of plain film and ventriculography, imaging was only performed if a mass was suspected, and their results were more suggestive than definitive. Following more than a century of technological development, we can now rely on imaging to non-invasively diagnose meningioma with great confidence and precisely delineate the locations of these tumors relative to their surrounding structures to inform treatment planning. Asymptomatic meningiomas may be identified and their growth monitored over time; moreover, imaging routinely serves as an essential tool to survey tumor burden at various stages during the course of treatment, thereby providing guidance on their effectiveness or the need for further intervention. Modern radiological techniques are expanding the power of imaging from tumor detection and monitoring to include extraction of biologic information from advanced analysis of radiological parameters. These contemporary approaches have led to promising attempts to predict tumor grade and, in turn, contribute prognostic data. In this supplement article, we review important current and future aspects of imaging in the diagnosis and management of meningioma, including conventional and advanced imaging techniques using CT, MRI, and nuclear medicine.

Published
2019

23. Bone morphogenetic proteins inhibit the tumorigenic potential of human brain tumour-initiating cells

Author

Piccirillo, S. G. M., Reynolds, B. A., Zanetti, N., Lamorte, G., Binda, E., Broggi, G., Brem, H., Olivi, A., Dimeco, F., and Vescovi, A. L.

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): S. G. M. Piccirillo [1, 2]; B. A. Reynolds [3]; N. Zanetti [2]; G. Lamorte [2]; E. Binda [4]; G. Broggi [5]; H. Brem [6]; A. Olivi [6]; F. [...]

Published
2006
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25. Short course radiotherapy concomitant with temozolomide in GBM patients: A phase II study

Author

Fariselli, L, Cuppini, L, Gaviani, P, Marchetti, M, Pinzi, V, Milanesi, I, Simonetti, G, Tramacere, I, Dimeco, F, Salmaggi, A, Silvani, A, Fariselli L., Cuppini L., Gaviani P., Marchetti M., Pinzi V., Milanesi I., Simonetti G., Tramacere I., DiMeco F., Salmaggi A., Silvani A., Fariselli, L, Cuppini, L, Gaviani, P, Marchetti, M, Pinzi, V, Milanesi, I, Simonetti, G, Tramacere, I, Dimeco, F, Salmaggi, A, Silvani, A, Fariselli L., Cuppini L., Gaviani P., Marchetti M., Pinzi V., Milanesi I., Simonetti G., Tramacere I., DiMeco F., Salmaggi A., and Silvani A.

Abstract

Purpose: Despite recent advances, the prognosis of glioblastoma (GBM) remains poor. The aim of this study was to assess the efficacy and tolerability of multiple daily fraction radiotherapy performed with multiple temozolomide (TMZ) administrations in newly diagnosed patients with GBM. Methods: This trial was a prospective, open-label, monocentric, nonrandomized, single arm, phase II study. The primary endpoint was the proportion of progression-free patients at 12 months, and the secondary endpoints were overall survival (OS) and toxicity. Thirty-five patients underwent two radiotherapy courses concomitant with TMZ after surgery. At each course, radiation was delivered 3 times daily, 2 Gy/fraction, for 5 consecutive days, and the total dose was 60 Gy; concurrent TMZ was administered in a total dose of 150-200 mg/m2/day. Results: The primary endpoint failed to be applied; Macdonald criteria could be used in 16 (46%) patients with local or intracerebral recurrence (group A). In 12 patients, due to suspicion of radiation necrosis vs recurrence, Macdonald criteria were not applied (group B). The OS was 22 months, and OS probabilities at 12, 18, and 24 months were 82%, 59%, and 44%, respectively. Hematologic toxicities generally did not exceed grade 2. The quality of life and cognitive functioning did not significantly change between baseline and the first follow-up. In the multivariate analysis, necrosis and pseudoprogression were significant prognostic factors of OS. Conclusions: To improve local control and OS, a more aggressive treatment schedule should be explored. The related higher necrosis risk and its implications regarding local control deserve further investigation.

Published
2017

26. Erratum: The Immune Landscape of Cancer (Immunity (2018) 48(4) (812–830.e14), (S1074761318301213), (10.1016/j.immuni.2018.03.023))

Author

Thorsson, V., Gibbs, D. L., Brown, S. D., Wolf, D., Bortone, D. S., Ou Yang, T. -H., Porta-Pardo, E., Gao, G. F., Plaisier, C. L., Eddy, J. A., Ziv, E., Culhane, A. C., Paull, E. O., Sivakumar, I. K. A., Gentles, A. J., Malhotra, R., Farshidfar, F., Colaprico, A., Parker, J. S., Mose, L. E., N. S., Vo, Liu, J., Liu, Y., Rader, J., Dhankani, V., Reynolds, S. M., Bowlby, R., Califano, A., Cherniack, A. D., Anastassiou, D., Bedognetti, D., Mokrab, Y., Newman, A. M., Rao, A., Chen, K., Krasnitz, A., Hu, H., Malta, T. M., Noushmehr, H., Pedamallu, C. S., Bullman, S., Ojesina, A. I., Lamb, A., Zhou, W., Shen, H., Choueiri, T. K., Weinstein, J. N., Guinney, J., Saltz, J., Holt, R. A., Rabkin, C. S., Caesar-Johnson, S. J., Demchok, J. A., Felau, I., Kasapi, M., Ferguson, M. L., Hutter, C. M., Sofia, H. J., Tarnuzzer, R., Wang, Z., Yang, L., Zenklusen, J. C., Zhang, J. J., Chudamani, S., Lolla, L., Naresh, R., Pihl, T., Sun, Q., Wan, Y., Wu, Y., Cho, J., Defreitas, T., Frazer, S., Gehlenborg, N., Getz, G., Heiman, D. I., Kim, J., Lawrence, M. S., Lin, P., Meier, S., Noble, M. S., Saksena, G., Voet, D., Zhang, H., Bernard, B., Chambwe, N., Knijnenburg, T., Kramer, R., Leinonen, K., Miller, M., Reynolds, S., Shmulevich, I., Zhang, W., Akbani, R., Broom, B. M., Hegde, A. M., Ju, Z., Kanchi, R. S., Korkut, A., Li, J., Liang, H., Ling, S., Liu, W., Lu, Y., Mills, G. B., K. -S., Ng, Ryan, M., Wang, J., Zhang, J., Abeshouse, A., Armenia, J., Chakravarty, D., Chatila, W. K., de Bruijn, I., Gao, J., Gross, B. E., Heins, Z. J., Kundra, R., La, K., Ladanyi, M., Luna, A., Nissan, M. G., Ochoa, A., Phillips, S. M., Reznik, E., Sanchez-Vega, F., Sander, C., Schultz, N., Sheridan, R., Sumer, S. O., Sun, Y., Taylor, B. S., Anur, P., Peto, M., Spellman, P., Benz, C., Stuart, J. M., Wong, C. K., Yau, C., Hayes, D. N., Wilkerson, M. D., Ally, A., Balasundaram, M., Brooks, D., Carlsen, R., Chuah, E., Dhalla, N., Holt, R., Jones, S. J. M., Kasaian, K., Lee, D., Ma, Y., Marra, M. A., Mayo, M., Moore, R. A., Mungall, A. J., Mungall, K., Robertson, A. G., Sadeghi, S., Schein, J. E., Sipahimalani, P., Tam, A., Thiessen, N., Tse, K., Wong, T., Berger, A. C., Beroukhim, R., Cibulskis, C., Gabriel, S. B., Ha, G., Meyerson, M., Schumacher, S. E., Shih, J., Kucherlapati, M. H., Kucherlapati, R. S., Baylin, S., Cope, L., Danilova, L., Bootwalla, M. S., Lai, P. H., Maglinte, D. T., Van Den Berg, D. J., Weisenberger, D. J., Auman, J. T., Balu, S., Bodenheimer, T., Fan, C., Hoadley, K. A., Hoyle, A. P., Jefferys, S. R., Jones, C. D., Meng, S., Mieczkowski, P. A., Perou, A. H., Perou, C. M., Roach, J., Shi, Y., Simons, J. V., Skelly, T., Soloway, M. G., Tan, D., Veluvolu, U., Fan, H., Hinoue, T., Laird, P. W., Bellair, M., Chang, K., Covington, K., Creighton, C. J., Dinh, H., Doddapaneni, H., Donehower, L. A., Drummond, J., Gibbs, R. A., Glenn, R., Hale, W., Han, Y., Hu, J., Korchina, V., Lee, S., Lewis, L., Li, W., Liu, X., Morgan, M., Morton, D., Muzny, D., Santibanez, J., Sheth, M., Shinbrot, E., Wang, L., Wang, M., Wheeler, D. A., Xi, L., Zhao, F., Hess, J., Appelbaum, E. L., Bailey, M., Cordes, M. G., Ding, L., Fronick, C. C., Fulton, L. A., Fulton, R. S., Kandoth, C., Mardis, E. R., Mclellan, M. D., Miller, C. A., Schmidt, H. K., Wilson, R. K., Crain, D., Curley, E., Gardner, J., Lau, K., Mallery, D., Morris, S., Paulauskis, J., Penny, R., Shelton, C., Shelton, T., Sherman, M., Thompson, E., Yena, P., Bowen, J., Gastier-Foster, J. M., Gerken, M., Leraas, K. M., Lichtenberg, T. M., Ramirez, N. C., Wise, L., Zmuda, E., Corcoran, N., Costello, T., Hovens, C., Carvalho, A. L., de Carvalho, A. C., Fregnani, J. H., Longatto-Filho, A., Reis, R. M., Scapulatempo-Neto, C., Silveira, H. C. S., Vidal, D. O., Burnette, A., Eschbacher, J., Hermes, B., Noss, A., Singh, R., Anderson, M. L., Castro, P. D., Ittmann, M., Huntsman, D., Kohl, B., Le, X., Thorp, R., Andry, C., Duffy, E. R., Lyadov, V., Paklina, O., Setdikova, G., Shabunin, A., Tavobilov, M., Mcpherson, C., Warnick, R., Berkowitz, R., Cramer, D., Feltmate, C., Horowitz, N., Kibel, A., Muto, M., Raut, C. P., Malykh, A., Barnholtz-Sloan, J. S., Barrett, W., Devine, K., Fulop, J., Ostrom, Q. T., Shimmel, K., Wolinsky, Y., Sloan, A. E., De Rose, A., Giuliante, F., Goodman, M., Karlan, B. Y., Hagedorn, C. H., Eckman, J., Harr, J., Myers, J., Tucker, K., Zach, L. A., Deyarmin, B., Kvecher, L., Larson, C., Mural, R. J., Somiari, S., Vicha, A., Zelinka, T., Bennett, J., Iacocca, M., Rabeno, B., Swanson, P., Latour, M., Lacombe, L., Tetu, B., Bergeron, A., Mcgraw, M., Staugaitis, S. M., Chabot, J., Hibshoosh, H., Sepulveda, A., Su, T., Wang, T., Potapova, O., Voronina, O., Desjardins, L., Mariani, O., Roman-Roman, S., Sastre, X., Stern, M. -H., Cheng, F., Signoretti, S., Berchuck, A., Bigner, D., Lipp, E., Marks, J., Mccall, S., Mclendon, R., Secord, A., Sharp, A., Behera, M., Brat, D. J., Chen, A., Delman, K., Force, S., Khuri, F., Magliocca, K., Maithel, S., Olson, J. J., Owonikoko, T., Pickens, A., Ramalingam, S., Shin, D. M., Sica, G., Van Meir, E. G., Eijckenboom, W., Gillis, A., Korpershoek, E., Looijenga, L., Oosterhuis, W., Stoop, H., van Kessel, K. E., Zwarthoff, E. C., Calatozzolo, C., Cuppini, L., Cuzzubbo, S., Dimeco, F., Finocchiaro, G., Mattei, L., Perin, A., Pollo, B., Chen, C., Houck, J., Lohavanichbutr, P., Hartmann, A., Stoehr, C., Stoehr, R., Taubert, H., Wach, S., Wullich, B., Kycler, W., Murawa, D., Wiznerowicz, M., Chung, K., Edenfield, W. J., Martin, J., Baudin, E., Bubley, G., Bueno, R., De Rienzo, A., Richards, W. G., Kalkanis, S., Mikkelsen, T., Scarpace, L., Girard, N., Aymerich, M., Campo, E., Gine, E., Guillermo, A. L., Van Bang, N., Hanh, P. T., Phu, B. D., Tang, Y., Colman, H., Evason, K., Dottino, P. R., Martignetti, J. A., Gabra, H., Juhl, H., Akeredolu, T., Stepa, S., Hoon, D., Ahn, K., Kang, K. J., Beuschlein, F., Breggia, A., Birrer, M., Bell, D., Borad, M., Bryce, A. H., Castle, E., Chandan, V., Cheville, J., Copland, J. A., Farnell, M., Flotte, T., Giama, N., Ho, T., Kendrick, M., Kocher, J. -P., Kopp, K., Moser, C., Nagorney, D., O'Brien, D., O'Neill, B. P., Patel, T., Petersen, G., Que, F., Rivera, M., Roberts, L., Smallridge, R., Smyrk, T., Stanton, M., Thompson, R. H., Torbenson, M., Yang, J. D., Zhang, L., Brimo, F., Ajani, J. A., Gonzalez, A. M. A., Behrens, C., Bondaruk, J., Broaddus, R., Czerniak, B., Esmaeli, B., Fujimoto, J., Gershenwald, J., Guo, C., Lazar, A. J., Logothetis, C., Meric-Bernstam, F., Moran, C., Ramondetta, L., Rice, D., Sood, A., Tamboli, P., Thompson, T., Troncoso, P., Tsao, A., Wistuba, I., Carter, C., Haydu, L., Hersey, P., Jakrot, V., Kakavand, H., Kefford, R., Lee, K., Long, G., Mann, G., Quinn, M., Saw, R., Scolyer, R., Shannon, K., Spillane, A., Stretch, O., Synott, M., Thompson, J., Wilmott, J., Al-Ahmadie, H., Chan, T. A., Ghossein, R., Gopalan, A., Levine, D. A., Reuter, V., Singer, S., Singh, B., Tien, N. V., Broudy, T., Mirsaidi, C., Nair, P., Drwiega, P., Miller, J., Smith, J., Zaren, H., Park, J. -W., Hung, N. P., Kebebew, E., Linehan, W. M., Metwalli, A. R., Pacak, K., Pinto, P. A., Schiffman, M., Schmidt, L. S., Vocke, C. D., Wentzensen, N., Worrell, R., Yang, H., Moncrieff, M., Goparaju, C., Melamed, J., Pass, H., Botnariuc, N., Caraman, I., Cernat, M., Chemencedji, I., Clipca, A., Doruc, S., Gorincioi, G., Mura, S., Pirtac, M., Stancul, I., Tcaciuc, D., Albert, M., Alexopoulou, I., Arnaout, A., Bartlett, J., Engel, J., Gilbert, S., Parfitt, J., Sekhon, H., Thomas, G., Rassl, D. M., Rintoul, R. C., Bifulco, C., Tamakawa, R., Urba, W., Hayward, N., Timmers, H., Antenucci, A., Facciolo, F., Grazi, G., Marino, M., Merola, R., de Krijger, R., Gimenez-Roqueplo, A. -P., Piche, A., Chevalier, S., Mckercher, G., Birsoy, K., Barnett, G., Brewer, C., Farver, C., Naska, T., Pennell, N. A., Raymond, D., Schilero, C., Smolenski, K., Williams, F., Morrison, C., Borgia, J. A., Liptay, M. J., Pool, M., Seder, C. W., Junker, K., Omberg, L., Dinkin, M., Manikhas, G., Alvaro, D., Bragazzi, M. C., Cardinale, V., Carpino, G., Gaudio, E., Chesla, D., Cottingham, S., Dubina, M., Moiseenko, F., Dhanasekaran, R., Becker, K. -F., Janssen, K. -P., Slotta-Huspenina, J., Abdel-Rahman, M. H., Aziz, D., Bell, S., Cebulla, C. M., Davis, A., Duell, R., Elder, J. B., Hilty, J., Kumar, B., Lang, J., Lehman, N. L., Mandt, R., Nguyen, P., Pilarski, R., Rai, K., Schoenfield, L., Senecal, K., Wakely, P., Hansen, P., Lechan, R., Powers, J., Tischler, A., Grizzle, W. E., Sexton, K. C., Kastl, A., Henderson, J., Porten, S., Waldmann, J., Fassnacht, M., Asa, S. L., Schadendorf, D., Couce, M., Graefen, M., Huland, H., Sauter, G., Schlomm, T., Simon, R., Tennstedt, P., Olabode, O., Nelson, M., Bathe, O., Carroll, P. R., Chan, J. M., Disaia, P., Glenn, P., Kelley, R. K., Landen, C. N., Phillips, J., Prados, M., Simko, J., Smith-McCune, K., Vandenberg, S., Roggin, K., Fehrenbach, A., Kendler, A., Sifri, S., Steele, R., Jimeno, A., Carey, F., Forgie, I., Mannelli, M., Carney, M., Hernandez, B., Campos, B., Herold-Mende, C., Jungk, C., Unterberg, A., von Deimling, A., Bossler, A., Galbraith, J., Jacobus, L., Knudson, M., Knutson, T., Ma, D., Milhem, M., Sigmund, R., Godwin, A. K., Madan, R., Rosenthal, H. G., Adebamowo, C., Adebamowo, S. N., Boussioutas, A., Beer, D., Giordano, T., Mes-Masson, A. -M., Saad, F., Bocklage, T., Landrum, L., Mannel, R., Moore, K., Moxley, K., Postier, R., Walker, J., Zuna, R., Feldman, M., Valdivieso, F., Dhir, R., Luketich, J., Pinero, E. M. M., Quintero-Aguilo, M., Carlotti, C. G., Dos Santos, J. S., Kemp, R., Sankarankuty, A., Tirapelli, D., Catto, J., Agnew, K., Swisher, E., Creaney, J., Robinson, B., Shelley, C. S., Godwin, E. M., Kendall, S., Shipman, C., Bradford, C., Carey, T., Haddad, A., Moyer, J., Peterson, L., Prince, M., Rozek, L., Wolf, G., Bowman, R., Fong, K. M., Yang, I., Korst, R., Rathmell, W. K., Fantacone-Campbell, J. L., Hooke, J. A., Kovatich, A. J., Shriver, C. D., Dipersio, J., Drake, B., Govindan, R., Heath, S., Ley, T., Van Tine, B., Westervelt, P., Rubin, M. A., Lee, J. I., Aredes, N. D., Mariamidze, A., Serody, J. S., Demicco, E. G., Disis, M. L., and Vincent, B. G.

Subjects
immune, cancer, methods
Published
2019

27. Multisession radiosurgery for sellar and parasellar benign meningiomas: Long-term tumor growth control and visual outcome

Author

Marchetti, M, Bianchi, S, Pinzi, V, Tramacere, I, Fumagalli, M, Milanesi, I, Ferroli, P, Franzini, A, Saini, M, Dimeco, F, Fariselli, L, Marchetti M., Bianchi S., Pinzi V., Tramacere I., Fumagalli M. L., Milanesi I. M., Ferroli P., Franzini A., Saini M., Dimeco F., Fariselli L., Marchetti, M, Bianchi, S, Pinzi, V, Tramacere, I, Fumagalli, M, Milanesi, I, Ferroli, P, Franzini, A, Saini, M, Dimeco, F, Fariselli, L, Marchetti M., Bianchi S., Pinzi V., Tramacere I., Fumagalli M. L., Milanesi I. M., Ferroli P., Franzini A., Saini M., Dimeco F., and Fariselli L.

Abstract

BACKGROUND: Concern about radiation-induced optic neuropathy (RION) has governed recent thinking about the role of radiation therapy in the treatment of meningiomas involving the anterior optic pathways. Despite this concern, during the last few years, the use of radiosurgery for such lesions has increased steadily. OBJECTIVE: To define both the tumor control rate and the risk of RION over a long-term follow-up period in a large cohort of patients treated with multisession radiosurgery. METHODS: The local control and visual outcome of 143 patients who underwent multisession radiosurgery (mRS) were evaluated. Neurological outcome was also analyzed. The data for the present study were obtained from a prospectively maintained database. RESULTS: The mean follow-up was 44 months (range, 12-113 months). All patients underwent mRS. The median prescription dose was 25 Gy delivered in 3 to 5 fractions. The prescription isodose, which typically encompassed at least 95% of the tumor, ranged from 65% to 86% (median, 80%). The mean tumor volume was 11.0 cm 3 (range, 0.1-126.3 cm 3; median, 8 cm 3). The progression-free survival at 3, 5, and 8 years was 100%, 93%, and 90%, respectively. Compared with baseline, visual function improved in 36% of patients, whereas 7.4% experienced a worsening in visual function (5.1% excluding the patients with progressive disease). CONCLUSION: Good local control rate and a low risk of RION indicate that mRS is a safe and effective treatment option in cases of large meningiomas. ABBREVIATIONS: AOP, anterior optic pathway AVP, anterior visual pathway mRS, multisession radiosurgery PD, progressive disease RION, radiation-induced optic neuropathy sRS, stereotactic radiosurgery.

Published
2016

28. P05.02 A phase I/IIa dose escalation study evaluating the safety and efficacy of autologous CD34+ enriched hematopoietic progenitor cells genetically modified for human interferon-α2 in patients with GBM and an unmethylated MGMT promoter (TEM-GBM-001)

Author

Gentner, B, primary, Ciceri, F, additional, DiMeco, F, additional, Legnani, F, additional, Eoli, M, additional, Pollo, B, additional, Farina, F, additional, Mazzoleni, S, additional, Russo, C, additional, Naldini, L, additional, and Finocchiaro, G, additional

Published
2019
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29. Survival gain in glioblastoma patients treated with dendritic cell immunotherapy is associated with increased NK but not CD8+T cell activation in the presence of adjuvant temozolomide

Author

Pellegatta, S, Eoli, M, Cuccarini, V, Anghileri, E, Pollo, B, Pessina, S, Frigerio, S, Servida, M, Cuppini, L, Antozzi, C, Cuzzubbo, S, Corbetta, C, Paterra, R, Acerbi, F, Ferroli, P, Dimeco, F, Fariselli, L, Parati, E, Bruzzone, M, Finocchiaro, G, Pellegatta, Serena, Eoli, Marica, Cuccarini, Valeria, Anghileri, Elena, Pollo, Bianca, Pessina, Sara, Frigerio, Simona, Servida, Maura, Cuppini, Lucia, Antozzi, Carlo, CUZZUBBO, STEFANIA, CORBETTA, CRISTINA, Paterra, Rosina, Acerbi, Francesco, Ferroli, Paolo, DiMeco, Francesco, Fariselli, Laura, Parati, Eugenio A., Bruzzone, Maria Grazia, Finocchiaro, Gaetano, Pellegatta, S, Eoli, M, Cuccarini, V, Anghileri, E, Pollo, B, Pessina, S, Frigerio, S, Servida, M, Cuppini, L, Antozzi, C, Cuzzubbo, S, Corbetta, C, Paterra, R, Acerbi, F, Ferroli, P, Dimeco, F, Fariselli, L, Parati, E, Bruzzone, M, Finocchiaro, G, Pellegatta, Serena, Eoli, Marica, Cuccarini, Valeria, Anghileri, Elena, Pollo, Bianca, Pessina, Sara, Frigerio, Simona, Servida, Maura, Cuppini, Lucia, Antozzi, Carlo, CUZZUBBO, STEFANIA, CORBETTA, CRISTINA, Paterra, Rosina, Acerbi, Francesco, Ferroli, Paolo, DiMeco, Francesco, Fariselli, Laura, Parati, Eugenio A., Bruzzone, Maria Grazia, and Finocchiaro, Gaetano

Abstract

In a two-stage phase II study, 24 patients with first diagnosis of glioblastoma (GBM) were treated with dendritic cell (DC) immunotherapy associated to standard radiochemotherapy with temozolomide (TMZ) followed by adjuvant TMZ. Three intradermal injections of mature DC loaded with autologous GBM lysate were administered before adjuvant TMZ, while 4 injections were performed during adjuvant TMZ. According to a two-stage Simon design, to proceed to the second stage progression-free survival (PFS) 12 months after surgery was expected in at least 8 cases enrolled in the first stage. Evidence of immune response and interaction with chemotherapy were investigated. After a median follow up of 17.4 months, 9 patients reached PFS12. In these patients (responders, 37.5%), DC vaccination induced a significant, persistent activation of NK cells, whose increased response was significantly associated with prolonged survival. CD8+T cells underwent rapid expansion and priming but, after the first administration of adjuvant TMZ, failed to generate a memory status. Resistance to TMZ was associated with robust expression of the multidrug resistance protein ABCC3 in NK but not CD8+T cells. The negative effect of TMZ on the formation of T cell-associated antitumor memory deserves consideration in future clinical trials including immunotherapy

Published
2018

30. Radiosurgery reirradiation for high-grade glioma recurrence: a retrospective analysis

Author

Pinzi, V, Orsi, C, Marchetti, M, Milanesi, I, Bianchi, L, Dimeco, F, Cuccarini, V, Farinotti, M, Ferroli, P, Finocchiaro, G, Franzini, A, Fumagalli, M, Silvani, A, Fariselli, L, Pinzi V., Orsi C., Marchetti M., Milanesi I. M., Bianchi L. C., DiMeco F., Cuccarini V., Farinotti M., Ferroli P., Finocchiaro G., Franzini A., Fumagalli M. L., Silvani A., Fariselli L., Pinzi, V, Orsi, C, Marchetti, M, Milanesi, I, Bianchi, L, Dimeco, F, Cuccarini, V, Farinotti, M, Ferroli, P, Finocchiaro, G, Franzini, A, Fumagalli, M, Silvani, A, Fariselli, L, Pinzi V., Orsi C., Marchetti M., Milanesi I. M., Bianchi L. C., DiMeco F., Cuccarini V., Farinotti M., Ferroli P., Finocchiaro G., Franzini A., Fumagalli M. L., Silvani A., and Fariselli L.

Abstract

Despite various treatment strategies being available, recurrent high-grade gliomas (r-HGG) are difficult to manage. To obtain local control, radiosurgery (SRS) reirradiation has been considered as potential treatment. In the present study, a retrospective analysis was performed on r-HGG patients treated with salvage single- (s-SRS) or multi-fraction SRS (m-SRS). The aim of this study was to evaluate the effectiveness of salvage SRS in terms of overall survival (OS); toxicity was analyzed as well. Between 2004 May and 2011 December, 128 r-HGG patients (161 lesions) treated with CyberKnife® SRS reirradiation were retrospectively analyzed. Toxicity was graded according to Radiation Therapy Oncology Group and by Common Terminology Criteria for Adverse Events v.3 criteria. OS from the diagnosis date and OS from reirradiation were estimated using the Kaplan–Meier method. Median follow-up was 9 months (range 15 days–82 months). All patients completed SRS without high-grade toxicity. Radiation necrosis was observed in seven patients (6 %) with large volume lesions. The median survival from initial diagnosis was 32 months. The 1-, 2-, and 3-years survival rates from diagnosis were 95, 62, and 45 % respectively. Median survival following SRS was 11.5 months. The 1-, 2-, and 3-years survival rate following SRS was 48, 20, and 17 % respectively. On multivariate analysis, age <40 years, salvage surgery before SRS, and other post-SRS therapies (second-line chemotherapy and/or surgery) were found to significantly improve survival (p = 0.03). SRS represents a safe and feasible option to treat r-HGG patients with low complication rates and potential survival benefit.

Published
2015

31. Erratum to: Radiosurgery reirradiation for high-grade glioma recurrence: a retrospective analysis[DOI 10.1007/s10072-015-2172-7]

Author

Pinzi, V, Orsi, C, Marchetti, M, Milanesi, I, Bianchi, L, Dimeco, F, Cuccarini, V, Farinotti, M, Ferroli, P, Finocchiaro, G, Franzini, A, Fumagalli, M, Silvani, A, Fariselli, L, Pinzi V., Orsi C., Marchetti M., Milanesi I. M., Bianchi L. C., DiMeco F., Cuccarini V., Farinotti M., Ferroli P., Finocchiaro G., Franzini A., Fumagalli M. L., Silvani A., Fariselli L., Pinzi, V, Orsi, C, Marchetti, M, Milanesi, I, Bianchi, L, Dimeco, F, Cuccarini, V, Farinotti, M, Ferroli, P, Finocchiaro, G, Franzini, A, Fumagalli, M, Silvani, A, Fariselli, L, Pinzi V., Orsi C., Marchetti M., Milanesi I. M., Bianchi L. C., DiMeco F., Cuccarini V., Farinotti M., Ferroli P., Finocchiaro G., Franzini A., Fumagalli M. L., Silvani A., and Fariselli L.

Abstract

Despite various treatment strategies being available, recurrent high-grade gliomas (r-HGG) are difficult to manage. To obtain local control, radiosurgery (SRS) reirradiation has been considered as potential treatment. In the present study, a retrospective analysis was performed on r-HGG patients treated with salvage single- (s-SRS) or multi-fraction SRS (m-SRS). The aim of this study was to evaluate the effectiveness of salvage SRS in terms of overall survival (OS); toxicity was analyzed as well. Between 2004 May and 2011 December, 128 r-HGG patients (161 lesions) treated with CyberKnife(®) SRS reirradiation were retrospectively analyzed. Toxicity was graded according to Radiation Therapy Oncology Group and by Common Terminology Criteria for Adverse Events v.3 criteria. OS from the diagnosis date and OS from reirradiation were estimated using the Kaplan-Meier method. Median follow-up was 9 months (range 15 days-82 months). All patients completed SRS without high-grade toxicity. Radiation necrosis was observed in seven patients (6 %) with large volume lesions. The median survival from initial diagnosis was 32 months. The 1-, 2-, and 3-years survival rates from diagnosis were 95, 62, and 45 % respectively. Median survival following SRS was 11.5 months. The 1-, 2-, and 3-years survival rate following SRS was 48, 20, and 17 % respectively. On multivariate analysis, age <40 years, salvage surgery before SRS, and other post-SRS therapies (second-line chemotherapy and/or surgery) were found to significantly improve survival (p = 0.03). SRS represents a safe and feasible option to treat r-HGG patients with low complication rates and potential survival benefit

Published
2015

32. Erratum to: Radiosurgery reirradiation for high-grade glioma recurrence: a retrospective analysis[DOI 10.1007/s10072-015-2172-7]

Author

Pinzi V., Pinzi, V, Orsi, C, Marchetti, M, Milanesi, I, Bianchi, L, Dimeco, F, Cuccarini, V, Farinotti, M, Ferroli, P, Finocchiaro, G, Franzini, A, Fumagalli, M, Silvani, A, Fariselli, L, Pinzi V., Orsi C., Marchetti M., Milanesi I. M., Bianchi L. C., DiMeco F., Cuccarini V., Farinotti M., Ferroli P., Finocchiaro G., Franzini A., Fumagalli M. L., Silvani A., Fariselli L., Pinzi V., Pinzi, V, Orsi, C, Marchetti, M, Milanesi, I, Bianchi, L, Dimeco, F, Cuccarini, V, Farinotti, M, Ferroli, P, Finocchiaro, G, Franzini, A, Fumagalli, M, Silvani, A, Fariselli, L, Pinzi V., Orsi C., Marchetti M., Milanesi I. M., Bianchi L. C., DiMeco F., Cuccarini V., Farinotti M., Ferroli P., Finocchiaro G., Franzini A., Fumagalli M. L., Silvani A., and Fariselli L.

Abstract

Despite various treatment strategies being available, recurrent high-grade gliomas (r-HGG) are difficult to manage. To obtain local control, radiosurgery (SRS) reirradiation has been considered as potential treatment. In the present study, a retrospective analysis was performed on r-HGG patients treated with salvage single- (s-SRS) or multi-fraction SRS (m-SRS). The aim of this study was to evaluate the effectiveness of salvage SRS in terms of overall survival (OS); toxicity was analyzed as well. Between 2004 May and 2011 December, 128 r-HGG patients (161 lesions) treated with CyberKnife(®) SRS reirradiation were retrospectively analyzed. Toxicity was graded according to Radiation Therapy Oncology Group and by Common Terminology Criteria for Adverse Events v.3 criteria. OS from the diagnosis date and OS from reirradiation were estimated using the Kaplan-Meier method. Median follow-up was 9 months (range 15 days-82 months). All patients completed SRS without high-grade toxicity. Radiation necrosis was observed in seven patients (6 %) with large volume lesions. The median survival from initial diagnosis was 32 months. The 1-, 2-, and 3-years survival rates from diagnosis were 95, 62, and 45 % respectively. Median survival following SRS was 11.5 months. The 1-, 2-, and 3-years survival rate following SRS was 48, 20, and 17 % respectively. On multivariate analysis, age <40 years, salvage surgery before SRS, and other post-SRS therapies (second-line chemotherapy and/or surgery) were found to significantly improve survival (p = 0.03). SRS represents a safe and feasible option to treat r-HGG patients with low complication rates and potential survival benefit

Published
2015

34. OS1.3 Clinical significance of plasma EVs in Glioblastoma patients

Author

Del Bene, M, primary, Osti, D, additional, Rappa, G, additional, Santos, M, additional, Matafora, V, additional, Richichi, C, additional, Faletti, S, additional, Beznoussenko, G, additional, Mironov, A, additional, Bachi, A, additional, Fornasari, L, additional, Bongetta, D, additional, Gaetani, P, additional, DiMeco, F, additional, Lorico, A, additional, and Pelicci, G, additional

Published
2018
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36. STEREOTACTIC RADIOTHERAPY FOR RECURRENT HIGH-GRADE GLIOMAS: A RETROSPECTIVE ANALYSIS

Author

Pinzi, V, Milanesi, I, Marchetti, M, Dimeco, F, Franzini, A, Ferroli, P, Silvani, A, Finocchiaro, G, Orsi, C, Fariselli, L, Pinzi V., Milanesi IM, Marchetti M, Dimeco F, Franzini A, Ferroli P, Silvani A, Finocchiaro G, Orsi C, Fariselli L, Pinzi, V, Milanesi, I, Marchetti, M, Dimeco, F, Franzini, A, Ferroli, P, Silvani, A, Finocchiaro, G, Orsi, C, Fariselli, L, Pinzi V., Milanesi IM, Marchetti M, Dimeco F, Franzini A, Ferroli P, Silvani A, Finocchiaro G, Orsi C, and Fariselli L

Published
2014

37. Mutations targeting the coagulation pathway are enriched in brain metastases

Author

Richichi, C. (Cristina), Fornasari, L. (Lorenzo), Melloni, G.E.M. (Giorgio E. M.), Brescia, P. (Paola), Patanè, M. (Monica), Del Bene, M. (Massimiliano), Mustafa, D.A.M. (Dana), Kros, J.M. (Johan), Pollo, B. (Bianca), Pruneri, G. (Giancarlo), Sciandivasci, A. (Angela), Munzone, E. (Elisabetta), Dimeco, F. (Francesco), Pelicci, P.G. (Pier Giuseppe), Riva, L. (Laura), Pelicci, G. (Giuliana), Richichi, C. (Cristina), Fornasari, L. (Lorenzo), Melloni, G.E.M. (Giorgio E. M.), Brescia, P. (Paola), Patanè, M. (Monica), Del Bene, M. (Massimiliano), Mustafa, D.A.M. (Dana), Kros, J.M. (Johan), Pollo, B. (Bianca), Pruneri, G. (Giancarlo), Sciandivasci, A. (Angela), Munzone, E. (Elisabetta), Dimeco, F. (Francesco), Pelicci, P.G. (Pier Giuseppe), Riva, L. (Laura), and Pelicci, G. (Giuliana)

Abstract

Brain metastases (BMs) are the most common malignancy of the central nervous system. Recently it has been demonstrated that plasminogen activator inhibitor serpins promote brain metastatic colonization, suggesting that mutations in serpins or other members of the coagulation cascade can provide critical advantages during BM formation. We performed whole-exome sequencing on matched samples of breast cancer and BMs and found mutations in the coagulation pathway genes in 5 out of 10 BM samples. We then investigated the mutational status of 33 genes belonging to the coagulation cascade in a panel of 29 BMs and we identified 56 Single Nucleotide Variants (SNVs). The frequency of gene mutations of the pathway was significantly higher in BMs than in primary tumours, and SERPINI1 was the most frequently mutated gene in BMs. These findings provide direction in the development of new strategies for the treatment of BMs.

Published
2017
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38. Mutations targeting the coagulation pathway are enriched in brain metastases

Author

Richichi, C, Fornasari, L, Melloni, GEM, Brescia, P, Patane, M, Del Bene, M, Mustafa, Dana, Kros, J.M., Pollo, B, Pruneri, G, Sciandivasci, A, Munzone, E, DiMeco, F, Pelicci, PG, Riva, L, Pelicci, G, Richichi, C, Fornasari, L, Melloni, GEM, Brescia, P, Patane, M, Del Bene, M, Mustafa, Dana, Kros, J.M., Pollo, B, Pruneri, G, Sciandivasci, A, Munzone, E, DiMeco, F, Pelicci, PG, Riva, L, and Pelicci, G

Published
2017

39. STEREOTACTIC RADIOTHERAPY FOR RECURRENT HIGH-GRADE GLIOMAS: A RETROSPECTIVE ANALYSIS

Author

Pinzi, V., Milanesi, I. M., Marchetti, M., Dimeco, F., Franzini, A., Paolo Ferroli, Silvani, A., Finocchiaro, G., Orsi, C., Fariselli, L., Pinzi, V, Milanesi, I, Marchetti, M, Dimeco, F, Franzini, A, Ferroli, P, Silvani, A, Finocchiaro, G, Orsi, C, and Fariselli, L

Subjects
re-irradiation, MED/36 - DIAGNOSTICA PER IMMAGINI E RADIOTERAPIA, neurooncology, glioblastoma, radiosurgery, radiotherapy
Published
2014

41. Application of an aviation model of incident reporting and investigation to the neurosurgical scenario: Method and preliminary data

Author

Ferroli, P, Caldiroli, D, Acerbi, F, Scholtze, M, Piro, A, Schiariti, M, Orena, E, Castiglione, M, Broggi, M, Perin, A, Dimeco, F, Dimeco, F., ORENA, ELEONORA FRANCESCA, Ferroli, P, Caldiroli, D, Acerbi, F, Scholtze, M, Piro, A, Schiariti, M, Orena, E, Castiglione, M, Broggi, M, Perin, A, Dimeco, F, Dimeco, F., and ORENA, ELEONORA FRANCESCA

Abstract

Object: Incident reporting systems are universally recognized as important tools for quality improvement in all complex adaptive systems, including the operating room. Nevertheless, introducing a safety culture among neurosurgeons is a slow process, and few studies are available in the literature regarding the implementation of an incident reporting system within a neurosurgical department. The authors describe the institution of an aviation model of incident reporting and investigation in neurosurgery, focusing on the method they have used and presenting some preliminary results.Methods: In 2010, the Inpatient Safety On-Board project was developed through cooperation between a team of human factor and safety specialists with aviation backgrounds (DgSky team) and the general manager of the Fondazione IstitutoNeurologico Carlo Besta. In 2011, after specific training in safety culture, the authors implemented an aviation-derived prototype of incident reporting within the Department of Neurosurgery. They then developed an experimental protocol to track, analyze, and categorize any near misses that happened in the operating room. This project officially started in January 2012, when a dedicated team of assessors was established. All members of the neurosurgical department were asked to report near misses on a voluntary, confidential, and protected form (Patient Incident Reporting System form, Besta Safety Management Programme). Reports were entered into an online database and analyzed by a dedicated team of assessors with the help of a facilitator, and an aviation-derived root cause analysis was performed.Results: Since January 2012, 14 near misses were analyzed and classified. The near-miss contributing factors were mainly related to human factors (9 of 14 cases), technology (1 of 14 cases), organizational factors (3 of 14 cases), or procedural factors (1 of 14 cases).Conclusions: Implementing an incident reporting system is quite demanding; the process should involve

Published
2012

43. Endothelial cells create a stem cell niche in glioblastoma by providing NOTCH ligands that nurture self-renewal of cancer stem-like cells

Author

Zhu, T, Costello, M, Talsma, C, Flack, C, Crowley, J, Hamm, L, He, X, Hervey Jumper, S, Heth, J, Muraszko, K, Dimeco, F, Vescovi, A, Fan, X, Zhu, TS, Costello, MA, Talsma, CE, Flack, CG, Crowley, JG, Hamm, LL, Hervey Jumper, SL, Heth, JA, Muraszko, KM, DiMeco, F, Fan, X., VESCOVI, ANGELO LUIGI, Zhu, T, Costello, M, Talsma, C, Flack, C, Crowley, J, Hamm, L, He, X, Hervey Jumper, S, Heth, J, Muraszko, K, Dimeco, F, Vescovi, A, Fan, X, Zhu, TS, Costello, MA, Talsma, CE, Flack, CG, Crowley, JG, Hamm, LL, Hervey Jumper, SL, Heth, JA, Muraszko, KM, DiMeco, F, Fan, X., and VESCOVI, ANGELO LUIGI

Abstract

One important function of endothelial cells in glioblastoma multiforme (GBM) is to create a niche that helps promote self-renewal of cancer stem-like cells (CSLC). However, the underlying molecular mechanism for this endothelial function is not known. Since activation of NOTCH signaling has been found to be required for propagation of GBM CSLCs, we hypothesized that the GBM endothelium may provide the source of NOTCH ligands. Here, we report a corroboration of this concept with a demonstration that NOTCH ligands are expressed in endothelial cells adjacent to NESTIN and NOTCH receptor-positive cancer cells in primary GBMs. Coculturing human brain microvascular endothelial cells (hBMEC) or NOTCH ligand with GBM neurospheres promoted GBM cell growth and increased CSLC self-renewal. Notably, RNAi-mediated knockdown of NOTCH ligands in hBMECs abrogated their ability to induce CSLC self-renewal and GBM tumor growth, both in vitro and in vivo. Thus, our findings establish that NOTCH activation in GBM CSLCs is driven by juxtacrine signaling between tumor cells and their surrounding endothelial cells in the tumor microenvironment, suggesting that targeting both CSLCs and their niche may provide a novel strategy to deplete CSLCs and improve GBM treatment. ©2011 AACR.

Published
2011

44. Identification of cell surface glycoprotein markers for glioblastoma-derived stem-like cells using a lectin microarray and LC-MS/MS approach

Author

He, J, Liu, Y, Xie, X, Zhu, T, Soules, M, Dimeco, F, Vescovi, A, Fan, X, Lubman, D, DiMeco, F, VESCOVI, ANGELO LUIGI, Lubman, DM, He, J, Liu, Y, Xie, X, Zhu, T, Soules, M, Dimeco, F, Vescovi, A, Fan, X, Lubman, D, DiMeco, F, VESCOVI, ANGELO LUIGI, and Lubman, DM

Abstract

Despite progress in the treatment of glioblastoma, more than 95% of patients suffering from this disease still die within 2 years. Recent findings support the belief that cancer stem-like cells are responsible for tumor formation and ongoing growth. Here a method combining lectin microarray and LC-MS/MS was used to discover the cell surface glycoprotein markers of a glioblastoma-derived stem-like cell line. Lectin microarray analysis of cell surface glycans showed that two galactose-specific lectins Trichosanthes kirilowii agglutinin (TKA) and Peanut agglutinin (PNA) could distinguish the stem-like glioblastoma neurosphere culture from a traditional adherent glioblastoma cell line. Agarose-bound TKA and PNA were used to capture the glycoproteins from the two cell cultures, which were analyzed by LC-MS/MS. The glycoproteins were quantified by spectral counting, resulting in the identification of 12 and 11 potential glycoprotein markers from the TKA and PNA captured fractions respectively. Almost all of these proteins were membrane proteins. Differential expression was verified by Western blotting analysis of 6 interesting proteins, including the up-regulated Receptor-type tyrosine-protein phosphatase zeta, Tenascin-C, Chondroitin sulfate proteoglycan NG2, Podocalyxin-like protein 1 and CD90, and the down-regulated CD44. An improved understanding of these proteins may be important for earlier diagnosis and better therapeutic targeting of glioblastoma. © 2010 American Chemical Society.

Published
2010

45. Distinct pools of cancer stem-like cells coexist within human glioblastomas and display different tumorigenicity and independent genomic evolution.

Author

Piccirillo, S. g., Combi, L., Cajola, L., Patrizi, A., Redaelli, S., Bentivegna, A., Baronchelli, S., Maira, Giulio, Pollo, B., Mangiola, Annunziato, Dimeco, F., Dalprà, L., Vescovi, A. l., Piccirillo , S.g., Combi , L., Cajola , L., Patrizi , A., Redaelli , S., Bentivegna , A., Baronchelli , S., Maira , Giulio, Pollo , B., Mangiola, Annunziato (ORCID:0000-0002-1378-4524), Dimeco , F., Dalprà , L., Vescovi , A.l., Piccirillo, S. g., Combi, L., Cajola, L., Patrizi, A., Redaelli, S., Bentivegna, A., Baronchelli, S., Maira, Giulio, Pollo, B., Mangiola, Annunziato, Dimeco, F., Dalprà, L., Vescovi, A. l., Piccirillo , S.g., Combi , L., Cajola , L., Patrizi , A., Redaelli , S., Bentivegna , A., Baronchelli , S., Maira , Giulio, Pollo , B., Mangiola, Annunziato (ORCID:0000-0002-1378-4524), Dimeco , F., Dalprà , L., and Vescovi , A.l.

Published
2009

46. Distinct pools of cancer stem-like cells coexist within human glioblastomas and display different tumorigenicity and independent genomic evolution

Author

Piccirillo, S, Combi, R, Cajola, L, Patrizi, A, Redaelli, S, Bentivegna, A, Baronchelli, S, Maira, G, Pollo, B, Mangiola, A, Dimeco, F, Dalpra', L, Vescovi, A, Piccirillo, SGM, DiMeco, F, COMBI, ROMINA, REDAELLI, SERENA, BENTIVEGNA, ANGELA, DALPRA', LEDA, VESCOVI, ANGELO LUIGI, Piccirillo, S, Combi, R, Cajola, L, Patrizi, A, Redaelli, S, Bentivegna, A, Baronchelli, S, Maira, G, Pollo, B, Mangiola, A, Dimeco, F, Dalpra', L, Vescovi, A, Piccirillo, SGM, DiMeco, F, COMBI, ROMINA, REDAELLI, SERENA, BENTIVEGNA, ANGELA, DALPRA', LEDA, and VESCOVI, ANGELO LUIGI

Abstract

Glioblastomas (GBMs) contain transformed, self-maintaining, multipotent, tumour-initiating cancer stem cells, whose identification has radically changed our perspective on the physiology of these tumours. Currently, it is unknown whether multiple types of transformed precursors, which display alternative sets of the complement of properties of true cancer stem cells, can be found in a GBM. If different subsets of such cancer stem-like cells (CSCs) do exist, they might represent distinct cell targets, with a differential therapeutic importance, also depending on their characteristics and lineage relationship. Here, we report the presence of two types of CSCs within different regions of the same human GBM. Cytogenetic and molecular analysis shows that the two types of CSCs bear quite diverse tumorigenic potential and distinct genetic anomalies, and, yet, derive from common ancestor cells. This provides critical information to unravel the development of CSCs and the key molecular/genetic components underpinning tumorigenicity in human GBMs. © 2009 Macmillan Publishers Limited. All rights reserved.

Published
2009

49. Ephrina2 receptor in human glioblastoma cancer stem cells and identification of new, putative therapeutic targets.

Author

Vescovi, A, Binda, E, Mazza, T, Dimeco, F, Vescovi, AL, Vescovi, A, Binda, E, Mazza, T, Dimeco, F, and Vescovi, AL

Abstract

Human glioblastomas (hGBMs) have been shown to embody a relatively small subset of cells which bear the defining features of somatic stem cells and the ability to establish, expand and perpetuate these tumors. They are defined cancer stem cell or tumor propagating cells (TPCs). This has caused a paradigmatic shift in the way we interpret hGBM physiology, for it identifies TPCs as a major culprit to be tackled for the development of novel therapeutics. Hence, we inferred that the study of regulatory mechanisms of normal neurogenesis may lead us to identify specific inhibitors of TPCs. METHODS: TPCs from human GBMs were used to determine the role of a neural stem cell regulator, the EphA2 receptor, in modulating self-renewal and tumorigenicity. We used a combined series of in vitro experiments which include primary tissue cultures, FACS analysis, next generation sequencing screening and in vivo, orthotopic xenografting experiments entailing the intracerebral delivery of putative therapeutic agents. RESULTS: We determined the over-expression of the Ephrin receptor type A2 (EphA2) in hGBM TPCs. EphA2 upregulation causally underlies self-renewal and expansion of the TPCs pool. Most important, both the EphA2 cognate ligand ephrinA1-Fc causes EphA2 downregulation in TPCs and suppress TPC self-renewal and intracranial tumorigenicity. This points to EphA2 as a key effector in TPCs self-renewal and tumorigenicity. Notably, intracranial administration of ephrinA1-Fc causes both down-regulation of EphA2 in hGBMs orthotopic xenografts pre-established in mice, whose growth and expansion throughout the brain parenchyma is significantly hindered in the absence of cytotoxic effects. CONCLUSIONS: We identify TPCs as a major target of EphA2 overexpression in hGBM, that drives their self-renewal and tumorigenicity. We propose TPCs as a specific cellular target in which enforced down-regulation of a molecular target such as EphA2 may be exploited for therapeutic purposes, under therapy

Published
2014

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