Osteosarcopenia in Finland: prevalence and associated factors.

This cross-sectional study investigated osteosarcopenia prevalence and its correlates among 2142 adults aged 55 and older in Finland. Findings show 3.9% had osteosarcopenia, while 13.8% and 11.1% had probable sarcopenia only or osteoporosis only, respectively. Osteosarcopenia was associated with low BMI, impaired mobility, ADL limitations and depression. Sarcopenia appeared to drive these associations more than osteoporosis. Osteosarcopenia may be a risk factor for functional decline, hospitalization, and institutionalization, warranting further research. PURPOSE: Osteosarcopenia is a disorder consisting of concurrent osteoporosis and sarcopenia. This cross-sectional study using nationally representative data from Finland in 2000 aimed to determine the prevalence of osteosarcopenia in Finland. In addition, associations of sociodemographic, lifestyle, anthropometric, physical and mental function indicators, chronic conditions and various biomarkers with osteosarcopenia were examined. METHODS: The study included 2142 subjects aged 55 and over (mean age 68.0 years, SD 9.0). Probable sarcopenia was defined as grip strength < 27 kg for men and < 16 kg for women. Osteoporosis was defined as either ultrasound-based bone density measurement of T < -2.5, or self-reported, pre-existing diagnosis of osteoporosis. Participants were categorized into 4 groups: no sarcopenia and no osteoporosis, probable sarcopenia only, osteoporosis only, and osteosarcopenia. Information on sociodemographic, lifestyle, anthropometric, physical and mental function indicators, chronic conditions and various biomarkers were collected via structured interview, questionnaires, clinical examination, and blood and urine samples. RESULTS: The prevalence of probable sarcopenia, osteoporosis and osteosarcopenia was 13.8%, 11.1%, and 3.9%, respectively. Osteosarcopenia was associated with low BMI, slow gait speed, impaired mobility, impaired ability in the activities of daily living and depression. Of the two components, probable sarcopenia appeared to contribute to these associations more than osteoporosis. CONCLUSION: According to representative population-based study, about every fifth person with probable sarcopenia also has osteoporosis. Mobility and ADL limitations were more common among people with osteosarcopenia than those with osteoporosis or probable sarcopenia alone. Future studies are needed to examine osteosarcopenia as an independent risk factor for functional decline, hospitalization, and institutionalization.

Prognostic and predictive value of ALDH1, SOX2 and SSEA-4 in bladder cancer.

Transurethral resection of bladder tumor (TUR-BT) and radical cystectomy (RC) are standard treatment options for bladder cancer (BC). Neoadjuvant chemotherapy (NAC) prior to RC improves outcome of some patients but currently there are no valid biomarkers to identify patients who benefit from NAC. Presence of cancer stem cells (CSC) has been associated with poor outcome and resistance to chemotherapy in various cancers. Here we studied the expression of stem cell markers ALDH1, SOX2 and SSEA-4 with immunohistochemistry in tissue microarray material consisting of 195 BC patients treated with RC and 74 patients treated with TUR-BT followed by NAC and RC. Post-operative follow-up data of up to 22 years was used. Negative to weak cytoplasmic SOX2 staining was associated with lymphovascular invasion and non-organ confined disease. It was also associated with shortened cancer-specific survival, but the finding was not statistically significant. Contrary to previous reports, none of the other tested biomarkers were associated with cancer-specific mortality or clinicopathological characteristics. Neither were they associated with response to NAC. Despite the promising results of previously published studies, our results suggest that CSC markers ALDH1, SOX2 and SSEA-4 have little if any prognostic or predictive value in BC treated with RC.

SORLA regulates endosomal trafficking and oncogenic fitness of HER2.

The human epidermal growth factor receptor 2 (HER2) is an oncogene targeted by several kinase inhibitors and therapeutic antibodies. While the endosomal trafficking of many other receptor tyrosine kinases is known to regulate their oncogenic signalling, the prevailing view on HER2 is that this receptor is predominantly retained on the cell surface. Here, we find that sortilin-related receptor 1 (SORLA; SORL1) co-precipitates with HER2 in cancer cells and regulates HER2 subcellular distribution by promoting recycling of the endosomal receptor back to the plasma membrane. SORLA protein levels in cancer cell lines and bladder cancers correlates with HER2 levels. Depletion of SORLA triggers HER2 targeting to late endosomal/lysosomal compartments and impairs HER2-driven signalling and in vivo tumour growth. SORLA silencing also disrupts normal lysosome function and sensitizes anti-HER2 therapy sensitive and resistant cancer cells to lysosome-targeting cationic amphiphilic drugs. These findings reveal potentially important SORLA-dependent endosomal trafficking-linked vulnerabilities in HER2-driven cancers.

A Strong Contractile Actin Fence and Large Adhesions Direct Human Pluripotent Colony Morphology and Adhesion.

Cell-type-specific functions and identity are tightly regulated by interactions between the cell cytoskeleton and the extracellular matrix (ECM). Human pluripotent stem cells (hPSCs) have ultimate differentiation capacity and exceptionally low-strength ECM contact, yet the organization and function of adhesion sites and associated actin cytoskeleton remain poorly defined. We imaged hPSCs at the cell-ECM interface with total internal reflection fluorescence microscopy and discovered that adhesions at the colony edge were exceptionally large and connected by thick ventral stress fibers. The actin fence encircling the colony was found to exert extensive Rho-ROCK-myosin-dependent mechanical stress to enforce colony morphology, compaction, and pluripotency and to define mitotic spindle orientation. Remarkably, differentiation altered adhesion organization and signaling characterized by a switch from ventral to dorsal stress fibers, reduced mechanical stress, and increased integrin activity and cell-ECM adhesion strength. Thus, pluripotency appears to be linked to unique colony organization and adhesion structure.