The level of stem cell proliferation must be tightly controlled for proper development and tissue homeostasis. Multiple levels of gene regulation are often employed to regulate stem cell proliferation to ensure that the amount of proliferation is aligned with the needs of the tissue. Here we focus on proteasome-mediated protein degradation as a means of regulating the activities of proteins involved in controlling the stem cell proliferative fate in the C. elegans germ line. We identify five potential E3 ubiquitin ligases, including the RFP-1 RING finger protein, as being involved in regulating proliferative fate. RFP-1 binds to MRG-1, a homologue of the mammalian chromodomain-containing protein MRG15 (MORF4L1), which has been implicated in promoting the proliferation of neural precursor cells. We find that C. elegans with reduced proteasome activity, or that lack RFP-1 expression, have increased levels of MRG-1 and a shift towards increased proliferation in sensitized genetic backgrounds. Likewise, reduction of MRG-1 partially suppresses stem cell overproliferation. MRG-1 levels are controlled independently of the spatially regulated GLP-1/Notch signalling pathway, which is the primary signal controlling the extent of stem cell proliferation in the C. elegans germ line. We propose a model in which MRG-1 levels are controlled, at least in part, by the proteasome, and that the levels of MRG-1 set a threshold upon which other spatially regulated factors act in order to control the balance between the proliferative fate and differentiation in the C. elegans germ line.

The TEACHH model is useful to identify patients with spinal metastases with predicted short, intermediate, and long LE. Its prognostic ability is similar to the Chow model.

Background There is a lack of consensus regarding the management of T4a larynx cancer. We evaluated the outcomes of organ preservation and laryngectomy for T4a laryngeal cancer. Methods Retrospective analysis of patients with T4a larynx cancer at BC Cancer from 1984 to 2014 was performed. Outcomes in patients treated with surgery alone (Sx) (n = 47), surgery with adjuvant radiotherapy (Sx/RT) (n = 94), radiation alone (RT) (n = 152), and radiation with concurrent chemoradiotherapy (chemoRT) (n = 36) were compared. Results The 5‐year overall survival (OS) was 40% for chemoRT, 34% for RT, 23% for Sx, and 45% for Sx/RT. On multivariate analysis (MVA), Sx/RT (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.48‐0.91) and chemoRT (HR, 0.44; 95% CI, 0.26‐0.72) were associated with better OS than RT alone (P = .001). Sx had similar OS compared to RT (HR, 1.17; 95% CI, 0.82‐1.68). Conclusions ChemoRT and Sx/RT were associated with better OS compared to single modality treatment. ChemoRT may be considered as an option for T4a larynx cancer.

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