Advancing Biomedical Science through Tissue Arrays |
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Array-Based Pathology Model
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An Example of Pathology-Model Based Target Validation |
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| Background: In vitro studies had shown that molecule y could stimulate proliferation of peripheral blood lymphocytes and increase cytotoxicity of NK cells. In the absence of a suitable antibody, a RNA probe was generated for fast ISH tissue profiling. The purpose of the ISH analysis was to determine the origin of molecule y and to identify any disease processes that might be associated with the molecule. | ||
| Procedures | Results | Picture |
| Probe production | In vitro transcription produced high quality RNA probe (1 - sense template; 2- anti-sense template; 3 - sense RNA probe; 4 - anti-sense RNA probe). |
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| ISH tissue profiling was performed in standard normal tissue and caner arrays, and our inflammatory pathology model. | ISH tissue profiling showed a unique distribution of molecule y in normal tissues (blue bars) and increased levels (of the molecule) in a wide range of inflammatory (red bars) and cancerous (yellow bars) conditions |
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| ISH tissue profiling of molecule y in normal tissue arrays. | Picture shows high expression of molecule y (black-brown staining indicated by blue arrows) in small intestine Paneth cells that are thought to secret molecules for regulation of microbial flora in the gut. |
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| ISH tissue analysis of molecule y in inflammatory pathology model. |
      The
right picture shows high expression level of molecule y in
the infiltrating lymphocytes (black staining indicated by
blue arrows) of a case of inflammatory bowl disease. |
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| ISH tissue analysis of molecule y in inflammatory pathology model. |
  The
right picture shows high level of molecule y in the regenerating
epithelial cells (black staining indicated by blue arrows) in a
case of chronic thyroiditis. |
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| ISH tissue profiling of molecule y in cancer tissue arrays. |
The
right picture shows high level of molecule y in the infiltrating
lymphocytes (black staining indicated by blue arrows) and mild
level in the cancer cells (right lower part) in a case of colon
cancer. |
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| Summary & Conclusion |
In normal tissues, molecule y was detected in Paneth cells of the small intestine, epithelial cells of the prostate and germ cells of the testes. Increased levels of the molecule were observed in a wide range of inflammatory and cancerous conditions including lymphocytes of the reactive lymph node/tonsil, crohn disease, ulcerative colitis, regenerating epithelial cells of chronic thyroiditis, and infiltrating lymphocytes and tumor cells of many tumor types. The increased levels demonstrated in these conditions indicate that the expression of molecule y may be associated with inflammation and general cell stress. |
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