Despite advances in radiation, chemotherapy and surgery, the overall prognosis in soft tissue sarcomas remains poor. Newer modalities are necessary. The finding of a significant subset of soft tissue sarcomas with steroid receptor suggests that endocrine therapy may be such a modality. However, the functionality of these receptors remains to be demonstrated.
The specific aims are therefore to develop in vitro and in vivo soft tissue sarcoma models characterized by steroid receptors and then carry out appropriate endocrine manipulations on them. Soft tissue sarcomas will be obtained fresh and placed in tissue culture and athymic mice. A portion will be kept for light and electron microscopy and steroid receptor analysis via a modified DCC method. Once a tumor line develops in tissue culture or athymic mice it will be manipulated by addition/ablation experiments based on its steroid receptor characterization. For example, a liposarcoma which was estrogen receptor positive would have in vitro growth studies with increasing doses of estradiol and studies with estradiol and tamoxifen. For in vivo studies, the growth, latency, metastasis of tumor in animals treated with estradiol, tamoxifen and oophorectomy would be compared. Similar experiments would be carried out on an estrogen receptor negative tumor and the results analyzed. Comparable experiments on other soft tissue sarcoma models would be carried out. It would be assumed that these sets of experiments would define the function of the steroid receptor in this group of tumors and clarify the role of endocrine therapy as a modality of treatment.
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| Lim, C L; Walker, M J; Mehta, R R et al. (1986) Estrogen and antiestrogen binding sites in desmoid tumors. Eur J Cancer Clin Oncol 22:583-7 |
