Bovine meat and milk factor protein expression in tumor-free mucosa of colorectal cancer patients coincides with macrophages and might interfere with patient survival.

Bovine milk and meat factors (BMMFs) are plasmid-like DNA molecules isolated from bovine milk and serum, as well as the peritumor of colorectal cancer (CRC) patients. BMMFs have been proposed as zoonotic infectious agents and drivers of indirect carcinogenesis of CRC, inducing chronic tissue inflammation, radical formation and increased levels of DNA damage. Data on expression of BMMFs in large clinical cohorts to test an association with co-markers and clinical parameters were not previously available and were therefore assessed in this study.

Structural expression of bovine milk and meat factors in tissues of colorectal, lung and pancreatic cancer patients.

Chronic inflammation, linked to the presence of bovine milk and meat factors (BMMFs) and specific subsets of macrophages, results in oxygen radical synthesis and induction of mutations in DNA of actively replicating cells and replicating single stranded DNA. Cancers arising from this process have been characterized as indirect carcinogenesis by infectious agents (without persistence of genes of the agent in premalignant or cancers cells). Here, we investigate structural properties of pleomorphic vesicles, regularly identified by staining peritumor tissues of colorectal, lung and pancreatic cancer for expression of BMMF Rep.

Analysis of chronic inflammatory lesions of the colon for BMMF Rep antigen expression and CD68 macrophage interactions.

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).

A specific class of infectious agents isolated from bovine serum and dairy products and peritumoral colon cancer tissue.

The analyses of 109 replication-competent genomic DNA sequences isolated from cow milk and its products (97 in the bovine meat and milk factors 2 group - BMMF2, and additional 4 in BMMF1) seems to place these in a specific class of infectious agents spanning between bacterial plasmid and circular ssDNA viruses. Satellite-type small plasmids with partial homology to larger genomes, were also isolated in both groups. A member of the BMMF1 group H1MBS.

Wound healing revised: a novel reepithelialization mechanism revealed by in vitro and in silico models.

Wound healing is a complex process in which a tissue's individual cells have to be orchestrated in an efficient and robust way. We integrated multiplex protein analysis, immunohistochemical analysis, and whole-slide imaging into a novel medium-throughput platform for quantitatively capturing proliferation, differentiation, and migration in large numbers of organotypic skin cultures comprising epidermis and dermis. Using fluorescent time-lag staining, we were able to infer source and final destination of keratinocytes in the healing epidermis.

Spatial quantification and classification of skin response following perturbation using organotypic skin cultures.

Motivation: For a mechanistic understanding of skin and its response to an induced perturbation, systems biology is gaining increasing attention. Unfortunately, quantitative and spatial expression data for skin, like for most other tissues, are almost not available.

Results: Integrating organotypic skin cultures, whole-slide scanning and subsequent image processing provides bioinformatics with a novel source of spatial expression data.

Robust gridding of TMAs after whole-slide imaging using template matching.

Tissue microarrays (TMAs) represent an important approach for the high-throughput cellular analysis of large numbers of tissue samples on one single slide in research related to diagnostics and oncology. Whole-slide imaging now enables full scanning and subsequent image analysis of such TMAs. In contrast to automatically spotted RNA microarrays, TMAs are fabricated manually and mechanically by arranging hundreds of tissue cores in a single paraffin block.