Validation of putative genomic biomarkers of nephrotoxicity in rats

Wang, Er-jia; Snyder, Ronald D.; Fielden, Mark R.; Smith, Roger; Gu, Yi-Zhong

doi:10.1016/j.tox.2007.12.031

Cited by 102 publications

(93 citation statements)

References 36 publications

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“…*P < 0.05 and **P < 0.01. ,Mki67,Fga,Fgg,Krt8,Krt18, and Krt19, were selected as candidate biomarkers because (i) there was the strong evidence supporting their usefulness as nephrotoxicity biomarkers in rats and other species (Alchi et al, 2005., Davis et al, 2004Dieterich et al, 2009;Kharasch et al, 2006;Thukral et al, 2005;Wang et al, 2008) and (ii) these selected genes were considered to be biologically related to the gene categories, such as tissue remodeling, inflammatory responses, and cell growth. The usefulness of these genes as nephrotoxicity biomarkers in mice was evaluated further through expression profiling under several experimental conditions using real time RT-PCR.…”

Section: Discussionmentioning

confidence: 99%

“…It is highly expressed in damaged tissues and plays a role in wound healing, possibly by regulating inflammation and fibrosis (Butler, 1989;Wolak et al, 2009). Several studies have reported that these biomarker genes are more sensitive for detection of early kidney injury in rats and humans than other routinely used biomarkers, such as plasma creatinine and UN (Ichimura et al, 2004;Mishra et al, 2005;Nickolas et al, 2008;Sieber et al, 2009;Vaidya et al, 2006;Wang et al, 2008).…”

Section: A2mmentioning

confidence: 99%

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Predictive genomic biomarkers for drug-induced nephrotoxicity in mice

et al. 2012

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-The present study aimed to establish candidate biomarker genes for the early detection of nephrotoxicity in mice, with a particular focus on nephrotoxicity caused by polyene macrolides. Comprehensive gene expression changes were evaluated using microarrays in a mouse model in which acute nephrotoxicity was induced by amphotericin B deoxycholate, trade name Fungizone. The upregulated genes identified through microarray analysis of kidney tissue of Fungizone-treated mice included several genes that have been reported as nephrotoxicity biomarkers in rats, and 14 genes were selected as candidate nephrotoxicity biomarkers. The usefulness of these genes as nephrotoxicity biomarkers in mice was evaluated further through expression profiling under several experimental conditions using real time RT-PCR. Expression of genes encoding kidney injury molecule 1, lipocalin 2, tissue inhibitor of metalloproteinase 1, and secreted phosphoprotein 1 was highly upregulated by Fungizone, nystatin, natamycin, amphotericin B methyl ester, and liposomal amphotericin B, and their area under the ROC curve values were more than 0.95. These genes were more sensitive at detecting nephrotoxicity than traditional clinical chemistry and histopathology parameters. This study provides novel evidence that these nephrotoxicity biomarker genes identified are translatable to mice, and that they are useful for early and sensitive detection of nephrotoxicity.

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Section: Discussionmentioning

confidence: 99%

Section: A2mmentioning

confidence: 99%

Predictive genomic biomarkers for drug-induced nephrotoxicity in mice

et al. 2012

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“…A peptide antibiotic, bacitracin, interacts with and inhibits PDI through disulfide bond formation with activity in the high micromolar range (16). Although bacitracin is widely used as a PDI inhibitor in research, its clinical use is hampered by its nephrotoxicity and low membrane permeability (17)(18)(19). Therefore, the development of safer and more effective small-molecule PDI inhibitors remains an attractive approach for cancer treatment.…”

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confidence: 99%

Discovery of an orally active small-molecule irreversible inhibitor of protein disulfide isomerase for ovarian cancer treatment

Butkevich

Yamada

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

189

214

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Protein disulfide isomerase (PDI), an endoplasmic reticulum chaperone protein, catalyzes disulfide bond breakage, formation, and rearrangement. The effect of PDI inhibition on ovarian cancer progression is not yet clear, and there is a need for potent, selective, and safe small-molecule inhibitors of PDI. Here, we report a class of propynoic acid carbamoyl methyl amides (PACMAs) that are active against a panel of human ovarian cancer cell lines. Using fluorescent derivatives, 2D gel electrophoresis, and MS, we established that PACMA 31, one of the most active analogs, acts as an irreversible small-molecule inhibitor of PDI, forming a covalent bond with the active site cysteines of PDI. We also showed that PDI activity is essential for the survival and proliferation of human ovarian cancer cells. In vivo, PACMA 31 showed tumor targeting ability and significantly suppressed ovarian tumor growth without causing toxicity to normal tissues. These irreversible small-molecule PDI inhibitors represent an important approach for the development of targeted anticancer agents for ovarian cancer therapy, and they can also serve as useful probes for investigating the biology of PDIimplicated pathways.oral bioavailability | drug resistance | BODIPY-conjugation

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“…After conducting two-dimensional gel electrophoresis followed by MALDI-TOF-MS analysis of cisplatin-treated cells to determine which proteins are differentially expressed (5), we selected annexin A5 as a marker candidate based on GEO microarray data showing increased expression of annexin A5 mRNA in rats injected with various nephrotoxicants (6). Annexin A5 is a calcium-regulated, phospholipid-binding protein that belongs to the annexin family and has a molecular mass of [32][33][34][35] kDa.…”

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confidence: 99%

Role of Annexin A5 in Cisplatin-induced Toxicity in Renal Cells

Jeong

Park

Kwon

et al. 2014

Journal of Biological Chemistry

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Background: There is increasing evidence that annexin A5 is related to cytotoxicity, but the precise function has yet to be elucidated. Results: Cisplatin induces mitochondrial translocation of annexin A5, and annexin A5 mediates VDAC oligomerization. Conclusion: Annexin A5 may play a role as a mediator of cisplatin-induced apoptosis in renal epithelial cells. Significance: Learning how annexin A5 is involved in the apoptotic pathway is crucial for understanding cisplatin-induced toxicity.

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Validation of putative genomic biomarkers of nephrotoxicity in rats

Cited by 102 publications

References 36 publications

Predictive genomic biomarkers for drug-induced nephrotoxicity in mice

Predictive genomic biomarkers for drug-induced nephrotoxicity in mice

Discovery of an orally active small-molecule irreversible inhibitor of protein disulfide isomerase for ovarian cancer treatment

Role of Annexin A5 in Cisplatin-induced Toxicity in Renal Cells

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