Despite developing refinements of chemotherapy regimens for osteosarcoma, multi-drug resistant cases are frequently seen and patients with metastatic or recurrent disease continue to have a very poor prognosis. Recently, the expression of the longevity gene Sirt1 was found to be relatively higher expressed in tumors compared with the normal tissues. Association of high level of Sirt1 expression with the development of multi-drug resistance in tumor cells has also been indicated. Thus, it is interesting to study the therapeutic potential of regulating Sirt1 activity for the treatment of osteosarcoma. In the present study, we evaluated the effects of two Sirt1 activators, resveratrol and isonicotinamide, on growth and apoptosis in four human osteosarcoma cell lines, HOS, Saos-2, U-2 OS and MG-63. We found that Sirt1 protein was expressed in all osteosarcoma cell lines. Instead of promoting cell survival, both resveratrol and isonicotinamide decreased cell growth and induced cell apoptosis in a dose-dependent fashion. Furthermore, the pro-apoptotic effect of resveratrol could be enhanced by L-asparaginase-induced nutrition restriction of cultured osteosarcoma cells. Our results demonstrated that Sirt1 activators elicited pro-apoptotic effects in osteosarcomas. Thus, Sirt1 could be a potential target in the treatment of osteosarcoma. However, due to the non-specificity of the Sirt1 activators used further studies, such as knock-down of Sirt1 by siRNA, are needed to confirm the effect of Sirt1 activation on malignant cells.
We report a prospective study of 232 consecutive patients with hip fractures. All were over 64 years of age and living independently before admission to a geriatric orthopaedic ward. We assessed the value, at admission, of predicting factors for independent living at one year after injury. The most important factors were: (1) preinjury function in activities of daily living (grade A or B on the Katz et al (1963) scale); (2) absence of other medical conditions which would impair rehabilitation; and (3) cognitive function better than 7 on the Pfeiffer (1975) mental questionnaire. The odds ratios (95% CI) for these three predictors were 3.5 (1.3 to 9.1), 2.9 (1.3 to 6.1) and 2.4 (1.9 to 4.9), respectively. When all predictors were positive at admission, 92% were living independently at one year; with one, two or three negative predictors, the percentages living independently were 76, 61 and 27, respectively. The median values of the total number of days in hospital, irrespective of diagnosis, during the first year were 12, 24, 29 and 149 days for the four groups. The mortality at one year was predictable on admission only by the number of medical conditions: with no other diagnosis than the fracture the mortality was 0%; with one or two additional conditions the mortality was 14%; and with three or more additional diagnoses it was 24%. These simple and robust predictors can be used to optimise resources for rehabilitation.