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.