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

FK 973, a new substituted dihydrobenzoxazine, was obtained by chemical modification of a novel antibiotic which was isolated from the fermentation products of streptomyces sandaensis No. 6897. FK 973 had cytotoxic effects against in vitro cultured human and murine glioma cells. The concentration of FK 973 required to inhibit cell growth by 50% was 0.06-5 micrograms/ml, after 2-day exposure of this drug against human glioblastoma (ONS-6, 12, 23, and ONS-12/ACNU), human medulloblastoma (ONS-76, 81), human neuroblastoma (ST), and murine glioblastoma (RSV-M glioma). FK 973 showed antitumor efficacy in the meningeal gliomatosis models by RSV-M glioma cells. The median survival time (MST) of models treated by FK 973 (i.t.) was 30 days. However, the MST of control group was 23 days. In the in vitro neurotoxicity test, FK 973 proved to be slightly more toxic than ACNU and MTX, but it had no crucial problems, compared with ADM.
 ...
PMID:[Antitumor efficacy of FK 973 on malignant glioma cells]. 275 17

A case of Maffucci's syndrome with brain-stem tumor is reported. A 17-year-old man with a history of diplopia and unsteady gait for 5 months was admitted to our hospital on May 6, 1987. Neurological findings on admission disclosed left VIIth cranial nerve and bilateral VIIth nerve palsies and mild quadriplegia with a bilateral Babinski sign. His left limbs were deformed and disproportionally shortened since birth, and there were multiple enchondroma of the phalanges. Several bluish subcutaneous soft tumors were present on his left hand. Histological examination of a skin lesion confirmed the cavernous hemangioma. A CT scan showed diffuse symmetrical low density area in the brain-stem. No contrast enhancement was noted. Sagittal magnetic resonance imaging (MRI) demonstrated swelling of the brain stem especially in the pons and medulla oblongata. Left vertebral angiogram showed an avascular mass in the region brain stem. Brain-stem glioma being strongly suspected, both radiation therapy and chemotherapy were performed. After 66 Gy irradiation and ACNU administration, his neurological deficits gradually improved. The patient was discharged from the hospital on foot on August 7, 1987. The sagittal MRI taken on January 24, 1988 disclosed that the brain-stem swelling was apparently diminished. Maffucci's syndrome is a congenital, non-hereditary mesodermal dysplasia associated with multiple enchondromas and subcutaneous hemangioma. Although numerous tumors of the central nervous system have been described in association with Maffucci's syndrome, to our knowledge, no mention has been made of lesions in the brain-stem. The present case is an extremely rare instance of this syndrome complicated by the occurrence of a brain-stem tumor.
 ...
PMID:[A case of Maffucci's syndrome with brain-stem tumor]. 280 30

The chemotherapy of malignant brain tumors has been, only partially successful yet. Recently major concern is drug resistance, one of possible mechanisms of such drug resistance stems from inducible repair enzyme, especially in case of chloroethylnitrosoureas as ACNU or BCNU. We examined the changes of acquired resistance to ACNU in rat glioma cells by pretreatment with O6-methylguanine, which is a substrate for O6-methylguanine methyltransferase. ACNU-resistant (9L/AC) cells had established after 10 times treatments of ACNU. 9L/AC cells were pretreated with 2 mM O6-methylguanine for 2 hours, and subsequently challenged with increasing doses of ACNU for 2 hours. In vitro colony formation assay the survival fraction of 9L and 9L/AC cells ranged from 0.39 to 0.63 by 2-hour reaction of 1-3 mM O6-methylguanine. Based on the dose-response curve for ACNU in 9L/AC cells, by O6-methylguanine pretreatment (2 mM), ACNU-resistance decreased markedly to one-third, one-fifth, and one-two hundredth at 12, 24, 36 microM ACNU, respectively. In contrast, the survival of 9L cells against ACNU was similar under O6-methylguanine pretreatment or nontreatment condition. Therefore, ACNU-resistance is considerably related to DNA repair enzyme induction, and the substrates may potentiate the cell-killing effect of ACNU in the resistant glioma cells.
 ...
PMID:[Circumvention of ACNU-resistance in rat glioma cells by pretreatment with O6-methylguanine]. 291 93

Drug delivery to the tumor has been one of the major subjects in the field of brain tumor chemotherapy because of blood brain barrier. Recent studies including quantitative autoradiographic studies revealed that blood brain barrier is present and intact in the brain adjacent to tumor where viable tumor cells are infiltrating, and also in the tumors which are early in the development. In 1972 Rapoport et al demonstrated that it is possible to transiently and reversibly open the blood brain barrier by an intracarotid infusion of a hyperosmoral solution. This technique is found to increase cerebrovascular permeability to chemotherapeutic agents. Six cases of glioma, including 4 astrocytoma grade 4, 1 astrocytoma grade 3, 1 astrocytoma grade 2, were treated during operation with intracarotid infusion of ACNU 100 mg/body/5 min. (1.3-2.2 mg/kg) following intracarotid infusion of 20% mannitol 200 ml (1.3-1.6 ml/sec) through the catheter in the internal carotid artery set preoperatively, and ACNU concentration in tumor tissues and blood were measured at 5, 10, 15, 20, 25, 30, 40, 60 minutes after that. On every case mannitol contrast enhancement CT was studied by the intracarotid infusion of 60% conray 100 ml/5 min. following the intracarotid infusion of 20% mannitol 200 ml comparing with contrast enhancement CT and plain CT. Maximum ACNU concentrations in blood were 2.12-4.12 micrograms/ml (mean 3.1 +/- 0.74) at 5 min. after the intraarterial administration of mannitol and ACNU on every case. At 20 min. following the administration ACNU levels were decreased to half level (mean 1.49 +/- 0.42 microgram/ml) and 0.58 +/- 0.18 microgram/ml at 60 min.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[ACNU delivery to malignant glioma tissue by osmotic blood brain barrier modification with intracarotid infusion of hyperosmoral mannitol]. 299 32

The authors tried to establish a model of primary, autochthonous avian sarcoma virus-induced rat glioma for experimental chemotherapy and radiotherapy. It was found that the intracerebral inoculation of 2 X 10(6) FFU/5 microliter of an infectious cells-free homogeneous sub-group D Schmidt-Ruppin avian sarcoma virus into 3-day-old inbred Fischer rats induced brain tumors in all rats. The mean survival time of the inoculated rats was 58.7 +/- 12 days. With regard to the classification of the induced brain tumors in Fischer rats, astrocytoma accounted for 70%. This ASV-induced tumor in rats fulfills the following criteria for a desirable animal model. Spontaneously arising. Glial origin. Intraparenchymal growth. Uniformly fatal within a reasonable time period. In the present study, the therapeutic effects of anticancer drugs, such as ACNU and vincristine were evaluated and additionally, the effect of ACNU used in conjunction with radiation was also evaluated in this model. The mean survival time of rats was prolonged significantly with ACNU (20 mg/kg) or radiation therapy (1,000 rads), respectively, and in cases where ACNU was used together with radiation, the mean survival time was prolonged further still, but not very significantly, in comparison with radiation therapy alone. In conclusion, the ASV-induced rat glioma model was considered to be closely akin to a spontaneous brain tumor in terms of morphology, blood supply and kinetics of the primary tumor. Moreover, the therapeutic sensitivity of this model to anticancer drugs was fairly similar to that of human anaplastic astrocytoma. Considering these observations, this model seems to be an excellent experimental brain tumor model which is useful for evaluating the effect of new therapies against malignant brain tumors.
 ...
PMID:[Treatment of autochthonous rat brain tumors with chemotherapy and radiotherapy]. 303 11

The effect of chemotherapy against glioma in mouse was evaluated by 31P NMR spectroscopy and flow cytometry. We found that administration of ACNU or tegafur at a dose less than LD50 resulted in the partial suppression of the ratio of inorganic phosphate (Pi)/phosphocreatine (PCr) and phosphomonoester (PME)/creatine phosphate (PCr) after 24 or 48 hr, although these ratios are usually increased together with growth of tumors. Flow cytometric analysis of glioma in vivo showed an accumulation in cells containing tetraploid DNA by G2M block 24-48 hr after treatment. However, the change occurred at a period slightly later than that of the Pi/PCr ratio. In contrast, histological change was noted at eight days after administration. Hence, it is concluded that in vivo 31P NMR spectroscopy can detect a change in metabolic pathways in tumors as early as 24-48 hr after the administration of chemotherapeutic agents.
 ...
PMID:Early stage detection of chemotherapeutic effect on 203 GL glioma in mice as studied by P-31 NMR and flow cytometry. 314 36

In case of chemotherapy against brain tumors, it is most important to choose suitable drugs for brain tumors, since human tumors have different drug sensitivity and growth. Heretofore, the nitrosourea-induced rat glioma cell, such as C6, or immunodeficient mice were usually used for predicting the drug sensitivity of brain tumors. We took notice of Murphy's system for the chemosensitivity test, in which a human tumor is transplanted into the chorioallantoic membrane (CAM) of a chick embryo. By modifying the conventional Murphy's system, we studied the efficiency of this system in predicting the drug sensitivity of brain tumors. First, we compared the result of a drug sensitivity test using CAM of a chick embryo with that using nude mice. Next we studied the effect of chemotherapeutic agents against brain metastasis of a chick embryo caused by the intravenous injection of mouse B16 melanoma cells. The tumor reduction rate of the sensitivity test using a chick embryo tended to agree with that using nude mice. In the drug sensitivity test against brain metastasis, ACNU was the most effective. This result supports the result of the clinical study. In conclusion, the drug sensitivity test using a chick embryo is thought to be useful and the advantages or disadvantages of this system are discussed.
 ...
PMID:[Response to antitumor agents of human transplantable glioma implanted into chorioallantoic membrane of chick embryo]. 316 46

The cytotoxic and cytogenetic effects 1-(4-amino-2-methyl 1-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) and 1, 3-bis (2-chloroethyl)-1-nitrosourea (BCNU) treatments on five cell lines derived from human malignant glioma were studied. Compared to sensitive cell line SF-126, SF-188 cells were 3- to 6.9 fold more resistant to the cytotoxic effect and 8 to 14 fold more resistant to the induction of sister chromatid exchanges (SCEs). Cytotoxic effects and induction of SCEs were intermediate for SF-268, SF-210 and SF-295 cell lines compared with SF-126 and SF-188. There was a good correlation between susceptibility to the cytotoxic effects and formation of DNA interstrand crosslinks for cells treated with ACNU and BCNU. The effects of cis-diamminedichloroplatinum (II) (cis-Pt) and nitrogen mustard (HN2) in these cells were also studied. Cis-Pt was equally cytotoxic and induced the same number of SCEs and DNA interstrand cross-links in all five cel lines. In contrast to the results obtained by treatment with chloroethylnitrosoureas (CENUs), SF-126 cells treated with HN2 were more resistant to the cytotoxic effects, the induction of SCEs, and the induction of DNA interstrand cross-links than were SF-188 cells. The repair of O6-methylguanine after treatment of these cell lines with (3H) methylnitrosourea were quantitated. SF-126 cells showed no detectable repair of O6-methylguanine, SF-268, SF-210 and SF-295 cells had intermediate levels of repair, and SF-188 had very high level of repair. These results suggest that cellular resistance to CENUs dose not result in cross-resistance to HN2 or cis-Pt, and that one of mechanisms of cellular resistance to CENUs is increased repair of O6-alkylguanine derivatives in DNA, which prevents DNA interstrand cross-links and then reduces both cytotoxic effects and the induction of SCEs in cell resistant to CENUs.
 ...
PMID:[Mechanisms of cellular resistance to chloroethylnitrosourea in cell lines derived from human brain tumors]. 316 99

We report the DNA sites damaged by the antitumor drug, nimustine hydrochloride (ACNU), in highly reiterated DNA sequences of rat glioma cells. A reiterated fragment of 370 base pairs (bp), obtained after Hind III restriction endonuclease digestion of rat glioma C6 or 9L cells DNA, was divided into 167 and 203 bp by subsequent Hae III enzyme reaction. The reaction of end-labelled 167 and 203 bp fragments with ACNU resulted in scission breaks corresponding to the locations of guanine. Moreover, ACNU and subsequent piperidine hydrolysis produced more frequent breaks of the phosphodiester bonds at the guanine positions, thus forming alkali-labile sites. These results indicate that the preferred site of DNA strand scission induced by ACNU is at guanine positions.
 ...
PMID:In vitro damage of isolated DNA from two brain tumor cell lines induced by a water-soluble antitumor nitrosourea. 316 79

In case of chemotherapy against brain tumors, it is most important to choose suitable drugs for brain tumors, since human tumors have different drug sensitivity and growth. Heretofore, human tumor clonogenic assays or human glioma-bearing nude mice models were usually used for predicting the drug sensitivity of brain tumor. Human tumor clonogenic assays are one of the best in vitro tests for anticancer drug activity. However, plating efficiency is low, sometimes preventing evaluation of drug sensitivity, and the slow growth of colonies means that culture time is long. Assays using immunodeficient mice are used for predicting the drug sensitivity of human tumors; usually results reflect the sensitivity of the parent tumor. However, procedure using athymic nude mice are slow and expensive. We took notice of Murphy's system for the chemosensitivity test, in which a human tumor is transplanted into the chorioallantoic membrane (CAM) of a chick embryo, because in this system, various kinds of human tumors could be grafted in high rate. By modifying the conventional Murphy's system, we studied the efficiency of this system in predicting the drug sensitivity of brain tumors. We compared the result of a drug sensitivity test using CAM of a chick embryo with that using nude mice. First, we studied the effect of chemotherapeutic agents such as ACNU, bleomycin. Next, we studied the effect of combination treatment of CAP or CAPF. The tumor reduction rate of the sensitivity test using a chick embryo tended to agree with that using nude mice.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Chemosensitivity test for human gliomas]. 319 94


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>