Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antitumor activity of 6-thioguanine against L-1210 leukemia was studied in combination with various antitumor agents in clinical stages, such as mitomycin-C, carbazilquinone, cyclophosphamide, 3,3'-dimesyloxydipropylamine tosylate (864T), 4-hydroperoxyisophosphamide, and 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chlorethyl)-1-nitrosourea hydrochloride (ACNU). The combination treatments with 6-thioguanine and each of six agents, especially with ACNU, showed a distinct therapeutic effect against the early L-1210 leukemia at dosage levels not producing any significant antitumor activity with each agent alone (ip-ip). The excellent antitumor activity of the combination of 6-thioguanine with ACNU was also proved in various sites of tumor inoculation and routes of drug administration systems, i.e., ip-iv, iv-ip, and iv-iv systems. Moreover, the effectiveness of the combination of these two drugs was clearly shown against advanced L-1210 leukemia which was refractory to each agent alone.
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PMID:Combination chemotherapy of 6-thioguanine with various antitumor agents against murine leukemia L-1210. 20 34

ACNU was highly effective for Sato lung carcinoma transplanted intravenously or intramuscularly by using a large single dose, and the cytotoxic action of ACNU for SLC showed clear dependence upon tumor size. Nonspecific activation of host-defence mechanism by Propionibacterium acnes contributed to the suppression for the regrowth of solid SLC treated by ACNU.
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PMID:Effect of 1(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) on Sato lung carcinoma (SLC). Preliminary result of immunochemotherapy for SLC by combination of ACNU and Propionibacterium acnes. 45 Mar 90

Anti-tumor activities of ACNU and X-irradiation on methylcholanthrene induced glioma in C57BL mice were studied in vitro and in vivo. In vitro experiments using cultured glioma cells (MGB cells), the synchronization of cell cycle was done by excess addition of thymidine, and the anti-tumor cell effect were investigated by mean of determinations of DNA synthesis, mitotic index and the number of the living cells following the treatments. As the results, it appeared obvious that ACNU was most effective on MGB cells in S phase and X-irradiation in M phase. As to the combined therapy of ACNU and X-irradiation, the anti-tumor effect was most remarkable when the cells were treated by X-irradiation in the G2, M phase, which were hervested by addition of ACNU 44 hours before irradiation. However simultaneous treatment of ACNU and X-irradiation on the cells in G1 phase was not so remarkable. In vivo experiments the anti-tumor effect of ACNU and X-irradiation on subcutaneously or intracranially transplanted glioma in mice was investigated. Either ACNU 10 mg/kg or local X-irradiation 1240 rads showed inhibitory effect on the tumor growth and prolonged the survival time of the tumor bearing mice. The combination therapy was more effective than ACNU or X-irradiation alone, particularly combination therapy of ACNU and repeated small doses irradiation of X-ray was remarkably effective. Evidence obtained indicates that the combination therapy of ACNU and X-irradiation have synnergistic anti-tumor effect on experimental mouse glioma.
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PMID:[The anti-tumor effect of ACNU and X-irradiation on mouse glioma (author's transl)]. 50 42

In order to establish the standard of administration of ACNU against brain tumors, pharmacokinetic analysis of ACNU in tumor tissue, cystic fluid, cerebrospinal fluid and blood was performed. The sample specimens were obtained sequentially after intravenous administration of 1--2 mg/kg/BW of ACNU and quantitatively analysed by high-performance liquid chromatography in 3 cases of glioblastoma and each one case of astrocytoma, meningioma and brain metastasis. Concentrations of ACNU in blood was calculated by two compartment open model and those in cystic fluid was calculated by one compartment model using BMDP-3R program. The half-time in blood was 2.6--4.1 min, and its distribution was very fast. The penetration of ACNU into the tumor tissue was sufficient, because the central compartment was 23% and the tissue compartment was 77%. The transmission rate constant into the cyst was 1.8 and the elimination rate constant was 0.96. The maximum concentration in the cystic fluid 42 min after intravenous injection of 2 mg/kg/BW of ACNU was 0.27--0. 35 mg/dl. In conclusion, 3--4 mg/kg/BW of ACNU should be injected intravenously at one time.
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PMID:[Pharmacokinetic analysis of ACNU in brain tumors (author's transl)]. 52 72

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.
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PMID:Effectiveness of interferon-beta, ACNU, and radiation therapy in pediatric patients with brainstem glioma. 128 18

A 35-year-old woman was admitted to our hospital with a 3 month history of progressive paraparesis and impairment of bowel and bladder function. MRI suggested a malignant glioma at the level of T9 to L1. Laminectomy and subtotal removal of the tumor was performed. The surgical specimen was a glioblastoma multiforme. An aggressive adjuvant therapy was scheduled to prevent rapid local regrowth and leptomeningeal dissemination. Radiotherapy with a total dose of 65Gy was delivered with chemotherapy including ACNU (2mg/kg) and vincristine (0.2mg/kg). Lymphokine-activated killer (LAK) cells were given intrathecally with a total dose of 1.6 x 10(9) LAK cells with 3 x 10(4) units of IL-2. MRI taken 6 months after surgery revealed no residual tumor, and no malignant cell was detected in the patient's CSF. After physiotherapy, she became able to walk with a stick and was discharged. Chemotherapy (ACNU 2mg/kg/8 weeks) had been further continued for 2 years. She did well until 14 months after surgery, when paraparesis recurred and rapidly progressed to completism. MRI revealed a spinal cord swelling with marked edema, suggesting delayed radiation necrosis. Two years after surgery, MRI showed a marked atrophy of the spinal cord, and no residual tumor. But 3 years after surgery, a round tumor at the level of T11 and T12 was revealed on MRI, and she was admitted to our hospital again. A spinal cord amputation was performed, and the tumor was totally removed without worsening her neurological symptoms. Surgical specimen of the tumor was glioblastoma multiforme again.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[A case of spinal cord glioblastoma multiforme]. 131 Aug 3

Twelve patients with supratentorial gliomas were treated with intra-arterial ACNU followed by intravenous maintenance chemotherapy. Six of the patients, treated from February 1987 through May 1989, received doses of 120-200 mg/m2 (high dose treatment group); six patients, treated from June 1989 through October 1990, received doses of 80-100 mg/m2 (low dose treatment group). The drug was given via the supraophthalmic portion of the internal carotid artery or vertebral artery at a rate of 10 mg/min. The response rate (CR + PR) on CT scan was 50% (3/6) in the high dose treatment group and 17% (1/6) in the low dose treatment group. Survival periods from first operation, however, did not differ between the high and low dose treatment groups. Bone marrow suppression was dose-related and reversible at these doses. Severe neurotoxicities (hemiparesis and aphasia) developed in the patients who received 200 mg/m2 of ACNU; in one case, this was irreversible. High dose intra-arterial ACNU chemotherapy is effective in reducing tumor size on CT scan but the prognosis is not improved. The dose limiting factor of intra-arterial nitrosourea is neurotoxicity, and doses of more than 200 mg/m2 are considered to be dangerous.
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PMID:[Intra-arterial chemotherapy with ACNU in the treatment of malignant gliomas]. 131 68

Forty patients with malignant supratentorial gliomas received iterative intraarterial (IA) infusions of ACNU, 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea at a dose of 150 mg repeated every 6 weeks. Group A consisted of eighteen patients previously treated with surgery, radiation therapy (RT) and sometimes chemotherapy, who received IA ACNU at tumor recurrence. Group B consisted of twenty two patients who received IA ACNU in the postoperative pre-RT period. In group A, 8/18 patients (44%) had an objective response, including 6/12 anaplastic astrocytomas (AA) and 2/6 glioblastoma multiforme (GBM), while 10/18 patients (56%) did not respond. Median survival time was 6 months for GBM and 12 months for AA. In group B, 6/22 patients (27%) had an objective response (4/18 GBM and 2/4 AA) and 16/22 patients (73%) did not respond. Nine patients had such an extensive tumor after one or two courses of IA ACNU that RT was cancelled. Median survival time was 8 months for GBM and 8 months for AA. Three patients (8%) had ophthalmologic toxicity on the infused side. There was no case of leukoencephalopathy.
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PMID:Treatment of malignant gliomas with surgery, intraarterial chemotherapy with ACNU and radiation therapy. 133 43

The effect of recombinant human interleukin 1 beta (rHuIL-1 beta) on myelosuppression induced by 3-[(4-amino-2-methyl-5-pyrimidynyl)methyl]-1-(2-chloroethyl)-1-nit rosourea hydrochloride (ACNU) was studied. In in vivo study using BALB/c mice, pretreatment with 1 microgram/mouse of rHuIL-1 beta as a single intraperitoneal (i.p.) injection had a significant preventive effect on thrombocytopenia as well as granulocytopenia induced by ACNU at an intravenous dose of 60 mg/kg. Facilitated recovery by rHuIL-1 beta administered seven days after injection of high-dose ACNU was also observed. Experimental combination immunochemotherapy with high-dose ACNU and rHuIL-1 beta was performed in nude mice inoculated with human glioblastoma subcutaneously. The elongation of the survival time of the tumor bearing nude mice was also observed in combined use of high dose ACNU with rHuIL-1 beta. Seven patients with malignant brain tumors received intravenous 2.5-3 mg/kg ACNU. All patients were subcutaneously injected with 2 x 10(4)-U or more rHuIL-1 beta twice a week or daily. The mean nadir of leukocyte, granulocyte, and thrombocyte counts of the 7 patients received 2.5-3 mg/kg ACNU were significantly higher than in matched historical controls. In combination with rHuIL-1 beta, it may be possible to use chemotherapeutic agents at a relatively high dose.
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PMID:Preventive effects of interleukin 1 beta for ACNU-induced myelosuppression in malignant brain tumors: the experimental and preliminary clinical studies. 133 50

The prognosis of malignant glioma is extremely poor. We applied conventionally fractionated irradiation combined with 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU), uneven fractionated irradiation with ACNU, low dose rate telecobalt therapy as a boost, and intraoperative irradiation against 110 malignant gliomas to investigate the efficacy of these methods as alternative treatments for malignant glioma. Although local tumor control by uneven fractionated irradiation was better than that by the other methods, no significant improvement was obtained in survival rates. As a result of multiple regression analysis, age and histology were major factors for survival rates, and the difference of treatment methods was not important. Both low-dose rate telecobalt therapy as a boost and intraoperative irradiation showed little advantage because of the high risk of brain necrosis associated with them.
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PMID:Treatment results by uneven fractionated irradiation, low-dose rate telecobalt therapy as a boost, and intraoperative irradiation for malignant glioma. 133 4


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