High blood pressure. Causes, symptoms, treatments

Separation and quantitative determination of imipramine and desipramine from rat biological samples by high pressure liquid chromatography.

2017-05-22

Receptor status was confirmed by reverse transcriptase polymerase chain reaction. Cellular activity was measured by a methylthiotetrazole proliferation assay in addition to ER nuclear translocation and mitogen-activated protein kinase activity by immunoassays.

Many forms of endocrine therapy for steroid-sensitive tumours involve regimes of steroid agonist deprivation by administration of steroid antagonists. The partial or short-lived response to such therapy results from the inevitable progression of the tumour cells to a state of steroid insensitivity. Several cell culture systems have shown that steroid ablation results in loss of steroid sensitivity and we have used an in vitro model here to study the influence of steroid antagonists on this progression. Growth of androgen-responsive S115 mouse mammary tumour cells in the long-term absence of steroid results in a loss of androgen-sensitivity. We have studied here the effects of the pure antiandrogen ICI 176,334 on the growth of S115 cells and on their progression to steroid autonomy. Although a pure antiandrogen in its action on these cells with very low toxicity, it had no protective effect against loss of cellular or molecular androgen-responsive parameters. The clinical implications for endocrine therapy are discussed.

Docetaxel followed by hormone therapy of limited duration may provide disease control in subgroups of men experiencing failure after local treatments for PC.

This study examined the optical characteristics of bicalutamide-loaded magnetic/ethylene glycol composite nanoparticles (BMP), as well as their anti-cancer activity against cancer cells. The gamma-Fe2O3 magnetic nanoparticles (MNPs), approximately 20 nm in diameter, were prepared via a chemical co-precipitation method and coated with two surfactants to yield a water-based product. The characteristics of the particles were determined via X-ray diffraction (XRD), field emission scanning electron microscopy, and Raman spectrophotometry. The Raman spectra of the BMP showed peaks at 222, 283, 395, 520, 669 and 1316 cm(-1), with broadened band in comparison to the Raman spectra of the magnetic nanoparticles. The BMP absorbance evidenced a rapid increase, with a broad peak at 409 nm, thus reflecting a good loading of the bicalutamide onto the magnetic nanoparticles. The results of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that the MNPs were non-toxic against human brain cancer cells (SH-SY5Y), human cervical cancer cells (Hela), human liver cancer cells (HepG2), breast cancer cells (MCF-7), colon cancer cells (CaCO2) and human prostate cancers (Du 145, PC3) tested herein. In particular, BMPs were cytotoxic at 56% against DU145 cells, at 74.37% in SH-SY5Y cells, and at 58% in Hela cells. Our results demonstrated the biological applicability of BMP nanoparticles as anticancer agents and as agents for enhanced drug delivery against human prostate cancer cells. Our results indicated that the MNPs were biostable and that the BMP functioned effectively as drug delivery vehicles.

The androgen receptor (AR) is a transcription factor that mediates androgen action. We have used the green fluorescent protein (GFP) technique to investigate dynamics of nuclear trafficking of human AR in living cells. In the absence of ligand, the GFP-AR fusion protein is distributed between cytoplasm and nuclei. Androgen exposure leads to a rapid and complete import of GFP-AR to nuclei of CV-1 cells (>=90% nuclear in 30 minutes), whereas a pure antiandrogen, Casodex, elicits a slower (<40% nuclear in 30 minutes) and incomplete transfer. Unliganded ARs with mutations in the basic amino acids of the bipartite nuclear localization signal (NLS) within the second zinc finger and the hinge region are predominantly cytoplasmic and their androgen-dependent nuclear import is severely compromised ((3/4)20% nuclear in 30 minutes). Interestingly, substitutions of the Leu residues flanking the bipartite NLS lead to inefficient nuclear transfer in response to androgen ((3/4)20% nuclear in 30 minutes). The ligand-binding domain of AR, which represses bipartite NLS activity, contains an agonist-specific NLS. The small nuclear RING finger protein SNURF, which interacts with AR through a region overlapping with the bipartite NLS, facilitates AR import to nuclei and retards its export on hormone withdrawal. More AR is associated with the nuclear matrix in the presence than absence of coexpressed SNURF. We suggest that the SNURF-mediated tethering of AR in nuclei represents a novel mechanism for activating steroid receptor functions.

DHT inhibits adipogenic differentiation of hMSCs and human preadipocytes through an AR-mediated pathway, but it does not affect the proliferation of either hMSCs or preadipocytes. Androgen effects on fat mass represent the combined effect of decreased differentiation of fat cell precursors, increased lipolysis, and reduced lipid accumulation.

This ongoing programme is clarifying the role of early or adjuvant antiandrogen therapy in prostate cancer. Patients with localized disease do not appear to derive clinical benefit from added bicalutamide. However, adding bicalutamide 150 mg to standard care provides significant clinical benefits in patients with locally advanced prostate cancer, irrespective of primary therapy.