No abstract

Emerging information indicates that epigenetic modification (i.e. histone code and DNA methylation) may be integral to the maintenance and differentiation of neural stem cells (NSC), but their actual involvements have not yet been illustrated. In this study, we demonstrated the dynamic nature of epigenetic marks during the differentiation of quiescent adult rat NSCs in neurospheres. A subpopulation of OCT4+ NSCs in the neurosphere contained Histone marks, trimethylated Histone 3 on lysine 27 (3me-H3K27), 2me-H3K4, and acetylated H4 (Ac-H4). A major decrease of these marks was found prior to or during differentiation, and was further diminished or reprogrammed in diverse subpopulations of migrated NSCs expressing nestin or β-III-tubulin. The DNA methylation mark 5-methyl-cytosine (5-MeC) and the DNA methyltransferase (DNMT) 1 and 3a expression also correlated to the state of differentiation; they were highly present in undifferentiated NSCs but down-regulated in migrated populations. In contrast, the DNA methyl-CpG-binding protein (MBD1) was low in undifferentiated NSCs in neurospheres, but highly appeared in differentiating NSCs. Furthermore, we found a outward translocation of DNA-methylation marks 5-MeC, DNMT1, DNMT3a, and MBD1 in NSCs as differentiation began and proceeded; the 5-MeC from homogeneous nucleus to peripheral-nucleus, and DMNT1a and 3a from nuclear to cytoplasm, indicating chromatin remodeling. Treatment with DNA a methylation inhibitor, 5-aza-cytidine, altered DNA methylation and disrupted migration as indicated by a reduction of migrated neurons and differentiation. These results indicate that chromatin is dynamically remodeled when NSCs transform from the quiescent state to active growth, and that DNA methylation modification is essential for neural stem cell differentiation.

In the absence of level I data, GTV and histology should be considered to personalize radiation dose for stereotactic ablative body radiotherapy. We suggest lower prescription doses (i.e., 12 Gy × 4 or 10 G × 5) should be avoided for squamous cell carcinomas if normal tissue tolerances are met.

Spinal cord compression (SCC) from spinal metastasis is a common complication in cancer and if left untreated, permanent paraplegia or quadriplegia will occur. Timely diagnosis is crucial in preventing permanent neurologic damage. Once SCC is suspected, diagnostic imaging of the spine should be obtained to confirm diagnosis. Treatment consists of surgery, radiotherapy or a combination of both. Stereotactic body radiotherapy has also been incorporated into the management of SCC. The treatment decision should be made based on multiple factors, including tumor histology, retropulsion of bony fragments, performance status of the patient and status of extraspinal systemic disease. This review focuses on the pathophysiology, diagnosis and management of SCC.