Cisplatin is a widely used chemotherapeutic agent in head and neck squamous cell carcinoma (HNSCC). Resistance to cisplatin is a common feature of HNSCC. To identify genes that may regulate cisplatin sensitivity, we carried out a cDNA microarray analysis of gene expression in cisplatin-sensitive and
P53 mutation correlates with cisplatin sensitivity in head and neck squamous cell carcinoma lines
β Scribed by Carol R. Bradford; Shaobo Zhu; Haruko Ogawa; Tetsuya Ogawa; Matthew Ubell; Ajita Narayan; Garfield Johnson; Gregory T. Wolf; Susan G. Fisher; Thomas E. Carey
- Publisher
- John Wiley and Sons
- Year
- 2003
- Tongue
- English
- Weight
- 137 KB
- Volume
- 25
- Category
- Article
- ISSN
- 1043-3074
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β¦ Synopsis
Background:
A critical factor for successful organ preservation treatment in head and neck cancer may be selecting tumors that respond to chemotherapy and radiation. previous results in patients indicated that tumors that overexpressed p53 were more sensitive to chemotherapy than those that did not overexpress p53.
Methods:
To determine the relationship of p53 mutations to sensitivity to cisplatin in vitro, 23 head and neck squamous cell carcinoma (hnscc) cell lines were analyzed for cisplatin sensitivity, p53 expression, and p53 mutation status.
Results:
Mutations of the p53 gene were identified in 13 of 23 of the cell lines tested. mutation of the p53 gene was significantly associated with high levels of expression of the p53 protein. the average id(50) (drug dose required to inhibit 50% of cell growth) for cell lines with mutant p53 was 6.8 microm, whereas the average id(50) for cell lines with wild-type p53 was 13.7 microm.
Conclusions:
These in vitro data support a role for mutation of the p53 tumor suppressor gene as a marker for response to cisplatin in hnscc.
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## Abstract ## Background Resistance to chemotherapy is a major limitation in the treatment of head and neck squamous cell carcinomas (HNSCCs), accounting for high mortality rates in patients. Here, we investigated the role of replication protein A (RPA) in cisplatin and etoposide resistance. ##
Nonfunctional p53 and especially upregulation of Bcl-x(L) result in advanced disease and poor prognosis of patients suffering head and neck squamous cell carcinoma (HNSCC). Aberrancies of Bcl-x(L) and/or p53 in HNSCC lead to inability of anticancer drugs to induce apoptosis. Bcl-x(L) and/or mutated
## Abstract ## Background Cisplatin treatment is beneficial for approximately 20% of patients with head and neck squamous cell carcinoma (HNSCC). Tools to predict the clinical outcome and evaluate intrinsic cisplatin sensitivity are, therefore, required. ## Methods Cisplatin sensitivity, lysosom