Gene Therapy in Brain Tumours: Implications of the Size of Glioblastoma on its Curability

Izquierdo, Marta López; Cortés, M. L.; Martı́n, Verónica; Felipe, Pablo de; Izquierdo, J.M.; Pérez-Higueras, Antonio; Paz, José Flávio da; Isla, Arantxazu; Blázquez, Martín G.

doi:10.1007/978-3-7091-6513-3_21

Cited by 34 publications

(21 citation statements)

References 9 publications

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“…Nevertheless magnetic resonance images show a comparable fibrous scar to the one obtained previously with the Hstk/ganciclovir system 3,4 or to the C6 infected in vivo by the retrovirus LlinSp, indicating absence of a devastating effect in the brain. The control animals treated with producer cells and linamarin in the absence of tumor ( Figure 6) also provide evidence against brain damage with the full treatment.…”

Section: Discussionsupporting

confidence: 60%

“…[3][4] Wistar male rats weighing 250-300 g were anesthetized with a mixture of ketamine (50 mg/ml), valium (5 mg/ml) and atropine (1mg/ml) in a 5:4:1 ratio by volume at a dose of 0.3 ml/100 g of body weight, before placing them in a stereotactic apparatus. C6 glioma cells or the same cells transfected with the pLlinSp plasmid and selected by puromycin resistance were injected at a concentration of 10 5 cells/ l in complete PBS (with calcium and magnesium) supplemented with 0.1% glucose.…”

Section: Wistar Rat Brain Inoculation Of C6lin Transfected Cells and mentioning

confidence: 99%

“…Malignant brain tumors (glioblastoma) have been cured in the rat animal model provided the volume of the tumor does not exceed 100-150 mm 3 in size. 4 When the same treatment is applied to humans, [4][5][6][7] complete remission of the tumor is not achieved, although there is in some cases a measurable size reduction probably responsible for a considerable increase in the expected survival time of these patients. 4,7 A more aggressive killer-suicide system would represent a promising strategy for one of the most frequent (1 per 50 000 people per year) and deadly (mortality close to 100%) brain tumors in human beings.…”

Section: Introductionmentioning

confidence: 99%

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Successful use of a plant gene in the treatment of cancer in vivo

et al. 1998

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A new strategy for cancer gene therapy has been substrate, linamarin, followed by cell death. We show that developed using a plant gene which encodes the enzyme, the system can eradicate very large intracerebral gliomas linamarase, that hydrolyzes the cyanogenic glucoside subin vivo helped by a cyanide bystander effect. Animals strate, linamarin, into glucose, acetone and cyanide. Retroshowing a total regression of the tumor by magnetic resonviral vectors that carry linamarase as a potential killer-suicance imaging (MRI), do not show other appreciable toxic ide gene cause a marked sensitization to the innocuous effects.

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Section: Discussionsupporting

confidence: 60%

Section: Wistar Rat Brain Inoculation Of C6lin Transfected Cells and mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Successful use of a plant gene in the treatment of cancer in vivo

et al. 1998

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“…14 Titers were estimated by infecting NIH/3T3 cells as described previously. 25 Each supernatant was tested once.…”

Section: Cell Culturementioning

confidence: 99%

Use of the 2A sequence from foot-and-mouth disease virus in the generation of retroviral vectors for gene therapy

et al. 1999

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We describe the construction of retroviral plasmid vectors lation gives rise to a bicistronic mRNA and two indein which two genes are linked by a minimum of 96 nucleopendent protein products. The system offers advantages tides encoding the 2A sequence from the picornavirus footto other alternative ways to create polycistronic mRNAs and-mouth disease virus (FMDV). Transcription and transand can be used in gene therapy delivery vectors.

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“…Malignant tumors induced in the right cerebral hemisphere of Wistar rats are very aggressive and usually lethal to the animal within 15 to 25 days. 19 We inoculated 10 rats on day 0 with a 1:1 mixture of rat glioblastoma C6 cells and CRIP-tricistronic vector-producing cells (5 × 10 5 cells of each). As a control, nine more rats were inoculated with a 1:1 mixture of C6 and CRIP packaging an empty vector (pBabe-puro).…”

Section: Els These Results Suggest That Therapeutic Strategies Aiminmentioning

confidence: 99%

A tricistronic retroviral vector expressing natural antiangiogenic factors inhibits angiogenesis in vitro, but is not able to block tumor progression in vivo

et al. 2002

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Neovascularization is needed for solid tumors to grow beyond a diameter of 2-3 mm. 1 Angiogenesis is accomplished by a series of sequential steps involving the motility and growth of endothelial cells: initiation and termination of these processes is tightly controlled by the balance between stimulatory and inhibitory factors. 1 Therefore, the delivery of inhibitory molecules and/or the removal of angiogenesis inducers could represent an effective approach to target and suppress tumor angiogenesis. Over the last decade, a number of anti-angiogenic agents were demonstrated to derive from a proteolytic cleavage of native proteins, as is the case for angiostatin, 2 endostatin, 3 platelet factor 4 (PF4), 4 or the 16-kDa N-terminal fragment of prolactin (16K PRL). 5 These factors, being 'natural' inhibitors of angiogenesis, are good candidates for an antiangiogenic therapy, as they should be much better tolerated by a patient than exogenous, synthetic drugs. Under most circumstances, however, angiogenesis inhibition appears to be cytostatic rather then cytotoxic, and therefore tumor growth inhibition would probably require prolonged maintenance therapy with the anti-angiogenic agents. The maintenance of this pro-

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Gene Therapy in Brain Tumours: Implications of the Size of Glioblastoma on its Curability

Cited by 34 publications

References 9 publications

Successful use of a plant gene in the treatment of cancer in vivo

Successful use of a plant gene in the treatment of cancer in vivo

Use of the 2A sequence from foot-and-mouth disease virus in the generation of retroviral vectors for gene therapy

A tricistronic retroviral vector expressing natural antiangiogenic factors inhibits angiogenesis in vitro, but is not able to block tumor progression in vivo

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