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At least 415 records · Page 23Linked to original sources
PubMed1989

[Enhancement of the effect of X-irradiation against cultured human glioblastoma cells by pretreatment with ACNU].

Human glioblastoma A-7 (GB A-7) cells can apparently recover from potentially lethal X-irradiation. The authors, using a colony-forming assay, studied the influence of pretreatment with 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) on the effectiveness of X-irradiation against GB A-7 cells grown in monolayers and as multicellular spheroids. Pre-exposure to ACNU inhibited the recovery of irradiated GB A-7 cells. In monolayer cells, the combination treatment was most effective when ACNU was applied 2 to 8 hours prior to irradiation, and the larger the X-ray dose, the more potent the effect. ACNU pretreatment was more effective against large spheroids (enhancement ratio 1.86) than against small ones (1.34). Large spheroids showed necrosis, whereas small ones did not. Isobolographic analysis disclosed that the effect of combining X-irradiation and ACNU is within an additive envelope at the surviving fraction of 10(-2), while supra-additive at the surviving fraction of 10(-3). These results suggest that the potency of X-irradiation is augmented by ACNU pretreatment through an interactive mechanism. Further, suppression of recovery from X-ray induced potentially lethal damage was influenced by the presence of necrosis.

Brain Neoplasms↗
PubMed1989

[Cystic pineocytoma successfully treated with synchronized chemoradiotherapy. Case report].

A case of pineocytoma associated with intraventricular and meningeal metastasis is reported. The patient, a 25-year-old female, was admitted complaining of headache. Computed tomography revealed an irregular-shaped pineal lesion enhanced by contrast medium and accompanied by a cyst. An intraventricular cystic metastatic lesion and meningeal metastasis were also suggested. Biopsy of the pineal region proved the lesion to be a pineocytoma without neuronal or glial differentiation. Ventriculoperitoneal shunting was performed, and radiation therapy combined with chemotherapy (ACNU and vincristine) was administered. This treatment apparently destroyed both the primary and metastatic lesions, and the patient returned to her normal life. In 4 years of follow-up there has been no recurrence of the tumor. Pineocytoma with meningeal metastasis usually has a poor prognosis, but in this case combined radiation therapy and chemotherapy was curative. Although pineocytoma is rarely accompanied by a cyst, in cases of a pineal lesion coexistent with a cyst, a diagnosis of pineocytoma should be considered.

Adult↗
PubMed1989

Effect of combined treatment with magnetic induction hyperthermia and chemotherapy in a rabbit brain tumor model.

The effects of interstitial magnetic induction hyperthermia alone and in combination with chemotherapy were evaluated in a rabbit brain tumor model. VX2 carcinoma cells were implanted intracerebrally in 28 rabbits. The animals were divided into four groups of seven each, and the experimental protocols were started on the 7th day after inoculation. Group 1 underwent hyperthermia alone by means of implantation of a needle (Fe-Pt alloy) in the tumor, which was maintained at 45 degrees C for 30 minutes. Group 2 received 12.5 mg/kg ACNU intravenously via a lateral ear vein. In Group 3, 10 minutes after injection of ACNU, hyperthermia was induced in the same manner as in Group 1. Group 4 were controls and received no treatment. The four groups were evaluated and compared in terms of length of survival and pathological features of their brain tumors at the time of death. The mean survival times of Groups 1, 2, 3, and 4 were 14.7, 14.7, 17.3, and 12.3 days, respectively. Statistically significant differences were found between Groups 1 and 4 and between Groups 3 and 4, but not between Groups 1 and 2. Pathological findings in the hyperthermia group included necrosis around the implant. The tumor cells surrounding the necrotic area had degenerated and the vessels were dilated and static. Thus, in this rabbit brain tumor model, hyperthermia alone was significantly superior to no treatment, and combined treatment with hyperthermia and chemotherapy was more effective than either treatment alone.

Animals↗
PubMed1989

Responses of pineocytoma to radiation therapy and chemotherapy--report of two cases.

Pineal parenchymal tumors are so rare that their responses to radiation and/or chemotherapy are not well known. Two cases of pineocytoma, which responded well to radiation therapy and chemotherapy, are reported. A 45-year-old female received radiation therapy in a total dose of 5000 rads to the tumor. Three months after the completion of therapy, computed tomography (CT) showed complete disappearance of the tumor, and she remains well as of 1 year after treatment. The second patient, a 6-year-old girl, underwent four cycles of intravenous infusion of ACNU (25 mg) over 10 months. CT demonstrated complete disappearance of the tumor and, 18 months post-operatively, there was no evidence of tumor recurrence. The results in these two cases indicate that postoperative radiation therapy and/or chemotherapy should be strongly considered for patients with pineal parenchymal tumors.

Child↗
PubMed1990

Effects of X-irradiation alone and in combination with ACNU on human glioblastoma cells in vitro.

The combined effects of x-irradiation and 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloro-ethyl)-3-nitrosourea (ACNU) on multicellular glioblastoma A-7 spheroids were analyzed by means of cell survival and dose-response curves. The actual dose-response curve for small spheroids was almost identical to that estimated from the cell survival curve. It was strongly suggested that a small number of radiation-resistant cells, which were not detected in the cell survival curve, were present in large spheroids with central necrosis. The enhancing effect of ACNU was greater with large spheroids than with monolayer cells or small spheroids. A possible explanation for this is that ACNU is higher effective against the few radiation-resistant cells that may be present in larger spheroids.

Cell Line↗
PubMed1990

Intra-arterial ACNU chemotherapy employing 20% mannitol osmotic blood-brain barrier disruption for malignant brain tumors.

The clinical effects and problems of intra-arterial water-soluble antitumor nitrosourea (ACNU) therapy following osmotic blood-brain barrier modification are discussed. Twenty-one patients with malignant brain tumors were divided into two groups. Group 1 consisted of 16 patients treated by operation, irradiation, and two or more courses of intracarotid infusion of ACNU 100 mg/body (1.7-2.2 mg/kg) following 20% mannitol 200 ml (1.3-1.6 ml/sec) (7 grade 4 astrocytomas, 5 grade 3 astrocytomas, and 4 others). Group 2 consisted of five patients treated by operation, irradiation, and repeated intracarotid infusion of ACNU 100 mg/body alone (grade 4 astrocytoma). The 2-year survival rate in Group 1 was 79% (11 of 14 cases followed up for longer than 2 years) and the 3-year survival rate was 67%. Five of seven grade 4 astrocytoma patients (71%) in Group 1 survived for more than 1 year 6 months, whereas four of five grade 4 astrocytoma in Group 2 died within 1 year 6 months. The measurement of the ACNU concentration in tumor tissues and blood in 11 brain tumors, after intracarotid infusion of ACNU with blood-brain barrier disruption, showed peak values in the tumor tissues of 3.02-32.53 micrograms/gm (mean, 9.67 micrograms/gm), about three to five times as high as that in blood in most cases. This method used in Group 1 appears to be relatively safe without permanent neurological deficits and offers a potential therapeutic effect when used in combination with appropriate premedication in suitable patients.

Adolescent↗
PubMed1990

Diffuse low-density areas in white matter on CT scans after intracarotid ACNU infusion--report of three cases.

Since 1984, we have treated 11 malignant glioma patients with intracarotid infusion of ACNU [1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)- 3-nitrosourea hydrochloride] in addition to surgical removal and irradiation. We experienced three patients, who showed clinical manifestation of leukoencephalopathy and computed tomographic (CT) findings of diffuse low-density areas in the white matter on the side of ACNU infusion. Two of the three patients showed an additional CT finding of ring enhancement in the temporo-occipital region. The histological diagnosis of the first case was radiation necrosis, while that of the others was recurrent tumor with coagulation necrosis in the surrounding brain. Our experience suggests that intracarotid ACNU infusion increases the hazard of radiation necrosis, and the optimum dose and effective mode of administration should be evaluated.

Brain↗
PubMed1991

Complete remission of metastatic teratoma from malignant testicular tumor using salvage chemotherapy with VP-16 (etoposide), CDDP, and ACNU--case report.

A 26-year-old male with an intracranial teratoma, metastasizing from a testicular yolk sac tumor refractory to cis-diamminedichloroplatinum (CDDP), vinblastin, and bleomycin (PVB) therapy, was successfully treated with a combination of etoposide (VP-16), CDDP, and ACNU (salvage chemotherapy). Emergency surgery for subcortical hemorrhage discovered the metastasis, diagnosed as a yolk sac tumor. CDDP chemotherapy failed to prevent recurrence, and total removal was impossible due to subdural invasion. He underwent radiation therapy and salvage chemotherapy. A third operation found only scar tissue. Maintenance salvage chemotherapy was continued. He was doing well 30 months after the first operation.

Adult↗
PubMed1991

Treatment of malignant glioma with high dose intra-arterial ACNU and autologous bone marrow transplantation--case report.

A 44-year-old female with malignant astrocytoma received subtotal removal and high dose (200 mg/m2) intra-arterial 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2- chloroethyl)-3-nitrosourea hydrochloride (ACNU) with autologous bone marrow transplantation. Tumor remission with minimal bone marrow suppression was achieved. However, she developed severe encephalopathy and computed tomographic scans revealed a low-density area at the ACNU delivery site. She received glycerol solution to treat the brain edema and recovered completely from the encephalopathy. Intra-arterial ACNU exceeding 200 mg/m2 possibly causes neurotoxicity.

Adult↗
PubMed1991

Intraoperative radiation therapy for malignant glioma.

Intraoperative radiation therapy (IORT) was used as part of the initial therapy for malignant glioma in 32 of 73 patients with histologically verified anaplastic astrocytoma (grade III astrocytoma) and glioblastoma multiforme. The initial treatment for all cases was subtotal or total tumor resection combined with external irradiation and chemotherapy. IORT was performed 1 week after tumor resection, with doses of 10-50 Gy (mean 26.7 Gy) in one session. Fourteen of 32 cases had IORT two times because of tumor recurrence. The IORT patients had survival rates at 24 and 36 months after initial treatment of 57.1 and 33.5% (median survival 26.2 months). The other 41 patients had 23.6 and 13.1% survivals (median survival 20.7 months), which were significantly lower (p less than 0.01). Tumor recurrence within the original lesion site was suspected because of clinical condition, computed tomography, and magnetic resonance imaging studies in 65.6% of the IORT group (21 cases) 12 months after initial treatment. Twenty cases of death in the IORT group, including five autopsy cases, demonstrated regional tumor recurrence with a high incidence of intraventricular tumor invasion. The authors consider IORT is beneficial for selected malignant glioma patients, including tumor recurrence, because of prolonged survival.

Adolescent↗
PubMed1991

[Establishment of ACNU-resistant rat gliosarcoma cell lines and their characteristics].

One of the most serious problems in cancer chemotherapy is the acquired drug resistance of tumor cells. In order to investigate the mechanism of acquired resistance to 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU), nine resistant cells were isolated from rat gliosarcoma 9L cells and characterized. ACNU-resistant cells were easily isolated after a single treatment even with low-dose ACNU (5 micrograms/ml). However, in spite of repeatedly high-pressure dose of ACNU, more than 30 fold increase to parental 9L cell resistance was not achieved. At this time, further increase in selection pressure resulted in cell death. The resistant ratios of these resistant cells were stable in the absence of ACNU for more than 1 year. Luria and Delbrück's fluctuation test indicated that the appearance of ACNU-resistant cells occurred spontaneously at a rate of (4.40-8.02) x 10(-7)/cell/generation. In karyotypic analysis, the mode was higher in the resistant cells than in 9L cells, but a homogeneously staining region or double minute chromosome, which was considered to be a result of gene amplification, was not observed. In growth kinetics, all the resistant cells except R1 and R12 cells had higher saturation density and plating efficacy than parental 9L cells. These findings seemed to be due to cellular modification associated with ACNU resistance.

Animals↗
PubMed1992

Effectiveness of interferon-beta, ACNU, and radiation therapy in pediatric patients with brainstem glioma.

Sixteen pediatric patients with brainstem glioma were treated with a combination of interferon-beta, 1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitroso ure a hydrochloride (ACNU), and radiation therapy (IAR therapy). All patients received 1-1.5 million IU/day of interferon-beta intravenously for 1 week of each 6-week cycle. In addition, ACNU (2-3 mg/kg) was given on the 2nd day of each cycle. Conventional focal irradiation (1.5-2 Gy/day for 5 days to a total dosage of 40-60 Gy) was administered beginning on day 3. Patients underwent at least two 6-week cycles. Adverse effects included nausea, vomiting, and myelosuppression, but were mild and transient. Response to treatment was evaluated by the reduction in tumor size measured on postcontrast computed tomographic scans and magnetic resonance images. Responses occurred in 10 of 11 patients with the intrinsic type of brainstem glioma, including three complete and seven partial responses. Two of five patients with exophytic type gliomas partially responded. The median survival was 15.7 months, a remarkable improvement over the natural course of this disease. These results indicate that IAR therapy is a useful primary treatment for pediatric patients with brainstem gliomas.

Adolescent↗
PubMed1993

Effect of interferon-gamma on ACNU-induced DNA damage and cytotoxicity in human glioblastoma cells.

Interferons (IFNs) are a natural body defense with powerful effects on tumor growth, including gliomas. The direct effects of IFN-gamma on (1-4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU)-induced deoxyribonucleic acid (DNA) damage and cytotoxicity were investigated in two human glioblastoma cell lines, A-172 and T98G, using a single cell microgel electrophoresis technique and a microculture tetrazolium assay. The results demonstrated a synergistic effect of IFN-gamma with ACNU on intracellular damage in both cell lines. 10 micrograms/ml ACNU induced a cell inhibition rate of 23.9% in A-172 cells, and almost no effect on T98G cells. 1000 U/ml IFN-gamma and 10 micrograms/ml ACNU caused a significant increase in cell inhibition, 51.2% for A-172 and 72.3% for T98G cells. DNA damage in individual A-172 and T98G cells exposed to ACNU was enhanced significantly by IFN-gamma (p < 0.001). The findings suggest a direct effect of IFN-gamma on ACNU-induced cell damage in human glioma, in addition to its effect on immunomodulation.

Brain Neoplasms↗