Showing papers by "Charles Huggins published in 1957"

Hormonal influences on mammary tumors of the rat ii. retardation of growth of a transplanted fibroadenoma in intact female rats by steroids in the androstane series

Abstract: Many members of the androstane series profoundly retarded the growth of a transplanted benign mammary fibroadenoma of the rat; the restraint of tumor growth was in direct proportion to the amount of the administered compound until its maximal effect was achieved. Certain steroids closely related to the androstane inhibitors accelerated the growth of the tumor. These effects of divergent sort depend on the molecular structure of the steroid. The molecular structure of androstane derivatives, which is of high significance in modifying the rate of growth of the benign mammary tumor, consists of multiple components. These include (a) the presence and number of ketone and hydroxyl groups in special orientation at specific sites, (b) the sites of dehydrogenation in the molecule, and (c) the presence, number, and state of hydrogenation of alkyl groups at designated molecular positions. These multiple factors determine whether androstane compounds will inhibit growth of the tumor, enhance it, or fail to influence its growth. The androstane compounds which caused either the restraint or the promotion of tumor growth had the common property of inducing proliferation of the normal mammary epithelium. Two mechanisms are involved in the restraint of growth of mammary fibroadenoma by androstane inhibitors. The primary effect is the abolition of action of phenolic estrogens and progesterone when dihydrotestosterone is administered concurrently, presumably through direct action at the tumor cell level A secondary contributory suppressive effect is the depression of ovarian activity, and consequently of the production of phenolic estrogens and progesterone, by these compounds. Transplanted mammary fibroadenoma in the rat possesses neoplastic traits and also some growth properties of normal mammary epithelium; inhibition of these latter by hormonal methods commonly retarded the growth of the tumor. But in hypophysectomized rats dihydrotestosterone failed to inhibit the growth of a mammary fibroadenoma with unusually low hormonal dependence as determined by functional tests of its growth.

Metastatic cancer of the breast treated by adrenalectomy; evaluation and the five-year results.

Abstract: Adrenalectomy was performed in 52 patients with metastatic mammary cancer. There were two postoperative deaths. Objective remissions of varying duration followed in 12 of 32 patients who had bilateral adrenalectomy alone and in 8 of 18 patients who also underwent oophorectomy. The extent of the lesions had little effect on the result, for two patients with metastases so extensive that one appeared moribund survived more than five years with great regression of the neoplasm. Experience led to four criteria for selecting patients most likely to be helped by adrenalectomy: age between 40 and 65 years, indications of slowness of neoplastic growth, a high titer of estrogenic substances in the urine, and a rather well-differentiated appearance of the tumor under the microscope. There was no evidence that simultaneous oophorectomy helped in women older than 54 years.

Differential hypothermia in experimental hepatic surgery; application of this technique to a problem in clinical surgery.

Abstract: Introduction "The whole problem in cases of resection of the liver has turned upon the question of the control of hemorrhage from the wound." 1 Oozing from the cut liver surface results in considerable blood loss and obscures the operative field, making identification and control of bleeding from major vessels difficult. Various techniques of mass hemostasis have been developed to cope with this problem; through-and-through mattress sutures, with or without compression plates, 1,2 cautery, 3 exteriorization and gradual removal of peripheral hepatic lesions. 4 Although success has been reported with these methods, they have the following disadvantages: (1) deliberate resection with definitive hemostasis and control of biliary leakage is not permitted; (2) devitalized tissue is left within the abdomen, and (3) the techniques are suitable only for small peripheral lesions. Preliminary isolation and ligation of vessels supplying and draining the right or left lobe before hepatic lobectomy has been described

Regression of Human Metastatic Mammary Cancer Induced by 3-Methylcholanthrene

Abstract: Summary 3-Methylcholanthrene was administered intramuscularly for 22–102 days to six women with metastatic mammary cancer; five of these patients had been treated earlier with adrenalectomy-oophorectomy. The compound had no beneficial effect in one case. In five cases, there was subjective and objective evidence of inhibition of the malignant process, and in one woman the recession was of major magnitude and had clinical therapeutic significance. The regression of metastatic human mammary cancer induced by 3-methylcholanthrene was remarkable, since the responding neoplasms were not dependent on hormones but were of undifferentiated types which have been hitherto refractory to inhibitory influences. In all the patients there were temporary decreases in the levels of circulating hemoglobin and serum proteins during the administration of 3-methylcholanthrene. These proteins increased in amount after the injections of the polycyclic hydrocarbon were discontinued. It must be emphasized that the administration of 3-methylcholanthrene to man is potentially dangerous, since the compound may give rise to new neoplasms; but a carcinogenic effect was not observed in the patients in the brief period of 9 months.