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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.
Internet cím:	Szerző által megadott URL Intézményi repozitóriumban (DEA) tárolt változat
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001-es BibID:	BIBFORM029715
Első szerző:	Horowitz, Marc
Cím:	Regional [14C]misonidazole distribution in experimental RT-9 brain tumors / Horowitz M., Blasberg R., Molnar P., Strong J., Kornblith P., Pleasants R., Fenstermacher J.
Dátum:	1983
ISSN:	0008-5472
Megjegyzések:	Regional [14C]misonidazole-derived radioactivity (MISO) was measured by quantitative autoradiography in experimental RT-9 brain tumors 0.5, 2, and 4 hr after an i.v. bolus (25 mg) and constant infusion (10 mg/hr). Misonidazole (MISO) concentration in plasma and brain was also measured by high-pressure liquid chromatography; the brain/plasma MISO ratio ranged between 0.5 and 0.7. MISO equivalents were calculated from tissue or plasma 14C radioactivity and [14C]MISO specific activity data. The MISO/MISO equivalents ratio, which represents the nonmetabolized fraction of [14C]MISO, fell gradually in plasma (0.89 at 4 hr) and more rapidly in brain (0.67 at 4 hr) and tumor (0.30 at 4 hr). MISO distributed uniformly throughout the brain at all three time periods. In contrast, MISO distribution in tumor was variable, and tumor concentrations relative to that in brain increased with time. The average tumor/brain MISO ratio was 1.3, 1.7, and 2.6 at 0.5, 2, and 4 hr, respectively, which suggests tumor uptake and binding of MISO or, more likely, MISO-derived 14C-labeled metabolites. In addition, MISO distribution in tumor tissue was strikingly heterogeneous at 4 hr, resulting in an average high/low tumor activity ratio of 4/1 and an average high tumor/brain ratio of 5/1. Tumor regions with high MISO activity correlated in part to viable-appearing cells around necrotic foci.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:	Cancer Research. - 43 : 8 (1983), p. 3800-3807. -
További szerzők:	Blasberg, Ronald Molnár Péter Pál (1951-) (pathológus) Strong, J. Kornblith, Paul Pleasants, Roger Fenstermacher, Joseph D.
Internet cím:	Szerző által megadott URL Intézményi repozitóriumban (DEA) tárolt változat
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