Drs. Carbone and Rizzo    Michele Carbone, M.D.
Assistant Professor
Maurizio Bocchetta, Ph.D.
Research Assistant Professor
Oncology Institute
Cardinal Bernardin Cancer Center
Dr. Carbone's Phone:�(708) 327-3250
E-mail:� [EMAIL PROTECTED]
Dr. Bocchetta's Phone: (708) 327-3134
E-mail: [EMAIL PROTECTED]
Fax:�(708) 327-3238
    Dr. Bocchetta

SV40 AS A POTENTIAL CARCINOGEN IN HUMANS�
The research of Drs. Bocchetta and Carbone focuses on the molecular biology
of simian virus 40 (SV40).� This virus is highly oncogenic in rodents, but
the biologic effects in humans are still unclear.� In recent years they have
identified SV40 sequences in several human tumors such as osteosarcomas,
mesotheliomas, ependymomas, and choroid plexus tumors.� Mesothelioma is a
malignancy of the membrane lining the serous cavities.� This tumor has been
associated to asbestos exposure.� Yet the mechanism by which asbestos
induces mesothelioma is unknown.� Moreover, at least 20% of mesotheliomas in
the United States are not associated with asbestos exposure, and only a
minority of people exposed to high concentrations of asbestos develop
mesothelioma. � This suggests that additional factors render certain
individuals more susceptible to asbestos carcinogenicity.
They have found the presence of SV40 in 60 to 83% of mesotheliomas in the
U.S.� They have also demonstrated that SV40 Tag, isolated from frozen
biopsies of human mesothelioma, binds each of the retinoblastoma family
proteins: � pRb, p107, and pRb2/p130.� These proteins are phosphorylated in
a cell cycle-dependent manner, have cell growth suppressive properties, and
bind to specific members of the E2F family and various cyclins.�
Furthermore, in SV40-positive mesothelioma cell extracts, SV40 Tag retains
its ability to bind and to inactivate p53, a cellular protein that when
normally expressed, plays an important role in suppressing tumor growth.�
These findings raised the possibility that SV40 may play a central role
(alone or in combination with asbestos) in the onset and/or the progression
of mesothelioma.� Presently, they are investigating the molecular mechanisms
by which SV40 and asbestos may interact during the process of mesothelial
cell transformation.
Graduate Student and Resident Participation
In order to create a lively, diversified environment, their research group
is composed of investigators with different expertise and research
backgrounds.� Any contribution by Loyola's students and staff is welcome.�
The techniques they employ range from tissue culture to advanced molecular
biology and biochemistry.� All interested individuals should contact Dr.
Carbone, Dr. Bocchetta, or Dr. Rizzo directly.
Selected Publications
Testa JR, Carbone M, Hirvonen A, Khalili K, Krynska B, Linnainmaa K, Pooley
FD, Rizzo P, Rusch V, Xiao GH.� A multi-institutional study confirms the
presence and expression of simian virus 40 in human malignant
mesotheliomas.�Cancer Res. 1998;58(20):4505-9.
Pass HI, Donington JS, Wu P, Rizzo P, Nishimura M, Kennedy R, Carbone M.�
Human mesotheliomas contain the simian virus-40 regulatory region and large
tumor antigen DNA sequences.� J Thorac Cardiovasc Surg.� 1998;116(5):854-9.
De Luca A, Baldi A, Esposito V, Howard CM, Bagella L, Rizzo P, Caputi M,
Pass HI, Giordano GG, Baldi F, Carbone M, Giordano A. � The retinoblastoma
gene family pRb/p105, p107, pRb2/p130, and simian virus-40 large T-antigen
in human mesotheliomas.�Nat Med.�1997;3(8):913-6.
Carbone M, Rizzo P, Grimley PM, Procopio A, Mew DJ, Shridhar V, de
Bartolomeis A, Esposito V, Giuliano MT, Steinberg SM, Levine AS, Giordano A,
Pass HI.� Simian virus-40 large T-antigen binds p53 in human
mesotheliomas.�Nat Med. 1997;3(8):908-912.
Carbone M, Rizzo P, Procopio A, Giuliano M, Pass HI, Gebhardt MC, Mangham C,
Hansen M, Malkin DF, Bushart G, Pompetti F, Picci P, Levine AS, Bergsagel
JD, Garcea RL.� SV40-like sequences in human bone tumors.�Oncogene.
1996;13(3):527-35.
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