Recent comprehensive next-generation genome and transcriptome analyses in lung cancer patients, several clinical observations, and compelling evidence from mouse models of lung cancer have uncovered a critical role for Notch signaling in the initiation and progression of non-small-cell lung cancer (NSCLC). Notably, Rumi is a "protein O-glucosyltransferase" that regulates Notch signaling through O-glucosylation of Notch receptors, and is the only enzymatic regulator whose activity is required for both ligand-dependent and ligand-independent activation of Notch. We have conducted a detailed study on RUMI's involvement in NSCLC development and progression, and have further explored the therapeutic potential of its targeting in NSCLC. We have determined that Rumi is highly expressed in the alveolar and bronchiolar epithelia, including club cells and alveolar type II cells. Remarkably, RUMI maps to the region of chromosome 3q that corresponds to the major signature of neoplastic transformation in NSCLC, and is markedly amplified and overexpressed in NSCLC tumors. Notably, RUMI expression levels are predictive of poor prognosis and survival in NSCLC patients. Our data indicates that RUMI modulates Notch activity in NSCLC cells, and that its silencing dramatically decreases cell proliferation, migration, and survival. RUMI downregulation causes severe cell cycle S-phase arrest, increases genome instability, and induces late apoptotic-nonapoptotic cell death. Our studies demonstrate that RUMI is a novel negative prognostic factor with significant therapeutic potential in NSCLC, which embodies particular relevance especially when considering that, while current Notch inhibitory strategies target only ligand-dependent Notch activation, a large number of NSCLCs are driven by ligand-independent Notch activity.
is properly cited.Purpose. We describe characteristics, utility, and safety of fiberoptic bronchoscopy (FOB) in an intensive care unit (ICU). Methods. Prospective and descriptive cohort of patients admitted to a respiratory ICU from March 2010 to June 2012. Results. A total of 102 FOBs were performed in 84 patients among 580 patients that were admitted to the ICU. Mean age was 48 ± 17 years. FOB was useful in 65% of diagnostic procedures and 83% of therapeutic procedures, with an overall utility of 75%. Indications and utility according to indication were pneumonia in 31 cases, utility of 52%; percutaneous tracheostomy guidance in 26 cases, utility of 100%; atelectasis in 25 cases, utility of 76%; airway exploration in 16 cases, utility of 75%; hemoptysis in two cases, utility of 100%; and difficult airway intubation in two cases, utility of 100%. A decrease in oxygen saturation (SpO 2 ) of >5% during FOB was present in 65% of cases, and other minor complications were present in 3.9% of cases. Conclusions. Reasons for performing FOB in the ICU have remained relatively stable over time with the exception of the addition of percutaneous tracheostomy guidance. Our series documents current indications and also the utility and safety of this procedure.
Primary tracheobronchial amyloidosis (TBA) is a rare disease characterized by extracellular focal or diffuse submucosal deposits of amyloid proteins. Various types of endobronchial lesions have been described in TBA when bronchoscopy is performed using white light. Narrow-band imaging bronchoscopy has been mainly employed for detecting preneoplastic and neoplastic endobronchial lesions as it provides more detailed images of the microvasculature reflective of an altered angiogenesis process. Here, we describe bronchoscopic findings with white light and narrow-band imaging in 2 patients presenting with central airway obstructive disease later confirmed as having primary TBA.
We present the case of a 33-year-old woman who was being treated for bronchial asthma for 4 years. A tracheal tumor was evident on a computed tomography of the thorax and removed with argon plasma coagulation. It was diagnosed as pleomorphic adenoma of the trachea. It is a rare tracheal tumor without definite treatment guidelines. Our endoscopic approach to this rare lesion is discussed.
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