Treatment of glioma by engineered interleukin 4-secreting cells.

The ability of interleukin-4 (IL-4) to mediate an antitumor response to human gliomas was studied in vivo in nude mice. To allow the effect of IL-4 to be exerted over a relatively short distance and at an optimal concentration, a transfected tumor cell line expressing a high level of IL-4 was used in mixed tumor transplantation assays. There was a significant inhibition of growth of the U87 human glioma line when the IL-4-secreting cell line, LT-1, was implanted s.

Growth of human acoustic neuromas, neurofibromas and schwannomas in the subrenal capsule and sciatic nerve of the nude mouse.

To develop a reproducible in vivo model for the growth of human acoustic neuromas and neurofibromas, we implanted tumor specimens (6 acoustic neuromas; 4 neurofibromas; 3 schwannomas arising in skin and soft tissues) from 13 different patients into the subrenal capsules of 67 nude mice and sciatic nerves of 64 nude mide. The animals were anesthetized and the tumors were microscopically implanted. Serial tumor volumes were determined at intervals up to 2 months by reopening the incision and directly measuring the tumor size with a micrometer.

Isolation and characterization of cDNA clones to mouse macrophage and human endothelial cell tissue transglutaminases.

The deduced amino acid sequences for tissue transglutaminases from human endothelial cells and mouse macrophages have been derived from cloned cDNAs. Northern blot analysis of both tissue transglutaminases shows a message size of approximately 3.6-3.

Inhibition of growth and angiogenesis of human neurofibrosarcoma by heparin and hydrocortisone.

A human neurofibrosarcoma was removed at surgery from a patient with neurofibromatosis and implanted into the subrenal capsule of female nude mice (nu/nu). A solid tumor grew and was transferred to 78 additional mice for this study. The animals were randomly assigned to one of four groups: 1) control, 27 animals; 2) oral heparin (200 or 500 U/ml), 17 animals; 3) oral hydrocortisone (0.

Transfer and expression of the lacZ gene in rat brain neurons mediated by herpes simplex virus mutants.

Three mutants of herpes simplex virus type 1 (HSV-1) were used to deliver and express the Escherichia coli lacZ gene in cells of the rat central nervous system. Because the lacZ gene was inserted in place of the genes encoding one of the immediate-early viral proteins ICP0 or ICP4 or the early viral protein thymidine kinase, these mutants were compromised or defective in their ability to replicate. All mutant vectors exhibited reduced pathogenesis in animals as compared to the wild type HSV-1 strain KOS.

Growth of human schwannomas in the subrenal capsule of the nude mouse.

To develop a reproducible in vivo model for the growth of human schwannomas we implanted tumor specimens from 14 different patients (13 acoustic neurinomas; 1 trigeminal schwannoma) into the subrenal capsule of 108 nude mice. In 11 experiments, the animals were implanted with only solid tumor from the surgical specimens. In two experiments, the tumor implants were made from solid tumors and cell clusters.

Regulation of tissue transglutaminase gene expression as a molecular model for retinoid effects on proliferation and differentiation.

Retinoids (structural and functional analogs of vitamin A) are potent antiproliferative agents whose mode of action is poorly understood. It has been suggested that the molecular events that underscore their action involve alterations in gene expression, but no gene has yet been shown to be directly regulated by these molecules. Several years ago, we found that retinoic acid caused an accumulation of the enzyme tissue transglutaminase in murine peritoneal macrophages and in human promyelocytic leukemia (HL-60) cells.

The molecular basis of retinoic acid action. Transcriptional regulation of tissue transglutaminase gene expression in macrophages.

Retinoic acid acts as an acute and specific inducer of tissue transglutaminase in mouse resident peritoneal macrophages. We have isolated cDNA clones for this enzyme and used them to demonstrate that this induction is due to the accumulation of tissue transglutaminase mRNA that occurs within minutes of exposure of macrophages to retinoic acid. The retinoic acid-induced increase in tissue transglutaminase mRNA is independent of concurrent protein synthesis and is due to an increased transcription of the tissue transglutaminase gene.

A simple method of eluting proteins from two-dimensional gels.

Apo A-I lipoprotein was extracted from the appropriate pieces of two-dimensional gel patterns, by electrophoresis onto hydroxylapatite overlaying a slab of polyacrylamide sodium dodecyl sulfate gel. The extracted protein was then eluted from the hydroxylapatite by washing with increasing concentrations of phosphate buffer. The recovered protein was electrophoretically homogeneous.