c-Cbl Expression Correlates with Human Colorectal Cancer Survival and Its Wnt/ß-Catenin Suppressor Function Is Regulated by Tyr371 Phosphorylation.

The proto-oncogene ß-catenin drives colorectal cancer (CRC) tumorigenesis. Casitas B-lineage lymphoma (c-Cbl) inhibits CRC tumor growth through targeting nuclear ß-catenin by a poorly understood mechanism. In addition, the role of c-Cbl in human CRC remains largely underexplored. Using a novel quantitative histopathologic technique, we demonstrate that patients with high c-Cbl-expressing tumors had significantly better median survival (3.7 years) compared with low c-Cbl-expressing tumors (1.8 years; P = 0.0026) and were more than twice as likely to be alive at 3 years compared with low c-Cbl tumors (P = 0.0171). Our data further demonstrate that c-Cbl regulation of nuclear ß-catenin requires phosphorylation of c-Cbl Tyr371 because its mutation compromises its ability to target ß-catenin. The tyrosine 371 (Y371H) mutant interacted with but failed to ubiquitinate nuclear ß-catenin. The nuclear localization of the c-Cbl-Y371H mutant contributed to its dominant negative effect on nuclear ß-catenin. The biological importance of c-Cbl-Y371H was demonstrated in various systems, including a transgenic Wnt-8 zebrafish model. c-Cbl-Y371H mutant showed augmented Wnt/ß-catenin signaling, increased Wnt target genes, angiogenesis, and CRC tumor growth. This study demonstrates a strong link between c-Cbl and overall survival of patients with CRC and provides new insights into a possible role of Tyr371 phosphorylation in Wnt/ß-catenin regulation, which has important implications in tumor growth and angiogenesis in CRC.

Incidental finding of right subclavian vein aneurysm: A case report and review of the literature.

We present a case of a 94-year-old female who was shown to have an incidental subclavian venous aneurysm on CT during stroke workup. Subclavian venous aneurysms are a rare finding with only 13 reported in our literature search. Patients can present clinically with pain or supraclavicular swelling, or not unusually with no symptoms at all. These aneurysms can be detected on multiple imaging modalities, with ultrasound providing information on presence of a thrombus. Recent advances in minimally invasive procedures provide a new avenue of management for these aneurysms, with multiple cases involving an endovascular approach.

Performance of High Throughput SARS-CoV-2 Antigen Testing Compared to Nucleic Acid Testing.

OBJECTIVE: Independent assessment of SARS-CoV-2 antigen (COV2Ag) tests remains important as varying performance between assays is common. We assessed the performance of a new high-throughput COV2Ag test compared to SARS-CoV-2 nucleic acid amplification tests (NAAT). METHODS: A total of 347 nasopharyngeal samples collected from January to October 2021 were assessed by NAAT as part of standard-of-care testing (CDC LDT or GeneXpert System, Cepheid) and COV2Ag using the ADVIA Centaur CoV2Ag assay (Siemens Healthineers). RESULTS: Among NAAT positive specimens we found 82.4% agreement and in NAAT negative specimens we found 97.3% agreement (overall agreement 85.6%). In symptomatic persons, COV2Ag agreed with NAAT 90.0% (n = 291), and in asymptomatic persons, 62.5% (n = 56). Agreement between positive NAAT and COV2Ag increased at lower cycle threshold (Ct) values. CONCLUSION: The COV2Ag assay exceeded the World Health Organization minimum performance requirements of ≥ 80% sensitivity and ≥ 97% specificity. The COV2Ag assay is helpful for large scale screening efforts due to high-throughput and reduced wait times.