Microspectrofluorometric evaluation of single- and double-stranded DNA in short-term cultured human glioma cells

Abstract

Seven cerebral gliomas in short-term culture were studied by microspectrofluorometry and acridine orange staining to assess their nuclear content of single- and double-stranded DNA. Benign gliomas showed a diploid DNA pattern, whereas malignant gliomas revealed a higher frequency of DNA aneuploidy and hyperploidy. The content of single-stranded DNA remained relatively low in benign gliomas; however, that in malignant gliomas varied widely. After ACNU treatment, the double-stranded DNA histograms showed S-phase-specific accumulation in all cases but 1 with increasing concentrations of ACNU. The single-stranded DNA content decreased considerably in 2 cases, which responded well to chemotherapy and showed clinical amelioration.     

Positron emission tomographic evaluation of histological malignancy in gliomas using oxygen-15 and fluorine-18-fluorodeoxyglucose

HEADTOME III, a high resolution PET, has been employed using ¹⁵O and ¹⁸F labelled pharmaceuticals to evaluate histological malignancy of gliomas preoperatively.

PET study was applied on eighteen preoperative gliomas including two recurrent cases. Haemocirculatory and metabolic indices of regional cerebral blood flow (rCBF), cerebral blood volume (rCBV), oxygen extraction fraction (rOEF), cerebral metabolic rates for oxygen (rCMRO₂) and glucose (rCMRGI) were measured in the viable portion of the tumour, and the contralateral grey and white matter. In the tumour region, rCBF and rCBV were variable and unrelated to grades of tumour malignancy. rCMRO₂ and rOEF values reduced significantly (p < 0.01) relative to the contralateral brain tissue. The average rCMRGI value was 3.00 ± 1.06 mg 100 ml^–1 min^–1 (mean ± SD) for 7 low grade gliomas (grade II), and 5.91 ± 3.61 mg 100 ml^–1 min^–1 for 11 high-grade gliomas (grade III and IV). These results would support that anaerobic glycolysis increased in the metabolism of gliomas with malignancy. In comparison with normal volunteers, rCBF, rCMRO₂, and rCMRGI values in the contralateral grey matter of gliomas were markedly reduced (p < 0.01, p < 0.05, p < 0.01, respectively) possibly due in part to raised intracranial pressure and depressed cerebral functional activity, so that rOEF was increased to a level of approximately 0.5.

PET has been a convincing tool to provide satisfactory information on biological characteristics in the diagnosis of gliomas and the pathophysiological state of brain tissue, and should ultimately make it possible to plan an appropriate therapy.     

Early and late stage positron emission tomography (PET) studies on the haemocirculation and metabolism of seemingly normal brain tissue in patients with gliomas following radiochemotherapy

Haemocirculatory and metabolic changes in seemingly normal brain tissue following radiochemotherapy including nimustine hydrochloride (ACNU) and tegafur (FT) were analyzed using oxygen-15 and fluorine-18 positron emission tomography (PET) in seven patients with gliomas. At an early stage (within one month) after radiochemotherapy, marginal increases in regional cerebral blood flow (rCBF) and cerebral blood volume (rCBV) were found contralateral to the tumour in gray matter which was apparently normal brain structure, as seen on computerized tomography (CT). The oxygen extraction fraction (rOEF) decreased significantly (p less than 0.05 by a paired-t test) from that of the pretreatment study, due to surgical decompression and radiochemotherapy. At the late stage (three to thirty-one months with a mean of thirteen months), rCBF decreased significantly from the early stage study (p less than 0.05); oxygen consumption (rCMRO2) fell in all cases significantly from the pretreatment study (p less than 0.01) and from the early stage study (p less than 0.05); consequently, rOEF remained unchanged at a level similar to the early stage study. Glucose consumption (rCMRG1) increased slightly as compared with the early stage study but failed to be restored to the level of the pretreatment study. Noteworthy was a coupling reduction of rCBF and rCMRO2--presumably, a late delayed effect of radiochemotherapy. These preliminary results indicate that with PET studies it may be possible to predict damage to normal brain tissue after radiochemotherapy.     

A histologically-verified triple cancer--report of a rare case involving a primary brain tumor

Histologically-verified triple cancers that include a malignant brain tumor are rare. According to the Japan Autopsy Annuals, only 8 cases since 1958 have been so far documented. A case combining a malignant melanoma, a medulloblastoma, and a thyroid cancer is herein presented, along with a review of the literature. In March, 1983, a 27-year-old female who, 7 years prior to admission, had had malignant melanoma on the right hand removed, complained of headaches and vertigo. A CT scan revealed a right cerebellar mass lesions, which subsequently proved to medulloblastoma. Three years later, a struma was found and subtotal thyroidectomy revealed a papillary adenocarcinoma.     

Spontaneous transection of Raimondi peritoneal catheter

Three cases of spontaneous transection of a Raimondi peritoneal catheter are reported. Two cases were in infants aged 14 and 10 months, respectively, with communicating hydrocephalus, and the other was in a 10-year-old boy with noncommunicating hydrocephalus associated with a pinealoma. The mechanism of this complication is discussed.     

Radiochemotherapy-related changes in the brain parenchyma of glioma patients evaluated repeatedly by C15O2, C15O, 15O2, and 18F-fluorodeoxyglucose (FDG) PET

The aim of this study was to evaluate effects of radiochemotherapy on blood flow and metabolism using C15O2, C15O, 15O2, and 18F-fluorodeoxyglucose positron emission tomography (PET). Conventional, external radiotherapy (180-200 cGy/5 fractions/week) using 60Co or a 10 MV linear accelerator was given in conjunction with chemotherapy of nimustine hydrochloride (ACNU) and tegafur (FT-207) in eight patients with gliomas. Regional cerebral blood flow (rCBF), blood volume (rCBV), oxygen extraction fraction (rOEF), oxygen consumption (rCMRO2), and glucose consumption (rCMRG1) were longitudinally examined before the treatment, and at an early stage (within one month) and a late stage (three to thirty-one months with a mean of 12 months) after radiochemotherapy. Contralateral gray and white matter to the tumor was selected as regions of interest (ROIs), because these portions were irradiated with larger doses compared to other brain parenchymal regions through parallel opposing fields. Maximum doses to the ROIs varied between 20 and 61 Gy. Calculated as a function of time-dose-fractionation, nominal standard doses (NSD) ranged from 566 to 1729 ret, and 344 to 1062 neuret; equivalent doses (ED) equaled 432 to 1327 rads. At the early stage, rCBF and rCBV increased in the contralateral gray and white matter; gray matter rOEF decreased significantly (p less than 0.05 by a paired-t test) from that of the pretreatment study, probably due to decompression of the tumor bulk and radiochemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prognostic significance of regional blood flow, blood volume, oxygen extraction fraction, and metabolic rates of oxygen and glucose as measured by positron emission tomography in patients with gliomas

We tested clinical significance of hemocirculatory and metabolic values and ratios as determined by positron emission tomography (PET) in twenty-three patients with cerebral gliomas. Regional cerebral blood flow (rCBF), blood volume (rCBV), oxygen extraction fraction (rOEF), and metabolic rates of oxygen (rCMRO2) and glucose (rCMRGl) were measured prior to treatment using PET with 15O2, C15O, 15O2, and 18F-fluorodeoxyglucose tracers. For the quantitative analysis, regions of interest were delineated on tumor regions including peak activity, the contralateral gray and white matter. The regional values and the ratios of tumor/gray matter and tumor/white matter were compared to performance status (PS) according to the five functional grades system which are defined by the Japan Society for Cancer Therapy, tumor progression-free time (PFT), survival time (ST) from the time of the PET study, regardless of type of therapy. As with rCMRGl, the tumor values and the ratios of tumor/gray matter and tumor/white matter correlated significantly with PS (tumor/gray: p less than 0.05, tumor/white: p less than 0.01). Both the gray rCBF and the tumor/gray rCBF ratio had close relation with PS and/or PFT (p less than 0.05). The gray matter rCMRO2 and the tumor/gray matter rCMRO2 ratio related significantly (gray matter: p less than 0.01, tumor/gray: p less than 0.05) to each clinical parameter of PS, PFT, and ST. These indicate that values and ratios as determined by PET can be useful in predicting the prognosis of glioma patients.     

Changes in the (11C-methyl)-L-methionine uptake index in gliomas following radiotherapy

We have studied changes in the (11C-methyl)-L-methionine (C-11 Met) uptake index in six glioma cases subsequent to radiotherapy, using positron emission tomography (PET) to evaluate the effects of radiotherapy on the amino acid metabolism of the tumor. The uptake index of the tumor represented as a percentage of the total count in the atrial blood recorded during a period of 45 min, showed an average of 0.037% and 0.039% prior to and within two months after the therapy, respectively. Out of three cases where a fall in the index was seen, two cases showed tumor regression in the size of the contrast enhanced lesion measured by CT; all three cases had a relatively long period of clinical and neurological amelioration. However, following a short period of clinical improvement, the other three patients with a rise in the index showed no change or tumor progression on CT. These findings indicate that changes in the C-11 Met uptake index can be a sensitive and precise indicator for evaluating the effect of radiotherapy on gliomas.