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Breast Clinic


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Breast Clinic

  1. 1. Biology and Therapy of Breast Cancer Metastasis in the Brain and Bone in Nude Mice Lee Su Kim Department of Surgery, Hallym University, College of Medicine Phone No. : +82-31-380-3772 Fax No. : +82-31-385-0157 e-mail : Background The majority of the death of women with breast cancer is the result of metastasis that are resistant to conventional therapies. Patients with breast cancer brain metastases cannot be cured and have a poor prognosis, despite development in diagnostic and therapeutic modalities. Especially, the high mortality rate from breast cancer metastasis has led to the intensive search for molecular alterations contributing to metastatic progression, with the aim of designing targeted therapies. Several reasons account for the failure to treat metastases. First, breast cancers are biologically heterogeneous and contain subpopulations of breast cancer cells with different angiogenic, invasive, and metastatic properties. Second, the process of metastasis selects for a small subpopulation of cells that preexist within parental neoplasm. Third, and perhaps the greatest obstacle for therapy, is that the outcome of metastasis depends on multiple interactions (‘cross-talk’) of metastatic cells with homeostatic mechanisms which the breast cancer cells usurp. Most recent data demonstrate that the organ microenvironment can influence the growth, invasion, and response of metastases to chemotherapy. Therapy of metastasis should therefore be targeted against both the metastatic tumor cells and homeostatic factors that promote metastasis. Two sites where breast cancer metastases are commonly found are brain and bone. Breast cancer is the second most common cause of brain metastasis, after lung cancer, with clinical diagnosis in 10 to 15% of patients, and found at autopsy in 20 to 30% of patients. Bone metastases are found in a higher percentage of patients, up to 90% of
  2. 2. women with metastatic breast cancer. Proposition in breast cancer research works to Columbia University Department of Surgery Although it is well known that breast cancers can metastasize to the brain and bone, relatively little is known about how theses metastases form, and what phenotypes are characteristic of breast cancers with the ability to grow in these organ environments. Without such information, the rational design of new therapies to prevent or control the growth of metastases is impossible. In large part, the progress in understanding the biology of breast cancer metastasis has been limited by the lack of suitable cell lines and experimental models. We propose to develop experimental models, based on the nude mouse models we have already established, to study the pathogenesis of breast cancer metastasis in the brain and bone. Especially, we propose to investigate how these interactions between tumor cells and normal tissue environments affect the development of metastases, using nude mouse models of human cancer metastasis, with a special focus on breast cancer. For the brain metastasis model, we focus on the role of angiogenic factors, including VEGF, and use a model of injection of tumor cells in the intra-carotid artery to simulate dissemination to the brain. For the bone metastasis model, we will analyze the expression of osteolytic cytokine from bone metastasized tissue, and develop a model of breast cancer bone metastasis, utilizing direct injection into mouse tibia bone through knee joint and formation of bone metastases after systemic injection. On the other hand, we propose to study the immunogenic characteristics of breast cancer and the design of effective immunotherapeutic modalities for solid tumor, regional lymph node metastases, and visceral and CNS metastases.
  3. 3. Biographical Sketches M.D., Chung-Ang University College of Medicine (Seoul, Korea), 1985 M.S., Chung-Ang University College of Medicine (Seoul, Korea), 1992 Diplomate, Surgery, Korean Surgical Society, 1993 Ph.D., Chung-Ang University College of Medicine (Seoul, Korea), 1995 Assistant Professor, Department of Surgery Hallym University College of Medicine, 1996 Associate Professor, Department of Surgery Hallym University College of Medicine, 2000 Postdoctoral fellow, UT M.D. Anderson Cancer Center (Houston, TX), 2000 – 2002 Selected Key Publications 1. Dina Chelouche Lev, Lee Su Kim, Vladislava Melnikova, Maribelis Ruiz, Honnavara N. Ananthasswamy and Janet E. Price. Dual blockade of EGFR and ERK1/2 phosphorylation potentiates growth inhibition of breast cancer cells. Submitted for publication to Clinical Cancer Research. 2. Lee Su Kim, Weixin Lu and Janet E. Price. Vascular endothelial growth factor expression promotes the growth of breast cancer brain metastases in nude mice. Submitted for publication to Cancer Research. 3. Weixin Lu, Jindong Su, Lee Su Kim, Corazon D. Bucana, Cherrie Donawho, Junqing He, Isaiah J. Fidler, and Zhongyun Dong. Active Specific Immunotherapy against occult brain metastasis. Submitted for publication to Cancer Research. 4. Claudia Miller, Galina Kiriakova, Lee Su Kim, Kristin L. Weber and Janet E. Price. Characterization of a novel breast cancer cell line established from a bone metastasis. In preparation. 5. Jin Hee Sohn, Lee Su Kim, Seoung Wan Chae, and Hyung Sik Shin. Fine
  4. 4. needle aspiration cytologic findings of breast mucinous neoplasms. Differential diagnosis between mucocelelike tumor and mucinous carcinoma. Acta Cytologica 45(5) : 723-729, 2001 6. Lee Su Kim, Bae Jung Hun, Jung Jin Kim and Sung Kim. The effect of long- term tamoxifen therapy on endometrium evaluated by transvaginal sonography in postmenopausal women undergone breast cancer surgery. J Kor Cancer Assoc 32(3) : 539-544, 2000 7. Lim Min Gyun, Lee Su Kim, Dong Gun Kim and Sung Kim. Identification of Pseudomonas aeruginosa isolated from burn patients by Nested PCR based on outer membrane lipoprotein oprL gene. J Kor Burn Assoc 2(2) : 96-104, 1999 8. Lee Su Kim, Jin Hee Shon and Bong Hwa Lee. Correlation of breast cancer with atypical ductal hyperplasia on fine-needle aspiration cytology speciemens. J Kor Cancer Assoc 31(3) : 517-522, 1999 9. Jin Hee Shon and Lee Su Kim. Infiltrating duct carcinoma encountered in paraffin-injected breast. Plastic Reconstr Surg 102(5) : 1773-1774, 1998 10. Lee Su Kim, Gyun Dong Park, and Sung Kim. Prognostic significance of peritumoral lymphatic vessel invasion in breast cancer. J Kor Cancer Assoc 30(5) : 945-950, 1998 11. Lee Su Kim, Sung Kim and Bong Hwa Lee. Prognostic significance of tumor angiogenesis in breast cancer. J Kor Surg Soc 55(1) : 34-43, 1998 12. Dong Young Nho and Lee Su Kim. Germline mutation of BRCA2 gene in Korean breast/ovarian cancer families. J Kor Cancer Assoc 30(2) : 242-252, 1998