These results support a biphasic model of changes in AD, which could affect the selection of patients for clinical trials and the use of magnetic resonance imaging as a surrogate marker of disease modification.
Background: Frontotemporal dementia (FTD) is frequently caused by genetic mutations in GRN, C9orf72 and MAPT. Neurofilament light chain (NfL) is a promising blood biomarker in genetic FTD, with elevated levels in symptomatic mutation carriers. A better understanding of NfL dynamics is essential for its use in upcoming therapeutic trials. We investigated longitudinal serum NfL trajectories in presymptomatic and symptomatic genetic FTD. over time was associated with atrophy rate in several grey matter regions, but not with rate of change in clinical parameters. Interpretation: This study confirms the value of blood NfL as a disease progression biomarker in genetic FTD and indicates that longitudinal NfL measurements could help identify mutation carriers approaching symptom onset and capture the rate of brain atrophy. The stable levels in C9orf72-and MAPT-associated FTD offer potential for NfL as a marker of treatment effect in therapeutic trials.
Background: SOX2 and SOX9 are commonly overexpressed in glioblastoma, and regulate the activity of glioma stem cells (GSCs). Their specific and overlapping roles in GSCs and glioma treatment remain unclear.
Methods: SOX2 and SOX9 levels were examined in human biopsies. Gain and loss of function determined the impact of altering SOX2 and SOX9 on cell proliferation, senescence, stem cell activity, tumorigenesis and chemoresistance.
Results: SOX2 and SOX9 expression correlates positively in glioma cells and glioblastoma biopsies. High levels of SOX2 bypass cellular senescence and promote resistance to temozolomide. Mechanistic investigations revealed that SOX2 acts upstream of SOX9. mTOR genetic and pharmacologic (rapamycin) inhibition decreased SOX2 and SOX9 expression, and reversed chemoresistance.
Conclusions: Our findings reveal SOX2-SOX9 as an oncogenic axis that regulates stem cell properties and chemoresistance. We identify that rapamycin abrogate SOX protein expression and provide evidence that a combination of rapamycin and temozolomide inhibits tumor growth in cells with high SOX2/SOX9.
The lateral aspect of the knee is stabilized by a complex arrangement of ligaments, tendons, and muscles. These structures can be demonstrated with routine spin-echo magnetic resonance (MR) imaging sequences performed in the sagittal, coronal, and axial planes. Anterolateral stabilization is provided by the capsule and iliotibial tract. Posterolateral stabilization is provided by the arcuate ligament complex, which comprises the lateral collateral ligament; biceps femoris tendon; popliteus muscle and tendon; popliteal meniscal and popliteal fibular ligaments; oblique popliteal, arcuate, and fabellofibular ligaments; and lateral gastrocnemius muscle. Injuries to lateral knee structures are less common than injuries to medial knee structures but may be more disabling. Most lateral compartment injuries are associated with damage to the cruciate ligaments and medial knee structures. Moreover, such injuries are frequently overlooked at clinical examination. Structures of the anterolateral quadrant are the most frequently injured; posterolateral instability is considerably less common. Practically all tears of the lateral collateral ligament are associated with damage to posterolateral knee structures. Most injuries of the popliteus muscle and tendon are associated with damage to other knee structures. MR imaging can demonstrate these injuries. Familiarity with the musculotendinous anatomy of the knee will facilitate accurate diagnosis with MR imaging.
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