Drug resistance is one of the important factors that determine tumor response to chemotherapy. Several candidates for resistance to various chemotherapeutic agents have been elucidated. O6-methylguanine-DNA methyltransferase (MGMT) removes methylation damage induced by nitrosourea from the O6 position of DNA guanines before cell injury. Glutathione-S-transferase (GST) pi is also involved in nitrosourea resistance. We examined the expression of MGMT and GST pi in 18 glioblastomas (GBM) using immunohistochemistry and compared the results with patients' survival after administration of 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU)-based chemotherapy. According to the Kaplan-Meier's method, although median progression free survival (PFS) of eight patients whose tumors retained high MGMT (3+ approximately 2+), and 10 patients whose tumors showed low MGMT expression (1+ approximately 0) were nine and 15 months, respectively (p = 0.09), median overall survival (OS) of the two groups were 12 and 22 months, respectively, which were significantly different (p = 0.01). GST pi expression in GBM was not a prognostic factor. It is suggested that GBM with strong staining of MGMT activity may show more resistance to ACNU-based chemotherapy compared to that with low MGMT. The simple immunohistochemical analysis of MGMT in GBM can be a useful method to determine whether ACNU or another treatment regimen should be recommended.
The radiation risk of skin cancer by histological types has been evaluated in the atomic bomb survivors. We examined 80,158 of the 120,321 cohort members who had their radiation dose estimated by the latest dosimetry system (DS02). Potential skin tumors diagnosed from 1958 to 1996 were reviewed by a panel of pathologists, and radiation risk of the first primary skin cancer was analyzed by histological types using a Poisson regression model. A significant excess relative risk (ERR) of basal cell carcinoma (BCC) (n ¼ 123) was estimated at 1 Gy (0.74, 95% confidence interval (CI): 0.26, 1.6) for those age 30 at exposure and age 70 at observation based on a linear-threshold model with a threshold dose of 0.63 Gy (95% CI: 0.32, 0.89) and a slope of 2.0 (95% CI: 0.69, 4.3). The estimated risks were 15, 5.7, 1.3 and 0.9 for age at exposure of 0-9, 10-19, 20-39, over 40 years, respectively, and the risk increased 11% with each oneyear decrease in age at exposure. The ERR for squamous cell carcinoma (SCC) in situ (n ¼ 64) using a linear model was estimated as 0.71 (95% CI: 0
The current study suggests that PR in the astrocytic tumors correlates with histologic grade and PR may participate in the growth of these tumors and tumor angiogenesis. The measurement of PR in these tumors may indirectly represent tumor growth potential.
tau protein and the absence of 14-3-3 protein, as well as decreased concentrations of neuron-specific enolase, S100 protein, and prostaglandin E 2 . All patients presented with unique MRI features. Brain biopsy showed severe spongiform morphology, but comparatively preserved neurons and mild astrocytic gliosis. Accumulations of PrP Sc were not detected using the 3F4 antibody, and microglial activation was subtle. SPECT revealed hypoperfusion throughout both hemispheres. MRS revealed a reduced N-acetyl aspartate/ creatine ratio. Conclusion: Results from this study suggested that increased DWI signals could reflect severe spongiform changes in CJD180 patients.
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