No abstract

We studied the link between loss of E-cadherin-mediated adhesion and acquisition of malignant properties in threedimensional, human tissue constructs that mimicked the initial stages of squamous cell cancer progression. Suppression of E-cadherin expression in early-stage, skin-derived tumor cells (HaCaT-II-4) was induced by cytoplasmic sequestration of h h-catenin upon stable expression of a dominant-negative E-cadherin fusion protein (H-2K d -Ecad). In monolayer cultures, expression of H-2K d -Ecad resulted in decreased levels of E-cadherin, redistribution of h h-catenin to the cytoplasm, and complete loss of intercellular adhesion when compared with control II-4 cells. This was accompanied by a 7-fold decrease in h h-catenin-mediated transcription and a 12-fold increase in cell migration. In three-dimensional constructs, E-cadherin-deficient tissues showed disruption of architecture, loss of adherens junctional proteins from cell contacts, and focal tumor cell invasion. Invasion was linked to activation of matrix metalloproteinase (MMP)-mediated degradation of basement membrane in H-2K d -Ecad-expressing tissue constructs that was blocked by MMP inhibition (GM6001). Quantitative reverse transcription-PCR showed a 2.5-fold increase in MMP-2 and an 8-fold increase in MMP-9 in cells expressing the H-2K d -Ecad fusion protein when compared with controls, and gel zymography showed increased MMP protein levels. Following surface transplantation of three-dimensional tissues, suppression of E-cadherin expression greatly accelerated tumorigenesis in vivo by inducing a switch to highgrade carcinomas that resulted in a 5-fold increase in tumor size after 4 weeks. Suppression of E-cadherin expression and loss of its function fundamentally modified squamous cell carcinoma progression by activating a highly invasive, aggressive tumor phenotype, whereas maintenance of E-cadherin prevented invasion in vitro and limited tumor progression in vivo. (Cancer Res 2005; 65(5): 1783-91)

Salivary glands (SGs) exhibit several important features which are also common to endocrine glands: selfcontainment due to a surrounding capsule, highly efficient protein production and the ability to secrete proteins into the bloodstream. We have hypothesized that SGs are potentially useful as gene transfer targets for the correction of inherited monogenetic endocrine disorders. In the present communication, we extend our studies and attempt to test our hypothesis by comparing the efficacy of two commonly used viral vectors and the resulting serum and salivary distribution of transgene encoded hormones.

Background The intranasal endoscopic prelacrimal recess approach (PLRA) access to all aspects of the maxillary sinus while preserving the inferior turbinate and nasolacrimal duct and its use have been reported in the treatment of many maxillary sinus and lateral skull base diseases. Objective To retrospectively assess the effectiveness of a 10-year multicenter follow-up for the resection of inverted papilloma of the maxillary sinus (IPMS) via a PLRA. Methods A total of 71 patients were admitted and underwent IPMS excision via an intranasal endoscopic PLRA from 2003 to 2013. All patients underwent high-resolution computed tomography scanning of the nasal sinus, and some also underwent magnetic resonance imaging examination. Results Based on the Krouse staging system, all 71 patients belong to T3 staging. The PLRA was employed to remove IPMS in 71 patients. The postoperative pathological examination of the excised tissue revealed inverted papilloma, and cancerization was identified in 3 patients. The median follow-up time was 37.3 months (range: 13–134 months). Of the 71 patients, reoccurrence was seen in 5 patients (7.04%); 5 patients (7.04%) experienced numbness of the upper lid and the ala of the nose and 4 (5.63%) experienced mild collapse of the ala of the nose. Conclusions These multicenter follow-up results demonstrated that the PLRA is a safe and effective method for the excision of primary or recurrent IPMS with lower postoperative complications and recurrent rate.