Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intratubular epithelial dysplasia (IED) of the renal tubules has not been fully described in human renal cell carcinoma (RCC). This lesion has been found in male Syrian hamsters exposed to estrogens. One article reports IED in human kidney showing nephrosclerosis and RCC. We examined "normal" kidney tissue adjacent to 110 cases of RCC in an attempt to identify possible precursor lesions. There were 73 male and 37 female patients (M/F = 2:1). The ages ranged from 27 to 86 years (median 64 years). IED was identified in 30 cases. The lesions consisted of foci of crowded tubular epithelium with large, vesicular nuclei two to three times the size of nuclei of benign tubular cells with eosinophilic macronucleoli. The tubules were occasionally filled with dysplastic cells mimicking carcinoma in situ. The lesions were predominantly cortical and periglomerular. They either were subtle and focal or, less commonly, involved tubules diffusely. Eighteen of the 73 male patients (24%) had these lesions compared with 12 of 37 female patients (32%). They were more usually seen in the clear cell (21 of 66) and sarcomatoid (three of four) variants of RCC than in the oncocytic/granular cell (four of 25) or tubulopapillary (two of 14) variants. One case of collecting duct RCC showed no evidence of IED. Immunohistochemical assessment of 20 dysplastic and 20 nondysplastic lesions with their adjacent RCC for cytokeratin, vimentin, cathepsin-D, and epidermal growth factor receptors was inconclusive. Our findings suggest that IED associated with RCC might represent previously unrecognized precursor lesions along the spectrum ranging from dysplasia to frank carcinoma. The biological significance of these lesions, their preponderance in women, and the phenotypic and genotypic characteristics require further investigation.
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PMID:Dysplastic tubular epithelium in "normal" kidney associated with renal cell carcinoma. 757 98

In recent years, the concept of collecting duct carcinoma (CDC) has been established. CDCs constitute about 0.4 to 2% of RCCs. Macroscopically, CDCs occur in the renal medulla. On the cut surface, they are generally firm, white or grey and poorly circumscribed. Histologically, CDCs are characterized by various cytological and histological appearances. Furthermore, desmoplastic stromal reaction around the tumor and atypical hyperplastic changes or carcinoma in situ in the adjacent medullary collecting duct are frequently observed. Histological distinction from papillary RCCs is most important, because both tumors share some structural and histochemical features, and it seems that some investigators have confused diagnostic criteria for CDCs. On the other hand, the concept of medullary carcinoma, which preferentially occurs in a black race and shows histological features similar to those of CDC, has also recently been established. Although there have been few studies on chromosomal abnormalities of CDCs and consistent abnormalities have not been identified, a recent study using microsatellite analysis has shown a high frequency (60%) of LOH in 1q32.1-32.2. Further studies are needed to elucidate the genetic characteristics of CDCs and to determine the relationship or difference between CDCs and medullary carcinomas.
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PMID:Review of collecting duct carcinoma with focus on clinical and pathobiological aspects. 1237 Nov 57

Drug-induced kidney injury (DIKI) remains a significant concern during drug development. Whereas FDA-endorsed urinary protein biomarkers encounter limitations including the lack of translatability, there is a considerable interest surrounding the application of microRNAs (miRNAs) in the renal biomarker space. Current knowledge about the value of these novel biomarkers for subacute preclinical rodent studies is still sparse. In this work, Wistar rats were treated with three nephrotoxic compounds-cisplatin (CIS, proximal tubule, 2.5 mg/kg, intraperitoneal [i.p.]), puromycin (PUR, glomerulus, 20/10 mg/kg, i.p.) and N-phenylanthranylic acid (NPAA, collecting ducts, 500 mg/kg, per os)-for up to 28 days to evaluate the performance of a panel of 68 urinary miRNAs as potential nephron segment-specific biomarkers. Out of these 68 kidney injury associated-miRNAs, our selection strategy ultimately revealed rno-miR-34c-5p significantly dysregulated after CIS single administration, and rno-miR-335 and rno-miR-155-5p significantly dysregulated after PUR treatment. In contrast, NPAA daily administration strongly altered the expression profile of 28 miRNAs, with rno-miR-210-3p displaying the most robust changes. A thorough evaluation showed that these miRNA candidates could complement urinary protein biomarkers to detect CIS- or PUR-induced kidney injury in a subacute setting, with a mechanistic (based on rno-miR-34c-5p) and/or a kidney injury detection potential. Our results also provide the first evidence that urinary miRNAs could enhance the detection of collecting duct damage. Overall, these data improve our understanding of the utility of urinary miRNAs as DIKI biomarkers in a subacute DIKI preclinical setting and support the value of using urinary biomarker panels comprising proteins and miRNAs.
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PMID:Assessment of a Urinary Kidney MicroRNA Panel as Potential Nephron Segment-Specific Biomarkers of Subacute Renal Toxicity in Preclinical Rat Models. 3016 41