The formation of the eight independent endorgan compartments (sacculus, utricle, horizontal canal, anterior canal, posterior canal, lagena, amphibian papilla, and basilar papilla) of the Xenopus laevis inner ear is illustrated as the otic vesicle develops into a complex labyrinthine structure. The morphology of transverse sections and whole-mounts of the inner ear was assessed in seven developmental stages (

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Both accelerated senescence and conventional growth arrest are likely to represent alternative responses to apoptosis in irradiated GBM cells.

Genetic heterogeneity is recognized as a major contributing factor of glioblastoma resistance to clinical treatment modalities and consequently low overall survival rates. This genetic diversity results in variations in protein expression, both intratumorally and between individual glioblastoma patients. In this regard, the spectraplakin protein, microtubule actin cross-linking factor 1 (MACF1), was examined in glioblastoma. An expression analysis of MACF1 in various types of brain tumor tissue revealed that MACF1 was predominately present in grade III-IV astroctyomas and grade IV glioblastoma, but not in normal brain tissue, normal human astrocytes and lower grade brain tumors. Subsequent genetic inhibition experiments showed that suppression of MACF1 selectively inhibited glioblastoma cell proliferation and migration in cell lines established from patient derived xenograft mouse models and immortalized glioblastoma cell lines that were associated with downregulation of the Wnt-signaling mediators, Axin1 and β-catenin. Additionally, concomitant MACF1 silencing with the chemotherapeutic agent temozolomide (TMZ) used for the clinical treatment of glioblastomas cooperatively reduced the proliferative capacity of glioblastoma cells. In conclusion, the present study represents the first investigation on the functional role of MACF1 in tumor cell biology, as well as demonstrates its potential as a unique biomarker that can be targeted synergistically with TMZ as part of a combinatorial therapeutic approach for the treatment of genetically multifarious glioblastomas.

The unfolded protein endoplasmic reticulum stress response has emerged as a cellular physiological target to invoke tumor cell killing due to its homeostatic and cytoprotective functions. In this study, thapsigargin and tunicamycin, two endoplasmic reticulum stress inducers, were investigated for their efficacy on glioblastomas. We demonstrate that clinically relevant concentrations of thapsigargin and tunicamycin eliminate the glioblastoma cell reproductive capacity as a consequence of cell death. The mode of glioblastoma-induced cell death was determined to be via apoptosis as supported by increased C/EBP homologous protein (CHOP) levels and caspase 3 activity, two proteins with established roles in endoplasmic reticulum stress-induced cell death. In conclusion, this study provides evidence that glioblastomas are responsive to endoplasmic reticulum stress induction as a cellular program to eradicate this tumor via programmed cell death.