Direct Antitumor Effects of an LH-RH Agonist

Foekens, J.A.; Klijn, J.G.M.

doi:10.1007/978-3-642-73530-1_3

Cited by 3 publications

(3 citation statements)

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ABSTRACTPrevious work showed that hamster and human pancreatic tumors but not normal pancreata exhibit low-affinity cell-membrane receptors for luteinizing hormonereleasing hormone (LHRH (1)(2)(3)(4). The use of LHRH agonists for treatment of prostatic and breast cancer is based on suppression of pituitary-gonadal function and the consequent creation of a state of sex-steroid deficiency (1-4).

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confidence: 99%

“…Inhibition ofthe growth of sex hormone-dependent tumors by analogues of luteinizing hormone-releasing hormone (LHRH) has been demonstrated experimentally and clinically (1)(2)(3)(4). The use of LHRH agonists for treatment of prostatic and breast cancer is based on suppression of pituitary-gonadal function and the consequent creation of a state of sex-steroid deficiency (1)(2)(3)(4).…”

mentioning

confidence: 99%

“…The use of LHRH agonists for treatment of prostatic and breast cancer is based on suppression of pituitary-gonadal function and the consequent creation of a state of sex-steroid deficiency (1)(2)(3)(4). In addition to these indirect effects, LHRH agonists and antagonists exert direct effects on these tumors (2-9) that probably are mediated by specific high-affinity LHRH receptors found on these cells (4,5,7,(10)(11)(12)(13).…”

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confidence: 99%

See 2 more Smart Citations

Localization of receptors for luteinizing hormone-releasing hormone in pancreatic and mammary cancer cells.

Szende¹,

Srkalović²,

Tı́már³

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

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Previous work showed that hamster and human pancreatic tumors but not normal pancreata exhibit low-affinity cell-membrane receptors for luteinizing hormonereleasing hormone (LHRH (1)(2)(3)(4). The use of LHRH agonists for treatment of prostatic and breast cancer is based on suppression of pituitary-gonadal function and the consequent creation of a state of sex-steroid deficiency (1-4). In addition to these indirect effects, LHRH agonists and antagonists exert direct effects on these tumors (2-9) that probably are mediated by specific high-affinity LHRH receptors found on these cells (4, 5, 7, 10-13). Since 1984, it has been shown repeatedly that LHRH agonists and antagonists also suppress the growth of experimental pancreatic cancers (14-17). Exocrine pancreatic cancers could be sex steroid-sensitive (18), and the regression of experimental pancreatic cancers induced by treatment with LHRH agonists or antagonists (14-17) could be explained, in part, by the deprivation of estrogen or androgen. Direct effects mediated by LHRH receptors may also be involved, since LHRH analogues inhibit the growth of Mia PaCa-2 pancreatic cancer cells in vitro (19). Hamster and human pancreatic tumors but not normal pancreata exhibit cell-membrane receptors for LHRH (20,21). However, only low-affinity cell membrane LHRH receptors were found in pancreatic cancer cells (20,21). Here, we extend the examination of LHRH receptors in pancreatic tumor cells to include the nucleus as well as the cell membrane. In addition, we carried out electron microscopic immunohistochemical studies using an antibody to the LHRH receptor to examine (22) (25) was applied. A series of dilutions of the primary antibody in phosphate-buffered saline (PBS: 0.14 M NaCl/8 mM Na2HPO4/3 mM KH2PO4, pH 7.6)/0.05% Tween 80 from 1:10 to 1:10,000 was used for overnight incubation. Colloidal gold-conjugated secondary antibody (goat anti-rabbit IgG antibody conjugated to G10 gold particles, Janssen Pharmaceutica, Olen, Belgium) was diluted 1:50 in PBS/0.05% Tween 80 and incubated with the sections for 1 hr at room temperature. To eliminate nonspecific reactions, all grids were preincubated with normal rabbit serum (1:10) in PBS/ 0.05% Tween 80 for 15 min. Negative controls were incubated only with the gold-conjugated secondary antibody. Sections were viewed, without contrasting and after staining with uranyl acetate, in a JEM 100B electron microscope (JEOL).The average number of gold grains over various cellular structures and in the background was calculated after counting them with a Kontron (Zurich) MOP calculator. Ten photographic pictures (magnification: original, x 15,000-25,000; photooptic, x 35,000-60,000) from each sample were used for counting the grains. The values are given in grains per gm2 for each cellular compartment. LHRH receptors were measured by radioreceptor assay methods in the nuclear and membrane fraction of untreated hamster pancreatic tumor homogenates, as described previously (10,11,13,20,21). The method ofMarian and Conn (26) Abbrevi...

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