The Journal of pathology
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The Journal of pathology · Jun 2009
ReviewHuman testicular (non)seminomatous germ cell tumours: the clinical implications of recent pathobiological insights.
Human germ cell tumours (GCTs) comprise several types of neoplasias with different pathogeneses and clinical behaviours. A classification into five subtypes has been proposed. Here, the so-called type II testicular GCTs (TGCTs), ie the seminomas and non-seminomas, will be reviewed with emphasis on pathogenesis and clinical implications. ⋯ The different non-seminomatous histological elements can be recognized using various markers, such as AFP and hCG, while others need confirmation. The value of micro-satellite instability as well as BRAF mutations in predicting treatment resistance needs validation in prospective trials. The availability of representative cell lines, both for seminoma and for embryonal carcinoma, allows mechanistic studies into the initiation and progression of this disease.
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The Journal of pathology · Feb 2009
A new role for the neuronal ubiquitin C-terminal hydrolase-L1 (UCH-L1) in podocyte process formation and podocyte injury in human glomerulopathies.
Glomerular epithelial cell (podocyte) injury is characterized by foot process retraction, slit diaphragm reorganization, and degradation of podocyte-specific proteins. However, the mechanisms underlying podocyte injury are largely unknown. The ubiquitin C-terminal hydrolase-L1 (UCH-L1) is a key modulator of ubiquitin modification in neurons. ⋯ In contrast, minimal change glomerulonephritis, a reversible disease, demonstrated minimal UCH-L1 and ubiquitin expression with intact alpha-actinin-4 but internalized nephrin. Glomerular kidney diseases typically not associated with foot process effacement (SLE class IV, ANCA+ necrotizing GN, amyloidosis, IgA nephritis) expressed intermediate to no UCH-L1 and ubiquitin. These studies show a role for UCH-L1 and ubiquitin modification in podocyte differentiation and injury.
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The Journal of pathology · Dec 2008
Genome-wide microRNA expression profiling in renal cell carcinoma: significant down-regulation of miR-141 and miR-200c.
We investigated expression profiles of microRNA (miRNA) in renal cell carcinoma [clear cell carcinomas (CCC) and chromophobe renal cell carcinomas (ChCC)] and in normal kidneys by using a miRNA microarray platform which covers a total of 470 human miRNAs (Sanger miRBase release 9.1). Unsupervised hierarchical cluster analysis revealed that CCC and ChCC were separable and that no subgroups were identified in CCCs. We found that 43 miRNAs were differentially expressed between CCC and normal kidney, of which 37 were significantly down-regulated in CCC and the other 6 were up-regulated. ⋯ We established by quantitative RT-PCR that, in CCCs in which miR-141 and miR-200c were down-regulated, ZFHX1B, a transcriptional repressor for CDH1/E-cadherin, tended to be up-regulated. Furthermore, we found that overexpression of miR-141 and miR-200c caused down-regulation of ZFHX1B and up-regulation of E-cadherin in two renal carcinoma cell lines, ACHN and 786-O. On the basis of these findings, we suggest that down-regulation of miR-141 and miR-200c in CCCs might be involved in suppression of CDH1/E-cadherin transcription via up-regulation of ZFHX1B.