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)

1. The effect of topical CCNU treatment on lipid peroxidation of glial tumors transplanted on rat brain has been investigated in 22 rats. 2. Four groups have been selected as normal brain tissue, normal brain tissue+CCNU, tumour tissue, tumour tissue+CCNU. In these groups malondialdehyde (MDA) levels have been measured as a marker of lipid peroxidation. 3. Lipid peroxidation was high in tumour tissue in respect to controls (P < 0.05). In normal tissues topical CCNU treatment caused increase in lipid peroxidation (P < 0.05). In tumor tissues, topical CCNU decreased lipid peroxidation (P < 0.05). It is concluded that further studies have to be performed in order to determine whether increases in lipid peroxidation on CCNU treated normal brain tissues is a result of the inhibitory effect on cellular defence systems or promotion of free radical production.
 ...
PMID:The effect of topical CCNU(1-(2-chloroethyl)-3 cyclohexyl 1 nitrosurea) treatment on lipid peroxidation of glial tumours transplanted on rat brain. 759 Jan

A case of a malignant childhood glioma is reported with tumor-progression after surgery and radiotherapy during chemotherapy with cisplatinum, vincristine and CCNU, that responded temporally to oral treatment with VP16 and trofosfamide. A Phase II study with this combination is suggested.
 ...
PMID:Second temporal remission in a malignant glioma with trofosfamide and etoposide: a case report. 877 6

Because of the methodological difficulties associated with the MTT assay in screening short-term cultures derived from human malignant glioma, a chemosensitivity assay based on the protein staining using sulforhodamine B (SRB) has been optimized for use with these cells. SRB at a fixed dye concentration achieved maximal staining density at 20 min for most cell lines and this intensity was not further increased by using dye concentrations above 0.2%. A delay in staining after fixation did not significantly decrease staining intensity, but delay in dye extraction after fixation and staining did. There was an excellent quantitative and qualitative linear relationship between cell number determined by either the SRB assay or by cell counting, but not with the MTT assay which consistently underestimated the number of cells in assay plates. The MTT assay appeared to be incapable of detecting less than about 150 cells/well, while these small numbers of cell were readily detectable by either cell counting or SRB staining. There was a close correlation between chemosensitivity values derived from the MTT and SRB assays for procarbazine, CCNU and vincristine when the endpoint is taken as either the ID25, ID50 or ID75. The results indicate that the SRB is capable of producing broadly similar results to the MTT assay, but is more sensitive in the detection of small numbers of cells with a linear relationship between cell number and SRB staining intensity over a wide range of cell numbers. It is capable of producing data from short-term cultures from malignant glioma and offers technical advantages over the MTT assay in that plates may safely be stored at certain points during the assay without the need for immediate processing. The SRB assay provides a useful alternative to the MTT assay for determining the sensitivity of short-term cultures of human glioma to cytotoxic drugs.
 ...
PMID:Assay of anticancer drugs in tissue culture: comparison of a tetrazolium-based assay and a protein binding dye assay in short-term cultures derived from human malignant glioma. 879 8

Heterogeneity in drug sensitivity must, in part, account for the relative lack of success with single agent chemotherapy for glioblastoma multiforme (GBM). In order to develop in vitro model systems to investigate this, clones derived from the VM spontaneous murine astrocytoma have been characterised with regard to drug sensitivity. Six clonal cell lines have been tested for sensitivity to a panel of cytotoxic drugs using an intermediate duration 35S-methionine uptake assay. These lines have previously been extensively characterised with regard to morphological, antigenic, kinetic, tumourigenic potential in syngeneic animals and chromosomal properties and display considerable heterogeneity. The present study indicates that heterogeneity extends to sensitivity to all classes of cytotoxic drugs. The greatest difference in sensitivity between the clones was seen in response to cell cycle-specific drugs like the Vinca alkaloids (14-fold and 20-fold for vincristine (VCR) and vindesine (VIND) respectively), while the nitrosoureas, CCNU and BCNU displayed a smaller fold difference in sensitivity (4.3 and 3.6-fold difference respectively). All the clones were considerably more resistant to the adriamycin (ADM), cis-platinum (C-PLAT) and the Vinca alkaloids than the parental cell line although the difference in sensitivity between the clones and parental cell line were less marked for the nitrosoureas and procarbazine (PCB). It has also been possible to examine the relationship between drug sensitivity and the phenotypic and genotypic properties of these clonal cell lines. There is a relationship between chromosome number and sensitivity of a wide variety of cytotoxic drugs including the nitrosoureas, Vinca alkaloids, PCB, C-PLAT, BLEO but not ADR or 5-FU. Clones with small numbers of chromosomes were more resistant than clones with gross polyploidy. Similarly, sensitivity to Vinca alkaloids and ADM, but not other classes of drugs, was greatest in cells with numerous cytoplasmic processes and which did not express large amounts of cell surface fibronectin. Preliminary experiments have been conducted on reconstituting clonal mixtures of cells with different sensitivity to Vinca alkaloids and results from these studies indicate that the drug resistance phenotype is dominant, with clonal mixtures of sensitive and resistant cell adopting the sensitivity of the more resistant partner. These cell lines should prove to be useful models for examining the cell biological basis of drug resistance in glioma and may lead to the identification and exploitation of novel cellular targets in new therapies for GBM.
 ...
PMID:Heterogeneity of chemosensitivity in six clonal cell lines derived from a spontaneous murine astrocytoma and its relationship to genotypic and phenotypic characteristics. 925 17

In cerebral glioma combination chemotherapy with procabazine, CCNU and vincristine (PCV) is used as adjuvant therapy in cases of recurrence. Standard PCV is usually well tolerated, but intensive PCV (CCNU 130 mg/m2 on day 1, procarbazine 75 mg/m2 on day 8-21, vincristine 1.4 mg/m2 on day 8 and 29; 6 courses every 6 weeks) is less well tolerated. We observed central neurotoxic side effects (focal neurological deficit, cognitive disturbances, slowing of EEG background activity, atrophy on cerebral MR) in combination with hematological and hepatic toxicity in four of 26 PCV treated patients with recurrent glioma. Prolonged myelo-suppression and/or ongoing (partial reversible in two patients) neurological deficit still influence daily life in three of four patients months after discontinuation of chemotherapy. Despite the fact that all four patients used anticonvulsants and have been treated with radiotherapy in the past, we have the strong impression that central neurotoxic side effects are related to intensive PCV therapy. We advocate to use the standard PCV regimen in patients with recurrent glioma, because of this potential toxicity and the lack of evidence that intensive PCV leads to better tumor control than standard PCV in cerebral glioma.
 ...
PMID:Neurotoxicity of combination chemotherapy with procarbazine, CCNU and vincristine (PCV) for recurrent glioma. 954 59

We report two patients with acute myeloid leukemia (AML) following therapy for malignant glioma; one was a young women treated heavily with alkylating agents for glioblastoma and the other a young man treated with high doses of procarbazine, lomustine, and vincristine (PCV) for anaplastic astrocytoma. We found 26 other examples of therapy related leukemia in adult and pediatric brain tumor patients. Including our two, there were 12 patients with malignant glioma; median interval from treatment to diagnosis of AML was 31 months. Nine adult malignant glioma patients all received nitrosoureas, some as the sole form of chemotherapy. No definite cases occurred after radiotherapy alone. Based upon analogy with other cancers, the cumulative dose of chemotherapy, especially alkylating agents, is the major risk factor for development of secondary AML. Agents implicated include carmustine (BCNU), lomustine (CCNU), and procarbazine. Conventional radiotherapy appears not to confer additional risk. Progressive macrocytosis, early dose reductions for thrombocytopenia, and refractory anemia may provide early diagnostic clues. Current glioma therapy is leukemogenic but the number of patients who survive the interval required to induce AML is small; nevertheless, the identification of chemosensitive types of glioma, and subgroups of patients who derive the most benefit from chemotherapy, may result in increasing numbers of patients at risk of long term complications. If regimens such as PCV continue to prove valuable in neurooncology the risk of leukemia will require integration into the clinical decision process. A search for more effective therapy with minimal mutagenicity remains critical.
 ...
PMID:Acute leukemia following treatment of malignant glioma. 987 84

Combination chemotherapy with procarbazine, CCNU and vincristine (PCV) may be effective in patients with recurrent glioma. Response monitoring is mandatory, but radiological response evaluation is often difficult. We evaluated Thallium-201 (201Tl) SPECT as a response parameter in ten patients treated with intensive PCV chemotherapy for recurrent glioma. 201Tl-SPECT studies showed early changes (decreasing volume and intensity) in nine patients and these changes were more pronounced than radiological findings. 201Tl-SPECT results after completion of chemotherapy seemed to correlate with clininal findings during follow up. We conclude that 201Tl-SPECT may contribute to the assessment of response in patients treated with PCV chemotherapy for recurrent glioma.
 ...
PMID:Thallium-201 SPECT as response parameter for PCV chemotherapy in recurrent glioma. 1006 98

The activity of temozolomide, which has shown clinical activity against malignant glioma, has been assessed in vitro against short-term cultures derived from these tumors using an intermediate duration microtitration assay with MTT reduction as the end-point This assay has previously been shown to correlate closely with a monolayer clonogenic assay. Sensitivity was assessed in 15 short-term cultures (passage levels 3-9) derived from WHO grade III and IV astrocytomas. These cultures had a median ID50 value of 258 microM for temozolomide and 16.13 microM for CCNU. Maximum serum concentrations of temozolomide are of the order of 75 microM but only three of 15 (20%) cultures had ID50s below this value. Fourteen of 15 (93%) cultures displayed cross-resistance between temozolomide and CCNU, although one line which was extremely resistant to CCNU retained sensitivity to temozolomide. Comparative studies of published clonogenic survival curves indicate that the short-term glioma cell lines used in this study have similar sensitivities to established glioma cell lines, whilst colon carcinoma cell lines and bladder carcinoma are often more resistant to these drugs. Cell lines from testicular teratoma cell lines may show exquisite sensitivity to temozolomide and this level of sensitivity is seen only occasionally in short-term cultures derived from malignant glioma.
 ...
PMID:Sensitivity of short-term cultures derived from human malignant glioma to the anti-cancer drug temozolomide. 1021 48

In an effort to overcome chemoresistance of human malignant glioma cells, the modulation of drug-induced cell death by hyperthermia was assessed in 4 human malignant glioma cells lines, LN-18, LN-229, T98G and U87MG. Compared to normothermic conditions, pulsed 24 h drug exposure enhanced the sensitivity of glioma cells most strikingly with teniposide, treosulfan, topotecan and cisplatin, moderately with vincristine, CCNU and doxorubicin, but not with gemcitabine. Susceptibility to hyperthermia-mediated drug sensitization, varied significantly with T98G and LN-229 being strongly sensitized and U87MG being most resistant to the effects of hyperthermia. Hyperthermia did not significantly modulate drug-induced changes in cell cycle distribution. The degree of sensitization was independent of p53 status and of multidrug resistance (mdr) activity. Hyperthermia may thus be a useful approach to overcome, chemoresistance of human malignant glioma cells.
 ...
PMID:Hyperthermia enhanced chemosensitivity of human malignant glioma cells. 1092 13

Once thought to be rare, oligodendroglial tumors might actually represent up to 25% of primary glial neoplasms. In recent years, the histologic criteria for the diagnosis of oligodendroglioma have been broadened to include most small cell, monomorphic glial neoplasms. These refinements have led to an increased recognition of oligodendroglial neoplasms, but uniform definitions of pure versus mixed oligodendroglioma as well as the criteria for high-grade (anaplastic) versus low-grade tumors remain elusive. From a prognostic standpoint, the presence of an oligodendroglial component in a malignant glioma predicts longer survivals times for patients treated with surgery, and radiation therapy with or without chemotherapy. High rates of response to PCV (procarbazine, CCNU and Vincristine) chemotherapy also have been noted among patients with anaplastic oligodendroglial neoplasms. Ongoing prospective trials seek to clarify the role of PCV chemotherapy when added to radiation therapy and surgery. In addition, the role of molecular markers as diagnostic aides and guides to therapy and prognosis are being explored for patients with pure and mixed anaplastic oligodendroglial tumors.
 ...
PMID:Multidisciplinary management of adult anaplastic oligodendrogliomas and anaplastic mixed oligo-astrocytomas. 1128 55


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