Medroxyprogesterone acetate and prednisone in advanced breast cancer. A randomized trial

Jakobsen, Anders; Frederiksen, P. L.; Møller, Klaus; Andersen, Asser S.; Brincker, H; Dombernowsky, P; Hansen, Per Krogh; Hesselius, Inge; Kjær, Mogens

doi:10.1016/0277-5379(86)90007-6

Cited by 11 publications

(5 citation statements)

References 7 publications

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“…The results show that glucocorticoids have modest activity in postmenopausal women. A description of these trials is given in Table 4 [ 5 , 15 , 18 , 19 , 22 , 38 , 47 , 55 , 56 ]. The three earliest trials used response criteria that are not readily comparable to presently used response criteria [ 5 , 19 , 22 ].…”

Section: Resultsmentioning

confidence: 99%

Systematic review of the clinical effect of glucocorticoids on nonhematologic malignancy

Keith

2008

BMC Cancer

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Section: Resultsmentioning

confidence: 99%

Systematic review of the clinical effect of glucocorticoids on nonhematologic malignancy

Keith

2008

BMC Cancer

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“…Of these antiangiogenic steroids, only medroxyprogesterone was assessed in clinical trials, primarily in patients with previously treated breast cancer (25). Study endpoints of partial or complete tumor responses showed only minimal clinical activity and no extension of survival.…”

Section: Antiangiogenic Steroids In Cancer Therapymentioning

confidence: 99%

Antiangiogenic Steroids in Human Cancer Therapy

Pietras

Weinberg

2005

Evidence-Based Complementary and Alternative Medicine

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Despite advances in the early detection of tumors and in the use of chemotherapy, radiotherapy and surgery for disease management, the worldwide mortality from human cancer remains unacceptably high. The treatment of cancer may benefit from the introduction of novel therapies derived from natural products. Natural products have served to provide a basis for many of the pharmaceutical agents in current use in cancer therapy. Emerging research indicates that progressive growth and spread of many solid tumors depends, in part, on the formation of an adequate blood supply, and this process of tumor-associated angiogenesis is reported to have prognostic significance in several human cancers. This review focuses on the potential application in antitumor therapy of naturally-occurring steroids that target tumor-associated angiogenesis. Squalamine, a 7,24 dihydroxylated 24-sulfated cholestane steroid conjugated to a spermidine at position C-3, is known to have strong antiangiogenic activity in vitro, and it significantly disrupts tumor proliferation and progression in laboratory studies. Work on the interactions of squalamine with vascular endothelial cells indicate that it binds with cell membranes, inhibits the membrane Na+/H+ exchanger and may further function as a calmodulin chaperone. These primary actions appear to promote inhibition of several vital steps in angiogenesis, such as blockade of mitogen-induced actin polymerization, cell–cell adhesion and cell migration, leading to suppression of endothelial cell proliferation. Preclinical studies with squalamine have shown additive benefits in tumor growth delay when squalamine is combined with cisplatin, paclitaxel, cyclophosphamide, genistein or radiation therapy. This compound has also been assessed in early phase clinical trials in cancer; squalamine was found to exhibit little systemic toxicity and was generally well tolerated by treated patients with various solid tumor malignancies, including ovarian, non-small cell lung and breast cancers. Clinical trials with squalamine alone or combined with standard chemotherapies or other biologic therapies, including antiangiogenic agents, should be considered for selected cancer patients, and further study of the mechanism of action and bioactivity of squalamine is warranted.

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“…This drug has been shown to inhibit vascularization, collagenolysis, and tumor growth in vivo (Gross et al, 1981;Oikawa et al, 1988;Fujimoto et a]., 1989a,b). Furthermore, the clinical efficacy of this agent has been studied for certain types of breast carcinoma (Jakobsen et al, 1986). Dose-response effect of MPA on PA levels of BAE cells The exquisite sensitivity of BAE cell PA production to MPA was demonstrated by decreases of PA activity at the following doses of MPA: lo-" M, lop7 M, M, and lo-' M, and this resulted in decreases of PA levels of 83%, 83%, 75%, and 39%, respectively, compared to the basal PA activity in the conditioned medium (data not shown).…”

Section: Effect Of Heparin On Bae Cell Pa Activitymentioning

confidence: 99%

Section: Effect Of Heparin On Bae Cell Pa Activitymentioning

confidence: 99%

Mechanism of action of angiostatic steroids: Suppression of plasminogen activator activity via stimulation of plasminogen activator inhibitor synthesis

Blei

Mignatti

et al. 1993

Journal Cellular Physiology

132

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Recently, a novel class of angiostatic steroids which block angiogenesis in several systems has been described. Since the elaboration of proteases is believed to be an important component of angiogenesis, we tested whether these steroids blocked the fibrinolytic response of endothelial cells to the angiogenic protein, basic fibroblast growth factor [bFGF]). Cultured bovine aortic endothelial (BAE) cells were incubated with bFGF and/or medroxyprogesterone acetate (MPA), an angiostatic steroid which has been shown to inhibit vascularization, collagenolysis, and tumor growth. When bFGF (3 ng/ml) was added to confluent monolayers of BAE cells, plasminogen activator (PA) activity in the medium was increased threefold. In contrast, MPA at 10(-6) M, 10(-7) M, 10(-8) M, and 10(-9) M decreased PA levels in the medium by 83%, 83%, 75%, and 39%, respectively. The stimulation of PA levels in BAE cells by bFGF (3 ng/ml) was abrogated by the presence of 10(-6) M MPA. This decrease in PA activity was found to be mediated by a significant increase in plasminogen activator inhibitor type-1 (PAI-1) production. MPA, therefore, negated one of the important enzymatic activities associated with the angiogenic process. In contrast to the decreased levels of secreted PA in cultures exposed simultaneously to MPA and bFGF, cell-associated PA levels remained high, consistent with earlier observations indicating that PAI-1 does not inhibit cell-associated PA. Thus, angiostatic steroids may exert their inhibitory effects on angiogenesis by increasing the synthesis of PAI-1. This, in turn, inhibits PA activity and, therefore, plasmin generation, which is essential for the invasive aspect of angiogenesis.

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Medroxyprogesterone acetate and prednisone in advanced breast cancer. A randomized trial

Cited by 11 publications

References 7 publications

Systematic review of the clinical effect of glucocorticoids on nonhematologic malignancy

Systematic review of the clinical effect of glucocorticoids on nonhematologic malignancy

Antiangiogenic Steroids in Human Cancer Therapy

Mechanism of action of angiostatic steroids: Suppression of plasminogen activator activity via stimulation of plasminogen activator inhibitor synthesis

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