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@ARTICLE{Siqin:303254,
      author       = {S. Siqin$^*$ and M. Rahbari$^*$ and C. Ernst$^*$ and I.
                      Grewe$^*$ and K. Gunst$^*$ and M. Neßling$^*$ and S.
                      Kaden$^*$ and K. Richter$^*$ and L. Häfele$^*$ and L.
                      Feuerbach$^*$ and D. Krunic$^*$ and C. Tessmer$^*$ and I.
                      Hofmann$^*$ and E. Birgin and A. Brobeil and N. Rahbari and
                      M. Heikenwälder$^*$ and T. Bund$^*$},
      title        = {{E}xpression of {B}ovine {M}eat and {M}ilk {F}actor in
                      {H}epatocellular {C}arcinoma and {C}olorectal {L}iver
                      {M}etastasis {P}atients.},
      journal      = {Journal of medical virology},
      volume       = {97},
      number       = {8},
      issn         = {0146-6615},
      address      = {Bognor Regis [u.a.]},
      publisher    = {Wiley},
      reportid     = {DKFZ-2025-01599},
      pages        = {e70507},
      year         = {2025},
      note         = {#EA:D460#LA:D460#},
      abstract     = {Bovine meat and milk factors (BMMFs) are plasmid-like DNA
                      molecules isolated from cow's milk, meat, and human cancer
                      tissues proposed to contribute to the development of
                      specific types of cancer including colorectal cancer (CRC)
                      and breast cancer based on chronic inflammation-associated
                      indirect carcinogenesis. Chronic necro-inflammation of the
                      liver poses a strong risk factor for the induction of
                      hepatocellular carcinoma (HCC), which is associated with
                      high intake of meat. Whether BMMFs contribute to HCC
                      carcinogenesis or the development of colorectal liver
                      metastasis (CRLM) remains unknown. Therefore, in this study,
                      the presence of BMMFs was assessed in the liver of patients
                      with viral and nonviral hepatitis-related HCC (n = 25), CRLM
                      (14) and in healthy liver tissue from autopsy specimens (18)
                      using monoclonal antibodies against the conserved BMMF Rep
                      protein for immunohistochemistry, immunofluorescence
                      detection, and immunoblotting. Rep was expressed in all
                      tumor-distant and peritumor tissue specimens of HCC and CRLM
                      patients and associated with CD68+ macrophages around portal
                      triads. The number of Rep+CD68+cells was increased in HCC
                      and CRLM patients compared to healthy liver tissue, which
                      may indicate a link between BMMFs and tumor-associated
                      chronic inflammation in the liver. Exclusively in viral
                      hepatitis-linked HCC, Rep expression was also detected in
                      the tumor. In addition, specifically in the liver of healthy
                      individuals, we observed a well-defined gradient Rep
                      expression in hepatocytes around the central veins.
                      Altogether, these observations may indicate that the
                      presence of BMMFs in the liver is associated with chronic
                      inflammation and may represent a novel risk factor or
                      surrogate marker for liver cancer.},
      keywords     = {Humans / Carcinoma, Hepatocellular: pathology / Liver
                      Neoplasms: pathology / Liver Neoplasms: secondary /
                      Colorectal Neoplasms: pathology / Animals / Female / Male /
                      Cattle / Middle Aged / Aged / Immunohistochemistry / Liver:
                      pathology / Adult / Milk: chemistry / bovine meat and milk
                      factors (BMMFs) (Other) / chronic inflammation (Other) /
                      chronic viral hepatitis (Other) / colorectal liver
                      metastasis (Other) / hepatocellular carcinoma (Other) /
                      infectious indirect carcinogenesis (Other)},
      cin          = {D460 / D440 / W230 / B330 / W210 / W170},
      ddc          = {610},
      cid          = {I:(DE-He78)D460-20160331 / I:(DE-He78)D440-20160331 /
                      I:(DE-He78)W230-20160331 / I:(DE-He78)B330-20160331 /
                      I:(DE-He78)W210-20160331 / I:(DE-He78)W170-20160331},
      pnm          = {314 - Immunologie und Krebs (POF4-314)},
      pid          = {G:(DE-HGF)POF4-314},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40741925},
      doi          = {10.1002/jmv.70507},
      url          = {https://inrepo02.dkfz.de/record/303254},
}