Efficacy and immunomodulatory actions of ONO-4641, a novel selective agonist for sphingosine 1-phosphate receptors 1 and 5, in preclinical models of multiple sclerosis.

ONO-4641 is a next-generation sphingosine 1-phosphate (S1P) receptor agonist selective for S1P receptors 1 and 5. The objective of the study was to characterize the immunomodulatory effects of ONO-4641 using preclinical data. ONO-4641 was tested in both in-vitro pharmacological studies as well as in-vivo models of transient or relapsing-remitting experimental autoimmune encephalomyelitis (EAE). In vitro, ONO-4641 showed highly potent agonistic activities versus S1P receptors 1 and 5 [half maximal effective concentration (EC(50) ) values of 0·0273 and 0·334 nM, respectively], and had profound S1P receptor 1 down-regulating effects on the cell membrane. ONO-4641 decreased peripheral blood lymphocyte counts in rats by inhibiting lymphocyte egress from secondary lymphoid tissues. In a rat experimental autoimmune encephalomyelitis (EAE) model, ONO-4641 suppressed the onset of disease and inhibited lymphocyte infiltration into the spinal cord in a dose-dependent manner at doses of 0·03 and 0·1 mg/kg. Furthermore, ONO-4641 prevented relapse of disease in a non-obese diabetic mouse model of relapsing-remitting EAE. These observations suggest that ONO-4641 may provide therapeutic benefits in the treatment of multiple sclerosis.

Disruption of Tacc3 function leads to in vivo tumor regression.

The formation of the bipolar spindle is responsible for accurate chromosomal segregation during mitosis. The dynamic instability of microtubules has an important role in this process, and has been shown to be an effective target for cancer chemotherapy. Several agents that target non-microtubule mitotic proteins, including the motor protein Eg5, Aurora kinases and Polo-like kinases, are currently being developed as chemotherapeutic drugs. However, because the efficacies of these drugs remain elusive, new molecular targets that have essential roles in tumor cells are desired. Here, we provide in vivo evidence that transforming acidic coiled-coil-3 (Tacc3) is a potential target for cancer chemotherapy. Using MRI, we showed that Tacc3 loss led to the regression of mouse thymic lymphoma in vivo, which was accompanied by massive apoptosis. By contrast, normal tissues, including the thymus, showed no overt abnormalities, despite high Tacc3 expression. in vitro analysis indicated that Tacc3 depletion induced multi-polar spindle formation, which led to mitotic arrest, followed by apoptosis. Similar responses have been observed in Burkitt's lymphoma and T-ALL. These results show that Tacc3 is a vulnerable component of the spindle assembly in lymphoma cells and is a promising cancer chemotherapy target.

[Persistent primitive trigeminal artery presenting with Weber's syndrome: report of a case with three-dimensional CT angiographic evaluations].

We report a rare case of persistent primitive trigeminal artery(PPTA) presenting with brain stem infarction known as Weber's syndrome, and document its unique findings of three-dimensional CT angiography(3 D-CTA). A 69-year-old woman was admitted to our hospital because of gait disturbance and blepharoptosis on the right eye. Neurological examination on admission revealed the right oculomotor nerve palsy, left hemiparesis and dysarthria, all of which indicated the signs and symptoms of Weber's syndrome. Initial CT scan revealed no abnormality, but a subsequent 3 D-CTA demonstrated the PPTA originating from the right internal carotid artery penetrate into the clivus directly to the distal basilar artery, on top of which a small saccular aneurysm was incidentally visualized. Right internal carotid angiograms showed the PPTA run between the cavernous segment of the internal carotid artery and the distal portion of the basilar artery with the filling of both the posterior cerebral and superior cerebellar arteries. However, the proximal portion of the basilar artery was visualized through the right vertebral artery and there was no blood flow to its distal portion. Evidence of infarction was finally confirmed at the right midbrain and thalamus by the MRI performed 5 days after the onset. With a conservative treatment including physical therapy, the patient recovered well from the deficits and could walk by herself with a cane. With regard to the pathogenesis of vertebrobasilar insufficiency in a patient with PPTA, it is generally considered that microembolus from an atherosclerotic carotid artery may be its cause because of the presence of direct communication between the anterior and posterior circulations. In the present case, however, this mechanism may not be applied since there was no evidence of atherosclerotic plaque or stenotic lesions on the carotid arteries. Alternatively, an embolic occlusion may have occurred in the paramedian branches of the posterior cerebral artery since a dilated PPTA itself, which resembled fusiform-aneurysm in appearance, may become the origin of microembolus.

Activation of the cytoplasmic c-Abl tyrosine kinase by reactive oxygen species.

The ubiquitously expressed c-Abl protein tyrosine kinase localizes to both the nucleus and cytoplasm. The nuclear form of c-Abl is activated in the cellular response to genotoxic stress. Here we show that cytoplasmic c-Abl is activated by oxidative stress. The results also demonstrate that mitochondrial cytochrome c is released in the cellular response to H(2)O(2) and that this effect is mediated by a c-Abl-dependent mechanism. In concert with these results, we show that H(2)O(2)-induced apoptosis is attenuated in c-Abl-deficient cells. These findings demonstrate that cytoplasmic c-Abl is involved in the apoptotic response of cells to oxidative stress.

Function for p300 and not CBP in the apoptotic response to DNA damage.

The cellular response to ionizing radiation (IR) includes the induction of apoptosis. The p300/CBP proteins possess histone acetyltransferase activity and function as transcriptional coactivators of p53. We have prepared cells deficient in p300 or CBP to define the roles of these proteins in the cellular response to DNA damage. The present results demonstrate that p300, but not CBP, contributes to IR sensitivity of cells. The results also demonstrate that IR-induced apoptosis is impaired in the p300-, but not CBP-, deficient cells. These findings indicate that p300 functions in the apoptotic response to DNA damage.

Blood flow and metabolism of oligodendrogliomas: a positron emission tomography study with kinetic analysis of 18F-fluorodeoxyglucose.

To accurately characterize the pathophysiology and proliferating activity of oligodendrogliomas, we studied cerebral blood flow and metabolism using positron emission tomography (PET) in five patients with this tumor. Regional cerebral blood flow (rCBF), cerebral blood volume (rCBV), oxygen extraction fraction (rOEF), and cerebral metabolic rates of oxygen (rCMRO2) and of glucose (rCMRGl) were quantitatively measured in tumor lesions and the contralateral gray matter, rCMRGl was analyzed based on both kinetic and autoradiographic methods. Tumor rCBF and rCBV were lower than in the contralateral gray matter in all preoperatively examined patients. Oxygen metabolism, determined by rCMRO2 and rOEF, was consistently reduced in the tumor (rCMRO2, P<0.05 vs. gray matter, determined by the Student's t-test). Tumor rCMRGl was significantly lower than the gray matter rCMRGl in both kinetic (P<0.01) and autoradiographic (P<0.05) analyses. Kinetic tumor rCMRGl varied between 1.22 and 4.13 mg/100 ml/min, but was lower than the gray matter value in all patients. Autoradiographic tumor rCMRGl, which ranged from 1.02 to 5.79 mg/100 ml/min, was also reduced in all tumors but one; the remaining tumor, which had a relatively high value of autoradiographic rCMRGl (comparable to gray matter rCMRGl), infiltrated the contralateral hemisphere through the corpus callosum, and was characterized by high cellular density. In one patient who suffered from tumor recurrence 8 years and 10 months after initial treatment, phosphorylation constant (K3) and kinetic rCMRGl of the recurring tumor were higher than those of the original tumor. No other tumors have regrown or recurred during the postoperative follow-up periods, which ranged from 22 to 130 months (median = 101 months). Circulation and metabolism measured by PET provide in vivo biological characteristics, including proliferating activity, in oligodendrogliomas.

[Atypical neuroradiological features of microcystic meningioma: case report].

We report a rare case of microcystic meningioma presenting with atypical neuroradiological features. A 76-year-old woman was admitted to our hospital in October, 1996 because of head heaviness without obvious neurological deficits. Previous CT scan in 1989 revealed no abnormality, but a subsequent scan in 1992 showed a low-density area in the right frontal region. Since then the patient has been followed up as a case of cerebral infarction. At the time of the current admission, CT scan disclosed the low-density area as having grown to the size of 4 cm and heterogeneously enhanced after injection of contrast medium. On MRI the mass lesion was depicted as low-intensity on T1-weighted image and high-intensity on T2-weighted image. The mass was heterogeneously enhanced after administration of Gd-DTPA. Right internal and external carotid angiograms revealed neither tumor feeder nor tumor stain. Craniogram showed neither hyperostosis nor bone erosion, and yet bone scintigram demonstrated markedly increased uptake involving the right frontal bone near the tumor. At surgery the tumor was found to have originated from the dura in the right frontal convexity, which was well demarcated and separated from the surrounding brain tissue. Total removal designated as Simpson grade I procedure was accomplished. Light microscopy revealed abundant microcysts of varied size throughout the tumor tissue with the presence of whorl formation and psammoma body, but no malignancy was indicated. Electron microscopy further demonstrated interdigitation of the neighboring cell membranes, desmosomes, and intracytoplasmic filaments, which are pathognomonic findings of meningiomas. The microcysts were seen to reside in the extracellular spaces rather than in the cytoplasm. With these pathological findings, the tumor was finally diagnosed as microcystic meningioma.

p73 is regulated by tyrosine kinase c-Abl in the apoptotic response to DNA damage.

The protein p73 is a structural and functional homologue of the p53 tumour-suppressor protein but, unlike p53, it is not induced in response to DNA damage. The tyrosine kinase c-Abl is activated by certain DNA-damaging agents and contributes to the induction of programmed cell death (apoptosis) by p53-dependent and p53-independent mechanisms. Here we show that c-Abl binds to p73 in cells, interacting through its SH3 domain with the carboxy-terminal homo-oligomerization domain of p73. c-Abl phosphorylates p73 on a tyrosine residue at position 99 both in vitro and in cells that have been exposed to ionizing radiation. Our results show that c-Abl stimulates p73-mediated transactivation and apoptosis. This regulation of p73 by c-Abl in response to DNA damage is also demonstrated by a failure of ionizing-radiation-induced apoptosis after disruption of the c-Abl-p73 interaction. These findings show that p73 is regulated by a c-Abl-dependent mechanism and that p73 participates in the apoptotic response to DNA damage.

Role for p300 in stabilization of p53 in the response to DNA damage.

The nuclear p300/CBP proteins function as coactivators of gene transcription. Here, using cells deficient in p300 or CBP, we show that p300, and not CBP, is essential for ionizing radiation-induced accumulation of the p53 tumor suppressor and thereby p53-mediated growth arrest. The results demonstrate that deficiency of p300 results in increased degradation of p53. Our findings suggest that p300 contributes to the stabilization and transactivation function of p53 in the cellular response to DNA damage.

Long-term histopathology of intracranial aneurysms after endovascular treatment with coils. Report of two cases with ultrastructural evaluations by scanning electron microscopy.

We describe the results of electron microscopic examination in two patients with ruptured intracranial aneurysms who were successfully treated by endovascular coil embolization. The aneurysms were seen completely occluded on the follow-up angiograms. Autopsies of these patients were performed five and 26 months after endovascular treatment when they died of pneumonia and thalamic hemorrhage, respectively. The aneurysms were densely filled with the coils, which were readily identified through the thin and transparent wall of the aneurysmal dome. The orifice of the aneurysm was completely occluded so that macroscopically the coils were not directly visualized through the orifice. To examine any evidence of endothelialization across the orifice of the aneurysms, scanning electron microscopic examination was performed. In both cases, evidence of well regenerative endothelialization was observed across the aneurysmal orifice, being contiguous with the endothelial layer of the adjacent parent vessels. These ultrastructural findings indicate that the aneurysms are completely isolated from the lumen of the parent artery by a continuous lining of the regenerated endothelial cells following the endo vascular treatment with coils, and further suggest that aneurysms have a potential of being cured permanently by this treatment modality. This is, to the best of our knowledge, the first report in humans verifying a complete endothelialization of the luminal surface at the aneurysmal neck after coil embolization, as evidenced by scanning electron microscopy.

Reconstruction of thoracic wall defects after tumor resection using a polytetrafluoroethylene soft tissue (Gore-Tex) patch.

BACKGROUND: Recently, there have been a few reports recommending use of a 2 mm thick polytetrafluoroethylene soft tissue (Gore-Tex) patch for repair of thoracic wall defects. The potential role of these Gore-Tex patches was examined. METHODS: Five patients underwent chest wall tumor resection with thoracic wall reconstruction using a Gore-Tex patch (2 mm). We present a review of the complications experienced by five patients with Gore-Tex patches, as well as a review of the literature. RESULTS: Functionally and cosmetically, satisfactory results were obtained for 5 patients with Gore-Tex patch. There were no cases of infectious complications. However, we experienced one case of a flail chest postoperatively, in which reconstruction with two Gore-Tex patches of 30 x 15 cm, and 3 days of mechanical ventilation and chest wall support was needed. CONCLUSION: Our experience with Gore-Tex patches has been positive, and we recommend patch closure for thoracic wall defects.

[Spontaneous spinal epidural hematoma with spontaneous remission, diagnosed in MRI on superacute stage].

We report a case of spontaneous spinal epidural hematoma with spontaneous remission diagnosed by MRI on superacute stage. A 52-year-old man was admitted to our hospital because of severe shoulder-neck-back pain of acute onset. One hour after onset he had left hemiparesis and gradually became tetraparesis. He had no history of trauma, anticoagulant therapy, or a tendency to bleed. There was no abnormality in the laboratory data. CT scan of the head revealed no abnormality, but the scan of cervical region showed an abnormal high-density area in the left posterior region of spinal cord at C4-C7. MRI demonstrated an epidural mass lesion in the left posterior region of spinal cord at C3-Th3 compressing the left side of spinal cord posteriorly was iso-intensity on the T1-weighted image and high-intensity on the T2-weighted image. However, his motor function recovered almost completely without a slight motor weakness of left upper limb about two hours after onset spontaneously. He was initially treated with a corticosteroid agent, and he could walk next day after onset. After about 2 weeks of onset, MRI revealed a vanished epidural hematoma and no abnormal enhancement. After about 2 months of onset, spinal angiograms revealed no vascular anomaly. The mechanism of spontaneous recovery from tetraparesis is assumed that the spreading of hematoma in epidural space up- and downwards to the rostro-caudal direction results in decompression. MRI is useful to detect spinal epidural hematoma safely and accurately for its diagnosis. MRI is also proved to be an accurate and efficacious method for evaluation of its size, location, and extent in the spinal canal.

Rapid colorectal adenoma formation initiated by conditional targeting of the Apc gene.

Familial adenomatous polyposis coli (FAP) is a disease characterized by the development of multiple colorectal adenomas, and affected individuals carry germline mutations in the APC gene. With the use of a conditional gene targeting system, a mouse model of FAP was created that circumvents the embryonic lethality of Apc deficiency and directs Apc inactivation specifically to the colorectal epithelium. loxP sites were inserted into the introns around Apc exon 14, and the resultant mutant allele (Apc580S) was introduced into the mouse germline. Mice homozygous for Apc580S were normal; however, upon infection of the colorectal region with an adenovirus encoding the Cre recombinase, the mice developed adenomas within 4 weeks. The adenomas showed deletion of Apc exon 14, indicating that the loss of Apc function was caused by Cre-loxP-mediated recombination.

Tumor extent of slowly progressive oligodendroglioma determined by 18F-fluorophenylalanine positron emission tomography.

We report the use of positron emission tomography (PET) and 18F-fluorophenylalanine (18F-Phe) to determine the extent of a slowly progressive oligodendroglioma, which gradually grew over 10 years after the onset of convulsions. The tumor exhibited intense accumulation of 18F-Phe and was easily distinguished from the surrounding brain tissue. The tumor lesion indicated by 18F-phe PET was more extensive than the lesion detected by computerized tomography (CT) and was comparable to the hypointense lesion detected by T2-weighted magnetic resonance imaging (MRI). The tumor, a histologically verified oligodendroglioma, was extensively resected, and its extent corresponded to the high uptake region of 18F-Phe. The accuracy of the 18F-Phe PET technique for determining the extent of a tumor is valuable and will aid in the selection of an appropriate therapy modality for the management of oligodendrogliomas.

Subependymoma of the septum pellucidum: characterization by PET.

We report the evaluation of a subependymoma of the septum pellucidum by positron emission tomography (PET) with analysis of 18F-fluorodeoxyglucose (FDG) kinetics. The tumor showed exceedingly low rates of glucose metabolism (rCMRG1) and kinetic constants (K1, K2, and K3). This hypometabolism indicates low cellular density and slow growth.

[Hemocirculation and metabolism in intraventricular tumors: kinetic analysis of glucose metabolism].

To estimate hemocirculation and proliferating activity of intraventricular tumor, we measured kinetic rate constants (k1, k2, k3) and glucose metabolic rate (kinetic-rCMRGl) using dynamic positron emission tomography (PET), as well as regional cerebral blood flow (rCBF), blood volume (rCBV), oxygen extraction fraction (rOEF), oxygen metabolic rate (rCMRO2) and autoradiographic rCMRGl (arg-rCMRGl), in patients with intraventricular tumor. The subjects included ten patients, five males and five females, aged from 13 to 53 years with a mean age of 32 years old. Eight tumors were located in the lateral ventricle and two extended into the third ventricle through the foramen of Monro. Another two tumors were located in the fourth ventricle. Histological diagnosis was as follows: five cases of central neurocytoma, one subependymal giant cell astrocytoma, one ependymoma, one choroid plexus carcinoma, one subependymoma, and one meningioma. Tumor lesion on the PET images was determined using CT or MRI, which was performed at levels equivalent to those for the PET scans. For quantitative analysis, regions of interest (ROI) on PET images were delineated on the tumor and the contralateral gray matter. Hemocirculation (rCBF, rCBV) of the tumor was similar to or higher than that of the contralateral gray matter, which corresponded to neuroradiological findings of abundant tumor vessels. Oxygen metabolic parameters (rOEF, rCMRO2) were significantly lower than those of the contralateral gray matter. Especially, low rOEF resulted in an excessive blood flow beyond oxygen demand of the tumor. The raised metabolic rate (rCMRO2/rCMRGl), as compared with that of meningiomas or malignant gliomas, suggested aerobic glycolysis. The kinetic rate constants of tracer transport from blood to brain (k1), reverse transport from brain to blood (k2), and phosphorylation (k3) were analyzed according to the three-compartment model of 18F-fluorodeoxyglucose (18FDG). Tumor k1 and k2 values were similar to or higher than those of the contralateral gray matter, suggesting high permeability due to lack of blood-brain barrier and an abundant blood supply. Tumor k3 value, an indicator of hexokinase activity, and kinetic-rCMRGl were lower in six of eight patients. These six patients have been free from tumor recurrence or regrowth, postoperatively. In the other two patients, tumor kinetic-rCMRGl was similar to or higher than that of the contralateral gray matter, suggesting high activity of proliferation. However, one patient received irradiation and has been followed up, and the other received total resection and has shown no recurrence. Functional information concerning intraventricular tumor is obtained by PET analysis, and kinetic analysis of the rate constants is useful for interpreting a detailed metabolic process of glucose, and provides additional information on intraventricular tumor aggressiveness.

[Kinetics of glucose metabolism in central neurocytomas].

To estimate proliferating activity of central neurocytoma, we measured kinetic rate constants and glucose metabolic rate (kinetic-rCMRGI) using dynamic positron emission tomography (PET), as well as autoradiographic rCMRG1 (arg-rCMRG1), in patients with histologically verified central neurocytoma. The subject included five patients, four males and one female, aged from 23 to 53 years with a mean age of 41 years old. All tumors were located in the lateral ventricle and two extended into the third ventricle through the forearm of Monro. Tumor lesion on the PET images was determined using CT or MRI, which was performed at levels equivalent to those for the PET scans. The kinetic rate constants of tracer transport from blood to brain (k1), reverse transport from brain to blood (k2), and phosphorylation (k3) were analyzed according to the three compartment 18F-fluorodeoxyglucose (FDG) model. For quantitative analysis, regions of interest (ROI) on PET images were delineated on the tumor and the contralateral gray matter. Tumor k1 and k2 values were similar to or higher than those of the contralateral gray matter, suggesting high permeability due to lack of blood-brain barrier. Tumor k3 value, an indicator of hexokinase activity, and kinetic-rCMRG1 were exceedingly lower in three of five patients. These three patients have been free from tumor recurrence or regrowth, postoperatively. The other two patients, tumor kinetic-rCMRG1 was similar to or higher than that of the contralateral gray matter. One patient suffered from tumor regrowth shortly after resection, and the other has been followed up postoperatively. Thus, k3 and kinetic-rCMRG1 are indicative parameters of proliferative activity in central neurocytoma.

[Kinetic analysis of glucose metabolism in meningiomas--comparison with malignant gliomas].

We measured kinetic rate constants and glucose metabolic rate (kinetic-rCMRGl) using dynamic positron emission tomography (PET), as well as regional cerebral blood flow (rCBF), blood volume (rCBV), oxygen extraction fraction (rOEF), oxygen metabolic rate (rCMRO2) and autoradiographic rCMRGl (arg-rCMRGl), in patients with meningioma. Ten patients including one recurrent case, two males and eight females aged from 44 to 71 years with a mean age of 54 years old, were studied prior to surgical interventions. Histological diagnosis was as follows: seven cases of meningothelial type, two cases of angiomatous type and one fibrous type. For quantitative analysis, regions of interest (ROI) on PET images were delineated on the tumor and the contralateral gray matter in comparison with eight cases with malignant gliomas (five cases of malignant astrocytoma and three cases of glioblastoma, aged from 14 to 70 years with a mean age of 41 years old). Hemocirculation of the tumor was exceedingly higher than that of the contralateral gray matter, which corresponded to neuroradiological findings of abundant tumor vessels. Low rOEF implicated an excessive blood flow beyond oxygen demand of the tumor. The raised metabolic rate (rCMRO2/rCMRGl) suggested rather aerobic glycolysis as compared with malignant gliomas. The kinetic rate constants of tracer transport from blood to brain (k1), reverse transport from brain to blood (k2), and phosphorylation (k3) were analyzed according to the three compartment model of 18F-fluorodeoxyglucose (FDG). Tumor k1 and k2 values markedly increased in all examined cases, suggesting high permeability due to lack of blood-brain barrier and an abundant blood supply.(ABSTRACT TRUNCATED AT 250 WORDS)

[Positron emission tomographic findings of subependymal giant cell astrocytoma developed in tuberous sclerosis--a case report].

Tuberous sclerosis (TS) is well known to be occasionally associated with subependymal giant cell astrocytoma (SGCA). SGCA is considered to be a benign tumor in its clinical course and morphology. However, this tumor is grown sometimes so rapid and caused hydrocephalus. To our knowledge, little is known about hemocirculation and metabolism, particularly in relation with proliferating activity of TS and SGCA. We measured hemocirculation and metabolism of SGCA developed in a case of TS using positron emission tomography (PET). A 13-year-old-boy who had frequently developed convulsions four months after birth. He was diagnosed as TS and had been medically treated with anticonvulsants, since multiple intraventricular calcifications were detected by CT, at the age of five months. The convulsions had been well controlled. In March 1993, he presented with syncopal attack and admitted to our hospital. CT showed multiple subependymal nodules. Among the nodules, one of the left anterior horn exceeded 2cm in size obliterated Monro's foramen. The tumor was homogeneously enhanced with contrast medium. The lesion detected by postcontrast T1-weighted MR imaging had almost the same status as that by CT. T2-weighted image revealed cortical tubers as high intensity area at the left frontal and parietooccipital regions. PET was performed with the Headtome IV. Hemocirculation of the tumor was lower than that of contralateral gray matter, which suggested poor blood supply. The oxygen and glucose metabolism of the tumor were decreased compared with contralateral gray matter, indicative of a low activity of proliferation and a clinically benign tumor in the present case.(ABSTRACT TRUNCATED AT 250 WORDS)

[Longitudinal analysis of glucose metabolism in recurrent meningioma].

We repeatedly measured kinetic rate constants and glucose metabolic rate (kinetic rCMRG1) using dynamic positron emission tomography (PET) and autoradiographic rCMRG1 in a patient with recurrent meningioma. A 50-year-old woman who presented with a left visual disturbance was admitted to our hospital. MR images revealed a mass lesion occupying the left middle fossa. The patient underwent Simpson grade IV surgery. The histological diagnosis was meningothelial meningioma. One year later the tumor had grown back to almost the same size as before treatment and was removed again by Simpson grade IV procedure. Postoperatively, the patient underwent radiation therapy (54 Gy). Two years after the second operation, the tumor was found to have invaded the left orbit and was resected by Simpson grade IV procedure. After additional radiation therapy, the patient was discharged. The rate constants were analyzed preoperatively and whenever the tumor recurred according to the three compartment 18F-fluorodeoxyglucose (FDG) model. Preoperative PET indicated tumor k1 and k2 values higher than in the contralateral gray matter, suggesting high permeability due to absence of the blood-tumor barrier and an abundant blood supply. The tumor k3 value, an indicator of hexokinase activity, was as high as in the contralateral gray matter. When the tumor recurred, the tumor k1, k2 and k3 values remained consistently high, indicating high proliferative activity. In contrast, the contralateral gray matter k1, k2 and k3 values decreased to some extent, suggesting effects of surgery or radiotherapy. Tumor rCMRG1 values, both autoradiographic and kinetic, were enhanced markedly.(ABSTRACT TRUNCATED AT 250 WORDS)