Well-differentiated neuroendocrine tumors (WDNT, carcinoid tumors) are uncommon indolent neoplasms. The genetic alterations of these tumors are not well characterized. We used genome-wide high-density single nucleotide polymorphism (SNP) array analysis to detect copy number alterations in 29 WDNTs, including seven lung, seven nonileal gastrointestinal, and 15 ileal tumors, and compared with allelic imbalances in 15 pancreatic endocrine tumors (PETs). Most frequent allelic imbalances in WDNTs were losses of chromosome 18 in 10 tumors (34%), chromosome 21 or 21q in six (21%), chromosome 13 or 13q in five (17%) and chromosome 16 or 16q in four (14%) tumors, and amplification of chromosome 20 or 20p in seven (24%) tumors. We also found one tumor with loss of heterozygosity of chromosomes 10 and 15 without copy number loss. These allelic imbalances were associated with primary site of tumor: loss of chromosome 18 was present exclusively in ileal WDNTs (P 5 0.001), and loss of chromosome 21 or 21q was more frequent in nonileal gastrointestinal WDNTs (P 5 0.02). The tumors with loss of chromosome 21 were larger compared to tumors without loss (P 5 0.03). Chromosomal aberrations were less common in WDNTs from lung and gastrointestinal tract compared to PETs (P 5 0.001). Our study shows that genome-wide allelotyping using SNP array is a powerful new tool for the analysis of allelic imbalances in WDNTs, and some of these alterations are tumor site-dependent and are different than in PETs. V V C 2007 Wiley-Liss, Inc.
stimulation of the pudendal nerve upregulates neurotrophin expression and improves recovery in a rat model of SUI.METHODS: Rats received 1 hour of electrical stimulation (20 Hz, 0.3 mA, 0.1 ms pulse) or sham stimulation of the pudendal nerve immediately after simulated birth injury, consisting of vaginal distension and pudendal nerve crush. A separate cohort of rats received sham injury and no treatment. All rats underwent stimulation or sham stimulation for 1 hour twice per week for 2 weeks. Brain derived neurotrophic factor (BDNF) and bII-tubulin (neuronal cytoskeletal protein and marker of neuroregenerative response) expression in Onuf's nucleus was measured with RT-PCR. Leak point pressure (LPP) and external urethral sphincter electromyography (EUS EMG) was performed. Data was analyzed with a two-way ANOVA and Student-Newman-Keuls posthoc pairwise comparisons with p<0.05 statistically significant.RESULTS: Compared to sham stimulation, electrical stimulation significantly increased both BDNF and bII-tubulin expression in Onuf's nucleus, demonstrating an increased neuroregenerative response. Both LPP and baseline EUS EMG amplitude decreased significantly after injury compared to sham injury and increased significantly with stimulation compared to sham stimulation. During voiding, EUS EMG burst frequency, burst duration, and interburst interval were significantly decreased by injury compared to sham and after injury were significantly increased with electrical stimulation compared to sham.CONCLUSIONS: Pudendal nerve electrical stimulation appears to promote SUI recovery via strengthening the neuroregenerative response by upregulating BDNF expression in pudendal nerve cell bodies. Electrical stimulation may shorten postpartum SUI duration and could potentially serve as a preventative treatment for later SUI development.
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