[show abstract][hide abstract] ABSTRACT: Renal transplantation is the preferred therapy to extend life expectancy and quality of life for patients with chronic kidney disease. There are many barriers in the process of live kidney donation that prevent the timely progression from organ requirement to transplantation, including the progression of the live donor through a medical evaluation. We assess how easily patients complete the donor workup, how often the medical evaluation identifies significant incidental findings, and which surgical procedure is planned for organ retrieval.
We reviewed our donor database and the minutes from our multidisciplinary rounds from 2002 to 2008 to assess how medical, radiological and psychological findings were used to decide on the candidacy of potential donors.
Half (50.2%) of patients did not pass the initial health screen. Of the 467 patients who progressed beyond the health screen to the computed tomographic angiogram evaluation, 48 (10.3%) were excluded as donors and 419 (89.7%) were accepted. Of those accepted, 136 (32.5%) were conditional on further medical workup. Of the patients accepted (n=419), 375 (89.5%) were planned for laparoscopic left-sided approach.
The vast majority of patients who passed the initial health screen for kidney donation will be accepted as donors, but about one-third will require further workup. It is rare to identify life-threatening disease on screening computerized tomographic angiograph for kidney donor workup.
Canadian Urological Association journal = Journal de l'Association des urologues du Canada 01/2013; 7(1-2):41-5. · 1.66 Impact Factor
[show abstract][hide abstract] ABSTRACT: Metastatic renal cell carcinoma (RCC) is one of the most treatment-resistant malignancies and patients have a dismal prognosis with <10% five-year survival rate. Identification of markers that can predict the potential of metastases will have a great impact in improving patient outcome. In this study, we used differential proteomics with isobaric tags for relative and absolute quantitation (iTRAQ) labeling and LC-MS/MS analysis to identify proteins that are differentially expressed in metastatic compared to primary RCC. We identified 1256 non-redundant proteins and 456 of these were quantified. Further analysis identified 29 proteins that were differentially expressed (12 overexpressed and 17 under expressed) in metastatic vs. primary RCC. Dysregulated protein expressions of profilin-1 (Pfn1), 14-3-3 zeta/delta (14-3-3ζ), and galectin-1 (Gal-1) were verified on two independent sets of tissues by western blot and immunohistochemical analysis. Hierarchical clustering analysis showed the protein expression profile specific for metastatic RCC can distinguish between aggressive and non-aggressive RCC. Pathway analysis showed that dysregulated proteins are involved in cellular processes related to tumor progression and metastasis. Furthermore, preliminary analysis using a small set of tumors showed that increased expression of Pfn1 is associated with poor outcome and is a potential prognostic marker in RCC. In addition, 14-3-3ζ and Gal-1 also showed higher expression in the tumors with poor prognosis compared to those with good prognosis. Dysregulated proteins in metastatic RCC represent potential prognostic markers for kidney cancer patients and a greater understanding of their involved biological pathways can serve as the foundation of the development of novel targeted therapies for metastatic RCC.
[show abstract][hide abstract] ABSTRACT: Metastasis results in most of the cancer deaths in clear cell renal cell carcinoma (ccRCC). MicroRNAs (miRNAs) regulate many important cell functions and play important roles in tumor development, metastasis and progression. In our previous study, we identified a miRNA signature for metastatic RCC. In this study, we validated the top differentially expressed miRNAs on matched primary and metastatic ccRCC pairs by quantitative polymerase chain reaction. We performed bioinformatics analyses including target prediction and combinatorial analysis of previously reported miRNAs involved in tumour progression and metastasis. We also examined the co-expression of the miRNAs clusters and compared expression of intronic miRNAs and their host genes. We observed significant dysregulation between primary and metastatic tumours from the same patient. This indicates that, at least in part, the metastatic signature develops gradually during tumour progression. We identified metastasis-dysregulated miRNAs that can target a number of genes previously found to be involved in metastasis of kidney cancer as well as other malignancies. In addition, we found a negative correlation of expression of miR-126 and its target vascular endothelial growth factor (VEGF)-A. Cluster analysis showed that members of the same miRNA cluster follow the same expression pattern, suggesting the presence of a locus control regulation. We also observed a positive correlation of expression between intronic miRNAs and their host genes, thus revealing another potential control mechanism for miRNAs. Many of the significantly dysregulated miRNAs in metastatic ccRCC are highly conserved among species. Our analysis suggests that miRNAs are involved in ccRCC metastasis and may represent potential biomarkers.
[show abstract][hide abstract] ABSTRACT: Renal cell carcinoma is the most common neoplasm of the adult kidney. Currently to our knowledge there are no biomarkers for diagnostic, prognostic or predictive applications for renal cell carcinoma. miRNAs are nonprotein coding RNAs that negatively regulate gene expression and are potential biomarkers for cancer.
We analyzed 70 matched pairs of clear cell renal cell carcinoma and normal kidney tissues from the same patients by microarray analysis and validated our results by quantitative real-time polymerase chain reaction. We also performed extensive bioinformatic analysis to explore the role and regulation of miRNAs in clear cell renal cell carcinoma.
We identified 166 miRNAs that were significantly dysregulated in clear cell renal cell carcinoma, including miR-122, miR-155 and miR-210, which had the highest over expression, and miR-200c, miR-335 and miR-218, which were most down-regulated. Analysis of previously reported miRNAs dysregulated in RCC showed overall agreement in the direction of dysregulation. Extensive target prediction analysis revealed that many miRNAs were predicted to target genes involved in renal cell carcinoma pathogenesis. In renal cell carcinoma miRNA dysregulation can be attributed in part to chromosomal aberrations, co-regulation of miRNA clusters and co-expression with host genes. We also performed a preliminary analysis showing that miR-155 expression correlated with clear cell renal cell carcinoma size. This finding must be validated in a larger independent cohort.
Analysis showed that miRNAs are dysregulated in clear cell renal cell carcinoma and may contribute to kidney cancer pathogenesis by targeting more than 1 key molecule. We identified mechanisms that may contribute to miRNA dysregulation in clear cell renal cell carcinoma. Dysregulated miRNAs represent potential biomarkers for kidney cancer.
The Journal of urology 09/2011; 186(3):1077-83. · 4.02 Impact Factor
[show abstract][hide abstract] ABSTRACT: Renal cell carcinoma (RCC) with multinucleated giant cells has been reported in the literature. Different types of multinucleated giant cells have been described, including the osteoclast-like giant cells, rhabdoid cells, syncytial giant cells and tumor multinucleated giant cells.
We describe a unique case of a clear cell RCC with extensive giant cell component. Tumor giant cells were arranged in an alveolar pattern and formed more than 50% of the tumor. The rest of the tumor was a classic clear cell renal cell carcinoma. A rhabdoid component was also focally seen. The immunohistochemical profile of the giant cells showed positivity for RCC, vimentin and, very focal positivity for cytokeratins, and negatively for CD68. A traditional spindle cell sarcomatoid component was not seen. The patient had advanced disease at presentation with metastasis to peri-aortic lymph nodes.
Giant cells can rarely constitute a major component of renal cell carcinoma and it is not clear if these represent a sarcomatoid component or merely a higher grade of the epithelial component. These cells may have different immunohistochemical profiles in different cases and may therefore be of different derivation. This may necessitate the revision of current classification schemes for renal cell carcinoma. It is also not clear how the presence of the various types of giant cells in renal cell carcinoma and their amount affects the clinical outcome.
The Canadian Journal of Urology 06/2010; 17(3):5219-22. · 0.74 Impact Factor
[show abstract][hide abstract] ABSTRACT: Renal cell carcinoma (RCC) accounts for 3% of all adult malignancies and currently no diagnostic marker exists. Kallikrein-related peptidases (KLKs) have been implicated in numerous cancers including ovarian, prostate, and breast carcinoma. KLKs 5, 6, 10, and 11 have decreased expression in RCC when compared to normal kidney tissue. Our bioinformatic analysis indicated that the KLK 1, 6, and 7 genes have decreased expression in RCC. We experimentally verified these results and found that decreased expression of KLKs 1 and 3 were significantly associated with the clear cell RCC subtype (p<0.001). An analysis of miRNAs differentially expressed in RCC showed that 61 of the 117 miRNAs that were reported to be dysregulated in RCC were predicted to target KLKs. We experimentally validated two targets using two independent approaches. Transfection of miR-224 into HEK-293 cells resulted in decreased KLK1 protein levels. A luciferase assay demonstrated that hsa-let-7f can target KLK10 in the RCC cell line ACHN. Our results, showing differential expression of KLKs in RCC, suggest that KLKs could be novel diagnostic markers for RCC and that their dysregulation could be under miRNA control. The observation that KLKs could represent targets for miRNAs suggests a post-transcriptional regulatory mechanism with possible future therapeutic applications.
[show abstract][hide abstract] ABSTRACT: miRNAs are small, nonprotein coding RNAs that are differentially expressed in many malignancies. We previously identified 80 miRNAs that are dysregulated in clear cell renal cell carcinoma. In this study we validated over expression of the miR-17-92 cluster in clear cell renal cell carcinoma and tested the effect of 2 members of this cluster (miR-17-5p and miR-20a) on tumor proliferation. We also elucidated the role of miRNA in clear cell renal cell carcinoma pathogenesis with bioinformatics.
miRNA expression was validated by quantitative reverse transcriptase-polymerase chain reaction. The cell proliferation effect of miR-17-5p and miR-20a was tested in a renal adenocarcinoma cell line model. Multiple in silico analyses were done of dysregulated miRNAs.
We validated miR-71-92 cluster over expression in clear cell renal cell carcinoma by quantitative reverse transcriptase-polymerase chain reaction. Transfection of miR-20a inhibitor significantly decreased cell proliferation in a dose dependent manner. Transfection of miR-17-5p, which is not endogenously expressed in the ACHN cell line, led to increased cell proliferation compared to control values. This effect was suppressed by miR-17-5p inhibitor. Bioinformatics analysis identified 10 clusters of miRNAs dysregulated in clear cell renal cell carcinoma that followed the same expression patterns. We also identified matching patterns between reported chromosomal aberration in clear cell renal cell carcinoma and miRNA dysregulation for 37.5% of the miRNAs. Target prediction analysis was done using multiple algorithms. Many key molecules in clear cell renal cell carcinoma pathogenesis, including HIFs, mTOR, VEGF and VHL, were potential targets for dysregulated miRNAs.
A significant number of dysregulated proteins in clear cell renal cell carcinoma are potential miRNA targets. Also, many clear cell renal cell carcinoma dysregulated miRNAs are phylogenetically conserved.
The Journal of urology 12/2009; 183(2):743-51. · 4.02 Impact Factor
[show abstract][hide abstract] ABSTRACT: We seek to identify the differentially expressed miRNAs in the clear cell subtype (ccRCC) of kidney cancer.
We performed a miRNA microarray analysis to compare the miRNA expression levels between ccRCC tissues and their normal counterpart. The top dysregulated miRNAs were validated by quantitative RT-PCR analysis. Bioinformatics analysis was also performed.
A total of 33 dysregulated miRNAs were identified in ccRCC, including 21 upregulated miRNAs and many of these miRNAs have been reported to be dysregulated in other malignancies and have a potential role in cancer pathogenesis. The miRNAs showed a significant correlation with reported chromosomal aberration sites. We also utilized target prediction algorithms to identify gene targets. Preliminary analyses showed these targets can be directly involved in RCC pathogenesis.
We identified miRNAs that are dysregulated in ccRCC and bioinformatics analysis suggests that these miRNAs may be involved in cancer pathogenesis and have the potential to be biomarkers.
[show abstract][hide abstract] ABSTRACT: Renal cell carcinoma (RCC) is the most common neoplasm in the adult kidney. Unfortunately, there are currently no biomarkers for the diagnosis of RCC. In addition to early detection, biomarkers have a potential use for prognosis, for monitoring recurrence after treatment, and as predictive markers for treatment efficiency. In this study, we identified proteins that are dysregulated in RCC, utilizing a quantitative mass spectrometry analysis. We compared the protein expression of kidney cancer tissues to their normal counterparts from the same patient using LC-MS/MS. iTRAQ labeling permitted simultaneous quantitative analysis of four samples (cancer, normal, and two controls) by separately tagging the peptides in these samples with four cleavable mass-tags (114, 115, 116, and 117 Da). The samples were then pooled, and the tagged peptides resolved first by strong cation exchange chromatography and then by nanobore reverse phase chromatography coupled online to nanoelectrospray MS/MS. We identified a total of 937 proteins in two runs. There was a statistically significant positive correlation of the proteins identified in both runs (r(p) = 0.695, p < 0.001). Using a cutoff value of 0.67 fold for underexpression and 1.5 fold for overexpression, we identified 168 underexpressed proteins and 156 proteins that were overexpressed in RCC compared to normal tissues. These dysregulated proteins in RCC were statistically significantly different from those of transitional cell carcinoma and end-stage glomerulonephritis. We performed an in silico validation of our results using different tools and databases including Serial Analysis of Gene Expression (SAGE), UniGene EST ProfileViewer, Cancer Genome Anatomy Project, and Gene Ontology consortium analysis.
Journal of Proteome Research 08/2009; 8(8):3797-807. · 5.06 Impact Factor
[show abstract][hide abstract] ABSTRACT: We recently identified a group of proteins which are dysregulated in renal cell carcinoma (RCC). In this study, we performed bioinformatics and pathway analysis of these proteins. Proteins were mapped to gene ontology biological processes. The upregulated proteins tend to cluster in processes, such as cancer initiation and progression. In addition, we identified a number of pathways that are significantly enriched in RCC. Some of these are 'common' pathways which are dysregulated in many cancers, but we also identified a number of pathways which were not previously linked to RCC. In addition to their potential prognostic values, many of these pathways have a potential as therapeutic targets for RCC. To verify our findings, we compared our proteins to a pool of datasets from published reports. Although there were only a minimal number of common proteins, there was a significant overlap between the identified pathways in the two groups. Moreover, out of 16 individually discovered genes identified by a literature search, 10 were found to be related to our dysregulated pathways. We also verified the upregulation of the mammalian target of rapamycin signaling pathway in RCC by immunohistochemistry. Finally, we highlight the potential clinical applications of pathway analysis in kidney cancer.