Faculty Bibliography

BACKGROUND CONTEXT/BACKGROUND:Traumatic bilateral-atlantoaxial dislocations are rare injuries. Hangman fractures, conversely, represent 4% to 7% of all cervical fractures and frequently involve a combination C1-C2 fracture pattern. Presently, there is no report in the English literature of a traumatic C2-spondylolisthesis associated with a C1-C2 rotatory dislocation. This injury complex cannot be cataloged using current classification schemes and no established treatment recommendations exist. PURPOSE/OBJECTIVE:To report a unique case of a Hangman fracture associated with bilateral C1-C2 rotatory-dislocation, which does not fit into existing classification systems, and discuss our treatment approach. STUDY DESIGN/METHODS:A clinical case report and review of the literature. METHODS:Chart review and analysis of relevant literature. There were no study-specific conflicts of interest. RESULTS:A 26-year-old man sustained a traumatic C2-spondylolisthesis along with C1-C2 rotatory subluxation in an automobile collision. The patient was originally placed in a halo crown and vest and then taken for an open reduction and stabilization through a posterior approach for persistent C1-C2 subluxation. The patient is currently 16 months postoperative and back to work as a plumber. CONCLUSIONS:The injury complex encountered cannot be described using the available classification systems. Our treatment included initial stabilization with halo placement, followed by a posterior C1, C2, and C3 segmental reduction and fixation resulting in radiographic fusion and a good clinical outcome.

UNLABELLED:We demonstrate that the androgen receptor (AR) regulates a transcriptional program of DNA repair genes that promotes prostate cancer radioresistance, providing a potential mechanism by which androgen deprivation therapy synergizes with ionizing radiation. Using a model of castration-resistant prostate cancer, we show that second-generation antiandrogen therapy results in downregulation of DNA repair genes. Next, we demonstrate that primary prostate cancers display a significant spectrum of AR transcriptional output, which correlates with expression of a set of DNA repair genes. Using RNA-seq and ChIP-seq, we define which of these DNA repair genes are both induced by androgen and represent direct AR targets. We establish that prostate cancer cells treated with ionizing radiation plus androgen demonstrate enhanced DNA repair and decreased DNA damage and furthermore that antiandrogen treatment causes increased DNA damage and decreased clonogenic survival. Finally, we demonstrate that antiandrogen treatment results in decreased classical nonhomologous end-joining. SIGNIFICANCE/CONCLUSIONS:We demonstrate that the AR regulates a network of DNA repair genes, providing a potential mechanism by which androgen deprivation synergizes with radiotherapy for prostate cancer.