Human Papillomaviruses in Buschke-Lowenstein Tumors: Physical State of the DNA and Identification of a Tandem Duplication in the Noncoding Region of a Human Papillomavirus 6 Subtype

Six Buschke-Löwenstein tumors, i.e., highly differentiated squamous cell tumors of the genital region, were shown to contain human papillomavirus 6 (HPV 6) or HPV 11 genomes. The viral DNA was found in an episomal state, including a very small fraction of circular oligomers. HPV 6a and HPV 6d genomes were cloned from two of the tumors. Comparison with HPV 6b, cloned from a benign genital wart (E. -M. de Villiers, L. Gissmann, and H. zur Hausen, J. Virol. 40:932-935, 1981) by restriction mapping and partial sequence analysis, revealed a very high degree of homology with the different HPV 6 subtypes. A tandem duplication of 459 base pairs within the noncoding region of the genome was found in the new subtype HPV 6d. This structural rearrangement in a region containing the putative control elements for early gene transcription might influence the biological potential of that virus. No evidence for rearrangement of this region was found in the HPV DNA from the five other tumors

The search for infectious causes of human cancers: Where and why

AbstractSlightly more than 20% of the global cancer burden can presently be linked to infectious agents, including viruses, bacteria and parasites. This manuscript analyzes reasons for their relatively late discovery and highlights epidemiological observations that may point to an involvement of additional infectious agents in specific human cancers. Emphasis is placed on hematopoietic malignancies, breast and colorectal cancers, but also basal cell carcinomas of the skin and lung cancers in non-smokers

Recognition of Conserved Amino Acid Motifs of Common Viruses and Its Role in Autoimmunity

The triggers of autoimmune diseases such as multiple sclerosis (MS) remain elusive. Epidemiological studies suggest that common pathogens can exacerbate and also induce MS, but it has been difficult to pinpoint individual organisms. Here we demonstrate that in vivo clonally expanded CD4(+) T cells isolated from the cerebrospinal fluid of a MS patient during disease exacerbation respond to a poly-arginine motif of the nonpathogenic and ubiquitous Torque Teno virus. These T cell clones also can be stimulated by arginine-enriched protein domains from other common viruses and recognize multiple autoantigens. Our data suggest that repeated infections with common pathogenic and even nonpathogenic viruses could expand T cells specific for conserved protein domains that are able to cross-react with tissue-derived and ubiquitous autoantigens

Antioxidant-Induced Changes of the AP-1 Transcription Complex Are Paralleled by a Selective Suppression of Human Papillomavirus Transcription

Although E6 and E7 themselves possess intrinsic trans-activation capacity on their homologous promoters (14, 52), constitutive expression of E6 or E7 in immortalized or malignantly transformed human keratinocytes is mainly dependent on the availability of a defined set of transcription factors derived from the infected host cell. AP-1, for example, normally consisting of a heterodimer between c-Fos and c-Jun (for a review, see reference 4), seems to play a central role in transcriptional regulation of viral oncogene expression, since point mutations of the corresponding consensus sequences within the upstream regulatory region (URR) of HPV-16 or HPV-18 almost completely abolish the expression of URR-driven reporter plasmids in transient transfection assays Recent studies have shown that trans-activation and the DNA-binding affinity of AP-1 (1, 44) as well as that of other transcription factors such as NF-B (65, 78) or p53 (29) can be modulated not only via posttranslational modifications such as phosphorylation or dephosphorylation (for a review, see ref- erence 31) but also by alterations of the intracellular redox status. This can be achieved by certain cytokines, which are able to induce a prooxidant state within the cell by generating reactive oxygen intermediates (ROIs) Similar prooxidant conditions can also be generated either by exposing cells directly to hydrogen peroxide (40) or by genotoxic stress after UV irradiation (60), leading in both cases to the activation of AP-1 (74) and NF-B (44). While such intracellular redox changes are normally counterbalanced by antioxidant enzymes like Cu-Zn-superoxide dismutases (48) or oxidoreductases such as thioredoxin In a previous study, we showed that tumor necrosis factor alpha-induced transcription of a chemokine gene encoding monocyte chemoattractant protein 1 (MCP-1) could be completely abrogated when nonmalignant HPV-positive cells were incubated with PDTC prior to cytokine addition (57). Consistent with the aforementioned model of redox modulation of specific genes, detailed promoter analysis has revealed that NF-B and AP-1 are indeed the predominant transcription factors involved in the regulation of this particular chemokine Since AP-1 is also a central transcription factor for efficien

European Academy of Cancer Sciences:Position paper

The European Academy of Cancer Sciences (EACS) is an independent advisory body of well-recognised medical specialists and researchers striving to create a compelling interactive continuum of cancer research, from innovative basic research to implementation of state-of-the-art evidence-based cancer care and prevention. Achieving the above will entail bridging high-quality basic and preclinical cancer research to research on prevention, early detection and therapeutics as well as improving coordination of translational research efforts across Europe. The latter is expected to be expedited through quality assuring translational cancer research in Comprehensive Cancer Centres - entities that link research with the healthcare system - and networks of cancer research centres. Achieving a critical mass of expertise, resources and patients is crucial. Improving late translational research, which involves clinical studies to assess effectiveness, and added value for the health care is also a high priority. Both high-quality Big Data collections and the intelligent use of these data will promote innovation in cancer research and support outcomes research to assess clinical utility, quality of cancer care and long-term follow-up of treated patients. The EACS supports the mission-oriented approach recently proposed by the European Commission in Horizon Europe to deal with major challenges and would like to persuade the EU and its member states to formally launch a mission in cancer to boost and streamline the cancer research continuum in Europe. Building a coherent translational cancer research continuum with a focus on patients and individuals at risk will require, however, foresight as well as the extensive and continuous provision of evidence-based advice to inform policy

Presence of papillomavirus sequences in condylomatous lesions of the mamillae and in invasive carcinoma of the breast

BACKGROUND: Viruses including Epstein–Barr virus (EBV), a human equivalent of murine mammary tumour virus (MMTV) and human papillomavirus (HPV) have been implicated in the aetiology of human breast cancer. We report the presence of HPV DNA sequences in areolar tissue and tumour tissue samples from female patients with breast carcinoma. The presence of virus in the areolar–nipple complex suggests to us a potential pathogenic mechanism. METHODS: Polymerase chain reaction (PCR) was undertaken to amplify HPV types in areolar and tumour tissue from breast cancer cases. In situ hybridisation supported the PCR findings and localised the virus in nipple, areolar and tumour tissue. RESULTS: Papillomavirus DNA was present in 25 of 29 samples of breast carcinoma and in 20 of 29 samples from the corresponding mamilla. The most prevalent type in both carcinomas and nipples was HPV 11, followed by HPV 6. Other types detected were HPV 16, 23, 27 and 57 (nipples and carcinomas), HPV 20, 21, 32, 37, 38, 66 and GA3-1 (nipples only) and HPV 3, 15, 24, 87 and DL473 (carcinomas only). Multiple types were demonstrated in seven carcinomas and ten nipple samples. CONCLUSIONS: The data demonstrate the occurrence of HPV in nipple and areolar tissues in patients with breast carcinoma. The authors postulate a retrograde ductular pattern of viral spread that may have pathogenic significance

Epstein-Barr Virus Stimulates Torque Teno Virus Replication: A Possible Relationship to Multiple Sclerosis

Viral infections have been implicated in the pathogenesis of multiple sclerosis. Epstein-Barr virus (EBV) has frequently been investigated as a possible candidate and torque teno virus (TTV) has also been discussed in this context. Nevertheless, mechanistic aspects remain unresolved. We report viral replication, as measured by genome amplification, as well as quantitative PCR of two TTV-HD14 isolates isolated from multiple sclerosis brain in a series of EBV-positive and -negative lymphoblastoid and Burkitt's lymphoma cell lines. Our results demonstrate the replication of both transfected TTV genomes up to day 21 post transfection in all the evaluated cell lines. Quantitative amplification indicates statistically significant enhanced TTV replication in the EBV-positive cell lines, including the EBV-converted BJAB line, in comparison to the EBV-negative Burkitt's lymphoma cell line BJAB. This suggests a helper effect of EBV infections in the replication of TTV. The present study provides information on a possible interaction of EBV and TTV in the etiology and progression of multiple sclerosis

Wohin geht die Krebsforschung? : Nobelpreisträger Professor Harald zur Hausen im Campus-TV Interview

In einem Gespräch mit dem Nobelpreisträger Prof. Dr. Harald zur Hau­sen vom Deutschen Krebsforschungszentrum geht es um den aktuellen Stand der Krebsforschung. Joachim Kaiser sprach mit dem ehemaligen Chef des Deutschen Krebsforschungszentrums in Heidelberg, der 2008 den Nobelpreis für Physiologie und Medizin für seine bahnbrechenden Forschungen erhielt

Nobelpreisträger Prof. Harald zur Hausen im Campus-TV-Interview

Zum neunten Mal kommt ein Nobelpreisträger aus der Universität Heidelberg. Campus-TV – das Fernsehmagazin der Universität Heidelberg und weiterer Partner –besucht in der Sendung vom 22. Januar 2009 Professor zur Hausen im Deutschen Krebsforschungszentrum. Harald zur Hau-sen wurde vor wenigen Wochen mit dem Nobelpreis für Medizin ausgezeichnet. Der langjährige Leiter des Deutschen Krebsforschungszentrums in Heidelberg, kurz DKFZ, ist seit mehr als dreißig Jahren den Ursachen des Gebärmutterhalskrebses auf der Spur. Der neue Nobelpreisträger ist zugleich Honorarprofessor der Universität Heidelberg sowie Mitglied der Medizinischen Fakultät. Professor zur Hausen fand heraus, dass für etwa 70 Prozent aller Fälle beim Gebärmutterhalskrebs zwei Arten von Papillom-Viren verantwortlich sind. Nobel-preiswürdig war es dann auch, dass es dank seiner Forschung erstmals in der Geschichte der Medizin eine Impfung gegen Krebs, den Gebärmutterhalskrebs, gibt. Über seine Gefühle bei der Verleihung des Nobelpreises am 10. Dezember in Stockholm spricht Professor zur Hausen im Campus-TV-Interview. Außerdem erläu-tert er die Bedeutung seiner Forschung und bekräftigt erneut, wie wichtig die auf seinen Forschungen beruhende Impfung gegen den Gebärmutterhalskrebs ist