[A case of a teratocarcinoma with retroperitoneal location].
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Adult↗
Biomedical subjects
M Carbone
Publications and source records attributed to M Carbone.
A multi-institutional study confirms the presence and expression of simian virus 40 in human malignant mesotheliomas.
Exposure to the carcinogen asbestos is a major factor in the development of malignant mesothelioma. However, not all mesotheliomas are associated with asbestos exposure, and only a small minority of people exposed to asbestos develop mesothelioma. Therefore, the identification of the cofactors that render certain individuals more susceptible to asbestos or that cause mesothelioma in people not exposed to asbestos has been a major priority of the International Mesothelioma Interest Group. The possible association of SV40 with mesothelioma was recently discussed in a special session at the Fourth International Mesothelioma Interest Group Conference, and it was decided to conduct a multi-institutional study to independently verify the presence of this tumor virus in mesotheliomas. We report the results of this investigation: (a) DNA and protein analyses revealed SV40 sequences and SV40 large T antigen expression in 10 of 12 mesotheliomas tested (83%); and (b) electron microscopy demonstrated variable amounts of asbestos fibers in 5 (71%) of 7 corresponding lung tissues available for analysis. Our results demonstrate that SV40 DNA is frequently present and expressed in mesotheliomas in the United States. Because our data demonstrate that some patients test positive for both SV40 and asbestos, the possibility that these two carcinogens interact should be investigated in future studies.
Asbestos↗
Human mesotheliomas contain the simian virus-40 regulatory region and large tumor antigen DNA sequences.
BACKGROUND: A cohort (20%) of patients with mesothelioma will not have an exposure to asbestos. Recently, a DNA tumor virus (simian virus 40) has been shown to cause hamster mesotheliomas; we previously described simian virus 40-like DNA amino terminus sequences in 29 of 48 mesotheliomas. We analyzed an additional 42 mesotheliomas to determine (1) whether our initial observations were durable and (2) the extent to which the simian virus 40 genome is present in mesotheliomas. METHODS: Genomic DNA was extracted from snap frozen mesothelioma tumor samples and from the simian virus 40-induced hamster mesothelioma tumor H9A. Polymerase chain reaction primers were used to amplify various simian virus 40 large T-antigen regions including a 105-base pair amino terminus fragment, a 281-base pair carboxyl terminus fragment, and a 310-base pair fragment of the enhancer promoter region. Endonuclease digestions and Southern blotting were used to verify the expected product. RESULTS: Thirty of the 42 (71%) samples amplified T-antigen amino sequences, and specificity was verified by Southern hybridization. Sixteen of 42 samples (38%) amplified the appropriate size fragment for the carboxyl terminus, and digestion with BsaB1 matched that of H9A. Twenty-two of 42 samples (52%) amplified simian virus 40 regulatory sequences and Fok1 digestion matched that of the hamster control tumor. Sequence analysis (4 patients) revealed 100% homology with the regulatory region of simian virus 40 strain 776. CONCLUSIONS: These data suggest an association between the simian virus 40 virus and human mesothelioma that could be exploited for diagnostic/therapeutic options including early detection and potential vaccination strategies.
Animals↗
Bactericidal activity of lansoprazole and three macrolides against Helicobacter pylori strains tested by the time-kill kinetic method.
The bactericidal activities of macrolides (clarithromycin, roxithromycin and azithromicyn) and lansoprazole, alone and in combination, against Helicobacter pylori strains were evaluated. It was found that the association of lansoprazole and clarithromycin resulted in a marked synergism, while the combination of roxithromycin or azithromycin with lansoprazole had synergistic and additive effects.
2-Pyridinylmethylsulfinylbenzimidazoles↗
Surgical treatment of scoliosis associated with myelomeningocele.
Twenty-nine patients (mean age 12 years) with severe thoracolumbar and lumbar scoliosis due to myelomeningocele were treated by spinal fusion (7 by posterior arthrodesis with instrumentation, 3 by anterior arthrodesis with instrumentation, 19 by combined anterior and posterior fusion with instrumentation). Fusion was extended to the sacrum in 15 patients. Mean period of follow-up was 6.2 years. The average Cobb angle changes were as follows: thoracic and thoracolumbar curves preoperatively 86 degrees to 45 degrees at follow-up (the final average curve correction was 47%); lumbar curves preoperatively 97 degrees to 48 degrees at follow-up (the final average curve correction was 50%). Average pelvis obliquity changed from 26 degrees to 13 degrees at follow-up with an average correction of 49%. The combined anterior and posterior instrumentation and fusion gave the best correction of deformity (the final average thoracic and thoracolumbar curve correction was 55%; the final average lumbar curve correction was 61%). Independent of the method of stabilization, post-operative wound infection was a serious problem (24%). The combined fusion-instrumentation method reduced the rate of pseudoarthrosis to 14%.
Child↗
Blood saving in children.
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Blood Loss, Surgical↗
Identification of peptides for immunotherapy of cancer. It is worth the effort.
As the nature of the T cell immune response is defined by T cell receptor recognition of small protein fragments, referred to as peptides, the identification of peptides would lead us to understanding and directing the T-cell-mediated immune response. Immunogenic peptides might be used for vaccination and activation of the immune reaction against cancer- and virus-infected cells. Additionally, the knowledge of immunogenic peptides was expected to lead to blocking of allergic reactions and autoimmune diseases. Based on these assumptions, the search for immunogenic peptides was started in mice and man in the mid-1980s. After a decade of peptide identification and testing in vitro and in vivo, this may be a proper time to evaluate the results from the peptide-related work and determine the possible applications of this knowledge for the next decade. In this review we discuss the identification of peptides, their use in murine models, as well as clinical data from peptide vaccinations or therapies. Potential hazards and limitations of peptide use in immunotherapy and other possible applications for peptides or peptide motifs in immunotherapy are evaluated.
Animals↗
[Integrated study of fecal incontinence with defecography, anal ultrasonography, perineography, and manometry].
INTRODUCTION: Imaging methods such as defecography, anal US and perineography, combined with manometry, now permit to identify a growing number of causes of anorectal and pelvic floor deficiency. Fecal incontinence patients can thus be approached correctly relative to both diagnosis and treatment. We investigated the role of these techniques in the work-up of fecal incontinence. MATERIAL AND METHODS: Thirty-eight subjects suffering from fecal incontinence were examined. Defecography was carried out with a special commode and videorecorded on a VHS cassette. Anal US was performed with a 7-MHz rotating probe (type 1846) with 3-cm focus length. Perineography was carried out in 15 female patients. RESULTS: The anorectal angle (ARA) at rest was increased (mean: 106 degrees; normal range: 90-100 degrees) in 34 cases; involuntary barium leakage was seen in 8 patients, especially on coughing. On squeezing, ARA was normal in 10 cases (mean: 72 degrees; normal range: 60-90 degrees); in 5 cases of puborectal hypotonia there was no angular excursion between rest and squeezing (mean: 105 degrees). During evacuation, the average ARA value was 166 degrees in 21 cases and ARA stretched to verticalization in 8 cases (mean: 179 degrees). Morphofunctional anorectal changes appeared as rectal mucosal prolapse (12 cases), rectocele (10 cases), perineal descent syndrome (8 cases) and external rectal prolapse (3 cases). Anal US identified 15 interruptions in sphincterial rings: 12 patterns were hypoechoic, 2 mixed and 1 hyperechoic. Atrophic thinning of internal anal sphincter was seen in 5 idiopathic incontinence patients. Perineography demonstrated cystocele in 5 cases and cystourethrocele in 1 case. Manometry showed sphincterial hypotonia at rest in 15 cases, lower values of anorectal pressure on squeezing in 8 and smaller air volumes inhibiting external sphincterial tone in 19 cases. CONCLUSIONS: Defecographic studies with evaluation of ARA and its changes are an important tool with high diagnostic yield. When combined with other techniques, they provide differential criteria for sphincterial and puborectal causes and permits to identify associated pelvic floor dysfunctions. We believe that defecography, anal US (and perineography in complex disorders) are necessary techniques for the correct clinical approach to fecal incontinence patients, whose role and diagnostic yield are a valid support to manometry.
Adult↗
[Atypical Bouveret syndrome: gallbladder calculus migrated to the stomach in biliary ileus. Report of a case].
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Abdominal Pain↗
The biological activities of simian virus 40 large-T antigen and its possible oncogenic effects in humans.
Simian virus 40 (SV40) is an oncogenic virus which induces tumors in hamsters and transforms human cells in tissue culture. Between 1955 and 1963, polio vaccines and adenovaccines were contaminated with SV40; therefore, millions of people were exposed to this oncogenic virus. The SV40 proteins responsible for in vivo oncogenesis and in vitro cell transformation are encoded by the early region of the virus. These proteins are called T (tumor) antigens (Tags), because animals with tumors induced by SV40 have antibodies against these viral proteins. Recently, we and other research laboratories have found SV40 in specific types of human tumors: mesothelioma, ependymoma and choroid plexus tumors, osteosarcoma and sarcoma. The same tumor types will develop in hamsters which have been injected systemically with SV40. SV40 causes cell transformation in tissue culture and tumors in animals, because SV40 Tag binds and inactivates the cellular tumor suppressor gene products, Rb and p53. We found that SV40 Tag binds p53 and Rb in human mesotheliomas, possibly contributing to the malignant phenotype.
Animals↗
Simian virus 40 and human cancer.
Deoxyribonucleic acid (DNA) oncoviruses can induce neoplastic transformation by interfering with proliferative proteins. Simian virus 40 (SV40) has been shown to induce brain tumors, osteosarcoma, lymphoid tumors and malignant mesothelioma in hamsters and SV40-like DNA sequences corresponding to the Rb-pocket binding domain of SV40 T-antigen (Tag) have been detected in the same human tumors. Since only a small percentage of people exposed to asbestos fibers develop a malignant mesothelioma, SV40 has been suspected to co-operate with the fibers in the neoplastic transformation or even to itself induce the onset of malignant mesothelioma in patients without expositive history. The mechanism that seems to be involved in the SV40-induced carcinogenesis process is mediated by interaction of Tag, both with p53 and Rb proteins, leading to their functional inactivation that is responsible for the removal of their inhibitory cell cycle effect which determines the increase of the number of cells entering the G1-S phase. Up to now the source of SV40 human infections has not yet been completely identified even though administration from 1957-1965 of SV40 contaminated polio vaccines is highly suspected. Horizontal infection by sexual transmission has been also hypothesized. Due to the important public health implications further investigations are required in order to establish both the source and the carcinogenetic role of simian virus 40 in humans.
Animals↗
The detection of simian virus 40 in human tumors by polymerase chain reaction.
Simian virus (SV) 40 is a deoxyribonucleic acid (DNA) virus that induces mesotheliomas, ependymomas, bone tumors, and lymphomas in hamsters. In recent years SV40 sequences have been detected in approximately 60% of mesotheliomas and ependymomas, in 33% of bone tumors and sarcomas, and in 13% of lymphomas. Because the amount of human specimens available for molecular studies is usually minimal, the method most commonly used to demonstrate SV40 in human specimens is the polymerase chain reaction (PCR). PCR is a highly sensitive and useful technique. In the PCR reaction, different sets of primers are used for targeting different regions of DNA. The regions of the SV40 genome targeted by PCR include the large T-antigen, the small t-antigen, the origin of replication, and viral protein-1 capsid protein. The use of these different sets of primers to test human tumor specimens for SV40 produce a different percentage of positive results. This is because these experiments revealed that some primers are more specific than others which may also detect sequences belonging to other DNA papovaviruses. Therefore, the combined use of different sets of primers is recommended when it is important to distinguish SV40 from other related papovaviruses such as BK and JC, which can also be occasionally present in human cells. Furthermore, these experiments demonstrated that polymerase chain reaction analyses for simian virus 40 can be performed better and easier when using deoxyribonucleic acid extracted from fresh and/or frozen tissue. Deoxyribonucleic acid from paraffin embedded specimens should not be used routinely for simian virus 40 testing because of the high risk of obtaining false negative results. However, these paraffin derived deoxyribonucleic acids can be used reliably in molecular laboratories specialized in these type of analyses. This paper describes the methods that we have developed to test simian virus 40 in human specimens.
Base Sequence↗
Cellular immunity and immunotherapy against deoxyribonucleic acid virus-induced tumors.
An important role in the immune defense against deoxyribonucleic acid virus induced tumors is mediated by T-cells, as is evident from aetiological, animal model, and clinical data. In this review the most recent observations in this field are described for three prominent members of this family of viruses, namely human papillomavirus associated with human cervical cancer, human adenovirus associated with lung infections in humans and tumors in rodents, and simian virus 40 associated with rodent tumors and human mesothelioma, osteosarcoma and ependymoma.
Animals↗
Immunobiology and immune defense mechanisms of mesothelioma cells.
Malignant mesothelioma (MM) is an aggressive tumor whose incidence is expected to rise in future years. Patients with this neoplasm have a poor prognosis. Immunotherapy has been shown to be effective in some neoplasms (e.g. melanoma), significantly improving their prognosis but we do not yet have sufficient data on the capability of MM cells to elicit an immune response. A "three step" event is required to determine an immune response: adhesion, recognition, and costimulation between the antigen presenting cells and the immunoeffector cells. Lack of one of these three steps leads to a defective immune response. The most important mechanism determining the defective immune response to the tumor cells is supposed to be the deficiency of the molecules involved in this "three step event", the release of immuno-depressant factors by the tumor cells and/or the tumor infiltrating cells and the lack of surface immunogen epitopes. Investigations on MM cells are not univocal, suggesting that, at least in some cases, an effective immune response to this neoplasm can occur. Blocking the release of immunodepressant factors by malignant mesothelioma cells and identification of effective, specific immunogen epitopes seem to be the most promising objective to achieve.
Asbestos↗
Recurrent chromosome 6 abnormalities in malignant mesothelioma.
The long latency period between asbestos exposure and the onset of malignant mesothelioma (MM) suggests that a multistep tumorigenesis process occurs whilst the capability of asbestos fibres to interfere directly with chromosomes focuses on the critical role of the chromosomal abnormalities in this neoplasm. The aim of our study was to identify any recurrent chromosomal changes in ten primary MM cell cultures derived from pleural effusions of patients with MM from the same geographic area and environmental and/or occupational exposure to asbestos fibers. Cytogenetic analysis was performed in accordance with International System for Human Cytogenetic Nomenclature. Our results confirmed a great number of cytogenetic abnormalities in MM cells. Recurrent loss of the long arms of chromosome 6 (6q-) was the most frequent abnormality detected (four epithelial and two mixed subtypes) while, on the whole, abnormalities of chromosome 6 were found in nine out of ten cases whereas chromosome 6 was normal only in the case with fibromatous subtype. Monosomy 13 and 17 was found in five cases, monosomy 14 in four cases and 22 in three cases. Since deletion of 6q- was detected even in relatively undisturbed karyotype, we hypothesize a multistep carcinogenic process in which deletion of 6q- is an early event in the development and progression of malignant mesothelioma.
Adult↗
Evidence for and implications of SV40-like sequences in human mesotheliomas and osteosarcomas.
Pleural mesotheliomas and osteosarcomas develop in hamsters injected intracardially with SV40. Using primers specific for the RB-pocket binding domain of SV40 we analysed with the polymerase chain reaction frozen specimens from 48 human mesotheliomas and 145 human bone tumours. We found that 60% of human mesotheliomas and 33% of human bone tumours contained SV40-like DNA. Immunostaining, Western blot and RNA in situ hybridization experiments revealed SV40 Tag expression in human mesotheliomas. Osteosarcomas were not studied for Tag expression because not enough material was available. Finally, antibodies anti-Tag were detected in the sera collected from patients with mesothelioma. These data indicate that SV40, or a closely related virus, is/are present in human mesothelioma and osteosarcoma.
Animals↗
Simian virus 40-like DNA sequences and large-T antigen-retinoblastoma family protein pRb2/p130 interaction in human mesothelioma.
The oncoprotein of the Simian virus 40, SV40 large T-antigen (Tag), is reported to target and inactivate growth-suppressive proteins such as the retinoblastoma (Rb) family and p53 leading to transformation of human cell lines in vitro, to produce tumours in rodents, and to be detected in several human cancers including mesothelioma. In support of the potential role of SV40 Tag in the pathogenesis of certain human cancers, we have found SV40-like sequences in 8/25 bioptic specimens of mesothelioma from patients with exposure to asbestos fibres. We have also demonstrated that the SV40 Tag detected in human mesothelioma binds the retinoblastoma family protein pRb2/p130 in 5/5 specimens studied. We submit that the tumorigenic potential of SV40 Tag in some human mesotheliomas may arise from its ability to interact with and thereby inactivate several tumour and/or growth suppressive proteins in cooperation with asbestos fibres in inducing pleural mesothelioma.
Aged↗
Further validation of SV40-like DNA in human pleural mesotheliomas.
We have confirmed in a second set of patients having human pleural mesothelioma that DNA for regions of the amino terminus of SV40 Tag can be amplified by the polymerase chain reaction. Moreover, other regions, including the carboxy terminus for Tag, and the regulatory region of SV40, are present in these specimens.
DNA, Viral↗