844 THE CARCINOGENIC STIMULUS II 



Cortisone may induce the regression of transplanted animal lymphosarcomas 

 (Heilman and Kendall, 1944), not all tumors of this type responding, however. 

 Both cortisone and testosterone independently induced regression of a transplanted 

 lymphosarcoma in pyridoxine deficient rats (Stoerk, 1950), but alone neither 

 was as effective as pyridoxine deficiency per se. Remissions may be obtained in 

 acute human levikemia with cortisone. 



The effect of cortisone on certain non-lymphomatous transplanted tumors is 

 similar to that observed for lymphosarcomas (Higgins and Woods, 1 950 ; Higgins 

 et al., 1950), but many are non-responsive. The Walker tumor grows at a reduced 

 rate in adrenalectomized rats (Talalay et al., 1952; Ingle and Baker, 1951) and 

 tumor size is increased by administering cortisone (Ingle et al., 1950). It has been 

 suggested that the regression of non-lymphomatous tumors by cortisone results 

 from suppression of adrenal cortical activity (Selye, 1955). 



According to Bloom (1952), cortisone induced regression of a canine mast cell 

 tumor. Regression of a carcinogen-induced skin cancer of mice has resulted from 

 administration of a cortical steroid (Zachariae and Asboe-Hansen, 1954). 



The question arises as to whether the effect of adrenalectomy in breast cancer 

 is due to sex hormone withdrawal or the action of specific corticoids of the adrenal 

 cortex? Clinical evidence favors the concept that the benefits of adrenalectomy 

 stem from the withdrawal of extragonadal sex steroid, estrogen or androgen. 

 Experimentally the growth of mammary adenomas of rats has been inhibited by 

 adrenalectomy (Huggins et al., 1956). The growth of mouse mammary cancers 

 arising in young females of the RIII strain is decellerated greater by adrenalec- 

 tomy superimposed on ovariectomy than by ovariectomy alone (Liebelt and 

 Eckles, 1957). The sex steroid secretion by the adrenals of this strain is not appre- 

 ciable even in mice which have been castrated for several months. 



By reducing the host's immune response to foreign tissue, prior treatment 

 with cortisone has favored the growth of homologous (AUam et al., 1954; Foley, 

 1952) and heterologous (Toolan, 1953) tumor grafts. Cortisone is not always 

 effective in bridging this barrier and in one study was useful only when combined 

 with ionizing radiation (Werder<?i al., 1953). Natural resistance to transplantation 

 is more easily overcome than an acquired immune state (Werder et al., 1953). 



INFLUENCE OF CORTISONE ON METASTASIS 



(3) INJECTION l/ 1' ,' -' \ (4) PERSISTENCE 



OF P=P'' / ,-' AND INCREASED 



CORTISONE I f<|' .'' DEVELOPMENT 



U/l OF METASTASES 



(2) EXCISION OF V-Cy 



NEOPLASM V I 



Fie. ':?q. Influence of cortisone on metastases (d transplanted ^ ^ 



^ , , , OR INDUCED 



01 transplanted mouse neoplasms. neoplasm 



(?) The influence of the pituitary gland on the genesis, growth and secretion of tumors 



The development of experimental thyroid (Fig. 2, p. 825), adrenal cortical (Fig. 

 22, p. 833) and gonadal neoplasms (Fig. 8, p. 827) seems to be dependent upon 

 pituitary trophic hormonal stimuli. Suppression of pituitary secretory activity {e.g. 

 by thyroid hormone) may inhibit tumorigenesis which would otherwise have 



