Increasing evidence indicates that at diagnosis tumor dissemination has taken place. It is imperative that there be an understanding of the changes occurring as a result of tumor removal and how the growth of residual tumor is affected. This could aid in design of more effective therapy. In past years under the aegis of this grant our efforts have, for the most part, been aimed at elucidating alterations of host immunity resulting from primary tumor removal. Recently we have also directed our attention toward identifying changes occuring in residual tumor. This proposal is directed toward continuing studies relative to the effect of primary tumor removal on metastatic or incompletely removed tumor.
The aims of the proposal are to investigate (1) the biological effects of primary tumor removal on remaining tumor, (2) the mechanism(s) responsible for the changes in residual tumor cells following primary tumor removal, and (3) the influence of various regimens of systemic therapy on the changes observed with primary tumor removal so as to construct a more precise biological rationale for the use of systemic adjuvant therapy. In these studies we will continue to use two models. In one, C3H mice bearing a large """"""""primary"""""""" and a small distant tumor focus ('metastases"""""""") will be used. Changes in kinetics and estrogen receptor (ER) of tumor cells will be evaluated in the metastases following manipulation of the primary tumor with and without systemic therapy, i.e., alkylating agents, antimetabolites, etc., alone and in combination. All changes will be correlated with tumor growth and survival. The ER will be determined using fluorescent ligand binding (17-FE). Using an aliquot of the same cell suspension kinetic parameters will be detemined in-vitro. The role of humoral and cellular factors as instigators of the changes will be investigated. The second model will employ a DMBA tumor in Fischer rats. Investigations will be directed toward determining why a profound difference in the proportion of ER containing tumor cells exists between the primary and the spontaneously occurring lymph node metastases.
| Fisher, B; Saffer, E; Rudock, C et al. (1989) Effect of local or systemic treatment prior to primary tumor removal on the production and response to a serum growth-stimulating factor in mice. Cancer Res 49:2002-4 |
| Fisher, B; Gunduz, N; Coyle, J et al. (1989) Presence of a growth-stimulating factor in serum following primary tumor removal in mice. Cancer Res 49:1996-2001 |
| Fisher, B; Saffer, E A; Deutsch, M (1986) Influence of irradiation of a primary tumor on the labeling index and estrogen receptor index in a distant tumor focus. Int J Radiat Oncol Biol Phys 12:879-85 |
