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001-es BibID:BIBFORM029725
Első szerző:Groothuis, Dennis
Cím:The effect of an amino acid-lowering diet on the rate of melphalan entry into brain and xenotransplanted glioma / Groothuis D. R., Lippitz B. E., Fekete I., Schlageter K. E., Molnar P., Colvin O. M., Roe C. R., Bigner D. D., Friedman H. S.
Dátum:1992
ISSN:0008-5472
Megjegyzések:Melphalan (L-phenylalanine mustard, L-PAM, alkeran; molecular weight, 305,000) is transported across tumor cell membranes and the blood-brain barrier by the large neutral amino acid (LNAA) transport system. Normally, plasma LNAA levels are high enough and the affinity low enough that this system does not transport much melphalan into the brain. However, plasma amino acids can be reduced by fasting and protein-free diet. We used this method to reduce competition and to increase melphalan transport into brain tumors. In nude mice fasted for 12 h and then fed a protein-free diet for 2 and 6 h, mean plasma LNAA levels were 46% and 42% of control values. Nude mice with xenotransplanted D-54MG human gliomas were used to study tissue distribution and uptake kinetics of [3H]melphalan in a control group and a diet group (after a 12-h fast and 2 h of a 0% protein diet). The K1 (blood-to-tissue transfer constant) of melphalan, determined by graphical analysis and by nonlinear fitting to a 2-compartment model, was higher in the diet group in all tumor regions except the necrotic center of subcutaneous tumors; the increase was significant in the tumor periphery of brain and s.c. tumors. The ratio of K1s (diet to control) varied from 1.2 to 1.3 in brain tumors, 1.9 to 2.1 in subcutaneous tumors, and 1.8 to 3.1 in tumor-free brain. The apparent [3H]melphalan distribution space was significantly higher in the tumor periphery of both brain and subcutaneous tumors of the 15- and 30-min diet group. We also measured blood-brain barrier transport of [alpha-14C]aminoisobutyric acid and blood flow (with [131I]iodoantipyrine): the K1 of [alpha-14C]aminoisobutyric acid was 28.1 +/- 6.6 (SE) in brain tumors and 24.3 +/- 8.9 microliters/g/min in subcutaneous tumors. Blood flow was 58.2 --> 3.9 in brain tumors and 5.2 +/- 0.4 ml/100 g/min in subcutaneous tumors. Fasting, when combined with a protein-free diet, reduces plasma amino acid levels and thereby reduces competition between melphalan and LNAAs. This may increase the amount of melphalan that can enter a brain tumor without increasing the administered drug dose and suggests a therapeutic manipulation that can be used to increase the delivery of melphalan.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Cancer Research. - 52 : 20 (1992), p. 5590-5596. -
További szerzők:Lippitz, Bodo E. Fekete István (1951-) (neurológus, pszichiáter) Schlageter, Kurt E. Molnár Péter Pál (1951-) (pathológus) Colvin, Michael O. Roe, Charles R. Bigner, Darell Friedman, Henry S.
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2.

001-es BibID:BIBFORM029685
Első szerző:Groothuis, Dennis
Cím:Regional blood flow in avian sarcoma virus (ASV)-induced brain tumors / Groothuis D., Blasberg R. G., Molnár P., Bigner D., Fenstermacher J. D.
Dátum:1983
ISSN:0340-5354
Megjegyzések:Regional blood flow (F) was measured in avian sarcoma virus (ASV)-induced brain tumors in rats. Blood flow was variable in individual as well as different tumors; tumor F did not correlate with histologic classification, tumor size, central versus peripheral tumor regions, intraparenchymal location, cell density, or specific cytologic characteristics. Low values of F did correlate with tumor necrosis and hydrocephalus; high values of F correlated with tumorous invasion or association with choroid plexus. Mean tumor F was not significantly different from that of the same anatomic, tumor-free brain region of the contralateral hemisphere, but F in brain tissue adjacent to the tumor was depressed significantly. Depression of F was observed in tumor-free cortex and corpus callosum, especially in the hemisphere ipsilateral to the main tumor mass and in those animals with hydrocephalus.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Neurology. - 33 : 6 (1983), p. 686-696. -
További szerzők:Blasberg, Ronald Molnár Péter Pál (1951-) (pathológus) Bigner, Darell Fenstermacher, Joseph D.
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3.

001-es BibID:BIBFORM029686
Első szerző:Molnár Péter Pál (pathológus)
Cím:Regional blood-to-tissue transport in avian sarcoma virus (ASV)-induced brain tumors / Molnar P., Blasberg R. G., Groothuis D., Bigner D., Fenstermacher J. D.
Dátum:1983
ISSN:0340-5354
Megjegyzések:Regional blood-to-tissue transport of 14C-alpha-aminoisobutyric acid (AIB) was measured in avian sarcoma virus (ASV)-induced rat brain tumors and expressed as a unidirectional transfer rate constant (K). The magnitude of K was variable and did not correlate with histologic classification or specific features of the tumors, with the possible exception of sarcomas. Averaged mean K was highest for anaplastic astrocytomas and lowest for gemistocytic astrocytomas (GA); however, the range of measurement within the individual tumor classifications (except GA) was broad. K was not consistently related to tumor size or tumor location; choroid plexus and subependymal tumors were exceptions and had higher K values. The averaged mean K of tumor-free brain in the contralateral hemisphere (CBA) was comparable to that of control animals. The averaged mean K in brain adjacent to tumor was greater than in CBA and generally one-third to one-half of the value in tumor periphery, indicating that these tumors affect the permeability characteristics of adjacent brain capillaries. Estimates of the fractional extraction (E) of AIB by the tumors ranged between 0.009 and 0.2; E's in this range indicate that tumor capillaries are not freely permeable to this solute.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Neurology. - 33 : 6 (1983), p. 702-711. -
További szerzők:Blasberg, Ronald Groothuis, Dennis Bigner, Darell Fenstermacher, Joseph D.
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4.

001-es BibID:BIBFORM029740
Első szerző:Warnke, Peter C.
Cím:Intravenous adenosine selectively increases blood flow to xenotransplanted intracerebral gliomas / Warnke P. C., Molnar P., Bigner D. D., Heistad D. H., Groothuis D. R.
Dátum:1987
ISSN:0028-3878
Megjegyzések:Adenosine was infused intravenously at 10 mumol/(kg.min) into athymic ("nude") rats with intracerebral D-54MG xenotransplanted brain tumors, in an attempt to increase tumor blood flow. Cerebral blood flow (F) was measured with 14C-iodoantipyrine and quantitative autoradiography. Mean arterial blood pressure was 95 +/- 9.4 (SE) mm Hg in the adenosine group and 112 +/- 6.0 mm Hg in the controls. Averaged mean whole tumor F was significantly higher in adenosine-treated brain tumors (117.6 +/- 20.8 ml/[hg.min]) than in controls (62.2 +/- 9.7 ml/[hg.min]). Regionally, there were significant increases of F in tumor periphery and brain around tumor, but not in tumor center or any tumor-free brain regions. Focal values of F less than 5 ml/(hg.min) were present in some necrotic regions of adenosine-treated tumors. These results, obtained in unanesthetized rats with transplanted gliomas from a human cell line, confirm our earlier observations in avian sarcoma virus-induced brain sarcomas in dogs, and suggest that adenosine or perhaps other vasodilators could be used to selectively increase the delivery of lipid-soluble chemotherapeutic drugs to brain tumors.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Neurology. - 37 : 12 (1987), p. 1870-1873. -
További szerzők:Molnár Péter Pál (1951-) (pathológus) Bigner, Darell Heistad, D. H. Groothuis, Dennis
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