Probing local lateral forces of focal adhesions and cell-cell junctions of living cells by torsional force spectroscopy.

The number and strength of mechanical connections of cells to their local environment can be indicative of their migration and invasion potential. Gaining direct access to the mechanical properties of individual connections and bringing them into a relationship with the state of disease, however, is a formidable task. Here, we present a method to directly sense focal adhesions and cell-cell contacts with a force sensor to quantify the lateral forces of their anchoring points. We found local lateral forces of 1.0-1.5 nN for focal adhesions and slightly higher values at the interfaces between cells where cell-cell contacts are located. Interestingly, a modified surface layer was observed exhibiting considerably reduced tip friction directly next to the area of a retracting cell edge on the substrate. We expect that this technique can improve the understanding of the relationship between mechanical properties of cell connections and the pathological state of cells in the future.

Characteristics and outcome in patients with central nervous system involvement treated in European pediatric acute myeloid leukemia study groups.

BACKGROUND: There is no consensus on the treatment for pediatric patients with acute myeloid leukemia and initial central nervous system (CNS) involvement. METHODS: To evaluate different CNS-directed treatment options (intrathecal [IT] therapy, CNS irradiation, hematopoietic stem cell transplantation [HSCT]), 261 patients (excluding acute promyelocytic leukemia) with initial CNS involvement treated in trials with similar intensive chemotherapy by four cooperative European study groups (1998-2013) were studied and compared with CNS-negative patients from the Berlin-Frankfurt-Münster group. RESULTS: Patient characteristics in the different study groups were comparable. Young age, high white blood cell count, extramedullary involvement other than the CNS, monoblastic morphology, and inv(16) were associated with CNS involvement (each P < 0.0001). There were no major differences in outcome between the study groups. The cumulative incidence of relapse (CIR) regarding the CNS was higher in initially CNS-positive versus initially CNS-negative patients (all: 8 ± 2% vs. 3 ± 1%, P(Gray) = 0.001; isolated: 4 ± 1% vs. 1 ± 0%, P(Gray) = 0.03). However, global outcome of the CNS-positive cohort (overall survival, 64 ± 3%; event-free survival 48 ± 3%; and CIR 33% ± 3%) did not differ significantly from CNS-negative patients. Risk groups defined by cytogenetics were of likewise prognostic significance in CNS-positive and -negative patients. CNS treatment with cranial irradiation was not superior compared to IT therapy and systemic chemotherapy (± HSCT). CONCLUSION: Although CNS relapses occurred more frequently in initially CNS-positive patients, their global outcome was similar as in CNS-negative patients. Intensified IT therapy was heterogeneous; however, at least eight applications, preferably with triple IT chemotherapy, seem to be appropriate to accompany dose-intensive systemic chemotherapy.