An improved rat brain-tumor model

1980 ◽  
Vol 53 (6) ◽  
pp. 808-815 ◽  
Author(s):  
Naoki Kobayashi ◽  
Norman Allen ◽  
Nancy R. Clendenon ◽  
Li-Wen Ko

✓ The widely used intracerebral tumor implantation method by freehand injection into parietal or hippocampal areas of the rat brain has proven inadequate for reliable experimental therapeutic studies. Problems include poor intracerebral growth yields and significant rates of spread to extracranial tissues, lungs, and spinal cord. Major variables have been examined experimentally on a model using nitrosourea-induced nervous system tumor cell lines in syngeneic rats. A rapid stereotaxic method greatly improved the consistency of tumor placement. The optimal site was found to be the caudate nucleus. The production of a spheroid intracerebral growth was further facilitated by the use of 1% agar in the cell suspension medium and by an injection volume of 10 µl containing at least 104 cells. Further improvements involved injection technique and flushing of the operative field. These modifications have resulted in a 99% to 100% yield of intracerebral growth, with a marked reduction in the number and size of extracranial extensions and with distant metastasis rates of 0% to 5%. These results have continually improved with further experience. The method is satisfactory for radiation and chemotherapeutic trials in which survival time as an index of tumor size may be used as an end point.

1989 ◽  
Vol 9 (1) ◽  
pp. 87-95 ◽  
Author(s):  
Michihiro Kirikae ◽  
Mirko Diksic ◽  
Y. Lucas Yamamoto

We examined the rate of glucose utilization and the rate of valine incorporation into proteins using 2-[18F]fluoro-2-deoxyglucose and L-[1-14C]-valine in a rat brain tumor model by quantitative double-tracer autoradiography. We found that in the implanted tumor the rate of valine incorporation into proteins was about 22 times and the rate of glucose utilization was about 1.5 times that in the contralateral cortex. (In the ipsilateral cortex, the tumor had a profound effect on glucose utilization but no effect on the rate of valine incorporation into proteins.) Our findings suggest that it is more useful to measure protein synthesis than glucose utilization to assess the effectiveness of antitumor agents and their toxicity to normal brain tissue. We compared two methods to estimate the rate of valine incorporation: “kinetic” (quantitation done using an operational equation and the average brain rate coefficients) and “washed slices” (unbound labeled valine removed by washing brain slices in 10% thrichloroacetic acid). The results were the same using either method. It would seem that the kinetic method can thus be used for quantitative measurement of protein synthesis in brain tumors and normal brain tissue using [11C]-valine with positron emission tomography.


1993 ◽  
Vol 11 (3) ◽  
pp. 299-305 ◽  
Author(s):  
Hidenori Ogasawara ◽  
Tohru Uozumi ◽  
Katsuzo Kiya ◽  
Kaoru Kurisu ◽  
Takashi Mikami ◽  
...  

1980 ◽  
Vol 52 (4) ◽  
pp. 529-532 ◽  
Author(s):  
Esref Tel ◽  
Takao Hoshino ◽  
Marvin Barker ◽  
Charles B. Wilson

✓ In Fischer 344 rats, 9L tumors were implanted in the left cerebral hemisphere. Compared with control animals not operated on, rats treated with an LD10 dose of BCNU 1 hour before or 1 or 12 hours after surgery on Day 16 postimplant had an increased life span of over 200% (greater than a 6 log cell kill). Minimal effect on survival was found when BCNU was administered during surgery. On the other hand, BCNU administered 12 hours before or 24 or 72 hours after surgery did not show any additive effect of surgery on BCNU treatment. These results suggest that in a clinical setting, a bolus of BCNU administered to tumor patients within 12 hours of surgery might increase substantially the total tumor cell kill compared with surgical resection alone.


Radiology ◽  
2020 ◽  
Vol 294 (1) ◽  
pp. 117-126 ◽  
Author(s):  
Philippe Robert ◽  
Véronique Vives ◽  
Anne-Laure Grindel ◽  
Stéphane Kremer ◽  
Guillaume Bierry ◽  
...  

2003 ◽  
Vol 16 (2) ◽  
pp. 67-76 ◽  
Author(s):  
Brian D. Ross ◽  
Thomas L. Chenevert ◽  
Michael Garwood ◽  
Boklye Kim ◽  
Lauren D. Stegman ◽  
...  

1993 ◽  
Vol 79 (4) ◽  
pp. 577-583 ◽  
Author(s):  
Bruce F. Kimler ◽  
Changnian Liu ◽  
Richard G. Evans ◽  
Robert A. Morantz

✓ The authors attempted to confirm published reports that pentobarbital protects against radiation-induced damage to normal rat brain, as well as enhances radiotherapeutic efficacy in a rat brain tumor model. They evaluated animal survival in 9L gliosarcoma-burdened rats that received whole-brain radiation therapy (16, 24, 32, or 40 Gy) while under intraperitoneal pentobarbital (60 mg/kg) or intramuscular ketamine (60 mg/kg) sedation. The animals were examined at autopsy to attribute death to either intracranial tumor growth or normal brain toxicity in the absence of discernible tumor. There was no difference between the two anesthesia groups regarding the survival of unirradiated animals. Radiation therapy produced a significant dose-dependent prolongation in animal survival, which was limited by the development of normal tissue toxicity at the higher doses. When compared to ketamine anesthesia, pentobarbital anesthesia appeared to offer some protection (not statistically significant) against early (but not late) toxicity at selected radiation doses. A reduction in the number of deaths from tissue toxicity suggested an increased antitumor effect, but again this was not statistically significant. Only in one case was there even a marginal significant difference (p = 0.045) between overall therapeutic efficacy in rats sedated with pentobarbital versus ketamine. While there may be a radioprotective effect of pentobarbital in rat brains without intracranial tumor, there is no conclusive evidence for either radioprotection or significant improvement of radiotherapeutic efficacy in this 9L rat brain tumor model.


1991 ◽  
Vol 74 (1) ◽  
pp. 112-115 ◽  
Author(s):  
Wesley A. King ◽  
Keith L. Black ◽  
Kiyonobu Ikezaki ◽  
Scott Conklin ◽  
Donald P. Becker

✓ The efficacy of U-74006F and U-78517F in the treatment of blood-tumor barrier permeability and tumor-associated neurological dysfunction was evaluated in a brain-tumor model in rats. U-74006F is a 21-aminosteroid and U-78517F is a 2-methylamino chroman. Rats with stereotactically implanted Walker 256 tumors were treated with methylprednisolone, U-74006F, U-78517F, or vehicle (0.05 N HCl) on Days 6 through 10 following implantation. Neurological function and vascular permeability were assessed on Day 10. Methylprednisolone and U-74006F were equally effective at preventing neurological dysfunction compared to the control group (p < 0.01); U-78517F was slightly less effective than U-74006F and methylprednisolone but was significantly better than vehicle in preventing neurological dysfunction. Delivery of methylprednisolone resulted in a significant decrease in tumor vascular permeability (p < 0.006) while U-74006F and U-78517F had no effect on permeability. This suggests that U-74006F and U-78517F prevented tumor-associated neurological dysfunction by a mechanism other than decreasing permeability in tumor capillaries, and that U-74006F or U-78517F could prove useful in the treatment of brain tumors.


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