Expression and distribution of vascular endothelial growth factor protein in human brain tumors

Marked neovascularization is a hallmark of many neoplasms in the nervous system. Recent reports indicate that the endothelial mitogen vascular endothelial growth factor (VEGF) may play a critical role in the regulation of vascular endothelial proliferation in malignant gliomas. Using novel monoclonal antibodies to the VEGF polypeptide we have determined the expression and cellular distribution of VEGF protein in a representative series of 171 human central nervous system (CNS) tumors by immunohistochemistry and immunoblotting. In agreement with previous in situ hybridization data, 19 out of 20 glioblastomas (95%) showed immunoreactivity for VEGF, whereas both the percentage of immunoreactive tumors and the extent of immunoreactivity for VEGF were significantly lower in astrocytomas. Of the pilocytic astrocytomas (WHO grade I) 44% were immunoreactive for VEGF, but we observed several cases with pronounced vascular proliferates in the absence of VEGF. In ependymomas, meningiomas, hemangioblastomas, and primitive neuroectodermal tumors, there was no correlation between VEGF expression, vascular endothelial proliferation and the grade of malignancy. Oligodendrogliomas and the oligodendroglial component of mixed gliomas lacked immunoreactive VEGF, indicating that endothelial growth factors other than VEGF may regulate tumor angiogenesis in these neoplasms. Western blot analysis showed a predominant VEGF protein species of 23 kDa and confirmed the immunohistochemical data in all cases. Our findings demonstrate that VEGF is expressed in a wide spectrum of brain tumors in which it may induce neovascularization. However, other angiogenic factors also appear to contribute to the vascularization of CNS neoplasms. Received: 18 April 1996 / Revised, accepted: 20 August 1996     

Concentric sclerosis (Baló): Morphometric and in situ hybridization study of lesions in six patients

Brain tissues from 6 patients with concentric sclerosis (Baló) were examined by in situ hybridization, immunocytochemistry, morphometry, and histological methods. The patients were 24 to 48 years old and had progressive cerebral symptoms and signs that lasted 15 to 100 days. Large demyelinative lesions, most frequent in the frontal white matter, contained alternating bands of demyelinated and partly myelinated white matter that were arranged in concentric or mosaic patterns. In the areas of demyelination, axons were relatively well preserved and there were perivascular inflammatory infiltrates. In 2 specimens, lesions contained regions with the characteristic appearance of actively demyelinating multiple sclerosis plaques. Oligodendroglial densities were highest in normal-appearing white matter, lower in partially myelinated areas, and lowest in demyelinated areas, which also contained many hypertrophic astrocytes closely associated with oligodendroglia. Messenger RNA levels for myelin-related proteins followed the same pattern; they were lowest in demyelinated areas, higher in partially myelinated areas, and highest in normal-appearing white matter beyond lesion margins. Our findings suggest that concentric sclerosis is a variant of multiple sclerosis, that oligodendroglial loss is important in the pathogenesis of demyelination, and that partially myelinated areas probably represent stages of ongoing myelin breakdown rather than remyelination of previously demyelinated areas.     

Fibrous mastocytoma in a patient with generalized cutaneous mastocytosis

A 57-year-old woman with cutaneous mastocytosis of 23 years duration developed a hyperpigmented abdominal plaque composed of confluent indurated papules that enlarged for a period of 1 year to 12 x 8 cm. Biopsy showed dermal infiltration by closely packed spindle-shaped mast cells, fibroblasts, collagen, and scattered lymphocytes, predominantly T-suppressor cells. Electron microscopy showed close contact between mast cells, fibroblasts, and lymphocytes. Piecemeal mast cell degranulation and extrusion of mast cell granules was seen, with rare mast cell granules in fibroblasts, and collagen fibers in peripheral and perinuclear endoplasmic reticulum of mast cells. the term Fibrous mastocytoma is suggested for this tumor-like dermal fibrosis, possibly induced by lymphokines.     

Effect of body positions and splints in bioelectrical impedance analysis.

The objective of this study was to evaluate body composition as measured by bioelectric impedance analysis using splints and body positions differing from the standard supine position. Forty-three patients, randomized into two groups of different body positions, and 101 healthy volunteers were prospectively studied. Resistance and reactance of body tissues were measured by bioelectric impedance analysis. Body composition is described by a three-compartment model composed of body fat, body cell mass, and extra cellular mass. The patients were measured in the standard supine position and then randomized into two groups. They were then remeasured with the appropriate splinting device or position change. Volunteers were measured in the standard supine position and all four alternative positions. There was a statistically significant difference demonstrated in whole body resistance, whole body reactance, body cell mass, and the ratio of extracellular mass to body cell mass in some body positions. The percentage of change with different body positions and splints, when compared with the standard supine position, was generally below 2%, a clinically insignificant difference. We conclude that the reliability of resistance and reactance as measured by bioelectric impedance analysis is clinically valid using any of the tested body positions and/or splints. The three-compartment model may be a useful concept to measure body composition changes in both healthy and sick persons.     

Echinomycin (NSC 526417) in recurrent and metastatic nonsquamous cell carcinoma of the cervix. A phase II trial of the Gynecologic Oncology Group.

Eighteen evaluable patients with recurrent or metastatic nonsquamous carcinoma of the uterine cervix were treated with 1,500 micrograms/m2 of echinomycin every 4 weeks. Seven patients had received prior chemotherapy. There was one complete response (5.6%), 95% confidence interval for response of 0-27%. The major toxicity was nausea and vomiting, which was moderate to severe in eight patients. Myelosuppression was minimal. Echinomycin in this dose and schedule displays minimal activity in patients with advanced nonsquamous carcinoma of the cervix.