Abstract
Natural killer (NK) cells are important in surveillance against malignant cells. The activity of NK cells can be modulated by naturally occurring mediators; interferon, interleukin-2, and hormones. Low-dose aminoglutethimide (Ag 250 mg/day) inhibits the peripheral aromatization of androstenedione hence decreasing circulating estrogens. Of ten patients treated, seven were evaluable. There was a statistically significant increase in NK activity (P = 0.0025) following the administration of Ag. There was no consistent shift in NK cell number (Leu-11b positive cells). In vitro Ag did not alter NK activity whereas 17-beta-estradiol did. These data are consistent with an indirect effect of Ag on NK activity. Hence in vivo Ag which causes a reduction in serum estrogens in postmenopausal patients, also induces an increase in NK activity.
MeSH Terms
Aged
Aminoglutethimide/therapeutic use
Breast Neoplasms/drug therapy,immunology
Cell Line
Cytotoxicity, Immunologic/drug effects
Estradiol/pharmacology
Female
Humans
Killer Cells, Natural/drug effects,immunology
Menopause
Middle Aged
Chemicals
Aminoglutethimide
Estradiol
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Berry J
Green B J
Matheson D S
References (20)
20 references, click to expand
-
Oestrogen as an inhibitor of human NK cell cytolysis.
FEBS Lett. 1985 Oct 21;191(1):145-8
PMID: 4054302
-
Aminoglutethimide inhibits extraglandular estrogen production in postmenopausal women with breast carcinoma.
J Clin Endocrinol Metab. 1978 Dec;47(6):1257-65
PMID: 263348
-
Endocrine effects of low dose aminoglutethimide alone in advanced postmenopausal breast cancer.
Br J Cancer. 1983 May;47(5):621-7
PMID: 6221746
-
Variation in natural killer activity in peripheral blood during the menstrual cycle.
Br Med J (Clin Res Ed). 1985 Mar 23;290(6472):884-6
PMID: 3919830
-
Aminoglutethimide for the treatment of advanced postmenopausal breast cancer.
Eur J Cancer Clin Oncol. 1983 Jan;19(1):11-17
PMID: 6682769
-
beta-Estradiol reduces natural killer cells in mice.
J Immunol. 1978 Dec;121(6):2193-8
PMID: 722074
-
Aminoglutethimide induced hormone suppression and response to therapy in advanced postmenopausal breast cancer.
Br J Cancer. 1983 Oct;48(4):585-94
PMID: 6684948
-
The use of aminoglutethimide in the treatment of patients with metastatic carcinoma of the breast.
Cancer. 1980 Aug 15;46(4 Suppl):1066-74
PMID: 6249490
-
Spontaneous human lymphocyte-mediated cytotoxicity against tumor target cells. IX. The quantitation of natural killer cell activity.
J Clin Immunol. 1981 Jan;1(1):51-63
PMID: 7334070
-
A monoclonal antibody detecting a 39,000 m.w. molecule that is present on B lymphocytes and chronic lymphocytic leukemia cells but is rare on acute lymphocytic leukemia blasts.
J Immunol. 1983 Dec;131(6):3064-72
PMID: 6358359
-
Natural killer (NK) activity in peripheral blood lymphocytes of patients with benign and malignant breast disease.
Br J Cancer. 1982 Oct;46(4):611-6
PMID: 7138766
-
Human chronic myelogenous leukemia cell-line with positive Philadelphia chromosome.
Blood. 1975 Mar;45(3):321-34
PMID: 163658
-
Do NK cells play a role in anti-tumor surveillance?
Immunol Today. 1980 Nov;1(5):96-100
PMID: 25290166
-
Kinetic, hormonal and clinical studies with aminoglutethimide in breast cancer.
Cancer. 1977 Jun;39(6 Suppl):2948-58
PMID: 194681
-
Hormonal modulation of human natural killer cell activity in vitro.
J Reprod Immunol. 1985 Feb;7(2):105-10
PMID: 3981483
-
Trimethoprim-induced augmentation of human natural killer activity in vitro.
Immunopharmacology. 1982 Feb;4(1):73-7
PMID: 6977516
-
Natural cytotoxicity of peripheral blood lymphocytes and regional lymph node cells in breast cancer in women.
J Natl Cancer Inst. 1981 Sep;67(3):585-90
PMID: 6944530
-
Effective inhibition by low dose aminoglutethimide of peripheral aromatization in postmenopausal breast cancer patients.
Br J Cancer. 1985 Jul;52(1):31-5
PMID: 4015950
-
Studies of human natural killer cells. I. In vivo parameters affecting normal cytotoxic function.
Int J Cancer. 1982 Apr 15;29(4):383-90
PMID: 7085128
-
Effect on natural killer and antibody-dependent cellular cytotoxicity of adjuvant cytotoxic chemotherapy including melphalan in breast cancer.
Cancer Immunol Immunother. 1983;16(2):98-100
PMID: 6420047