Shinji Sugimoto

Immunohistochemical analysis of giant cell glioblastoma.

Giant cell glioblastoma (GCG) is one of a group of rare tumors in which the cell population is abnormally large and includes multinucleated cells of gigantic sizes. Immunohistochemical studies were performed on four GCG cases and found that all giant cells and/or tumor cells were positive for glial fibrillary acidic protein (GFAP), S‐100 protein, and vimentin, thus verifying the tumors glial origin. The nuclei of multinucleated giant cells of three adult cases were frequently immunostained for proteins expressed during the cell cycle (proliferating cell nuclear antigen (PCNA) and Ki‐67), thereby demonstrating the proliferative capacity of these cells. By contrast, those of a 12 year old girl expressed these cell cycle markers rather infrequently. Alpha I‐anti‐trypsin was detected with relatively high frequency in the giant cells, and its presence may explain their bizarre sizes and pericellular reticulin fiber formation. A literature review of 32 cases revealed that the GCG that occurs preferentially in young girls is a type of pleomorphic xanthoastrocytoma. By contrast, GCG in adult males has the same age incidence as ordinary glioblastomas and, as these, expresses high levels of cell cycle‐related proteins. Thus, GCG, which is subclassified morphologically as ordinary glioblastoma, has distinct biological and clinical characteristics, with that in children requiring re‐evaluation because of its similarities to pleomorphic xanthoastrocytoma.

Modification of tumor blood flow and enhancement of therapeutic effect of ACNU on experimental rat gliomas with angiotensin II

Blood flow was measured in transplanted rat gliomas before and during a constant intravenous infusion of angiotensin II using hydrogen clearance methods. The brain tumor models were produced in syngeneic Wister-King-Aptekman male rats with stereotaxic inoculation of ethylnitrosourea-induced glioma cells (KEG-1). Induced hypertension up to 150 mmHg (mean arterial pressure) with the infusion of angiotensin II resulted in a significant increase of blood flow to tumor center compared to the normotensive state (p < 0.001). Blood flow measured simultaneously in brain tissue of tumor-free contralateral hemisphere did not change.The therapeutic effect of administration of the simultaneous 1-(4-Amino-2-methyl-5-pyrimidinyl)methyl3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) and angiotensin II was evaluated in four experimental groups with the tumor-bearing rats. Twelve days after tumor implantation, the rats were administered angiotensin II to increase the mean arterial blood pressure to 150 mmHg, followed by intravenous injection of ACNU injection. The increased blood pressure was steadily maintained for 20 minutes. The ACNU/induced hypertension group showed a median survival time of 27.0 days, which was significant longer (p < 0.02) than that of an ACNU treatment group (22.0 days), a hypertension treatment group (19.0 days), or a no treatment group (18.5 days).The enhanced therapeutic effect can be attributed to improving chemotherapeutic drug delivery due to increased blood flow in the tumor.

Potentiation of 3-(4-Amino-2-Methyl-5-Pyrimidinyl) Methyl-1-(2-Chloroethyl)-Nitrosourea Cytotoxicity in Resistant Human Glioma Cell by Pretreatment with 5-(3-Methyl-1-Triazeno) Imidazole-4-Carboxamide

In our previous studies, we reported the results that O6-alkylguanine DNA alkyltransferase (O6-AT) plays an important role in determining the cellular resistance to treatment with chloroethylnitrosourea (CENU) [1–3]. The mechanism of cellular resistance has not been fully understood, but it is clear that O6-AT repairs O6-chloroethylguanine before it can rearrange to form the DNA interstrand cross-link [4–5], and this results in cellular resistance to the cytotoxic effects of CENUs. O6-AT also prevents the induction of sister chromatid exchanges (SCEs) by CENUs, since the increased induction of SCEs is due to higher levels of DNA interstrand cross-links [1,2,6]. The reduction of O6-AT activity in tumor cells which are resistant to CENUs may be used to improve the clinical effectiveness of CENUs, since this activity protects the cytotoxic effects of these agents. This has been approached by pretreatment with a monofunctional methylating agent [2,7,8]. 5-(3-dimethyl-1-triazeno) imidazole-4-carboxamide (DTIC) is a chemotherapeutic agent used primarily to treat malignant melanoma, sarcoma, and lymphoma. DTIC requires metabolic activation through oxidative N-demethylation leading to the formation of the N-demethyl derivative, 5-(3-methyl-1-triazeno) imidazole-4-carboxamide (MTIC), a potent alkylating agent. Recently, MTIC has been shown to alkylate DNA in the O6 of guanine and to be more cytotoxic in O6-AT deficient cells (Mer−) than in O6-AT proficient cells (Mer+) [9,10].

Irradiation Effects on Tumor Blood Flow and Tumor Vascular Permeability in a Rat Transplanted Glioma Model: A Quantitative Autoradiographic Study

Both radiotherapy and chemotherapy have been mainstays in the treatment of brain tumors. Because the delivery of chemotherapeutic drugs to a brain tumor is currently considered to be dependent upon tumor blood flow and/or tumor vascular permeability, it is important to have a clear understanding of irradiation effects on these transport processes. We report the preliminary results of local blood flow (F) and blood-to-tissue transfer constant (K) measurements with quantitative autoradiography (QAR) in a rat-transplanted glioma model.

Loss of Heterozygosity of Chromosomes 10 and 17 in Human Malignant Astrocytomas

Astrocytomas are the most common tumors of the human central nervous system. Tumors of this type can be classified into four histopathologic grades of malignancy according to Kernohan [1]. Glioblastoma (astrocytoma grade IV) is always lethal despite surgery, radiotherapy, and/or chemotherapy. Low-grade or anaplastic astrocytomas vary in their response to treatment. However, a recurrent tumor is often less well differentiated, suggesting that astrocytoma can be a progressive disease. It is now believed that the genes responsible for tumorigenesis are recessive oncogenes.

Aneurysm of the Vein of Galen in an Infant: Case report

A case of an aneurysm of the vein of Galen treated by a successful direct surgical procedure during the infancy is presented together with five year’s follow-up observation.

Primary Intracranial Endodermal Sinus Tumor with Intracranial and Spinal Metastases

A case of a 12-year-old boy with primary intracranial endodermal sinus tumor with spinal and posterior fossa metastases is presented, with sequential changes of radiological findings and alphafetoprotein levels during the clinical course. Reported cases of intracranial endodermal sinus tumor with metastases of the spinal cord and other regions, and those with good results and long survival without spinal metastasis, are compared from the therapeutic point of view. Radiosensitivity of the tumor and the value of preventive spinal irradiation is discussed. It can be concluded that surgical extirpation of the tumor for histological confirmation, radiation therapy with or without spinal irradiation, and adjuvant chemotherapy are the treatment of choice for malignant germ cell tumors.