Modulation of P-Glycoprotein-Mediated Multidrug Resistance by Monoclonal Antibodies, Immunotoxins or Antisense Oligodeoxynucleotides in Kidney Carcinoma and Normal Kidney Cells

Oncology ◽  
1993 ◽  
Vol 50 (4) ◽  
pp. 303-308 ◽  
Author(s):  
T. Efferth ◽  
M. Volm
Keyword(s):  
Monoclonal Antibodies ◽  
Multidrug Resistance ◽  
Antisense Oligodeoxynucleotides ◽  
Kidney Cells ◽  
Normal Kidney ◽  
P Glycoprotein ◽  
Kidney Carcinoma

scholarly journals New monoclonal antibodies against bilitranslocase as a diagnostic tool in determining the progress of clear cell renal cell carcinoma

2017 ◽  
Vol 86 (5-6) ◽  
Author(s):  
Alexandra Bogožalec Košir ◽  
Tjaša Lukan ◽  
Mateja Kukovec ◽  
Sendi Montanič ◽  
Vivijana Snoj ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Monoclonal Antibodies ◽  
Cell Carcinoma ◽  
Cell Line ◽  
Diagnostic Tool ◽  
Renal Cell ◽  
Clear Cell ◽  
Kidney Cells ◽  
Normal Kidney ◽  
Cell Renal Cell Carcinoma

Background: Monoclonal antibodies (mAbs) are an important tool in diagnostics and research, especially when we are dealing with a protein marker of unknown primary structure as in the case of bilitranslocase (BTL). BTL is also expressed on kidney cells, where it acts as an organic anion transporter. We have shown earlier that there are differences in bilitranslocase expression in normal kidney cells versus early grade kidney cancer.Methods: We developed monoclonal antibodies against extra- and intra-cellular domains of bilitranslocase protein model. To also gain a deeper insight in bilitranslocase expression in clinical samples, we assessed BTL expression in different grades of clear cell kidney cell carcinoma (ccRCC).Results: Both new monoclonal antibodies bind to a protein in UOK171 cells but not in the negative control. Binding of mAb is specifc. mAb produced by cell line 2A9/2E9 (peptide 298–310; intracellular domain) is more suitable for immunohistochemical analyses as it gives stronger intensity of binding than mAb produced by cell line 11C9/2G9 (peptide 235–246; extracellular domain). Antibody 2A9/2E9 stains bilitranslocase in proximal renal tubules of normal kidneys but not in the surrounding stroma. Staining decreases in grade I compared to normal kidney, gradually increases in grades II and III, and decreases again in grade IV of ccRCC tissue.Conclusions: Our results show that these antibodies can be used in different immunoassays. Furthermore, specificity and afnity of our mAbs allowed us to use them in the analysis of progressive grades of clear cell renal cell carcinoma in a limited number of patients. Tus, mAbs developed here can be used as a diagnostic tool that could help distinguish between early and late grades of clear cell renal cell carcinoma.

Modulation of Multidrug Resistance Gene (mdr-1) with Antisense Oligodeoxynucleotides

1996 ◽  
Vol 91 (1) ◽  
pp. 93-98 ◽  
Author(s):  
Chao Liu ◽  
Imran Ahmad Qureshi ◽  
Xun-Jie Ding ◽  
Yi-Fei Shan ◽  
Yi-Wei Huang ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Multidrug Resistant ◽  
Polymerase Chain Reaction Method ◽  
Antisense Oligodeoxynucleotides ◽  
Multidrug Resistance Gene ◽  
Glycoprotein Synthesis ◽  
P Glycoprotein ◽  
Anti Cancer ◽  
Initiator Codon ◽  
Mdr 1

1. Multidrug resistance is the major obstacle to successful cancer chemotherapy. Circumventing multidrug resistance therefore represents a high priority for clinical anti-cancer treatment. Among many reversal strategies, antisense oligodeoxynucleotides may offer a molecular targeting tool for overcoming cellular multidrug resistance. 2. Two 17-mer phosphorothioate antisense oligomers, complementary to the 5′ end of the ATG initiator codon-containing region and loop-forming site (located at nucleotides 991–1007 from the first ATG codon) in mdr-1 cDNA sequence, were synthesized. The purpose was to study their effects on the function and expression of P-glycoprotein and mdr-1 gene. 3. The results showed that 10 μmol/l antisense oligomers could significantly inhibit the growth of multidrug resistant K562/Adm cells cultured in adriamycin-containing medium. No such effect was observed for parental (sensitive) K562/S cells. Intracellular daunorubicin accumulation increased greatly in the K562/Adm cells after they were treated with oligomers for 48 h and P-glycoprotein synthesis was strikingly reduced. 4. Further investigation with [α-32P]dCTP incorporation by the reverse transcriptase—polymerase chain reaction method revealed that antisense oligomers could result in a reduction in the level of mdr-1 mRNA, probably through hindering mdr-1 gene transcription. 5. The high reversal efficiency and specificity of antisense oligomers in regulating mdr-1 gene expression suggest a potential clinical application in gene therapy for drug resistant malignancies.

Transfection with Protein Kinase Cα Confers Increased Multidrug Resistance to MCF-7 Cells Expressing P-Glycoprotein

1991 ◽  
Vol 3 (6) ◽  
pp. 181-189 ◽  
Author(s):  
Gang Yu ◽  
Shakeel Ahmad ◽  
Angelo Aquino ◽  
Craig R. Fairchild ◽  
Jane B. Trepel ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Protein Kinase ◽  
P Glycoprotein ◽  
Protein Kinase Cα ◽  
Mcf 7
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