Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antitumor and radiosensitizing properties of 5-bromo-2'-deoxyuridine (BUdR) appear to be due, in part, to its incorporation into cellular DNA. To optimize conditions for incorporation of 5-bromo-2'-deoxyuridine-5'-monophosphate (BrdUMP) into DNA, we investigated the metabolism of BUdR to its DNA precursor form, the 5'-triphosphate BrdUTP, in the U251 human glioblastoma cell line. The results demonstrated that BrdUTP accumulated rapidly in this cell line, achieving steady-state values within 2 hr of drug addition. The level of BrdUTP accumulation was proportional to the amount of exogenous BUdR up to a concentration of 100 microM, without apparent saturation. Exposure of glioblastoma cells to BUdR was associated with substantial selective decreases in both the cellular dCTP and TTP pools, the extent of which was dependent on the exogenous BUdR concentration. In the absence of exogenous BUdR, BrdUTP was eliminated rapidly from cells with an initial half-life of approximately 15 min. As the cellular BrdUTP level declined, the dCTP and TTP levels increased to control values. Incorporation of BrdUMP into DNA appeared linear with time as long as the cellular BrdUTP level remained constant. This incorporation was not enhanced by the addition of 5-fluoro-2'-deoxyuridine (FUdR), a potent inhibitor of thymidylate synthetase, which at a concentration of 10 nM had no effect on TTP pools in this cell line. Thus, the decrease in cellular TTP pools mediated by BrdUTP allows the halogenated pyrimidine to enhance its own incorporation into DNA.
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PMID:Decrease in TTP pools mediated by 5-bromo-2'-deoxyuridine exposure in a human glioblastoma cell line. 156 79

In the course of a study on glioblastoma tissue and cultured cell lines, a glitter drop technique for random sampling was introduced (1). Here, we report the initial description of the details of this procedure and its application to cell counts from explant slides and to determining bromodeoxyuridine (BUdR) labeling indices (LI) in tissues. The method is without bias, easy to perform and takes only a short time. It compares well with three other generally used random sampling procedures.
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PMID:Random sampling by glitter drop method. 230 83

Twelve cases of malignant gliomas (anaplastic astrocytoma 4, glioblastoma 8, recurrent 3, primary 9) were treated with ACNU and radiation with sensitizing agents after the surgical removal of the tumor. BUdR, Vidarabine (Ara-A), Aciclovir (ACV) were applied for sensitizing agents. BUdR was administrated intraarterially prior to radiation (380 rad, two times a week), and Ara-A and ACV intravenously during and after the radiation. Total dosage of the radiation was 50-60 Grey for each case. All recurrent and eight primary patients died. The mean survival time of the recurrent patients was 17.7 months, while that of the primary patients was 13.4 months. One of the primary patient was glioblastoma and is still surviving more than 24 months by now. The complete response (CR) rate of the primary tumor patients observed by computerized tomography (CT) scan was 5/9. We can expect the availability of this trial for malignant gliomas because of high CR rate in primary tumor cases.
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PMID:[A trial of ACNU and radiation therapy with sensitizing agents for malignant gliomas]. 262 8

Bromodeoxyuridine (BUdR) is a radiosensitizer that can be incorporated into cellular DNA as a substitute for thymidine at the time of DNA synthesis. As the steady-state arterial concentration of BUdR given by means of intravenous infusion was recently presented, the possibility of revival of BUdR as a radiosensitizer administered by the intravenous route was suggested. Based on the experience of BAR therapy and phase-I studies by NIH and UCSF, 12 hours of BUdR at a dose of 800-1,000 mg/m2 for five days a week was given to 23 patients with primary and secondary malignant brain tumors during radiation therapy. Radiation therapy was planned at a weekly dose of 10 Gy for five to six weeks. Fifteen patients received 1,000 mg/m2 of BUdR; six of them tolerated more than three weeks of treatment. In eight patients given doses of 800 mg/m2, five patients tolerated more than three weeks. The most remarkable toxic effects were myelosuppression and stomatitis, which were major obstacles to maintaining the schedule. More than 50% reduction of tumor volume was obtained in five of 12 cases of evaluated gliomas (42%) and three of four cases of metastatic tumors (75%). The median time to tumor progression in seven patients with glioblastoma was 37 weeks.
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PMID:Clinical trial of intravenous infusion of bromodeoxyuridine (BUdR) for radiosensitization of malignant brain tumors. 304 98

Eighty three patients suffering from brain tumors have been treated by anticancer pellets containing 5-FU, urokinase, mitomycin and BUdR in dimethylsiloxan (Silastic) for three years. Constant and prolonged release of the chemicals from the anticancer pellet had already been proved in vitro. The amount of daily release were 1-3/1,000 of original volume. Tissue concentration of 5-FU was measured by bioassay system using staphylococcus 209 P strain with plate dilution method. In spite of the rapid disappearance of serum 5-FU, the local high accumulation of 5-FU was demonstrated in vivo. In rat neurogenic tumor, 1.104 microgram/g was detected on 60 days after the application of anticancer pellet containing 500 mg of 5-FU. The growth of tumor was also suppressed. The clinical study consists of 83 patients, 30 of glioblastoma, 19 of metastatic brain tumor, 13 of astrocytoma, 7 of oligodendroglioma, 4 of ependymoblastoma, 4 of malignant lymphoma and 6 of others. The median survival time of gliblastoma was prolonged to 71.5 weeks by the implantation of anticancer pellet from 40 weeks of control group. However, the median survival time of astrocytoma and metastatic brain tumor were 24 and 6 months, respectively, which have no significant difference from control groups. In the patients of metastatic brain tumor, the regrowth of metastatic foci in the brain was completely suppressed. However, most of them were succumbed from the original tumors. The concentration of 5-FU in several human tissue was measured in ten patients with different time intervals after the implantation of the anticancer pellet. Although they have different histologic patterns, the concentrations of 5-FU in human brain tumors were ranged from 0.05 to 0.67 microgram/g by 14 months after the implantation of the anticancer pellet. The adjacent cystic fluids also contain from 0.62 to 4.9 microgram/ml of 5-FU for two years. These results mean that they are keeping higher level of 5-FU than the tumoricidal level of 5-FU (0.056 microgram/g) for more than two years. On the other hand, no respective accumulation was demonstrated in other tissues. None of the patients showed any adverse reactions except a continuous slight fever up to 38 degrees C.
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PMID:[Treatment of brain tumors with anticancer pellet--experimental and clinical study (author's transl)]. 709 76

Spheroids initiated directly from human primary gliomas were used to investigate the effects of EGF, bFGF, NGF and PDGF(bb) on cell proliferation, migration and invasion into foetal rat brain tissue. EGF increased tumour spheroid volume in 10 of 13 glioblastomas studied, whereas 5 of 11 tumours responded to bFGF. NGF increased the spheroid volume in 2 of 5 tumours. In 8 tumours, PDGF(bb) had no effect on tumour spheroid volume. An increase in BUdR-labelling indices confirmed that cell proliferation was responsible for the volume increase observed in stimulated spheroids. EGF stimulated cell migration in 5 and bFGF in 3 of 8 tumours studied. NGF stimulated cell migration in 1 of 5 glioblastomas, whereas 1 of 3 glioblastomas responded to PDGF(bb). The effects of growth factors on the invasion of spheroids prepared from the glioblastoma biopsy specimens were also studied in vitro using foetal rat brain aggregates as target tissue. EGF stimulated invasion in 7 of 8 glioblastomas studied, whereas bFGF stimulated invasion in 2 of these tumours. NGF or PDGF(bb) did not increase the invasiveness of the glioblastoma tissue. Our results represent the net effect of the growth factors on a complex tumour-cell population. We conclude that exogenously administered growth factors, EGF in particular, increase the cell proliferation as well as migratory and invasive capacities of cultured primary brain tumour biopsies in vitro.
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PMID:Effects of EGF, bFGF, NGF and PDGF(bb) on cell proliferative, migratory and invasive capacities of human brain-tumour biopsies in vitro. 838 Nov 11

The growth potential of 174 intracranial gliomas was estimated by calculating the bromodeoxyuridine labeling index (BUdR LI). Each patient received a 30-min infusion of BUdR, 200 mg/m2, before tumor removal. Excised tumor specimens were stained immunohistochemically to determine the BUdR LI, or percentage of S-phase cells. A Cox proportional-hazards stepwise model was used to determine the correlation between the BUdR LI and survival. Among patients with glioblastomas, the BUdR LI did not improve the prediction once age was entered in the model. Among patients with malignant or low-grade astrocytomas, the BUdR LI was the best single predictor of survival. The relative predictive abilities of BUdR LI and histopathology were determined by analyzing malignant astrocytoma and glioblastomas together. Distinguishing between malignant astrocytomas and glioblastomas did not significantly improve the prediction of survival once the BUdR LI and age were entered into the model. Equations derived from the model indicate that the probability of survival is a function of age and BUdR LI in patients with glioblastoma or malignant astrocytoma, but is a function of BUdR LI alone in patients with low-grade astrocytoma. The equations also show a substantial difference in the impact of increased BUdR LI on survival among patients with glioblastoma or malignant astrocytoma and those with low-grade astrocytoma. Without highly effective treatments for specific tumor phenotypes, the survival of a patient with an intracranial glioma appears to depend strongly on the proliferative potential of the tumor. Thus, accurate estimates of the proliferative potential are important in predicting the survival of individual patients with gliomas as well as in evaluating the effectiveness of various types of treatment.
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PMID:Prognostic significance of the proliferative potential of intracranial gliomas measured by bromodeoxyuridine labeling. 838 91

Effects of hyperthermia on the cell kinetics of glioblastoma cells were investigated using flow cytometry. Pulse-labeling with 5-bromodeoxyuridine (BUdR) and chasing of the labeled cells revealed temporary accumulation of the labeled cells in G2M phase and a reduction of DNA synthesis. The level of cyclin B rises rapidly in G2 phase and falls at the end of mitosis in normal cycling cells. Cyclin B binds to p34cdc2, resulting in histone kinase activity which is necessary for the initiation of mitosis. The amount of p34cdc2 remains constant throughout the cell cycle. The level of cyclin B was measured using an anti-cyclin B antibody and flow cytometry in order to investigate the cause of the G2 accumulation induced by hyperthermia. A low level of cyclin B, in comparison with that of normal cycling cells, persisted for more than 3 h after hyperthermia. These results indicate that the temporary accumulation of cells in G2M phase after hyperthermia may be caused, at least in part, by an insufficient level of cyclin B.
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PMID:Effect of hyperthermia on cyclin B expression in a human glioblastoma cell line. 854 68

Boron-neutron capture therapy (BNCT) is currently under investigation as a novel therapeutic modality for glioblastoma. This study was undertaken to determine whether boron-containing compounds 4-borono-2-fluoro-D,L-phenylalanine (FBPA) and FBPA-fructose have direct effects upon kinetics of A172, a glioblastoma cell line. Flow cytometry analyzed cell-cycle distribution and S-phase kinetics (bromo deoxyuridine [BUdR] incorporation). BUdR incorporation was increased during a 1-hr pulse after 24-hr or 72-hr exposure of cells to varying concentrations of FBPA or FBPA-fructose. Results suggest that boron-containing compounds may effect cell kinetics apart from neutron activation, and this effect should be further evaluated for potential impact upon tumor responsiveness to BNCT.
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PMID:In vitro effects of boron-containing compounds upon glioblastoma cells. 940 53

Prominin-1 (CD133) is a commonly used cancer stem cell marker in central nervous system (CNS) tumors including glioblastoma (GBM). Expression of Prom1 in cancer is thought to parallel expression and function in normal stem cells. Using RNA in situ hybridization and antibody tools capable of detecting multiple isoforms of Prom1, we find evidence for two distinct Prom1 cell populations in mouse brain. Prom1 RNA is first expressed in stem/progenitor cells of the ventricular zone in embryonic brain. Conversely, in adult mouse brain Prom1 RNA is low in SVZ/SGZ stem cell zones but high in a rare but widely distributed cell population (Prom1(hi)). Lineage marker analysis reveals Prom1(hi) cells are Olig2+Sox2+ glia but Olig1/2 knockout mice lacking oligodendroglia retain Prom1(hi) cells. Bromodeoxyuridine labeling identifies Prom1(hi) as slow-dividing distributed progenitors distinct from NG2+Olig2+ oligodendrocyte progenitors. In adult human brain, PROM1 cells are rarely positive for OLIG2, but express astroglial markers GFAP and SOX2. Variability of PROM1 expression levels in human GBM and patient-derived xenografts (PDX) - from no expression to strong, uniform expression--highlights that PROM1 may not always be associated with or restricted to cancer stem cells. TCGA and PDX data show that high expression of PROM1 correlates with poor overall survival. Within proneural subclass tumors, high PROM1 expression correlates inversely with IDH1 (R132H) mutation. These findings support PROM1 as a tumor cell-intrinsic marker related to GBM survival, independent of its stem cell properties, and highlight potentially divergent roles for this protein in normal mouse and human glia.
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PMID:Prominin-1 (CD133) defines both stem and non-stem cell populations in CNS development and gliomas. 2518 84


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