mTOR pathway activation in multiple myeloma cell lines and primary tumour cells: pomalidomide enhances cytoplasmic-nuclear shuttling of mTOR protein.

mTOR is a protein kinase that plays a central role in regulating critical cellular processes. We evaluated the activation and cellular localization of the mTOR pathway in multiple myeloma (MM) and analyzed the role of pomalidomide in regulating mTOR. By immunohistochemistry cytoplasmic p-mTOR stained positive in 57 out 101 (57.6%) cases with a nuclear p-mTOR localization in 14 out 101 samples (13.8%). In the 70 MM samples analyzed for the entire pathway, p-mTOR expression significantly correlated with p-AKT, p-P70S6K, and p-4E-BP1 suggesting that the AKT/mTOR pathway is activated in a subset of MM patients. Immunofluorescence assays demonstrated that mTOR protein is distributed throughout the cytoplasm and the nucleus at baseline in MM cell lines and in plasma cells of 13 MM patients and that pomalidomide facilitated the shift of the mTOR protein in the nucleus. By western blotting, treatment with pomalidomide increased nuclear mTOR and p-mTOR expression levels in the nucleus with a concomitant decrease of the cytoplasmic fractions while does not seem to affect significantly AKT phosphorylation status. In MM cells the anti-myeloma activity of pomalidomide may be mediated by the regulation of the mTOR pathway.

Predictive effects of muscle strength after hospitalization in old patients.

BACKGROUND AND AIMS: Frailty is a common situation that often influences clinical outcomes, disability or institutionalization. The present study aims to evaluate the weight of hand grip strength (HGS) reduction in terms of death or re-hospitalizations, at 3-month and 1-year follow-up. METHODS: Observational study performed on hospitalized patients aged 65 years or more. The HGS was measured twice: at hospital admission and discharge. The statistical analysis was performed using SPSS, version 18 for Windows. The χ (2) test was used to evaluate the relationship between HGS and different variables. Three-month and 1-year survival and hospital re-admissions have been analyzed using Kaplan-Meier's curves. The analyses have been adjusted for age and gender. RESULTS: A total of 201 hospitalized patients have been recruited. Of them, 76 were males. The mean age was 81.79 ± 7.409 years. Of all the patients enrolled, 66.2 and 45.3 % did not show any impairment performing activities of daily living and instrumental activities of daily living, respectively. Moreover, patients were not cognitively impaired [SPMSQ (short portable mental status questionnaire ) m ± SD = 1.47 ± 0.794]. At 3-month follow-up patients with strength reduction had a relative risk of death more than seven times higher than the others (p = 0.047). Same results were observed at 1-year follow-up (95 % CI = 1.85-9.84; p = 0.000). There was no significant relationship between HGS and hospital re-admissions. CONCLUSIONS: Effects of strength reduction occurring during a period of hospitalization could produce effects even after hospitalization itself. This increases the relevance of maintaining usual physical performance of patients even during hospitalization.