No abstract

β-catenin is a master regulator in the cellular biology of development and neoplasia. Its dysregulation is implicated as a driver of colorectal carcinogenesis and the epithelial-mesenchymal transition in other cancers. Nuclear β-catenin staining is a poor prognostic sign in synovial sarcoma, the most common soft-tissue sarcoma in adolescents and young adults. We show through genetic experiments in a mouse model that expression of a stabilized form of β-catenin greatly enhances synovial sarcomagenesis. Stabilization of β-catenin enables a stem-cell phenotype in synovial sarcoma cells, specifically blocking epithelial differentiation and driving invasion. β-catenin achieves its reprogramming in part by upregulating transcription of TCF/LEF target genes. Even though synovial sarcoma is primarily a mesenchymal neoplasm, its progression towards a more aggressive and invasive phenotype parallels the epithelial-mesenchymal transition observed in epithelial cancers, where β-catenin's transcriptional contribution includes blocking epithelial differentiation.

were performed using a 2-tailed Student's t test, with a P value of less than 0.05 considered significant.Study approval. All mouse experiments were conducted with the approval of the IACUC of the University of Utah and in accordance with international legal and ethical standards. Clinical analyses were performed with approval from the IRB of the University of Utah and in accordance with legal and ethical standards. As only extant records were reviewed, the requirement for consent was waived by the IRB. Author contributionsKBJ and MLH conceived the experiments. JJB, BEI, HJ, MLH, YW, MH and KBJ performed experiments. JJB, AG, and KBJ analyzed data. MRC contributed mice and resources. KBJ wrote the manuscript, and all authors edited it.

Purpose Extracorporeal membrane oxygen (ECMO) is increasingly used as an advanced form of life support for cardiac and respiratory failure. Unfortunately, in infrequent instances, circulatory and/or respiratory recovery is overshadowed by neurologic injury that can occur in patients who require ECMO. As such, knowledge of ECMO and its implications on diagnosis and treatment of neurologic injuries is indispensable for intensivists and neurospecialists. Recent findingsThe most common neurologic injuries include intracerebral hemorrhage, ischemic stroke, seizure, cerebral edema, intracranial hypertension, global cerebral hypoxia/anoxia, and brain death. These result from events prior to initiation of ECMO, failure of ECMO to provide adequate oxygen delivery, and/or complications that occur during ECMO. ECMO survivors also experience neurological and psychological sequelae similar to other survivors of critical illness. Summary Since many of the risk factors for neurologic injury cannot be easily mitigated, early diagnosis and intervention are crucial to limit morbidity and mortality from neurologic injury during ECMO.