Data mining correlated elevated PITX2 in >30% of cancers analyzed, maximally in colon (4.4-fold), confirmed in co-immunostaining of colon and renal cancer microarrays wherein ABCB1 concomitantly increased in RCC.
Multidrug resistance (MDR) in a variety of human tumors such as renal cell carcinoma (RCC) is thought to be caused by expression of the mdr1 gene and may be reversed by applying chemosensitizers such as Dexverapamil that inhibit the mdr1 gene product P-glycoprotein.
Two criteria suggest that primary multidrug resistance in human adenocarcinomas of the kidney results, at least in part, from expression of the mdr1 gene: (1) mdr1 mRNA levels are elevated in four unselected kidney adenocarcinoma cell lines that show a multidrug-resistant phenotype; and (2) multidrug resistance in these kidney cancer cell lines is reversed by verapamil and quinidine, agents known to reverse mdr1-associated drug resistance in cell lines selected for multidrug resistance in vitro.
The MDR1-targeted RNAi resulted in decreased MDR1 gene mRNA level (P < 0.001), almost abolished P-gp expression and reversed MDR to different chemotherapy drugs in the RCC A498 cell line.
Stage adjusted disease specific survival rate, according to MDR-1 expression and therapy in patients affected by RCC in early stage (stage I), has revealed that the group of patients with high MDR-1 expression and without adjuvant therapy showed poor survival (p < 0.05).
These findings suggest that the common SNPs in the MDR1 gene have no influence on the expression of its transcript in RCC segments as well as in the normal kidney cortex.
We hypothesized that inhibition of multidrug resistant transporters by elacridar (dual inhibitor of P-glycoprotein and ABCG 2) might overcome sunitinib resistance in experimental renal cell carcinoma.
Association of axitinib plasma exposure and genetic polymorphisms of ABC transporters with axitinib-induced toxicities in patients with renal cell carcinoma.
ATP-binding cassette transporter super-family including ABCC1 and MDR-1 were involved in multi-drug resistance (MDR) of renal cell carcinoma (RCC) patients.
Comparisons of the expression levels between normal kidneys and renal cell carcinomas showed that only the mean MRP gene expression level was higher in renal cell carcinomas than in normal kidneys (p = 0.018).
We examined the expression of MRP mRNA by means of slot-blotting samples of 11 renal pelvic and/or ureteral tumors, 33 bladder tumors, one lung metastasis from a ureter tumor, 7 non-cancerous urothelia from patients with transitional-cell carcinoma (TCC) and one urothelium from a patient with renal-cell carcinoma (RCC).
All the N276 compounds also remarkably enhanced the sensitivity to VBL and DXR in both MDR1- and MRP-overexpressing renal cell carcinoma (RCC) cell line (NKK1), whereas they showed no potentiation of these anticancer agents in an RCC cell line (KPK1) expressing neither MDR1 nor MRP.
The expression of MRP2 in renal cell carcinoma was studied by reverse transcription-PCR and immunoblotting in samples from patients undergoing tumor-nephrectomy without prior chemotherapy.
These results indicate that MRP2 expression in renal cell carcinoma may be regulated by conjugated bilirubin in the body and decreased during in vitro culture.
In conclusion, ABCB1 and ABCC2 genotypes modulate the expression in the unaffected renal cortex of RCC patients, possibly contributing to inter-individual differences in drug and xenobiotics elimination.
Our finding suggested that women, higher initial dose per body weight or body surface area, the ABCC2 -24CC genotype, and HLA-A*24 are associated with the risk of sorafenib-induced HGSR in Japanese RCC patients.
Six peptides derived from these antigens, including multidrug resistance-associated protein 3(503-511), multidrug resistance-associated protein 3(1293-1302), polycomb group protein enhancer of zeste homologue 2(291-299), polycomb group protein enhancer of zeste homologue 2(735-743), Her2/neu342-350 and Her2/neu485-493, efficiently induced peptide specific and renal cell carcinoma reactive cytotoxic T lymphocytes from human leukocyte antigen-A24+ patients with renal cell carcinoma.
Five renal cell carcinomas cultured successfully in vitro for 14 days showed significantly decreased expression of multi-drug resistance-associated proteins 2 and 6 (MRP2 and MRP6) mRNAs.
To this end, aberrant promoter methylation of ABCG2 has been reported to cause its repression in a few cancer types including renal carcinoma and multiple myeloma.
This study is to investigate the association of a functional germline variant on ABCG2 that affects the pharmacokinetics of sunitinib with sunitinib-induced toxicity of RCC patients in the Japanese population.
We hypothesized that inhibition of multidrug resistant transporters by elacridar (dual inhibitor of P-glycoprotein and ABCG 2) might overcome sunitinib resistance in experimental renal cell carcinoma.