Chinghai Kao, Ph.D.

Associate Professor, Department of Urology
Associate Professor, Microbiology & Immunology

 Description and summary of research focus of the laboratory

My research focuses on the regulation of prostate-specific antigen (PSA) promoter in the hormonal-refractory prostate cancer and the development of gene therapy strategy for prostate cancer and osteosarcoma.  Adenocarcinoma of prostate has become a significant health problem and is one of the leading cancers in the industrialized Western world.  It is the most commonly diagnosed cancer and the second leading cause of death from cancer among males in the United States. In local advanced diseases and/or metastatic prostate cancer, androgen withdrawal is able to delay the progression of the disease; but, inevitably, the neoplasm will develop to a hormone-resistant stage, androgen-independent (AI), and will finally lead to death. Human prostate secretes a chymotrypsin-like serine protease, PSA, which is secreted almost exclusively by the prostate epithelial cells that line prostatic acini and ducts. Because PSA secretion property of prostate epithelial cells is inherited by majority of prostate carcinomas and more than 99% of metastatic prostate lesions were found to stain positively for PSA, it has become an useful marker for the detection and monitoring of prostate cancer.  Specially, serum PSA appears to be most useful in staging disease and in monitoring patients after definitive therapy at present.  Upon anti-androgen treatment of prostate cancer, the serum PSA levels of the patients usually dropped precipitously.  However, more than 50% of patients showed a steadily increasing serum PSA 6 months after surgical castration and/or anti-androgen therapy.  The rebound of serum PSA represents progression of prostate cancer to the androgen-independent stage and the failure of endocrine therapy.  Once initial hormone therapy has failed, median survival is only 6 months. Rebound of PSA suggests that the existence of nonandrogen factors in hormone refractory prostate cancers may upregulate PSA promoter activity in these cells.  Understanding the regulation of PSA promoter in hormone refractory cancer cells should provide clues how prostate cancer progresses from AD to AI status; this study will also help in designing an improved PSA promoter for the expression of therapeutic genes in hormone refractory disease. Osteosarcoma is a bone cancer that occurs primarily in teenagers and young adults.  Five-year survival was less than 20 percent, and more than 80 percent of patients developed recurrent disease despite complete resection of the primary tumor. Recurrence of osteogenic sarcoma is usually manifested by metastatic disease.  Osteogenic sarcoma has a propensity to metastasize selectively to the lung parenchyma.  This behavior is likely biologically determined by a unique interaction between metastasizing cells and host tissue. Although chemotherapy appeared to extend the disease-free interval between primary therapy and the development of pulmonary metastases, it did not affect post-thoracotomy survival.  A new agent with selective activity against osteogenic sarcoma, particularly one with a novel mechanism of action, could be a significant complement to current therapies for osteogenic sarcoma.  A recent immunohistochemical study demonstrated that osteocalcin stained positive in primary osteoblastic osteosarcoma and chondroblastic osteosarcoma specimens,  as well as in five of seven fibroblastic osteosarcomas.  These observations support the development of osteocalcin promoter-based toxic gene therapy for the treatment of osteosarcoma pulmonary metastases.  Currently, we are combining several treatment strategies, including chemo gene therapy and local regional delivery of adenovirus, to target this lethal disease.

  • Gotoh A, Ko S-C, Shirakawa T, Cheon J, Kao C, Miyamoto T, Gardner TA, HoL-J, Cleutjens C, Trapman J, Graham FL, Chung LWK.  Development ofprostate-specific antigen (PSA) promoter-based gene therapy forandrogen-independent (AI) human prostate cancer. J. Urol. 160:220-229, 1998.
  • Shirakawa T, Ko S-C, Gardner TA, Cheon J, Miyamoto T, Gotoh A, Chung LWK, Kao C.  In vivo suppression of osteosarcoma pulmonary metastatsis withintravenous osteocalcin promoter-based toxic gene therapy. Cancer GeneTherapy 5:274-280, 1998.
  • Shirakawa T, Gardner TA, Ko S-C, Bander N, Woo S, Gotoh A, Chung LWK, Kao C.  Cytotoxicity of adenoviral-mediated cytosine deaminase plus5-fluorocytosine gene therapy is superior to thymidine kinase plusacyclovir in a human renal cell carcinoma model. J. Urol. 162:949-954, 1999.
  • Yeung F, Trapman J, Kao C, Chung LWK. Regions of prostate specific antigen(PSA) promoter that confer androgen-independent expression of PSA inprostate cancer cells. J Biol. Chem. 275:40846-40855, 2000.
  • Gardner TA, Ko S-C, Yang L, Cadwell JJS, Chung LWK, Kao C. Serum-freerecombinant adenovirus production using a hollow fiber capillary system. BioTechniques 30: 422-427, 2001.

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  • B.Sc.,1981, National Cheng Kung University, Tainan, Taiwan
  • M.S., 1983, National Taiwan University Institute of Biochemical Science, Taipei, Taiwan
  • Ph.D.,1992, University of Wisconsin, Madison, WI
  • Post Doctoral,1992-1993,University of Wisconsin, Madison, WI
  • Post Doctoral,1993-1995, M.D. Anderson Cancer Center, Houston, TX

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