Inhibition of tumor growth in a glioma model treated with boron neutron capture therapy.

This investigation attempts to determine whether increased survival time seen when the F98 glioma model is treated with boron neutron capture therapy (BNCT) is a result of inhibition of tumor growth caused by radiation-induced alterations in endothelial cells and normal tissue components. This indirect effect of radiation has been called the tumor bed effect. A series of tumor-bearing rats was studied, using a standardized investigational BNCT protocol consisting of 50 mg/kg of Na2B12H11SH injected intravenously 14 to 17 hours before neutron irradiation at 4 x 10(12) n/cm2.

Adoptive immunotherapy of a rat glioma using lymphokine-activated killer cells and interleukin 2.

The aim of the present study was to develop an animal model to test the therapeutic potential of purified adherent lymphokine-activated killer (A-LAK) cells against an intracerebrally implanted rat glioma, designated F98. Highly purified A-LAK cells demonstrated greater activity against F98 tumor cells than conventional lymphokine-activated killer cells, as determined by means of 51Cr-release and clonogenic assays. Therapeutic efficacy was evaluated by means of a Winn neutralization assay, in which F98 targets and A-LAK cells or control nonadherent mononuclear cells were incubated for 18 h in vitro and then implanted stereotactically into the right caudate nuclei of Fischer rats.

Boron neutron capture therapy of a rat glioma.

The purpose of the present study was to utilize a well-established rat glioma to evaluate boron neutron capture therapy for the treatment of malignant brain tumors. Boron-10 (10B) is a stable isotope which, when irradiated with thermal neutrons, produces a capture reaction yielding high linear energy transfer particles (10B + 1nth----[11B]----4He(alpha) + 7Li + 2.79 MeV).

Theoretical basis and clinical methodology for stereotactic interstitial brain tumor irradiation using iododeoxyuridine as a radiation sensitizer and 145Sm as a brachytherapy source.

A technique to produce radiation enhancement during interstitial brain tumor irradiation by using a radiation sensitizer (iododeoxyuridine-IdUrd) and by stimulation of Auger electron cascades through absorption of low-energy photons in iodine is described. Clinical studies using iododeoxyuridine, 192Ir as a brachytherapy source, and external radiation have produced promising results. Substituting 145Sm for 192Ir in this protocol is planned to evaluate the enhanced dose resulting from photon activation therapy.

Ultrastructural microvascular response to boron neutron capture therapy in an experimental model.

A CD 344 rat glioma model currently used to investigate boron neutron capture therapy (BNCT) was used to demonstrate an increased survival rate after thermal neutron irradiation enhanced by administration of 10B-enriched polyhedral borane, Na2B12H11SH. To investigate the possible effects of BNCT on normal and tumor microvasculature, we subjected animals to sublethal neutron irradiation with and without intravenous injection of 50 mg/kg of enriched 10B and performed histological and ultrastructural analyses. In the rats that did not undergo tumor transplantation, minimal detectable morphological changes in the microvasculature of the central nervous system were observed after treatment, both in the immediate posttreatment phase and at 10 months.

Pre-clinical studies on boron neutron capture therapy.

The present report provides an overview of the multidisciplinary research effort on BNCT that currently is in progress at The Ohio State University. Areas under investigation include the preparation of boron containing monoclonal antibodies, the synthesis of boron containing derivatives of promazines and phathalocyanines, the development of a rat model for the treatment of glioblastoma by means of BNCT, the design of an accelerator-based neutron irradiation facility, and 10B concentration measurements using alpha track autoradiographic methods. Progress in each of these areas is described and the direction of future research is indicated.

The degradation of phospholipids, formation of metabolites of arachidonic acid, and demyelination following experimental spinal cord injury.

Spinal cord injury has been studied using a cat compression model. Very early changes in lipid metabolism were found that compromise the integrity of the plasma membrane and decrease the activities of ATPases. Up to 18% of the ethanolamine plasmalogens are lost, with very marked elevations of the free fatty acids, arachidonic acid, diacylglycerols, prostaglandins, thromboxanes, and leukotrienes.

Lysosomal isozyme patterns in ethylnitrosourea-induced brain tumors.

Isozyme patterns for five acid hydrolases, acid phosphatase (AP), aryl-sulfate (AS), beta-glucuronidase (beta-Glu), N-acetylglucosaminidase (NAG) and beta-galactosidase (beta-Gal), were studied in isolated lysosomes from ethylnitrosourea (ENU)-induced gliomas and compared with normal and newborn rat brains. With polyacrylamide gel electrophoresis (PAGE), AP was separated into three bands, acidic (A), intermediate (B) and basic (C). In tumors and newborn brains there was a decrease in A and C but a significant increase in B.

An improved rat brain-tumor model.

The widely used intracerebral tumor implantation method by freehand injection into parietal or hippocampal areas of the rat brain has proven inadequate for reliable experimental therapeutic studies. Problems include poor intracerebral growth yields and significant rates of spread to extracranial tissues, lungs, and spinal cord. Major variables have been examined experimentally on a model using nitrosourea-induced nervous system tumor cell lines in sygeneic rats.

The effect of dimethyl sulfoxide on gray matter injury in experimental spinal cord trauma.

The possible effect of dimethyl sulfoxide upon the development of lesions in the gray matter after experimental spinal cord trauma has been investigated with the use of cytochrome oxidase assay and quantitative histologic measurement of total liquefaction necrosis. Observations were made in 17 unconditioned dogs receiving an impact trauma of 400 gm cm force. Experimental animals were given 2.

Inhibition of Na+-K+-activated ATPase activity following experimental spinal cord trauma.

The specific activity of the membrane-bound enzyme, Na+-K+-activated adenosine triphosphatase (ATPase), has been shown to be decreased following experimental impact injury (400 gm-cm) to the spinal cord in dogs. The prompt and significant (p less than 0.01) fall in activity was evident as early as 5 minutes after injury, and remained at 56% to 67% of control for the 1-hour period studied.

Acid hydrolase and cytochrome oxidase activities in nitrosourea induced tumors of the nervous system.

Nitrosourea induced tumors of the nervous system in rats have proven useful for biochemical studies combined with morphological approaches. The pattern of enzyme activities for acid hydrolases and cytochrome oxidase resemble those previously observed in spontaneous nervous system tumors of man. The activities of 4 acid hydrolases were generally high in the gliomas.

Sequential development of ethylnitrosourea-induced neurinomas: morphology, biochemistry, and transplantability.

Sequential evaluations were made of the morphology and biochemistry of trigeminal nerves from control and ethylnitrosourea (ENU)-exposed rats from 1 day to 6 months of age. Distinct increases in cellularity were evident as early as 20 days after exposure to ENU. Corresponding increases in N-acetyl-beta-glucosaminidase and beta-glucuronidase were detected at the same time.