Some SV40 References the IOM didn't cite (but which were included in the references in a March 2002 Scandals)
|
: J Acquir Immune Defic Syndr 2002 Feb 1;29(2):109-16 |
Detection of polyomavirus simian virus 40
tumor antigen DNA in AIDS-related systemic non-Hodgkin lymphoma.
Vilchez RA, Lednicky JA, Halvorson SJ, White ZS, Kozinetz CA, Butel JS.
Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.
rvilchez@bcm.tmc.edu
Systemic non-Hodgkin lymphoma (S-NHL) is a common malignancy during HIV
infection, and it is hypothesized that infectious agents may be involved in the
etiology. Epstein-Barr virus DNA is found in <40% of patients with AIDS-related
S-NHL, suggesting that other oncogenic viruses, such as polyomaviruses, may play
a role in pathogenesis. We analyzed AIDS-related S-NHL samples, NHL samples from
HIV-negative patients, peripheral blood leukocytes from HIV-infected and
-uninfected patients without NHL, and lymph nodes without tumors from
HIV-infected patients. Specimens were examined by polymerase chain reaction
analysis with use of primers specific for an N-terminal region of the
oncoprotein large tumor antigen ( T-ag ) gene conserved among all three
polyomaviruses (simian virus 40 [SV40], JC virus, and BK virus).
Polyomavirus T-ag DNA sequences, proven to be
SV40-specific, were detected more frequently in AIDS-related S-NHL samples (6 of
26) than in peripheral blood leukocytes from HIV-infected patients (6 of 26 vs.
0 of 69; p =.0001), NHL samples from HIV-negative patients (6 of 26 vs. 0 of 10;
p =.09), or lymph nodes (6 of 26 vs. 0 of 7; p =.16).
Sequences of C-terminal T-ag DNA from SV40 were
amplified from two AIDS-related S-NHL samples. Epstein-Barr virus DNA
sequences were detected in 38% (10 of 26) AIDS-related S-NHL samples, 50% (5 of
10) HIV-negative S-NHL samples, and 57% (4 of 7) lymph nodes. None of the S-NHL
samples were positive for both Epstein-Barr virus DNA and SV40 DNA. Further
studies of the possible role of SV40 in the pathogenesis of S-NHL are warranted.
PMID: 11832678 [PubMed - indexed for MEDLINE]
|
Cancer Immunol Immunother 2002 Feb;50(12):682-90 |
SV40 Tag-specific cytotoxic T lymphocytes
generated from the peripheral blood of malignant pleural mesothelioma patients.
Bright RK, Kimchi ET, Shearer MH, Kennedy RC, Pass HI.
Laboratory of Prostate Cancer Biology, Robert W. Franz Cancer Research Center,
Earle A. Chiles Research Institute, and the Oregon Cancer Center, 4805 NE Glisan
Street, Portland, OR 97213, USA, rbright@providence.org
Malignant pleural mesothelioma (MPM) is an aggressive cancer, with survival of
less than one year following diagnosis and treatment with current protocols.
Recent studies have demonstrated the presence
of the simian virus 40 (SV40)-like, large tumor antigen (Tag) in nearly 60% of
MPMs. SV40 Tag is a viral-encoded tumor-specific antigen, and thus a
potential target for the induction of anti-tumor immunity and the development of
therapeutic vaccines. We describe here evidence for the existence of SV40
Tag-specific immune responses in patients with MPM whose tumors express Tag.
Humoral immunity was demonstrated by the detection of IgG titers against Tag in
serum samples from 1/3 of patients examined. CTLs were generated from the
peripheral blood of an HLA-A2(+) MPM patient with a synthetic peptide
representing an HLA-A2 binding epitope in SV40 Tag. The CTLs demonstrated
epitope fine specificity, in that other peptides from SV40 Tag and a peptide
from influenza virus were not recognized in the context of HLA-A2. Moreover, the
CTLs were capable of recognizing mesothelioma tumor cells that expressed SV40
Tag, in an MHC class I restricted manner.
PMID: 11862420 [PubMed - in process
AN: 21849853
|
Oncogene 2002 Feb 21;21(9):1434-42 |
SV40 infection induces telomerase activity in
human mesothelial cells.
Foddis R, De Rienzo A, Broccoli D, Bocchetta M, Stekala E, Rizzo P, Tosolini
A, Grobelny JV, Jhanwar SC, Pass HI, Testa JR, Carbone M.
Cancer Immunology Program, Department of Pathology, Cardinal Bernardin Cancer
Center, Loyola University Chicago, Maywood, Illinois, IL 60153, USA.
Mesotheliomas are malignant tumors of the pleural and peritoneal membranes which
are often associated with asbestos exposure and with Simian virus 40 (SV40)
infection. Telomerase activity is repressed in somatic cells and tissues but is
activated in immortal and malignant cells. We evaluated telomerase activity in
seven primary malignant mesothelioma biopsies and matched lung specimens and 20
mesothelioma cell lines and eight corresponding primary tumor cultures. All the
tumor biopsies, and nearly all primary cell mesothelioma cultures and cell lines
were telomerase positive. The findings in cell lines paralleled those observed
in primary cultures in cases where paired samples were available.
Next, we found that SV40, a DNA tumor virus
present in approximately 50% of mesothelioma biopsies in the USA, induced
telomerase activity in primary human mesothelial cells, but not in primary
fibroblasts. Telomerase activity became detectable as early as 72 h following
wild-type (strain 776) SV40 infection, and a clear DNA ladder was detectable 1
week after infection. The amount of telomerase activity increased during passage
in cell culture and appeared to parallel increases in the cellular amounts of
the SV40 large T-antigen. Thus, SV40 infection leads to telomerase activity
before the infected mesothelial cells become transformed and immortalized.
SV40 infection of human fibroblasts did not cause detectable telomerase
activity. We also determined that the SV40 small t-antigen (tag) plays an
important role in inducing telomerase activity because this activity was
undetectable or minimal in mesothelial cells infected and/or transformed by SV40
tag mutants. Asbestos alone did not induce telomerase activity, and asbestos did
not influence telomerase activity in mesothelial cells infected with SV40.
Induction of telomerase activity by SV40 may be related to the very high rate of
mesothelial cell immortalization that is characteristically associated with SV40
infection of mesothelial cells.
PMID: 11857086 [PubMed - indexed for MEDLINE]
AN: 21846811
|
: J Natl Cancer Inst 2002 Feb 6;94(3):229 |
Re: Debate on the Link Between SV40 and Human
Cancer Continues.
Kops SP.
PMID: 11830616 [PubMed - in process]
AN: 21819111
|
J Natl Cancer Inst 2002 Feb 6;94(3):229-30 |
Re: Debate on the Link Between SV40 and Human
Cancer Continues.
Carbone M, Pass HI.
M. Carbone, Cardinal Bernardin Cancer Center, Loyola University Medical School
Chicago, Maywood IL.
PMID: 11830615 [PubMed - in process]
AN: 21819110
|
J Natl Cancer Inst 2001 Sep 5;93(17):1284-6 |
Debate on the link between SV40 and human
cancer continues.
Nelson NJ.
Publication Types:
· News
PMID: 11535696 [PubMed - indexed for MEDLINE]
AN: 21427132
|
Chin Med J (Engl) 2001 Apr;114(4):382-6 |
Simian virus 40 large tumor antigen forms
specific complexes with p53 and pRb in human brain tumors.
Zhen H, Zhang X, Zhang Z, Fei Z, He X, Liang J, Huang W, Liu X, Zhang P.
Department of Neurosurgery, Xijing Hospital, Institute of Neurosurgery of PLA,
Fourth Military Medical University, Xi'an 710032, China. zh_ha@263.net
OBJECTIVE: To study the role of simian virus 40 (SV40) early region gene coding
product large tumor antigen (Tag) expression and the interaction between Tag and
tumor suppressors p53 and pRb in human brain tumorigenesis. METHODS: Tag was
investigated by immunoprecipitation followed by silver staining and Western blot
in 65 cases of human brain tumors and 8 cases of normal brain tissues. Tag-p53
and Tag-pRb complexes were screened in 18 and 15 Tag positive tumor tissues,
respectively. RESULTS: Tag was found in all 8 ependymomas and 2 choroid plexus
papillomas, 90% of pituitary adenomas (9/10), 73% of astrocytomas (11/15), 70%
of meningiomas (7/10), 50% of glioblastomas multiforme (4/8), 33% of
medulloblastomas (2/6). 5 oligodendrogliomas, 1 pineocytoma, and 8 normal brain
tissues were negative for Tag. Tag-p53 complex was detected in all 18 Tag
positive tumors. Tag-pRb complex was found in all 15 Tag positive tumors.
CONCLUSION: SV40 Tag is expressed in human
brain tumors and can form specific complexes with tumor suppressors p53 and pRb.
The inactivation of p53 and pRb due to the formation of Tag-p53 and Tag-pRb
complexes may be an important mechanism in the etiopathogenesis of human brain
tumors.
PMID: 11780459 [PubMed - indexed for MEDLINE]
|
Dis Markers 2001;17(3):167-72 |
Increasing evidence for involvement of SV40
in human cancer.
Butel JS.
Department of Molecular Virology and Microbiology, Baylor College of Medicine,
One Baylor Plaza, Houston, TX 77030, USA. jbutel@bcm.tmc.edu
SV40, a small DNA virus, is known to possess
strong oncogenic potential. Millions of people were exposed to SV40 as an
unknown contaminant of some early poliovaccines. This article briefly summarizes
the increasing evidence of the association of SV40 with certain types of human
cancer, including mesotheliomas and brain tumors. Unanswered questions
pertaining to the pathogenesis of human infections by SV40 and the functional
role of the virus in tumor development are noted. It is concluded that SV40
should be considered a candidate human tumor virus and that vigorous efforts to
clarify the role of the virus in human disease should be supported.
Publication Types:
· Review
· Review, Tutorial
PMID: 11790883 [PubMed - indexed for MEDLINE]
AN: 21650496
|
Semin Cancer Biol 2001 Feb;11(1):15-23 |
Cellular transformation by SV40 large T
antigen: interaction with host proteins.
Ali SH, DeCaprio JA.
Department of Adult Oncology, Dana-Farber Cancer Institute and Harvard Medical
School, Boston, MA 02115, USA.
SV40 large T antigen (TAg) is a powerful
oncoprotein capable of transforming a variety of cell types. The
transforming activity of TAg is due in large part to its perturbation of the
retinoblastoma (pRB) and p53 tumor suppressor proteins. In addition, TAg binds
to several other cellular factors, including the transcriptional co-activators
p300 and CBP, which may contribute to its transformation function. Several other
features of TAg that appear to contribute to its full transformation potential
are yet to be completely understood. Study of TAg therefore continues to provide
new insights into the mechanism of cellular transformation. Copyright 2001
Academic Press.
Publication Types:
· Review
· Review, Tutorial
PMID: 11243895 [PubMed - indexed for MEDLINE]
AN: 21139788
|
: Semin Cancer Biol 2001 Feb;11(1):23-30 |
Role of T antigen interactions with p53 in
tumorigenesis.
Pipas JM, Levine AJ.
Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA
15260, USA.
SV40 induces neoplastic transformation by
disabling several key cellular growth regulatory circuits. Among these
are the Rb- and p53-families of tumor suppressors. The multifunctional,
virus-encoded large T antigen blocks the function of both Rb and p53. Large T
antigen uses multiple mechanisms to block p53 activity, and this action
contributes to tumorigenesis, in part, by blocking p53-mediated growth
suppression and apoptosis. Since the p53
pathway is inactivated in most human tumors, T antigen/p53 interactions offer a
possible mechanism by which SV40 contributes to human cancer. Copyright
2001 Academic Press.
Publication Types:
· Review
· Review, Tutorial
PMID: 11243896 [PubMed - indexed for MEDLINE]
AN: 21139789
|
Semin Cancer Biol 2001 Feb;11(1):31-8 |
SV40 and cell cycle perturbations in
malignant mesothelioma.
Testa JR, Giordano A.
Human Genetics Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
JR.Testa@fccc.edu
Although epidemiological findings have
established that exposure to asbestos fibers is the major cause of malignant
mesothelioma (MM), recent studies have implicated simian virus 40 (SV40) in the
etiology of some of these tumors. Cytogenetic and molecular genetic
evidence suggests that multiple somatic genetic events are required for
tumorigenic conversion of a mesothelial cell. As with many other types of
cancer, in MM critical oncogenic events exert their action via perturbations of
the cell cycle. Interactions between the
retinoblastoma (Rb) family of proteins and oncoproteins encoded by SV40 lead to
cell cycle alterations. Likewise, inhibition of the p53 tumor suppressor by SV40
can inactivate a crucial cell cycle checkpoint, thereby permitting cells to
undergo mitosis regardless of the presence of DNA damage. Many MMs
exhibit loss and/or inactivation of the tumor suppressors p16(INK4a)and
p14(ARF), components of the pRb and p53 cell cycle regulatory pathways,
respectively. Recent investigations have demonstrated that SV40 large T antigen,
isolated from frozen biopsies of human MM specimens, binds to and inactivates
various tumor suppressor gene products such as pRb and p53.
In this review, we discuss how SV40-oncosuppressor interactions can lead to
functional alterations of the pRb- and p53-dependent cell cycle regulatory
pathways and thereby contribute to neoplastic transformation of human
mesothelial cells. Copyright 2001 Academic Press.
Publication Types:
· Review
·
Review, Tutorial
PMID: 11243897 [PubMed - indexed for MEDLINE]
AN: 21139790
|
Semin Cancer Biol 2001 Feb;11(1):39-47 |
Simian virus 40 regulatory region structural
diversity and the association of viral archetypal regulatory regions with human
brain tumors.
Lednicky JA, Butel JS.
Department of Molecular Virology and Microbiology, Baylor College of Medicine,
Houston, TX 77030, USA.
The regulatory region (RR) of simian virus 40 (SV40) contains enhancer/promoter
elements and an origin of DNA replication. Natural SV40 isolates from simian
brain or kidney tissues typically have an archetypal RR arrangement with a
single 72-basepair enhancer element. A rare simpler, shorter SV40 RR exists that
lacks a duplicated sequence in the G/C-rich region and is termed protoarchetypal.
Occasionally, SV40 strain variants arise de novo that have complex RRs, which
typically contain sequence reiterations, rearrangements, and/or deletions. These
variants replicate faster and to higher titers in tissue culture; we speculate
that such faster-growing variants were selected when laboratory strains of SV40
were initially recovered. SV40 strains with
archetypal RRs have been found in some human brain tumors. The possible
implications of these findings and a brief review of the SV40 RR structure are
presented. Copyright 2001 Academic Press.
Publication Types:
· Review
· Review, Tutorial
PMID: 11243898 [PubMed - indexed for MEDLINE]
AN: 21139791
|
J Neurosurg 2001 Jul;95(1):96-101 |
Detection of simian virus 40 DNA sequence in
human primary glioblastomas multiforme.
Kouhata T, Fukuyama K, Hagihara N, Tabuchi K.
Department of Neurosurgery, Saga Medical School, Japan.
OBJECT: Deoxyribonucleic acid oncoviruses can induce neoplastic transformation
of cells because their viral proteins interfere with antiproliferative cellular
proteins. Simian virus 40 (SV40) is a DNA virus
that induces the emergence of ependymomas, choroid plexus tumors, mesotheliomas,
osteosarcomas, sarcomas, and various tumors when injected into newborn hamsters.
Recently, approximately 60% of human ependymomas, choroid plexus tumors, and
mesotheliomas were reported to contain and express SV40 DNA sequences. In this
study the presence of SV40 DNA sequences was investigated in human brain tumors.
METHODS: Three of 32 glioblastomas mutiforme (GBMs), but none of two ependymomas
and five medulloblastomas, were found to possess SV40 DNA sequences when
examined using polymerase chain reaction (PCR). The DNA sequence analysis of PCR-amplified
fragments disclosed that the samples were identical to the regulatory region of
SV40. All three GBMs, which arose in elderly patients with wild-type p53, were
considered to be primary (de novo) tumors. Although each of the three tumors was
immunohistochemically negative for SV40 T antigen, in situ hybridization
successfully demonstrated the messenger RNA for SV40 T antigen. CONCLUSIONS:
The results of this study indicate that latent
infection of SV40 in elderly people may be implicated in the tumorigenesis of
certain primary GBMs.
PMID: 11453404 [PubMed - indexed for MEDLINE]
AN: 21345940
|
Semin Cancer Biol 2001 Feb;11(1):49-61 |
Association of SV40 with human tumours.
Jasani B, Cristaudo A, Emri SA, Gazdar AF, Gibbs A, Krynska B, Miller C,
Mutti L, Radu C, Tognon M, Procopio A.
Immunocytochemistry and Molecular Pathology Unit, Department of Pathology,
University of Wales College of Medicine, CF14 4XN, Cardiff, UK.
SV40 was discovered as a contaminant of poliovirus vaccines that were
inadvertently administered to millions of people in Europe and the United States
between 1955 and 1963. Shortly afterwards, SV40 was proven to be oncogenic in
rodents and capable of transforming human and animal cells in vitro. The
possibility that SV40 might cause tumours in humans thus became a subject of
scientific and public interest and scrutiny. However, largely due to a lack of
significant epidemiological evidence, interest in assessing SV40's potential
carcinogenic role in humans diminished.
Recently, many laboratories have reported the presence of SV40-like DNA in a
high proportion of human mesotheliomas, ependymomas and osteosarcoma (the three
main types of tumours caused by virus in hamsters), renewing the question
whether SV40 might be a human tumour virus. Molecular data from these studies
are reviewed to re-evaluate the potential role of SV40 as a human carcinogen.
Copyright 2001 Academic Press.
Included in this reference list is some of the epidemiological evidence in favor of there being a relationship between SV40 and cancer. To the extent to which there is not more, to what extent is it due to the question not being adequately studied? (To adequately assess the risk, comparisons between those vaccinated with polio vaccine, other vaccines, and NO vaccines would have had to have been made.)
Publication Types:
· Review
· Review, Tutorial
PMID: 11243899 [PubMed - indexed for MEDLINE]
AN: 21139792
|
Semin Cancer Biol 2001 Feb;11(1):5-13 |
The role of the SV40 ST antigen in cell
growth promotion and transformation.
Rundell K, Parakati R.
Department of Microbiology-Immunology, Northwestern University, and The Robert
H. Lurie Comprehensive Cancer Center, Chicago, IL 60611, USA. krundell@northwestern.edu
The simian virus 40 small-t (ST) antigen plays
a key role in permissive and nonpermissive infections, increasing virus yields
in lytic cycles of primate cells and enhancing the ability of large-T (LT) to
transform rodent or even human cells. In the absence of ST, tumors in
rodent model systems appear primarily in lymphoid and other proliferative
tissues and transformation is reduced in several in vitro systems. The functions
of ST largely reflect its binding and inhibition of protein phosphatase 2A,
although a recently described dnaJ domain also contributes to its biology. The
dnaJ domain is present in LT and a third early gene product, the 17kT protein,
for which a potential role in transformation deserves further evaluation.
Copyright 2001 Academic Press.
Publication Types:
· Review
· Review, Tutorial
PMID: 11243894 [PubMed - indexed for MEDLINE]
AN: 21139787
|
Semin Cancer Biol 2001 Feb;11(1):63-71 |
SV40 and the pathogenesis of mesothelioma.
Rizzo P, Bocchetta M, Powers A, Foddis R, Stekala E, Pass HI, Carbone M.
Cancer Immunology Program, Cardinal Bernardin Cancer Center, Department of
Pathology, Loyola University Chicago, Maywood, IL 60153, USA.
Malignant mesothelioma, a tumor of the pleura,
pericardium, and peritoneum, is presently a worldwide problem. Current therapy
is ineffective in slowing the course of the disease, and median survival from
the time of diagnosis is rarely greater than 1 year. While the tumor was almost
unknown prior to the second half of the twentieth century, it is presently
responsible for more than 2000 deaths per year in the US alone. Mesothelioma is
frequently associated with exposure to asbestos, but the incidence of cases
involving individuals with low levels of asbestos exposure is increasing. For
this reason, there has been much interest in studying whether there are
alternative factors that act alone or in conjunction with asbestos in producing
this malignancy. In the last decade, simian virus 40 (SV40) has become the most
notable suspected agent. Copyright 2001 Academic Press.
Publication Types:
· Review
· Review, Tutorial
PMID: 11243900 [PubMed - indexed for MEDLINE]
AN: 21139793
|
Semin Cancer Biol 2001 Feb;11(1):73-80 |
Strategies to circumvent SV40 oncoprotein
expression in malignant pleural mesotheliomas.
Schrump DS, Waheed I.
Thoracic Oncology Section, Surgery Branch, National Cancer Institute, Bethesda,
MD, 20892, USA. schrump@pop.nci.nih.gov
Although nearly 60% of mesotheliomas contain
SV40 early region DNA sequences, the role of T/t antigens in initiating and
maintaining the transformed state of mesothelioma cells remains unclear.
The majority of mesothelioma cells which contain SV40 early region sequences
exhibit extremely low basal expression of SV40 oncoproteins; however, T/t
antigen expression can be induced under conditions of cellular stress.
Abrogation of SV40 T/t expression by antisense techniques induces apoptosis in
part via restoration of p53 function, and enhances chemosensitivity in SV40 (+)
MPM cells by mechanisms which have not been fully elucidated.
This review briefly summarizes our ongoing
efforts to define the role of SV40 oncoproteins in modulating the malignant
phenotype of mesothelioma cells, and highlights strategies which may prove
efficacious in vivo for circumventing SV40 T/t antigen expression in
mesotheliomas. Copyright 2001 Academic Press.
Publication Types:
· Review
· Review, Tutorial
PMID: 11243901 [PubMed - indexed for MEDLINE]
AN: 21139794
|
Front Biosci 2001 Apr 1;6:E12-22 |
Simian virus 40 detection in human
mesothelioma: reliability and significance of the available molecular evidence.
Jasani B, Jones CJ, Radu C, Wynford-Thomas D, Navabi H, Mason M, Adams M,
Gibbs A.
Department of Pathology, University of Wales College of Medicine, Heath Park,
Cardiff, CF14 4XN, Wales, UK. Jasani@cf.ac.uk
Simian virus 40 was discovered as a contaminant of early poliovirus vaccines
that were inadvertently administered to millions of people in Europe and the
United States between 1955 and 1963. Although
SV40 was proven to be oncogenic in rodents and capable of transforming human and
animal cells in vitro, its role in human cancer could not be proven
epidemiologically. The matter was forgotten until 1993 when SV40 was
accidentally found to cause
mesotheliomas in hamsters injected intra-cardially. Subsequently, DNA
sequences associated with its powerful oncogenic principal, the large T antigen,
were found with high frequency in human pleural mesothelioma using the
polymerase chain reaction (PCR). Since then many laboratories have confirmed the
human findings. However, a few laboratories have failed to reproduce these data
and the authors of the studies have claimed that the detection of SV40 DNA may
simply represent PCR contamination artefacts. The controversy raised by this
viewpoint is reviewed in this article together with a critical appraisal of the
reliability of the molecular techniques used to detect SV40 DNA, in order to
evaluate the potential aetiopathogenic role of SV40 in human mesothelioma.
If SV40
was “proven to be oncogenic in rodents
and capable of transforming human and animal cells in vitro”,
why wasn’t it studied more aggressively? Why did it take an accident to
initiate more interest?
Publication Types:
· Review
· Review Literature
PMID: 11282566 [PubMed - indexed for MEDLINE]
AN: 21180146
|
Cancer Res 2001 May 1;61(9):3556-60 |
A genetically tractable model of human glioma
formation.
Rich JN, Guo C, McLendon RE, Bigner DD, Wang XF, Counter CM.
Department of Medicine, Duke University Medical Center, Durham, North Carolina
27710, USA. rich0001@mc.duke.edu
Gliomas remain one of the deadliest forms of cancer. Improved therapeutics will
require a better understanding of the molecular nature of these tumors. We,
therefore, mimicked the most common genetic changes found in grade III-IV
gliomas, disruption of the p53 and RB pathways and activation of telomere
maintenance and independence from growth factors,
through the ectopic expression of the SV40
T/t-Ag oncogene, an oncogenic form of H-ras (H-ras(V12G)), and the human
telomerase catalytic subunit hTERT in normal human astrocytes. The resulting
cells displayed many of the hallmarks of grade III-IV gliomas, including greatly
expanded life span and growth in soft agar and, most importantly, were
tumorigenic with pathology consistent with grade III-IV neuroectodermal tumors
in mice. This model system will, for the first time, allow the biological
significance of selected genetic alterations to be studied in human gliomas.
PMID: 11325817 [PubMed - indexed for MEDLINE]
AN: 21225302
|
Rev Med Virol 2000 Jan-Feb;10(1):31-43 |
Does SV40 infection contribute to the
development of human cancers?
Shah KV.
Department of Molecular Microbiology and Immunology, Johns Hopkins University
School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205, USA.
A large number of recent studies have reported
the detection of simian virus 40 (SV40) nucleotide sequences in a number of
unrelated human cancers which include paediatric and adult brain tumours,
pleural mesotheliomas, bronchopulmonary carcinomas and osteosarcomas. Most of
the data have been gathered by the use of PCR assays. These observations imply
that SV40 is circulating in human communities by person-to-person transmission
and that the virus is capable of wide dissemination in the infected individual.
These claims must be regarded with skepticism for a variety of reasons. There
are several inconsistencies in the reported data; for example, there is a wide
variation (0-23%) in the frequency of SV40 sequences in normal tissues. The
results of PCR assays have been difficult to confirm by less error-prone and
independent assays and the relationship of the virus to the tumour cell is not
characterised. The SV40 sequences reported from humans are essentially identical
to those of wild-type SV40; it is difficult to conceive that a highly
species-specific polyomavirus like SV40 would cross the species barrier, become
a human infection, and acquire pathogenic potential for the new host without
significant adaptive change in its genome. The available evidence, although not
extensive, does not indicate that SV40 is circulating in human communities. It
is premature to discuss or speculate on the potential role of SV40 in the
development of human cancer until the presence of SV40 in cancers and in human
communities is established unequivocally, the risk factors for SV40 infection
are elucidated, and the effect of SV40 exposure on the development of specific
cancers is examined in the context of other known risk factors for those cancers.
Copyright 2000 John Wiley & Sons, Ltd.
Publication Types:
· Review
· Review, Tutorial
PMID: 10654003 [PubMed - indexed for MEDLINE]
AN: 20121062
|
Brain Pathol 2000 Jan;10(1):85-92 |
Low frequency of SV40, JC and BK polyomavirus
sequences in human medulloblastomas, meningiomas and ependymomas.
Weggen S, Bayer TA, von Deimling A, Reifenberger G, von Schweinitz D,
Wiestler OD, Pietsch T.
Department of Neuropathology, University of Bonn Medical Center, Germany.
Several reports have suggested a role for polyomaviruses in the pathogenesis of
human brain tumors. This potential involvement is not conclusively resolved. For
the present study, a highly sensitive PCR-assay with fluorescence-labelled
primers was developed to search for polyomavirus sequences in human brain tumor
and control DNA samples. The assay was shown to detect approximately one viral
large T-antigen (TAg) gene per 250 cells. We identified simian virus 40
(SV40)-like sequences in 2/116 medulloblastomas, in 1/131 meningiomas, in 1/25
ependymomas and in 1/2 subependymomas. A single case of ependymoma contained
SV40 VP-1 late gene sequences. Moreover, one of the meningioma samples showed JC
virus sequences. In contrast, 60 hepatoblastoma samples and 31 brain samples
from schizophrenic patients were consistently negative. BK virus sequences were
not detectable in any of our samples. Immunohistochemical analysis of two SV40
positive tumor biopsies failed to detect large TAg in the tumor cells. In the JC
positive meningioma, immunoreactivity for the viral late gene product (VP-1) was
not observed. Our data do not entirely rule out
SV40 and JC virus as an initiative agent with a hit-and-run mechanism. However
the low frequency of virus sequences and the absence of TAg protein expression
argue against a major role of these viruses in the pathogenesis of human
medulloblastomas, meningiomas and ependymomas.
PMID: 10668898 [PubMed - indexed for MEDLINE]
AN: 20132382
|
J Virol 2001 Oct;75(20):9799-807 |
Overexpression of simian virus 40 small-T
antigen blocks centrosome function and mitotic progression in human fibroblasts.
Gaillard S, Fahrbach KM, Parkati R, Rundell K.
Department of Microbiology-Immunology and the Robert H. Lurie Comprehensive
Cancer Center, Northwestern University, Chicago, Illinois 60611-3010, USA.
Recombinant adenoviruses that express high levels of the simian virus 40 (SV40)
small-t (ST) antigen have been used to study the requirement for ST to drive
cell cycle proliferation of confluent human diploid fibroblasts. This occurs
when either large-T (LT) antigen or serum is added to provide a second signal.
While cells readily completed S phase in these experiments, they were found to
accumulate with 4N DNA content. Cellular and nuclear morphology, as well as the
biochemical status of cyclin B complexes, showed that these cells entered
mitosis but were blocked prior to mitotic metaphase. The defect appears to
reflect an inability of cells overexpressing ST to form organized centrosomes
that duplicate and separate normally during the cell cycle and, therefore, the
absence of a mitotic spindle. The ability of ST to bind protein phosphatase 2A
was required for this pattern, suggesting that altered phosphorylation of key
centrosomal components may occur when ST is overexpressed.
Although the possible significance of ST
effects on the centrosome cycle is not fully understood, these findings suggest
that ST could influence chromosomal instability patterns that are a hallmark of
SV40-transformed cells and LT expression.
PMID: 11559813 [PubMed - indexed for MEDLINE]
AN: 21443975
|
Zhonghua Liu Xing Bing Xue Za Zhi 2000 Feb;21(1):19-21 |
[A study of simian virus 40 infection and its
origin in human brain tumors]
[Article in Chinese]
Bu X, Zhang X, Zhang X, et Al.
Department of Neurosurgery, Henan Provincial People's Hospital, Zhengzhou
450003, China.
OBJECTIVE: To study the status of simian virus 40 (SV40) infection and its
origin in human brain tumors. METHODS: Polymerase chain reaction (PCR) and Dot
blot hybridization were used to detect SV40 DNA sequences in 516 human brain
tumor tissues, 80 peripheral blood cells and 50 sperm fluids from healthy
individuals, 100 human embryo tissues from artificial abortion, 30 normal brain
tissues and two human glioma cell lines: SHG44 and BT325. RESULTS:
SV40 DNA sequences were found in 36.4% of human
brain tumors (188/516), 16.3% of healthy peripheral blood cells (13/80), 22.0%
of healthy semen (11/50), 8.0% of human embryo tissues (8/100) and 6.7% of
normal brain tissues (2/30). SV40 DNA sequences were also detected in
SHG44 and BT325 cell lines. The positive rates
of SV40 DNA in human brain tumors, peripheral blood cells and semen from healthy
donors were significantly higher than those in human normal brain and embryo
tissues (P < 0.05). CONCLUSIONS: (1)
SV40 has a higher infection rate in human brain tumors, (2) SV40 is closely
related to the etiopathogenesis of human brain tumors, (3) the ways of SV40
spread may due to both horizontal and diaplacental infections in human
population.
PMID: 11860751 [PubMed - in process]
AN: 21851553
|
Bull World Health Organ 2000;78(2):195-8 |
Simian virus 40, poliovirus vaccines, and
human cancer: research progress versus media and public interests.
Butel JS.
Department of Molecular Virology and Microbiology, Baylor College of Medicine,
Houston, TX 77030-3498, USA.
From 1955 through early 1963, millions of people were inadvertently exposed to
simian virus 40 (SV40) as a contaminant of poliovirus vaccines; the virus had
been present in the monkey kidney cultures used to prepare the vaccines and had
escaped detection. SV40 was discovered in 1960 and subsequently eliminated from
poliovirus vaccines. This article reviews current knowledge about SV40 and
considers public responses to reports in the media.
SV40 is a potent tumour virus with broad tissue
tropism that induces tumours in rodents and transforms cultured cells from many
species. It is also an important laboratory model for basic studies of molecular
processes in eukaryotic cells and mechanisms of neoplastic transformation. SV40
neutralizing antibodies have been detected in individuals not exposed to
contaminated poliovirus vaccines. There have been many reports of detection of
SV40 DNA in human tumours, especially mesotheliomas, brain tumours and
osteosarcomas; and DNA sequence analyses have ruled out the possibility that the
viral DNA in tumours was due to laboratory contamination or that the virus had
been misidentified. However, additional studies are necessary to prove
that SV40 is the cause of certain human cancers. A recently published review
article evaluated the status of the field and received much media attention. The
public response emphasized that there is great interest in the possibility of
health risks today from vaccinations received in the past.
Publication Types:
· Review
· Review, Tutorial
PMID: 10743284 [PubMed - indexed for MEDLINE]
AN: 20207687
|
Genes Chromosomes Cancer 2000 May;28(1):23-30 |
Presence and expression of the simian
virus-40 genome in human giant cell tumors of bone.
Gamberi G, Benassi MS, Pompetti F, Ferrari C, Ragazzini P, Sollazzo MR,
Molendini L, Merli M, Magagnoli G, Chiesa F, Gobbi AG, Powers A, Picci P.
Laboratory of Oncologic Research, Rizzoli Institute, Bologna, Italy.
gabriella.gamberi@ior.it
SV40 DNA sequences have been found in human tumors, such as mesotheliomas,
ependymomas, and bone tumors, suggesting that SV40 may be involved in their
etiology. The FOS oncogene could play an important role in bone development
because SV40 is able to induce FOS in cell culture. In this study, the presence
of SV40 sequences, large T antigen (Tag), and FOS protein expression were
investigated in 120 giant cell tumors (GCTs), moderately benign bone tumors that
in some cases can progress to a malignant phenotype. Polymerase chain reaction (PCR),
using primers that amplify the RB1 pocket binding domain and the intron of Tag,
was used to analyze GCT for the presence of SV40 DNA. Tag and FOS protein
expression was evaluated by immunohistochemistry. SV40 sequences were found in
30/107 GCTs, and of these, 22/30 samples expressed Tag protein (73%) and 15/30
overexpressed the FOS oncogene (50%). FOS was undetectable in 77 SV40-negative
GCTs. Sequence analysis of the amplified DNAs confirmed that the amplified
sequences corresponded to SV40 DNA. The correlation between FOS overexpression
and SV40-positive GCTs was highly statistically significant (P < 0.001).
These results show that SV40 DNA sequences and
SV40 Tag are present in GCTs and might induce FOS activity. These data suggest
that SV40 might play a role in the development and progression of some GCTs.
Copyright 2000 Wiley-Liss, Inc.
PMID: 10738299 [PubMed - indexed for MEDLINE]
|
Br J Cancer 2000 May;82(10):1677-81 |
High incidence of SV40-like sequences
detection in tumour and peripheral blood cells of Japanese osteosarcoma
patients.
Yamamoto H, Nakayama T, Murakami H, Hosaka T, Nakamata T, Tsuboyama T, Oka M,
Nakamura T, Toguchida J.
Institute for Frontier Medical Sciences, and Department of Orthopaedic Surgery,
Faculty of Medicine, Kyoto University, Japan.
Recent studies have revealed the evidence for
the significance of SV40 genome in human malignancies. In this paper, the
presence of SV40-like sequences was investigated in 54 Japanese osteosarcomas in
which mutations of the retinoblastoma (Rb), p53, MDM2, and CDK4 genes had been
already analysed. Using polymerase chain reaction and Southern hybridization,
SV40-like sequences were detected in 25 cases (46.3%). In most cases, only a
part of SV40 genome was detected, and the regulatory region containing enhancer
sequences was most frequently found (21/54, 38.9%). There was no apparent
relationship between the presence of SV40-like sequences and tumour suppressor
genes mutations in each tumour. The SV40-like sequences were also detected in
peripheral blood cells of substantial proportion of the patients (43.3%),
whereas the incidence was much lower (4.7%) in normal healthy controls.
This difference is statistically highly
significant (P < 0.0001), suggesting that the presence of SV40-like sequences,
even if only a part, may play some roles to predispose individuals to
osteosarcoma.
PMID: 10817503 [PubMed - indexed for MEDLINE]
AN: 20275204
|
Anticancer Res 2000 Mar-Apr;20(2A):875-7 |
Comment on:
· Anticancer Res. 2000 Mar-Apr;20(2A):879-84.
· Anticancer Res. 2000 Mar-Apr;20(2A):885-9.
· Anticancer Res. 2000 Mar-Apr;20(2A):891-4.
· Anticancer Res. 2000 Mar-Apr;20(2A):895-8.
Simian virus 40: the link with human
malignant mesothelioma is well established.
Carbone M, Rizzo P, Pass H.
Cardinal Bernardin Cancer Center, Loyola University Medical Center, Maywood, IL
60153, USA.
Mesotheliomas are malignancies of the pleural, pericardial, and peritoneal
surfaces with a mean survival of less than 1 year from the time of diagnosis
(1). While mesotheliomas were extremely rare in the first half of this century,
the incidence of these tumors has increased enormously in the last several
decades. Presently, 2-3 thousand people in the US develop and die of
mesothelioma each year (1). It is estimated that approximately 80% of
mesotheliomas develop in people with a history of occupational asbestos exposure
or in individuals with family member(s) professionally exposed to asbestos that
brought home fibers on their clothing (1).
Although conventional wisdom dictates that asbestos is the most commonly
associated "environmental" factor with mesothelioma, asbestos does not transform
human mesothelioma cells in tissue culture (2). This suggests that additional
carcinogens act in concert with asbestos to cause mesothelioma. Recent evidence
indicated that Simian Virus 40 (SV40) preferentially causes mesotheliomas in
hamsters, and that SV40 is present in up to 80% of human mesotheliomas in the US
and in Europe (reviewed in ref. 3 and 4).
Publication Types:
· Comment
PMID: 10810369 [PubMed - indexed for MEDLINE]
AN: 20270666
|
Crit Rev Eukaryot Gene Expr 2000;10(1):45-61 |
The nuclear matrix as a target for viral and
cellular oncogenes.
Deppert W.
Heinrich-Pette-Institut fur Experimentelle Virologie und Immunologie an der
Universitat Hamburg, Germany.
As the key integrator of nuclear structure and function, the nuclear matrix is
likely to be an important target for structural and functional alterations
during the process of neoplastic transformation. Here I summarize and discuss
data demonstrating that the major transforming protein of the small DNA tumor
virus simian virus 40 (SV40), the SV40 large tumor antigen (large T),
specifically targets the chromatin and the nuclear matrix during viral
transformation. I then turn to recent evidence endorsing the concept that mutant
p53--the most commonly expressed oncogene in human cancer--might exert its
oncogenic activities by specifically interacting with the nuclear matrix.
The data suggest that SV40 large T and mutant
p53 might be members of a new family of oncogenes that exert their oncogenic
functions by directly modulating nuclear structure and function.
Publication Types:
· Review
· Review, Tutorial
PMID: 10813394 [PubMed - indexed for MEDLINE]
AN: 20271502
|
Clin Ter 2000 Nov-Dec;151(6):433-8 |