The evidence for tamoxifen and chemotherapy as treatment for metastatic melanoma

Rusthoven, James J.

doi:10.1016/s0959-8049(97)10162-9

Cited by 16 publications

(8 citation statements)

References 20 publications

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“…Several phase II trials were conducted with the anti-oestrogen tamoxifen as a single agent or combined with chemotherapy (reviewed by Rusthoven [4]), with contradictory results.…”

Section: Introductionmentioning

confidence: 99%

Androgen receptors in human melanoma cell lines IIB-MEL-LES and IIB-MEL-IAN and in human melanoma metastases

et al. 2002

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The presence and characteristics of androgen receptors (ARs) have been described by our group in one human melanoma cell line. We have now investigated their presence in two other human melanoma cell lines, IIB-MEL-LES and IIB-MEL-IAN, as well as in biopsies from human metastatic melanoma. Scatchard analysis revealed a single binding component for both cell lines, the apparent dissociation constant obtained being 15 nM, with a binding capacity of 280 fmol/mg total cell protein, for IIB-MEL-LES cells and 14 nM, with a binding capacity of 206 fmol/mg total cell protein for IIB-MEL-IAN cells. When specificity was assessed, not only androgen and anti-androgen but also non-androgenic compounds were able to compete for [3H]R1881 binding, as seen before. When immunocytochemistry of IIB-MEL-LES and IIB-MEL-IAN cells was performed for ARs, both cell lines were deeply stained in the nucleus, whereas no staining was found for oestrogen or progesterone receptors. Every specimen of melanoma metastases tested for the presence of ARs was deeply stained, and in the majority the intensity of the staining was high. Several hormones and anti-hormones were tested for their ability to affect cell proliferation. In both cell lines, testosterone, dihydrotesterone, oestradiol and progesterone significantly stimulated cell proliferation, and this was reversed by hydroxyflutamide, bicalutamide or tamoxifen.

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“…Several phase II trials were conducted with the anti-oestrogen tamoxifen as a single agent or combined with chemotherapy (reviewed by Rusthoven [4]), with contradictory results.…”

Section: Introductionmentioning

confidence: 99%

Androgen receptors in human melanoma cell lines IIB-MEL-LES and IIB-MEL-IAN and in human melanoma metastases

et al. 2002

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“…Tamoxifen has been used in clinical trials for patients with melanoma since the late 1970s. Initially it showed promise as a single agent and then was combined with chemotherapy in 1984 (Rusthoven 1998). Since then, a number of phase II clinical trials have combined tamoxifen with different chemotherapeutic agents with overall response rates ranging from 8% to 60%.…”

Section: Serms and Skin Biologymentioning

confidence: 99%

“…Since then, a number of phase II clinical trials have combined tamoxifen with different chemotherapeutic agents with overall response rates ranging from 8% to 60%. However, treatment of melanoma with tamoxifen still remains controversial, since it is still unclear whether the strength of evidence from the randomized trials outweighs the combined evidence from numerous nonrandomized trials (Rusthoven 1998).…”

Section: Serms and Skin Biologymentioning

confidence: 99%

Effect of estrogens on skin aging and the potential role of SERMs

Stevenson

Thornton

2007

CIA

126

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Abstract:In humans, structural and functional changes attributable to aging are more visibly evident in the skin than in any other organ. Estrogens have signifi cant effects on skin physiology and modulate epidermal keratinocytes, dermal fi broblasts and melanocytes, in addition to skin appendages including the hair follicle and the sebaceous gland. Importantly, skin aging can be signifi cantly delayed by the administration of estrogen. This paper reviews the effects of estrogens on skin and the mechanisms by which estrogens can alleviate the changes due to aging that occur in human skin. The relevance of estrogen replacement therapy (HRT) in postmenopausal women and the potential value of selective estrogen receptor modulators (SERMs) as a therapy for diminishing skin aging are also highlighted.

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“…For women with ER-positive breast tumors, tamoxifen results in a 50% annual reduction in the recurrence rate and a 28% annual reduction in the death rate [115,116]. Women with metastatic disease who have ER-positive tumors also benefit from treatment with tamoxifen [117]. In addition, findings that tamoxifen could reduce the incidence of contralateral breast cancer led to breast cancer prevention trials [118].…”

Section: Tamoxifen and Sermsmentioning

confidence: 99%

Advances in estrogen receptor biology: prospects for improvements in targeted breast cancer therapy

2003

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39 AIB1 = amplified in breast cancer; AF-1 = activation function-1; AF-2 = activation function-2; cAMP = cyclic AMP; CBP = CREB-binding protein; DES = diethylstilbestrol; E2 = 17β-estradiol; ER = estrogen receptor; ERE = estrogen response element; EGF = epidermal growth factor; EGFR = epidermal growth factor receptor; FDA = Food and Drug Administration; HAT = histone acetyltransferase; IGF1 = insulin-like growth factor-1; LBD = ligand-binding domain; MAPK = mitogen-activated protein kinase; NR = nuclear receptor; PKA = protein kinase A; SERM = selective estrogen receptor modulator.Available online http://breast-cancer-research.com/content/6/1/39 IntroductionEstrogen receptors (ERs) are members of the nuclear receptor (NR) superfamily that mediate the pleiotropic effects of the steroid hormone estrogen in a diverse range of developmental and physiological processes [1]. Although estrogens are important physiological regulators in the reproductive system, in bone metabolism, and in the maintenance of the cardiovascular and central nervous systems, they have also been associated pathologically with an increased risk for breast and endometrial cancer [2][3][4][5]. Consequently, ERs have been found to be essential in the initiation and development of most of these cancers. Current endocrine therapies for ER-positive breast cancers are primarily designed to target either estrogen or ER levels and/or activity. Use of a partial antiestrogen, tamoxifen, in the management of early-stage breast cancer has clearly demonstrated an increase in both disease-free and overall survival. In addition, recent studies demonstrate that tamoxifen can be used as a chemopreventive agent for hormone-dependent breast cancer. The major concerns of long-term therapy with tamoxifen are its uterotropic effects, which result in an increased risk for endometrial cancer, and the acquired clinical resistance to tamoxifen. This has led to the active pursuit of better selective ER modulators (SERMs) that display the optimal agonistic or antagonistic activities in various estrogen target tissues.In this article we review the emerging studies of ER action that reveal the roles of a wide spectrum of receptor coregulators and their interaction with other cellular signaling pathways. An understanding of the molecular factors that modulate the activity of the estrogen-signaling network provides insight into the mechanism by which SERMs exert their tissue-specific effects. The identification of factors that are responsible for such effects is enabling the development of new ways to overcome resistance to endocrine therapy. Review Advances in estrogen receptor biology: prospects for improvements in targeted breast cancer therapy AbstractEstrogen receptor (ER) has a crucial role in normal breast development and is expressed in the most common breast cancer subtypes. Importantly, its expression is very highly predictive for response to endocrine therapy. Current endocrine therapies for ER-positive breast cancers target ER function at multiple levels. These i...

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The evidence for tamoxifen and chemotherapy as treatment for metastatic melanoma

Cited by 16 publications

References 20 publications

Androgen receptors in human melanoma cell lines IIB-MEL-LES and IIB-MEL-IAN and in human melanoma metastases

Androgen receptors in human melanoma cell lines IIB-MEL-LES and IIB-MEL-IAN and in human melanoma metastases

Effect of estrogens on skin aging and the potential role of SERMs

Advances in estrogen receptor biology: prospects for improvements in targeted breast cancer therapy

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