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Research in Progress

One of the main areas of focus of this research group deals with the development of molecular biological based screens for the discovery of novel agents effective in the treatment of some types of cancer.  These screens will be used to evaluate extracts from a wide range of natural products including plants, marine organisms as well as various micro organisms.  In addition to this random screening program Dr. Pasco also uses clues from traditional medical systems of India, China, and others for identifying source materials that may yield anti cancer agents.

 The laboratories directly under Dr. Pasco’s supervision are focused on the detection of novel anticancer activities within natural products.  Examples of these assays currently in use are listed below:

1. Antiinflammatory-Recent studies have demonstrated the importance of inflammation in various aspects of tumor progression. A battery of luciferase reporter gene constructs are introduced into the human chondrocyte cell line SW1353.  Constructs contain either the promoter for the human cyclooxygenase-2 gene or binding sites for individual transcription factors important for mediating inflammatory signals such as NF-kappa B, AP-1 or Ets2.  This assay has identified compounds that inhibit various aspects of transcription factor activation and have been isolated from plants with scientifically documented antiinflammatory properties.

2. Immune modulation-Luciferase reporter gene construct containing sites for NF-kappa B introduced into the human monocyte cell line THP-1.  Most activators of  monocytes /macrophages influence the activity of this transcription factor and therefore information regarding the activity of this factor is useful for detecting compounds from natural products that modulate macrophage function.

3. Prostate cancer-Luciferase reporter gene construct containing sites for the androgen receptor is introduced into the human prostate cancer cell line LNCaP.  Cells are treated with dehydrotestosterone alone or in combination with plant extracts to detect the presence of compounds that inhibit androgen receptor function.

4. Antiangiogenesis-Screen designed to detect inhibitors of VEGF expression in liver tumors.  The expression and secretion of VEGF by tumor cells is crucial for the development of the vascular system of the tumor.  The Hep 3B cell line is transfected with a luciferase construct containing the promoter of the human VEGF gene.  This screen will detect inhibitors of VEGF expression induced by a combination of hypoxia and cytokines.

 Dr. Pasco's long term research plans includes the search for more effective approaches for the treatment of cancer and other chronic disorders.  These approaches will include both modern medical practices in addition to alternative or traditional therapies.  Through the balanced use of both approaches a new health care system can be developed that focuses on the health of the whole person, physical, mental and spiritual.

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