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

1
Amy Sun
Amy Sun
2
Raymond L. Lam
Raymond L. Lam
3
Amy Harman
Amy Harman
4
Anna C. Pavlick
Anna C. Pavlick
5
Gary A. Herman
Gary A. Herman
6
Lisa M. Dauffenbach
Lisa M. Dauffenbach
7
Christopher A. Kerfoot
Christopher A. Kerfoot
8
Pearl Huang
Pearl Huang
9
Jonathan Cheng
Jonathan Cheng
10
Tim Demuth
Tim Demuth
11
Robert Iannone
Robert Iannone
1 Merck & Co., Inc.

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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 log-transformation 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

Funding

No external funding was declared for this work.

Conflict of Interest

The authors declare no conflict of interest.

Ethical Approval

No ethics committee approval was required for this article type.

Data Availability

Not applicable for this article.

Amy Sun. 2014. \u201cInduction of CDC2 Phosphorylation in Skin Biopsies from Patients with Solid Tumors Undergoing DNA-Damaging Chemotherapy\u201d. Global Journal of Medical Research - K: Interdisciplinary GJMR-K Volume 14 (GJMR Volume 14 Issue K1): .

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Crossref Journal DOI 10.17406/gjmra

Print ISSN 0975-5888

e-ISSN 2249-4618

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v1.2

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March 13, 2014

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English

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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 log-transformation 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

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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

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