Intermediate filaments and anaplastic change of ENU-induced gliomass: immunohistochemical study with vimentin and astroprotein (GFAP).

To study the expression of two different subclasses of intermediate filaments in ethylnitrosourea-induced rat cerebral gliomas, the number of cells immunopositive for each subunit protein, vimentin and astroprotein (GFAP), was quantitatively analyzed. Vimentin is a subunit protein of non-specific intermediate filaments which appear transiently in immature glial cells, while astroprotein (GFAP) is a subunit protein of glial filaments, normally expressed in mature astrocytes. Although most normal astrocytes were negative for vimentin, many tumor cells showed weak to strong immunoreaction for vimentin.

[Local cerebral blood flow and glucose metabolism in experimental meningeal carcinomatosis].

Patients with meningeal carcinomatosis often evolve signs of impairment in higher mental function. Yet, common findings of histological observation are only a sheet of tumor cells on the cortical surface, and no intracerebral mass are noted. To elucidate mechanism of mental disturbances in meningeal carcinomatosis, local cerebral blood flow and glucose metabolism were evaluated in a model of experimental meningeal carcinomatosis.

[Intrathecal ACNU against malignant leptomeningeal tumors--toxicity and therapeutic effect in experimental animals].

Leptomeningeal dissemination is one of the major causes which increase the morbidity and mortality of the patients with malignant brain tumors. The incidence of this complication is increasing, however, no sufficient treatment is available at present. Therefore, in an attempt to establish a new treatment, we studied toxicity and therapeutic effect of intrathecal ACNU (nimustine hydrochloride) using experimental animals.

[Possibility of overcoming of ACNU resistance in an ACNU-resistant subline of C6 rat glioma].

Membrane-modifying agents such as reserpine, calcium antagonists (nicardipine, verapamil) and calmodulin inhibitor (trifluoperazine) were found to enhance the cytotoxicity of ACNU in vitro and in vivo in ACNU-resistant C 6 (C 6/ACNU) glioma. In in vitro experiments, uptake and retention studies with [14C] ACNU revealed that intracellular uptake and retention of ACNU in C 6 cells were larger than those in C 6/ACNU cells, and that these membrane-modifying agents increased the cellular uptake and retention of ACNU in C 6, especially in C 6/ACNU cells. The amount of ACNU in C 6/ACNU cells reached the same level as that detected in C 6/ACNU cells.

[A case of alveolar soft-part sarcoma with recurrent cerebral metastasis--operative management of the cerebral metastasis].

A female patient noticed a painless swelling at the right thigh at the age of 12. Two years later, she had total removal for the tumor and irradiation. The diagnosis of the tumor was alveolar soft-part sarcoma.

Solitary late recurrence of renal cell carcinoma.

Solitary late recurrence is an unpredictable behavior pattern of renal cell carcinoma. We describe a patient with recurrence at the cranial bone 10 years after surgical management and another with recurrence at the sacral bone 13 years after treatment with radiotherapy and alpha-interferon. Both patients have been followed satisfactorily for 9 months.

Development of experimental meningeal gliomatosis models in rats.

Experimental models of meningeal gliomatosis (MG) have been produced by intracisternal inoculation of rat C6 and 9L glioma cells into Wistar and Fischer 344 rats, respectively. Tumor growth was steady and rapid in both MG models when more than 10(6) tumor cells were implanted. The median survival time of the rats inoculated with tumor cells was inversely related to the number of the cells inoculated.

[Studies on the mechanism of ACNU resistance in sublines of rat C6 glioma and 9L gliosarcoma in vitro].

One of the serious problems in chemotherapy of brain tumors is that tumor cells are able to acquire resistance to initially effective cytotoxic agents. In order to study the mechanism of this resistance against chemotherapeutic agents, especially ACNU, two variant cell lines (C6/ACNU and 9L/ACNU) resistant to ACNU [1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride] were selected previously in vivo from rat C6 glioma and 9L gliosarcoma, respectively. Uptake and retention of ACNU in these resistant cells were studied with [14C]ACNU.

[Development of experimental meningeal gliomatosis models using nude mice].

Experimental models of meningeal gliomatosis (MG) have been produced by intracisternal inoculation of human glioma cell lines into nude mice. The tumor growth was steady and fast in MG nude mice if 10(7) cells were implanted. Median survival time (MST) of nude mice inoculated with tumor cells was inversely related to the number of cells inoculated.

[Mechanism and overcoming of resistance in ACNU-resistant sublines of rat brain tumors].

One of the most serious problems in chemotherapy of brain tumors is that tumor cells are able to acquire resistance to initially effective cytotoxic agents. In order to study the mechanism of such resistance to ACNU and the means to overcome it, two variant cell lines (C6/ACNU and 9L/ACNU) resistant to ACNU were selected in vivo. Uptake and retention of ACNU in these resistant cells were studied with [14C] ACNU.

[Cisplatin, vinblastine and bleomycin (PVB) combination chemotherapy in the treatment of intracranial malignant germ cell tumors--a preliminary report of a phase II study--The Japanese Intracranial Germ Cell Tumor Study Group].

Cisplatin, vinblastine and bleomycin (PVB) combination chemotherapy was undertaken in 30 patients with primary intracranial malignant germ cell tumors in 11 neurosurgical clinics. The response rate of 17 evaluable patients with nonrecurrent tumors was 64.7% (eight CR and three PR), and that in eight patients with recurrent tumors was 50% (two CR and two PR).

[Cortical somatosensory evoked potential associated with experimental chronic cord compression by epidural neoplasm in rabbits].

An experimental model of spinal cord compression was developed in rabbits by epidural neoplasms which were injected anterior to the T 13 vertebral body and grew into the spinal canal through the intervertebral foramina. With this experimental model, the neurological condition of the animals was monitored using a scale and changes of somatosensory evoked potentials (SEPs) were studied to evaluate the neurophysiological effect of experimental chronic cord compression. The animals were immobilized with pancuronium bromide and artificial respiration was maintained through a tracheostomy.

[Meningeal gliomatosis model in nude mice].

The nude mouse has been proposed as a model animal for testing the chemosensitivity of human cancer cells, and encouraging results have been obtained. Murine brain tumor models were successfully prepared by direct inoculation of glioma cells into the cerebral hemisphere, an immunologically privileged area. However, the blood-brain barrier was destroyed mechanically by this manipulation.

[Antitumor efficacy of activated macrophages against murine glioma cells].

A crucial manifestation of malignant gliomas is the regrowth of already-invaded neoplastic cells after surgical intervention. One possible approach for inhibiting such tumor growth is to utilize the tumoricidal potential of macrophages. In order to investigate the clinical application of this concept, peritoneal exudate cells (PEC) activated in vitro and in vivo by immunomodulating agents were tested for cytotoxic activity against murine glioma (203-glioma) cells.

Regional cerebral ischemia in the gerbil: measurement of regional cerebral blood flow by quantitative autoradiography.

Alterations in the regional CBF after occlusion of the posterior communicating, middle cerebral, or common carotid artery were investigated in the gerbil with a quantitative autoradiographic technique using [14C]iodoantipyrine. Occlusion of the posterior communicating artery produced severe ischemia in the ipsilateral hippocampus, thalamus, and dorsal mesencephalon. Occlusion of the middle cerebral artery produced severe ischemia in the ipsilateral rostral and central cerebral cortex and lateral caudate-putamen.

[Clinical studies of adoptive immunotherapy of human disseminated brain tumors with LAK cells and recombinant interleukin-2].

In previous in vitro studies, the authors showed that recombinant interleukin-2 (rIL-2) stimulated peripheral blood lymphocytes (PBL) from patients with malignant brain tumors to generate cells that were lytic for fresh autologous tumor but not for lymphocytes or lymphoblasts. We then tried the adoptive transfer of such lymphokine-activated killer-(LAK) cells induced from patients with meningeal gliomatosis (MG) and meningeal carcinomatosis (MC). PBL fractions were separated into a plastic bag by leukophoreses using HEMONETICS V 50.

Enhanced effect of reserpine upon growth-inhibitory action of ACNU on ACNU-resistant C6 glioma.

Reserpine was found to enhance the cytotoxicity of ACNU on ACNU-resistant C6 glioma (C6/ACNU) cells in vitro. When reserpine was added along with ACNU to the C6/ACNU cells in vitro. When reserpine was added along with ACNU to the C6/ACNU culture in vitro at a concentration of 10 microM, the IC50 of ACNU for C6/ACNU cells decreased to the level of that for C6 cells and ACNU resistance was completely overcome in vitro.

[Overcoming of ACNU resistance in a subline of rat glioma in vitro and in vivo by reserpine].

Reserpine was shown to enhance the cytotoxicity of ACNU in both C6 and C6/ACNU rat glioma cells in vitro and also to enhance the chemotherapeutic effect of ACNU in C6/ACNU-bearing rats (C6/ACNU meningeal gliomatosis rats), in which ACNU resistance could be partially overcome by reserpine. When reserpine was added to the culture at a concentration of 10 microM, the IC50 of ACNU for C6/ACNU cells decreased to the level of that for C6 cells. Intracellular uptake of ACNU in C6/ACNU cells increased and the efflux from the cells decreased when 20 microM reserpine was added to the culture.

Successful combination chemotherapy (cisplatinum, vinblastine, and bleomycin) against peritoneal dissemination of intracranial germ cell tumor.

We found combination chemotherapy with cisplatinum, vinblastine, and bleomycin (PVB therapy) effective in the treatment of a patient with a pineal germ cell tumor with peritoneal dissemination. The metastatic complication may have been attributable to the ventriculoperitoneal shunt tube. After the first course of PVB therapy, the disseminated tumors were decreased in size; no residual tumors were detected after the third course by laparoscopic examination, computed tomographic scanning, or echogram.

[Surgery of high-flow arteriovenous malformation: with special reference to normal perfusion pressure breakthrough phenomenon].

Hemodynamic changes are of importance while removing large and high-flow arteriovenous malformations (AVM), because a phenomenon called "normal perfusion pressure breakthrough" may occur. In this report, we evaluated hemodynamic changes in 14 cases of high-flow AVM with cerebral angiogram and intraoperative monitoring of cortical-surface blood flow. The criteria we used for high-flow AVM are; nidus larger than 4 cm, a few large feeders, high-flow shunt in the nidus, and reduced circulation or dilated arteries in the adjacent brain tissue.