No abstract

The steroid hormone oestrogen is central to normal female physiology, reproduction and behaviour, through its effects on cellular processes including cell proliferation and cell survival. The effects of oestrogen are mediated by nuclear ERs (oestrogen receptors). ER status is important for the development, progression and treatment of breast cancer. miRNAs (microRNAs) are small non-coding RNAs that bind the 3'-UTR (untranslated region) of target mRNAs to reduce their stability and/or translation. miRNAs participate in oestrogen signalling by regulating oestrogen-responsive genes and pathways. Interestingly expression and maturation of miRNAs can also be regulated by ER signalling at multiple levels. In addition to regulating the expression of miRNAs at the transcriptional level, ER appears to be able to regulate the biogenesis of miRNAs. In the present review, we summarize recent findings on miRNA biogenesis and describe various mechanisms by which oestrogen signalling can modulate the production of miRNAs.

BackgroundDicer, an RNase III-type endonuclease, is the key enzyme involved in RNA interference and microRNA pathways. Aberrant expression of Dicer is reported in several human cancers. Our aim was to assess the prognostic role of Dicer in breast cancer.MethodsThe entire series comprised 666 invasive breast cancers (IBCs), 480 DCIS cases (397 associated with IBC and 83 pure DCIS) and 305 lymph node metastases. Cytoplasmic Dicer expression by immunohistochemistry was scored as negative (no staining) and positive (weak, moderate or strong staining).ResultsDicer staining was assessable in 446 IBC, 128 DCIS and 101 lymph node metastases. Expression of Dicer was observed in 33% (145/446) of IBCs, 34% (44/128) of DCIS and 57% (58/101) of lymph node metastases. Dicer expression was increased in nodal metastases compared to primary tumours (p<0.001); and was associated with ER negativity (p<0.001), HER2 positivity (p<0.001), high Ki67 labeling index (p<0.001) and expression of basal-like biomarkers (p = 0.002). Dicer positivity was more frequent in the HER2 overexpressing (p<0.001) and basal-like (p = 0.002) subtypes compared to luminal A subtype. Dicer expression was associated with reduced overall survival (OS) on univariate analysis (p = 0.058) and remained an independent predictor of OS on multivariate analysis (HR 2.84, 95% CI 1.43–5.62, p = 0.003), with nodal status (HR 2.61, 95% CI 1.18–5.80, p = 0.018) and PR (HR 0.28, 95% CI 0.13–0.59, p = 0.001). Further, moderate or strong expression of Dicer was associated with improved disease-free survival in the HER2-overexpressing subtype compared to negative or weak expression (p = 0.038).ConclusionDeregulated Dicer expression is associated with aggressive tumour characteristics and is an independent prognostic factor for OS. Our findings suggest that Dicer is an important prognostic marker in breast cancer and that its prognostic role may be subtype specific.

This case highlights clinical, aetiological and histopathological features of this rare finding.

An open study to investigate the PAF-acether antagonist activity of Tanakan in healthy male volunteers examined the effect of a single 15-ml oral dose on ex vivo platelet aggregation induced by adrenaline, adenosine diphosphate (ADP), collagen or PAF-acether. Aggregometry was performed on platelet-rich plasma samples from blood taken 1 h before dosing with Tanakan and 2, 4 and 8 h after intake of Tanakan. Following dosing with Tanakan there was a reduction in platelet aggregation at all doses of PAF, with 1 μM ADP and adrenaline, the most significant decreases occurred with 75 nM PAF-acether 4 h after intake (p < 0.05) and 300 nM PAF-acether 4 h (p < 0.01) and 8 after intake (p < 0.05). There were no concomitant changes in coagulation, skin bleeding time, haematological and biochemical laboratory tests, blood pressure or pulse. The results provide a possible explanation for the clinical efficacy of Tanakan in the treatment of peripheral vascular disease; they also confirm that a single oral dose of 15 ml Tanakan is well tolerated.