Action of vitamin D and E on the erythrocyte membrane. II. Morphological changes in the erythrocytes studied by transmission electron microscopy]

Man, rabbit, guinea-pig erythrocytes treated "in vitro" with high doses of cholecalcipherol or alpha-tocopherol release K+ and haemoglobin and show ultrastructural damages. These damages consist in a change of the red cells profile as well as in the desappearance of the glycocalix, in alterations of the membrane and of the cortical cytoplasm structure. These ultrastructural alterations are of a different degree, depending on the animal species; they partly resemble the erythrocyte changes induced by retinol. Our results are in partial agreement with the Dingle and Lucy's hypothesis on the common action of liposoluble vitamines on the erythrocyte membrane.     

Real world experience with teriflunomide in multiple sclerosis: the TER-Italy study

Journal of Neurology - To identify baseline factors associated with disease activity in patients with relapsing–remitting multiple sclerosis (RRMS) under teriflunomide treatment. This was an...     

Monofocal acute large demyelinating lesion mimicking brain glioma

Neurological Sciences - We report the case of a 34-year-old woman with clinical, neuroradiological and intraoperative histological findings, suggesting a low-grade astrocytic tumour. The...     

Bovine seminal ribonuclease is cytotoxic for both malignant and normal telomerase-positive cells

Bovine seminal-ribonuclease (BS-RNase) is a member of the 'ribonucleases with special biological actions' family since it possesses specific anti-tumour, anti-spermatogenic and embryotoxic activities and exerts an immunosuppressive effect on T lymphocytes. In previous studies it was demonstrated that BS-RNase induced apoptosis in proliferating, malignant and normal cells and that telomerase activity loss also caused apoptotic death in neoplastic cells. Since an obvious relationship between cell proliferation and telomerase activity exists, the aim of this work was to study if the pro-apoptotic cytotoxic action exerted by BS-RNase on proliferating malignant cells (HT29) and proliferating normal cells (PHA-stimulated lymphocytes) could be linked to a possible BS-RNase effect on telomerase activity. In BS-RNase-treated HT29 cells (Na-butyrate-differentiated or not) and human lymphocytes (proliferating or not), we investigated cell vitality (MTT method) and morphology (SEM), BS-RNase localization (immunofluorescence), telomerase activity (TRAP-ELISA method), hTR mRNA expression (RT-PCR), and hTERT levels (western blot). While no BS-RNase effect was detectable on not proliferating cells, a clear relationship was noticed between the diminished number of vital elements of both proliferating cell populations after treatment (48 h and 72 h for HT29 and PHA-stimulated lymphocytes, respectively) with 50 microg/ml BS-RNase and the decrease of their telomerase activity. At the same time, we found that hTR levels, the RNA subunit of telomerase, in proliferation-inhibited BS-RNase-treated cells were diminished. Moreover, by immunofluorescence technique, we detected BS-RNase in the HT29 cell nucleolus after 3-h treatment. Therefore, as hTR has been recently proven to co-fractionate with nucleoli, we hypothesize that a BS-RNase direct action on the telomerase hTR subunit could be a possible mechanism of action by which BS-RNase exerts its pro-apoptotic effects only on proliferating cells.     

miR-30e* is an independent subtype-specific prognostic marker in breast cancer

Background:

Breast cancer clinical outcome is affected by tumor molecular features, and the identification of subtype-specific prognostic biomarkers is relevant for breast cancer translational research. Gene expression signatures proved to be able to complement prognostic information provided by classical clinico-pathological features. Recently, microRNAs (miRNAs) have been causally linked to tumorigenesis and cancer progression and have been associated with patient outcome, also in breast cancer.

Methods:

MicroRNAs associated with the development of distant metastasis were identified in a cohort of 92 ESR1+/ERBB2− lymph node-negative breast cancers from patients not receiving adjuvant treatment. Results were confirmed and further investigated in a total of 1246 miRNA and gene expression profiles of the Molecular Taxonomy of Breast Cancer International Consortium data set. Moderated t-test, univariable and multivariable Cox regression models were used for statistical analyses.

Results:

miR-30e* was identified as independent protective prognostic factor in lymph node-negative untreated patients with ESR1+/ERBB2− tumours and retained a significant association with a good prognosis in treated patients with the same tumor subtype as well as in the ERBB2+ subtype, but not in ESR1−/ERBB2− tumours.

Conclusions:

We highlighted a relevant and subtype-specific role in breast cancer for miR-30e* and demonstrated that adding miRNA markers to gene signatures and clinico-pathological features can help for a better prognostication.