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)

Present methods for treating cerebral glioma are inadequate and the possible benefit of using photosensitization therapy to obtain improved local control of the tumour has been studied in the laboratory and in clinical trials. The biological basis for photoradiation therapy and the laboratory studies and clinical trials using photoradiation to treat cerebral tumours are discussed. Photoradiation therapy results in selective tumour destruction in an intracerebral glioma model with an effect up to 1 cm in depth. Clinical studies using haematoporphyrin derivative and up to 260 J/cm2 of red light from laser sources indicate that the therapy is well tolerated and may be of value as an adjuvant treatment of cerebral tumours.
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PMID:Photoradiation therapy of brain tumours. 269 34

MX2, a new lipophilic morpholino anthracycline, has been reported to have superior chemotherapeutic effects to adriamycin against murine and human tumor cells. In this study the chemotherapeutic effect of MX2 against C6 glioma cells was examined as well as the photocytotoxicity of MX2 and the combination effect of MX2 and photodynamic therapy (PDT) in vitro. Colony formation is inhibited even with only 2 hour treatment with MX2 in a dose-dependent manner. In this colony forming efficiency assay the drug concentration required for 50% inhibition of colony formation for C6 glioma cells was 24.0 +/- 4.5 ng/ml. Mild photocytotoxicity of MX2 against C6 glioma cells was observed at a high concentration (100 ng/ml) of MX2 following exposure to white light but not red light. In combination, MX2 and the photosensitizer haematoporphyrin derivative (HpD) exhibited an additive cytotoxic effect against C6 glioma cells when the cells were treated with MX2 either immediately after red light illumination following incubation with HpD or at an interval of 24 hours before incubation with HpD. We conclude that MX2 may be clinically useful against malignant glioma alone, and in combination with other therapies such as PDT.
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PMID:[Antitumor effect of MX2, a new morpholino anthracycline against C6 glioma cells and its combination effect with photodynamic therapy in vitro]. 757 42

The photonecrotic effectiveness of a morpholinothiolporphyrin derived from haematoporphyrin was measured in an animal model of cerebral glioma. The dose administered was 20 mg kg-1 and the laser dose varied from 0 to 200 J cm-2. The tumour necrosis was at least as good as that of HpD, and this therapeutic response may be attributed to the targeting of specific 'photopotent' subcellular sites.
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PMID:Evaluation of a morpholinothiolporphyrin for use in photodynamic therapy. 808 Jul 21

Photodynamic therapy is a binary treatment combining the selective uptake of a photosensitizer into a tumour followed by irradiation of the tumour with light of the appropriate wavelength to cause activation of the sensitizer as selective tumour kill. Photodynamic therapy has been extensively investigated in laboratory studies in the treatment of cerebral tumours and has been utilised in clinical trials to treat a variety of tumours including cerebral glioma. The clinical trials have usually used PDT as an adjuvant therapy following tumour resection but studies are being undertaken to use the treatment in combination with stereotactic techniques. The photosensitizer haematoporphyrin derivative (HpD) has been shown to be selectively localised into all grades of glioma with a direct correlation between the grade of glioma and HpD level in the tumour. The levels were highest in the glioblastoma multiforme (mean uptake of 5.9 micrograms HpD/g tumour wet weight) and lower in the intermediate grade anaplastic astrocytoma (2.4 micrograms/g) and low grade astrocytoma (1.6 micrograms/g). Uptake into normal brain tissue taken from HpD sensitized patients was 0.2 microgram/g. HpD was also localised into the brain adjacent to the tumour region.
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PMID:Photodynamic therapy of brain tumours. 821 3

A series of monomeric porphyrins (2-8) based on porphyrin C (1) have been tested as sensitisers for photodynamic therapy (PDT) of cerebral glioma using the in vitro/in vivo C6 intracerebral animal tumour model. The in vivo screening, consisting of cytotoxicity, phototoxicity (red light) and subcellular localisation studies, revealed two sensitisers (porphyrin 7, molecular weight 863 Da and porphyrin 8, molecular weight 889 Da), which had greater photoactivity than porphyrin C and similar photoactivity to haematoporphyrin derivative (HpD) although at a 5-fold higher dose than HpD. Both sensitisers showed intracellular localisation to discrete organelle sites and exhibited considerably less 'dark' cytotoxicity than HpD. The kinetics of uptake of porphyrins 7 and 8 was studied in the mouse C6 glioma model as well as in biopsy samples from normal brain, liver, spleen and blood. Maximal drug uptake levels in tumour occurred 9 and 6 h after intraperitoneal injection for 7 and 8 respectively, at which time the tumour to normal brain ratios were 15:1 and 13:1 respectively. The effect of PDT using porphyrin 7 activated by the gold metal vapour laser tuned to 627.8 nm was studied in Wistar rats bearing intracerebral C6 glioma. At a drug dose of 10 mg porphyrin 7 kg-1 body weight and laser doses of up to 400 J cm-2 light, selective tumour kill with sparing of normal brain was achieved, with a maximal depth of tumour kill of 1.77+/-0.40. mm. Irradiation following a higher drug dose of 75 mg porphyrin 7 kg-1 body weight resulted in a greater depth of tumour kill, but also significantly increased the likelihood and extent of necrosis in normal brain.
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PMID:Evaluation of porphyrin C analogues for photodynamic therapy of cerebral glioma. 859 67

The present study describes the sensitivity of glioma cells to a haematoporphyrin derivative (Photosan-3) under laser activation (argon-pumped dye laser). The effects of photodynamic therapy (PDT) on cell growth, directional migration and cell invasion were investigated on two human glioma cell lines (GaMg and U-251 Mg). The directional cell migration and spheroid growth was determined for both cell lines exposed to increasing laser energy output (15-35J/cm2) with concentrations of 5 and 7 micrograms/ml of Photosan-3. Both cell lines showed a dose-dependent migratory response to increasing laser irradiation, that was more prominent in the 7 micrograms/ml treatment group. This effect occurred during the first 4 days after drug exposure. Also, spheroids from both cell lines showed a drug and laser output energy dose-dependent inhibition of growth which became apparent after a lag period of 6 days. The lag period was characterized by a decreased growth rate as compared with the control group. During this period the outer cell layers of the spheroids fell apart. The remaining spheroid tissue was not able to migrate and to regrow when exposed to the highest laser energy outputs (30-35J/cm2, 5 and 7 micrograms/ml Photosan-3). These spheroids showed, however, the ability for invasion when confronted with normal brain cell aggregated in vivo. Light microscopic observations of co-cultures between tumour tissue and brain cell aggregates revealed a normal tumour morphology. This indicates that the remaining tumour cells were not dead and could be stimulated to invade the normal tissue when exposed to a normal brain microenvironment.
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PMID:Effects of photodynamic therapy on glioma spheroids. 923 Oct 6

Photodynamic therapy (PDT) could be a useful adjuvant in glioblastoma treatment. The fact that epidermal growth factor (EGF) and its receptor are involved in glioblastoma growth control led us to investigate the relationships between EGF and PDT with respect to three different glioma cell lines (C6, T98 G, U87 MG) responsive to growth stimulation by EGF. Flow cytometric analysis revealed that each cell line expressed EGF receptors. PDT was then applied to the cells using haematoporphyrin derivative (HPD) as photosensitizer and argon laser irradiation. When cells were incubated for 2 h with HPD (0.1-10 micrograms/ml) and then laser-irradiated (lambda = 514 nm; energy density 25 J/cm2), all three cell lines showed photosensitivity. The median lethal dose was respectively 3, 4.5 and 2.7 micrograms/ml for C6, T98 G and U87 MG. EGF (2-50 ng/ml) had no effect on HPD- and laser-induced toxicity when added to cells before PDT, whereas toxicity decreased for all three cell lines when EGF was added after PDT. HPD (1-2 micrograms/ml, incubation times 30-180 min) also induced an increase in EGF receptor expression for the C6 line.
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PMID:Influence of epidermal growth factor on photodynamic therapy of glioblastoma cells in vitro. 944 Jan 40

Uptake, intracellular concentration, localization and photodynamic effects of a haematoporphyrin derivative (HpD, Photosan-3) were compared in human glioma (BMG-1, wild-type p53) and squamous carcinoma (4451, mutated p53) cell lines. Concentration and time dependence of cellular uptake of HpD was assayed from methanol extracts and whole cell suspension spectroscopy, while localization was studied by fluorescence microscopy-based image analysis. Colony-forming ability, apoptosis, cell-cycle progression and cytogenetic damage (micronuclei formation) were investigated as parameters of photodynamic response following irradiation with red light. BMG-1 cells were more sensitive to the photodynamic treatment than 4451 cells, although the 4451 cells accumulated a higher amount of HpD and did not differ significantly from BMG-1 cells with respect to intracellular localization. Photodynamically-induced cytogenetic damage and apoptosis were considerably higher in BMG-1 cells as compared to 4451 cells. The present results strongly suggest that manifestation of the photodynamically-induced lesions in the form of cytogenetic damage and apoptosis are among the important determinants of cellular sensitivity to HpD-PDT besides the photodynamic dose (intracellular concentration of the photosensitizer and the light dose).
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PMID:Cellular uptake, localization and photodynamic effects of haematoporphyrin derivative in human glioma and squamous carcinoma cell lines. 1263 83

Photodynamic therapy (PDT) using a photosensitizer, such as haematoporphyrin derivative (HpD), in conjunction with visible light is a promising new modality to treat localized cancer. Cell death caused by PDT (through the generation of reactive oxygen species) can occur either by apoptosis (interphase death or as a secondary event following mitosis) and/or necrosis depending on the cell type, concentration and intracellular localization of the sensitizer, and the light dose. Since, apoptosis induced by PDT treatment plays an important role in determining the photodynamic efficacy, in the present work we have investigated the role of apoptotic cell death in relation to the observed differences in sensitivity to HpD-PDT between a human glioma cell line (BMG-1) carrying wild-type tumour suppressor gene p53 and a human squamous carcinoma cell line (4451) with mutated p53. HpD (photosan-3; PS-3) -PDT induced apoptosis was studied by: [A] flow-cytometric analysis of DNA content (sub G0/G1 population); [B] phosphatidylserine externalization (Annexin-V +ve cells); [C] cell size and cytoskeleton reorganization (light-scatter analysis); and [D] fluorescence microscopy (morphological features). PS-3-PDT induced a significantly higher level of apoptosis in BMG-1 cells as compared to 4451 cells. This was dependent on the concentration of PS-3 as well as post-irradiation time in both the cell lines. At 2.5 microg/ml of PS-3 the fraction of BMG-1 cells undergoing apoptosis (60%) was nearly 6 folds higher than 4451 cells (10%). In BMG-1 cells the induction of apoptosis increased with PS-3 concentration up to 5 microg/ml (>80%). However, a decrease was observed at a concentration of 10 microg/ml, possibly due to a shift in the mode of cell death from apoptosis to necrosis. In 4451 cells, on the other hand, the increase in apoptosis could be observed even up to 10 microg/ml of PS-3 (60%). Present results show that the higher sensitivity to PS-3-PDT in glioma cells arise on account of a higher level of apoptosis and suggest that induction of apoptosis is an important determinant of photodynamic sensitivity in certain cell types.
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PMID:Role of apoptosis in photodynamic sensitivity of human tumour cell lines. 1526 33

MX2, a novel lipophilic morpholino anthracycline, has been reported to have superior chemotherapeutic effects to Adriamycin (ADM) against murine and human tumour cells. In this study the chemotherapeutic effect of MX2 against C6 glioma cells in vitro and in vivo was examined as well as the photocytotoxicity of MX2 and the combination effect of MX2 and photodynamic therapy (PDT) in vitro. The drug concentration required for 50% inhibition of cell growth (IC50) of MX2 for C6 glioma cells was 6.5 +/- 1.0 ng/ml, which was lower than for ADM and nitrosourea (ACNU). The growth of C6 glioma cells inoculated intracerebrally in mice was inhibited by intravenous (iv) injection of MX2 at doses ranging from 1.0-3.0 mg/kg suggesting that MX2 may be clinically effective against human malignant gliomas. Mild photocytotoxicity of MX2 against C6 cells in vitro was observed at high concentrations of MX2 illuminated with white light but not red light (> 630 nm). In combination, MX2 and the photosensitizer haematoporphyrin derivative (HpD) resulted in cyto- and photo-toxicity of C6 glioma cells irrespective of whether the cells were treated with MX2 either immediately after red light illumination following incubation with HpD, or at an interval of 24 hours before incubation with HpD. We conclude that MX2 may be clinically useful against malignant glioma alone, and in combination with other therapies such as PDT.
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PMID:Antitumour effect of MX2, a new morpholino anthracycline against C6 glioma cells and its cytotoxic effect in combination with photodynamic therapy. 1863 26


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