Glioblastoma multiforme (GBM) tumors are the most common malignant primary brain tumors in adults. Although many GBM tumors are believed to be caused by self-renewing, glioblastoma-derived stem-like cells (GSCs), the mechanisms that regulate self-renewal and other oncogenic properties of GSCs are only now being unraveled. Here we showed that GSCs derived from GBM patient specimens express varying levels of the transcriptional repressor REST, suggesting heterogeneity across different GSC lines. Loss- and gain-of-function experiments indicated that REST maintains self-renewal of GSCs. High REST-expressing GSCs (HR-GSCs) produced tumors histopathologically distinct from those generated by low REST-expressing GSCs (LR-GSCs) in orthotopic mouse brain tumor models. Knockdown of REST in HR-GSCs resulted in increased survival in GSC-transplanted mice and produced tumors with higher apoptotic and lower invasive properties. Conversely, forced expression of exogenous REST in LR-GSCs produced decreased survival in mice and produced tumors with lower apoptotic and higher invasive properties, similar to HR-GSCs. Thus, based on our results, we propose that a novel function of REST is to maintain self-renewal and other oncogenic properties of GSCs and that REST can play a major role in mediating tumorigenicity in GBM.
OBJECTIVES
To present our experience with bladder cancer among a renal transplant population and to review critically the relevant literature.
PATIENTS AND METHODS
In all, 1865 renal graft recipients were followed for a mean (sd) of 6.5 (5) years. Seven recipients (all men) developed a urothelial bladder tumour. The stage and grade of the tumours were determined. The method of the treatment was selected on the basis of the tumour characteristics and graft function. Patients were regularly followed; the endpoints were cancer‐specific survival, recurrence or metastasis.
RESULTS
All patients presented with gross haematuria. There was non‐muscle‐invasive disease in two patients who were treated by transurethral resection and adjuvant intravesical bacille Calmette‐Guérin immunotherapy. One patient died 24 months later due to complications of end‐stage renal disease. To date the second patient is alive and free of the recurrence. Five recipients with muscle‐invasive disease had a radical cystectomy and orthotopic bladder substitution. The mean (sd) time to the last follow‐up or death was 14.6 (3.1) months. Three patients died with stable graft function; two from distant metastasis and one from a cerebrovascular stroke. The remaining two patients are still alive, free of disease and with good graft function.
CONCLUSIONS
Urothelial bladder tumours are generally uncommon. The presence of haematuria in renal allograft recipients should be thoroughly investigated. Early diagnosis and prompt treatment are required for managing such tumours, because they are aggressive. Orthotopic bladder substitution is feasible with a good functional outcome for patients in whom cystectomy is indicated.
Diabetes mellitus (DM) is an alarming metabolic disease in which insulin secreting β-cells are damaged to various extent. Unfortunately, although currently available treatments help to manage the disease, however, patients usually develop complications, as well as decreased life quality and increased mortality. Thus, efficient therapeutic interventions to treat diabetes are urgently warranted. During the past years, mesenchymal stem cells (MSCs) have made their mark as a potential weapon in various regenerative medicine applications. The main fascination about MSCs lies in their potential to exert reparative effects on an amazingly wide spectrum of tissue injury. This is further reinforced by their ease of isolation and large ex vivo expansion capacity, as well as demonstrated multipotency and immunomodulatory activities. Among all the sources of MSCs, those isolated from umbilical cord-Wharton's jelly (WJ-MSCs), have been proved to provide a great source of MSCs. WJ-MSCs do not impose any ethical concerns as those which exist regarding ESCs, and represent a readily available non-invasive source, and hence suggested to become the new gold standard for MSC-based therapies. In the current review, we shall overview achievements, as well as challenges/hurdles which are standing in the way to utilize WJ-MSCs as a novel efficient therapeutic modality for DM.
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