The selective vitamin D receptor agonist, elocalcitol, reduces endometriosis development in a mouse model by inhibiting peritoneal inflammation.

BACKGROUND: Endometriosis, which is characterized by the growth of endometrial tissue at ectopic locations as well as vascular development and inflammation, is still an unmet clinical need since an optimal drug that allows for both pain and infertility management does not exist. Since both the eutopic and the ectopic endometrium express the vitamin D receptor (VDR), and VDR agonists are endowed with anti-proliferative and anti-inflammatory properties, we evaluated the effect of elocalcitol, a VDR agonist with low calcaemic liability, in a mouse model of experimentally induced endometriosis. METHODS AND RESULTS: Endometriosis was induced by injection of syngeneic endometrial tissue fragments into adult Balb/c female mice. After having confirmed by immunohistochemistry that endometriotic lesions developing in mice expressed VDR, the mice were administered with elocalcitol (100 µg/kg) or vehicle orally, once a day, for various durations of time. In this model, elocalcitol was able to reduce total lesion weight up to 70% upon treatment for 1 week before and 2 weeks after disease induction. Interestingly, a therapeutic effect was also observed on already established lesions. Elocalcitol was shown to reduce the capacity of mouse endometrial cells to adhere to collagen. In addition in treated mice, a decreased state of peritoneal inflammation was demonstrated by the inhibition of macrophage recruitment and inflammatory cytokine secretion. CONCLUSIONS: The VDR agonist elocalcitol inhibits lesion development in a validated mouse model of endometriosis, and exerts a protective effect on both the implantation and organization of transferred endometrial tissue. These preliminary data in mice provide a sound rationale for further testing in primate models and eventually in humans.

Choline and phosphatidylcholine fluorescent derivatives localization in carcinoma cells studied by laser scanning confocal fluorescence microscopy.

In this study, we have shown the intracellular distribution of choline and phosphatidylcholine fluorescent derivatives in human breast carcinoma cells using confocal microscopy. The fluorescent choline derivatives ethanamimium 2-hydroxy-N,N-dimethyl-N-[2-N-(2,1,3-benzoxadiazol-4-amine,-N-methyl,-7- nitro)-ethyl] bromide (NBD-choline) and C(6)-NBD-phosphatidylcholine (C(6)-NBD-PC) were used in this work. NBD-choline was easily internalised into drug sensitive MCF-7 and in multidrug resistant MCF-7/DX cells. The probe was found to localise in the endoplasmic reticulum of sensitive cells and in the Golgi of multidrug resistant cells. In contrast, very low accumulation was found in normal MCF10A cells. For C(6)-NBD-PC, a similar pattern of localisation was found in tumour cells, but a significant uptake was also observed in normal cells. Unlike NBD-choline, C(6)-NBD-PC appears not to discriminate between normal and tumour cells. These results are consistent with previously published results showing higher levels of (11)C-choline uptake in malignant lesions seen with positron emission tomography (PET) in vivo imaging. Our results suggest that using NBD-choline and laser scanning confocal fluorescence microscopy (LSCFM) could be a useful tool to study choline metabolism in cancer cells and to consolidate PET imaging findings.

Endometrial stromal progesterone receptor-A/progesterone receptor-B ratio: no difference between women with and without endometriosis.

The aim of the present study was to investigate whether alterations of the P receptor-A/P receptor-B ratio could be considered an etiopathogenetic factor for endometriosis. We failed to observe statistically significant differences in both P receptor-A/P receptor-B messenger RNA and protein ratio between endometrial stromal cells derived from women with and without endometriosis.