Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phase III Trial 8,301 tested the efficacy and safety of intraarterial (IA) BCNU for the treatment of newly resected malignant glioma, comparing IA BCNU vs intravenous (IV) BCNU (200 mg/m2 q 8 wks), each regimen without or with IV 5-FU (1 g/m2/d x 3 two wks after BCNU). All patients also received radiation therapy. 505 patients entered the study; 448 were in the Valid Study Group (VSG). Excluding 190 patients who for medical reasons were not eligible for IA BCNU, 315 patients were randomized between IA (167) and IV (148) BCNU. Actuarial analysis (log-rank) demonstrated worse survival for the IA group (p = 0.002). Serious toxicity was observed in the IA group; 16 patients (9.5%) developed irreversible encephalopathy with CT evidence of cerebral edema, and 26 patients developed visual loss ipsilateral to the infused carotid artery. 5-FU did not influence survival. Survival between the IV and the IA BCNU patients with glioblastoma multiforme did not differ, but was worse for IA BCNU patients with anaplastic astrocytoma than for IV BCNU (p = 0.002). Neuropathologically, IA BCNU produced white matter necrosis. IA BCNU is neither safe nor effective. Phase II Trial 8420, compared IA cisplatin, 60 mg/m2 every 4 wks, vs IV PCNU, 100 mg/m2 q 8 wks; 311 patients were randomized. Preliminary results have been presented. Severe encephalopathy occurred in only 1.5% of patients receiving IA cisplatin. The median survival of the IV PCNU patients was 11.8 months; that of the IA cisplatin patients was 9.4 months, not statistically different.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Chemotherapy of malignant gliomas: studies of the BTCG. 144 62

In a series of experiments on the combined use of radio- and chemotherapy for malignant glioma, X-rays combined with ACNU or 5-FU treatment caused a supra-additive effect on multicellular spheroids in vitro. In the present experiment, the effect of X-rays combined with 5-FU treatment on subcutaneously transplanted rat gliomas of RGC-6 cells was analyzed. The dose-survival curve for X-rays given to tumors in air-breathing rats was biphasic with a terminal slope (D0 = 4.3 Gy) that was parallel to that for tumors in previously killed rats. The hypoxic cell fraction thus obtained from the ratio of the surviving fraction in two parallel curves at 20 Gy was about 7% in the subcutaneous tumors in air-breathing rats. X-ray-induced, potentially lethal cellular damage recovered within 8 hours in these tumors. The surviving fraction of cells in the tumors decreased to a minimum at 4-6 hours after a 5-FU injection, but increased thereafter. A biphasic dose-response curve for 5-FU was also obtained for cells in these tumors, indicating the presence of 5-FU resistant cells. The effect of X-irradiation given at about 8 hours after a 5-FU injection was greater than the additive effect of both agents acting independently. This was true when an X-ray dose of more than 5 Gy was given.
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PMID:[Analysis on combined effect of X-rays with 5-FU on rat subcutaneous gliomas]. 150 45

To test the results of blood-brain barrier (BBB) disruption in the treatment of brain tumor, RG-C6 glioma was transplanted into the brains of rats. Intracarotid infusions of normal saline and hyperosmotic mannitol were then made, followed by intravenous injection of Evans blue dye plus albumin (EB, MW 68,000), horseradish peroxidase (HRP, MW 40,000), and 5-fluorouracil (5-FU, MW 130). Uptake of the drug and the consistency of drug levels in the normal brain and tumor varied widely among these three agents. Both EB and HRP penetrated the brain tumors but did not stain the normal brain tissues. After BBB opening, penetration of EB and HRP into the normal brain was drastically increased; however, the uptake of EB and HRP in the tumor was not increased. The concentration of 5-FU in the tumor was higher than that in the serum and, although it increased 1.5-fold after BBB opening, the increase was not statistically significant. Conversely, there was a progressive increase in concentrations of 5-FU in the tumor-free brain regions (p less than 0.05). These observations suggest that an intracarotid infusion of hyperosmotic mannitol may increase neurotoxicity because it allows greater delivery of anticancer drugs into the normal brain tissue than into the tumor tissues.
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PMID:Hyperosmotic blood-brain barrier disruption in brains of rats with an intracerebrally transplanted RG-C6 tumor. 310 Jul 31

Combined effects of ACNU and 5-Fu on rat glioma clone-6 cells grown exponentially as monolayers and in multicell spheroids (500-600 micron in diameter) were analyzed by the colony-forming assay. Cells in spheroids with central necroses were more sensitive to ACNU than cells in monolayer, although a large fraction of the cells in these spheroids was resistant to 5-Fu. The effect of ACNU was enhanced by the combined treatment with 5-Fu for cells in both spheroids and monolayers, and was more remarkable when 5-Fu was administered 24 hr prior to ACNU treatment. The enhancement was mainly due to a decrease in the number of spheroid-cells resistant to 5-Fu. Isobologram analysis indicated that the enhancement was supra-additive when a low concentration of 5-Fu was combined with a high concentration of ACNU. It is suggested that a low dose of 5-Fu combined with a high dose of ACNU may preferentially kill more cells in solid tumors.
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PMID:Combined effect of ACNU and 5-FU on rat glioma cells in spheroids and monolayer cultures. 346 Sep 69

The effects of combination chemotherapy of ACNU and 5-FU on cells grown exponentially as monolayers, cells in multi-cell spheroids and in s.c. transplanted tumors of rat glioma clone-6 cells were analyzed by the colony-forming assay. The cytotoxic effect of ACNU on cells in spheroids was enhanced by continuous 5-FU pretreatment for several hours, but further enhancement was obtained only if the 5-FU pretreatment lasted for more than 12 hr. The combined effect was decreased by a drug-free interval due to recovery from potentially lethal 5-FU damage, but ACNU treatment immediately after 5-FU treatment suppressed PLD recovery. Analysis with sequential trypsinization of spheroids indicated that ACNU showed more marked cytotoxicity on cells in the deeper layers in spheroids than on those in the outer layers, whereas the effect of 5-FU decreased towards the deeper cell layers. Enhancement of treatment with ACNU combined with 5-FU was evident for cells in the outer layers, but was more remarkable in the deeper layers. The combined effect of ACNU and 5-FU on s.c. tumors was similar to that in spheroids. The effect of combined treatment of ACNU with 5-FU on increase in body weight was within the additive range of both drugs acting independently, but was more than additive for the growth delay of s.c. tumors.
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PMID:Experimental combination chemotherapy of ACNU and 5-FU against cultured glioma model (spheroid) and subcutaneous rat glioma. 347 9

The effects of the anticancer drugs Nimustine (ACNU), Aclacinomycin A (ACR), Adriamycin (ADM), Bleomycin (BLM), Cisplatin (CDDP), and 5-Fluorouracil (5-FU) on the multicellular spheroid of a chemically-induced 9L rat glioma was studied. The multicellular spheroid in which cells grow in vitro as three-dimensional aggregates represents a biological model, which is intermediate between monolayer cells in vitro and solid tumors. Spheroids were initiated in bacteriological grade petri dishes seeded with 10(6) 9L rat glioma cells, cultured for four days and thereafter transferred and further developed in a spinner flask. Spheroids of 200-400 micron diameter were sorted and exposed for 24 hours to 5-FU and one hour for other drugs. After treatment both cytotoxic effect and growth delay were analyzed. Following disaggregation using collagenase, pronase and DNAase, cytotoxic effect on multicellular spheroids was measured by colony forming assay and were compared with those effects on 9L monolayer culture cells in the exponential growth. For growth delay assay, multicellular spheroids were individually transferred to 16 mm well containing 0.4 ml agarose base and 2 ml culture medium. Spheroid size was measured twice a week and growth curves were drawn. The growth delay was determined as the treated group vs. control differences in time required to a size four times that of the initial volume. For cells both in the monolayer culture and the multicellular spheroid, the dose response curve for ADM, BLM and 5-FU was "biphasic" and that for ACNU, ACR and CDDP "shoulder-threshold" type.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effects of anticancer drugs on multicellular spheroid of 9L rat brain tumor]. 386 69

Nineteen patients with brain tumors were orally administered 300 mg of UFT (a combination of FT and uracil with a molar ratio being 1:4) before operation and the concentrations of FT, 5-FU and Uracil in tumors and serum were measured by chemical assay. Time course of FT in serum rapidly attenuated, but 5-FU was kept almost constant below 0.014 micrograms/ml. T/B ratio (5-FU in tumor/5-FU in blood) in 11 samples of meningioma was 6.86 +/- 3.67, while in 8 samples obtained from glioblastoma was significantly higher (23.79 +/- 11.43, p less than 0.001). In malignant brain tumors there was a correlation between the concentration of 5-FU and Uracil in tumor (gamma = 0.67). This correlation was more enhanced when the value of Uracil in tumor was over 15 micrograms/g (gamma = 0.81). The concentration of 5-FU in cyst was low, but tended to accumulated later. This result may be based on the diffusion of 5-FU from the surrounding solid part of tumor into the cyst. Our present study demonstrated that enhancing effect of 5-FU in brain tumors, particularly solid malignant glioma, was yielded after oral administration of UFT.
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PMID:[5-FU concentration in brain tumors after co-administration of FT and uracil]. 630 60

Increasingly vigorous chemotherapy of cancer including primary and metastatic central nervous system disease has resulted in prolonged good-quality survival. However, there has been an associated increase in neurotoxicity from both radiation therapy and chemotherapy. All classes of chemotherapeutic agents contain drugs that are potentially neurotoxic, often only at high doses. Mechlorethamine, the first nitrogen mustard, is not neurotoxic at conventional dosage, but at high doses, it may produce both an acute and a delayed encephalopathy. Methotrexate administered intrathecally often induces reversible aseptic meningitis, but chronic administration, either intrathecally or high-dose intravenously, may produce fatal leukoencephalopathy. 5-Fluorouracil at high dosage may cause cerebellar ataxia, but may also do so at low dosage when combined with thymidine infusions. Cytosine arabinoside at high dosage may also produce cerebellar ataxia. Vincristine produces a peripheral neuropathy, and less commonly causes both autonomic and cranial neuropathy. The enzyme L-asparaginase can produce a dose-related reversible encephalopathy. BCNU, now the mainstay of glioma chemotherapy, may combine with radiation to produce long-term cerebral atrophy. Both intracarotid and high-dose intravenous BCNU administration may cause encephalopathy. Several other chemotherapeutic agents have also been reported to cause neurotoxicity under certain circumstances.
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PMID:Neurological complications of antineoplastic therapy. 638 4

The penetration of [3H]thymidine, [3H]D-leucine, [125I]albumin, and the drugs [3H]5-fluorouracil and [3H]vinblastine into human glioma spheroids (in vitro tumor models) was studied by a method based on rapid freezing, freeze drying, vapor fixation, wax embedding, dry sectioning, and contact autoradiography. No significant disturbances in the distribution of water soluble substances were observed. Thymidine and D-leucine penetrated the whole spheroids relatively fast, whereas albumin showed reduced penetration. The concentration of albumin was highest at the periphery of the spheroids, but only smaller amounts were detected in the deeper regions. A significant difference between the penetration patterns of the drugs studied was also observed. Fluorouracil penetrated rather freely, but the penetration of vinblastine was limited.
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PMID:Penetration of substances into tumor tissue--a methodological study on cellular spheroids. 723 41

Bromodeoxyuridine (BUdR), a nonhypoxic radiosensitizing drug, is a halogenated pyrimidine analog that is incorporated into the DNA of dividing cells in a competitive process with thymidine. BUdR sensitizes cells to radiation therapy. 5-Fluorouracil (5-FU) inhibits the endogenous synthesis of thymidine, resulting in increased incorporation of the BUdR. Neurons and glial cells have a very low mitotic rate; they will not incorporate BUdR and will not be sensitized. BUdR and 5-FU are best delivered intra-arterially (IA) because of their regional advantage. We infused BUdR +/- 5-FU over 8 1/2 weeks, before and during 59.4-Gy focal conformal external beam radiation therapy, through a permanently implanted pump with a catheter placed retrograde through the external carotid artery to the carotid bifurcation. Sixty-two patients with grades III or IV glioma were entered into one of two trials, with 23 patients receiving BUdR alone and 39 patients receiving BUdR + 5-FU. The maximum tolerated dose (MTD) of BUdR alone was 400 mg/m2/d for 8 1/2 weeks. The Kaplan-Meier median survival (KMS) was 20 months. In the BUdR + 5-FU trial, the MTD of BUdR was also 400 mg/m2/d and 5-FU was 5 mg/m2/d with a KMS of 17 months. The KMS of all 62 patients in both trials 1 and 2 was 18 months. Pathologic grading used both the original World Health Organization (WHO) and 1993 modified WHO systems. The KMS of grade IV patients was 13.8 months (48 patients) with the original system and 17 months (58 patients) with the modified system.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Radiosensitization with carotid intra-arterial bromodeoxyuridine +/- 5-fluorouracil biomodulation for malignant gliomas. 793 3


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