INTRODUCTION Since George Beatson and A. Schinzinger produced remissions of advanced breast cancer by performing bilateral oophorectomy in premenopausal patients more than 100 years ago, the effect of antihormonal therapy on breast cancer has been known. Initial endocrine therapy included oophorectomy, hypophysectomy, and adrenalectomy. The latter two were abandoned when tamoxifen citrate was a...

Phospholipase D (PLD) hydrolyses cellular lipids to produce the important lipid second messenger phosphatidic acid. A PLD enzyme expressed by Pseudomonas aeruginosa (PldA) has been shown to be important in bacterial infection, and NAPE-PLD has emerged as being key in the synthesis of endocannabinoids. In order to better understand the biology and therapeutic potential of these less explored PLD...

An increasing number of premenopausal women use contraception whereas postmenopausal women use hormone replacement therapy (HRT). This long-term hormone therapy poses a high risk of interactions with dietary supplements. Taking estrogens at the same time as selective estrogen receptor modulators (SERMs), biologically-active compounds of glycine soja, Ginkgo biloba or Pimpinella anisum, may dist...

About 70% of breast tumors express estrogen receptor alpha (ERα), which mediates the proliferative effects of estrogens on breast epithelial cells, and are candidates for treatment with antiestrogens, steroidal or non-steroidal molecules designed to compete with estrogens and antagonize ERs. The variable patterns of activity of antiestrogens (AEs) in estrogen target tissues and the lack of syst...

Luminal A breast cancer is the most common breast cancer subtype which is usually treated with selective estrogen receptor modulators (SERMS) like tamoxifen. Nevertheless, one third of estrogen receptor positive breast cancer patients initially do not respond to endocrine therapy and about 40% of luminal A breast tumors recur in five years. In this study, we investigated an alternative treatmen...

Clinical observations suggest that human breast tumors can adapt to endocrine therapy by developing hypersensitivity to estradiol (E2). To understand the mechanisms responsible, we examined estrogenic stimulation of cell proliferation in a model system and provided in vitro and in vivo evidence that long-term E2 deprivation (LTED) causes ‘adaptive hypersensitivity’. The enhanced responses to E2...

Significant medical need exists for new therapy that will increase bone strength beyond what is achieved with anticatabolic bone agents such as bisphosphonates. PTH has shown its ability to increase cancellous bone mass and has a positive impact in reducing the incidence of vertebral fractures. However, its high cost and mode of administration marginalize its widespread usage across the world. ...