Tumor necrosis factor receptor type 1 (TNFR1) and c-Myc are important in signal transduction in tumor necrosis factor-a (TNF-a)-induced cytotoxicity, whereas activation of nuclear factor-kB (NF-kB) protects against TNF-a-induced apoptosis. This study investigated the expression of NF-kB, TNFR1, and c-Myc in human astrocytoma tissues by reverse transcriptase-polymerase chain reaction (PCR) and immunohistochemical analysis. TNFR1 messenger ribonucleic acid (mRNA) and c-Myc mRNA were frequently expressed in malignant astrocytomas, especially in glioblastomas, compared with low-grade astrocytomas by PCR analysis. TNFR1 and c-Myc mRNAs were barely detectable in normal brain tissues. NF-kB p50 and p65 subunit mRNAs were detected in various grades of astrocytomas, with frequent expression in malignant astrocytomas. The presence of activated NF-kB was confirmed by nuclear localization in neoplastic astrocytes as determined by immunohistochemistry. Both p50 and p65 subunits were inhomogeneously expressed in neoplastic astrocytes of glioblastoma, but only in a few scattered tumor cells in low-grade astrocytoma, and almost undetectable in normal brain tissues. These results indicate that TNFR1 and c-Myc are overexpressed in malignant astrocytomas, and this may increase the cellular sensitivity to the cytotoxic action of TNF-a. NF-kB p50 and p65 were simultaneously induced and activated in malignant astrocytomas. Our results suggest that the constitutive activation of NF-kB subunits in malignant astrocytoma, especially in glioblastoma, could be associated with the resistance to TNF-a immunotherapy, and indicates new therapeutic strategies for malignant astrocytomas.
Low-density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor (LRP) has been proposed to mediate the cellular uptake and clearance of inactivated protease-inhibitor complexes in regulating proteinase activity at the cell surface, which is necessary for cellular migration and invasive processes. In this study, we investigated the presence of both LRP and urokinase-type plasminogen activator receptor (uPAR) in glioblastoma by reverse transcriptase-polymerase chain reaction (RT-PCR), and the cellular localization of LRP in glioblastoma tissues by immunohistochemical analysis. LRP mRNA was frequently expressed in glioblastomas and anaplastic astrocytomas compared with low-grade astrocytomas by RT-PCR analysis, and was well correlated with uPAR expression. The immunohistochemistry of LRP on sequential frozen sections showed that neoplastic glial cells and endothelial cells of glioblastomas exhibited intense LRP immunoreactivity, whereas LRP was almost undetectable in low-grade astrocytomas or in normal glial cells and endothelial cells of normal brain tissue. Glioblastomas from 11 patients in which the expression of LRP mRNA was observed by PCR displayed strong to moderate LRP immunoreactivity, with predominantly diffuse cytoplasmic and cell-surface localization. In normal brain tissues, LRP immunoreactivity was identified in the pyramidal neurons of the cerebral cortex. These results indicate that LRP is present both in the cellular cytoplasm and on the cell surface of glioblastomas with an increased expression of uPAR. Altered LRP expression might contribute to the stimulation of cell-surface proteolytic activity that in turn facilitates the invasiveness of glioblastoma in vivo.
A 64-year-old woman had gastric heterotopic of the duodenal bulb without any specific complaints. The lesion with irregular excrescence was diagnosed by means of target biopsies through endoscopy, and 3 years later, no noteworthy changes were observed in the endoscopic findings of the lesion, and it was also proved by an endoscopic Congo red test that the excrescence had a function of acid output. This is the second report of congenital heterotopic gastric mucosa of the duodenum which was confirmed not only by histological, but also functional examination.
Forty patients with stomach cancer, including 25 patients with early carcinoma, were examined endoscopically during the perfusion of Indigo carmine dye into the celiac artery in association with vasomotors. In all of these patients the diagnosis had been established definitively by aimed biopsies before the procedure. This new endoscopic examination is useful not only to determine the margin of the superficial carcinoma, even when it is covered with regenerative epithelium, but also to detect small lesion less than 10 mm in diameter. Liver function tests in 31 patients who underwent the examination have negated the possibility of acute toxicity of the dye. But this new method should be employed with caution in hypertensive or high-risk patients.
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