Lars Granholm

Sialyllactotetraosylceramide, a Ganglioside Marker for Human Malignant Gliomas

The ganglioside composition of surgically removed human glioma tissue was shown to differ from that of normal adult brain tissue. First, it contained reduced amounts of the major normal brain gangliosides of the gangliotetraose series. Second, it contained increased proportions of gangliosides not detected in normal brain tissue. One of these was isolated and established as being sialyllactotetraosylceramide 3′‐isoLM1. Radioimmunoassay for this ganglioside antigen in human glioma tissue revealed that 14/14 specimens of grades III and IV were positive but only 1/4 of grade II. Normal brain tissue was negative. These results suggest that sialyllactotetraosylceramide is a marker for human malignant gliomas.

Estrogen and progestin receptors in intracranial meningiomas

Tissue samples from 16 meningioma patients were analysed for the cytosolic estrogen receptor concentration using isoelectric focusing and 11 of the 16 cases were also analysed for the cytosolic progestin receptor concentration using sucrose gradient centrifugation. In this study, 15 of the 16 (94%) and 9 of the 11 (82%) meningiomas had detectable estrogen and progestin receptors, respectively. The mean estrogen receptor concentration in female subjects was 8.9 fmol/mg protein and in males 3.0 fmol/mg protein. This sexual difference in receptor content was statistically significant. When the progestin receptor concentrations were plotted against the estrogen receptor concentrations in the same tumors, a relatively good positive correlation was obtained in female patients (r = 0.87). These findings confirm and extend previous reports on the existence of sex steroid receptors in human brain tumors and might open up the possibility of selective endocrine therapy against meningiomas, especially in case of poor-risk patients.

Effect of dexamethasone treatment on volume and contrast enhancement of intracranial neoplasms.

In a prospective study the effect of dexamethasone treatment on tumor volume and contrast enhancement was evaluated by computed tomography (CT) in 15 patients with intracranial lesions. Histological diagnoses were confirmed in 13 patients who had undergone surgical intervention. A CT study of the head, with and without contrast medium, was performed prior to the dexamethasone treatment and at various intervals during the treatment for 8–19 days. The volume, attenuation, and contrast enhancement of the tumor were measured and related to the time after the start of the treatment. In six meningiomas there was no change in the volume and enhancement of the tumors. Out of four gliomas, there was an increase in volume of two tumors, whereas the other two cases showed a decrease in the tumor volume. In one glioma a distinct decrease in enhancement was observed. In three cases of metastasis a decrease in enhancement and tumor volume was noted. An acoustic neurinoma and an unverified lesion, considered radiologically to be a glioma, also showed a decrease in tumor volume and contrast enhancement. In lumors that responded to the treatment, a decrease both in volume of the tumor and peritumoral brain edema as well as a decrease in contrast enhancement of the tumor were observed.

Prolonged survival and vascularization of xenografted human glioblastoma cells in the central nervous system of Cyclosporine A treated rats

Glioblastoma cells from three established lines were transplanted in oculo and in cerebrum to rat hosts. A very low dose of Cyclosporine A was found sufficient to allow graft survival whereas grafts in non-immunosuppressed animals did not survive. Moderate immunosuppression permitted long term graft survival without aggressive growth of glioblastoma cells, creating a protracted course during which neither cell rejection nor tumor proliferation occurred. A tumor reminiscent of a glioblastoma was only seen in one animal on high immunosuppression. Phenotypic changes such as the induction of glial fibrillary acidic protein (GFAP) production and an astrocytic morphology were observed in the cells growing in oculo but not in cerebrum. Vascularization was easily demonstrated with laminin immunofluorescence but the endothelial proliferation typical of glioblastomas was not seen.

A qualitative comparison of the glucocorticoid receptor in cytosol from human brain and rat brain.

The glucocorticoid receptor in cytosol from human brain was studied using isoelectric focussing in slabs of polyacrylamide gel. [3H]Dexamethasone was used as tracer for receptor analysis. The glucocorticoid receptor from human brain was compared to the glucocorticoid receptor in rat brain. A similar peak of radioactivity with a pI of about 6.1 was obtained by isoelectric focussing of cytosol from both human brain and rat brain. The trypsin-induced fragmentation patterns of the glucocorticoid receptor from human brain and rat brain were very similar when analyzed by isoelectric focussing. The hormone specificity of the glucocorticoid receptor in human brain and in rat brain cytosol was compared by competition experiments using unlabelled dexamethasone, betamethasone, cortisol and corticosterone as competitors. No difference between human brain and rat brain cytosol was detected. It is concluded that the hormone specificity and the protein structure of the glucocorticoid receptors in human brain and in rat brain are similar.

Induction of GFAP production in human glioma lines grafted into the anterior chamber of the rat eye

Three established glial fibrillary acidic protein (GFAP)-negative cell lines from human gliomas were transplanted to the anterior chamber of the rat eye. Short-term survival was seen with all transplants. The cells expressed GFAP following transplantation. For comparison, 4 GFAP-positive cell lines were transplanted. With grafting of 5000 cells of any of 6 bipolar cell lines, the transplanted cells could be seen to develop multiple, slender processes reminiscent of mature astrocytes. When 50,000 cells were grafted, vascularized cell mats covering the corneae were seen. The induction of GFAP production and the phenotypic changes were interpreted as signs of differentiation induced by the new environment. All transplanted cells were rejected after 8 weeks.