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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   
3.

Background and Purpose:   

Management of rib fractures constitutes a major part of the trauma workload of any unit. Rib fractures result in disrupted chest wall mechanics and ventilatory insufficiency. The ability of a lung injury scoring system to predict the degree of respiratory dysfunction after rib fractures was evaluated.  相似文献   
4.
A 48‐year‐old male patient with long‐standing ulcerative colitis since February 2001 which was diagnosed by endoscopy, developed acute digital ischemia affecting both hands with fixed colour changes in the left index finger which was followed shortly by digital ulceration. Magnetic resonance angiography (MRA) of both upper limbs showed evidence of vasculitis affecting digital arterioles on both sided and right subclavian occlusion. The patient received pulse methylprednisolone followed by cyclophosphamide pulse therapy, the latter continuing on a monthly basis for 6 months with appreciable improvement and remission of the vasculitic process; follow‐up MRA showed reperfusion of the previously occluded subcalvian artery. To the authors’ knowledge vasculitis complicating the course of ulcerative colitis is a rare association and is only sporadically reported in the literature. This rare entity should be diagnosed early and aggressively treated; MRA is a very promising diagnostic tool that is suitable for both diagnosis and follow‐up of patients with this rare entity.  相似文献   
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Dysfunction of the central dopaminergic neurotransmission has been suggested to play an important role in the etiology of certain neuropsychiatric disorders such as drug abuse. It has been shown that the dopamine D2 receptor (DRD2) gene dysfunction is associated with multi-drug addiction. Addiction to opium is the most common form of drug abuse in Iran. We studied the allelic association between DRD2 Taq I A polymorphism in 100 opium-dependent Iranian patients and 130 unrelated controls. A 310 bp (base pair) region surrounding Taq I site at the DRD2 locus was amplified by polymerase chain reaction (PCR) and the PCR product was incubated with Taq I restriction enzyme. The A1 allele remained intact while the A2 allele was cut. Significant association was observed between A1 allele and addiction in the patients group (P < 0.0001). Moreover, the frequency of A1A1 genotype was significantly higher in opium users than controls (P < 0.0001). Our result indicates that DRD2 might be involved in the pathophysiology of opium addiction.  相似文献   
7.
Hard capsules are made of pure gelatin and small quantities of additives, including colouring agents permitted for use in food. In this study, the effects of three colouring agents (sunset yellow, quinoline yellow and erythrosine) on true and pseudo-cholinesterases (ChE) are assessed in erythrocytes and plasma, respectively. Results indicated that the synthetic compounds affected both true and pseudo ChE activity. The concentration of sunset yellow which caused 50% inhibition (IC50) of true ChE was about 64% that of pseudo-ChE; for erythrosine, IC50 was approximately the same for both true and pseudo-ChE; and for quinoline yellow, IC50 for true ChE was 25% of pseudo-ChE, although its effect on both true and pseudo-ChE was greater than seen with the other two dyes. Inhibitions of both true and pseudo-ChE were of mixed type (competitive and non-competitive). The enzyme-inhibitor dissociation constant (Ki) indicated that quinoline yellow was most potent and erythrosine was least potent out of the three compounds. Inhibition of both true and pseudo-ChE by each of the three dyes was abolished by dialysis, indicating that the effects were reversible.  相似文献   
8.
Dendritic cells (DCs) are potent antigen presenting cells and possess a direct anti-tumor cytotoxic ability. Nevertheless, the mechanism of anti-tumor cytotoxicity by DCs and the methods for its evaluation are not fully elucidated. In order to clarify this mechanism of cytotoxicity, we examined the ability of DCs 1) to suppress [3H] thymidine (3H-TdR) uptake by tumor cells; 2) to induce cytolysis on 51Cr-labeled tumor cells; 3) and to induce DNA fragmentation on 3H-TdR labeled tumor cells (JAM test). Cytolysis and DNA fragmentation are markers of necrotic and apoptotic mechanisms of cytotoxicity in vitro, respectively. DCs inhibited approximately 38.6% to 54.8% of the growth of B4D6, NB4, U937, and Daudi cells as evaluated by the uptake of 3H-TdR. However no cytolysis was verified by 51Cr-release assay. On the other hand, cytotoxicity rates found using the JAM test ranged from 3 to 81% depending on the cell line and the effector to target cell ratio. The discrepancy of cytotoxicity between 51Cr-release assay and the JAM test may be due to the phagocytosis of apoptotic tumor cells or the absorption of released 51Cr by DCs surrounding the target cells. In conclusion, the JAM test was more sensitive than the 4-h and the 10-h 51Cr-release assay to investigate cytotoxicity mediated by DCs toward hematopoietic tumor cell lines in vitro.  相似文献   
9.
Clear cell carcinoma has been described in numerous anatomic sites. Renal location is the most frequent. The occurrence in the gallbladder is exceptional. We report the case of a 71-Year-old woman who presented with sub-acute angiocrolitis. Computer tomographic scan revealed a polypoid mass close to the neck of the gallbladder; there was no renal lesion. Histological analysis of the gallbladder showed a primitive clear cell carcinoma with a papillary pattern associated with carcinoma in situ. Immunohistochemical study confirmed the primitive character of the tumor, characterized by an expression of KL-1, EMA and ACE and an absence of vimentin, CD 10 and CD15. Clear cell carcinomas of the gallbladder are uncommon neoplasms which could only be diagnosed on clinical, histological and immunohistochemical arguments.  相似文献   
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