Alpha-1-antitrypsin in human brain tumors

1987 ◽  
Vol 67 (2) ◽  
pp. 258-262 ◽  
Author(s):  
Raymond Sawaya ◽  
Mario Zuccarello ◽  
Robert Highsmith

✓ This study was undertaken to confirm the presence of alpha-1-antitrypsin (α1-AT) in human brain tumors and to attempt to elucidate its significance. Seventy-seven consecutive unselected patients with various brain tumors were entered in this study. The α1-AT and α2-macroglobulin contents of the tumor extracts were qualitatively assessed by Ouchterlony immunodiffusion techniques. Plasminogen activator (PA) activity was assayed electrophoretically on sodium dodecyl sulfate gels. The patients were divided into two groups according to the positivity of their tumors to α1-AT. Sixty-eight percent of the tumors were positive for α1-AT, and all specimens were negative for α2-macroglobulin. Clinical and biological parameters obtained in all study patients failed to show statistically significant differences between the two groups with the exception of PA activity (p = 0.001), the peritumoral edema as seen on computerized tomography, and the preoperative serum fibrinogen level. These three parameters were higher in the group with specimens positive to α1-AT. This study supports the hypothesis that α1-AT is produced primarily by tumor cells in proportion to the regional proteolytic and inflammatory activity, and may protect the tumor cells.

1970 ◽  
Vol 33 (2) ◽  
pp. 167-171 ◽  
Author(s):  
Edward R. Laws ◽  
John S. O'Connor

✓ The energy-dependent membrane transport ATPases have been quantitatively determined in 59 human brain tumors and control cerebral cortex. The values for total ATPase were significantly decreased in the 11 types of brain tumors tested, while in the glioma group there was a consistent further decrease in ATPase with increasingly malignant types. The findings suggest that a deficiency in ATPase is a characteristic of neoplasia in the central nervous system.


1977 ◽  
Vol 47 (6) ◽  
pp. 923-932 ◽  
Author(s):  
Darell D. Bigner ◽  
Charles B. Wilson

✓ The authors provide a summary of a workshop on “Cancer of the Brain.” This conference reviewed the current knowledge about the etiology and pathogenesis of human brain tumors and the experimental induction of comparable animal brain tumors, and considered new lines of research.


1988 ◽  
Vol 68 (2) ◽  
pp. 165-180 ◽  
Author(s):  
Duncan K. Fischer ◽  
Terence L. Chen ◽  
Raj K. Narayan

✓ Various strategies have been used to identify and characterize the antigens associated with human brain tumors. These approaches have included the raising of polyclonal and monoclonal antibodies against tumor antigens and, more recently, efforts toward the direct biochemical identification of such proteins. This review summarizes the progress made in this area, suggests reasons for the broad antigenic cross-reactivity and heterogeneity revealed by these studies, and proposes additional methods for deciphering the complex antigenic composition of human brain tumors.


1993 ◽  
Vol 79 (5) ◽  
pp. 729-735 ◽  
Author(s):  
David Barba ◽  
Joseph Hardin ◽  
Jasodhara Ray ◽  
Fred H. Gage

✓ Gene therapy has many potential applications in central nervous system (CNS) disorders, including the selective killing of tumor cells in the brain. A rat brain tumor model was used to test the herpes simplex virus (HSV)-thymidine kinase (TK) gene for its ability to selectively kill C6 and 9L tumor cells in the brain following systemic administration of the nucleoside analog ganciclovir. The HSV-TK gene was introduced in vitro into tumor cells (C6-TK and 9L-TK), then these modified tumor cells were evaluated for their sensitivity to cell killing by ganciclovir. In a dose-response assay, both C6-TK and 9L-TK cells were 100 times more sensitive to killing by ganciclovir (median lethal dose: C6-TK, 0.1 µg ganciclovir/ml; C6, 5.0 µg ganciclovir/ml) than unmodified wild-type tumor cells or cultured fibroblasts. In vivo studies confirmed the ability of intraperitoneal ganciclovir administration to kill established brain tumors in rats as quantified by both stereological assessment of brain tumor volumes and studies of animal survival over 90 days. Rats with brain tumors established by intracerebral injection of wild-type or HSV-TK modified tumor cells or by a combination of wild-type and HSV-TK-modified cells were studied with and without ganciclovir treatments. Stereological methods determined that ganciclovir treatment eliminated tumors composed of HSV-TK-modified cells while control tumors grew as expected (p < 0.001). In survival studies, all 10 rats with 9L-TK tumors treated with ganciclovir survived 90 days while all untreated rats died within 25 days. Curiously, tumors composed of combinations of 9L and 9L-TK cells could be eliminated by ganciclovir treatments even when only one-half of the tumor cells carried the HSV-TK gene. While not completely understood, this additional tumor cell killing appears to be both tumor selective and local in nature. It is concluded that HSV-TK gene therapy with ganciclovir treatment does selectively kill tumor cells in the brain and has many potential applications in CNS disorders, including the treatment of cancer.


1971 ◽  
Vol 35 (3) ◽  
pp. 303-308 ◽  
Author(s):  
Tatsuya Kobayashi ◽  
Louis Bakay ◽  
Joseph C. Lee

✓ The deposition of Hg203-chlormerodrin was studied in intracranial tumors in mice induced by implantation of 20-methyl cholanthrene by tissue assay, as well as light microscopic and electron microscopic autoradiography. The investigations were carried out in astrocytomas, glioblastomas, and meningeal tumors. The chlormerodrin content of the tumors exceeded that of normal brain with a significant tumor/brain ratio ranging from 5.8 to 22.5. It was found that the chlormerodrin molecule becomes rapidly incorporated in the tumor cells, with a preference for that portion of the cytoplasm associated with the vacuolar system.


1970 ◽  
Vol 33 (3) ◽  
pp. 281-286 ◽  
Author(s):  
Philippe Benda ◽  
Takesada Mori ◽  
William H. Sweet

✓ Specimens of 16 human brain tumors were studied by the indirect fluorescent-antibody technique to reveal the localization of the particular cerebroprotein found in strikingly increased amounts in human glial tumors as well as in the brain of a patient with Tay-Sachs disease. The cerebro-protein fraction named “10B” by Bogoch was found exclusively in reactive astrocytes, both in astrocytomas and in glioblastomas multiforme. Both the cytoplasm and the cell processes fluoresced upon exposure to antiserum to the “10B” proteins of Tay-Sachs disease. Fluorescence of fibrillary astrocytes located in white matter at some distance from a tumor might be related to discrete edematous changes or constitute an early step in the transition of normal glia to reactive or neoplastic astrocytes. There was no such staining of frankly neoplastic cells or of normal ganglion cells.


1989 ◽  
Vol 70 (3) ◽  
pp. 379-384 ◽  
Author(s):  
Takafumi Nishizaki ◽  
Tetsuji Orita ◽  
Yasuhiro Furutani ◽  
Yukihide Ikeyama ◽  
Hideo Aoki ◽  
...  

✓ Cell proliferation potential was assessed by measuring the labeling indices of the monoclonal antibody Ki-67 and of 5-bromodeoxyuridine (BUdR), and the cellular deoxyribonucleic acid (DNA) content in 48 human brain tumors. The diagnostic and prognostic value of flow-cytometric DNA analysis was also evaluated using ethanol-fixed paraffin-embedded BUdR-labeled specimens; these were the same specimens as were used for measuring the BUdR and Ki-67 labeling indices. Both the Ki-67 and the BUdR labeling indices correlated with the degree of malignancy estimated from conventional histological preparations. The Ki-67 labeling index was 1.7 times greater than the BUdR labeling index. The relationship of DNA aneuploidy to the labeling indices or to morphology in cases of glioma was examined. All of the tumors with an aneuploid line corresponded to malignant glioma classified by histological criteria, although malignant glioma did not always show DNA aneuploidy. In addition, the cases with aneuploid lines showed high BUdR and Ki-67 labeling indices. The cell kinetic data, which indicate the biological character of tumors, allowed prediction of the prognosis of the patients with gliomas. In contrast, despite the presence of an aneuploid line, three of 13 meningiomas showed a benign histological pattern without an aggressive clinical course, and neither the Ki-67 nor the BUdR labeling index was high. These results indicate an unequivocal relationship between DNA aneuploidy and clinical behavior; in general, both labeling indices may prove to be objective indicators of the outcome of patients with brain tumors.


1987 ◽  
Vol 67 (3) ◽  
pp. 336-340 ◽  
Author(s):  
Terry Lichtor ◽  
George J. Dohrmann

✓ Glucose utilization in vivo and hexokinase activity and mitochondrial oxygen consumption in vitro were measured in a series of human brain tumors. Several relatively slow-growing tumors appeared to have depressed electron-transport activities coupled with a compensatory elevated glucose utilization. These data suggest that a decrease in oxidative metabolism and a corresponding increase in glycolysis are not necessarily correlated with malignancy in certain human brain tumors.


1991 ◽  
Vol 74 (6) ◽  
pp. 979-984 ◽  
Author(s):  
Tetsuya Shiraishi ◽  
Kazuo Tabuchi ◽  
Toshihiro Mineta ◽  
Nobuaki Momozaki ◽  
Masashi Takagi

✓ Nucleolar organizer regions (NOR's) are loops of deoxyribonucleic acid (DNA) which transcribe to ribosomal ribonucleic acid (RNA) by RNA polymerase I. They possess vital significance in the ultimate synthesis of cellular proteins. A silver colloid staining technique for demonstration of NOR-associated proteins (Ag-NOR's) was applied to paraffin-embedded sections from 128 varied brain tumors and to chromosomal preparations from cultured brain-tumor cells. There was a statistically significant difference in the mean number of Ag-NOR's per nucleus between low-grade tumors (1.98/nucleus) and high-grade tumors (2.95/nucleus). It is suggested that the mean number of Ag-NOR's may represent the proliferative potential of brain tumors. Furthermore, high-grade tumors usually showed relatively large Ag-NOR's in a scattered distribution. In chromosomal preparations, the cultured cells displayed five to 12 Ag-NOR's on acrocentric chromosomes. Five of eight cell lines examined demonstrated ectopic Ag-NOR's. This simple staining technique can be easily applied to routinely processed paraffin-embedded sections and will become a useful tool for quick estimation of the proliferative potential of human brain tumors.


1973 ◽  
Vol 38 (4) ◽  
pp. 420-427 ◽  
Author(s):  
Saburo Nakamura ◽  
Mitsusuke Miyagami ◽  
Nobuo Moriyasu

✓ Ultrastructural localization of ATPase was demonstrated in 15 human brain tumors; ATPase activity in the tumor cell was outside the cell membrane and appeared in varying degrees according to the type of tumor. Nonglial tumors such as meningiomas and chromophobe pituitary adenomas showed more intense enzyme activity than gliomas; malignant tumors such as medulloblastoma and glioblastoma multiforme showed low activity. Blood vessels in the tumor showed poor ATPase activity in both endothelium and basement membrane; the lack of ATPase in the vascular wall may contribute to the breakdown of the blood-brain barrier.


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