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.

752 records · Page 42Linked to original sources
PubMed2002

Enhanced bystander cytotoxicity of P450 gene-directed enzyme prodrug therapy by expression of the antiapoptotic factor p35.

Cytochrome P450 gene-directed enzyme prodrug therapy substantially augments intratumoral activation of anticancer prodrugs, such as cyclophosphamide (CPA), leading to a strong increase in antitumor effect without a corresponding increase in host toxicity. Attempts to additionally increase tumor cell kill by enhancing the intrinsic chemosensitivity of P450-expressing tumor cells by chemical means (depletion of cellular glutathione) or by coexpression of proapoptotic factors was shown to result in the desired increase in chemosensitivity, but with a decrease in net production of bystander cytotoxic drug metabolites because of accelerated death of the prodrug-activating tumor cells. Moreover, tumor cell P450 activity declined during the course of apoptosis induced by P450-activated CPA, limiting the potential of the tumor cell for continued production of activated drug metabolites. This limitation could be overcome by retroviral delivery of the baculovirus-encoded caspase inhibitor p35 to P450-expressing tumor cells. p35 substantially prolonged the activation of CPA by P450 "factory cells," leading to an increase in their bystander cytotoxicity toward P450-deficient tumor cells. This effect was greatest in tumor cells treated with CPA for an 8-h period, a schedule designed to model the effective time period of drug exposure in bolus CPA-treated patients in vivo. Notably, retroviral transduction of tumor cells with p35 did not induce drug resistance, as shown by the absence of long-term tumor cell survival or detectable colony formation activity after CPA treatment. These findings demonstrate that antiapoptotic factors, such as p35, can be used in a novel manner to enhance prodrug activation gene therapy by delaying tumor cell death, thereby increasing the net production of bystander cytotoxic metabolites and, hence, the overall effectiveness of the anticancer strategy.

Animals↗
PubMed1994

Effect of berberine alone or in combination with argon ion laser treatment on 9L rat glioma cell line.

The cell-killing effect and its possible mechanism of berberine used alone or in combination with argon ion laser treatment on 9L rat glioma cells were studied. The survival fraction of 9L cells after single treatment of berberine has been investigated using both colony formation and microtitration (MTT) method, the half lethal dose of berberine (LD50) has been estimated to be 60 micrograms/ml. After the addition of low energy laser treatment, the LD50 of berberine markedly decreased to 10 micrograms/ml. The inhibitory effect of berberine on biosynthesis for DNA, RNA, and protein of 9L cells was enhanced by argon ion laser. Moreover, when morphologic change was examined, the 9L cells showed lysis, encystation, and degeneration after berberine treatment; the laser treatment enhanced the cell-killing effect. The study proves the cell-killing effect of berberine combined with laser treatment on 9L rat glioma cell line, hence introducing the possibility of berberine as a photosensitive agent.

Animals↗
PubMed1994

Linear contrast enhancement at the operative site on early post-operative CT after removal of brain tumors.

It is unclear whether a linear contrast enhancement at the edges of the operative site on early CT scan indicates a residual tumor or rather reflects postoperative changes. We have studied 15 patients treated with surgical removal of malignant brain tumor, submitted to periodic CT scan. The enhancement of linear contrast was due to a residual tumor, when seen on very early CT scan (within 24 hours after surgery). If occurring later, this enhancement was either generated by a residual tumor or by post-operative changes.

Adolescent↗
PubMed1996

Gene therapy for malignant gliomas using replication incompetent retroviral and adenoviral vectors encoding the cytochrome P450 2B1 gene together with cyclophosphamide.

Cyclophosphamide is an inactive prodrug which is converted by hepatic cytochrome P450 2B1 to cytotoxic metabolites which produce interstrand DNA cross-linking in a cell cycle-independent fashion. The limited ability of these metabolites to cross the blood-brain barrier contributes to the poor activity of cyclophosphamide against brain tumors. In this study we demonstrate that replication deficient retroviral and adenoviral vector-mediated gene transfer of cytochrome P450 2B1 into 9L glioma cells significantly increases the sensitivity of these tumor cells to cyclophosphamide in vitro, and prolongs the survival of animals bearing intracerebral 9L tumors treated with cyclophosphamide in vivo. Attempts to improve the effectiveness of retrovirally mediated transduction of the P450 2B1 gene by increasing the concentration of cyclophosphamide delivered to the tumors using intracarotid and intratumoral injections did not prolong animal survival, although survival was increased when a second treatment with P450-expressing retroviral vectors and cyclophosphamide was administered. These results suggest that in situ transduction of tumor cells with the P450 2B1 gene using retroviral and adenoviral vectors increases their sensitivity to cyclophosphamide and may have a potential role in the therapy of malignant gliomas.

Adenoviridae↗
PubMed1996

Retroviral delivery and tetracycline-dependent expression of IL-1beta-converting enzyme (ICE) in a rat glioma model provides controlled induction of apoptotic death in tumor cells.

Interleukin 1beta-converting enzyme (ICE) is a member of a growing family of cysteine proteases shown to be a crucial component in the activation of a genetic program that leads to autonomous cell death in mammalian cells. In this study, a murine ICE-lacZ fusion gene was introduced into a novel retroviral vector designed to achieve regulated ectopic expression of a foreign gene in mammalian cells. By delivering the ICE-lacZ gene within a retroviral vector and under the control of a tetracycline-regulated promoter, we were able to utilize the intrinsic cell death program of ICE as a means for tumoricidal therapy in a rat brain tumor model. Both in culture and in vivo suppression of ICE-lacZ expression was extremely tight in the presence of tetracycline, as determined by the lack of X-galactosidase-positive tumor cells and by cell viability. When tetracycline was withdrawn, ICE-lacZ gene expression was rapidly turned on and apoptosis-mediated cell death occurred in essentially all tumor cells.

Animals↗
PubMed1998

Expression of a cleaved brain-specific extracellular matrix protein mediates glioma cell invasion In vivo.

Malignant gliomas (primary brain tumors) aggressively invade the surrounding normal brain. This invasive ability is not demonstrated by brain metastases of nonglial cancers. The brain-specific, brain-enriched hyaluronan binding (BEHAB)/brevican gene, which encodes an extracellular hyaluronan-binding protein, is consistently expressed by human glioma and is not expressed by tumors of nonglial origin (Jaworski et al., 1996). BEHAB/brevican can be cleaved into an N-terminal fragment that contains a hyaluronan-binding domain (HABD) and a C-terminal fragment (Yamada et al., 1995). Here, using antisera to peptides in the predicted N-terminal and C-terminal proteolytic fragments, we demonstrate that the BEHAB/brevican protein is cleaved in invasive human and rodent gliomas. A role for this protein in glioma cell invasion was tested by transfecting a noninvasive cell line with the BEHAB/brevican gene. The noninvasive 9L glioma cell was transfected with either full-length BEHAB/brevican or the HABD and tested for invasion in in vitro and in vivo invasion assays. Although both constructs increased invasion in vitro, only the HABD increased invasion by tumors growing in vivo. Experimental intracranial tumors from full-length transfectants showed no increase in invasion over control tumors, whereas tumors from HABD transfectants showed a marked potentiation of tumor invasion, producing new tumor foci at sites distant from the main tumor mass. This work demonstrates a role for a brain-specific extracellular matrix protein in glioma invasion, opening new therapeutic avenues for a uniformly fatal disease.

Amino Acid Sequence↗
PubMedDate not supplied

Long-term survival in a rodent brain tumor model by bradykinin-enhanced intra-arterial delivery of a therapeutic herpes simplex virus vector.

Recently, it was demonstrated that bradykinin (BK) enhances intracarotid delivery of herpes simplex virus type I (HSV) vectors to rat brain tumors, and that gene transfer takes place predominantly in the tumor periphery. The aim of the present study was to apply these findings to the treatment of experimental rat brain tumors. The HSV mutant, hrR3, which is disrupted in the ribonucleotide reductase gene, was injected intra-arterially with titers of 1 x 10(8), 1 X 10(9), and 1 x 10(10) plaque-forming units (pfu) both with and without BK into Fischer 344 rats with intracerebral, syngeneic 9L tumors. Starting on day 3 after vector administration, animals were treated by intraperitoneal injection of 60 mg/kg/day ganciclovir (GCV) or placebo. 1 x 10(10) pfu hrR3 in combination with BK and GCV treatment was able to eradicate tumors in 80% of the animals; 1 x 10(9) pfu cured 40% of the rats, and 1 x 10(8) pfu achieved an extension of survival time but no tumor cures. Control groups had 100% mortality within 30 days after injection of tumor cells, with the exception of the group with injection of 1 x 10(10) pfu of virus and GCV treatment, which had one long-term survivor. No apparent complications of this novel type of brain tumor gene therapy were encountered. In conclusion, intra-arterial injection of attenuated HSV vectors with blood-tumor barrier modification and subsequent systemic GCV application appears to be a promising approach for the treatment of malignant brain tumors.

Animals↗
PubMed1998

Involvement of heat shock elements and basal transcription elements in the differential induction of the 70-kDa heat shock protein and its cognate by cadmium chloride in 9L rat brain tumor cells.

Exposure of 9L rat brain tumor cells to 40-100 microM CdCl2 for 2 h leads to an induction of a wide spectrum of heat shock proteins (HSPs). We have demonstrated that induction of the 70-kDa HSP (HSP70) and enhanced expression of its cognate (HSC70) by cadmium are concentration dependent and that the induction kinetics of these HSP70s are different. The increased synthesis of the HSP70s is accompanied by the increase in hsp70 and hsc70 mRNA levels, indicative of transcriptional regulation of the heat shock genes. Electrophoretic mobility shift assay (EMSA) using probes encompassing heat shock element (HSE), TATA, GC, and CCAAT boxes derived from the promoter regions of the heat shock genes shows distinguished binding patterns between hsp70 and hsc70 genes in both control and cadmium-treated cells. The results indicate that, in addition to the HSEs, the basal transcription elements are important in the regulation of the heat shock genes. The binding patterns of the corresponding transcription factors of these elements are examined by EMSA by using extended promoter fragments from respective heat shock genes with sequential addition of excess oligonucleotides encompassing individual transcription elements. Taken together, our results show that the differential induction of hsp70 and hsc70 involves multiple transcription factors that interact with HSE, TATA, GC, and CCAAT boxes.

Animals↗
PubMed1998

Identification of mitogen-activated protein kinase-activated protein kinase-2 as a vimentin kinase activated by okadaic acid in 9L rat brain tumor cells.

Organization of intermediate filament, a major component of cytoskeleton, is regulated by protein phosphorylation/dephosphorylation, which is a dynamic process governed by a balance between the activities of involved protein kinases and phosphatases. Blocking dephosphorylation by protein phosphatase inhibitors such as okadaic acid (OA) leads to an apparent activation of protein kinase(s) and to genuine activation of phosphatase-regulated protein kinase(s). Treatment of 9L rat brain tumor cells with OA results in a drastically increased phosphorylation of vimentin, an intermediate filament protein. In-gel renaturing assays and in vitro kinase assays using vimentin as the exogenous substrate indicate that certain protein kinase(s) is activated in OA-treated cells. With specific protein kinase inhibitors, we show the possible involvement of the cdc2 kinase- and p38 mitogen-activated protein kinase (p38MAPK)-mediated pathways in this process. Subsequent in vitro assays demonstrate that vimentin may serve as an excellent substrate for MAPK-activated protein kinase-2 (MAPKAPK-2), the downstream effector of p38MAPK, and that MAPKAPK-2 is activated with OA treatment. Comparative analysis of tryptic phosphopeptide maps also indicates that corresponding phosphopeptides emerged in vimentin from OA-treated cells and were phosphorylated by MAPKAPK-2. Taken together, the results clearly demonstrate that MAPKAPK-2 may function as a vimentin kinase in vitro and in vivo. These findings shed new light on the possible involvement of the p38MAPK signaling cascade, via MAPKAPK-2, in the maintenance of integrity and possible physiological regulation of intermediate filaments.

Animals↗
PubMed1998

Neutron capture therapy with a new boron-porphyrin compound in the rat 9L glioma model.

Neutron capture therapy with a new boron-porphyrin compound was tested in a rat brain tumor model. Although the concentration of boron in the tumor was too low to elicit a therapeutic effect, prominent histopathologic changes, such as necrosis, congestion and bleeding were observed in the tumors of the rats which were administered the boron neutron capture therapy.

Animals↗