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Influences of social housing conditions on chemotherapeutic efficacy : tumor, host and temporal factors Kerr, Leslie Roxanne

Abstract

Stressful life events and the ability to cope with stress may play an important role in both cancer progression and treatment. A better understanding of the factors that influence tumor and host responses to cancer treatments, including chemotherapy, is essential for the development of improved treatment strategies. Utilizing the transplantable, androgenresponsive Shionogi carcinoma (SCI 15), this thesis tested the hypothesis that psychosocial stressors (social housing conditions), tumor growth rate and/or size, and the temporal relationship between formation of experimental housing conditions and chemotherapy initiation would differentially influence chemotherapeutic efficacy. The possible roles of corticosterone, testosterone and growth hormone in mediating the effects of social housing conditions on tumor and host responses to chemotherapy were also examined. The experimental housing conditions used in these studies included DD/S mice that were reared individually then group-housed (IG), mice that were reared in groups then individually housed (GI) and mice that did not experience a change from their original rearing conditions (II or GG). The studies in this thesis demonstrated that housing conditions differentially influence both SCI 15 tumor and host responses to chemotherapy. Importantly, the temporal relationship between formation of experimental housing condition and chemotherapy initiation significantly influenced the direction and magnitude of the effects of social housing conditions on chemotherapeutic efficacy. The differential effects of housing conditions on tumor and host responses to chemotherapy may be mediated by alterations in basal corticosterone and growth hormone but not testosterone levels within the first week following formation of experimental housing conditions and initiation of chemotherapy. However, the differential effects of housing conditions on tumor and host responses to chemotherapy were independent of tumor growth rate and, at least in terms of host response to chemotherapy, were also independent of tumor burden. The final study of this thesis examined whether social housing conditions and gender interact to affect differentially the growth of a variant of the SCI 15 tumor, designated SCI 15V, that grows equally well in male and female DD/S mice. For both males and females, a change in social housing condition and the direction of change were critical in determining whether SCI 15V tumor growth rates increased or decreased compared to those of mice that did not experience a change. Moreover, social housing condition and exposure to acute daily novelty stress appeared to interact to produce differential effects on SCI 15V tumor growth rates in males and females. The data presented within this thesis indicate that social housing conditions can influence significantly tumor and host responses to chemotherapy. Moreover, these data demonstrate that the direction and magnitude of the effects of social housing conditions on chemotherapeutic efficacy is dependent on the temporal relationship between the formation of experimental housing conditions and initiation of chemotherapy and that the differential effects observed may be mediated, in part, through alterations in basal hormone levels.

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