Induction of CDC2 Phosphorylation in Skin Biopsies from Patients with Solid Tumors Undergoing DNA-Damaging Chemotherapy

Article ID

E4CZU

Induction of CDC2 Phosphorylation in Skin Biopsies from Patients with Solid Tumors Undergoing DNA-Damaging Chemotherapy

Amy Sun
Amy Sun Merck & Co., Inc.
Raymond L. Lam
Raymond L. Lam
Amy Harman
Amy Harman
Anna C. Pavlick
Anna C. Pavlick
Gary A. Herman
Gary A. Herman
Lisa M. Dauffenbach
Lisa M. Dauffenbach
Christopher A. Kerfoot
Christopher A. Kerfoot
Pearl Huang
Pearl Huang
Jonathan Cheng
Jonathan Cheng
Tim Demuth
Tim Demuth
Robert Iannone
Robert Iannone
DOI

Abstract

This study was to clinically validate phosphorylated CDC2(pCDC2) as a biomarker for Wee1 kinase inhibitors by measuring pCDC2 in skin biopsies from patients receiving DNA damaging chemotherapy. Skin biopsies were performed at scheduled times after chemotherapy. Total CDC2 and pCDC2 in epidermal cells, hair follicle and bulb from skin biopsies were determined using chromogenic multiplex immunohis-tochemistry with multispectral image analysis. Statistical analyses were performed for each cell type after logtransformation of data. Thirty-one patients (29-88 years) completed the study. Significant induction of pCDC2 in response to chemotherapy was detected. Epidermis was most consistently evaluable across skin biopsies, demonstrating strong induction of pCDC2. The percentage of cells positive for total CDC2 and pCDC2 showed a 1.40-fold induction from baseline to 24h post-infusion (p=0.012) and a 2.05-fold increase from baseline to 48h (p

Induction of CDC2 Phosphorylation in Skin Biopsies from Patients with Solid Tumors Undergoing DNA-Damaging Chemotherapy

This study was to clinically validate phosphorylated CDC2(pCDC2) as a biomarker for Wee1 kinase inhibitors by measuring pCDC2 in skin biopsies from patients receiving DNA damaging chemotherapy. Skin biopsies were performed at scheduled times after chemotherapy. Total CDC2 and pCDC2 in epidermal cells, hair follicle and bulb from skin biopsies were determined using chromogenic multiplex immunohis-tochemistry with multispectral image analysis. Statistical analyses were performed for each cell type after logtransformation of data. Thirty-one patients (29-88 years) completed the study. Significant induction of pCDC2 in response to chemotherapy was detected. Epidermis was most consistently evaluable across skin biopsies, demonstrating strong induction of pCDC2. The percentage of cells positive for total CDC2 and pCDC2 showed a 1.40-fold induction from baseline to 24h post-infusion (p=0.012) and a 2.05-fold increase from baseline to 48h (p<0.001). The results suggest that pCDC2 may be used to assess the degree of Wee1 kinase inhibition in the chemotherapy setting. [Clinicaltrials.gov; NCT00800865]

Amy Sun
Amy Sun Merck & Co., Inc.
Raymond L. Lam
Raymond L. Lam
Amy Harman
Amy Harman
Anna C. Pavlick
Anna C. Pavlick
Gary A. Herman
Gary A. Herman
Lisa M. Dauffenbach
Lisa M. Dauffenbach
Christopher A. Kerfoot
Christopher A. Kerfoot
Pearl Huang
Pearl Huang
Jonathan Cheng
Jonathan Cheng
Tim Demuth
Tim Demuth
Robert Iannone
Robert Iannone

No Figures found in article.

Amy Sun. 2014. “. Global Journal of Medical Research – K: Interdisciplinary GJMR-K Volume 14 (GJMR Volume 14 Issue K1): .

Download Citation

Journal Specifications

Crossref Journal DOI 10.17406/gjmra

Print ISSN 0975-5888

e-ISSN 2249-4618

Classification
Not Found
Article Matrices
Total Views: 4749
Total Downloads: 2321
2026 Trends
Research Identity (RIN)
Related Research
Our website is actively being updated, and changes may occur frequently. Please clear your browser cache if needed. For feedback or error reporting, please email [email protected]

Request Access

Please fill out the form below to request access to this research paper. Your request will be reviewed by the editorial or author team.
X

Quote and Order Details

Contact Person

Invoice Address

Notes or Comments

This is the heading

Lorem ipsum dolor sit amet, consectetur adipiscing elit. Ut elit tellus, luctus nec ullamcorper mattis, pulvinar dapibus leo.

High-quality academic research articles on global topics and journals.

Induction of CDC2 Phosphorylation in Skin Biopsies from Patients with Solid Tumors Undergoing DNA-Damaging Chemotherapy

Amy Sun
Amy Sun Merck & Co., Inc.
Raymond L. Lam
Raymond L. Lam
Amy Harman
Amy Harman
Anna C. Pavlick
Anna C. Pavlick
Gary A. Herman
Gary A. Herman
Lisa M. Dauffenbach
Lisa M. Dauffenbach
Christopher A. Kerfoot
Christopher A. Kerfoot
Pearl Huang
Pearl Huang
Jonathan Cheng
Jonathan Cheng
Tim Demuth
Tim Demuth
Robert Iannone
Robert Iannone

Research Journals