Check for updates
(1 + N)2 ≤ |g + Niu|| ||g - Niu||.
By (1), the right member
=|g2 + N2u | ≤ N + Nº,
where we have now selected N > |g2|.
The contradiction (1 + N)2 ≤ N + N2 shows that b + d = 0. Applying the same argument to if shows that a = c, whence f*(x) = f(x).
1 Gelfand, I., and Neumark, M., “On the Imbedding of Normed Rings into the Ring of Operators in Hilbert Space,” Rec. Math., 12 (54), 197-213 (1943).
PREVENTION OF ADRENAL CORTICAL CARCINOMA BY DIETHYLSTILBESTROL*, t BY GEORGE W. WOOLLEY AND C. C. LITTLE ROSCOE B. JACKSON MEMORIAL LABORATORY, BAR HARBOR, MAINE Communicated August 8, 1946
It has been observed that adrenal cortical carcinomas, normally expected in JAX strain ce mice when gonadectomized soon after birth, did not appear following treatment of such mice with a synthetic estrogenic hor- mone, diethylstilbestrol.
In the present experiments fusion pellets, 25 per cent diethylstilbestrol in cholesterol, av. wt. 4.8 mg., were used.1 These were introduced into the subcutaneous tissue of the right axilla when the mice were approxi- mately 7 weeks of age. Only one pellet was used at this age in each mouse and none were implanted later in life.
Experimental mice were prepared by removing the gonads of strain ce mice immediately after birth. Adrenal cortical carcinomas had previously been observed in 100 per cent of gonadectomized female mice of this strain 6 months of age and older.2 In gonadectomized male mice these tumors also had occurred starting at 7 months.3
Diethylstilbestrol treated mice of both sexes observed up to 14 months of age did not have these tumors (table 1).
Diet and other environmental factors were kept as near constant as possible in all groups.
Although time has not been sufficient for protection to be observed for mice of extremely advanced ages, the present results are encouraging for continued protection, since nodular hyperplasia of the adrenal cortex which preceded the occurrence of carcinomas in previous experiments was also prevented by the use of diethylstilbestrol pellets.
Downloaded from https://www.pnas.org by NATIONAL INSTITUTES OF HEALTH NIH on April 4, 2026 from IP address 130.14.25.182.
Further study needs to be made to find a protective agent for tumors of the adrenal cortex which will not at the same time cause other serious body disturbances. In the present experiments pituitary tumors of the type caused by estrogenic hormones were observed in the diethylstilbestrol treated mice as early as 7 months of age.
The problem of whether the presence of pituitary tumors is related to the direct tumor inhibitory action of stilbestrol on the adrenal cortex or whether stilbestrol impairs pituitary action on the adrenal cortex depends for its solution upon further investigation now being planned.
The possibility that the inhibitory action may result from certain effects of a grossly unchanged pituitary must also be considered.
| MONTHS OF AGE AT AUTOPSY | GONADECTOMIZED FEMALES NON-TREATED STILBESTROL | GONADECTOMIZED MALES NON-TREATED STILBESTROL | ||||||
|---|---|---|---|---|---|---|---|---|
| TOTAL NO. | NO. WITH TUMOR | TOTAL NO. | TREATED NO. WITH TUMOR | TOTAL NO. | NO. WITH TUMOR | TOTAL NO. | TREATED NO. WITH TUMOR | |
| 2 | 2 | 0 | 1 | 0 | 4 | 0 | 1 | 0 |
| 3 | 3 | 0 | 1 | 0 | 2 | 0 | 1 | 0 |
| 4 | 4 | 0 | 1 | 0 | 4 | 0 | 1 | 0 |
| 5 | 1 | 0 | 1 | 0 | 1 | 0 | 1 | 0 |
| 6 | 5 | 5 | 0 | 0 | 5 | 0 | 0 | 0 |
| 7 | 4 | 4 | 2 | 0 | 2 | 2 | 2 | 0 |
| 8 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 0 |
| 9 | 2 | 2 | 1 | 0 | 6 | 3 | 1 | 0 |
| 10 | 2 | 2 | 1 | 0 | 4 | 4 | 0 | 0 |
| 12 | 6 | 6 | 1 | 0 | 5 | 5 | 1* | 0 |
| 14 | 2 | 2 | 1 | 0 | 1 | 1 | 1 | 0 |
* This animal was a little under 12 months of age.
The effectiveness of stilbestrol as a substitute for natural gonadal secre- tion in preventing adrenal cortical tumor formation is, however, clear.
* This work has been aided by grants to the Roscoe B. Jackson Memorial Laboratory from the Commonwealth Fund, The Anna Fuller Fund, The International Cancer Research Foundation, The Jane Coffin Childs Memorial Fund and The National Ad- visory Cancer Council.
t Technical assistance of Miss Margaret M. Dickie is gratefully acknowledged.
1 These pellets were kindly prepared by Dr. Michael B. Shimkin, National Cancer Institute, Bethesda, Md.
2 Woolley, G. W., and Little, C. C., Cancer Research, 5 (4), 193-202 (1945).
3 Woolley, G. W., and Little, C. C., Ibid., 5 (4), 211-219 (1945).