Acquisition of resistance to anticancer agents is a serious problem for cancer chemotherapy. The present study analyzed the relationship between expression of the a isoform of deoxyribonucleic acid (DNA) topoisomerase II (topo IIα) and chemosensitivity to topo II inhibitors by modulating the level of topo IIα expression. A phosphorothioate analogue of an 18-nucleotide oligomer which is complementary to the translation initiation site of the human topo IIα messenger ribonucleic acid sequence was used to suppress the expression of topo IIα in a human glioma cell line (U373MG). The topo IIα activity of the treated cells was reduced to 1/3 of untreated cells in a decatenation assay using kinetoplast DNA. Antisense oligoDNA-treated cells showed mild resistance to the topo II inhibitors, etoposide and adriamycin, of about 2.0 fold and 1.5 fold, respectively, compared to control cells. Only partial reduction in the activity of topo IIα in the glioma cell line can cause a measurable resistance to topo II inhibitors, implying that the degree of topo II expression is correlated with chemosensitivity to topo II inhibitors.
Significantly reduced activities of glutamine synthetase (GS), which is predominantly present in glial cells, occur in the early stage of congenital hydrocephalic rat (LEW-HYR) brain development. GS activity is reported to be related to brain dysfunction. The effect of ventriculoperitoneal (VP) shunt on the suppression of GS activity was studied in the LEW-HYR. VP shunting improved the attenuation of GS activity in the LEW-HYR and the response of GS activity to methionine sulfoximine (a competitive GS inhibitor) treatment was similar to that seen in normal siblings. However, no enhancement of GS activity by hydrocortisone could be detected, although this enhancement occurs in the normal siblings. These results suggest that VP shunting is not completely effective in improving the suppression of brain GS activity in the LEW-HYR, since the suppression of GS activity in the LEW-HYR might be programmed genetically.
This study investigated the relationship between neurotransmitters and improvement of symptoms after ventriculoperitoneal shunting in congenital hydrocephalus (LEW-HYR) rats. Twenty-four patent hydrocephalus rats, aged 12-14 days, were randomly assigned to the following four groups: ventriculoperitoneal shunt group, obstructed shunt group, burr hole group, and no treatment group. In addition, six normal rats served as control group. Head to body length ratio was measured before and 7 days after the procedures. Coordination movement was evaluated on the 7th postoperative day. High performance liquid chromatography (HPLC) was used to measure the concentrations of dopamine (DA), norepinephrine (NE), serotonin, homovanillic acid (HVA), 3-methoxyl-4-hydroxyphenylenglycol, 5-hydroxy-indolacetic acid (5-HIAA), and 3, 4-dihydroxyphenylacetic acid in the whole cerebral cortex, the thalamus and hypothalamus, the midbrain, the lower brainstem, the cerebellum, and the striatum. Fluorohistochemical studies were also performed. Significant improvements were observed in body proportion and coordination movement in the ventriculoperitoneal shunt group compared to the burr hole group and the no treatment group. HPLC and fluorohistochemical studies revealed that concentrations of NE in the thalamus and hypothalamus and DA in the striatum were significantly lower in the burr hole group and the no treatment group. Concentrations of HVA and 5-HIAA in the cerebellum were significantly lower in the control group. The present study indicates that ventriculoperitoneal shunting may improve the changes in concentrations of neurotransmitter in specific neurons caused by hydrocephalus, and this may contribute to the improvement of the symptoms.
A 73-year-old female developed middle meningeal arteriovenous fistula during embolization of a falx meningioma. The cause of this complication was thought to be perforation by the guide wire during catheterization at the sharp bend in the sphenoidal portion of the middle meningeal artery. Embolization of the fistula and the feeding artery to the meningioma with polyvinyl alcohol particles 250-355μm size resulted in complete obliteration of the fistula. Computed tomography showed no epidural or subdural hematoma. Introduction of the microcatheter beyond the sharp bend in the middle meningeal artery should not be attempted to avoid the possibility of iatrogenic middle meningeal arteriovenous fistula.
A 65-year-old female presented with visual acuity loss. Magnetic resonance imaging confirmed the presence of a partially thrombosed giant aneurysm on the basilar tip. Cerebral angiography showed the opacified lumen of the aneurysm was 25 × 15 mm with a broad-based neck. Using a transfemoral approach, a microcatheter was guided through the vertebral artery and placed directly into the aneurysm under local anesthesia. Interlocking detachable coils were deposited into the patent portion of the aneurysm, resulting in 95% obliteration of the aneurysm and preservation of the parent artery. No complication was observed during or after surgery. Follow-up angiography 2 months later demonstrated the aneurysm was 95% occluded. No coil compaction was observed. Endovascular coil embolization therapy provides a therapeutic option for management of basilar tip aneurysms.
A 50-year-old male presented with a choroid plexus papilloma in the foramen magnum manifesting as dysesthesia in the right hand and severe headache. Magnetic resonance imaging clearly showed that the tumor was located in the cerebellomedullary cistern, without extension into the fourth ventricle. However, differentiation from hemangioblastoma or foramen magnum tumor was difficult by neuroimaging. Intraoperative observation found the tumor was located extraventricularly and attached to the choroid plexus of the foramen of Magendie. The tumor was grossly totally resected. Histological examination proved the tumor was a choroid plexus papilloma without malignancy. His neurological deficits resolved almost completely.
A 43-year-old male presented with swelling involving the right eye. Ti weighted magnetic resonance imaging demonstrated a round tumor in the lateral region of the right orbit, which was isointense relative to the cerebral gray matter and homogeneously enhanced by gadolinium-diethylenetriaminepenta-acetic acid with a flow-void signal area in the mass. The tumor was totally resected through the transcranial and fronto-orbitotemporal approach after embolization of feeding arteries arising from the external carotid artery. The histological findings were characteristic of hemangiopericytoma. No radiation therapy was administered. The transcranial and fronto-orbitotemporal approach provides a wide operative field with excellent exposure of the highly vascular orbital tumor.
A 43-year-old male presented with recurrent Lhermitte-Duclos disease (LDD), a rare pathological entity of the cerebellum of which the etiology is still controversial. He had undergone subtotal removal of a cerebellar lesion, misdiagnosed as a benign astrocytoma, 8 years previously. Subtotal removal of the recurrent tumor completely resolved the presenting symptoms. Recurrence of LDD is not as rare as generally assumed. Patients with LDD require long-term observation even when the initial treatment appeared curative.
A 49-year-old Japanese male with Lhermitte-Duclos disease subsequently developed a very rare association with Cowden''s disease. Partial tumor removal established the diagnosis of Lhermitte-Duclos disease. Follow-up examinations discovered the presence of Cowden''s disease. Long-term follow-up of patients with Lhermitte-Duclos disease is essential to identify signs of Cowden''s disease, which carries the risk of developing malignancy.
Three patients presented with unilateral sensori-neural hearing disturbance as the initial symptom of cerebellar tumors: a 19-year-old female with a medulloblastoma (Case 1), a 45-year-old male with a cerebellar low-grade glioma (Case 2), and a 49-year-old female with a cerebellar hemangioblastoma (Case 3). In Cases 1 and 2, the whole length of the eighth cranial nerve was intact according to magnetic resonance imaging and intraoperative findings. In Case 3, the intracerebellar tumor had bulged into the cerebellopontine cistern, compressing the eighth cranial nerve near the brainstem. Auditory evoked brainstem responses showed only the first wave in all three patients, and the following waves could not be discriminated. Unilateral sensori-neural hearing disturbance occurs very rarely in patients with intramedullary cerebellar lesions because the auditory neural pathway is bilaterally innervated. Intramedullary tumors may cause unilateral sensori-neural hearing disturbance by infiltrating or causing edematous changes of the eighth cranial nerve or the cochlear nucleus in the brainstem, or by compressing the nerve in the cistern. The symptoms are the same as those of acoustic neurinoma, so intramedullary cerebellar tumors should be considered in the differential diagnosis of unilateral sensorineural hearing disturbance.