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@ARTICLE{Bund:167919,
      author       = {T. Bund$^*$ and E. Nikitina$^*$ and D. Chakraborty$^*$ and
                      C. Ernst$^*$ and K. Gunst$^*$ and B. Boneva$^*$ and C.
                      Tessmer$^*$ and N. Volk and A. Brobeil and A. Weber and M.
                      Heikenwalder$^*$ and H. zur Hausen$^*$ and E.-M. de
                      Villiers$^*$},
      title        = {{A}nalysis of chronic inflammatory lesions of the colon for
                      {BMMF} {R}ep antigen expression and {CD}68 macrophage
                      interactions.},
      journal      = {Proceedings of the National Academy of Sciences of the
                      United States of America},
      volume       = {118},
      number       = {12},
      issn         = {1091-6490},
      address      = {Washington, DC},
      publisher    = {National Acad. of Sciences},
      reportid     = {DKFZ-2021-00638},
      pages        = {e2025830118},
      year         = {2021},
      note         = {#EA:F200#LA:F200#},
      abstract     = {Consumption of Eurasian bovine meat and milk has been
                      associated with cancer development, in particular with
                      colorectal cancer (CRC). In addition, zoonotic infectious
                      agents from bovine products were proposed to cause colon
                      cancer (zur Hausen et al., 2009). Bovine meat and milk
                      factors (BMMF) are small episomal DNA molecules frequently
                      isolated from bovine sera and milk products, and recently,
                      also from colon cancer (de Villiers et al., 2019). BMMF are
                      bioactive in human cells and were proposed to induce chronic
                      inflammation in precancerous tissue leading to increased
                      radical formation: for example, reactive oxygen and reactive
                      nitrogen species and elevated levels of DNA mutations in
                      replicating cells, such as cancer progenitor cells (zur
                      Hausen et al., 2018). Mouse monoclonal antibodies against
                      the replication (Rep) protein of H1MSB.1 (BMMF1) were used
                      to analyze BMMF presence in different cohorts of CRC
                      peritumor and tumor tissues and cancer-free individuals by
                      immunohistochemistry and Western blot. BMMF DNA was isolated
                      by laser microdissection from immunohistochemistry-positive
                      tissue regions. We found BMMF Rep protein present
                      specifically in close vicinity of CD68+ macrophages in the
                      interstitial lamina propria adjacent to CRC tissues,
                      suggesting the presence of local chronic inflammation. BMMF1
                      (modified H1MSB.1) DNA was isolated from the same tissue
                      regions. Rep and CD68+ detection increased significantly in
                      peritumor cancer tissues when compared to tissues of
                      cancer-free individuals. This strengthens previous
                      postulations that BMMF function as indirect carcinogens by
                      inducing chronic inflammation and DNA damage in replicating
                      cells, which represent progress to progenitor cells for
                      adenoma (polyps) formation and cancer.},
      keywords     = {BMMF (Other) / antigen (Other) / chronic inflammation
                      (Other) / colon cancer (Other)},
      cin          = {F200 / W170 / F180},
      ddc          = {500},
      cid          = {I:(DE-He78)F200-20160331 / I:(DE-He78)W170-20160331 /
                      I:(DE-He78)F180-20160331},
      pnm          = {316 - Infektionen, Entzündung und Krebs (POF4-316)},
      pid          = {G:(DE-HGF)POF4-316},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:33723077},
      doi          = {10.1073/pnas.2025830118},
      url          = {https://inrepo02.dkfz.de/record/167919},
}