Angiogenic activity of rat mammary carcinomas induced by 7, 12-dimethylbenz[a]anthracene and its inhibition by medroxyprogesterone acetate: possible involvement of antiangiogenic action of medroxyprogesterone acetate in its tumor growth inhibition

Oikawa, Tsutomu; Hiragun, Akiyoshi; Yoshida, Y.; Ashino-Fuse, Hiromi; Tominaga, Takeshi; Iwaguchi, Takao

doi:10.1016/0304-3835(88)90218-2

Cited by 45 publications

(18 citation statements)

References 14 publications

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“…Consistent with previous findings (Gross et aL, 1981;Oikawa et al, 1988;Jikihara et al, 1992), results in this study showed that MPA inhibited angiogenesis in the rabbit corneal assay system. Wilks et af.…”

Section: Discussionsupporting

confidence: 95%

Angiostatic activities of medroxyprogesterone acetate and its analogues

Yamamoto

Terada

Nishizawa

et al. 1994

Intl Journal of Cancer

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The effects of medroxyprogesterone acetate (MPA) (I) and related compounds (II-VI) upon angiogenesis induced by basic fibroblast growth factor (bFGF) or transforming growth factor-alpha (TGF-alpha) were investigated using a rabbit corneal system for assay of angiogenesis. Dexamethasone (Dex) was used as a positive control. The MPA analogues tested were 6,6'-dehydro-MPA (II), megestrol acetate (III), 1-dehydromegestrol acetate (IV), melengestrol acetate (V), and 1-dehydromelengestrol acetate (VI). The inhibitory activities of these steroids using bFGF were in the order: Dex = MPA = (VI) = (V) > (IV) > (III). Steroid (II) was inactive. 5 alpha-dihydrotestosterone was weakly active, while estradiol-17 beta and progesterone were inactive. The angiostatic activity of MPA was completely abolished by mefipristone (RU 486) which showed no anti-angiogenic activity in this assay. With TGF-alpha, the order of angiostatic activities was Dex = (VI) > (IV) > (III) > (V). Steroid (II) was again inactive. Dex, MPA, and all the MPA analogues except steroid (II) markedly inhibited the activity of plasminogen activator secreted by cultured calf pulmonary artery endothelial cells, but did not inhibit growth of these cells. The binding affinities of MPA and its analogues to glucocorticoid, progesterone and androgen receptors were determined, but were found not to be correlated with their angiostatic activities.

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Section: Discussionsupporting

confidence: 95%

Angiostatic activities of medroxyprogesterone acetate and its analogues

Yamamoto

Terada

Nishizawa

et al. 1994

Intl Journal of Cancer

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“…23) 4) Some hormonal agents have been reported to have anti-angiogenic activity and to induce tumor hypoxia. [24][25][26] It is conceivable that a subclone resistant to apoptosis under hypoxia as well as hormonal agents may selectively survive in hormone-responsive breast cancer. 5) Almost all recurrent breast cancers eventually become resistant to hormonal agents.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia Reduces Hormone Responsiveness of Human Breast Cancer Cells

Kurebayashi¹,

Otsuki

Moriya

et al. 2001

Japanese Journal of Cancer Research

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Resistance to hormonal therapy frequently occurs following successful treatment in breast cancer. The mechanism responsible for this acquired resistance is still unknown. It has been suggested that a hypoxic tumor microenvironment promotes malignant progression of cancer, i.e., hypoxia may promote estrogen-independent growth (a more malignant phenotype) of breast cancer. To clarify this hypothesis, the effects of hypoxia on the growth responses to hormonal agents and the expression levels of estrogen receptor (

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“…As the mechanism of MPA effect, the mechanism directly mediated by receptors (ER, progesterone receptor) [20, 21, 22, 23], a mechanism mediated by the hypothalamus-pituitary gland-adrenal gland system [24, 25], and a mechanism mediated by angiogenesis [26, 27]have been considered. Furthermore, the inhibitory effect on IL-6 was reported recently [9, 10, 11].…”

Section: Discussionmentioning

confidence: 99%

An Analysis of Serum Interleukin-6 Levels to Predict Benefits of Medroxyprogesterone Acetate in Advanced or Recurrent Breast Cancer

Nishimura

Nagao²,

Miyayama³

et al. 2000

Oncology

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Treatment of advanced or recurrent breast cancer with medroxyprogesterone acetate (MPA) shows high response rates and the accessory effects of appetite stimulation, improvement in performance status (PS) and bone marrow protection. In recent years, interleukin-6 (IL-6) has been reported to cause cachexia. In this study, to clarify the significance of IL-6 in advanced or recurrent breast cancer, the relationship between the IL-6 level and clinical findings or effect of MPA was investigated. Sixty-five patients with recurrent or advanced breast cancer participated in a prospective study. The age of patients ranged from 28 to 79 years with an average age of 51.3 years. IL-6 level was investigated in these patients dosed with 800 mg/day of MPA and in 17 postoperative nonrecurrent patients. Serum MPA level was measured by high-performance liquid chromatography and IL-6 level was measured prior to MPA administration, 4 weeks (in 59 cases) and 12 weeks (in 32 patients) after MPA administration by ELISA. Serum IL-6 level was significantly higher in recurrent cases, especially in those with visceral metastasis. Further, in patients for whom MPA therapy was effective, the IL-6 level prior to the treatment was clearly low. The IL-6 level was significantly increased after 4 weeks. However, response to MPA was significantly higher and PS was improved in those cases demonstrating less increased IL-6 levels after 4 weeks. In addition, the effect of MPA was significantly related to a higher serum concentration of MPA-positive ER, and longer disease-free interval, although there was no significant predictive factor for the clinical effect of MPA therapy in multivariate analysis. In conclusion, MPA therapy was effective in cases demonstrating a low IL-6 level and less increased IL-6 levels after 4 weeks. PS was improved in those cases in which the degree of IL-6 increase was suppressed by MPA, and many such cases showed low IL-6 levels prior to MPA therapy. Furthermore, PS was improved even in nonresponders to MPA. Therefore, it is suggested that MPA therapy might be useful in treating recurrent breast cancer, and its benefits might be mediated by IL-6.

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Angiogenic activity of rat mammary carcinomas induced by 7, 12-dimethylbenz[a]anthracene and its inhibition by medroxyprogesterone acetate: possible involvement of antiangiogenic action of medroxyprogesterone acetate in its tumor growth inhibition

Cited by 45 publications

References 14 publications

Angiostatic activities of medroxyprogesterone acetate and its analogues

Angiostatic activities of medroxyprogesterone acetate and its analogues

Hypoxia Reduces Hormone Responsiveness of Human Breast Cancer Cells

An Analysis of Serum Interleukin-6 Levels to Predict Benefits of Medroxyprogesterone Acetate in Advanced or Recurrent Breast Cancer

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