Publications (2)6.02 Total impact
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Article: Thymidylate synthase and dihydropyrimidine dehydrogenase gene expression in breast cancer predicts 5-FU sensitivity by a histocultural drug sensitivity test.
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ABSTRACT: Thymidylate synthase (TS), Dihydropyrimidine dehydrogenase (DPD) and Thymidine Phosphorylase (TP) gene expressions are reported to be predictive markers for 5-fluorouracil (5-FU) sensitivity in gastrointestinal cancer. However, in breast cancer, it is still controversial whether those molecular markers predict 5-FU sensitivity or not. One possible reason for the difficulty may be the histological heterogeneity in breast cancer specimens. In this study, TS, DPD and TP mRNA expression in 40 breast cancer tumors were semi-quantified separately in cancer cells (Ca), cancerous stroma (Str) and normal glands (Nor) using laser capture microdissection and real time RT-PCR (LCM+RT-PCR). The histoculture drug response assay (HDRA) for 5-FU sensitivity was performed for 22 tumors. TS and TP mRNA expressions were higher in Ca than Str, although DPD gene expression was lower in Ca than Str. The group of high TS and high DPD gene expression in Ca was resistant to 5-FU, and the group of low TS and low DPD gene expression in Ca was sensitive to 5-FU (P=0.048 chi-square test). TS and DPD mRNA expressions measured using LCM+RT-PCR might be useful predictive markers for 5-FU sensitivity in human breast cancer.Cancer Letters 07/2005; 223(1):103-11. · 4.24 Impact Factor -
Article: Inverse correlation between the expression of O6-methylguanine-DNA methyl transferase (MGMT) and p53 in breast cancer.
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ABSTRACT: Expression of O(6)-methylguanine-DNA methyl transferase (MGMT), a DNA repair protein, has been associated with tumor resistance to alkylating agents such as cyclophosphamide. Promoter hypermethylation of MGMT is a strong predictor of survival, and expression of mutant p53 protein may be associated with downregulated MGMT expression in brain tumors. In order to clarify further the correlation between MGMT and p53 expression, we investigated the expression levels of both MGMT and p53 in breast cancer. MGMT and p53 expression was examined in tissues from 48 consecutive cases of primary breast cancer patients using immunohistochemical staining with antibodies specific for MGMT and p53. The prognosis for survival was analyzed based on MGMT and p53 immunoreactivity and clinicopathological characteristics. Expression of either MGMT or p53 was classified as negative or positive based on immunohistochemical staining. The expression of MGMT showed a significant inverse correlation with three clinicopathological characteristics, the status of the estrogen receptor, local recurrence and distant metastasis. There was a significant correlation between the expression level of p53 and the lymphatic involvement, estrogen receptor status and distant metastasis. MGMT and p53 were correlated with distant metastasis and local recurrence, but Kaplan-Meier curves did not show a significant difference. MGMT immuno-negative specimens showed a significantly higher expression of p53 (P = 0.026, chi(2) test). p53 may be associated with the regulation of MGMT expression in breast cancers.Japanese Journal of Clinical Oncology 04/2005; 35(3):121-5. · 1.78 Impact Factor
