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Background

Clear cell renal cell carcinoma (ccRCC) is known to occur across the adult lifetime traversing the spectrum of age-related organismal changes. Little is known as to how the aging process may affect the course of renal cell carcinoma (RCC) and the repertoire of genes involved.

Methods

Using The Cancer Genome Atlas (n?=?436) and Cancer Genomics of the Kidney (n?=?89) datasets, we applied regression analysis to examine associations between patient age and gene expression profiles in ccRCC tumors and normal kidney tissues. Pathway enrichment analysis was performed to identify cellular process that is affected by aging in ccRCC. Moreover, connectivity mapping analysis was used to predict age-dependent response to drug treatments.

Results

Our analysis revealed different age-dependent gene expression spectra in ccRCC and normal kidney tissues. These findings were significant and independently reproducible in both datasets examined. Age up-regulated genes, showing higher expression in older patients, were significantly enriched (false discovery rate <0.05) in normal tissues for pathways associated with immune response and extracellular matrix organization, whereas age up-regulated genes in tumors were enriched for metabolism and oxidation pathways. Strikingly, age down-regulated genes in normal cells were also enriched for metabolism and oxidation, while those in tumors were enriched for extracellular matrix organization. Further in silico analysis of potential drug targets predicted preferential efficacy of Phosphoinositide 3-kinase inhibitor or immunotherapy in association with age.

Conclusion

We report on previously unrecognized associations between age and molecular underpinnings of RCC, including age-associated expression of genes implicated in RCC development or treatment.  相似文献   
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Mandibulofacial dysostosis (Treacher Collins Syndrome) is an autosomal dominant genetic disorder that probably derives from inhibition of the facial structures from the first and second branchial arches. The facial pattern of the syndrome is a convex facial profile with a prominent nose above a retruded chin. The eyes are deformed by antimongoloid slant of the palpebral fissures and facial bones are hypoplastic. The alterations are caused by mutation in gene 5q32-33.1, which encodes the nucleolar phosphoprotein treacle. Computed tomography images are able to demonstrate craniofacial bones, allowing the morphological analysis of these bones in individuals with complex deformities. The purpose of this paper is to present the results of a clinical and computed tomography investigation of two patients with Treacher Collins syndrome.  相似文献   
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BACKGROUND: There is no consensus regarding the optimal rate of follow-up in the post-bariatric surgery patient population. METHODS: The records of all patients who underwent laparoscopic Roux-en-Y gastric bypass from 2001 to 2003 were reviewed. Using patient zip codes, travel distances were calculated between the patients' places of residence and our clinic. Patients were then assigned to 1 of 3 cohorts according to the following distances: (1) < 50 miles, (2) 50 to 100 miles, and (3) > 100 miles. Patient compliance with follow-up appointments at 3 weeks, 3 months, 6 months, 9 months, and 12 months was analyzed. Linear trends were identified using the Mantel-Haenszel test. Age and sex were analyzed as possible predictors of compliance using the chi(2) test. P values < .05 were considered statistically significant. RESULTS: The study group comprised 150 patients (127 females and 23 males). The 3 cohorts contained 115, 21, and 14 patients, respectively. All patients in each cohort were compliant with the 3-week follow-up appointment. Although there were differences in compliance between cohorts at each of the remaining appointments, only the 9-month (70.3% vs 61.9% vs 35.7%) visit showed statistical significance (P = .035). The 6-month visit trended toward significance (85.2% vs 76.2% vs 64.3%; P = .088). Males were more likely to be compliant with the 12-month follow-up (P = .040). When controlling for sex, travel distance was also a predictor of compliance at this follow-up visit (P = .024). Age was not predictive of compliance (P = .827). CONCLUSION: Based on our findings, we conclude that travel distance from the clinic does not significantly affect compliance at the initial follow-up, 3-month, and 12-month appointments. However, distance does tend to affect compliance at the 6-month appointment and significantly affects compliance at the 9-month appointment. Males are more likely to be compliant at the 12 month follow-up visit. We must continue to strive for 100% follow-up in our post-bariatric surgery patients.  相似文献   
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