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Lara Feulner Hamed S. Najafabadi Simon Tanguay Janusz Rak Yasser Riazalhosseini 《Urologic oncology》2019,37(2):166-175
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.
Darren R. Feldman MD Yasser Ged MBBS Chung-Han Lee PhD Andrea Knezevic MS Ana M. Molina MD Ying-Bei Chen PhD Joshua Chaim DO Devyn T. Coskey MS Samuel Murray MS Satish K. Tickoo MD Victor E. Reuter MD Sujata Patil PhD Han Xiao MD Jahan Aghalar MD Arlyn J. Apollo MD Maria I. Carlo MD Robert J. Motzer MD Martin H. Voss MD 《Cancer》2020,126(24):5247-5255
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Seventy patients, aged 1–20 years, were seen at Jordan University Hospital with high blood pressure (BP) over a 3-year period. BP values ranged from 140 to 230 mmHg for systolic pressure and from 90 to 130 mmHg for diastolic pressure. Essential hypertension was seen in only 6 patients (8.6%); secondary hypertension (n=64 or 91.4%) was due to renal parenchymal diseases (RPD) in 46 patients (65.7%), reno-vascular lesions in 8 (11.4%), renal transplantation in 5 (7.2%), teenage pregnancy in 4 (5.7%), and phaeochromocytoma in 1 patient (1.4%). The aetiologies of RPD were as follows: end-stage renal disease requiring dialysis in 14 patients, acute glomerulonephritis in 14, idiopathic nephrotic syndrome in 10, chronic renal insufficiency in 5, and polycystic kidney in 3 patients. Surgical cure of hypertension was achieved in 5 of the children with reno-vascular lesions and in the patient with phaeochromocytoma. 相似文献
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Salwa AlDahlawi BDS MSc ; Ameneh Eslami MD ; Lari Häkkinen DDS PhD ; Hannu S. Larjava DDS PhD 《Wound repair and regeneration》2006,14(3):289-297
The alphavbeta6 integrin is an exclusively epithelial integrin that is highly expressed during fetal development. In adult tissue, alphavbeta6 integrin is expressed during inflammation, carcinogenesis, and in wound healing. We previously reported that alphavbeta6 integrin is highly expressed in poorly healing human wounds and its over-expression is associated with chronic wounds in a mouse model. The objective of this study was to investigate the role of alphavbeta6 integrin in compromised wound healing induced by hydrocortisone treatment or aging by using young and old mice deficient in or overexpressing the beta6 integrin subunit in the epidermis. Untreated aged beta6 integrin-deficient (beta6-/-) animals showed a significant delay in wound healing when compared to their age-matched controls or younger beta6-/- mice. The most significant delay was observed at the stages where granulation tissue deposition was occurring. Hydrocortisone treatment significantly delayed wound healing in wild-type and beta6 integrin-deficient mice in comparison with the untreated controls. However, hydrocortisone treatment in beta6 integrin overexpressing animals did not cause a significant delay in wound healing. The results of this study suggest that alphavbeta6 integrin plays an important role in wound healing in animals compromised by either age or stress mimicked by hydrocortisone. 相似文献
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Yasser Samman Imran Masood Vijay Vardhan Killampalli Neil Howell E. Kaya Alpar Sunil K. Banerjee 《European Journal of Trauma》2005,31(2):133-137
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7.
Ming Yang Chang Emma Parker Salwa Ibrahim John R Shortland Meguid El Nahas John L Haylor Albert C M Ong 《Nephrology, dialysis, transplantation》2006,21(8):2078-2084
BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited human kidney disease and is caused by germline mutations in PKD1 (85%) or PKD2 (15%). It has been estimated that around 1% of tubular cells give rise to cysts, and cell hyperproliferation has been noted to be a cardinal feature of cystic epithelium. Nevertheless, it is uncertain whether the increase in proliferative index observed is an early or late feature of the cystic ADPKD kidney. METHODS: Two Pkd2 mouse mutants (WS25 and WS183) have been recently generated as orthologous models of PKD2. To determine the effect of Pkd2 dosage on cell proliferation, cyst formation and renal fibrosis, we studied renal tissue from Pkd2(WS25/WS25) and Pkd2(+/-) mice by histological analysis. We also examined the proliferative index in archival nephrectomy tissue obtained from patients with ADPKD and normal controls. RESULTS: The proliferative index of non-cystic tubules in Pkd2 mutant mice as assessed by proliferating cell nuclear antigen and Ki67-positive nuclei was between 1-2%, values 5-10 times higher than control tissue. Similarly, the proliferative index of non-cystic tubules in human ADPKD kidneys was 40 times higher than corresponding controls. In Pkd2 mutant mice, significant correlations were found between the fibrosis score and the mean cyst area as well as with the proliferative index. Of significance, proliferating tubular cells were uniformly positive for polycystin-2 expression in Pkd2(+/-) kidney. CONCLUSION: These results suggest that an increase in cell proliferation is an early event preceding cyst formation and can result from haploinsufficiency at Pkd2. The possible pathogenic link between tubular cell proliferation, interstitial fibrosis and cyst formation is discussed. 相似文献
8.
Yasser EMAD Yasser RAGAB Ahmed EL‐MARAKBI Salama MOHAMED HANFI 《International journal of rheumatic diseases》2007,10(4):326-329
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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Maria Shahmoradgoli Najafabadi Mina Ohadi Mohammad Taghi Joghataie Faraz Valaie Yasser Riazalhosseini Hamid Mostafavi Fariba Mohammadbeigi Hossein Najmabadi 《American journal of medical genetics. Part B, Neuropsychiatric genetics》2005,(1):39-41
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