Pituitary models

pre-printPituitary tumor animal models provide researchers a microenvironment that simulates the clinical situation; however, in comparison with astrocytoma and meningioma tumor research where intracranial xenograft transplantations are increasingly being used to test various therapeutic modalities, in vivo therapeutic research on pituitary animal models focuses on direct drug therapy to the tumor because of the lack of established intracranial pituitary tumor models. The rat subcutaneous prolactin-secreting pituitary model allows investigators to noninvasively measure tumor size and the effect of direct tumor-guided therapy in a serial manner and is considered biologically relevant because it has proven to be histologically, immunocytochemically, and ultrastructurally consistent with human pituitary tumors

Antiprogestin mifepristone inhibits the growth of cancer cells of reproductive and non-reproductive origin regardless of progesterone receptor expression

<p>Abstract</p> <p>Background</p> <p>Mifepristone (MF) has been largely used in reproductive medicine due to its capacity to modulate the progesterone receptor (PR). The study of MF has been expanded to the field of oncology; yet it remains unclear whether the expression of PR is required for MF to act as an anti-cancer agent. Our laboratory has shown that MF is a potent inhibitor of ovarian cancer cell growth. In this study we questioned whether the growth inhibitory properties of MF observed in ovarian cancer cells would translate to other cancers of reproductive and non-reproductive origin and, importantly, whether its efficacy is related to the expression of cognate PR.</p> <p>Methods</p> <p>Dose-response experiments were conducted with cancer cell lines of the nervous system, breast, prostate, ovary, and bone. Cultures were exposed to vehicle or increasing concentrations of MF for 72 h and analysed for cell number and cell cycle traverse, and hypodiploid DNA content characteristic of apoptotic cell death. For all cell lines, expression of steroid hormone receptors upon treatment with vehicle or cytostatic doses of MF for 24 h was studied by Western blot, whereas the activity of the G1/S regulatory protein Cdk2 in both treatment groups was monitored <it>in vitro </it>by the capacity of Cdk2 to phosphorylate histone H1.</p> <p>Results</p> <p>MF growth inhibited all cancer cell lines regardless of tissue of origin and hormone responsiveness, and reduced the activity of Cdk2. Cancer cells in which MF induced G1 growth arrest were less susceptible to lethality in the presence of high concentrations of MF, when compared to cancer cells that did not accumulate in G1. While all cancer cell lines were growth inhibited by MF, only the breast cancer MCF-7 cells expressed cognate PR.</p> <p>Conclusions</p> <p>Antiprogestin MF inhibits the growth of different cancer cell lines with a cytostatic effect at lower concentrations in association with a decline in the activity of the cell cycle regulatory protein Cdk2, and apoptotic lethality at higher doses in association with increased hypodiploid DNA content. Contrary to common opinion, growth inhibition of cancer cells by antiprogestin MF is not dependent upon expression of classical, nuclear PR.</p

Can a single model explain both breast cancer and prostate cancer?

<p>Abstract</p> <p>Background</p> <p>The Estradiol-Dihydrotestosterone model of prostate cancer (PC) showed how the interaction of hormones with specific hormone receptors affected apoptosis. The same hormone can produce different effects, depending on which hormone receptor it interacts with.</p> <p>Model</p> <p>This model proposes that the first step in the development of most PC and breast cancer (BC) occurs when aromatase converts testosterone to estradiol (E2). A sufficiently high enough local level of E2 results in telomerase activity. The telomerase activity allows cell division and may lead to BC or PC, which will proliferate if the rate of cell division is greater than the rate of cell death. The effect of hormones on their hormone receptors will affect the rate of cell death and determine whether or not the cancer proliferates.</p> <p>Conclusion</p> <p>By minimizing bcl-2 and maximizing apoptotic proteins, new systemic treatments for BC and PC can be developed that may be more effective than existing treatments.</p