Drug delivery systems for oestrogenic hormones and antagonists: the need for selective targeting in estradiol-dependent cancers

Mechanisms of oncogene-induced genomic instability

“…In addition, we observed downregulation of vitamin D receptor (VDR) expression during OIS (Figures 2A&B). This is in line with previous reports showing reduced nuclear VDR activity in mouse fibroblasts expressing oncogenic Ras [96], instability of VDR transcripts in tumor cells [97], and stress-induced senescence in mouse vascular smooth muscle cells lacking VDR [98]. …”

Improved antitumoral properties of pure antiestrogen RU 58668-loaded liposomes in multiple myeloma

“…In fact, clinical trials from phase I to II of oral tamoxifen administration in MM patients have been previously stopped for high neurotoxicity [57,58]. In these trials, tamoxifen was probably not appropriate due to its poor efficacy [14] but it is likely that its administration through drug delivery systems like those described previously [25] and here would have given more encouraging results.…”

“…At micromolar concentrations, we found that it decreases the proliferation of several MM cell lines, mainly by arresting cells at the G1-phase of the cell cycle. Previous investigations have shown that both tissue and cell distribution profiles of anticancer drugs can be controlled by their entrapment in submicronic colloidal systems [24,25]. Furthermore, we previously reported that drug delivery nanosystems improve the antitumoral activity of RU in breast cancer cells and tumors from MCF-7 cells xenografts [26].…”

Improved anti-tumoral capacity of mixed and pure anti-oestrogens in breast cancer cell xenografts after their administration by entrapment in colloidal nanosystems

“…In an in vitro test in which MELN cells were exposed to nanoparticles but separated from cells by culture inserts, both Both nanospheres and nanocapsules made of poly(d,l-lactic acid), PEG-functionalised or not (PEG-PLA and PLA, respectively) and containing the maximum obtainable level of incorporated AE (see [69] for a review) were analysed for their electric charge, their mean diameter, their AE-loading and their size stability at 4 • C. The nanoparticle size was measured by quasielastic laser light scattering using a Nanosizer N4 Plus (Coulter electronics, USA). The amount of AE (either RU or Tam) incorporated into the drug carriers as well as the half-lives of the AE-containing vectors were measured from the capacity of the chosen anti-oestrogen to inhibit E 2 -induced luciferase activity in MELN cells (MCF-7 breast cancer cells stably expressing a luciferase reporter gene driven by an E 2 -inducible promoter -ERE-␤ globin-LUC) [70].…”