Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Gliosarcoma”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 703 records · Page 39Linked to original sources
PubMed2005

In vivo delivery of BCNU from a MEMS device to a tumor model.

A drug delivery micrcoelectromechanical systems (MEMS) device was used to locally deliver a chemotherapeutic agent (BCNU) to an experimental tumor in rats. This MEMS device consists of an array of reservoirs etched into the silicon substrate. The drug release is achieved by the electrochemical dissolution of the gold membranes covering the reservoirs. A new Pyrex package was developed to improve the BCNU release kinetics and enhance device capacity. Co-formulation of BCNU with polyethylene glycol (PEG) led to complete and rapid release of drug in vivo. BCNU delivered from the MEMS device showed dose-dependent inhibiting effect on the tumor growth in the BCNU dosage range of 0.67 approximately 2 mg. BCNU delivered from the activated devices was as effective as equipotent subcutaneous injections of BCNU in inhibiting tumor growth. Further optimization using this MEMS device to deliver BCNU in combination with other therapeutic agents against the tumor challenge is possible because of the unique capability of the device to precisely control the temporal release profiles of multiple substances.

Animals↗
PubMed2000

Antigen-presenting capability of glial cells under glioma-harboring conditions and the effect of glioma-derived factors on antigen presentation.

The antigen-presenting capability of syngeneic rat glial cells was investigated under glioma-harboring conditions. Microglia induced a significant proliferation of glioma-primed splenocytes, but astrocytes did not. Furthermore, astrocytes suppressed the accessory cell function of microglia. The presence of both indomethacin and anti-interleukin (IL)-10 neutralizing antibody during priming of microglia enhanced splenocyte proliferation. The glioma culture supernatants down-regulated the interferon-gamma-induced expression of major histocompatibility complex class II molecules on microglia. The down-regulation was blocked by indomethacin and anti-IL-10 antibody. The results suggest that microglia but not astrocytes may function as antigen-presenting cells in glioma, and that glioma may suppress the antigen-presenting abilities of microglia.

Animals↗
PubMed1998

The role of microglia and tumor-primed lymphocytes in the interaction between T lymphocytes and brain endothelial cells.

We investigated the role of IFN-gamma activated microglia in the passage of T lymphocytes across a monolayer of brain endothelial cells (EC) in vitro. Microglia isolated from Fisher 344 (F344) newborn rats were stimulated with IFN-gamma (100 U/ml) for 48 h. T lymphocytes primed with glioma cells were 51Cr-labeled, and added to the monolayer of F344 brain EC. In the adhesion assay, when EC were cultured in medium containing the supernatant of reactive microglia before the assay was carried out, the number of T lymphocytes adhering was increased. In addition, this adhesion was blocked by the addition of anti-ICAM-1 mAb to the EC. In the migration assay, performed using the double chamber system, when reactive microglia adhered to the other side of EC, the number of T lymphocytes migrating to the underwell was also increased. When T lymphocytes were primed to tumor cells in vivo, both their adhesion and migration were enhanced. These results suggest that some soluble factors from reactive microglia are capable of enhancing the expression of ICAM-1 on the brain EC. As a consequence, large numbers of tumor-primed T lymphocytes can adhere to EC and migrate across the EC monolayer.

Animals↗
PubMed1999

Cell surface expression of MHC molecules in glioma cells infected with herpes simplex virus type-1.

9L glioma cells consistently expressed major histocompatibility complex (MHC) class I but not class II molecules. Herpes simplex type-1 virus (HSV-1) infection significantly reduced the expression of MHC I on the cell surface. Recombinant interferons could enhance the cell-surface expression of MHC I but had no effect on MHC II. This enhancement was partially inhibited by HSV-1 infection. HSV-1 mutants with deletions in ICP4, ICP6, ICP27, ICP47 and UL41 genes do not affect the infection induced inhibition, suggest that a different mechanism may be employed in the inhibition of cell-surface expression of MHC molecules.

Animals↗
PubMed2002

New drug delivery system for water-soluble drugs using silicone and its usefulness for local treatment: application of GCV-silicone to GCV/HSV-tk gene therapy for brain tumor.

Controlled release of a water-soluble low-molecular-weight drug from silicone and its usefulness as a local therapeutic drug were studied. For application to ganciclovir/helpes simplex virus thymidine kinase (GCV/HSV-tk) suicide gene therapy for brain tumor, two kinds of GCV-containing silicone formulations were prepared for evaluation. In vitro, GCV release from matrix-type formulation consisting of a single matrix was characterized by Fickian diffusion, while covered-rod-type formulation, in which the side surface of the outer layer was covered with 100% silicone, exhibited a near-zero-order release pattern. In an in vivo study using a rat 9L glioblastoma model, administration of GCV-silicone formulation into brain tumor yielded sustained intracerebral GCV concentration for 4 days after administration, with excellent antitumor effect equal to or better than that of daily intraperitoneal administration of aqueous solution of GCV, at a dose less than 1/100 of the total dose of solution for intraperitoneal administration. Furthermore, GCV was undetectable in blood, suggesting that decrease in systemic adverse reactions can be expected with intracerebral administration of GCV-silicone formulation.

Algorithms↗
PubMed2000

Ultrasound enhancement of liposome-mediated cell transfection is caused by cavitation effects.

Cationic liposomes (CL) are widely used vectors for gene transfer. Recently, ultrasound (US) was reported to enhance liposome-mediated gene transfer to eucaryotic cells in culture. The present study was aimed at studying the effects of 2-MHz pulsed Doppler US on malignant brain tumor cells transfection by cationic liposome/plasmid-DNA complexes (lipoplexes). Cationic liposomes consisting of DOSPA/DOPE were complexed with a plasmid carrying the cDNA encoding green autofluorescent protein (EGFP). Rodent (9L) and canine (J3T) glioma cells were exposed to pulsed US in the presence of EGFP-lipoplexes. A diagnostic transcranial Doppler device (MultiDop L) was used for insonation for 30, 60, and 90 s at 2 MHz/0.5 W/cm(2). To eliminate US reflection and cavitation, a custom-made absorption chamber was designed, where US is applied through a water tank before interacting with the cells and is fully absorbed after passing through the cell layer. Expression of the marker gene EGFP was quantified by FACS analysis and intravital fluorescent microscopy. Cell viability was accessed by Trypan Blue staining. US treatment of tumor cells on microplates for 60 s yielded a significant increase in transfection rates without damaging the cells, but 90-s treatment killed most of the cells. In the absorption chamber, no significant effects of US on transfection were noted. Additional experiments employed US contrast agent (Levovist, Schering) which was able to significantly increase tumor cell transfection rate by enhancing cavitation effects, and also severely damaged most cells when applied at a concentration of 200 mg/mL. In conclusion, our results support the assumption that US effects on lipoplex transfection rates in brain tumor cells in culture are mediated by cavitation effects.

Animals↗
PubMed2000

Increased tumor cures using combined radiosurgery and BCNU in the treatment of 9l glioma in the rat brain.

PURPOSE: Radiosurgery refers to the delivery of high, single focused beams of ionizing radiation to defined intracranial lesions. 1,3 Bis[2-chloroethyl]-1-nitrosourea (BCNU) and cis-diammine-1, 1-cyclobutane-dicarboxylate platinum (II) (carboplatin) are commonly used cytotoxic agents for the treatment of malignant gliomas of the brain. Drug therapies have exhibited a modest enhanced cell killing when combined with radiation in experimental animal tumor systems. The purpose of the present study was to investigate the role of cytotoxic drugs, such as BCNU and carboplatin, in combination with a single high dose of radiosurgery on the tumor control rates of 9L tumors in the rat brain. METHODS AND MATERIALS: Combined radiosurgery (25 Gy single dose) and/or chemotherapy (a single dose of BCNU, 7 mg/kg, i.p. 1.5 or 16 h prior to or 16 h after irradiation or a single dose of carboplatin, 30 mg/kg, administered either 1 h or 4 h prior to irradiation) was delivered 12 days after stereotactic tumor implantation. For dose escalation study, 4-10 mg/kg of BCNU was used. RESULTS: The radiation alone group showed a dose-dependent survival. A single dose of 25 Gy to the control group resulted in an increase of the median survival time from 20 days to 42 days, but all animals died of the tumor in 50 days. A significant prolongation of the median survival time of animals was more than 100 days, resulting in animal cures of 50% or more when combined with radiosurgery (25 Gy) and BCNU (7 mg/kg). BCNU alone did not prolong the median survival time of the animal with the 9L brain tumor. In contrast, there was no survival improvement when the animals were treated with combined radiosurgery and carboplatin. None of the long-term surviving animals showed any significant brain tissue damage as evaluated by histopathology and clinical observations. CONCLUSION: The data clearly suggest that the combined modalities of radiosurgery and concomitant BCNU represent an effective therapeutic regimen in the treatment of radioresistant human malignant gliomas of the brain. This study represents the first experimental report of the effectiveness of combined chemotherapy and radiosurgery.

Animals↗
PubMed2002

Safety of thrice-daily hyperfractionated radiation and BCNU for high-grade gliomas.

PURPOSE: To investigate the safety of thrice-daily hyperfractionated radiotherapy (RT) given in conjunction with BCNU (carmustine) in high-grade gliomas. METHODS AND MATERIALS: Patients >18 years old with newly diagnosed high-grade gliomas were eligible. The dose of radiation was 5040 cGy, with a 1440-cGy boost in 180 cGy fractions delivered thrice daily in two 6-day periods with a 2-week interval. BCNU (200 mg/m(2)) was administered on the first day of radiation, then every 7 weeks for 1 year and every 10 weeks for another year. RESULTS: Eighteen patients were enrolled. The mean age was 49.6 years. Sixteen patients had astrocytomas (Grade 3 or 4 in 5 and 11 patients, respectively) and 2 had oligoastrocytomas (Grade 3 and 4 in 1 patient each). One underwent total resection, 9 subtotal resection, and 8 biopsy only. Thirteen patients had stable disease, 4 regression, and 1 progression. The median time to progression was 37.8 weeks. The median overall survival was 44.4 weeks. Nine patients had neurologic toxicities, including 2 deaths at 69 and 139 weeks. CONCLUSION: This regimen is unacceptably toxic. Factors that could have contributed to the toxicity may include the total radiation dose, thrice-daily hyperfractionation, and the concurrent use of i.v. BCNU.

Adult↗
PubMed2002

Phase II study of topotecan plus cranial radiation for glioblastoma multiforme: results of Radiation Therapy Oncology Group 9513.

PURPOSE: A Phase II trial was conducted by the Radiation Therapy Oncology Group (RTOG) to compare the survival of patients with glioblastoma multiforme treated with topotecan combined with standard cranial radiotherapy (RT) for matched patients treated in prior RTOG studies. A secondary objective was to document the acute and late toxicities of this combination of chemotherapy and RT. METHODS AND MATERIALS: Eighty-seven patients with histologically confirmed glioblastoma multiforme received standard cranial RT (60 Gy/30 fractions in 6 weeks) plus topotecan 1.5 mg/m2 per day i.v. for 5 d/wk every 3 weeks for 3 cycles. Eighty-four patients were evaluated, of whom 60 (71%) were > or =50 years, 44 (52%) were men, and 61 (73%) had a Karnofsky performance status of > or =80. Twenty-nine percent of patients had undergone biopsies, 48% partial resections, and 21% gross total resections. Two resections were unspecified as to the extent of tumor removal. Fourteen percent of patients were recursive partitioning analysis Class III, 46% were Class IV, 35% were Class V, and 5% were Class VI. RESULTS: The median survival was 9.3 months. Sixty-seven patients (80%) had progression. The 1-year survival rate was 32%. One patient remained alive without recurrence. RTOG 9513 patients were matched with patients in an RTOG clinical trial database from previous clinical trials. The matching variables were age, Karnofsky performance status, mental status, and prior surgery. No statistically significant difference was found between the survival of the study patients and that of the matched patients from the RTOG database. Fifty-four percent of patients had Grade IV acute toxicity. The toxicity was primarily hematologic. Four patients had Grade III late central nervous system toxicities. CONCLUSION: Topotecan administered at a dose of 1.5 mg/m2 per day i.v. for 5 d/wk every 3 weeks for 3 cycles given concurrently with standard cranial RT for glioblastoma does not produce a statistically significant survival advantage over previously tested therapies. Other methods of administration of topotecan or other camptothecins may provide more effective radiosensitization.

Aged↗
PubMed1999

Functional magnetic resonance (fMR) imaging of a rat brain tumor model: implications for evaluation of tumor microvasculature and therapeutic response.

Functional MR (fMR) imaging techniques based on blood oxygenation level dependent (BOLD) effects were developed and applied to a rat brain tumor model to evaluate the potential utility of the method for characterizing tumor growth and regression following treatment. Rats bearing 9L brain tumors in situ were imaged during inhalation of room air and after administration of 100% oxygen + acetazolamide (ACZ) injected 15 mg/kg intravenously. Pixel-to-pixel fMR maps of normalized signal intensity change from baseline values were calculated from T2 weighted spin echo (SE) images acquired pre- and post- oxygen + ACZ administration. Resultant fMR maps were then compared to gross histological sections obtained from corresponding anatomical regions. Regions containing viable tumor with increased cellular density and localized foci of necrotic tumor cells consistent with hypoxia were visualized in the fMR images as regions with decreased signal intensities, indicating diminished oxyhemoglobin concentration and blood flow as compared to normal brain. Histological regions having peritumor edema, caused by increased permeability of tumor vasculature, were visualized in the fMR images as areas with markedly increased signal intensities. These results suggest that fMR imaging techniques could be further developed for use as a non-invasive tool to assess changes in tumor oxygenation/hemodynamics, and to evaluate the pharmacologic effect of anti-neoplastic drugs.

Acetazolamide↗
PubMed2003

Sarcomatous change after sellar irradiation in a growth hormone-secreting pituitary adenoma.

BACKGROUND: Although the benefits of radiotherapy for pituitary adenomas are well-documented, post-irradiation sarcomas of the sella are rarely seen, with only 20 cases (mainly of fibrosarcoma) reported in the medical literature. METHOD: We describe a case of post-irradiation sarcoma five years after surgery followed by external-beam irradiation for an extensive and locally invasive growth hormone-secreting tumor. The patient was subsequently given pegvisomant, an antagonist of growth hormone receptor, to control symptoms of growth hormone excess. RESULTS: The patient underwent transsphenoidal resection of the recurrent tumor, followed by adjuvant chemotherapy. This led to significant relief in the patient's symptoms including radiological evidence of tumor shrinkage, but the tumor regrew when, owing to dose-limiting toxicity, chemotherapy was stopped. CONCLUSIONS: Post-irradiation sarcomas of the pituitary are well-recognized but rare. They should be suspected in patients following sellar irradiation who show abrupt onset of new symptoms and appropriate radiological findings, and such tumors may respond to cytotoxic chemotherapy.

Adenoma↗
PubMed1998

Genomic changes in glioblastoma cell lines detected by comparative genomic hybridization.

Comparative genomic hybridization serves as a screening test for regions of copy number changes in tumor genomes. We have applied the technique to map DNA gains and losses in 5 cell lines derived from glioblastoma multiforme, the most common primary neoplasm of the central nervous system. The most frequent losses occurred on chromosomes 10 and 13. The most common gains were observed on chromosomes 5, 6, 7 and 20. Some novel sites of genomic alterations were also observed. Analysis of common areas of loss and gain in these cell lines provides a basis for future attempts to more finely map these genetic changes and for elucidation of genes involved in tumor progression.

Aged↗
PubMed1999

Enhanced uptake of [3H] spermidine by 9L rat brain tumors after direct intratumoral infusion of inhibitors of enzymes of the polyamine biosynthetic pathway.

We have been exploring the feasibility of delivering ionizing radiation to brain tumor cells by using tritium labeled polyamines. Polyamines are taken up preferentially by dividing cells and form noncovalent bonds with DNA. Their uptake can be enhanced by drugs which deplete endogenous polyamines. To test this in vivo, 9L cells were implanted in the striatal region of the brain in male Fisher 344 rats. Osmotic pumps containing trace amounts of [3H] spermidine or [3H] putrescine with either difluoromethylornithine or combinations of 3 inhibitors of enzymes of the polyamine biosynthetic pathway were implanted subcutaneously and were connected to intratumoral cannulas. After 14-16 days the brains were removed and sliced in the coronal plane. The diameters of the tumors were measured and tumor tissue was dissected from each slice, weighed and lysed for scintillation counting. It was found that difluoromethylornithine enhanced the uptake of [3H] putrescine while a combination of inhibitors of enzymes of the polyamine biosynthetic pathway enhanced the uptake of [3H] putrescine and [3H] spermidine producing a localized region of radioactivity in the 9L tumor. It is estimated that if the [3H] polyamines were at higher specific activity (commercially available), instead of the trace dose given here, the [3H] polyamine uptake would be sufficient to kill 9L tumor cells within a 2 to 3 week period.

Adenosylmethionine Decarboxylase↗
PubMed2001

Extraneural metastases of primary brain tumors.

Extraneural metastasis (ENM) of primary brain tumors is arare occurence. Based on acritical analysis of the literature the present review focuses on illustrating special common features of these tumors with regard to immunological, cytokinetical and tumorbiological issues. In this respect much can be learned from the specific conditions following organ transplantation which is extensively discussed.

Adult↗
PubMed1998

Cytotoxicity of alpha-particle-emitting astatine-211-labelled antibody in tumour spheroids: no effect of hyperthermia.

The high linear energy transfer, alpha-particle-emitting radionuclide astatine-211 (211At) is of interest for certain therapeutic applications; however, because of the 55- to 70-microm path length of its alpha-particles, achieving homogeneous tracer distribution is critical. Hyperthermia may enhance the therapeutic efficacy of alpha-particle endoradiotherapy if it can improve tracer distribution. In this study, we have investigated whether hyperthermia increased the cytotoxicity of an 211At-labelled monoclonal antibody (MAb) in tumour spheroids with a radius (approximately 100 microm) greater than the range of 211At alpha-particles. Hyperthermia for 1 h at 42 degrees C was used because this treatment itself resulted in no regrowth delay. Radiolabelled chimeric MAb 81C6 reactive with the extracellular matrix antigen tenascin was added to spheroids grown from the D-247 MG human glioma cell line at activity concentrations ranging from 0.125 to 250 kBq ml(-1). A significant regrowth delay was observed at 125 and 250 kBq ml(-1) in both hyperthermia-treated and untreated spheroids. For groups receiving hyperthermia, no increase in cytotoxicity was seen compared with normothermic controls at any activity concentration. These results and those from autoradiographs indicate that hyperthermia at 42 degrees C for 1 h had no significant effect on the uptake or distribution of this antitenascin MAb in D-247 MG spheroids.

Alpha Particles↗
PubMed1996

Viral vector transduction of the human deoxycytidine kinase cDNA sensitizes glioma cells to the cytotoxic effects of cytosine arabinoside in vitro and in vivo.

Cytosine arabinoside (ara-C) is a cytidine analog that incorporates into replicating DNA and induces lethal DNA strand breaks. Although ara-C is a potent antitumor agent for hematologic malignancies, it has only minimal activity against most solid tumors. The rate-limiting step in intracellular ara-C activation is phosphorylation of the prodrug by deoxycytidine kinase (dCK). The present results demonstrate that both retroviral and adenoviral vector-mediated transduction of the dCK cDNA results in marked sensitization of glioma cells lines to the cytotoxic effects of ara-C in vitro. We also demonstrate that ara-C treatment of established intradermal and intracerebral gliomas transduced with dCK results in significant antitumor effects in vivo. These data suggest that viral vector transduction of the dCK gene followed by treatment with ara-C represents a new chemosensitization strategy for cancer gene therapy.

Adenoviridae↗
PubMed2000

Enhanced green fluorescent protein fusion proteins of herpes simplex virus type 1 thymidine kinase and cytochrome P450 4B1: applications for prodrug-activating gene therapy.

To monitor therapeutic transgene expression, we developed fusion genes of enhanced green fluorescent protein (EGFP) with two different prodrug-activating enzyme genes: herpes simplex virus type 1 thymidine kinase (HSV-tk) and rabbit cytochrome P450 4B1 (cyp4b1). Expression of the resulting fusion proteins, TK-EGFP and 4B1-EGFP, rendered transduced human and rodent glioma cells sensitive to cytotoxic treatment with the corresponding prodrugs ganciclovir and 4-ipomeanol. Ganciclovir and 4-ipomeanol sensitivity was comparable with that achieved with the native HSV-TK and CYP4B1 proteins. As shown by fluorescence microscopy, TK-EGFP was expressed predominantly intranuclearly, whereas 4B1-EGFP was detectable in the cytoplasm, thereby displaying the orthotopic subcellular distribution of the corresponding native enzymes. The fluorescence intensity correlated well with the corresponding prodrug sensitivity, as shown by fluorescence-activated cell sorter analysis. EGFP expression was also used for the selection of stably HSV-tk-transduced cells by flow cytometric cell sorting. Resulting cell populations showed a homogeneity of fluorescence intensity similar to single-cell clones after antibiotic selection. In conclusion, tk-egfp and 4b1-egfp fusion genes are valuable tools for monitoring prodrug-activating gene therapy in living cells. EGFP fusion genes/proteins provide a simple and reproducible means for the detection, selection, and characterization of cells expressing enzyme genes for prodrug activation.

Animals↗