We have previously described a new aspect of the Inhibitor of Apoptosis (IAP) family of proteins anti-apoptotic activity that involves the TAK1/JNK1 signal transduction pathway (1, 2). Our findings suggest the existence of a novel mechanism that regulates the antiapoptotic activity of IAPs that is separate from caspase inhibition but instead involves TAK1-mediated activation of JNK1. In a search for proteins involved in the XIAP/TAK1/JNK1 signaling pathway we isolated by yeast two-hybrid screening a novel X chromosomelinked IAP (XIAP)-interacting protein that we called ILPIP (hILP-Interacting Protein). Whereas ILPIP moderately activates JNK family members when expressed alone, it strongly enhances XIAP-mediated activation of JNK1, JNK2, and JNK3. The expression of a catalytically inactive mutant of TAK1 blocked XIAP/ILPIP synergistic activation of JNK1 thereby implicating TAK1 in this signaling pathway. ILPIP moderately protects against interleukin-1 converting enzyme-or Fas-induced apoptosis and significantly potentiates the anti-apoptotic activity of XIAP. In vivo co-precipitation experiments show that both ILPIP and XIAP interact with TAK1 and tumor necrosis factor receptor-associated factor 6. Finally, expression of ILPIP did not affect the ability of XIAP to inhibit caspase activation, further supporting the idea that XIAP protection against apoptosis is achieved by two separate mechanisms: one requiring JNK1 activation and a second involving caspase inhibition.
The data indicate a lower incidence of central compartment lymph node metastasis in those with CLT in this patient population, suggesting a potential protective role in tumor spread. The equal distribution of tumor mutations between the carcinomas with and without evidence of CLT argues against a mutation-specific antigen as the immunologic stimulus. Further research is needed to characterize the role of autoimmunity in thyroid cancer.
Positive risk factors for central LNM include male sex, extracapsular extension, angiolymphatic invasion, and advanced T stage. The follicular variant histological type has a significantly lower incidence of central neck metastasis. In contrast to recent studies, the BRAF mutation was not significantly associated with central neck LNM from PTC when using a strict definition of a central neck dissection.
Introduction. Controversy exists over whether tonsillectomy will affect speech in patients with known velopharyngeal insufficiency (VPI), particularly in those with cleft palate. Methods. All patients seen at the OHSU Doernbecher Children's Hospital VPI clinic between 1997 and 2010 with VPI who underwent tonsillectomy were reviewed. Speech parameters were assessed before and after tonsillectomy. Wilcoxon rank-sum testing was used to evaluate for significance. Results. A total of 46 patients with VPI underwent tonsillectomy during this period. Twenty-three had pre- and postoperative speech evaluation sufficient for analysis. The majority (87%) had a history of cleft palate. Indications for tonsillectomy included obstructive sleep apnea in 11 (48%) and staged tonsillectomy prior to pharyngoplasty in 10 (43%). There was no significant difference between pre- and postoperative speech intelligibility or velopharyngeal competency in this population. Conclusion. In this study, tonsillectomy in patients with VPI did not significantly alter speech intelligibility or velopharyngeal competence.
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