Mapping Proximity Associations of Core Spindle Assembly Checkpoint Proteins.

The spindle assembly checkpoint (SAC) is critical for sensing defective microtubule-kinetochore attachments and tension across the kinetochore and functions to arrest cells in prometaphase to allow time to repair any errors before proceeding into anaphase. Dysregulation of the SAC leads to chromosome segregation errors that have been linked to human diseases like cancer. Although much has been learned about the composition of the SAC and the factors that regulate its activity, the proximity associations of core SAC components have not been explored in a systematic manner. Here, we have taken a BioID2-proximity-labeling proteomic approach to define the proximity protein environment for each of the five core SAC proteins BUB1, BUB3, BUBR1, MAD1L1, and MAD2L1 in mitotic-enriched populations of cells where the SAC is active. These five protein association maps were integrated to generate a SAC proximity protein network that contains multiple layers of information related to core SAC protein complexes, protein-protein interactions, and proximity associations. Our analysis validated many known SAC complexes and protein-protein interactions. Additionally, it uncovered new protein associations, including the ELYS-MAD1L1 interaction that we have validated, which lend insight into the functioning of core SAC proteins and highlight future areas of investigation to better understand the SAC.

Results of interstitial brachytherapy for malignant brain tumors.

We evaluated the efficacy of brachytherapy in patients with malignant brain tumors and assessed the factors associated with longer disease control after treatment. From June 1989 to October 1995, 73 patients were treated with stereotactic brachytherapy with temporary placement of iodine-125 implants. The median age was 52 (range 9-79). Median KPS was 80. There were 48 patients with a glioblastoma multiforme, 13 with an anaplastic astrocytoma, and 12 with other tumors. Of the 67 evaluable patients, 20 underwent brachytherapy as part of the therapy for a newly diagnosed tumor (17 were glioblastomas) and 46 had brachytherapy at the time of progression (28 were glioblastomas). Median survival time for all patients undergoing brachytherapy from diagnosis was 70.3 weeks. Median survival from implant was 39.3 weeks. For patients with an anaplastic astrocytoma, median survival from diagnosis and implant was 158.1 and 36.9 weeks respectively. For patients with a glioblastoma multiforme, median survival from diagnosis and implant was 62.9 and 37.1 weeks respectively. Eleven patients (16%) developed radiation necrosis. Nine patients (13%) developed other complications. Age and histologic diagnosis were significant predictors of survival from diagnosis. Age and KPS were independent predictors of time to failure after implant. Certain characteristics, specifically younger age (<55), and a higher KPS (