Superinduction of human interferon-β(HuIFN-β) from human glioma cells has greater cytotoxicity than purified HuIFN-β derived from fibroblasts. However, superinduction requires several reagents like polyI:polyC, cycloheximide, and actinomycin D, which may contaminate the conditioned medium and obscure the effect of superinduced HuIFN-β. The present study used minimum doses of polyI:polyC and cycloheximide without actinomycin D to superinduce HuIFN-β. The superinduced HuIFN-β was purified by passing the medium through molecular sieve column chromatography. Fractionation of the eluate provided semipurified superinduced HuIFN-β which demonstrated a growth inhibitory effect against both the U251-MG autologous human glioma cell line and the SK-MG-1 homologous glioma cell line. This effect was neutralized by addition of anti-HuIFN-β monoclonal antibody (YSB-1). In a separate experiment, combinations of superinduction reagents were found not to have growth inhibitory effects because all inhibition in superinduced medium was completely neutralized by YSB-1. Superinduced HuIFN-β has a pure growth inhibitory effect on both autologous and homologous glioma cells, so may affect autocrine secretion of cytokines.

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The effects of specific antibodies against growth factors and receptors on deoxyribonucleic acid (DNA) synthesis in two established human glioma cell lines, A172 and TM-1, were examined. Anti-plateletderived growth factor (PDGF), anti-basic fibroblast growth factor (bFGF), and anti-epidermal growth factor receptor (EGF-R) antibodies inhibited thymidine incorporation by both cell lines in serum-free medium. Antibody specific to transforming growth factor-1α only slightly suppressed DNA synthesis by both cell lines. Although the antiproliferative effects of anti-PDGF and anti-bFGF antibodies decreased in serum-supplemented medium, the effect of anti-EGF-R antibody was little changed. The combination of anti-PDGF, anti-bFGF, and anti-EGF-R antibodies significantly inhibited thymidine incorporation by the two cell lines even in serum-supplemented medium. This preliminary study suggests that simultaneous blockade of multiple autocrine loops may provide a new approach to the treatment of human malignant gliomas.

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Production of tissue inhibitor of metalloproteinases-1 (TIMP-1), a specific inhibitor of matrix metalloproteinases, was investigated in human astrocytic tumors (n = 15) and normal brain tissues (n = 3). Enzyme immunoassay indicated that TIMP-1 levels in the culture media of tumor explants were significantly higher in glioblastomas as compared with anaplastic astrocytomas, astrocytomas, and normal brain tissues. Immunohistochemistry using a monoclonal antibody against TIMP-1 demonstrated that TIMP-1 was detectable mainly in tumor cells, especially in glioblastoma. These results suggest that increased expression of TIMP-1 is associated with the malignant progression of astrocytic tumors.

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The effect of cisternal drainage and intrathecal urokinase injection in preventing symptomatic vasospasm (SVS) after aneurysmal subarachnoid hemorrhage was studied in 60 patients with uniform background (Hunt & Kosnik grade III, younger than 70 yrs, undergoing surgery within 72 hrs after hemorrhage). The incidence of permanent neurological deficits caused by vasospasm was 5/16 without cisternal drainage, 5/34 with drainage alone, and 1/10 with drainage and urokinase injection. Analysis of patients without postoperative cisternal drainage showed the amount of subarachnoid clot on the initial computed tomographic scan was closely related to the occurrence of SVS (p < 0.05, unpaired t test). Analysis of patients with cisternal drainage showed the amount of bloody cerebrospinal fluid (CSF) drained during the 10 days after surgery and the duration of drainage placement were critical in preventing vasospasm (p < 0.05, unpaired t test). Greater CSF drainage significantly reduced the incidence of permanent neurological deficits caused by vasospasm (p < 0.01, χ2), but significantly increased the incidence of hydrocephalus requiring shunt procedures (p < 0.01, χ2). Urokinase injection via cisternal drainage achieved a further reduction in the occurrence of SVS. Intrathecal thrombolytic therapy after aneurysmal surgery is an effective method for SVS prophylaxis, and CSF drainage (> 1500 ml for 10 days) enhances the effect.

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The effects of relatively low dose gamma knife irradiation on acoustic schwannoma were evaluated. The signal intensity change and tumor shrinkage on magnetic resonance (MR) images, change in hearing, and complications in 28 patients (mean age 47.0 ± 13.6 yrs) were studied. Three patients had bilateral tumors. Six were already deaf when treated. The maximum tumor diameter was 35 mm. The mean dose delivered to the tumor was 12.1 ± 1.6 Gy at the periphery, and 25.2 ± 4.3 Gy at the center. The mean follow-up time was 16 months and the longest 24 months. Lowering of the MR signal intensity in the tumor center appeared after 3 months at earliest but generally after 6 months. Signs of tumor shrinkage appeared within 12 months on average. Cyst in the tumor enlarged rapidly after treatment in two patients. The percentage of hearing preservation was 85% (17/20) at 3 months, 80% (16/20) at 6 months, 72% (13/18) at 9 months, 75% (12/16) at 12 months, 67% (8/12) at 15 months, 60% (6/10) at 18 months, and 50% (2/4) at 24 months. Subtle changes in hearing were detected by speech tone audiometry. Temporary facial numbness and weakness was seen in one patient each. No patient had lower cranial nerve paresis. Relatively low dose gamma knife radiosurgery is effective in suppressing growth of acoustic schwannoma with preservation of hearing.

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A 68-year-old male presented with choroid plexus carcinoma in the left lateral ventricle manifesting as dysarthria and gait disturbance. Magnetic resonance imaging showed a homogeneously enhanced mass in the trigone of the left lateral ventricle. Selective left posterior cerebral arteriography showed the tumor was fed by the left medial posterior choroidal artery. Detailed examinations found no evidence of an extraneural primary focus. He underwent partial removal of the tumor followed by local Lineac irradiation (50 Gy). After irradiation, the serum level of carcinoembryonic antigen decreased and the size of the residual tumor was reduced.

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A 45-year-old male experienced a transient ischemic attack manifesting as left blurred vision and right hemiparesis. Angiography demonstrated an extracranial internal carotid artery aneurysm at the entrance of the carotid canal just above the C-1 vertebral arch. Intraluminal occlusion of the aneurysm was achieved with mechanically detachable coils under local anesthesia, and the carotid flow was preserved. There was no complication during or following the procedure. Treatment of aneurysms using detachable coils is an important alternative to surgical treatment when surgical access to the lesion is difficult.

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