About
> INNB
Experimental Neuro-Oncology and Gene Therapy |
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Istituto Nazionale
Neurologico Besta
http://www.istituto-besta.it
Unit of
Experimental Neuro-Oncology and Gene Therapy
via Celoria 11,
20133 Milano, Italy
phone
+39-02-2394-453 or -454
fax +39-02-26681688
The
laboratory of Experimental Neuro-Oncology developed its activity in the
Istituto Nazionale Neurologico Besta (INNB)
starting in 1992 and working
on two areas: the molecular genetics of brain tumors and the experimental
treatment of malignant gliomas.
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Previous
and Current Research |
The
laboratory contributed data on the most relevant tumor suppressor genes
involved in gliomagenesis (p53, p16, PTEN) and on patterns of chromosomal
losses in gliomas.
It is providing genetic exams of relevance for the definition of
prognosis/diagnosis and for decisions on the treatment of gliomas.
More
recently a genetic characterization of pediatric and adult medulloblastomas
has been started with the identification of gene expression patterns that
may identify different subsets of tumors. The laboratory is developing DNA
microarray and loss of heterozygosity (LOH) studies on meningiomas with the
goal of identifying genetic markers helping to select tumors that are more
prone to relapse.
The
PI and the laboratory have been active in the field of gene therapy. The PI
was the main investigator in Italy of the phase III clinical trial for GBM
based on retroviral transfer of HSV-tk: the laboratory includes a BL2
facility that was approved for the preparation of retroviral producer cells
for clinical use. The group developed preclinical experiments of immuno-gene
therapy based on viral transfer of IL-4 and IL-12 and on IL-4 expression by
neural stem progenitor cells grafted in the tumor.
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Future
Projects |
Skin-derived
stem cells are and will be used to evaluate their fate after grafting into
murine brain and their potential for the expression of therapeutic molecules
in the context of a brain tumor.
Another
project under development is based on the use of mesenchymal stem cells for
the expression of therapeutic molecules in experimental gliomas.
On
2003 the laboratory started the study
of cancer stem-like cells (CSC) in different brain tumors, with special
emphasis on the genetic characterization of CSC and CSC-derived tumors. This
project will be developed in the near future on a larger number of cases and
using the techniques of immune separation by magnetic beads and DNA microarray.
The
Unit has also
started a project on manipulation of murine Dendritic Cells (DC) to be used
for the vaccination of experimental gliomas. Different approaches for DC
maturation, pulsing and administration will be tested in experimental models.
In
the INNB all the critical structures for the treatment of neuro-oncological
patients are located in the same building: neurosurgery, neuroradiology, neuropathology,
clinical neuro-oncology, radiotherapy, and experimental neuro-oncology.
At the clinical level the Lab plan to apply for a phase I project of DC
vaccination in patients with relapsing glioblastomas.
The functional department of Neuro-Oncology in the INNB is the frame
for such study. This functional department is directed by Dr. Amerigo
Boiardi.
The INNB has renovated the animal facility. A new structure for GMP-GLP
storage of biological material in liquid nitrogen has been prepared. A new
Production Unit for Cell Therapy, organized by Dr. Eugenio Parati, has been
completed and should be active during year 2005.
In the department of Experimental Neurology and Diagnostics (director Dr.
Stefano Di Donato) two FACS are available as well as all the facilities for
the molecular genetic analysis (including qPCR, automated sequencing, DNA
fragment analysis, DHPLC).
The INNB is part of Genopolis, a public, non-profit Consortium, located at
the University of Milano-Bicocca (www.genopolis.it)
and is linked in an administrative consortium with the Ospedale Policlinico
and the Istituto Nazionale Tumori, both in Milano.
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Last
Publications
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Tiziana Piepoli, Cemile Jakupoglu, Wenli
Gu, Elena Lualdi, Blanca Suarez-Merino, Pietro L. Poliani, Maria Grazia
Cattaneo, Barbara Ortino, Dorota Goplen, Jian Wang, Rosa Mola, Francesca
Inverardi, Carolina Frassoni, Rolf Bjerkvig, Ortrud Steinlein, Lucia M.
Vicentini, Oliver Brüstle and Gaetano Finocchiaro
Expression studies in gliomas and glial cells do not support a tumor
suppressor role for LGI1
Supplemental Items. Figures
1S-4S and Tables 1S and 2S
Neuro-oncol 2006; 8(2): 96-108; first published on March 2, 2006 as DOI:
10.1215/15228517-2005-006
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Boiardi
A, Eoli M, Salmaggi A, Lamperti E, Botturi A, Broggi G, Bissola L,
Finocchiaro G, Silvani A.
Systemic
Temozolomide Combined with Loco-regional Mitoxantrone in Treating
Recurrent Glioblastoma.
J
Neurooncol. 2005 Nov;75(2):215-20.
PMID:
16283445 [PubMed - in process]
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Pellegatta
S, Tunici P, Poliani PL, Dolcetta D, Cajola L, Colombelli C, Ciusani E, Di
Donato S, Finocchiaro G.
The therapeutic potential of neural stem/progenitor cells in murine
globoid cell leukodystrophy is conditioned by macrophage/microglia
activation.
Neurobiol Dis. 2005 Sep 28; [Epub ahead of print]
PMID: 16199167 [PubMed - as supplied by publisher]
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Montanini
L, Regna-Gladin C, Eoli M, Albarosa R, Carrara F, Zeviani M, Bruzzone MG,
Broggi G, Boiardi A, Finocchiaro G.
Instability of mitochondrial DNA and MRI and clinical correlations in
malignant gliomas.
J Neurooncol. 2005 Aug;74(1):87-9.
PMID: 16078113 [PubMed - indexed for MEDLINE]
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Pellegatta
S, Finocchiaro G.
Cell therapies in neuro-oncology.
Neurol Sci. 2005 May;26 Suppl 1:S43-5.
PMID: 15883693 [PubMed - indexed for MEDLINE]
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Gu
W, Brodtkorb E, Piepoli T, Finocchiaro G, Steinlein OK.
LGI1:
a gene involved in epileptogenesis and glioma progression?
Neurogenetics. 2005 May;6(2):59-66. Epub 2005 Apr 13. Review.
PMID: 15827762 [PubMed - indexed for MEDLINE]
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Salsano
E, Pollo B, Eoli M, Giordana MT, Finocchiaro G.
Expression
of MATH1, a marker of cerebellar granule cell progenitors, identifies
different medulloblastoma sub-types.
Neurosci Lett. 2004 Nov 11;370(2-3):180-5.
PMID: 15488319 [PubMed - in process]
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Tunici
P, Bissola L, Lualdi E, Pollo B, Cajola L, Broggi G, Sozzi G, Finocchiaro
G.
Genetic alterations and in vivo tumorigenicity of neurospheres derived
from an adult glioblastoma.
Mol Cancer. 2004 Oct 06;3(1):25.
PMID: 15469606 [PubMed - in process]
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Montanini
L, Bissola L, Finocchiaro G.
KLF6 is not the major target of chromosome 10p losses in glioblastomas.
Int J Cancer. 2004 Sep 10;111(4):640-1. No abstract available.
PMID: 15239145 [PubMed - indexed for MEDLINE]
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Moroni
I, Bugiani M, D'Incerti L, Maccagnano C, Rimoldi M, Bissola L, Pollo B,
Finocchiaro G, Uziel G.
L-2-hydroxyglutaric aciduria and brain malignant tumors: a predisposing
condition?
Neurology. 2004 May 25;62(10):1882-4. Review.
PMID: 15159502 [PubMed - indexed for MEDLINE]
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Magrassi
L, Finocchiaro G, Milanesi G, Benvenuto F, Spadari S, Focher F.
Lack of enantioselectivity of herpes virus thymidine kinase allows safer
imaging of gene delivery.
Gene Ther. 2003 Dec;10(25):2052-8.
PMID: 14595377 [PubMed - indexed for MEDLINE]
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Beghini
A, Magnani I, Roversi G, Piepoli T, Di Terlizzi S, Moroni RF, Pollo B,
Fuhrman Conti AM, Cowell JK, Finocchiaro G, Larizza L.
The neural progenitor-restricted isoform of the MARK4 gene in 19q13.2
is upregulated in human gliomas and overexpressed in a subset of
glioblastoma cell lines.
Oncogene. 2003 May 1;22(17):2581-91.
PMID: 12735302 [PubMed - indexed for MEDLINE]
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Gariboldi
MB, Ravizza R, Petterino C, Castagnaro M, Finocchiaro G, Monti E.
Study of in vitro and in vivo effects of the piperidine nitroxide
Tempol--a potential new therapeutic agent for gliomas.
Eur J Cancer. 2003 Apr;39(6):829-37.
PMID: 12651210 [PubMed - indexed for MEDLINE]
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Benedetti
S, Pirola B, Poliani PL, Cajola L, Pollo B, Bagnati R, Magrassi L, Tunici
P, Finocchiaro G.
Dexamethasone inhibits the anti-tumor effect of interleukin 4 on rat
experimental gliomas.
Gene Ther. 2003 Jan;10(2):188-92.
PMID: 12571648 [PubMed - indexed for MEDLINE]
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Bissola
L, Eoli M, Pollo B, Merciai BM, Silvani A, Salsano E, Maccagnano C,
Bruzzone MG, Fuhrman Conti AM, Solero CL, Giombini S, Broggi G, Boiardi A,
Finocchiaro G.
Association of chromosome 10 losses and negative prognosis in
oligoastrocytomas.
Ann Neurol. 2002 Dec;52(6):842-5.
PMID: 12447941 [PubMed - indexed for MEDLINE]
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Martini
F, Lazzarin L, Iaccheri L, Vignocchi B, Finocchiaro G, Magnani I, Serra M,
Scotlandi K, Barbanti-Brodano G, Tognon M.
Different simian virus 40 genomic regions and sequences homologous with
SV40 large T antigen in DNA of human brain and bone tumors and of
leukocytes from blood donors.
Cancer. 2002 Feb 15;94(4):1037-48.
PMID: 11920474 [PubMed - indexed for MEDLINE]
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Manni
I, Tunici P, Cirenei N, Albarosa R, Colombo BM, Roz L, Sacchi A, Piaggio
G, Finocchiaro G.
Mxi1 inhibits the proliferation of U87 glioma cells through
down-regulation of cyclin B1 gene expression.
Br J Cancer. 2002 Feb 1;86(3):477-84.
PMID: 11875718 [PubMed - indexed for MEDLINE]
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Tunici
P, Gianni D, Finocchiaro G.
Gene therapy of glioblastomas: from suicide to homicide.
Prog Brain Res. 2001;132:711-9. Review. No abstract available.
PMID: 11545030 [PubMed - indexed for MEDLINE]
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Martinez
di Montemuros F, Tavazzi D, Salsano E, Piepoli T, Pollo B, Fiorelli G,
Finocchiaro G.
High frequency of the H63D mutation of the hemochromatosis gene (HFE) in
malignant gliomas.
Neurology. 2001 Oct 9;57(7):1342. No abstract available.
PMID: 11591868 [PubMed - indexed for MEDLINE]
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Negri
DR, Mezzanzanica D, Sacco S, Gadina M, Benigni F, Cajola L, Finocchiaro G,
Ghezzi P, Canevari S.
Role of cytokines in cancer cachexia in a murine model of intracerebral
injection of human tumours.
Cytokine. 2001 Jul 7;15(1):27-38.
PMID: 11509006 [PubMed - indexed for MEDLINE]
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Lualdi
E, Chiariello E, Finocchiaro G.
Identification of regulatory regions of the putative tumor suppressor gene
DMBT1.
Biochem Biophys Res Commun. 2000 Apr 13;270(2):673-5.
PMID: 10753682 [PubMed - indexed for MEDLINE]
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Selleri
S, Torchiana E, Pareyson D, Lulli L, Bertagnolio B, Savoiardo M, Farina L,
Carrara F, Filocamo M, Gatti R, Sghirlanzoni A, Uziel G, Finocchiaro G.
Deletion of exons 11-17 and novel mutations of the galactocerebrosidase
gene in adult- and early-onset patients with Krabbe disease.
J Neurol. 2000 Nov;247(11):875-7. No abstract available.
PMID: 11151421 [PubMed - indexed for MEDLINE]
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Farina
L, Bizzi A, Finocchiaro G, Pareyson D, Sghirlanzoni A, Bertagnolio B,
Savoiardo M, Naidu S, Singhal BS, Wenger DA.
MR imaging and proton MR spectroscopy in adult Krabbe disease.
AJNR Am J Neuroradiol. 2000 Sep;21(8):1478-82.
PMID: 11003282 [PubMed - indexed for MEDLINE]
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Benedetti
S, Pirola B, Pollo B, Magrassi L, Bruzzone MG, Rigamonti D, Galli R,
Selleri S, Di Meco F, De Fraja C, Vescovi A, Cattaneo E, Finocchiaro G.
Gene therapy of experimental brain tumors using neural progenitor cells.
Nat Med. 2000 Apr;6(4):447-50.
PMID: 10742153 [PubMed - indexed for MEDLINE]
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DiMeco
F, Rhines LD, Hanes J, Tyler BM, Brat D, Torchiana E, Guarnieri M, Colombo
MP, Pardoll DM, Finocchiaro G, Brem H, Olivi A.
Paracrine delivery of IL-12 against intracranial 9L gliosarcoma in rats.
J Neurosurg. 2000 Mar;92(3):419-27.
PMID: 10701528 [PubMed - indexed for MEDLINE]
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Sacco
M, Benedetti S, Cato EM, Caniatti M, Ceruti R, Scanziani E, Pirola B,
Villa A, Finocchiaro G, Vezzoni P.
Retrovirus-mediated IL-4 gene therapy in spontaneous adenocarcinomas from
MMTV-neu transgenic mice.
Gene Ther. 1999 Nov;6(11):1893-7.
PMID: 10602385 [PubMed - indexed for MEDLINE]
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Chiariello
E, Roz L, Albarosa R, Magnani I, Finocchiaro G.
Identification of PTEN-related sequences in glioma cells and in
non-neoplastic cell lines.
Cancer Lett. 1999 Apr 26;138(1-2):1-4.
PMID: 10378766 [PubMed - indexed for MEDLINE]
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Magnani
I, Chiariello E, Conti AM, Finocchiaro G.
A recurrent 19q11-12 breakpoint suggested by cytogenetic and
fluorescence in situ hybridization analysis of three glioblastoma cell
lines.
Cancer Genet Cytogenet. 1999 Apr 15;110(2):82-6.
PMID: 10214354 [PubMed - indexed for MEDLINE]
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Benedetti
S, Bruzzone MG, Pollo B, DiMeco F, Magrassi L, Pirola B, Cirenei N,
Colombo MP, Finocchiaro G.
Eradication of rat malignant gliomas by retroviral-mediated, in vivo
delivery of the interleukin 4 gene.
Cancer Res. 1999 Feb 1;59(3):645-52.
PMID: 9973213 [PubMed - indexed for MEDLINE]
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Director |
Gaetano
Finocchiaro
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Biographical
Sketch
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Date
of Birth: Milan, October 30, 1952
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Education
and Training (Institution
and Location, Degree, Year, Field of Study):
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Milan University, School of Medicine (MD, 1979, Neurology)
▪ Milan University, School of Medicine (1983, Board in Neurology)
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Yale
University (1984-1987, Post-doctoral fellow in Human Genetics)
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Milan University (1988, Board in Biochemistry and Clinical Chemistry)
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Research
and Professional Experience
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2004-1998
Director of the Departmental Structure of Experimental Neuro-Oncology,
Istituto Nazionale Neurologico Besta (INNB).
1998-1997 Director pro-tempore of the Unit of Biochemistry and Genetics,
INNB.
1997-1987
Neurologist and scientist in the staff of the Unit of Biochemistry and
Genetics.
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GF
obtained his background as a clinical neurologist at the INNB from 1980 to
1984. During the three years spent in the Department of Human Genetics at
the Yale Medical School (1984-1987) he worked on the biochemistry and the
molecular cloning of genes involved in the beta-oxidation of fatty acids. In
1987 he started the activity of molecular biology at INNB that was developed
in collaboration with Drs. Massimo Zeviani, Massimo Pandolfo and Franco
Taroni in the Unit directed by Dr. Stefano Di Donato. In 1992 he created the
laboratory of Molecular Neuro-Oncology from which originated the Unit of
Experimental neuro-oncology that he is directing since 1998.
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GF
is in the editorial Board of Neuro-Oncology, the official journal of the
American Society for Neuro-Oncology, and of Neurological Sciences, the
official journal of the Italian Society of Neurology. He acts as reviewer of
journals specialized in oncology or molecular biology including Cancer
Research, Gene Therapy, Oncogene, Human Gene Therapy and of national and
international grant agencies. He wrote more than 90 papers published in peer
reviewed journals.
GF
is a member of the scientific board of the Italian Association for
Neuro-Oncology and of the Italian Association supporting neurological
research. He was a member of the consulting committee for gene therapy of
the Italian Prime Minister. He was the PI of the only phase III gene therapy
trial developed in Italy.
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His
research interests in the last decade have been focused on novel treatments
for malignant gliomas and on their genetic analysis. GF developed in Italy
translational and clinical studies based on the gene transfer into brain
tumors and was the first to work on the therapeutic potential of neural stem
cells for gliomas. Presently the Unit of Experimental Neuro-Oncology is the
only Italian structure providing molecular genetic tests for tumors of the
nervous system.
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Staff |
Five
project areas are present in the laboratory, with six people in charge.
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Serena
Pellegatta
has a degree in Biology obtained at the University of Milan.
She is coordinating the work on dendritic cells and mesenchymal stem cells.
She is also the main investigator in a cell therapy project for a
non-oncologic disease, globoid cell leukodystrophy.
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Patrizia
Tunici
obtained her degree in Biology at the University of Milan.
She is the senior fellow working in the area of stem cell biology.
Her studies include neural and skin stem cells as well as cancer stem-like
cells deriving from brain tumors.
Since May 2005 Patrizia Tunici is at
Los Angeles CA, Cedars-Sinai
Medical Center,
Maxine Dunitz Neurosurgical Institute (Dr. John Yu's Laboratory) thru a
scholarhip by Arin (Fondo di Giò).
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Donata
Bianchessi (in the picture) and Lorella Valletta
have both a degree in biology and are in charge for the clinical genetic
screening of malignant gliomas. LOH studies in gliomas, methylation analysis
and DHPLC screening of mutations of the neurofibromatosis gene are the main
activities.
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Ettore
Salsano,
MD, is working at the INNB as a fellow in clinical neurology and
experimental neuro-oncology. He is involved in the study of the genetic
profile of medulloblastomas mostly using real-time PCR.
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Francesca
Menghi
obtained her degree in Biotechnology in the 2004 in Milan.
She is working on the molecular genetics of meningiomas using DNA microarray
and LOH analysis.
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Melania
Cusimano (degree in Biology) is working on
mesenchymal stem cells.
Luigi Poliani, MD is supporting the morphological analysis of experimental models.
Valentina Caldera (junior scholarship holder), Daniela Corno
(pre-doctoral student), Anna
Di Stefano (
pre-doctoral student), Linda Lupo
(
pre-doctoral student) and a student-technician, Rina Monasterio Munoz,
are also collaborating with the research team.
Mrs. Maria Pia Cavalli is working in the
Unit as administrative assistant.
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