N. Jeyabalan

Publications (2)6.42 Total impact

• Article: Multiple ErbB-2/Neu Phosphorylation Sites Mediate Transformation through Distinct Effector Proteins.

  D Dankort, N Jeyabalan, N Jones, D J Dumont, W J Muller
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  ABSTRACT: Amplification of the type I receptor tyrosine kinase ErbB-2 (HER2/Neu) is observed in 20-30% of human mammary carcinomas, correlating with a poor clinical prognosis. We have previously demonstrated that four (Tyr(1144), Tyr(1201), Tyr(1226/1227), or Tyr(1253)) of the five known Neu/ErbB-2 autophosphorylation sites can independently mediate transforming signals. The transforming potential of at least two of these autophosphorylation sites (Tyr(1144) and Tyr(1226/1227)) has been further correlated with their ability to associate with Grb2 and Shc adapter proteins, respectively. To confirm the specificity of these interactions, we have created a series of second site mutants in these phosphorylation sites. The results showed that Grb2 recruitment to site 1144 is absolutely required for transforming signal from this autophosphorylation site, whereas association of Shc-mediated transformation is dependent on conservation of the NPXY motif spanning Tyr(1227). A stretch of amino acid identity around tyrosines 1201 (ENPEYLTP)and 1253 (ENPEYLDL) exists, and mutation of key residues within this motif reveals distinct requirements for an intact protein tyrosine-binding protein (NPXY). We show that DOK-R, a protein tyrosine-binding site-containing protein implicated in Ras signaling, interacts with Neu/ErbB-2 at Tyr(1253) as do two unidentified proteins, p150 and p34, the latter correlating with transformation. Together these data argue that ErbB-2/Neu is capable of mediating transformation through distinct effector pathways.
  Journal of Biological Chemistry 11/2001; 276(42):38921-8. · 4.77 Impact Factor
• Article: Treatment of advanced ovarian carcinoma with carboplatin and paclitaxel in a patient with renal failure.

  N. Jeyabalan, H. W. Hirte, F. Moens
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  ABSTRACT: Platinum-based chemotherapy is the standard treatment for ovarian cancer. Since carboplatin elimination occurs largely through the kidneys, its use in patients with hemodialysis-dependent renal failure requires dose adjustments befitting the level of renal function. We employed the AUC (area under the concentration-time curve)- directed dosing strategy (the Calvert formula) to determine the carboplatin dose appropriate for an ovarian cancer patient with renal failure. Our approach is compared and defended against the empiric and thrombocyte nadir-directed dosing strategies. Since carboplatin clearance follows creatinine clearance, we also provide a review of methods and formulas used to determine creatinine clearance. An accurate method to determine creatinine clearance will enable others to use the AUC-directed dosing strategy to establish the carboplatin dose appropriate for patients with some residual renal function.
  International Journal of Gynecological Cancer 12/2000; 10(6):463-468. · 1.65 Impact Factor