Mesenchymal Stem Cell Graft Improves Recovery after Spinal Cord Injury in Adult Rats through Neurotrophic and Pro-Angiogenic Actions

Numerous strategies have been managed to improve functional recovery after spinal cord injury (SCI) but an optimal strategy doesn't exist yet. Actually, it is the complexity of the injured spinal cord pathophysiology that begets the multifactorial approaches assessed to favour tissue protection, axonal regrowth and functional recovery. In this context, it appears that mesenchymal stem cells (MSCs) could take an interesting part. The aim of this study is to graft MSCs after a spinal cord compression injury in adult rat to assess their effect on functional recovery and to highlight their mechanisms of action. We found that in intravenously grafted animals, MSCs induce, as early as 1 week after the graft, an improvement of their open field and grid navigation scores compared to control animals. At the histological analysis of their dissected spinal cord, no MSCs were found within the host despite their BrdU labelling performed before the graft, whatever the delay observed: 7, 14 or 21 days. However, a cytokine array performed on spinal cord extracts 3 days after MSC graft reveals a significant increase of NGF expression in the injured tissue. Also, a significant tissue sparing effect of MSC graft was observed. Finally, we also show that MSCs promote vascularisation, as the density of blood vessels within the lesioned area was higher in grafted rats. In conclusion, we bring here some new evidences that MSCs most likely act throughout their secretions and not via their own integration/differentiation within the host tissue

Anastrozole versus tamoxifen for the prevention of locoregional and contralateral breast cancer in postmenopausal women with locally excised ductal carcinoma in situ (IBIS-II DCIS): a double-blind, randomised controlled trial

Background Third-generation aromatase inhibitors are more effective than tamoxifen for preventing recurrence in postmenopausal women with hormone-receptor-positive invasive breast cancer. However, it is not known whether anastrozole is more effective than tamoxifen for women with hormone-receptor-positive ductal carcinoma in situ (DCIS). Here, we compare the efficacy of anastrozole with that of tamoxifen in postmenopausal women with hormone-receptor-positive DCIS. Methods In a double-blind, multicentre, randomised placebo-controlled trial, we recruited women who had been diagnosed with locally excised, hormone-receptor-positive DCIS. Eligible women were randomly assigned in a 1:1 ratio by central computer allocation to receive 1 mg oral anastrozole or 20 mg oral tamoxifen every day for 5 years. Randomisation was stratified by major centre or hub and was done in blocks (six, eight, or ten). All trial personnel, participants, and clinicians were masked to treatment allocation and only the trial statistician had access to treatment allocation. The primary endpoint was all recurrence, including recurrent DCIS and new contralateral tumours. All analyses were done on a modified intention-to-treat basis (in all women who were randomised and did not revoke consent for their data to be included) and proportional hazard models were used to compute hazard ratios and corresponding confidence intervals. This trial is registered at the ISRCTN registry, number ISRCTN37546358. Results Between March 3, 2003, and Feb 8, 2012, we enrolled 2980 postmenopausal women from 236 centres in 14 countries and randomly assigned them to receive anastrozole (1449 analysed) or tamoxifen (1489 analysed). Median follow-up was 7·2 years (IQR 5·6–8·9), and 144 breast cancer recurrences were recorded. We noted no statistically significant difference in overall recurrence (67 recurrences for anastrozole vs 77 for tamoxifen; HR 0·89 [95% CI 0·64–1·23]). The non-inferiority of anastrozole was established (upper 95% CI <1·25), but its superiority to tamoxifen was not (p=0·49). A total of 69 deaths were recorded (33 for anastrozole vs 36 for tamoxifen; HR 0·93 [95% CI 0·58–1·50], p=0·78), and no specific cause was more common in one group than the other. The number of women reporting any adverse event was similar between anastrozole (1323 women, 91%) and tamoxifen (1379 women, 93%); the side-effect profiles of the two drugs differed, with more fractures, musculoskeletal events, hypercholesterolaemia, and strokes with anastrozole and more muscle spasm, gynaecological cancers and symptoms, vasomotor symptoms, and deep vein thromboses with tamoxifen. Conclusions No clear efficacy differences were seen between the two treatments. Anastrozole offers another treatment option for postmenopausal women with hormone-receptor-positive DCIS, which may be be more appropriate for some women with contraindications for tamoxifen. Longer follow-up will be necessary to fully evaluate treatment differences

Cyclin D-1 protein over-expression is not associated with gene amplification in benign and atypical apocrine lesions of the breast.

Cyclin D-1 protein over-expression and/or gene amplification have been shown to be frequent events in subsets of breast carcinomas. Cyclin D-1 is generally considered as a weak oncogene, and its over-expression has been shown to occur in occasional benign breast lesions. In a previous series, we have shown that cyclin D-1 was over-expressed in subsets of apocrine metaplasia (APM) and apocrine adenosis (AA) of the breast and that such over-expression was mostly associated with a significant increase in the proliferative capacity of these lesions. We examined the mechanisms involved in cyclin D-1 over-expression in apocrine lesions. A total of 41 cases were analysed in this study. The cases were divided into: 18 cases of APM and 23 cases of AA. All cases analysed had been previously analysed by immunohistochemistry, and all showed over-expression of the cyclin D-1 protein. Fluorescence in situ hybridisation (FISH) was performed using a dual cyclin D-1 (spectrum orange)/chromosome 11 centromere (spectrum green) DNA probe. The results showed that none of the cases studied had concomitant gene amplification. These results suggest that other post-transcriptional mechanisms might be responsible for cyclin D-1 protein over-expression in benign apocrine lesions. Further studies are needed to understand the mechanisms involved in abnormal cyclin D-1 expression in these lesions

A multimodal approach to revisiting oxidation defects in Cr2O3

The oxidation of chromium in air at 700 °C was investigated with a focus on point defect behavior and transport during oxide layer growth. A comprehensive set of characterization techniques targeted characteristics of chromium oxide microstructure and chemical composition analysis. TEM showed that the oxide was thicker with longer oxidation times and that, for the thicker oxides, voids formed at the metal/oxide interface. PAS revealed that the longer the oxidation time, there was an overall reduction in vacancy-type defects, though chromium monovacancies were not found in either case. EIS found that the longer oxidized material was more electrochemically stable and that, while all oxides displayed p-type character, the thicker oxide had an overall lower charge carrier density. Together, the results suggest anion oxygen interstitials and chromium vacancy cluster complexes drive transport in an oxidizing environment at this temperature, providing invaluable insight into the mechanisms that regulate corrosion